Endocrine Flashcards
1
Q
What are the types of thyroid cancer?
A
Papillary
Follicular
Medullary
Anaplastic
Lymphoma
2
Q
Which the most common thyroid cancer?
A
Papillary -70% often young females
3
Q
What type of medication causes proximal myopathy?
A
Corticosteroids may cause proximal myopathy
4
Q
Which two conditions account for 90% of cases of hypercalcaemia:
A
- Primary hyperparathyroidism: commonest cause in non-hospitalised patients
- Malignancy: the commonest cause in hospitalised patients. This may be due to a number of processes, including;
PTHrP from the tumour e.g. squamous cell lung cancer
bone metastases
myeloma,: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
for this reason, measuring parathyroid hormone levels is the key investigation for patients with hypercalcaemia
5
Q
Which drug causes hypercalicaemia?
A
Thiazides, calcium-containing antacids
6
Q
What are other causes of hypercalcaemia?
A
sarcoidosis
other causes of granulomas may lead to hypercalcaemia e.g. tuberculosis and histoplasmosis
vitamin D intoxication
acromegaly
thyrotoxicosis
Milk-alkali syndrome
drugs:
thiazides
calcium-containing antacids
dehydration
Addison’s disease
Paget’s disease of the bone
usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
7
Q
what acid-base imbalance would you expect in cushings syndrome?
A
hypokalaemic metabolic alkalosis. This patient is presenting with the classical features of Cushing’s syndrome: central adiposity, stretch marks, bruising, hirsutism and acne. The condition is caused by an excess of corticosteroids and has been probably exacerbated by the corticosteroid therapy for her adhesive capsulitis.
Cushing’s syndrome causes hypokalaemic metabolic alkalosis because when the levels of cortisol are high, the cortisol that is not inactivated by 11β-hydroxysteroid dehydrogenase is free to bind to mineralocorticoid receptors. This causes an increase in water and sodium retention, increased potassium excretion, and increased hydrogen ions excretion. Lower levels of hydrogen ions cause alkalosis and less potassium causes hypokalemia.
8
Q
What are beginin causes of thyroid nodule?
A
Multinodular goitre
Thyroid adenoma
Hashimoto’s thyroiditis
Cysts (colloid, simple, or hemorrhagic)
9
Q
Which drugs can induce neutrophilia?
A
Glucocorticoids
10
Q
What is the best test to diagnose Addison’s disease?
A
ACTH stimulation test (short Synacthen test)
11
Q
What is the first-line management in patients with hypercalcaemia?
A
IV fluids, saline
11
Q
What is the management of hypercalcaemia?
A
The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days
Other options include:
calcitonin - quicker effect than bisphosphonates
steroids in sarcoidosis
Loop diuretics such as furosemide are sometimes used in hypercalcaemia, particularly in patients who cannot tolerate aggressive fluid rehydration. However, they should be used with caution as they may worsen electrolyte derangement and volume depletion.
11
Q
What is the mechanism of action of empagliflozin?
A
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule
12
Q
What is mechanism of action of SGLT-2 inhibitors?
A
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
Examples include canagliflozin, dapagliflozin and empagliflozin.
12
Q
What is the dietary advice for diabetes?
A
encourage high fibre, low glycaemic index sources of carbohydrates
include low-fat dairy products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
discourage the use of foods marketed specifically at people with diabetes
initial target weight loss in an overweight person is 5-10%
12
Q
What are the adverse effects of SGLT-2 inhibitors?
A
Important adverse effects include
urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.
12
Q
What are the HbAc1 targets for T2DM Management?
A
the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)
13
Q
Why is Raised total T3 and T4 but normal fT3 and fT4 normal in pregnancy?
A
suggest high concentrations of thyroid binding globulin, which can be seen during pregnancy
13
Q
What is a side affect of Metoclopramide and why?
A
galactorrhoea.
Metoclopramide is a dopamine receptor antagonist, hence blocking its action. Dopamine normally acts as a natural inhibitor of prolactin release from the pituitary gland. By blocking dopamine receptors, metoclopramide interferes with this inhibitory effect. As a result, prolactin secretion is disinhibited, leading to an increase in circulating prolactin levels, causing galactorrhoea, and the release of breast milk.
13
Q
What is an important side effect of sulfonylureas?
A
hypoglycaemia
13
Q
What is the BMI classification?
A
13
Q
What are the Important adverse effects of SGLT-2 inhibitors?
A
urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
14
Q
What is the treatment of MODY?
