Endocrine and Metabolic Conditions Flashcards
Addison’s Disease Definition
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.
Difference between primary and secondary adrenal insufficiency
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.
Name causes of primary adrenal insufficiency
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)
Name causes of secondary adrenal insufficiency
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)
Signs and symptoms of Addison’s disease
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.
First line investigations for Addison’s disease:
U+E and serum cortisol, where you may find:
Hyponatraemia (low sodium)
Hyperkalaemia (high potassium)
Low serum cortisol
Glucose (typically low)
What would you expect a blood gas to show in someone with Addison’s disease?
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.
Name some other findings one would expect in Addison’s disease
ACTH: High in primary insufficiency, low or low-normal in secondary insufficiency
Renin (high in Addison’s disease)
Aldosterone (low in Addison’s disease)
What is the gold standard investigation
for Addison’s disease?
An ACTH (Short Synacthen) test is the gold standard investigation to confirm the diagnosis.
Name further investigations for addison’s disease:
Testing for adrenal auto-antibodies
Chest X-ray for tuberculosis
CT scan of the adrenal glands
MRI of the brain
Management of adrenal insufficiency:
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
Management of Addison’s crisis:
Aggressive fluid resuscitation
Administration of intravenous/IM (if no access) steroids STAT
Glucose administration if hypoglycaemia is present
What is the most likely cause of Addison’s disease?
autoimmune
What does severe meningococcal infection cause with the adrenal gland?
Waterhouse-Friderichsen syndrome
Thought that meningococcal septicaemia is associated with disseminated intravascular coagulation (DIC) which leads to adrenal haemorrhage.
If someone take steroids for a long time and then suddenly stops what might this cause? (think adrenals) and what do we give?
Secondary adrenal insufficiency - give IV Hydrocortisone
what part of the adrenal gland is mineralocorticoid produced?
Zona glomerulosa
What part of the adrenal gland produces glucocorticoids?
zona fasciculata
First step of management for an adrenal crisis?
immediate administration of intravenous or intramuscular hydrocortisone 100 mg in adults
What is Cushing’s syndrome?
endocrine disorder characterized by excess glucocorticoids
What is Cushing’s disease?
glucocorticoid excess caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumour
What are the two main category causes of Cushing’s syndrome?
ACTH-dependent disease
ACTH-independent
What causes ACTH-dependent cushings?
pituitary tumor (Cushing’s disease) or ectopic ACTH-producing tumors (e.g. lung carcinoids, thymic carcinoids, and others).
What causes ACTH-independent cushings?
C: cancer adrenal adenoma
A: adrenal nodular hyperplasia
R: Rare causes: McCune-Albright syndrome
Steroid use
What are the signs and symptoms of cushings?
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
What investigations do we do for cushings?
24-hour urinary free cortisol test
Low-dose Dexamethasone suppression test
Explain the different results of low/high dose dexamethasone suppression tests?
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)
What further tests can you do to localise the source of cushings syndrome?
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
What is the medical management of cushings syndrome?
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.
what is surgical management of cushings disease?
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.
When might radiotherapy be considered for Cushing’s syndrome?
May be considered for cases where hypercortisolaemia persists post-surgery, or in cases where surgery is not possible or declined.
What happens post successful treatment of Cushing’s syndrome?
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.
What are the three functions of cortisol? (3As)
mAke glucose in the liver
Antistress pathway
Anti-inflammatory pathway
Why does cushings cause osteoporosis?
decreases the activity and lifespan of osteoblasts and increases the activity of osteoclasts
What causes false positives of 24hr urinary free cortisol?
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.
What is the most common underlying cause of Cushing’s?
exogenous corticosteroid exposure
What are the main side effects of steroids
insomnia, mania, depression, psychosis
What is nelson’s syndrome?
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
define diabetes insipidus/ arginine vasopressin disorder
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).
Which part of the body causes AVP deficiency
cranial
Which part of the body causes AVP resistance?
kidneys
Name some causes of AVP deficiency
C: congenital defect in ADH gene
I: idiopathic
V: vascular - sickle cell disease
I: infection - meningoencephalitis
T: tumour, tuberculosis, trauma
Name some causes of AVP resistance
D: drugs - lithium
I: inherited - wolfram’s syndrome
M: metabolic - low potassium high calcium
C: chronic renal disease
Signs and symptoms of diabetes insipidus?
