Endocrine and Metabolic Conditions

Question 1

Addison’s Disease Definition

Answer 1

Adrenal insufficiency is a clinical syndrome that arises due to the insufficient production of glucocorticoids and mineralocorticoids from the adrenal cortex.
It can be categorized as primary, commonly known as Addison’s disease, where the cause lies within the adrenal glands themselves, or secondary, where inadequate stimulation of the adrenal glands by the pituitary or hypothalamus is the culprit.

Question 2

Difference between primary and secondary adrenal insufficiency

Answer 2

In primary adrenal insufficiency (Addison’s disease), the adrenal glands are damaged, while secondary adrenal insufficiency is due to dysfunction in the hypothalamus or pituitary.

Question 3

Name causes of primary adrenal insufficiency

Answer 3

Auto-immune destruction (most common)
Surgical removal of the adrenal glands
Trauma to the adrenal glands
Infectious diseases, such as tuberculosis (more common in developing countries)
Haemorrhage (e.g., Waterhouse-Friderichsen syndrome)
Infarction
Less commonly, neoplasms, sarcoidosis, or amyloidosisAuto-immune destruction (most common)

Question 4

Name causes of secondary adrenal insufficiency

Answer 4

Congenital disorders
Fracture of the base of the skull
Pituitary or hypothalamic surgery or Neoplasms in the pituitary or hypothalamus
Infiltration or infection of the brain
Deficiency of corticotropin-releasing hormone (CRH)

Question 5

Signs and symptoms of Addison’s disease

Answer 5

Hypotension
Fatigue and weakness
Gastrointestinal symptoms
Syncope
Skin pigmentation due to increased ACTH which stimulates production of alpha melanocyte stimulating hormone (MSH).
In the case of auto-immune Addison’s disease, approximately 60% of patients may also have vitiligo or other autoimmune endocrinopathies.

Question 6

First line investigations for Addison’s disease:

Answer 6

U+E and serum cortisol, where you may find:
Hyponatraemia (low sodium)
Hyperkalaemia (high potassium)
Low serum cortisol
Glucose (typically low)

Question 7

What would you expect a blood gas to show in someone with Addison’s disease?

Answer 7

hyperkalaemic, hyponatraemic, hypoglycaemic metabolic acidosis

With less aldosterone, there is a reduced excretion of hydrogen ions, leading to their buildup in the blood. This causes an increase in the acidity of the blood, resulting in metabolic acidosis.

Question 8

Name some other findings one would expect in Addison’s disease

Answer 8

ACTH: High in primary insufficiency, low or low-normal in secondary insufficiency
Renin (high in Addison’s disease)
Aldosterone (low in Addison’s disease)

Question 9

What is the gold standard investigation
for Addison’s disease?

Answer 9

An ACTH (Short Synacthen) test is the gold standard investigation to confirm the diagnosis.

Question 10

Name further investigations for addison’s disease:

Answer 10

Testing for adrenal auto-antibodies
Chest X-ray for tuberculosis
CT scan of the adrenal glands
MRI of the brain

Question 11

Management of adrenal insufficiency:

Answer 11

Patient education on ‘sick day’ rules, carrying a steroid card, and wearing a medical alert bracelet
Doubling the regular steroid medication dose during any intercurrent illness
Replacement of both glucocorticoids (typically with hydrocortisone) and mineralocorticoids (typically with fludrocortisone)
Regular screening for complications including an adrenal crisis and osteoporosis

Question 12

Management of Addison’s crisis:

Answer 12

Aggressive fluid resuscitation
Administration of intravenous/IM (if no access) steroids STAT
Glucose administration if hypoglycaemia is present

Question 13

What is the most likely cause of Addison’s disease?

Answer 13

autoimmune

Question 14

What does severe meningococcal infection cause with the adrenal gland?

Answer 14

Waterhouse-Friderichsen syndrome

Thought that meningococcal septicaemia is associated with disseminated intravascular coagulation (DIC) which leads to adrenal haemorrhage.

Question 15

If someone take steroids for a long time and then suddenly stops what might this cause? (think adrenals) and what do we give?

Answer 15

Secondary adrenal insufficiency - give IV Hydrocortisone

Question 16

what part of the adrenal gland is mineralocorticoid produced?

Answer 16

Zona glomerulosa

Question 17

What part of the adrenal gland produces glucocorticoids?

Answer 17

zona fasciculata

Question 18

First step of management for an adrenal crisis?

Answer 18

immediate administration of intravenous or intramuscular hydrocortisone 100 mg in adults

Question 19

What is Cushing’s syndrome?

Answer 19

endocrine disorder characterized by excess glucocorticoids

Question 20

What is Cushing’s disease?

Answer 20

glucocorticoid excess caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumour

Question 21

What are the two main category causes of Cushing’s syndrome?

Answer 21

ACTH-dependent disease
ACTH-independent

Question 22

What causes ACTH-dependent cushings?

Answer 22

pituitary tumor (Cushing’s disease) or ectopic ACTH-producing tumors (e.g. lung carcinoids, thymic carcinoids, and others).

Question 23

What causes ACTH-independent cushings?

Answer 23

C: cancer adrenal adenoma
A: adrenal nodular hyperplasia
R: Rare causes: McCune-Albright syndrome
Steroid use

Question 24

What are the signs and symptoms of cushings?

Answer 24

Proximal myopathy
Striae and easy bruising
Osteoporosis and fractures
Glucose intolerance or diabetes mellitus
Obesity, particularly truncal or “centripetal” obesity
Hypertension
Hypokalaemia
Facial changes, such as moon face and acne
Hirsutism in women
Fat redistribution leading to interscapular and supraclavicular fat pads
Thin extremities due to muscle wasting
Thin, fragile skin
Erectile dysfunction in men
Psychological issues, such as depression or cognitive dysfunction
Osteopenia or osteoporosis

Question 25

What investigations do we do for cushings?

Answer 25

24-hour urinary free cortisol test Low-dose Dexamethasone suppression test

Question 26

Explain the different results of low/high dose dexamethasone suppression tests?

Answer 26

Not suppressed by low dose - Cushing’s syndrome (e.g. exogenous steroid use) Not suppressed by low dose but suppressed by high dose - Cushing’s disease (pituitary source) Not suppressed by low dose or by high dose dex – ectopic ACTH (not under axis control, likely ACTH-producing tumour)

Question 27

What further tests can you do to localise the source of cushings syndrome?

Answer 27

Plasma ACTH levels to distinguish between ACTH-dependent and independent causes High-dose dexamethasone suppression test for suspected Cushing's disease Inferior petrosal sinus sampling for suspected pituitary cause if MRI does not show pituitary tumour MRI of the pituitary and/or CT of chest and abdomen for tumor localization Cushing's syndrome is commonly associated with small cell lung cancer and can present with weight loss, increased skin pigmentation, and persisting respiratory symptoms

Question 28

What is the medical management of cushings syndrome?

Answer 28

Initial therapy often involves medications to decrease cortisol levels. These include Metyrapone, an inhibitor of cortisol synthesis; Ketoconazole, an adrenolytic agent; Mifepristone, a glucocorticoid receptor antagonist; and Pasireotide, a somatostatin analog.

Question 29

what is surgical management of cushings disease?

Answer 29

Resection of the pituitary tumor is the treatment of choice for Cushing's disease, often after initial control of hypercortisolaemia with medical therapy to improve surgical outcomes.

Question 30

When might radiotherapy be considered for Cushing's syndrome?

Answer 30

May be considered for cases where hypercortisolaemia persists post-surgery, or in cases where surgery is not possible or declined.

Question 31

What happens post successful treatment of Cushing's syndrome?

Answer 31

Successful treatment of Cushing's disease leads to cortisol deficiency and subsequently, steroid replacement post-operatively is essential. Patients need to carry a steroid card and ideally wear a medic alert bracelet in case of acute illness or emergency situations.

Question 32

What are the three functions of cortisol? (3As)

Answer 32

mAke glucose in the liver Antistress pathway Anti-inflammatory pathway

Question 33

Why does cushings cause osteoporosis?

Answer 33

decreases the activity and lifespan of osteoblasts and increases the activity of osteoclasts

Question 34

What causes false positives of 24hr urinary free cortisol?

Answer 34

depression, obesity, alcohol excess and inducers of liver enzymes In patients presenting with signs and symptoms of Cushing's syndrome but normal diurnal variation in cortisol levels, consider pseudo-Cushing's syndrome caused by chronic alcohol consumption.

Question 35

What is the most common underlying cause of Cushing's?

Answer 35

exogenous corticosteroid exposure

Question 36

What are the main side effects of steroids

Answer 36

insomnia, mania, depression, psychosis

Question 37

What is nelson's syndrome?

Answer 37

in the setting of Cushing’s syndrome a bilateral adrenalectomy has taken place. As a consequence, there is a loss of feedback to the brain and we get increased Corticotrophin-Releasing Hormone from the hypothalamus leading to increased stimulation of the anterior pituitary and enlargement of the pituitary and formation of an adenoma. This leads to symptoms of mass effect with headaches, visual field defects but also hormonal issues with compression of the posterior pituitary. Primary treatment is transphenoidal surgery

Question 38

define diabetes insipidus/ arginine vasopressin disorder

Answer 38

Arginine vasopressin disorder (formally diabetes insipidus) is an endocrine condition characterised by either an inadequate production (AVP-D) or an insufficient renal response (AVP-R) to arginine vasopressin (AVP), also called antidiuretic hormone (ADH).

Question 39

Which part of the body causes AVP deficiency

Answer 39

cranial

Question 40

Which part of the body causes AVP resistance?

Answer 40

kidneys

Question 41

Name some causes of AVP deficiency

Answer 41

C: congenital defect in ADH gene I: idiopathic V: vascular - sickle cell disease I: infection - meningoencephalitis T: tumour, tuberculosis, trauma

Question 42

Name some causes of AVP resistance

Answer 42

D: drugs - lithium I: inherited - wolfram's syndrome M: metabolic - low potassium high calcium C: chronic renal disease

Question 43

Signs and symptoms of diabetes insipidus?

Answer 43

Large volumes of dilute urine (>3 litres in 24 hours and a urine osmolality of <300 mOsm/kg) Nocturia Excessive thirst In children, additional symptoms may include: Failure to thrive Enuresis

Question 44

Investigation for diabetes insipidus?

Answer 44

Urea and electrolytes (sodium may be raised) Blood glucose (to rule out diabetes mellitus) Urine dip Paired serum and urine osmolality measurements Arginine vasopressin disorder is present when the serum osmolality is raised (>295 mOsm/kg) with inappropriately dilute urine (urine osmolality < 300 mOsm/kg).

Question 45

What to do if diagnosis of diabetes insipidus remains uncertain?

Answer 45

a water deprivation test This should only be done if there is evidence of hypovolaemia or hypernatraemia The patient is deprived of fluids while monitored for urine osmolality and body weight changes In AVP-D, urine osmolality increases with ADH administration In AVP-R, urine osmolality remains low/unchanged despite ADH administration

Question 46

What does the water deprivation test also distinguish arginine vasopressin deficiency from?

Answer 46

primary polydipsia which is a condition characterised by similar symptoms of polydipsia and polyuria. The latter condition is usually due to a psychological cause of excessive drinking. Upon testing, urine osmolality is normal both after fluid deprivation and after desmopressin is given.

Question 47

Management of arginine vasopressin deficiency?

Answer 47

AVP-D can be managed with desmopressin, a medication which mimics the action of endogenous ADH. Sodium levels should be monitored routinely due to the risk of hyponatraemia.

Question 48

Management of arginine vasopressin resistance?

Answer 48

AVP-R is managed by correcting any underlying metabolic abnormalities and discontinuing any offending drugs. High dose desmopressin has been used with variable results. Other potential treatments include using a thiazide diuretic (counter-intuitive, we know) and a non-steroidal anti-inflammatory drug to reduce urine volume.

Question 49

What is type 1 diabetes mellitus?