A
The treatment for MODY depends on the specific genetic subtype. For example, MODY2 often does not require specific treatment, as the hyperglycemia is mild and usually does not lead to complications. In contrast, MODY associated with HNF1A often respond well to treatment with low-dose sulfonylureas. Insulin therapy may be necessary in some cases, especially during pregnancy or if sulfonylureas are contraindicated or ineffective.
15
Q
What is the typical presentation of subacute thyroiditis (de Quervain’s thyroiditis)?
A
hyperthyroidism associated with a tender goitre after an upper respiratory tract infection which is the typical presentation
16
What are the phases of subacute (De Quervain's) thyroiditis?
There are typically 4 phases;
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal
17
What are the investigations for subacute (De Quervain's) thyroiditis?
thyroid scintigraphy: globally reduced uptake of iodine-131
18
What is the management of subacute (De Quervain's) thyroiditis?
usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops
19
What is Hyperosmolar Hyperglycaemic State ?
Hyperosmolar Hyperglycaemic State (HHS) is a life-threatening medical emergency that occurs primarily in individuals with type 2 diabetes mellitus. It is characterized by severe hyperglycemia, extreme dehydration, and a significant increase in plasma osmolality, without substantial ketosis or acidosis, which differentiates it from diabetic ketoacidosis (DKA).
20
What is the pathophysiology of Hyperosmolar Hyperglycaemic State ?
Insulin Deficiency: Relative insulin deficiency leads to hyperglycemia but is sufficient to suppress lipolysis and ketogenesis.
Osmotic Diuresis: Excess glucose is excreted in urine, pulling water and electrolytes along with it, leading to dehydration and electrolyte imbalances.
Increased Plasma Osmolality: The concentration of solutes in the blood rises, causing cellular dehydration and contributing to neurological symptoms.
Severe hyperglycaemia → Osmotic diuresis → Profound dehydration
Dehydration → Decreased renal perfusion → Reduced glucose excretion → Worsening hyperglycaemia
Increased serum osmolarity (>320 mOsm/kg) → Cellular dehydration, especially in the brain → Altered mental state
Minimal ketogenesis: Unlike DKA, insulin levels are sufficient to prevent lipolysis, so there is little to no ketone production.
21
What are the Precipitating factors of Hyperosmolar Hyperglycaemic State ?
intercurrent illness
dementia
sedative drugs
22
What are the clinical features of Hyperosmolar Hyperglycaemic State ?
whilst DKA presents within hours of onset, HHS comes on over many days, and consequently, the dehydration and metabolic disturbances may be more extreme
consequences of volume loss
clinical signs of dehydration
polyuria
polydipsia
systemic
lethargy
nausea and vomiting
neurological
altered level of consciousness
focal neurological deficits
haematological
hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
23
What is the management of Hyperosmolar Hyperglycaemic State ?
fluid replacement
fluid losses in HHS are estimated to be between 100 - 220 ml/kg
IV 0.9% sodium chloride solution
typically given at 0.5 - 1 L/hour depending on clinical assessment
potassium levels should be monitored and added to fluids depending on the level
insulin
should not be given unless blood glucose stops falling while giving IV fluids
venous thromboembolism prophylaxis
patients are at risk of thrombosis due to hyperviscosity
24
What are the complications of Hyperosmolar Hyperglycaemic State ?
vascular complications may occur due to hyperviscosity:
such as myocardial infarction
stroke
25
What is the diagnostic criteria Hyperosmolar Hyperglycaemic State ?
There are no precise diagnostic criteria but the following are typically seen
hypovolaemia
marked hyperglycaemia (>30 mmol/L)
significantly raised serum osmolarity (> 320 mosmol/kg)
can be calculated by: 2 * Na+ + glucose + urea
no significant hyperketonaemia (<3 mmol/L)
no significant acidosis (bicarbonate > 15 mmol/l or pH > 7.3 - acidosis can occur due to lactic acidosis or renal impairment)
26
Which patients should be followed up regularly by the local diabetic foot centre.
Low risk
* no risk factors except callus alone
Moderate risk
* deformity or
* neuropathy or
* non-critical limb ischaemia.
High risk
* previous ulceration or
* previous amputation or
* on renal replacement therapy or
* neuropathy and non-critical limb ischaemia together or
* neuropathy in combination with callus and/or deformity or
* non-critical limb ischaemia in combination with callus and/or deformity.
27
When should Refer to the local vascular team - to be seen within 2 weeks be considered?