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
Investigation for diabetes insipidus?
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).
What to do if diagnosis of diabetes insipidus remains uncertain?
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
What does the water deprivation test also distinguish arginine vasopressin deficiency from?
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.
Management of arginine vasopressin deficiency?
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.
Management of arginine vasopressin resistance?
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.
What is type 1 diabetes mellitus?
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.
What is believed to cause type 1 diabetes?
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.
What are the signs and symptoms of type 1 diabetes mellitus?
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.
What does diagnosis of type 1 diabetes involve?
Diagnosis involves first confirming diabetes and then identifying the underlying cause as type 1
If a patient is symptomatic of type 1 diabetes name one other result needed?
Random blood glucose ≥ 11.1mmol/l or Fasting plasma glucose ≥ 7mmol/l
2-hour glucose tolerance ≥ 11.1mmol/l
HbA1C ≥ 48mmol/mol (6.5%)
If a patient is asymptomatic of type 1 diabetes name two results which are required from different days?
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.
Explain the insulin therapy management for type 1 diabetes?
Individualised insulin regimens are essential. Short-acting insulin is administered after meals and snacks, while long-acting insulin is typically given at night-time
What are the target ranges for blood glucose and HbA1c levels?
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.
Name some other management strategies for type 1 diabetes?
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.
What is the hypoglycaemia management for type 1 diabetes?
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.
Explain the blood pressure control for type 1 diabetes
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.
What is the honeymoon period in type 1 diabetes?
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.
What are the sick day rules with type 1 and 2 diabetes in terms of ACEIs, diuretics and NSAIDs
Stop treatment if there is a risk of dehydration to reduce the likelihood of acute kidney injury (AKI).
What are the sick day rules in terms of insulin therapy for type 1 and 2 diabetes?
Do not stop insulin treatment; instead, consider adjusting the dose with guidance from the specialist diabetes team.
What are the sicks rules in terms of blood glucose monitoring for type 1 and 2 diabetes mellitus?
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.
What are the sick rules in terms of ketone monitoring for type 1 and 2 diabetes?
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.
What are the sick rules for eating in terms of diabetes type 1 and 2?
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).
What are the associated medical conditions with type 1 diabetes mellitus?
Growth and pubertal development (delay in puberty and obesity)
Associated illnesses:
Thyroid disease (most associated; screening recommended)
Coeliac disease
What are the most common autoantibodies associated with type 1 diabetes mellitus?
Islet cell autoantibodies
What is the first line treatment in type 1 diabetes?
basal bolus insulin
What is the classical feature of chronic diabetic sensory neuropathy?
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)
How does one work out a subcutaneous insulin regime including the basal bolus?
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
What is the primary investigation for diagnosing type 1 diabetes mellitus?
Measuring serum glucose
What does the glycemic index measure?
how quickly carbohydrate-containing foods affect blood sugars
What is type 2 diabetes mellitus?
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.
What contributes to type 2 diabetes mellitus?
Poor dietary habits
Lack of physical activity
Obesity
Signs and symptoms for type 2 diabetes mellitus?
Polyuria
Polydipsia
Unexplained weight loss
Blurry vision
Fatigue
How does one investigate type 2 diabetes mellitus is symptomatic?
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%)
How do the investigations for type 2 diabetes change if asymptomatic?
If the patient is asymptomatic, two results are required from different days.
What are the lifestyle modifications for type 2 diabetes?
Advice on diet, regular physical activity, and smoking cessation
What are the pharmacological interventions for type 2 diabetes?
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.
If one mono therapy and HbA1c > 58 mol/mol what do we consider in type 2 diabetes mellitus?
consider dual therapy with metformin, pioglitazone, a DPP‑4 inhibitor or a sulphonylurea (such as gliclizide).
If in type 2 diabetes mellitus dual therapy has not controlled drug glucose what do we then do?
triple therapy using the above medications can be considered. Otherwise, starting insulin may be necessary.
How often do we monitor HbA1c in type 2 diabetes mellitus?
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.
What type of basal insulin therapy do NICE recommend for type 2 diabetes?
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.
What are the name of long acting insulin analogues?
Levemir, Lantus, Insulin Degludec and Abasaglar (a biosimilar insulin).
Why are mixed insulin combinations not used as much?
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.