Answer 49

Type 1 diabetes mellitus (T1DM) is an autoimmune condition characterized by the destruction of the insulin-producing beta cells within the pancreas, leading to insulin deficiency.

Question 50

What is believed to cause type 1 diabetes?

Answer 50

combination of genetic predisposition and environmental triggers. Genes associated with the human leukocyte antigen (HLA) system contribute to susceptibility. Environmental triggers, such as viral infections, are proposed but not definitively identified.

Question 51

What are the signs and symptoms of type 1 diabetes mellitus?

Answer 51

Polyuria Polydipsia Weight loss - a distinguishing factor between T1DM and T2DM In severe cases, patients may present with diabetic ketoacidosis (DKA), characterised by hyperglycemia, metabolic acidosis, and ketonemia.

Question 52

What does diagnosis of type 1 diabetes involve?

Answer 52

Diagnosis involves first confirming diabetes and then identifying the underlying cause as type 1

Question 53

If a patient is symptomatic of type 1 diabetes name one other result needed?

Answer 53

Random blood glucose ≥ 11.1mmol/l or Fasting plasma glucose ≥ 7mmol/l 2-hour glucose tolerance ≥ 11.1mmol/l HbA1C ≥ 48mmol/mol (6.5%)

Question 54

If a patient is asymptomatic of type 1 diabetes name two results which are required from different days?

Answer 54

Autoantibody testing: Identification of specific antibodies (e.g. anti-GAD, ICA, IAA) contributes to confirming the autoimmune nature of T1DM. C-peptide levels: Evaluation of C-peptide production helps assess endogenous insulin secretion. Urine ketone testing: Presence of ketones may suggest concurrent DKA.

Question 55

Explain the insulin therapy management for type 1 diabetes?

Answer 55

Individualised insulin regimens are essential. Short-acting insulin is administered after meals and snacks, while long-acting insulin is typically given at night-time

Question 56

What are the target ranges for blood glucose and HbA1c levels?

Answer 56

Pre-meal blood glucose: 4-7 mmol/L (72-126 mg/dL) Bedtime blood glucose: 6-10 mmol/L (108-180 mg/dL) HbA1c: Less than 7% (53 mmol/mol) for most adults; individualised targets for children, elderly patients, and those at risk of hypoglycemia.

Question 57

Name some other management strategies for type 1 diabetes?

Answer 57

Lifestyle Interventions: Patients should receive guidance on nutrition, exercise, and alcohol consumption. Blood Glucose Monitoring: Regular self-monitoring of blood glucose (SMBG) is essential. Continuous Glucose Monitoring (CGM) Regular Follow-Up: Patients should receive ongoing care and education from diabetic specialist nurses and healthcare providers. Monitoring HbA1c levels at least every three months is crucial to assess long-term glycemic control. Psychosocial Support Comprehensive Care: T1DM management should address both short-term and long-term complications. Regular screening for microvascular complications (e.g. retinopathy, nephropathy, neuropathy) and macrovascular complications (e.g. cardiovascular disease) is essential.

Question 58

What is the hypoglycaemia management for type 1 diabetes?

Answer 58

Hypoglycemic episodes should be promptly treated with sugary drinks or snacks for conscious patients. For unconscious individuals, intramuscular glucagon or intravenous dextrose administration is necessary.

Question 59

Explain the blood pressure control for type 1 diabetes

Answer 59

Stricter blood pressure targets are recommended for individuals with T1DM, aiming for values of less than 135/85 mmHg, or less than 130/80 mmHg in the presence of end-organ damage. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are often preferred as first-line agents.

Question 60

What is the honeymoon period in type 1 diabetes?

Answer 60

Immediately after diagnosis, insulin requirements may be very low if the pancreas is still able to produce a significant amount of insulin. This is known as the 'honeymoon period'. It is important that children are closely monitored during this time. This is because insulin requirements can suddenly increase as the remaining beta cells are destroyed. Additionally, as the blood glucose may be normal in this period on very low insulin doses, parents may incorrectly think that the condition has gone away.

Question 61

What are the sick day rules with type 1 and 2 diabetes in terms of ACEIs, diuretics and NSAIDs

Answer 61

Stop treatment if there is a risk of dehydration to reduce the likelihood of acute kidney injury (AKI).

Question 62

What are the sick day rules in terms of insulin therapy for type 1 and 2 diabetes?

Answer 62

Do not stop insulin treatment; instead, consider adjusting the dose with guidance from the specialist diabetes team.

Question 63

What are the sicks rules in terms of blood glucose monitoring for type 1 and 2 diabetes mellitus?

Answer 63

Increase monitoring frequency to at least every 3–4 hours, including overnight. Adjust insulin doses based on results. Continue careful monitoring until blood glucose levels return to baseline. Seek urgent medical advice if blood glucose remains uncontrolled.

Question 64

What are the sick rules in terms of ketone monitoring for type 1 and 2 diabetes?

Answer 64

Check ketone levels regularly (at least every 3–4 hours, including overnight). Seek immediate medical advice if urine ketone level is greater than 2+ or blood ketone level is greater than 3 mmol/L.

Question 65

What are the sick rules for eating in terms of diabetes type 1 and 2?

Answer 65

Encourage maintaining regular meals and fluids, including carbohydrates, if appetite is reduced. Fluid and Carbohydrate Replacement: If unable to eat or vomiting, replace meals with carbohydrate-containing drinks (e.g. fruit juices, sugary drinks). Adjust fluid intake based on blood glucose levels (sugar-free fluids for high levels, sugary fluids for low levels).

Question 66

What are the associated medical conditions with type 1 diabetes mellitus?

Answer 66

Growth and pubertal development (delay in puberty and obesity) Associated illnesses: Thyroid disease (most associated; screening recommended) Coeliac disease

Question 67

What are the most common autoantibodies associated with type 1 diabetes mellitus?

Answer 67

Islet cell autoantibodies

Question 68

What is the first line treatment in type 1 diabetes?

Answer 68

basal bolus insulin

Question 69

What is the classical feature of chronic diabetic sensory neuropathy?

Answer 69

Sensory loss in a stocking distribution This is a length dependant predominantly sensory polyneuropathy. Therefore, it presents with glove and stocking sensory loss, usually beginning in the legs (i.e. where the length of sensory neurons is the longest)

Question 70

How does one work out a subcutaneous insulin regime including the basal bolus?

Answer 70

To do this one must work out the total 24 hour insulin requirement, then we must apply this to a basal bolus regime. The purpose of this is so simulate normal insulin secretion. There is always some insulin detectable in the blood but there are peaks corresponding to glycaemic load when meals are eaten. This is what we simulate. To work out the relative doses we consider there are 3 meals a day, so three-fifths of the total insulin for the 24 hour period should cover each of the meals in this cause 72 units. We then divide this by 3 to work out the number of short acting insulin units needed to be taken with each meal in this case 24 units. This works within 10-20 minutes and lasts for 3-5 hours. The remaining 2/5th is given as a long acting insulin like Lantus this has a much broader wave of activity lasting typically 18-24 hours

Question 71

What is the primary investigation for diagnosing type 1 diabetes mellitus?

Answer 71

Measuring serum glucose

Question 72

What does the glycemic index measure?

Answer 72

how quickly carbohydrate-containing foods affect blood sugars

Question 73

What is type 2 diabetes mellitus?

Answer 73

chronic metabolic condition characterized by inadequate insulin production from pancreatic beta cells, resulting in insulin resistance. This leads to an elevation in blood glucose levels, causing hyperglycaemia.

Question 74

What contributes to type 2 diabetes mellitus?

Answer 74

Poor dietary habits Lack of physical activity Obesity

Question 75

Signs and symptoms for type 2 diabetes mellitus?

Answer 75

Polyuria Polydipsia Unexplained weight loss Blurry vision Fatigue

Question 76

How does one investigate type 2 diabetes mellitus is symptomatic?

Answer 76

one of the following results is sufficient for diagnosis: Random blood glucose ≥ 11.1mmol/l Fasting plasma glucose ≥ 7mmol/l 2-hour glucose tolerance ≥ 11.1mmol/l HbA1C ≥ 48mmol/mol (6.5%)

Question 77

How do the investigations for type 2 diabetes change if asymptomatic?

Answer 77

If the patient is asymptomatic, two results are required from different days.

Question 78

What are the lifestyle modifications for type 2 diabetes?

Answer 78

Advice on diet, regular physical activity, and smoking cessation

Question 79

What are the pharmacological interventions for type 2 diabetes?

Answer 79

Initial drug treatment is usually metformin, with consideration of other agents like Pioglitazone, DPP‑4 inhibitors, sulphonylureas, or SGLT-2 inhibitors for those who cannot take metformin.

Question 80

If one mono therapy and HbA1c > 58 mol/mol what do we consider in type 2 diabetes mellitus?

Answer 80

consider dual therapy with metformin, pioglitazone, a DPP‑4 inhibitor or a sulphonylurea (such as gliclizide).

Question 81

If in type 2 diabetes mellitus dual therapy has not controlled drug glucose what do we then do?

Answer 81

triple therapy using the above medications can be considered. Otherwise, starting insulin may be necessary.

Question 82

How often do we monitor HbA1c in type 2 diabetes mellitus?

Answer 82

Measure HbA1c levels at 3-6 month intervals. If the patient is on insulin or is at risk of hypoglycaemia, self-monitoring of glucose at home is necessary.

Question 83

What type of basal insulin therapy do NICE recommend for type 2 diabetes?

Answer 83

basal insulin therapy with isophane (NPH) insulin as the first type to be used as it is most cost effective eg. Insulatard. Quick acting insulin analogues eg. Humalog, Novorapid, may be added in with meals if there is a big post meal glucose excursion.

Question 84

What are the name of long acting insulin analogues?

Answer 84

Levemir, Lantus, Insulin Degludec and Abasaglar (a biosimilar insulin).

Question 85

Why are mixed insulin combinations not used as much?

Answer 85

Mixed insulin combination which contain varying proportions of short and intermediate acting insulin such as Novomix 30 (30% short acting, 70% intermediate acting insulin) are more convenient because of fewer injections per day but may not be as successful.

Question 86

What are the blood pressure targets in diabetes? and what drugs do we use

Answer 86

Blood pressure control needs to be strict in diabetes because these patients are at higher risk of macro- and microvascular complications. NICE Hypertension Guidance [CG136] sets the same blood pressure targets as those who do not have diabetes, however in diabetics with HTN, ACE-inhibitors are first line as they are reno-protective

Question 87

What are the sick day rules for metformin when you have type 2 diabetes?

Answer 87

Stop treatment if there is a risk of dehydration to lower the risk of lactic acidosis.

Question 88

What are the sick day rules for sulfonylureas when you have type 2 diabetes?

Answer 88

Be cautious, as they may increase the risk of hypoglycemia, especially if dietary intake is reduced.

Question 89

What are the sick day rules for SGLT-2 inhibitors when you have type 2 diabetes?

Answer 89

Check for ketones and stop treatment if acutely unwell and/or at risk of dehydration due to the risk of euglycemic diabetic ketoacidosis (DKA).

Question 90

What are the sick day rules for GLP-1 receptor agonist when you have type 2 diabetes?

Answer 90

Stop treatment if there is a risk of dehydration to reduce the risk of AKI.

Question 91

What is diabetic ketoacidosis characterised by? (triad)

Answer 91

Hyperglycemia (blood glucose >11 mmol/L) Ketosis (blood ketones >3 mmol/L or urinary ketones ++ or higher) Acidosis (pH <7.3 or bicarbonate <15 mmol/L) Note: patients on SGLT-2 inhibitors may present with euglycemic DKA (where glucose is normal)

Question 92

How is diabetic ketoacidosis caused?

Answer 92

DKA occurs due to insulin deficiency (absolute or relative) leading to hyperglycaemia Ketones, including acetone, 3-beta-hydroxybutyrate, and acetoacetate, are produced from ketogenesis, whereby fatty acids are metabolised as an alternative energy source These ketones are responsible for the acidosis seen Hyperglycaemia causes an osmotic diuresis that contributes to severe dehydration as well as electrolyte imbalance Vomiting and decreased fluid intake secondary to altered mental state also exacerbate dehydration

Question 93

Name some common triggers for diabetic ketoacidosis?