Referral to a vascular team should be considered if there are signs of peripheral arterial disease or critical limb ischemia.
patient's foot pulses are not palpable, suggesting inadequate blood flow
28
What is the key parameter to monitor in patients with hyperosmolar hyperglycaemic state?
Serum osmolality
29
What is the firstline investigation in suspected primary hyperaldosteronism?
aldosterone/renin ratio
30
What are the different layers of the adrenal gland?
The adrenal gland has two main parts: the adrenal cortex and the adrenal medulla. The adrenal cortex is made up of three layers, each producing different hormones.
31
What are the layers of the adrenal cortex and what hormones do they produce?
Zona glomerulosa
The outermost layer that produces aldosterone, which regulates sodium and potassium levels
Zona fasciculata
The middle layer that produces cortisol, which helps the body respond to stress
Zona reticularis
The innermost layer that produces androgens, such as DHEA, which can be converted to estrogen or testosterone
32
Does digoxin causes gynaecomastia?
Yes
33
What drug should you give in the case of PHaeochromocytoma?
PHaeochromocytoma - give PHenoxybenzamine before beta-blockers
The first-line treatment for a phaeochromocytoma is a non-selective alpha blocker, in this case, phenoxybenzamine.
34
headache, sweating and palpitations.blood pressure is found to be 180/90 mmHg and a fine tremor is noted in both hands. His urine is sampled and shows raised levels of urinary metanephrines What is the diagnosis?
young man presenting with palpitations, tremor and a headache. Given his presentation, his most likely underlying diagnosis is a phaeochromocytoma. This is confirmed by the raised blood pressure on examination and the raised levels of urinary metanephrines.
35
What is Phaeochromocytoma ?
Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
Basics
bilateral in 10%
malignant in 10%
extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
36
What are the features of Phaeochromocytoma ?
Features are typically episodic
hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
37
What is the test for Phaeochromocytoma ?
24 hr urinary collection of metanephrines (sensitivity 97%*)
38
What is the management for Phaeochromocytoma ?
Surgery is the definitive management. The patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
39
What is the management of prolactinoma?
Prolactin release is persistently inhibited by dopamine
therefore cabergoline
39
What increases prolactin secretion?
thyrotropin releasing hormone
pregnancy
oestrogen
breastfeeding
sleep
stress
drugs e.g. metoclopramide, antipsychotics
40
What decreases prolactin secretion?
dopamine
dopaminergic agonists
41
Where is prolactin secreted from and what are its functions?
Anterior pituitary
Stimulates breast development (both initially and further hyperplasia during pregnancy)
Stimulates milk production
It decreases GnRH pulsatility at the hypothalamic level and to a lesser extent, blocks the action of LH on the ovary or testis.
42
Features of hypokalaemia coupled with hypertension are suggestive of....
primary hyperaldosteronism
43
44
What is Addisonian crisis?
a life-threatening medical emergency that occurs when the body has low levels of cortisol. Cortisol is a hormone that helps regulate blood sugar and the body's response to stress.
45
What should pregnant women with hypothyroidism do with medication?
Women with hypothyroidism may need to increase their thyroid hormone replacement dose by up to 50% as early as 4-6 weeks of pregnancy
46
What are the features of Addisonian crisis?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
47
What are the causes of Addisonian crisis?
sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison's, Hypopituitarism)
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
48
What is the management of adrenal crisis?
hydrocortisone 100 mg im or iv
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
49
What is the management for Addison's disease and when are the doses given?
Patients who have Addison's disease are usually given both glucocorticoid and mineralocorticoid replacement therapy.
This usually means that patients take a combination of:
hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the first half of the day
fludrocortisone
50
What should patients using glucocorticoids be educated about?
emphasise the importance of not missing glucocorticoid doses
consider MedicAlert bracelets and steroid cards
patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
discuss how to adjust the glucocorticoid dose during an intercurrent illness (see below)
Management of intercurrent illness
in simple terms the glucocorticoid dose should be doubled, with the fludrocortisone dose staying the same
the Addison's Clinical Advisory Panel have produced guidelines detailing particular scenarios - please see the CKS link for more details
51
What is the treatment for subclinical hypothyroidism?
Subclinical hypothyroidism with TSH level of level is 5.5 - 10mU/L: offer patients < 65 years a 6-month trial of thyroxine if TSH remains at that level on 2 separate occasions 3 months apart and they have hypothyroidism symptoms
52
What treatment worsens thyroid eye disease?