What are the blood pressure targets in diabetes? and what drugs do we use
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
What are the sick day rules for metformin when you have type 2 diabetes?
Stop treatment if there is a risk of dehydration to lower the risk of lactic acidosis.
What are the sick day rules for sulfonylureas when you have type 2 diabetes?
Be cautious, as they may increase the risk of hypoglycemia, especially if dietary intake is reduced.
What are the sick day rules for SGLT-2 inhibitors when you have type 2 diabetes?
Check for ketones and stop treatment if acutely unwell and/or at risk of dehydration due to the risk of euglycemic diabetic ketoacidosis (DKA).
What are the sick day rules for GLP-1 receptor agonist when you have type 2 diabetes?
Stop treatment if there is a risk of dehydration to reduce the risk of AKI.
What is diabetic ketoacidosis characterised by? (triad)
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)
How is diabetic ketoacidosis caused?
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
Name some common triggers for diabetic ketoacidosis?
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
Name one sign which was cause diabetic ketoacidosis to be classified as severe?
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)
Name some signs and symptoms of diabetic ketoacidosis?
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)
What bedside investigations do we do for diabetic ketoacidosis?
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)
What blood tests do we do for diabetic ketoacidosis?
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)
What imaging would we consider for diabetic ketoacidosis and why?
Consider chest X-ray as part of septic screen (if signs of infection as a trigger for DKA)
What is the initial management for diabetic ketoacidosis?
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
What is the second step in the management of diabetic ketoacidosis?
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
What is the third step of management of diabetic ketoacidosis?
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)
What should one consider giving to a diabetic ketoacidosis patient due to dehydration?
Ensure VTE prophylaxis with low molecular weight heparin is prescribed as patients are at high risk of developing clots
What is the ongoing emergency management for diabetic ketoacidosis?
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
At what value of blood glucose in diabetic ketoacidosis would one start a 10% glucose infusion?
14
When is diabetic ketoacidosis resolved?
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
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
cerebral oedema
The first step of diabetic ketoacidosis management if the patient has a systolic blood pressure under 90mmHg
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.
What is the criteria for mild diabetic ketoacidosis?
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
For children with diabetic ketoacidosis and a systolic BP below 90 what is the first step?
an initial intravenous bolus of 10 ml/kg 0.9% sodium chloride over 30 minutes
what anion gap indicates a severe DKA
> 16
What to do with short and long acting insulin when giving fixed rate intravenous insulin infusion due to diabetic ketoacidosis?
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.
What is the first investigation we do for diabetic ketoacidosis?
Capillary blood gas and capillary blood ketones
What is diabetic retinopathy?
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.
What are the two stages of diabetic retinopathy?
non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)
What are the three severity levels of non proliferative diabetic retinopathy?
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.
What does proliferative diabetic retinopathy include?
involves neovascularisation and fibrous proliferation on the retina or vitreous, posing a higher risk of severe vision loss.
What is the pathophysiology of diabetic retinopathy?
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.
What are the signs and symptoms of diabetic retinopathy?
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
What are the investigations used for diabetic retinopathy?
Fundoscopy
Optical coherence tomography
Fluorescein angiography
What do you see on fundoscopy for the different severities of diabetic retinopathy?
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.
What can optical coherence tomography be used to detect?
detect macular oedema
What is fluorescein angiography used to see in diabetic retinopathy?
Used in advanced cases to evaluate the extent of neovascularisation and guide treatment.
What management strategies are there for diabetic retinopathy?
Optimisation of blood glucose control
Laser photocoagulation
Intravitreal injections of anti-vascular endothelial growth factor
Vitrectomy surgery
What is laser photocoagulation used for?
proliferative diabetic retinopathy and clinically significant macular oedema.
What are anti-VEGF injections used for
diabetic macular oedema.
When would one do vitrectomy surgery?
for advanced cases with complications such as vitreous haemorrhage or retinal detachment.
What are the complications of diabetic retinopathy?
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.
For non-proliferative diabetic retinopathy what is the primary management?
Maintaining strict glycemic control
What retinal features are reason for immediate referral to an ophthalmologist?
proliferative retinopathy - R3 (new blood vessels), vitreous haemorrhage, advanced retinopathy with retinal detachments
What are the gastrointestinal complications of T2DM:
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.
