Endocrinology

Question 1

A young man with short stature, short 5th metacarpals, subcutaneous calcification, intellectual impairment and hypocalcemia.

Answer 1

Pseudohypoparathyroidism.
That is loss of function mutation affecting the G protein-linked receptor for PTH.

Question 2

Hormones involved in calcium regulation.

Answer 2

1- PTH ( Calcium increased)
2- Vit D ( Calcium Increased)
3- Calcitonin ( Calcium decreased)

Question 3

Diabetic Neuropathy

Answer 3

1. Distal. symmetrical polyneuropathy
2. Autonomic Neuropathy
3. Diabetic Amyotrophy

Question 4

Thyrotoxicosis

Answer 4

-Thyrotoxicosis is divided into
1- Graves’ Disease ( TSH-receptor antibody positive 95%, TPO antibody positive in 80%)
Exophthalmos, Lid retraction, Ptrtibial Myxoedema, Thyroid acropachy.
Carbimazole is the Rx.
2- Nodular Thyroid Disease ( Solitary toxic nodule, Toxic Multinodular goitre)
-Radioactive iodine therapy ( dose of 300- 500 MBq) is used to treat thyrotoxicosis.
3- Thyroiditis ( Viral, post partum, Drugs)

Question 5

Direct precursor to Oestradiol

Answer 5

Testosterone is derived from cholesterol and is converted to oestradiol by aromatase.

Question 6

Diabetes

Answer 6

0.2 U/kg or a flat dose of 10 U is the recommended starting dose for intermediate acting insulin.

Question 7

MODY

Answer 7

Monogenic diabetes/MODY is associated with gene mutations, most commonly HNF-1 alpha

Question 8

24 hours urinary free cortisol

Answer 8

Initial screening test to diagnose Cushing syndrome

Question 9

Weight Reduction

Answer 9

• it should be used in patients who have demonstrated dietary compliance with at least a 2.5 kg weight reduction.
  Orlistat functions through inhibiting the absorption of dietary fat from the GI tract. Consequently, its side effects include flatulence and diarrhoea.

Question 10

Short synacthen test is used to diagnose addison’s disease.

Answer 10

The link between Addison’s and primary hypothyroidism is that they are both conditions in the complex of autoimmune polyendocrine syndrome. Other possible associations of this cluster would be:

• Type 1 diabetes
• vitiligo
• pernicious anaemia, and
• chronic active hepatitis.

Question 11

Pheochromocytoma

Answer 11

Phenoxybenzamine should be intiated first to treat phaeochromocytoma.

Question 12

Diagnosis of Type 2 DM

Answer 12

Fasting glucose > 6.9 on two separate occasions

Question 13

Grave’s Eye disease

Answer 13

Block replace ( high dose carbimazole and thyroxine replacement) is initial choice for managing thyrotoxicosis in patients with significant thyroid eye disease.
» Radioiodine leads to transient worsening of thyroid eye disease.

Question 14

Tapering steroids

Answer 14

In patients on long-term glucocorticoid therapy, particularly those with low morning cortisol levels, switching to a shorter-acting glucocorticoid like hydrocortisone and tapering gradually is recommended to reduce the risk of adrenal insufficiency during the tapering process.

Question 15

Adrenal insufficiency
( Hyponatremia, Hyperkalemia, Postural hypotension)

Answer 15

Short synacthen test

Question 16

Acromegaly

Answer 16

Gold standard test to confirm growth hormone excess is IGF-1 serum levels

Question 17

Role of metformin in PCOS

Answer 17

Polycystic ovarian syndrome is recognised to be a condition associated with increased insulin resistance and metformin is effective through improvements in insulin sensitivity resulting in ovulation and improvements in hormonal perturbations

Question 18

Metformin adjustment in Ramadan

Answer 18

During Ramadan, one-third of the normal metformin dose should be taken before sunrise and two-thirds should be taken after sunset

Question 19

Addisons disease

Answer 19

• lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
  hyperpigmentation (especially palmar creases)
• vitiligo
• loss of pubic hair in women
• hypotension
• hypoglycaemia
• hyponatraemia and hyperkalaemia may be seen
  crisis: collapse, shock, pyrexia