If there is active Grave's eye disease then radioiodine therapy is not recommended as it can worsen the eye disease
53
Asymptomatic patients with an abnormal HbA1c or fasting glucose must be confirmed with....
a second abnormal reading before a diagnosis of type 2 diabetes is confirmed
54
During Ramadan how should the metformin doses be split?
one-third of the normal metformin dose should be taken before sunrise and two-thirds should be taken after sunset
55
Glucocorticoid treatment can induce
neutrophilia
56
proximal myopathy is a side effect of which type of medication?
Corticosteroids
57
What treatment in Subclinical hypothyroidism in the elderly?
watch and wait
58
Over-replacement with thyroxine increases the risk
osteoporosis
59
what is the T2DM initial therapy: if metformin is contraindicated (and no risk of CVD, established CVD or chronic heart failure)
choice of DPP-4 inhibitor or Pioglitazone or Sulfonylurea or even SGLT-2 (if NICE criteria met)
60
Causes of Primary Hypothyroidism?
Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the developed world. It is an autoimmune condition causing inflammation of the thyroid gland. It is associated with anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies.
Iodine deficiency is the most common cause of hypothyroidism in the developing world. In the UK, iodine is particularly found in dairy products and may be added to non-dairy milk alternatives (e.g., soya milk).
Treatments for hyperthyroidism have the potential to cause hypothyroidism:
Carbimazole
Propylthiouracil
Radioactive iodine
Thyroid surgery
Lithium inhibits the production of thyroid hormones in the thyroid gland and can cause a goitre and hypothyroidism.
Amiodarone interferes with thyroid hormone production and metabolism, usually causing hypothyroidism but can also cause thyrotoxicosis.
61
Causes of Secondary Hypothyroidism?
Tumours (e.g., pituitary adenomas)
Surgery to the pituitary
Radiotherapy
Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
Trauma
62
What is the presentation of hypothyroidism?
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (including oedema, pleural effusions and ascites)
Heavy or irregular periods
Constipation
63
What is the management of hypothyroidism?
Oral levothyroxine is the mainstay of treatment of hypothyroidism. Levothyroxine is a synthetic version of T4 and metabolises to T3 in the body.
The dose is titrated based on the TSH level, initially every 4 weeks.
Liothyronine sodium is a synthetic version of T3 and is very rarely used under specialist care where levothyroxine is not tolerated.
64
Explain TSH and T4 levels with Poor compliance with thyroxine
TSH HIGH and T4 is normal
Thyroxine (T4) is used as a replacement hormone in hypothyroidism. When taken regularly, it suppresses thyroid-stimulating hormone (TSH) by providing adequate thyroid hormone levels, maintaining normal thyroid function.
Poor compliance with thyroxine causes fluctuating thyroid hormone levels:
When thyroxine is taken sporadically, serum T4 levels may normalize on the days when it is taken due to its long half-life (~7 days).
However, the pituitary gland, which senses thyroid hormone levels, responds to periods of insufficient T4 (due to missed doses) by increasing TSH secretion to stimulate the thyroid gland.
65
Explain TSH and T4 levels with Steroid therapy?
TSH IS LOW and T4 is normal
Glucocorticoids suppress the secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus and TSH from the anterior pituitary.
This suppression occurs because:
Steroids inhibit the hypothalamus and reduce TRH production.
Less TRH means less stimulation of the pituitary, leading to decreased TSH secretion.
Glucocorticoids reduce TSH's amplitude and frequency of secretion.
This leads to transient low TSH levels, even if thyroid hormone levels (T4 and T3) remain normal.
The suppression of TSH is usually partial and transient with steroid therapy.
The thyroid gland continues to produce adequate T4 under the influence of residual TSH or basal thyroid activity.
T4 has a long half-life (about 7 days), so short-term changes in TSH do not immediately affect circulating T4 levels.
66
Sick euthyroid syndrome is most commonly seen in which type of patients?
Sick euthyroid syndrome is most commonly seen in chronically ill patients or those with starvation. The thyroid function tests are often low and the patient clinically euthyroid.
67
What is MEN?
Multiple Endocrine Neoplasia (MEN) is a rare, inherited disorder that affects the endocrine glands, causing them to develop tumors or overproduce hormones. These syndromes are caused by genetic mutations and are classified into distinct subtypes based on the affected genes and glands.
68
What is the cause, affected organs and symptoms of MEN1?
Cause: Mutation in the MEN1 gene, which encodes the tumor suppressor protein menin.
Affected Organs:
Parathyroid glands (most common): Leads to primary hyperparathyroidism, causing high calcium levels.
Pituitary gland: Can cause tumors like prolactinomas or growth hormone-secreting adenomas.