What are the neurological complications of T2DM
Autonomic Neuropathy - may lead to postural hypotension and associated symptoms like dizziness, falls, and loss of consciousness.
What are the vascular complications of T2DM:
Peripheral Arterial Disease (PAD) - patients present with foot discolouration, gangrene, intermittent claudication, rest pain, night pain and absent peripheral pulses (confirmed on doppler).
What are the foot complications of type 2 diabetes mellitus?
Diabetic Foot Infections - patients with vascular and neuropathic complications are at high risk for diabetic foot ulceration and subsequent infection.
What are the sexual dysfunction complications of T2DM
caused by a combination of factors including poor glycaemic control, neuropathy, microvascular complications, obesity, hypertension, depression, medication side effects, etc.
What are the cardiac complications of T2DM?
diabetes significantly increases the risk of cardiovascular disease, contributing to major morbidity and mortality.
What is diabetic nephropathy characterised by?
proteinuria, progressive decline in glomerular filtration rate (GFR), and high blood pressure
What is the pathogenesis of diabetic nephropathy?
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.
What screening should be done for diabetic nephropathy?
all patients should be screened annually using urinary albumin:creatinine ratio (ACR)
should be an early morning specimen
ACR > 2.5 = microalbuminuria
What is diabetic peripheral neuropathy?
Diabetic peripheral neuropathy (DPN) represents a spectrum of peripheral nerve disorders stemming from diabetes
What is the central driver behind diabetic neuropathy?
chronic hyperglycaemia - damage to peripheral nerves through various mechanisms, including accumulation of advanced glycation end products, oxidative stress, and inflammatory pathways.
What are the features of distal symmetrical sensory neuropathy?
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.
What are the features of small-fibre predominant neuropathy?
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.
What are the features of diabetic amyotrophy?
Originates from inflammation of the lumbosacral plexus or cervical plexus.
Characterised by severe pain around the thighs and hips, along with proximal weakness.
What are the features of mono neuritis multiplex?
Typically painful.
Defined as neuropathies involving two or more distinct peripheral nerves.
What are the features of autonomic neuropathy?
Presents with postural hypotension, gastroparesis, constipation, urinary retention, arrhythmias, and erectile dysfunction.
Name the three investigations?
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.
What are the complications of diabetic neuropathy?
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.
What is the management of diabetic neuropathy?
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
What is Charcot arthropathy?
chronic, progressive condition characterised by destructive changes in the bones and joints of patients with neuropathy, most commonly from diabetes
How does Charcot arthropathy present?
‘6Ds’: Destruction, Deformity, Degeneration, Dense bones, Debris, and Dislocation
Classically affect the tarsometatarsal joints
What are the investigations for Charcot arthropathy?
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
What is the conservative management for Charcot arthropathy?
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.
What is the medication management for Charcot arthropathy?
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.
What is the surgical management for Charcot arthropathy?
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.
What is hypercalcaemia of malignancy?
a paraneoplastic syndrome often associated with advanced stages of cancer, particularly breast cancer, lung cancer and multiple myeloma.
What hormone is increased in hypercalcaemia of malignancy?
parathyroid hormone-related protein (PTHrP)
What does increased levels of PTHrP cause?
increased bone resorption and renal tubular calcium reabsorption
When else might hypercalcaemia of malignancy arise?
may also arise due to local osteolytic activity or ectopic production of calcitriol in some lymphomas
What are the signs and symptoms of hypercalcaemia of malignancy?
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
How does one diagnose hypercalcaemia of malignancy?
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
How does one treat hypercalcaemia of malignancy?
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.
What is the level for high calcium in the blood?
when calcium levels exceed 2.65mmol/L
What is hyperlipidaemia?
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.
Name a common primary (genetic) cause of hyperlipidaemia?
Familial hypercholesterolaemia
If a patient has a total cholesterol level above 7.5 mmol/L, familial hypercholesterolaemia should be considered.
Name some common secondary causes of hyperlipidaemia?
Secondary causes include diabetes mellitus, hypothyroidism, nephrotic syndrome, and certain drugs such as thiazide diuretics, beta blockers, and oestrogens.
What are the signs and symptoms of hyperlipidaemia?
A family history of premature cardiac events
Clinical signs such as exanthomata
What investigations do we do for hyperlipidaemia?