Answer 93

Infections Dehydration and fasting Missing doses of insulin Medications e.g. steroid treatment or diuretics Surgery Stroke or myocardial infarction Alcohol excess or illicit drug use Pancreatitis

Question 94

Name one sign which was cause diabetic ketoacidosis to be classified as severe?

Answer 94

Blood ketones > 6mmol/L Bicarbonate < 5mmol/L Blood pH < 7 Anion gap above 16 Hypokalaemia on admission GCS less than 12 Oxygen saturations < 92% in air Systolic BP < 90mmHg Brady or tachycardia (heart rate < 60 or > 100bpm)

Question 95

Name some signs and symptoms of diabetic ketoacidosis?

Answer 95

Symptoms: Nausea and vomiting Abdominal pain Polyuria Polydipsia Weakness Signs: Dry mucous membranes Hypotension Tachycardia Altered mental state (drowsiness, confusion, coma) Kussmaul's breathing (deep, sighing breathing to compensate for metabolic acidosis by blowing off carbon dioxide) Fruit-like smelling breath (due to ketosis)

Question 96

What bedside investigations do we do for diabetic ketoacidosis?

Answer 96

Capillary blood glucose Blood or urinary ketones Urine dip +/- MSU (looking for evidence of a urinary tract infection which may precipitate DKA) ECG (for ischaemic changes which may precipitate DKA, or changes secondary to electrolyte imbalance e.g. hypokalaemia)

Question 97

What blood tests do we do for diabetic ketoacidosis?

Answer 97

Venous blood gas (for acid-base balance) Urea and electrolytes (for electrolyte imbalance and AKI) Full blood count and CRP (for infection markers) Blood cultures (if infection is suspected) HbA1c (to assess diabetic control over recent months)

Question 98

What imaging would we consider for diabetic ketoacidosis and why?

Answer 98

Consider chest X-ray as part of septic screen (if signs of infection as a trigger for DKA)

Question 99

What is the initial management for diabetic ketoacidosis?

Answer 99

Initial A to E assessment - Drowsy patients may require airway protection and an NG tube to prevent aspiration - Ensure adequate IV access - If hypotensive give up to 1L in fluid boluses then seek urgent senior input if not resolved - Consider urinary catheterisation and monitor fluid balance

Question 100

What is the second step in the management of diabetic ketoacidosis?

Answer 100

IV fluid replacement with normal saline - A regimen of large volumes of IV fluid replacement given relatively quickly initially then over longer durations should be followed - Slower infusion rates should be considered in young adults, the elderly, those with heart or kidney failure or other serious comorbidities - An example in a healthy adult would be 1L over 1 hour, then 2x 1L over 2 hours, then 2x 1L over 4 hours, then 1L over 6 hours - Potassium replacement should be added after the first bag, depending on serum potassium levels

Question 101

What is the third step of management of diabetic ketoacidosis?

Answer 101

After IV fluids have started, a fixed rate insulin infusion should be set up and withheld any existing insulin injections the patine is due. This is provided as an infusion of 50 units of Actrapid in 50ml of 0.9% NaCl, at a rate of 0.1 units/kg/hour Continue long-acting insulin if the patient is already on this Investigation and management of any underlying triggers (e.g. septic screen and start antibiotics if evidence of infection)

Question 102

What should one consider giving to a diabetic ketoacidosis patient due to dehydration?

Answer 102

Ensure VTE prophylaxis with low molecular weight heparin is prescribed as patients are at high risk of developing clots

Question 103

What is the ongoing emergency management for diabetic ketoacidosis?

Answer 103

Patients should be closely monitored with hourly blood glucose and ketones - The aim is for ketones to fall by > 0.5mmol/L/hour - Blood glucose should fall by 3 mmol/L/hour - If these targets are not met, the rate of insulin infusion should be continued

Question 103

At what value of blood glucose in diabetic ketoacidosis would one start a 10% glucose infusion?

Answer 103

14

Question 104

When is diabetic ketoacidosis resolved?

Answer 104

once ketones are less than 0.6 mmol/L and pH is over 7.3 - If at this point they are able to eat and drink, a subcutaneous regimen of insulin should be started (usually with the input of a specialist diabetes team) - The insulin infusion should be stopped half an hour after the first dose of subcutaneous short acting insulin has been given

Question 105

What is a rare but severe complication of diabetic ketoacidosis? Symptoms and signs include: headache, decline in consciousness, rise in blood pressure, drop in pulse and seizures

Answer 105

cerebral oedema

Question 106

The first step of diabetic ketoacidosis management if the patient has a systolic blood pressure under 90mmHg

Answer 106

a 500ml bolus of IV 0.9% saline should be given and repeated if necessary - if not, then a rate that replaces deficit and provides maintenance would be adequate.

Question 107

What is the criteria for mild diabetic ketoacidosis?

Answer 107

hyperglycaemia/ diagnosis of diabetes, blood ketones >3 mmol/L, urine ketones >2 + as well as a pH of 7.2-7.29, and/ or a bicarbonate of < 15 mmol/L

Question 108

For children with diabetic ketoacidosis and a systolic BP below 90 what is the first step?

Answer 108

an initial intravenous bolus of 10 ml/kg 0.9% sodium chloride over 30 minutes

Question 109

what anion gap indicates a severe DKA

Answer 109

>16

Question 110

What to do with short and long acting insulin when giving fixed rate intravenous insulin infusion due to diabetic ketoacidosis?

Answer 110

Subcutaneous short or rapid acting insulin should not be given alongside an intravenous insulin infusion. However, BSPED guidelines suggest that long acting insulin can be given alongside FRIII.

Question 111

What is the first investigation we do for diabetic ketoacidosis?

Answer 111

Capillary blood gas and capillary blood ketones

Question 112

What is diabetic retinopathy?

Answer 112

sight-threatening complication of diabetes mellitus, resulting from poor glycaemic control. This leads to vascular occlusion and leakage from the capillaries that supply the retina, causing retinal ischaemia, neovascularisation and, if left untreated, potential loss of sight.

Question 113

What are the two stages of diabetic retinopathy?

Answer 113

non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)

Question 114

What are the three severity levels of non proliferative diabetic retinopathy?

Answer 114

Mild NPDR: Microaneurysms and dot hemorrhages on fundoscopy. Moderate NPDR: Microaneurysms, dot and blot hemorrhages, cotton-wool spots, and hard exudates. Severe NPDR: Beaded veins, intraretinal microvascular abnormalities (IRMA), and extensive retinal hemorrhages.

Question 115

What does proliferative diabetic retinopathy include?

Answer 115

involves neovascularisation and fibrous proliferation on the retina or vitreous, posing a higher risk of severe vision loss.

Question 116

What is the pathophysiology of diabetic retinopathy?

Answer 116

Chronic hyperglycaemia in diabetes mellitus causes structural changes to the retinal capillaries, including thickening of the basement membrane and loss of pericytes. This results in capillary occlusion and leakage, leading to retinal ischaemia and formation of new, fragile vessels.

Question 117

What are the signs and symptoms of diabetic retinopathy?

Answer 117

Early stages of diabetic retinopathy may be asymptomatic. As the disease progresses, symptoms can include: Floaters or dark spots in the vision Blurred or distorted vision Difficulty seeing at night Sudden loss of vision

Question 118

What are the investigations used for diabetic retinopathy?

Answer 118

Fundoscopy Optical coherence tomography Fluorescein angiography

Question 119

What do you see on fundoscopy for the different severities of diabetic retinopathy?

Answer 119

Signs of milder disease include: Microaneurysms Hard exudates Blot haemorrhages Severe disease presents with: Engorged tortuous veins Cotton wool spots Large blot haemorrhages. In proliferative diabetic retinopathy (PDR), neovascularisation can be observed on the retina or optic disc.

Question 120

What can optical coherence tomography be used to detect?

Answer 120

detect macular oedema

Question 121

What is fluorescein angiography used to see in diabetic retinopathy?

Answer 121

Used in advanced cases to evaluate the extent of neovascularisation and guide treatment.

Question 122

What management strategies are there for diabetic retinopathy?

Answer 122

Optimisation of blood glucose control Laser photocoagulation Intravitreal injections of anti-vascular endothelial growth factor Vitrectomy surgery

Question 123

What is laser photocoagulation used for?

Answer 123

proliferative diabetic retinopathy and clinically significant macular oedema.

Question 124

What are anti-VEGF injections used for

Answer 124

diabetic macular oedema.

Question 125

When would one do vitrectomy surgery?

Answer 125

for advanced cases with complications such as vitreous haemorrhage or retinal detachment.

Question 126

What are the complications of diabetic retinopathy?

Answer 126

Vitreous Hemorrhage: Can cause sudden vision loss. Tractional Retinal Detachment: May lead to blindness. Macular Oedema: Causes central vision loss. Neovascular Glaucoma: Can result in severe pain and vision loss. Blindness: The ultimate complication in untreated or advanced cases.

Question 127

For non-proliferative diabetic retinopathy what is the primary management?

Answer 127

Maintaining strict glycemic control

Question 128

What retinal features are reason for immediate referral to an ophthalmologist?

Answer 128

proliferative retinopathy - R3 (new blood vessels), vitreous haemorrhage, advanced retinopathy with retinal detachments

Question 129

What are the gastrointestinal complications of T2DM:

Answer 129

Gastroparesis - a result of poor glycaemic control leading to nerve damage of the autonomic nervous system. Characterized by delayed gastric emptying, early satiety, abnormal stomach wall movements, and morning nausea.

Question 130

What are the neurological complications of T2DM

Answer 130

Autonomic Neuropathy - may lead to postural hypotension and associated symptoms like dizziness, falls, and loss of consciousness.

Question 131

What are the vascular complications of T2DM:

Answer 131

Peripheral Arterial Disease (PAD) - patients present with foot discolouration, gangrene, intermittent claudication, rest pain, night pain and absent peripheral pulses (confirmed on doppler).

Question 132

What are the foot complications of type 2 diabetes mellitus?

Answer 132

Diabetic Foot Infections - patients with vascular and neuropathic complications are at high risk for diabetic foot ulceration and subsequent infection.

Question 133

What are the sexual dysfunction complications of T2DM

Answer 133

caused by a combination of factors including poor glycaemic control, neuropathy, microvascular complications, obesity, hypertension, depression, medication side effects, etc.

Question 134

What are the cardiac complications of T2DM?

Answer 134

diabetes significantly increases the risk of cardiovascular disease, contributing to major morbidity and mortality.

Question 135

What is diabetic nephropathy characterised by?

Answer 135

proteinuria, progressive decline in glomerular filtration rate (GFR), and high blood pressure

Question 136

What is the pathogenesis of diabetic nephropathy?

Answer 136

hyperglycaemia-induced damage to the renal microvasculature leading to glomerulosclerosis and tubulointerstitial fibrosis. Over time, these changes result in decreased kidney function and eventually end-stage renal disease (ESRD). Histologically, it manifests as Kimmelstiel-Wilson nodules, diffuse glomerular basement membrane thickening, mesangial expansion, and arteriolar hyalinosis.

Question 137

What screening should be done for diabetic nephropathy?

Answer 137

all patients should be screened annually using urinary albumin:creatinine ratio (ACR) should be an early morning specimen ACR > 2.5 = microalbuminuria

Question 138

What is diabetic peripheral neuropathy?

Answer 138

Diabetic peripheral neuropathy (DPN) represents a spectrum of peripheral nerve disorders stemming from diabetes

Question 139

What is the central driver behind diabetic neuropathy?

Answer 139

chronic hyperglycaemia - damage to peripheral nerves through various mechanisms, including accumulation of advanced glycation end products, oxidative stress, and inflammatory pathways.

Question 140

What are the features of distal symmetrical sensory neuropathy?

Answer 140

Most common form of DPN. Resulting from loss of large sensory fibres. Presents with sensory loss in a 'glove and stocking' distribution, typically affecting touch, vibration and proprioception.