Pancreas/Enteropancreatic neuroendocrine tumors: Includes insulinomas, gastrinomas (leading to Zollinger-Ellison syndrome), and others. (leading to recurrent peptic ulceration)
Symptoms:
Hypercalcemia (fatigue, kidney stones).
Symptoms related to hormonal excess (e.g., acromegaly, Cushing’s syndrome, or peptic ulcers).
69
What is the cause, affected organs and symptoms of MEN type IIa?
Cause: Mutation in the RET proto-oncogene.
Subtypes:
MEN2A:
Medullary thyroid cancer (MTC): Nearly all patients.
Pheochromocytomas (adrenal gland tumors): Cause high blood pressure, palpitations.
Parathyroid hyperplasia: Causes hypercalcemia.
Whilst many develop parathyroid hyperplasia, only a relatively small proportion have hypercalcaemia as a result.
70
What is the cause, affected organs and symptoms of MEN type IIb?
Cause: Mutation in the RET proto-oncogene.
MEN2B:
Medullary thyroid cancer: More aggressive than in MEN2A.
Pheochromocytomas.
Distinct physical features: Marfanoid habitus, mucosal neuromas (lips, tongue).
Symptoms:
Neck swelling (thyroid cancer), sweating, and headaches (pheochromocytomas).
Features of hypercalcemia or mucosal neuromas in MEN2B.
71
What would cause Lower-than-expected levels of HbA1c (due to reduced red blood cell lifespan)?
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
Haemodialysis
72
What would cause Higher-than-expected levels of HbA1c (due to increased red blood cell lifespan)?
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
73
If metformin is contraindicated then what should be given?
if the patient has a risk of CVD, established CVD or chronic heart failure:
SGLT-2 monotherapy
if the patient doesn't have a risk of CVD, established CVD or chronic heart failure:
DPP-4 inhibitor or pioglitazone or a sulfonylurea
SGLT-2 may be used if certain NICE criteria are met
74
What PTh and calcium levels would you expect in lung cancer?
lung cancers can cause hypercalcaemia secondary to the secretion of PTH-related peptide (PTHrp). Although her smoking history is a risk factor for this, we would expect her PTH to be very low (rather than normal) as it would be suppressed by PTHrp.
75
In pregnant woman who develop hyperthyroidism in the first trimester what drug is prefered?
propylthiouracil is preferred over carbimazole due to lower risk of foetal malformation
76
Mechanism of action of Propylthiouracil
works by inhibiting the enzyme thyroid peroxidase, thereby reducing the production of thyroxine (T4). Additionally, it inhibits the peripheral conversion of T4 to the more active triiodothyronine (T3), providing a more comprehensive reduction in thyroid hormone levels
77
Why is it is crucial to manage hyperthyroidism during pregnancy?
to avoid complications such as preterm birth, low birth weight, and preeclampsia.
Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart failure and premature labour
78
What is given to treat hypothyroidism in pregnancy?
thyroxine is safe during pregnancy
serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum
women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy
breastfeeding is safe whilst on thyroxine
79
When should be measured in pregnancy and when during treatment of hyperthyroidism?
thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine the risk of neonatal thyroid problems
80
A diagnosis of Kallman's syndrome is suspected.
What would you expect to see on the patient's blood results?
Low FSH/LH and low testosterone
Kallmann's syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann's syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.
Kallman's syndrome is caused by a failure of the embryonic development of olfactory nerve fibres, which in turn prevents the normal embryonic migration of nerves that produce gonadotrophin releasing hormone (GnRH) from the olfactory region to the hypothalamus.
81
What pattern of thyroid function tests is indicative of a non-thyroidal illness syndrome (NTIS), also known as euthyroid sick syndrome?
TSH normal / low; thyroxine low; T3 low
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
82
Pathophysiology of DKA
DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
83
Main principles of management of DKA?
fluid replacement
most patients with DKA are deplete around 5-8 litres
isotonic saline is used initially, even if the patient is severely acidotic
please see an example fluid regime below.
insulin
an intravenous infusion should be started at 0.1 unit/kg/hour
once blood glucose is < 14 mmol/l an infusion of 10% dextrose should be started at 125 mls/hr in addition to the 0.9% sodium chloride regime
correction of electrolyte disturbance
serum potassium is often high on admission despite total body potassium being low
this often falls quickly following treatment with insulin resulting in hypokalaemia
potassium may therefore need to be added to the replacement fluids
if the rate of potassium infusion is greater than 20 mmol/hour then cardiac monitoring may be required
long-acting insulin should be continued, short-acting insulin should be stopped
84
What are the most common precipitating factors of DKA?
are infection, missed insulin doses and myocardial infarction.