Question 20

Causes of primary hyperparathyroidism

Answer 20

Causes of primary hyperparathyroidism

85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma

Question 21

Treatment of primary hyperparathyroidism

Answer 21

Investigations
- bloods
raised calcium, low phosphate
- PTH may be raised or (inappropriately, given the raised calcium) normal
- technetium-MIBI subtraction scan

x-ray findings
pepperpot skull
osteitis fibrosa cystica

Treatment
the definitive management is total parathyroidectomy

Question 22

Subacute (De Quervain’s) thyroiditis

Answer 22

Thyrotoxicosis with tender goitre = subacute (De Quervain’s) thyroiditis

The correct answer is naproxen. The diagnosis here is that of subacute (De Quervain’s) thyroiditis, given the history of following a viral illness, raised ESR, tender goitre and initial hyperthyroid phase. Ultimately, this condition is usually self-limiting, and simple analgesia is all that is required.

Question 23

Subacute Thyroiditis

Answer 23

Subacute thyroiditis (also known as De Quervain’s thyroiditis and subacute granulomatous thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism.

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

Investigations
thyroid scintigraphy: globally reduced uptake of iodine-131

Management
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

Question 24

Thyroid lymphoma

Answer 24

Hashimoto’s thyroiditis is associated with thyroid lymphoma

Question 25

Thyroid Cancer

Answer 25

- Papillary 70% Often young females - excellent prognosis - Follicular 20% - Medullary 5% Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2 - Anaplastic 1% Not responsive to treatment, can cause pressure symptoms - Lymphoma Rare Associated with Hashimoto's thyroiditis

Question 26

GLP 1 mimetics

Answer 26

Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide). Increased risk of severe pancreatitis and renal impairment. Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic. These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss. Liraglutide is the other GLP-1 mimetic. Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin) Dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown.

Question 27

Blood glucose

Answer 27

>>Average plasma glucose = (2 x HbA1c) - 4.5

Question 28

Lower than expected levels of HBA1C

Answer 28

Lower-than-expected levels of HbA1c (due to reduced red blood cell lifespan) - Sickle-cell anaemia - GP6D deficiency - Hereditary spherocytosis - Haemodialysis

Question 29

Higher than expected levels of HBA1C

Answer 29

Higher-than-expected levels of HbA1c (due to increased red blood cell lifespan) - Vitamin B12/folic acid deficiency - Iron-deficiency anaemia - Splenectomy

Question 30

Radioiodine treatment

Answer 30

1- Pregnancy 2- Thyroid Eye Disease 3- Age < 16 years

Question 31

Autoimmune Polyendocrinopathy Syndrome

Answer 31

APS type 2 has a polygenic inheritance and is linked to HLA DR3/DR4. Patients have Addison's disease plus either: - type 1 diabetes mellitus - autoimmune thyroid disease APS type 1 is occasionally referred to as Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC). It is a very rare autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21 Features of APS type 1 (2 out of 3 needed) - chronic mucocutaneous candidiasis (typically first feature as young child) - Addison's disease - primary hypoparathyroidism

Question 32

Grave's disease

Answer 32

Graves' disease: an autoimmune condition caused by IgG antibodies to the thyroid-stimulating hormone (TSH) receptor.

Question 33

Graves disease

Answer 33

Graves' disease is an autoimmune thyroid disease in which the body produces IgG antibodies to the thyroid-stimulating hormone (TSH) receptor. It is the most common cause of thyrotoxicosis and is typically seen in women aged 30-50 years. Features typical features of thyrotoxicosis specific signs limited to Grave's (see below) Features seen in Graves' but not in other causes of thyrotoxicosis - eye signs (30% of patients) - exophthalmos - ophthalmoplegia - pretibial myxoedema - thyroid acropachy, a triad of: digital clubbing - soft tissue swelling of the hands and feet - periosteal new bone formation Autoantibodies - TSH receptor stimulating antibodies (90%) - anti-thyroid peroxidase antibodies (75%) - Thyroid scintigraphy diffuse, homogenous, increased uptake of radioactive iodine