Question 141

What are the features of small-fibre predominant neuropathy?

Answer 141

Due to the loss of small sensory fibres. Manifests as deficits in pain and temperature sensation in a 'glove and stocking' distribution, often accompanied by episodes of burning pain.

Question 142

What are the features of diabetic amyotrophy?

Answer 142

Originates from inflammation of the lumbosacral plexus or cervical plexus. Characterised by severe pain around the thighs and hips, along with proximal weakness.

Question 143

What are the features of mono neuritis multiplex?

Answer 143

Typically painful. Defined as neuropathies involving two or more distinct peripheral nerves.

Question 144

What are the features of autonomic neuropathy?

Answer 144

Presents with postural hypotension, gastroparesis, constipation, urinary retention, arrhythmias, and erectile dysfunction.

Question 145

Name the three investigations?

Answer 145

Neurological examination: To assess the extent of sensory and motor deficits. Nerve conduction studies: To evaluate the nature and extent of neuropathy. Blood tests: Including glucose levels, HbA1c, B12 levels, thyroid function tests, and liver function tests, to identify potential differential diagnoses or contributory conditions.

Question 146

What are the complications of diabetic neuropathy?

Answer 146

If uncontrolled, DPN can lead to serious complications such as foot ulcers due to loss of sensation, and autonomic neuropathy can lead to various cardiac, gastrointestinal, and genitourinary disturbances.

Question 147

What is the management of diabetic neuropathy?

Answer 147

Management strategies for DPN primarily revolve around the control of blood glucose levels to slow the progression of the disease. Symptomatic management may include pain control with medications such as amitriptyline, duloxetine, gabapentin or pregabalin, as well as management of complications (e.g., treatment of foot ulcers, management of autonomic disturbances). tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain

Question 148

What is Charcot arthropathy?

Answer 148

chronic, progressive condition characterised by destructive changes in the bones and joints of patients with neuropathy, most commonly from diabetes

Question 149

How does Charcot arthropathy present?

Answer 149

'6Ds': Destruction, Deformity, Degeneration, Dense bones, Debris, and Dislocation Classically affect the tarsometatarsal joints

Question 150

What are the investigations for Charcot arthropathy?

Answer 150

X-rays are usually the first-line imaging study. They can demonstrate bone destruction, debris, sclerosis (dense bones), and dislocation. MRI can provide more detailed imaging, particularly in early disease or when osteomyelitis is suspected. Bone scans may be used in complex cases or when other imaging is inconclusive

Question 151

What is the conservative management for Charcot arthropathy?

Answer 151

Prolonged off-loading, often involving special footwear or plaster casts, to allow healing and prevent further damage. Use of orthotics for long-term management and prevention of recurrences.

Question 152

What is the medication management for Charcot arthropathy?

Answer 152

Bisphosphonates can help slow down the process of bone destruction. Neuropathic pain agents, such as gabapentin or pregabalin, for pain management. Topical anesthetics can also be used to manage pain.

Question 153

What is the surgical management for Charcot arthropathy?

Answer 153

Resection of bony prominences to prevent ulcers or improve fitting of footwear. Correction of severe deformities, usually after the acute phase has settled. Amputation may be required in severe cases or when there is a concurrent uncontrolled infection.

Question 154

What is hypercalcaemia of malignancy?

Answer 154

a paraneoplastic syndrome often associated with advanced stages of cancer, particularly breast cancer, lung cancer and multiple myeloma.

Question 155

What hormone is increased in hypercalcaemia of malignancy?

Answer 155

parathyroid hormone-related protein (PTHrP)

Question 156

What does increased levels of PTHrP cause?

Answer 156

increased bone resorption and renal tubular calcium reabsorption

Question 157

When else might hypercalcaemia of malignancy arise?

Answer 157

may also arise due to local osteolytic activity or ectopic production of calcitriol in some lymphomas

Question 158

What are the signs and symptoms of hypercalcaemia of malignancy?

Answer 158

The clinical manifestations typically include polyuria, polydipsia, constipation, nausea and neuropsychiatric symptoms such as confusion and lethargy. Severe cases can lead to coma or cardiac arrhythmias ‘Stones, abdominal moans and psychic groans’ Reduced neuronal excitability – atonal muscles

Question 159

How does one diagnose hypercalcaemia of malignancy?

Answer 159

Diagnosis is confirmed by elevated serum calcium levels in combination with appropriate clinical context Also check: Parathyroid hormone levels, Bone scan/PET scan (malignancy), ECG: shortened QTc may be present and bone profile

Question 160

How does one treat hypercalcaemia of malignancy?

Answer 160

Treatment involves hydration (IV fluids with crystalloid to help improve calcium excretion), administration of bisphosphonates or denosumab to inhibit osteoclast activity (e.g. IV Zoledronate/Pamidronate - Calcitonin is second line) and use of corticosteroids in certain contexts. In refractory cases or when rapid reduction of serum calcium is needed, haemodialysis may be indicated.

Question 161

What is the level for high calcium in the blood?

Answer 161

when calcium levels exceed 2.65mmol/L

Question 162

What is hyperlipidaemia?

Answer 162

Hyperlipidaemia is a medical condition characterised by abnormally high levels of lipids (or fats) in the blood, including cholesterol and triglycerides. High lipid levels can lead to the development of atherosclerosis and increase the risk of cardiovascular disease.

Question 163

Name a common primary (genetic) cause of hyperlipidaemia?

Answer 163

Familial hypercholesterolaemia If a patient has a total cholesterol level above 7.5 mmol/L, familial hypercholesterolaemia should be considered.

Question 164

Name some common secondary causes of hyperlipidaemia?

Answer 164

Secondary causes include diabetes mellitus, hypothyroidism, nephrotic syndrome, and certain drugs such as thiazide diuretics, beta blockers, and oestrogens.

Question 165

What are the signs and symptoms of hyperlipidaemia?

Answer 165

A family history of premature cardiac events Clinical signs such as exanthomata

Question 166

What investigations do we do for hyperlipidaemia?

Answer 166

Thorough history and examination Detailed family history of premature cardiac events Clinical signs such as exanthomata Cholesterol levels Fasting glucose levels Urea and electrolytes Thyroid function tests DNA testing

Question 167

What is the primary prevention for hyperlipidaemia?

Answer 167

a low dose statin (i.e atorvastatin 20mg) and is titrated based on treatment response

Question 168

What is the secondary prevention for hyperlipidaemia?

Answer 168

started on 80mg of a statin (often atorvastatin) in circumstances where they have had a cardiac/CV event as their first presentation of dyslipidaemia. A higher dose is required due to this being SECONDARY prevention of a cardiac/CV event

Question 169

When should one consider familial hypercholesterolaemia?

Answer 169

the total cholesterol level greater than 7.5 mmol/L and/or there is a personal or family history of premature coronary heart disease (an event before 60 years in an index person or first-degree relative [parents, siblings, children])

Question 170

Graphic showing choice of statin for hyperlipidaemia

Answer 170

Question 171

What tool do we use to measure the risk of people aged over 40 years at high risk of cardiovascular disease (CVD), defined as a 10-year risk of 10% or greater.

Answer 171

QRISK2 CVD risk assessment tool

Question 172

In what groups of people should QRISK2 not be used?

Answer 172

type 1 diabetics patients with an estimated glomerular filtration rate (eGFR) less than 60 ml/min and/or albuminuria patients with a history of familial hyperlipidaemia

Question 173

What cardioprotective diet is suggested for hyperlipidaemia?

Answer 173

total fat intake should be <= 30% of total energy intake saturated fats should be <= 7% of total energy intake intake of dietary cholesterol should be < 300 mg/day saturated fats should be replaced by monounsaturated and polyunsaturated fats where possible replace saturated and monounsaturated fat intake with olive oil, rapeseed oil or spreads based on these oils choose wholegrain varieties of starchy food reduce their intake of sugar and food products containing refined sugars including fructose eat at least 5 portions of fruit and vegetables per day eat at least 2 portions of fish per week, including a portion of oily fish eat at least 4 to 5 portions of unsalted nuts, seeds and legumes per week

Question 174

What physical activity is suggested for hyperlipidaemia?

Answer 174

Physical activity each week aim for at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic activity or a mix of moderate and vigorous aerobic activity do muscle-strengthening activities on 2 or more days a week that work all major muscle groups (legs, hips, back, abdomen, chest, shoulders and arms) in line with national guidance for the general population

Question 175

How does nephrotic syndrome lead to secondary hyperlipidaemia?

Answer 175

The loss of albumin in nephrotic syndrome reduces oncotic pressure and it is thought that this leads to hepatic lipoprotein synthesis and subsequent hyperlipidaemia. This diagnosis would be indicated in the presence of the nephrotic syndrome triad of proteinuria, hypoalbuminaemia and oedema in the absence of another cause of hyperlipidaemia

Question 176

Which lipid panel results is the single best predictor of a patient's risk for cardiovascular disease?

Answer 176

Total Cholesterol/HDL ratio The lower the ratio, the better

Question 177

Name a condition which would prevent you prescribing a statin for hypercholesterolaemia

Answer 177

Hypothyroidism Thyroid function should be tested before starting a statin. This is a reversible cause of hypercholesterolaemia. LFTs and a full lipid profile should also be taken. Measuring creatinine kinase before starting a statin is not recommended by NICE.

Question 178

In familial hypercholesterolaemia what lipoproteins are seen at very high levels?

Answer 178

LDLs LDLs are responsible for delivering cholesterol to cells. A number of mutations can give rise to familial hypercholesterolaemia, generally affecting either the instructions for producing the LDL receptor or the instructions for its function. Hypercholesterolaemia is the result of a loss of function mutation in the receptor responsible for removing LDLs from the bloodstream. High levels of LDL are associated with the process of atherosclerosis, which increases the risk of cardiovascular disease.

Question 179

What are the national guidelines for a hyperosmolar hyperglycaemic state?

Answer 179

Marked hyperglycaemia (30 mmol/L or more) without significant ketosis (<3 mmol/L) or acidosis (pH>7.3, bicarbonate >15 mmol/L) [though this condition may occur concomitantly with DKA] and, Osmolality 320 mosmol/kg or more: 2Na+ + glucose + urea

Question 180

What type of diabetes is hyperosmolar hyperglycaemic state seen in?

Answer 180

Type 2 diabetes - still have enough insulin to prevent the production of ketones

Question 181

What are the signs and symptoms of hyperosmolar hyperglycaemic state?

Answer 181

Profound dehydration with dry mucous membranes Excessive thirst (polydipsia) and urination (polyuria) Altered mental status, ranging from confusion to coma Neurological symptoms, such as seizures or focal deficits Hypotension and tachycardia

Question 182

What investigations do you do for hyperosmolar hyperglycaemic state?

Answer 182

Measurement of blood glucose levels Serum osmolality assessment Electrolyte panel (especially sodium and potassium levels) Urinalysis for ketones (typically absent in HHS) Evaluation of underlying causes (e.g infections)

Question 183

What is the initial management for hyperosmolar hyperglycaemic state?

Answer 183

Mainstay of treatment is fluid resucitation 0.9% NaCl should be used in the first instance Sodium levels are usually high on presentation due to dehydration; levels should not be lowered by more than 10mmol/L per 24 hours

Question 184

Why does sodium initially rise during treatment for hyperosmolar hyperglycaemic state?

Answer 184

Sodium levels initially rise during initial treatment as sugars improve; this is because the true hypernatraemia is usually higher than the initial hypernatraemia due to the effects of hyperglycaemia, causing a relative 'pseudo-hyponatraemia' This is not a reason to switch to hypotonic sodium chloride (0.45% sodium chloride) immediately, though this can be considered later

Question 185

In the hyperosmolar hyperglycaemic state at what rate should glucose levels fall during treatment?

Answer 185

should not fall by more than 5mmol/L per hour.

Question 186

When should insulin be considered for the treatment of hyperosmolar hyperglycaemic state?