85
What are the features of DKA?
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath ('pear drops' smell)
86
What is the diagnostic criteria of DKA?
87
Over-replacement with thyroxine increases the risk of...
osteoporosis
88
What are the side-effects of thyroxine therapy?
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
89
What are the interactions of levothyroxine ?
iron, calcium carbonate
absorption of levothyroxine reduced, give at least 4 hours apart
90
What is the initial starting dose of levothyroxine for elderly and other patients?
initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od
91
Following change in thyroxine dose thyroid function tests should be checked after...
8-12 weeks
92
What is the the therapeutic goal of levothyroxine therapy?
the therapeutic goal is 'normalisation' of the thyroid stimulating hormone (TSH) level. As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range
93
Hashimoto's thyroiditis is associated with what condition?
mucosa-associated lymphoid tissue (MALT) lymphoma
they also frequently develop gastric lesions, which do not respond to Helicobacter pylori triple-therapy.
Current theories suggest that lymphoma develops in response to areas of localised autoimmune stimulation. Although this would make you think patients with Hashimoto's should develop the MALT lymphoma in thyroid tissue (which they frequently do),
94
What is Latent autoimmune diabetes of adulthood (LADA)?
is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune -cell failure is slow.
Autoimmune origin: LADA is caused by an autoimmune attack on pancreatic beta cells, leading to progressive insulin deficiency.
Slower onset: Unlike classic Type 1 diabetes, which usually presents suddenly in childhood or adolescence, LADA develops gradually over months to years in adults (typically after age 30).
Initial misdiagnosis as Type 2 diabetes: Since it develops in adulthood and initially responds to lifestyle changes or oral hypoglycemics, many patients are mistakenly diagnosed with Type 2 diabetes.
Progression to insulin dependence: Over time, beta cell function declines, and patients eventually require insulin therapy, usually within a few years of diagnosis.
95
What is an example of thiazolidinediones and mechanism of action?
Pioglitazone
They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance.
96
What are the adverse effects of thiazolidinediones-Pioglitazone?
weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
97
What autoantibodies are found in graves and what is their action?
TSH receptor stimulating antibodies (90%)
-Also called Thyroid-Stimulating Immunoglobulins (TSI) or TSH Receptor Antibodies (TRAb).
Primary antibody in Graves' disease.
Stimulates the TSH receptor, leading to excessive thyroid hormone production (hyperthyroidism).
anti-thyroid peroxidase antibodies (75%)
Also found in Hashimoto's thyroiditis, but can be present in Graves' disease.
Targets thyroid peroxidase (TPO), an enzyme involved in thyroid hormone synthesis.
May contribute to thyroid inflammation and tissue damage.
Thyroglobulin Antibodies (Tg Ab)
Less common in Graves’ disease.
More frequently associated with Hashimoto’s thyroiditis.
Targets thyroglobulin (Tg), a precursor protein for thyroid hormone synthesis.
98
What medication is given to type 2 diabetics with hypertension?
ACE inhibitors or angiotensin II receptor blockers (ARB) are first-line
an ARB is preferred if the patient has a black African or African-Caribbean family origin
99
What is the definition of polyuria?
The production of more than 3L of urine in a 24hr period
100
What stimulates ADH secretion?
increase in serum osmolality
101
What should you do for a child with a palpable abdominal mass or unexplained enlarged abdominal organ?
refer very urgently (<48hr) for specialist assessment for neuroblastoma and Wilms' tumour
102
What is Neuroblastoma?
Neuroblastoma is one of the top five causes of cancer in children, accounting for around 7-8% of childhood malignancies. The tumour arises from neural crest tissue of the adrenal medulla (the most common site) and sympathetic nervous system.
Median age of onset is around 20 months
103
What are the features of neuroblastoma?
abdominal mass
pallor, weight loss
bone pain, limp
hepatomegaly
paraplegia
proptosis
104
What is seen in the investigations for neuroblastoma?
raised urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels
calcification may be seen on abdominal x-ray
biopsy
105
What is wilms tumour?
Wilms tumor (nephroblastoma) is a malignant kidney tumor that primarily affects children, typically between ages 2 and 5. It is the most common renal malignancy in children and arises from embryonic kidney cells that fail to develop properly.