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
What is the primary prevention for hyperlipidaemia?
a low dose statin (i.e atorvastatin 20mg) and is titrated based on treatment response
What is the secondary prevention for hyperlipidaemia?
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
When should one consider familial hypercholesterolaemia?
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])
Graphic showing choice of statin for hyperlipidaemia
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.
QRISK2 CVD risk assessment tool
In what groups of people should QRISK2 not be used?
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
What cardioprotective diet is suggested for hyperlipidaemia?
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
What physical activity is suggested for hyperlipidaemia?
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
How does nephrotic syndrome lead to secondary hyperlipidaemia?
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
Which lipid panel results is the single best predictor of a patient’s risk for cardiovascular disease?
Total Cholesterol/HDL ratio
The lower the ratio, the better
Name a condition which would prevent you prescribing a statin for hypercholesterolaemia
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.
In familial hypercholesterolaemia what lipoproteins are seen at very high levels?
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.
What are the national guidelines for a hyperosmolar hyperglycaemic state?
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
What type of diabetes is hyperosmolar hyperglycaemic state seen in?
Type 2 diabetes - still have enough insulin to prevent the production of ketones
What are the signs and symptoms of hyperosmolar hyperglycaemic state?
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
What investigations do you do for hyperosmolar hyperglycaemic state?
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)
What is the initial management for hyperosmolar hyperglycaemic state?
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
Why does sodium initially rise during treatment for hyperosmolar hyperglycaemic state?
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
In the hyperosmolar hyperglycaemic state at what rate should glucose levels fall during treatment?
should not fall by more than 5mmol/L per hour.
When should insulin be considered for the treatment of hyperosmolar hyperglycaemic state?
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)
What are the complications of the hyperosmolar hyperglycaemic state?
Hypovolemic shock
Cerebral oedema
Thromboembolic events
Acute kidney injury
Cardiac arrhythmias
Respiratory failure
Long-term neurological sequelae
What the diagnosis of the hyperosmolar hyperglycaemic state reliant on?
The diagnosis of Hyperosmolar Hyperglycaemic State (HHS) typically relies on confirming significantly elevated serum osmolality in the context of extreme hyperglycaemia without significant ketoacidosis
What is the complication patients are most at risk of developing during the initial treatment phase for Hyperosmolar Hyperglycaemic state?
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.
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?
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.
What should one also consider prescribing for the hyperosmolar hyperglycaemic state during treatment?
Ensure venous thromboembolism prophylaxis is prescribed (patients are high risk due to immobility and dehydration)
What is hyperparathyroidism?
Hyperparathyroidism (HPT) is a clinical condition resulting from the excessive secretion of parathyroid hormone (PTH)
What is primary hyperparathyroidism?
Commonly caused by a parathyroid gland adenoma, hyperplasia of all four glands, or parathyroid carcinoma.
What is secondary hyperparathyroidism?
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.
What is tertiary hyperparathyroidism?
Occurs after prolonged secondary hyperparathyroidism due to conditions like chronic kidney disease
What are the signs and symptoms of hyperparathyroidism?
Moans: Painful bones
Stones: Renal stones
Groans: Gastrointestinal symptoms (nausea, vomiting, constipation, indigestion)
Psychiatric Moans: Neurological effects (lethargy, fatigue, memory loss, psychosis, depression)
Hypercalcemia
What are the investigations for hyperparathyroidism?
Why is ALP high in hyperparathyroidism?
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
Why is phosphate high in tertiary hyperparathyroidism?
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.
What is the management for primary hyperparathyroidism?
Definitive management is parathyroidectomy.
What is the management for secondary hyperparathyroidism?
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
What is the management for tertiary hyperparathyroidism?
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.
In primary hyperparathyroidism what do we expect the serum 25-hydroxyvitamin D levels to be?
Decreased - its conversion is upregulated to raise serum calcium levels.
How does parathyroid hormone act on the bone to increase serum calcium levels?
Binds to osteoblasts, which stimulate osteoclasts via paracrine signalling
multiple endocrine neoplasis type 1 syndrome links which three conditions and therefore one should order a CT of the pancreas if in question?
pituitary tumours, parathyroid hyperplasia and pancreatic tumours
What is the definition of hyperthermia?
Hyperthermia is defined as an abnormally high core body temperature (over 38 degrees Celsius) that is outside of the normal homeostatic control mechanisms.