Answer 186

Insulin (0.05 units/kg/hour) can be commenced if blood sugars stop falling with fluids alone, or if there is significant ketosis (urine ketones 2+ or 3β-hydroxy butyrate greater than 1 mmol/L)

Question 187

What are the complications of the hyperosmolar hyperglycaemic state?

Answer 187

Hypovolemic shock Cerebral oedema Thromboembolic events Acute kidney injury Cardiac arrhythmias Respiratory failure Long-term neurological sequelae

Question 188

What the diagnosis of the hyperosmolar hyperglycaemic state reliant on?

Answer 188

The diagnosis of Hyperosmolar Hyperglycaemic State (HHS) typically relies on confirming significantly elevated serum osmolality in the context of extreme hyperglycaemia without significant ketoacidosis

Question 189

What is the complication patients are most at risk of developing during the initial treatment phase for Hyperosmolar Hyperglycaemic state?

Answer 189

hypokalaemia During the treatment of HHS, insulin administration can cause a shift of potassium into cells, leading to hypokalaemia. Given this patient’s dehydration and the potential for insulin therapy, hypokalaemia is a significant and common complication that requires close monitoring and urgent correction.

Question 190

In hyperosmolar hyperglycaemia if a few hours after initial treatment of 0.9% NaCl at 1l/hr the patients remains confused and more drowsy what do we start next?

Answer 190

Contact ITU regarding mannitol infusion and hypertonic saline Management with isotonic saline is appropriate as such patients tend to be significantly dehydrated. However, if the osmolarity is reduced too quickly patients can develop cerebral oedema and this is probably causative of the subsequent reduced consciousness. Managing cerebral oedema is complex and requires ITU input. Mannitol is used as a diuretic to reduce the intracranial pressure and hypertonic saline often brings the osmolarity back up.

Question 191

What should one also consider prescribing for the hyperosmolar hyperglycaemic state during treatment?

Answer 191

Ensure venous thromboembolism prophylaxis is prescribed (patients are high risk due to immobility and dehydration)

Question 192

What is hyperparathyroidism?

Answer 192

Hyperparathyroidism (HPT) is a clinical condition resulting from the excessive secretion of parathyroid hormone (PTH)

Question 193

What is primary hyperparathyroidism?

Answer 193

Commonly caused by a parathyroid gland adenoma, hyperplasia of all four glands, or parathyroid carcinoma.

Question 194

What is secondary hyperparathyroidism?

Answer 194

Normal physiological response to low calcium - Typically due to vitamin D deficiency, loss of extracellular calcium, calcium malabsorption, abnormal parathyroid hormone activity, or inadequate calcium intake.

Question 195

What is tertiary hyperparathyroidism?

Answer 195

Occurs after prolonged secondary hyperparathyroidism due to conditions like chronic kidney disease

Question 196

What are the signs and symptoms of hyperparathyroidism?

Answer 196

Moans: Painful bones Stones: Renal stones Groans: Gastrointestinal symptoms (nausea, vomiting, constipation, indigestion) Psychiatric Moans: Neurological effects (lethargy, fatigue, memory loss, psychosis, depression) Hypercalcemia

Question 197

What are the investigations for hyperparathyroidism?

Answer 197

Question 198

Why is ALP high in hyperparathyroidism?

Answer 198

ALP is an enzyme that is produced by osteoblasts during bone formation. It plays an important role in bone mineralization (the process by which calcium and phosphate are deposited in the bone matrix). When bone turnover is high—such as in hyperparathyroidism—osteoblast activity increases in an attempt to repair and form new bone to compensate for the increased bone resorption caused by osteoclasts. As a result, more ALP is produced and released into the bloodstream

Question 199

Why is phosphate high in tertiary hyperparathyroidism?

Answer 199

Chronic kidney disease (CKD) is the primary cause of secondary hyperparathyroidism, which can progress to tertiary hyperparathyroidism. In CKD, the kidneys lose their ability to effectively filter and excrete phosphate, leading to phosphate retention. Even in tertiary hyperparathyroidism, the kidneys often remain impaired, and their capacity to excrete phosphate is reduced, leading to high phosphate levels.

Question 200

What is the management for primary hyperparathyroidism?

Answer 200

Definitive management is parathyroidectomy.

Question 201

What is the management for secondary hyperparathyroidism?

Answer 201

Address underlying causes; vitamin D supplementation and phosphate binders may be needed In patients with normal renal function * Give 25 hydroxy vitamin D * Patient converts this to 1,25 dihydroxy vitamin D via 1a hydroxylase * Ergocalciferol 25 hydroxy vitamin D * Cholecalciferol 25 hydroxy vitamin D * In patients with renal failure - inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations *Give Alfacalcidol - 1a hydroxycholecalciferol

Question 202

What is the management for tertiary hyperparathyroidism?

Answer 202

Managed with medication like Cinacalcet, a calcimimetic that mimics the action of calcium on tissues (Specifically, it increases the sensitivity of the calcium-sensing receptors (CaSRs) on the surface of parathyroid cells to circulating calcium), or via total or subtotal parathyroidectomy.

Question 203

In primary hyperparathyroidism what do we expect the serum 25-hydroxyvitamin D levels to be?

Answer 203

Decreased - its conversion is upregulated to raise serum calcium levels.

Question 204

How does parathyroid hormone act on the bone to increase serum calcium levels?

Answer 204

Binds to osteoblasts, which stimulate osteoclasts via paracrine signalling

Question 205

multiple endocrine neoplasis type 1 syndrome links which three conditions and therefore one should order a CT of the pancreas if in question?

Answer 205

pituitary tumours, parathyroid hyperplasia and pancreatic tumours

Question 206

What is the definition of hyperthermia?

Answer 206

Hyperthermia is defined as an abnormally high core body temperature (over 38 degrees Celsius) that is outside of the normal homeostatic control mechanisms.

Question 207

By what two mechanisms does hyperthermia happen?

Answer 207

It occurs due to inadequate heat loss and/or excess heat production.

Question 208

What are the consequences of hyperthermia?

Answer 208

Consequences of hyperthermia include direct toxicity to cells and a generalised inflammatory response, both of which lead to end-organ damage.

Question 209

What are the causes of hyperthermia?

Answer 209

Heatstroke Sepsis Endocrine disorders: Hyperthyroidism Phaeochromocytoma Adrenal crisis Drugs (illicit or prescribed medications): Malignant hyperthermia Neuroleptic malignant syndrome Serotonin syndrome Anticholinergic toxicity Sympathomimetic overdose (e.g. cocaine) Status epilepticus Central nervous system disorders: Encephalitis Intracranial haemorrhage Stroke

Question 210

What are the risk factors for hyperthermia?

Answer 210

Extremes of age (young children and the elderly) Obesity Physical exertion Impaired sweating Cognitive impairment Dehydration

Question 211

What are the symptoms of hyperthermia?

Answer 211

Thirst Fatigue Weakness and lethargy Dizziness Headache Nausea and vomiting Sweating (skin may be dry in severe hyperthermia or due to certain causes e.g. anticholinergic toxicity) Muscle cramps Confusion and agitation

Question 212

What are the signs of hyperthermia?

Answer 212

High body temperature Tachycardia Hypotension Tachypnoea Oliguria Impaired consciousness Slurred speech Seizures

Question 213

How is fever distinguished from hyperthermia?

Answer 213

fever refers to a high core body temperature due to an increase in the body's thermoregulatory set-point due to pyrogens.

Question 214

What may the bedside tests show in hyperthermia?

Answer 214

ECG may show sinus tachycardia, arrhythmias or non-specific ST changes Urinalysis may show myoglobinuria due to rhabdomyolysis Arterial blood gas may show a respiratory alkalosis due to tachypnoea, a metabolic acidosis due to a raised lactate or a respiratory acidosis in obtunded patients

Question 215

What may the blood tests show in hyperthermia?

Answer 215

FBC may show a raised haematocrit due to dehydration U&Es may show an AKI due to dehydration LFTs may show acute liver injury Glucose may be either low or high Clotting screen may show a coagulopathy Creatine kinase is raised in rhabdomyolysis

Question 216

What may imaging show in hyperthermia?

Answer 216

Chest X-ray may show non-cardiogenic pulmonary oedema or aspiration pneumonia (in patients with a reduced level of consciousness)

Question 217

What is management for hyperthermia?

Answer 217

Take an A to E approach; airway protection may be required with intubation and ventilation Intensive care admission may be required for patients with evidence of organ failure Fluid resuscitation with cooled IV fluids: avoid potassium containing fluids and aim to lower sodium gradually in hypernatraemic patients Catheterise the patient to measure urine output Stop any causative medications Avoid antipyretics Treat complications e.g. correcting electrolyte imbalance Investigate and treat any precipitating causes e.g. hyperthyroidism

Question 218

Name some initial cooling measures in hyperthermia?

Answer 218

Removing excess clothing Placing ice packs or spraying cool water on the body Wetting and fanning the skin Cold-water immersion

Question 219

Name some more invasive cooling measure in hyperthermia?

Answer 219

bladder or gastric lavage with cooled fluids or cooled haemodialysis or cardiopulmonary bypass

Question 220

What are the complications of hyperthermia?

Answer 220

Rhabdomyolysis Lactic acidosis - increased oxygen demand with increased metabolic state leads to anaerobic respiration Disseminated intravascular coagulation Acute kidney injury Arrhythmias Liver failure Non-cardiogenic pulmonary oedema Hyperkalaemia Hypocalcaemia Death

Question 221

What is the definition of hypothermia?

Answer 221

Hypothermia refers to a core body temperature below 35°C - it is a pathological state which has significant adverse effects on many body systems and can lead to death.

Question 222

What is primary hypothermia?

Answer 222

Primary hypothermia is environmental, occurring for example after immersion in cold water or prolonged exposure to cold weather conditions

Question 223

What is secondary hypothermia?

Answer 223

Secondary hypothermia occurs secondary to an insult or illness such as infection, alcohol excess, hypothyroidism or major trauma

Question 224

Name the different degrees of hypothermia with their temperatures

Answer 224

Mild - 32 to 35°C Moderate - 28 to 32°C Severe - 20 to 28°C Profound - < 20°C

Question 225

What are the symptoms of hypothermia?

Answer 225

Shivering Hunger Dizziness Chills Slurred speech Paradoxical undressing

Question 226

What are the signs of hypothermia?

Answer 226

Tachycardia initially; bradycardias may occur if severe with arrhythmias Tachypnoea; respiratory depression followed by apnoeas if severe Cool peripheries secondary to vasoconstriction Hypotension Ataxia Reduced level of consciousness Pupils may be fixed and dilated if severe

Question 227

Why would you do a urine toxicology screen in hypothermia?

Answer 227

if drug intoxication is suspected (e.g. patient found unconscious outside

Question 228

What would an arterial blood gas show in hypothermia?

Answer 228

may show an initial respiratory alkalosis, followed by respiratory acidosis as hypothermia worsens

Question 229

What would an ECG show in hypothermia?

Answer 229

Prolonged PR, QRS and QT intervals Osborn (or J) waves - positive deflections where the QRS complex joins the ST segment Bradyarrhythmias e.g. sinus bradycardia, atrial fibrillation with a slow ventricular response, slow junctional rhythms and AV block Shivering artefact Ventricular ectopics Cardiac arrest (ventricular tachycardia, ventricular fibrillation or asystole)

Question 230

What does a J wave look like in someone with hypothermia?

Answer 230

Question 231

What blood tests would you do in someone with hypothermia and why?

Answer 231

FBC and CRP for inflammatory markers U&Es looking for renal complications of hypothermia and electrolyte derangement Coagulation screen as hypothermia can cause a coagulopathy Creatinine kinase as hypothermia can cause muscle damage and rhabdomyolysis Amylase as pancreatitis can result from hypothermia Bone profile and magnesium so that any electrolyte disturbance can be corrected Blood cultures if sepsis is suspected as a driver of hypothermia

Question 232

What imaging would you do in someone with hypothermia?