106
Diabetic ketoacidosis: if the ketonaemia and acidosis have not been resolved within 24 hours then what is the next step
The next best step in his management would be to arrange a review with a senior endocrinologist. This is because it is unusual for DKA not to have biochemically resolved by 24º despite appropriate treatment. It is important to identify and address the reasons for standard treatment failure.
107
How would Graves be seen on Thyroid scintigraphy?
diffuse, homogenous, increased uptake of radioactive iodine
108
How would toxic multi nodular goitre be seen on Thyroid scintigraphy?
Areas of intense uptake interspersed with some reduced activity
109
How would sub acute thyroiditis be seen on Thyroid scintigraphy?
Faint diffuse uptake or no uptake at all
110
How would toxic adenoma be seen on Thyroid scintigraphy?
single hot nodule with the rest of the gland suppressed
111
In a patient with long-standing type 1 diabetes, impaired hypoglycaemia awareness is most commonly due to...
neuropathy of parts of the autonomous nervous system
Neuropathy of the autonomic nervous system (often due to long-standing diabetes) impairs these responses, so adrenaline release is blunted, and warning symptoms are reduced or absent.
112
What is an important complication of fluid resuscitation in DKA, especially in young patients?
cerebral oedema can cause seizures
113
She was diagnosed with Hashimoto's thyroiditis four months ago and is currently being treated with levothyroxine 75 mcg od. What is the single most important blood test to assess her response to treatment?
TSH
114
What is the treatment for Diabetic neuropathy ?
NICE updated it's guidance on the management of neuropathic pain in 2013. Diabetic neuropathy is now managed in the same way as other forms of neuropathic pain:
first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
pain management clinics may be useful in patients with resistant problems
115
What are the Gastrointestinal autonomic neuropathy conditions caused by diabetes?
Gastroparesis
occurs secondary to autonomic neuropathy
symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)
Chronic diarrhoea
often occurs at night
Gastro-oesophageal reflux disease
caused by decreased lower esophageal sphincter (LES) pressure
116
What are the management options for Gastroparesis caused by diabetes?
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)
117
Why does addisons cause hypoglycaemia?
Glucocorticoids such as cortisol act by various mechanisms to increase blood glucose levels, one of these mechanisms being through an increase in hepatic gluconeogenesis. This means that a reduction in cortisol could lead to hypoglycaemia.
118
What type of anaemia is associated with addisons and why?
Pernicious anaemia is often associated with Addison's due to their overlapping autoimmune aetiologies. Pernicious anaemia occurs due to an autoimmune attack on the parietal cells within the gastric mucosa, these cells are responsible for the production of intrinsic factor. Intrinsic factor is vital for B12 absorption and therefore a deficiency of this will result in macrocytic, megaloblastic anaemia.
119
What is The Hba1c target for patients on a drug which may cause hypoglycaemia (eg sulfonylurea) ?
53 mmol/mol
120
Insulin-dependent diabetics must check their blood glucose how often?
Check before driving and every 2 hours regardless of if she has eaten or not is correct. The DVLA recommends that patients taking insulin for their diabetes mellitus should check their blood glucose concentration every 2 hours, even if they use continuous glucose monitoring systems and/or they are asymptomatic. This applies regardless of whether they have eaten or not. Some patients may lose their awareness of hypoglycaemia and not experience symptoms due to diabetic neuropathy, and may only experience symptoms when their blood glucose concentration is dangerously low. For this reason, patients should monitor every 2 hours in general. In some cases, the frequency of monitoring may need to be increased, however, nothing in this stem suggests the need to do so.
121
What is the mechanism of action of Carbimazole?
Carbimazole is used in the management of thyrotoxicosis. It is typically given in high doses for 6 weeks until the patient becomes euthyroid before being reduced.
Mechanism of action
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
in contrast propylthiouracil as well as this central mechanism of action also has a peripheral action by inhibiting 5'-deiodinase which reduces peripheral conversion of T4 to T3
122
What are the adverse effects of Carbimazole?
agranulocytosis
crosses the placenta, but may be used in low doses during pregnancy
123
What is myxoedema coma?
Myxedema coma is a life-threatening complication of severe hypothyroidism, characterized by altered mental status, hypothermia, and multi-organ dysfunction. It is a medical emergency requiring immediate treatment.
124
What are the features of myxoedema coma?
The patient's weight gain, fatigue, and dry, coarse skin suggest hypothyroidism. Her altered mental status, hypothermia, bradycardia, and hypotension are key features of myxoedema coma
Hypothermia, hyporeflexia, bradycardia and seizures, think myxoedemic coma
125
What is the treatment for myxoedema coma?