Question 34

Type 1 Diabetes

Answer 34

>>HbA1c should be monitored every 3-6 months Adults should have a target HbA1c level of 48 mmol/mol (6.5%) or lower. >>Self-monitoring of blood glucose Recommend testing at least 4 times a day, including before each meal and before bed. >>Blood glucose targets 5-7 mmol/l on waking and 4-7 mmol/l before meals at other times of the day. >Type of insulin offer multiple daily injection basal-bolus insulin regimens, rather than twice-daily mixed insulin regimens, as the insulin injection regimen of choice for all adults , twice-daily insulin detemir is the regimen of choice. Once-daily insulin glargine or insulin detemir is an alternative Offer rapid-acting insulin analogues injected before meals, rather than rapid-acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes Metformin NICE recommends considering adding metformin if the BMI >= 25 kg/m²

Question 35

Multiple Endocrine Neoplasia

Answer 35

MEN type I 3 P's Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia Pituitary (70%) Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration) Also: adrenal and thyroid Most common presentation = hypercalcaemia MEN Type IIa Medullary thyroid cancer (70%) 2 P's Parathyroid (60%) Phaeochromocytoma RET oncogene MEN Type IIb Medullary thyroid cancer 1 P Phaeochromocytoma Marfanoid body habitus Neuromas RET oncogene

Question 36

Diagnostic threshold for Gestational Diabetes

Answer 36

fasting glucose is >= 5.6 mmol/L 2-hour glucose is >= 7.8 mmol/L - Screening at 24-28 weeks

Question 37

Management of Gestational Diabetes

Answer 37

- If the fasting plasma glucose level is < 7 mmol/l a trial of diet and exercise should be offered if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started if glucose targets are still not met insulin should be added to diet/exercise/metformin gestational diabetes is treated with short-acting, not long-acting, insulin

Question 38

Metformin

Answer 38

If metformin is not tolerated due to GI side-effects, try a modified-release formulation before switching to a second-line agent.

Question 39

Metformin

Answer 39

Mechanism of action - acts by activation of the AMP-activated protein kinase (AMPK) - increases insulin sensitivity - Decreases hepatic gluconeogenesis - may also reduce gastrointestinal absorption of carbohydrates

Question 40

SGL-2 Inhibitors

Answer 40

SGLT-2 inhibitors 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. Important adverse effects include 1-urinary and genital infection (secondary to glycosuria). Fournier's gangrene has also been reported 2-Normoglycaemic ketoacidosis 3- increased risk of lower-limb amputation: feet should be closely monitored

Question 41

Physiological response to hypoglycaemia

Answer 41

Physiological response to hypoglycaemia Hormonal response: The first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released, but later. Sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system.

Question 42

Investigations of Hypoglycemia

Answer 42

- Insulinoma/ sulphonylurea High Insulin, High C-peptide - Exogenous Insulin/ Factitious disorder High Insulin Low C-peptide - Sepsis, Alcohol, Adrenal, Fasting, Starvation Low Insulin Low C-peptide

Question 43

Glycaemic index classification and Examples

Answer 43

High GI White rice (87), baked potato (85), white bread (80) Medium GI Couscous (65), boiled new potato (62), digestive biscuit (59), brown rice (58), Porridge (55) Low GI Fruit and vegetables, peanuts

Question 44

Glycaemic index of glucose

Answer 44

100

Question 45

Orlistat

Answer 45

Orlistat works by inhibiting gastric and pancreatic lipase to reduce the digestion of fat.

Question 46

Obesity Management

Answer 46

- conservative: diet, exercise - medical orlistat liraglutide - surgical

Question 47

Hungry Bone Syndrome

Answer 47

Hungry bone syndrome is the result of a sudden drop in previously high parathyroid hormone levels after parathyroidectomy.

Question 48

Anorexia Features

Answer 48

Anorexia features Most things low G's and C's raised: growth hormone, glucose, salivary glands, cortisol, cholesterol, carotinaemia

Question 49

Anorexia Nervosa

Answer 49

Physiological abnormalities hypokalaemia low FSH, LH, oestrogens and testosterone raised cortisol and growth hormone impaired glucose tolerance hypercholesterolaemia hypercarotinaemia low T3

Question 50

Subacute( De Quervain’s) thyroidoitis

Answer 50

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 Investigations thyroid scintigraphy: globally reduced uptake of iodine-131 Management 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