Answer 232

Chest X-ray as aspiration pneumonia and pulmonary oedema may complicate hypothermia CT head may be indicated e.g. elderly patients who become hypothermic after a fall and long lie

Question 233

What is the conservative management of hypothermia?

Answer 233

Take an A to E approach; patients may require escalation to intensive care for intubation and ventilation e.g. if reduced levels of consciousness Rewarming Core temperature monitoring may be required in more severe cases, with either a rectal or (if intubated) an oesophageal probe Cardiac monitoring

Question 234

In the conservative management of hypothermia what are the different types of rewarming?

Answer 234

Passive rewarming - e.g. removing cold or wet clothes, cover with a blanket and cover head to reduce heat loss (useful in mild hypothermia) Active external rewarming - usually using forced air systems such as a Bair Hugger Active core rewarming - e.g. warmed intravenous fluids and warmed humidified oxygen

Question 235

What is the medical management of hypothermia?

Answer 235

Fluid resuscitation as patients are usually dehydrated - careful fluid balance monitoring is needed due to the risk of fluid overload Monitoring for and treating complications of hypothermia (see below) Antiarrhythmic medication is rarely required for cardiac complications, with rewarming being the mainstay of treatment Consider thiamine for malnourished or critically unwell patients, or those with suspected alcohol excess Investigating for and treating causes of hypothermia (e.g. infection) In the case of a cardiac arrest secondary to severe hypothermia, Resuscitation Council guidelines should be followed (e.g. defibrillation for VF arrests) and resuscitation should be continued at least until the patient has been rewarmed

Question 236

What is the invasive management of hypothermia?

Answer 236

In severely hypothermic patients with life-threatening complications who are not responding to other treatments, options include cavity lavage using warm fluids and extracorporeal blood rewarming (e.g. cardiopulmonary bypass)

Question 237

What are the complications of hypothermia?

Answer 237

Frostbite, which in severe cases may warrant amputation of non-viable tissues Arrhythmias Hypotension (especially on rewarming due to vasodilation) Aspiration pneumonia Pulmonary oedema Pancreatitis Acute tubular necrosis - due to peripheral vasoconstriction Cardiac arrest and death

Question 238

What is the definition of hypoglycaemia?

Answer 238

Hypoglycaemia is a metabolic condition characterized by an abnormally low blood glucose level, typically defined as less than 3.5 mmol/L.

Question 239

What drugs and who is most at risk of hypoglycaemia?

Answer 239

Hypoglycaemia is common in patients with diabetes, especially those on insulin or sulphonylurea therapies. The prevalence increases with the duration of diabetes and the intensity of glucose-lowering treatment.

Question 240

Name some causes of hypoglycaemia?

Answer 240

Drugs: Insulin, Sulphonylureas, GLP-1 analogues, DPP-4 inhibitors, Beta-blockers Alcohol Acute liver failure Sepsis Adrenal insufficiency - reduced cortisol means less gluconeogenesis and glycogenolysis Insulinoma Glycogen storage disease

Question 241

What are the adrenergic symptoms of hypoglycaemia and at what blood glucose concentration?

Answer 241

(Blood glucose concentrations <3.3 mmol/L): Trembling Sweating Palpitations Hunger Headache

Question 242

What are the neuroglycopenic symptoms of hypoglycaemia and at what blood glucose concentration?

Answer 242

Blood glucose concentrations below <2.8 mmol/L): Double vision Difficulty concentrating Slurred speech Confusion Coma

Question 243

What are the investigations for hypoglycaemia?

Answer 243

Review medication history for potential drug-induced causes. Measure serum insulin, C-peptide, and proinsulin levels to differentiate between exogenous and endogenous insulin sources. Perform a 72-hour fast test to demonstrate episodic hypoglycaemia. Conduct 8am cortisol and/or synACTHen testing for adrenal insufficiency. Consider abdominal imaging (CT/MRI/PET) to locate an insulinoma.

Question 244

What does a high serum c-peptide and high serum insulin show about the insulin source?

Answer 244

High insulin AND high C-peptide and proinsulin imply endogenous production e.g. insulinoma

Question 245

What does a low serum c-peptide and high serum insulin show about the insulin source?

Answer 245

High insulin AND low C-peptide and proinsulin suggest exogenous administration.

Question 246

What is the management for mild hypoglycaemia?

Answer 246

ABCDE approach Consume 15-20g of fast-acting carbohydrate (e.g., glucose tablets, non-diet soda, sweets, fruit juice). Avoid chocolate due to slower absorption. Follow up with slower-acting carbohydrates (e.g., toast).

Question 247

What is the management for severe hypoglycaemia?

Answer 247

ABCDE approach Administer 200ml 10% dextrose IV (alternatively dextrose 20% can be administered via a large vein). Administer 1mg glucagon IM if no IV access (Note: this won't work if alcohol ingestion is the cause due to its action blocking gluconeogenesis). Manage prolonged or repeated seizures.

Question 248

Which type of diabetic medication increases the chance of having hypoglycaemia the most?

Answer 248

sulphonylureas

Question 249

What is DVLA advice on severe hypoglycaemia?

Answer 249

DVLA guidance states that if a patient has more than one severe episode of hypoglycaemia whilst awake or one episode of severe hypoglycaemia whilst driving then they must stop driving immediately and inform the DVLA.

Question 250

What is the best diagnostic test for distinguishing an insulinoma?

Answer 250

72 hour fast In patients with an insulinoma, the following will be observed at the time of hypoglycemia (low blood glucose): Inappropriately high insulin levels: Insulin should normally drop when blood glucose is low, but in insulinoma, it remains elevated. Elevated C-peptide levels: High C-peptide indicates that the insulin being measured is coming from the pancreas, not from an exogenous source (e.g., injected insulin). High or normal proinsulin levels: This is another marker that supports insulinoma. Low beta-hydroxybutyrate: Normally, beta-hydroxybutyrate rises during fasting as the body switches to ketone production for energy. In insulinoma, this switch does not happen effectively due to excess insulin, which inhibits ketogenesis.

Question 251

What is Whipple's Triad?

Answer 251

Whipple's triad is a set of three clinical criteria used to diagnose hypoglycemia (low blood sugar) caused by excessive insulin production, most commonly in cases of insulinoma or other conditions leading to inappropriate insulin secretion. symptoms of hypoglycaemia, low plasma glucose levels, relief of symptoms after raising plasma glucose

Question 252

What is hypoparathyroidism?

Answer 252

Hypoparathyroidism is a medical condition characterized by abnormally low levels of parathyroid hormone (PTH), leading to disturbances in calcium and phosphorus metabolism. It can be primary (due to parathyroid gland dysfunction) or secondary (resulting from other medical conditions or treatments).

Question 253

What are the risk factors for hypoparathyroidism?

Answer 253

Neck surgery or radiation therapy involving the parathyroid glands. Autoimmune conditions, such as autoimmune polyendocrine syndrome. Genetic factors and familial forms of the condition

Question 254

What is the pathophysiology of hypoparathyroidism?

Answer 254

Hypoparathyroidism results from decreased PTH production or function, which disrupts calcium and phosphorus homeostasis. This leads to decreased calcium absorption from the intestines, reduced bone resorption, and impaired renal reabsorption of calcium.

Question 255

What are the signs and symptoms of hypoparathyroidism?

Answer 255

Hypocalcemia-related manifestations: muscle cramps, paresthesias, tetany, and seizures Neuropsychiatric symptoms: anxiety, depression, and cognitive impairment Ocular symptoms: cataracts and impaired night vision Dental abnormalities: dental enamel hypoplasia and tooth discoloration CATs go numb - trousseau and chvostek's sign

Question 256

What are the investigations for hypoparathyroidism?

Answer 256

Serum calcium (low) and phosphate levels (high) Measurement of PTH levels (low/inappropriately normal) Assessment of vitamin D status Urinary calcium may be low ECG to detect cardiac abnormalities due to hypocalcaemia

Question 257

What cardiac abnormalities do you get in hypocalcaemia?

Answer 257

prolonged QT

Question 258

What is the management for hypocalcaemia?

Answer 258

Calcium and Vitamin D Supplementation: Oral calcium and active vitamin D (calcitriol) to maintain low-normal calcium levels. This is to avoid renal complications Regular Monitoring: Ongoing monitoring of calcium levels and PTH Addressing Symptoms: Symptomatic management of neuromuscular and psychological symptoms Potential Surgery: Parathyroid gland autotransplantation or glandular tissue implantation in refractory cases In acute severe hypocalcaemia, treatement with IV calcium may be required

Question 259

What are the complications of hypocalcaemia?

Answer 259

Severe hypocalcemia leading to seizures and cardiac arrhythmias Kidney stones due to increased urinary calcium excretion Impaired renal function Cataracts Neurological and neuropsychiatric sequelae

Question 260

What is the management of severe hypocalcaemia in which there is neuromuscular irritability?

Answer 260

Intravenous calcium gluconate is indicated in cases of severe hypocalcaemia presenting with neuromuscular irritability, such as carpopedal spasms or positive Chvostek's sign. This treatment provides immediate relief and correction of acute hypocalcaemia.

Question 261

Explain psuedohypoparathyroidism

Answer 261

This patient has presented with features consistent with a low calcium level (tiredness, paraesthesia and muscle cramping). The image shows shortening of the metacarpals which, along with the blood results is consistent with pseudohypoparathyroidism. Pseudohypoparathyroidism is caused by a resistance to the parathyroid hormone (PTH).

Question 262

What is the definition of hypothyroidism?

Answer 262

Hypothyroidism is an endocrine disorder characterized by an insufficient production of thyroid hormones, which are crucial for metabolism and energy utilization in the body.

Question 263

What are the different categories that cause hypothyroidism?

Answer 263

Autoimmune causes: Hashimoto's thyroiditis, Atrophic thyroiditis and Autoimmune polyendocrine syndromes. Iatrogenic causes: Surgical removal of the thyroid, Radioablation, and Radiation therapy. Congenital causes: Thyroid aplasia and Pendred syndrome (defect in thyroxine synthesis). Iodine deficiency/excess related causes: Infiltrative disorders, Sarcoidosis and Haemochromatosis.

Question 264

What are the signs and symptoms of hypothyroidism?

Answer 264

Peripheral Features: Dry, thick skin, Brittle hair, Scanty secondary sexual hair. Queen Anne's sign - loss of outer 1/3 of eyebrows Cold intolerance, may result in wearing additional layers of clothing Head and Neck Features: Macroglossia, puffy face, goitre (depending on cause). Cardiac Features: bradycardia, cardiomegaly. Neurological Features: Carpal tunnel syndrome, slow relaxing reflexes, cerebellar ataxia, peripheral neuropathy, difficulty concentrating Joint pain Menorrhagia

Question 265

What are the investigations for hypothyroidism?

Answer 265

First line investigations would include thyroid function tests, which would show a low T3/4 and raised TSH. Antibody testing (Anti-TPO, Anti-thyroglobulin, Anti-TSH receptor) is used to identify autoimmune causes. Imaging and biopsy may be used to identify congenital and infiltrative causes. Iodine levels can be assessed to determine whether deficiency or excess is contributing to hypothyroidism.

Question 266

What is the management for hypothyroidism?

Answer 266

The primary therapeutic strategy for hypothyroidism revolves around hormone replacement therapy, with levothyroxine as the first-line treatment. Review the patient and recheck TSH levels every 3 months after initiation of LT4 therapy and adjust the dose according to symptoms and TFT results. Once the TSH level is stable (2 similar measurements within the reference range 3 months apart), check TSH annually

Question 267

When do you increase the dose of levothyroxine for hypothyroidism?

Answer 267

During pregnancy, the dose of levothyroxine is usually increased by 25-50mcg due to increased metabolic demands

Question 268

Which antibodies are most associated with hypothyroidism?

Answer 268

Anti-thyroid peroxidase antibodies - these are strongly associated with Hashimoto's thyroiditis

Question 269

What is the tinel sign and what does it show?