By what two mechanisms does hyperthermia happen?
It occurs due to inadequate heat loss and/or excess heat production.
What are the consequences of hyperthermia?
Consequences of hyperthermia include direct toxicity to cells and a generalised inflammatory response, both of which lead to end-organ damage.
What are the causes of hyperthermia?
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
What are the risk factors for hyperthermia?
Extremes of age (young children and the elderly)
Obesity
Physical exertion
Impaired sweating
Cognitive impairment
Dehydration
What are the symptoms of hyperthermia?
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
What are the signs of hyperthermia?
High body temperature
Tachycardia
Hypotension
Tachypnoea
Oliguria
Impaired consciousness
Slurred speech
Seizures
How is fever distinguished from hyperthermia?
fever refers to a high core body temperature due to an increase in the body’s thermoregulatory set-point due to pyrogens.
What may the bedside tests show in hyperthermia?
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
What may the blood tests show in hyperthermia?
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
What may imaging show in hyperthermia?
Chest X-ray may show non-cardiogenic pulmonary oedema or aspiration pneumonia (in patients with a reduced level of consciousness)
What is management for hyperthermia?
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
Name some initial cooling measures in hyperthermia?
Removing excess clothing
Placing ice packs or spraying cool water on the body
Wetting and fanning the skin
Cold-water immersion
Name some more invasive cooling measure in hyperthermia?
bladder or gastric lavage with cooled fluids or cooled haemodialysis or cardiopulmonary bypass
What are the complications of hyperthermia?
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
What is the definition of hypothermia?
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.
What is primary hypothermia?
Primary hypothermia is environmental, occurring for example after immersion in cold water or prolonged exposure to cold weather conditions
What is secondary hypothermia?
Secondary hypothermia occurs secondary to an insult or illness such as infection, alcohol excess, hypothyroidism or major trauma
Name the different degrees of hypothermia with their temperatures
Mild - 32 to 35°C
Moderate - 28 to 32°C
Severe - 20 to 28°C
Profound - < 20°C
What are the symptoms of hypothermia?
Shivering
Hunger
Dizziness
Chills
Slurred speech
Paradoxical undressing
What are the signs of hypothermia?
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
Why would you do a urine toxicology screen in hypothermia?
if drug intoxication is suspected (e.g. patient found unconscious outside
What would an arterial blood gas show in hypothermia?
may show an initial respiratory alkalosis, followed by respiratory acidosis as hypothermia worsens
What would an ECG show in hypothermia?
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)
What does a J wave look like in someone with hypothermia?
What blood tests would you do in someone with hypothermia and why?
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
What imaging would you do in someone with hypothermia?
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
What is the conservative management of hypothermia?
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
In the conservative management of hypothermia what are the different types of rewarming?
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
What is the medical management of hypothermia?
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
What is the invasive management of hypothermia?
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)
What are the complications of hypothermia?
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
What is the definition of hypoglycaemia?
Hypoglycaemia is a metabolic condition characterized by an abnormally low blood glucose level, typically defined as less than 3.5 mmol/L.
What drugs and who is most at risk of hypoglycaemia?
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.
Name some causes of hypoglycaemia?
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
What are the adrenergic symptoms of hypoglycaemia and at what blood glucose concentration?
(Blood glucose concentrations <3.3 mmol/L):
Trembling
Sweating
Palpitations
Hunger
Headache
What are the neuroglycopenic symptoms of hypoglycaemia and at what blood glucose concentration?
Blood glucose concentrations below <2.8 mmol/L):
Double vision
Difficulty concentrating
Slurred speech
Confusion
Coma
What are the investigations for hypoglycaemia?
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.
What does a high serum c-peptide and high serum insulin show about the insulin source?
High insulin AND high C-peptide and proinsulin imply endogenous production e.g. insulinoma
What does a low serum c-peptide and high serum insulin show about the insulin source?
High insulin AND low C-peptide and proinsulin suggest exogenous administration.
What is the management for mild hypoglycaemia?
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).
What is the management for severe hypoglycaemia?
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.
Which type of diabetic medication increases the chance of having hypoglycaemia the most?
sulphonylureas
What is DVLA advice on severe hypoglycaemia?
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.
What is the best diagnostic test for distinguishing an insulinoma?
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.
What is Whipple’s Triad?
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
What is hypoparathyroidism?