Intravenous thyroxine and hydrocortisone
immediate thyroid hormone replacement is crucial, even before thyroid function test results are available to prevent further deterioration. Hydrocortisone is also given to prevent adrenal crises, which can be triggered by thyroxine treatment due to its role in cortisol clearance.
126
What is type 1 diabetics, blood glucose targets?
5-7 mmol/l on waking and
4-7 mmol/l before meals at other times of the day
127
What is the first line test for acromegaly?
Serum IGF-1 levels
128
What is the most common cause of primary hypoadrenalism/addisons in the UK, accounting for 80% of cases?
autoimmune adrenalitis
129
What are the features of addisons?
lethargy, weakness, anorexia, nausea & vomiting, weight loss, 'salt-craving'
hyperpigmentation (especially palmar creases)
ACTH is derived from a larger precursor molecule called proopiomelanocortin (POMC). When POMC is cleaved to produce ACTH, other melanocyte-stimulating hormones (MSH) are also produced. These MSHs have the effect of stimulating melanocytes in the skin to produce more melanin, the pigment responsible for skin colour
primary Addison's is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
vitiligo
loss of pubic hair in women
hypotension
hypoglycaemia
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
130
What are causes of addisons?
Autoimmune adrenalitis
Primary causes
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
Secondary causes
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
131
When do prescribe GLP-1 mimetics exenatide in diabetes treatment?
This class of drugs should be added only if the patient cannot tolerate triple therapy and they have a BMI greater than 35
If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic:
BMI ≥ 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
132
Side effects of glucocorticoids?
endocrine
impaired glucose regulation
increased appetite/weight gain
hirsutism
hyperlipidaemia
Cushing's syndrome
moon face
buffalo hump
striae
musculoskeletal
osteoporosis
proximal myopathy
avascular necrosis of the femoral head
immunosuppression
increased susceptibility to severe infection
reactivation of tuberculosis
psychiatric
insomnia
mania
depression
psychosis
gastrointestinal
peptic ulceration
acute pancreatitis
ophthalmic
glaucoma
cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
133
Side effects of mineral corticoids?
fluid retention
hypertension
134
What is the preferred investigation to diagnose type 1 diabestes?
What is not the preferred investigation to diagnose type 1 diabestes?
Random plasma glucose is the correct answer. This patient is presenting with symptoms of type 1 diabetes. Random plasma glucose > 11 mmol/L is diagnostic for type 1 diabetes. Alternatively, a fasting plasma glucose > 7 mmol/L can also be diagnostic.
HbA1c is not as useful for patients with a possible or suspected diagnosis of T1DM as it may not accurately reflect a recent rapid rise in serum glucose
135
What are clinical features of thyroid storm?
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically
136
What is the management of thyroid storm?
Thyrotoxic storm is treated with beta blockers, propylthiouracil and hydrocortisone
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
beta-blockers: typically IV propranolol
anti-thyroid drugs: e.g. methimazole or propylthiouracil
Lugol's iodine
dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
137
What are the Precipitating events of thyroid storm?
thyroid or non-thyroidal surgery
trauma
infection
acute iodine load e.g. CT contrast media
138
Amitriptyline is contradicted in which condition?
benign prostatic hyperplasia it is better to avoid amitriptyline due to the risk of urinary retention.
139
What are the causes of raised prolactin?
pregnancy
prolactinoma
physiological
polycystic ovarian syndrome
primary hypothyroidism
phenothiazines, metoclopramide, domperidone
140
DKA resolution is defined as:
pH >7.3 and
blood ketones < 0.6 mmol/L and
bicarbonate > 15.0mmol/L
141
What are the complications of DKA?
Complications may occur from DKA itself or the treatment:
gastric stasis
thromboembolism
arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia
acute respiratory distress syndrome
acute kidney injury
* children/young adults are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology etc. It usually occurs 4-12 hours following commencement of treatment but can present at any time. If there is any suspicion a CT head and senior review should be sought
142
Causes of hypoglycaemia
can be remembered by the mnemonic EXPLAIN
Exogenous drugs (typically sulfonylureas or insulin)
Pituitary insufficiency
Liver failure
Addison's disease
Islet cell tumours (insulinomas)
Non-pancreatic neoplasms
143
Blood pressure targets in type 2 diabetes
144
When should insulin and fluids be given to children when treating DKA?
When treating DKA in children, there is some evidence that cerebral oedema is more common if insulin is started early. Therefore, it is recommended to wait for at least an hour after IV fluids have been running before starting insulin treatment. There is no need to delay insulin treatment in adults.