Answer 269

The healthcare provider taps or lightly percusses over a nerve, typically at a point where the nerve passes close to the surface of the skin (e.g., at the wrist for the median nerve in carpal tunnel syndrome). If the nerve is damaged or compressed, the patient may feel a tingling sensation or “pins and needles” radiating along the distribution of that nerve. Shows carpal tunnel syndrome

Question 270

What is the most common cause of hypothyroidism worldwide?

Answer 270

Iodine deficiency

Question 271

What medication can affect the absorption of levothyroxine?

Answer 271

Iron supplements such as Ferrous Sulphate can interfere with the absorption of Levothyroxine in individuals with hypothyroidism, leading to under-treatment. Calcium carbonate can also interfere with levothyroxine absorption

Question 272

Which condition does levothyroxine treatment increase the risk of?

Answer 272

osteoporosis

Question 273

What is the extreme manifestation of levothyroxine and what is the treatment?

Answer 273

myxoedema coma - typically presents with confusion and decreased consciousness, although can also present with complete unresponsiveness as seen here. Associated features include hypotension, bradycardia, hypothermia, periorbital oedema and sparse hair. It can also lead to heart failure and respiratory failure. Treatment should be in an intensive setting, with intravenous hydrocortisone and intravenous levothyroxine.

Question 274

What happens to T3,T4 and TSH during pregnancy?

Answer 274

Low free T3 and T4 levels in the second and third trimester of pregnancy is normal. Thyroid-binding globulin (TBG) levels increase and the total amount of T3 and T4 increase. However, due to the increased binding of T3 and T4 by TBG, free T3 and free T4 assays will be lower. TSH levels usually remain normal when this occurs.

Question 275

Define obesity

Answer 275

Obesity is defined as an excessive accumulation of body fat that impairs health. It is often assessed using body mass index (BMI), a measure that relates an individual's weight to their height

Question 276

What BMI is considered to be obese?

Answer 276

A BMI of 30 or higher is considered indicative of obesity.

Question 277

Distinguish metabolic syndrome from obesity?

Answer 277

Metabolic syndrome is a constellation of metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia. While obesity is a component of metabolic syndrome, individuals with metabolic syndrome may not meet the BMI criteria for obesity.

Question 278

How many adults and children in the UK are obese?

Answer 278

In the UK, nearly two-thirds of adults are overweight or obese, and approximately one in four adults is classified as obese. The prevalence of childhood obesity is also a growing concern, with around one in three children aged 2 to 15 being overweight or obese.

Question 279

What are the risk factors for obesity?

Answer 279

Genetics: A family history of obesity can increase the likelihood of developing the condition. Environmental Factors: An obesogenic environment characterized by easy access to high-calorie foods and sedentary lifestyles contributes to obesity. Socioeconomic Status: Lower income individuals may have limited access to healthy foods and recreational facilities. Psychological Factors: Emotional stress and psychological factors can lead to overeating. Medical Conditions: Some medical conditions, such as polycystic ovary syndrome (PCOS) and hypothyroidism, can contribute to weight gain.

Question 280

What are the signs and symptoms of obesity?

Answer 280

Increased Body Weight: As a primary indicator, obesity is defined by an elevated BMI. Central Obesity: Accumulation of excess fat around the abdomen, leading to an "apple-shaped" body. Joint Pain: Obesity can cause joint strain and musculoskeletal pain. Fatigue: Individuals with obesity may experience reduced energy levels. Breathlessness: Obesity can result in shortness of breath, especially during physical activity. Sleep Apnea: Obesity is a common cause of obstructive sleep apnea. Psychological Impact: Obesity may lead to depression, low self-esteem, and poor body image. Look out for GORD and barrels oesophagus with the subsequent development of oesophageal adenocarcinoma

Question 281

State all the BMI reference ranges and what classification they correlate to:

Answer 281

Question 282

What are the investigations for obesity?

Answer 282

BMI Measurement: Calculate the BMI using an individual's weight and height. Waist Circumference: Measure the waist circumference to assess central obesity. Blood Pressure: Monitor blood pressure levels regularly. Fasting Blood Glucose: Screen for impaired glucose tolerance or diabetes. Lipid Profile: Assess lipid levels, including cholesterol and triglycerides. Liver Function Tests: Evaluate liver health as obesity can lead to non-alcoholic fatty liver disease (NAFLD).

Question 283

State the conservative management for obesity:

Answer 283

Dietary Changes: Encourage a balanced, calorie-controlled diet with portion control. Physical Activity: Promote regular exercise and increased physical activity. Behavioral Interventions: Offer cognitive-behavioral therapy and motivational counseling. Lifestyle Modifications: Focus on improving sleep patterns and stress management.

Question 284

State the medical management for obesity:

Answer 284

Pharmacotherapy: Consider medications such as orlistat (a lipase inhibitor) or GLP-1 receptor agonists (e.g. liraglutide) for individuals who do not achieve weight loss goals through lifestyle changes alone. Specifically regarding liraglutide, treatment should be discontinued after 12 weeks if the person has not lost at least 5% of their initial body weight.

Question 285

State the surgical management for obesity:

Answer 285

Bariatric Surgery: Recommended for individuals with severe obesity (BMI ≥ 40) or those with a BMI ≥ 35 with significant obesity-related comorbidities - e.g poorly controlled diabetes Types of Surgery: Options include gastric bypass, sleeve gastrectomy, adjustable gastric banding, and biliopancreatic diversion.

Question 286

Define thyrotoxicosis

Answer 286

The syndrome resulting from the presence of excessive thyroid hormones in the body, not always due to thyroid gland overactivity.

Question 287

Name some primary causes of thyrotoxicosis ( originating from the thyroid itself)

Answer 287

Grave's disease: Resulting from autoimmune stimulation of the thyroid gland by TSH receptor auto-antibodies. Toxic adenoma: Adenoma that produces thyroid hormones. Toxic multinodular goitre: Multiple thyroid nodules that produce thyroid hormones, leading to goitre. Medications: Such as amiodarone. Thyroiditis: Inflammation of the thyroid gland, e.g., de Quervain's thyroiditis. Radiation exposure

Question 288

Name some secondary causes of thyrotoxicosis

Answer 288

Amiodarone Lithium TSH producing pituitary adenoma Choriocarcinoma (beta-hCG can activate TSH receptors) Gestational hyperthyroidism Pituitary resistance to thyroxine (i.e., failure of negative feedback) Struma ovarii (ectopic thyroid tissue in ovarian tumours)

Question 289

Signs and symptoms of hyperthyroidism

Answer 289

↑ Basal metabolic rate Heat intolerance Tachycardia and arrhythmias Weight loss Diarrhoea Sweaty skin Insomnia and sleep disturbances Restlessness and tremors Goitre (depending on cause)

Question 290

Specific signs and symptoms of grave's disease:

Answer 290

Exophthalmos/proptosis: Bulging eyes Lid lag: Upper eyelid remaining higher than normal during downward gaze Thyroid acropachy: Soft tissue swelling in extremities, nail clubbing, and periosteal new bone growth. Pretibial myxoedema: Mucopolysaccharide deposition in the dermis leading to oedema and skin thickening, predominantly in the shins.

Question 291

Name the investigations for hyperthyroidism

Answer 291

Thyroid Function Tests (TFTs): Elevated levels of free thyroxine (FT4) and free triiodothyronine (FT3) with suppressed thyroid-stimulating hormone (TSH) are indicative of hyperthyroidism. Blood Tests for Thyroid Antibodies: Detecting thyroid antibodies, such as thyroid-stimulating immunoglobulins (TSIAb) or thyrotropin receptor antibodies (TRAb), can help diagnose the underlying cause, particularly in Grave's disease. Ultrasound of the Thyroid: Ultrasonography is used to visualise the thyroid gland and assess its size, structure, and any nodules. Radioiodine Uptake Test: This test measures the thyroid's ability to take up radioactive iodine. It helps determine the cause of hyperthyroidism (e.g., diffuse uptake in Grave's disease or focal uptake in a toxic nodule).

Question 292

What is first line treatment for hyperthyroidism?

Answer 292

Antithyroid drugs (ATDs): First-line treatment for most patients. Carbimazole or propylthiouracil (PTU) is used, with carbimazole being preferred due to fewer side effects. Carbimazole can cause agranulocytosis, a severe and potentially life-threatening condition characterized by a significant decrease in white blood cells (neutrophils). Patients should be advised to seek immediate medical attention if they experience symptoms like fever, sore throat, mouth ulcers, or other signs of infection while taking Carbimazole. In pregnant women or those planning pregnancy, PTU is preferred in the first trimester.

Question 293

What can be prescribed for symptomatic relief in hyperthyroidism?

Answer 293

Beta-blockers: Propranolol can be used for symptomatic relief, especially for symptoms associated with increased sympathetic activity.

Question 294

What is considered definitive treatment for hyperthyroidism?

Answer 294

Considered for definitive treatment, especially for relapsed disease or when ATDs are not suitable. Not typically used in patients under age 40 due to potential increased cancer risk. Radioiodine is a radioactive form of iodine that selectively concentrates in the thyroid gland. It damages the thyroid tissue, reducing its hormone-producing ability. Post-radioiodine therapy, patients often become hypothyroid, and they may require lifelong thyroid hormone replacement therapy.

Question 295

What is considered when there is a large goitre with suspicion of malignancy?

Answer 295

Surgery (Thyroidectomy): An option for those with large goiters causing compression, suspicion of malignancy, or when other treatments are contraindicated or refused. Requires preparation with ATDs to achieve euthyroid state before surgery to minimize risks.

Question 296

What do you need to do in hyperthyroidism to detect early signs of remission and relapse?

Answer 296

Regular monitoring is crucial, including thyroid function tests, to ensure appropriate dosing of medications and to detect early signs of remission or relapse.

Question 297

Define a thyroid storm:

Answer 297

Thyroid storm is a rare but life-threatening medical emergency caused by untreated or inadequately managed hyperthyroidism. It is often precipitated by stressors like surgery, trauma, or infection.

Question 298

What are the key features of a thyroid storm?

Answer 298

Restlessness and agitation High-output heart failure Profound tachycardia Fever Delirium and altered mental status

Question 299

Outline the management for a thyroid storm:

Answer 299

Counteract Peripheral Action of Thyroid Hormone: Intravenous propranolol and digoxin help control heart rate and manage cardiac symptoms. Inhibit Thyroid Synthesis: Propylthiouracil (PTU) through a nasogastric tube and Lugol's iodine are administered to reduce thyroid hormone production. Corticosteroids: Steroids like prednisolone or hydrocortisone are given to inhibit peripheral conversion of T4 to the more active T3 form. Supportive Care: Supportive measures include intravenous fluids, cooling measures for fever, and addressing any precipitating factors (e.g. infection). Remember triad of propranolol, PTU and steroids

Question 300

Name some complications of hyperthyroidism:

Answer 300

Thyroid eye disease Atrial fibrillation High output heart failure Osteopenia/osteoporosis Upper Airway Obstruction Thyroid Cancer Thyroid storm

Question 301

What is Amiodarone-induced thyrotoxicosis

Answer 301

Amiodarone-induced thyrotoxicosis (AIT) is a recognized adverse effect of the anti-arrhythmic agent, amiodarone, which is rich in iodine, a component of thyroid hormone. The condition manifests in two types: AIT type 1, a direct toxic effect of amiodarone on the thyroid gland causing thyroiditis, and AIT type 2, where amiodarone triggers underlying thyroid autoimmunity.

Question 302

What are the two types of Amiodarone-induced thyrotoxicosis (AIT)?

Answer 302

Type 1 (AIT 1): Primarily observed in patients with underlying thyroid nodules, amiodarone increases thyroid hormone production due to its high iodine content. This is more common in iodine-deficient areas. Type 2 (AIT 2): This is triggered by amiodarone in patients with a normally functioning thyroid gland, leading to a destructive thyroiditis. This type is more common in iodine-sufficient areas.

Question 303

What are the investigations for amiodarone-induced thyrotoxicosis?