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).
What are the risk factors for hypoparathyroidism?
Neck surgery or radiation therapy involving the parathyroid glands.
Autoimmune conditions, such as autoimmune polyendocrine syndrome.
Genetic factors and familial forms of the condition
What is the pathophysiology of hypoparathyroidism?
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.
What are the signs and symptoms of hypoparathyroidism?
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
What are the investigations for hypoparathyroidism?
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
What cardiac abnormalities do you get in hypocalcaemia?
prolonged QT
What is the management for hypocalcaemia?
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
What are the complications of hypocalcaemia?
Severe hypocalcemia leading to seizures and cardiac arrhythmias
Kidney stones due to increased urinary calcium excretion
Impaired renal function
Cataracts
Neurological and neuropsychiatric sequelae
What is the management of severe hypocalcaemia in which there is neuromuscular irritability?
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.
Explain psuedohypoparathyroidism
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).
What is the definition of hypothyroidism?
Hypothyroidism is an endocrine disorder characterized by an insufficient production of thyroid hormones, which are crucial for metabolism and energy utilization in the body.
What are the different categories that cause hypothyroidism?
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.
What are the signs and symptoms of hypothyroidism?
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
What are the investigations for hypothyroidism?
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.
What is the management for hypothyroidism?
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
When do you increase the dose of levothyroxine for hypothyroidism?
During pregnancy, the dose of levothyroxine is usually increased by 25-50mcg due to increased metabolic demands
Which antibodies are most associated with hypothyroidism?
Anti-thyroid peroxidase antibodies - these are strongly associated with Hashimoto’s thyroiditis
What is the tinel sign and what does it show?
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
What is the most common cause of hypothyroidism worldwide?
Iodine deficiency
What medication can affect the absorption of levothyroxine?
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
Which condition does levothyroxine treatment increase the risk of?
osteoporosis
What is the extreme manifestation of levothyroxine and what is the treatment?
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.
What happens to T3,T4 and TSH during pregnancy?
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.
Define obesity
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
What BMI is considered to be obese?
A BMI of 30 or higher is considered indicative of obesity.
Distinguish metabolic syndrome from obesity?
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.
How many adults and children in the UK are obese?
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.
What are the risk factors for obesity?
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.
What are the signs and symptoms of obesity?
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
State all the BMI reference ranges and what classification they correlate to:
What are the investigations for obesity?
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).
State the conservative management for obesity:
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.
State the medical management for obesity:
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.
State the surgical management for obesity:
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.
Define thyrotoxicosis
The syndrome resulting from the presence of excessive thyroid hormones in the body, not always due to thyroid gland overactivity.
Name some primary causes of thyrotoxicosis ( originating from the thyroid itself)
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
Name some secondary causes of thyrotoxicosis
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)
Signs and symptoms of hyperthyroidism
↑ Basal metabolic rate
Heat intolerance
Tachycardia and arrhythmias
Weight loss
Diarrhoea
Sweaty skin
Insomnia and sleep disturbances
Restlessness and tremors
Goitre (depending on cause)
Specific signs and symptoms of grave’s disease:
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.
Name the investigations for hyperthyroidism
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).
What is first line treatment for hyperthyroidism?
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.
What can be prescribed for symptomatic relief in hyperthyroidism?
Beta-blockers:
Propranolol can be used for symptomatic relief, especially for symptoms associated with increased sympathetic activity.
What is considered definitive treatment for hyperthyroidism?
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.
What is considered when there is a large goitre with suspicion of malignancy?
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.
What do you need to do in hyperthyroidism to detect early signs of remission and relapse?
Regular monitoring is crucial, including thyroid function tests, to ensure appropriate dosing of medications and to detect early signs of remission or relapse.
Define a thyroid storm:
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.
What are the key features of a thyroid storm?
Restlessness and agitation
High-output heart failure
Profound tachycardia
Fever
Delirium and altered mental status
Outline the management for a thyroid storm:
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
Name some complications of hyperthyroidism:
Thyroid eye disease
Atrial fibrillation
High output heart failure
Osteopenia/osteoporosis
Upper Airway Obstruction
Thyroid Cancer
Thyroid storm
What is Amiodarone-induced thyrotoxicosis
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.
What are the two types of Amiodarone-induced thyrotoxicosis (AIT)?
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.