Answer 303

Regular thyroid function tests (TFTs) are crucial in monitoring patients on amiodarone. If thyrotoxicosis is suspected: The patient's antibody status should be checked to determine if there's underlying autoimmunity. A thyroid uptake scan and a colour flow Doppler ultrasound should be performed. AIT type 1 typically shows normal uptake on scans and increased vascularity on Doppler imaging AIT type 2 shows decreased thyroid uptake and reduced vascularity on Doppler imaging.

Question 304

What is the management for type 1 amiodarone induced thyrotoxicosis?

Answer 304

For AIT type 1, anti-thyroid drugs such as carbimazole are typically used.

Question 305

What is the management for type 2 amiodarone induced thyrotoxicosis?

Answer 305

For AIT type 2, anti-inflammatory drugs like corticosteroids are often the treatment of choice.

Question 306

What are thyroid nodules?

Answer 306

Thyroid nodules are discrete lesions within the thyroid gland, often palpable and detected incidentally on imaging studies

Question 307

Name some risk factors for thyroid nodules:

Answer 307

malignancy risk factors including age under 20 or over 60, male gender, history of head and neck irradiation, and family history of thyroid cancer.

Question 308

How clinically may people present with thyroid nodules?

Answer 308

Asymptomatic Mass: Most thyroid nodules are asymptomatic and are detected incidentally on physical examination or imaging studies performed for other reasons. They can vary in size but generally do not cause any discomfort unless they grow large enough to compress nearby structures. Symptoms related to compression: Large nodules can cause symptoms due to compression of surrounding structures such as dysphagia (difficulty swallowing), dyspnoea (shortness of breath) or stridor due to tracheal compression and hoarseness due to recurrent laryngeal nerve involvement. Symptoms related to hormone production: Although most thyroid nodules are non-functional, some may produce excess thyroid hormones leading to hyperthyroidism. Symptoms suggestive of this include weight loss despite increased appetite, heat intolerance, palpitations, tremor and nervousness. Pain: Acute pain in the region of the nodule could suggest haemorrhage into a cystic nodule. Chronic pain is unusual but can occur with malignant transformation. Cervical Lymphadenopathy: The presence of enlarged cervical lymph nodes may indicate metastatic disease from a malignant nodule.

Question 309

How do you determine if a thyroid nodule is functioning or not?

Answer 309

Thyroid function tests are essential to determine if the nodule is functioning (producing thyroid hormone) or non-functioning. Further evaluation may include ultrasound for size and characteristics assessment, fine needle aspiration cytology for histological diagnosis, and radionuclide scanning in certain cases.

Question 310

What does the anterior pituitary secrete?

Answer 310

growth hormone (GH), prolactin, gonadotropins (LH and FSH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH).

Question 311

What does the posterior pituitary secrete?

Answer 311

releases oxytocin and antidiuretic hormone (ADH)

Question 312

What are the most common type of pituitary tumours?

Answer 312

Pituitary adenomas

Question 313

What are the clinical features of pituitary tumours?

Answer 313

Headaches Visual Field Defects - bitemporal hemianopia

Question 314

What are the investigations for pituitary tumours?

Answer 314

Imaging: Diagnosis typically involves a brain MRI to visualize the tumor and its exact location. Screening Tests for visual field defects: Visual field testing is essential to identify any impairment caused by pressure on the optic nerves. Hormone Tests: If the tumor is suspected of being a functioning adenoma, hormone tests may be conducted to assess hormonal imbalances.

Question 315

What is the management for pituitary tumours?

Answer 315

Neurosurgery: Trans-sphenoidal surgery is the primary treatment for pituitary adenomas. It involves accessing the pituitary gland through the sphenoid sinus to remove the tumor. Radiotherapy: In cases where complete tumor removal is not possible or when the tumor recurs after surgery, radiotherapy may be used to manage the residual tumor. Medications: Some functioning adenomas can be managed with medications that target hormone overproduction.

Question 316

What is the most common hormone secreting pituitary adenoma?

Answer 316

prolactinoma

Question 317

What are the signs of a prolactinoma in a female?

Answer 317

Women: Oligomenorrhea or amenorrhea, galactorrhea (breast milk production outside of pregnancy or breastfeeding), infertility, and vaginal dryness.

Question 318

What are the signs of a prolactinoma in a male?

Answer 318

Men: Erectile dysfunction, reduced facial hair growth.

Question 319

What is the pharmacological management of a prolactinoma?

Answer 319

Dopamine Agonists (e.g. Cabergoline): These drugs reduce serum prolactin levels, alleviate galactorrhea, and restore gonadal function. Hormone Replacement Therapy: Used when fertility and galactorrhea are not primary concerns, typically involving estrogen replacement.

Question 320

When is surgery indicated for a prolactinoma?

Answer 320

Trans-sphenoidal resection is indicated when medical treatment fails to manage the tumor effectively

Question 321

What is hypopituitarism?

Answer 321

is characterised by the partial or complete deficiency of hormones produced by the pituitary gland, affecting functions such as growth, reproduction, thyroid regulation, adrenal function, and water balance.

Question 322

How does growth hormone deficiency present?

Answer 322

Manifests as central obesity, dry skin, reduced muscle strength, and decreased exercise tolerance.

Question 323

How does FSH and LH deficiency present in males?

Answer 323

Infertility, sexual dysfunction, and hypogonadism.

Question 324

How does FSH and LH deficiency present in females?

Answer 324

Oligomenorrhea or amenorrhea, infertility, sexual dysfunction, and breast atrophy

Question 325

How does TSH deficiency present

Answer 325

hypothyroidism

Question 326

How does ACTH deficiency present?

Answer 326

Leads to adrenal deficiency, with symptoms including fatigue, reduced muscle mass, anorexia, myalgia, and gastrointestinal upset.

Question 327

How does ADH deficiency present?

Answer 327

Causes excessive thirst and urination due to water imbalance.

Question 328

What is acromegaly?

Answer 328

A disorder caused by excess amounts of growth hormone with characteristic clinical features.

Question 329

With which syndrome is a pituitary adenoma associated with?

Answer 329

Multiple Endocrine Neoplasia Syndrome Type 1

Question 330

What is the pathophysiology of acromegaly?

Answer 330

Excess growth hormone (GH) results in excess production of insulin-like growth factor 1 (IGF-1) The IGF-1 receptor is distributed on a wide variety of tissues, and excess stimulation results in excess growth of these tissues Excess growth hormone also results in increased gluconeogenesis, lipolysis, and insulin resistance

Question 331

What is the difference between gigantism and acromegaly?

Answer 331

The key difference between gigantism and acromegaly is the age of onset: gigantism occurs before epiphyseal plate closure, leading to excessive linear growth, while acromegaly occurs after plate closure, causing enlargement of bones and soft tissues.

Question 332

What is the history someone may present with if they have acromegaly?

Answer 332

Patients usually report a change in their physical appearance, bringing in pictures of the past to enable comparison, including: Growing taller (acromegaly is also referred to as gigantism, if it occurs prior to closure of the epiphyses in childhood) Gloves/socks/shoes no longer fitting, as their hands/feet grow Jaw/face growing Tongue growing Increased space between teeth Organomegaly resulting symptoms depending on organ involved, such as a goitre, breast enlargement/gynecomastia/galactorrhea, or abdominal mass Headaches may be present due to a pituitary adenoma with features of raised intracranial pressure (i.e. worst first thing in the morning) There may be visual disturbance due to pressure at the optic chiasm by the pituitary adenoma They may report their voice is deeper due to sinus and vocal cord thickening Sweating may increase to sweat gland hyperplasia Erectile dysfunction may occur; the mechanism of this is poorly understood Mood disturbances and fatigue are common A change in bowel habit may be reported, due to an increased risk of bowel cancer as a result of excess proliferation Symptoms of diabetes, such as polyuria and polydipsia Darkening of the skin folds due to development of acanthosis nigricans Shortness of breath and ankle swelling (acromegaly is associated with heart failure, via complex, multifactorial mechanisms) Osteoarthritis, due to increased weight Carpal tunnel syndrome due to oedema of the subcutaneous tissues

Question 333

What is the first line investigation for acromegaly?

Answer 333

IGF1 - first line investigation If raised, you then go on to do a confirmatory test: failure of suppression of growth hormone during an oral glucose tolerance test Also check the rest of the anterior pituitary profile due to concomitant hormone release being common from the adenoma including 30% of cases releasing prolactin (TFT, LH, FSH, Prolactin, Oestrogen, Testosterone, Cortisol) and HBA1c

Question 334

What bedside tests would you do for acromegaly?

Answer 334

Fundoscopy (for optic atrophy) Perimetry (to assess visual field defect formally) Urine dip (glycosuria) ECG (LVH due to HTN)

Question 335

What radiology tests would you do for acromegaly?

Answer 335

CXR (cardiomegaly) MRI Pituitary (adenoma) If considering an ectopic source, can do CTCAP

Question 336

What special tests would you do for acromegaly?

Answer 336

Sleep studies if considering obstructive sleep apnoea, which can occur due to hypertrophy of the tissues in the upper airways Surveillance colonoscopy due to risk of colorectal cancer

Question 337

What is the primary treatment of choice for acromegaly?

Answer 337

surgery to remove the adenoma is the primary treatment of choice. Transphenoidal (first line)/transfrontal resection of the pituitary +/- radiotherapy

Question 338

What is the medical treatment for acromegaly?

Answer 338

Somatostatin analogues (octreotide, lanreoride), which suppress growth hormone release - first line medical treatment Growth hormone antagonists (pegvisomant) Dopamine agonists (bromocriptine, cabergoline)

Question 339

What follow ups do you do for acromegaly after initial treatment?

Answer 339

Monitor for bowel malignancy (colonoscopy) and cardiac failure (with echocardiography) - these often have to continue even after the post-operative period, since the sequelae can be long term Other monitoring may be required to detect recurrence, in the form of serial IGF-1s/growth hormone, prolactin (concomitant prolactin release in the adenoma occurs in 30% of cases), visual fields, ECGs, plus MRI scans of pituitary

Question 340

What are the complications of acromegaly?

Answer 340

Visual fields defect Hypopituitarism (post-operatively/due to pressure on the remaining pituitary tissue by the adenoma) Obstructive sleep apnoea Type two diabetes mellitus Arthritis Carpal tunnel syndrome Hyperhidrosis Osteoporosis Hypertension Increased risk of colonic polyps which can become malignant Ischaemic heart disease Cerebrovascular disease Congestive cardiac failure Increased prevalence of regurgitant valvular heart disease

Question 341

What type of medications can increase prolactin?

Answer 341

Risperidone and other pscyhiatric medications such as Haloperidol, tricyclic and SSRI anti-depressants are all recognised to cause disturbances in prolactin levels because of their effects on the neurotransmitter dopamine. Opiates and their derivatives can also have this effect.

Question 342

In women with elevated prolactin and secondary amenorrhea what does one first need to rule out?

Answer 342

pregnancy

Question 343

What is the best order for replacing pituitary hormones in hypopituitarism?

Answer 343

Cortisol, Thyroxine, Sex hormones and if necessary, growth hormone. Administering thyroxine to cortisol deficient patients can make them very unwell

Question 344

What is the gold standard investigation to diagnose hypopituitarism?

Answer 344

Insulin tolerance test An insulin tolerance test stimulates hypoglycaemia (to less than 2.2 mmol/l) which in turn aggravates a stress response. Given that we know what the normal dynamic response to such stress would be for both ACTH/cortisol and growth hormone this makes it the best test in this situation to ascertain the fucntioning of the pituitary-adrenal axis.

Question 345

What is pituitary apoplexy?

Answer 345

Pituitary apoplexy is a rare emergency and is defined as bleeding into the pituitary gland that occurs in patients who have pituitary tumours. Classic symptoms include sudden onset headache which is usually retro-orbital in nature and nausea or vomiting. A swollen pituitary gland can compress the contents of the cavernous sinus leading to ocular palsies. 80% of patients will have deficiency of hormones, including a lack of ACTH meaning that cortisol levels are low. This is suggested here by the low sodium. When apoplexy is suspected immediate hydrocortisone should be given with MRI performed to confirm the diagnosis