What are the investigations for amiodarone-induced thyrotoxicosis?
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.
What is the management for type 1 amiodarone induced thyrotoxicosis?
For AIT type 1, anti-thyroid drugs such as carbimazole are typically used.
What is the management for type 2 amiodarone induced thyrotoxicosis?
For AIT type 2, anti-inflammatory drugs like corticosteroids are often the treatment of choice.
What are thyroid nodules?
Thyroid nodules are discrete lesions within the thyroid gland, often palpable and detected incidentally on imaging studies
Name some risk factors for thyroid nodules:
malignancy risk factors including age under 20 or over 60, male gender, history of head and neck irradiation, and family history of thyroid cancer.
How clinically may people present with thyroid nodules?
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.
How do you determine if a thyroid nodule is functioning or not?
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.
What does the anterior pituitary secrete?
growth hormone (GH), prolactin, gonadotropins (LH and FSH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH).
What does the posterior pituitary secrete?
releases oxytocin and antidiuretic hormone (ADH)
What are the most common type of pituitary tumours?
Pituitary adenomas
What are the clinical features of pituitary tumours?
Headaches
Visual Field Defects - bitemporal hemianopia
What are the investigations for pituitary tumours?
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.
What is the management for pituitary tumours?
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.
What is the most common hormone secreting pituitary adenoma?
prolactinoma
What are the signs of a prolactinoma in a female?
Women: Oligomenorrhea or amenorrhea, galactorrhea (breast milk production outside of pregnancy or breastfeeding), infertility, and vaginal dryness.
What are the signs of a prolactinoma in a male?
Men: Erectile dysfunction, reduced facial hair growth.
What is the pharmacological management of a prolactinoma?
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.
When is surgery indicated for a prolactinoma?
Trans-sphenoidal resection is indicated when medical treatment fails to manage the tumor effectively
What is hypopituitarism?
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.
How does growth hormone deficiency present?
Manifests as central obesity, dry skin, reduced muscle strength, and decreased exercise tolerance.
How does FSH and LH deficiency present in males?
Infertility, sexual dysfunction, and hypogonadism.
How does FSH and LH deficiency present in females?
Oligomenorrhea or amenorrhea, infertility, sexual dysfunction, and breast atrophy
How does TSH deficiency present
hypothyroidism
How does ACTH deficiency present?
Leads to adrenal deficiency, with symptoms including fatigue, reduced muscle mass, anorexia, myalgia, and gastrointestinal upset.
How does ADH deficiency present?
Causes excessive thirst and urination due to water imbalance.
What is acromegaly?
A disorder caused by excess amounts of growth hormone with characteristic clinical features.
With which syndrome is a pituitary adenoma associated with?
Multiple Endocrine Neoplasia Syndrome Type 1
What is the pathophysiology of acromegaly?
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
What is the difference between gigantism and acromegaly?
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.
What is the history someone may present with if they have acromegaly?
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
What is the first line investigation for acromegaly?
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
What bedside tests would you do for acromegaly?
Fundoscopy (for optic atrophy)
Perimetry (to assess visual field defect formally)
Urine dip (glycosuria)
ECG (LVH due to HTN)
What radiology tests would you do for acromegaly?
CXR (cardiomegaly)
MRI Pituitary (adenoma)
If considering an ectopic source, can do CTCAP
What special tests would you do for acromegaly?
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
What is the primary treatment of choice for acromegaly?
surgery to remove the adenoma is the primary treatment of choice.
Transphenoidal (first line)/transfrontal resection of the pituitary +/- radiotherapy
What is the medical treatment for acromegaly?
Somatostatin analogues (octreotide, lanreoride), which suppress growth hormone release - first line medical treatment
Growth hormone antagonists (pegvisomant)
Dopamine agonists (bromocriptine, cabergoline)
What follow ups do you do for acromegaly after initial treatment?
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
What are the complications of acromegaly?
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
What type of medications can increase prolactin?
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.
In women with elevated prolactin and secondary amenorrhea what does one first need to rule out?
pregnancy
What is the best order for replacing pituitary hormones in hypopituitarism?
Cortisol, Thyroxine, Sex hormones and if necessary, growth hormone. Administering thyroxine to cortisol deficient patients can make them very unwell
What is the gold standard investigation to diagnose hypopituitarism?
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.
What is pituitary apoplexy?
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