Question 51

Polyuria

Answer 51

Common (>1 in 10) diuretics, caffeine & alcohol diabetes mellitus lithium heart failure Infrequent (1 in 100) hypercalcaemia hyperthyroidism Rare (1 in 1000) chronic kidney disease primary polydipsia hypokalaemia Very rare (<1 in 10 000) diabetes insipidus

Question 52

Alcohol Bingeing

Answer 52

Alcohol bingeing can lead to ADH suppression in the posterior pituitary gland subsequently leading to polyuria

Question 53

DKA ( Joint British Diabetes Society)

Answer 53

glucose > 11 mmol/l or known diabetes mellitus pH < 7.3 bicarbonate < 15 mmol/l ketones > 3 mmol/l or urine ketones ++ on dipstick

Question 54

DKA

Answer 54

Pathophysiology DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies

Question 55

Cushings

Answer 55

- Iatrogenic: corticosteroid therapy - ACTH-dependent causes Cushing's disease (a pituitary adenoma → ACTH secretion) - ectopic ACTH secretion secondary to a malignancy - ACTH-independent causes adrenal adenoma

Question 56

Cushing's Syndrome

Answer 56

Cushing's syndrome - hypokalaemic metabolic alkalosis

Question 57

Tests to confirm Cushing's syndrome

Answer 57

The three most commonly used tests are: 1- overnight (low-dose) dexamethasone suppression test This is the most sensitive test and is now used first-line to test for Cushing's syndrome Patients with Cushing's syndrome do not have their morning cortisol spike suppressed 2- 24 hr urinary free cortisol two measurements are required 3- bedtime salivary cortisol two measurements are required

Question 58

differentiate between true Cushing's and pseudo-Cushing's

Answer 58

An insulin stress test is used to differentiate between true Cushing's and pseudo-Cushing's

Question 59

differentiate between pituitary and ectopic ACTH secretion.

Answer 59

Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion.

Question 60

High Dose Dexamethasone Suppression Test

Answer 60

Cortisol and ACTH Suppressed in Cushing's disease (i.e. pituitary adenoma → ACTH secretion)

Question 61

Obesity

Answer 61

Leptin is thought to play a key role in the regulation of body weight. It is produced by adipose tissue and acts on satiety centres in the hypothalamus and decreases appetite. More adipose tissue (e.g. in obesity) results in high leptin levels. - Ghrelin stimulates hunger. It is produced mainly by the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas. Ghrelin levels increase before meals and decrease after meals

Question 62

Pyridostigmine

Answer 62

Pyridostigmine is a long-acting acetylcholinesterase inhibitor that reduces the breakdown of acetylcholine in the neuromuscular junction, temporarily improving symptoms of myasthenia gravis.

Question 63

Myasthenia Gravis

Answer 63

Investigations - Single fibre electromyography: high sensitivity (92-100%) - CT thorax to exclude thymoma - CK normal - antibodies to acetylcholine receptors (positive in around 85-90% of patients).

Question 64

Myasthenia Gravis

Answer 64

- Long-acting acetylcholinesterase inhibitors pyridostigmine is first-line - Immunosuppressants prednisolone initially azathioprine, cyclosporine, mycophenolate mofetil may also be used - thymectomy

Question 65

Skin disorders associated with thyroid disease

Answer 65

Skin manifestations of hypothyroidism dry (anhydrosis), cold, yellowish skin non-pitting oedema (e.g. hands, face) dry, coarse scalp hair, loss of lateral aspect of eyebrows eczema xanthomata Skin manifestations of hyperthyroidism Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli thyroid acropachy: clubbing scalp hair thinning increased sweating

Question 66

Metformin

Answer 66

1. acts by activation of the AMP-activated protein kinase (AMPK) 2. increases insulin sensitivity 3. Decreases hepatic gluconeogenesis 4. may also reduce gastrointestinal absorption of carbohydrates

Question 67

Levothyroxine absorption

Answer 67

Iron/calcium carbonate tablets can reduce the absorption of levothyroxine - should be given 4 hours apart.

Question 68

Hypothyroidism ( Pregnancy)

Answer 68

Women with established hypothyroidism who become pregnant should have their dose increased by at least 25-50 micrograms levothyroxine due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value

Question 69

Side-effects of thyroxine therapy

Answer 69

Side-effects of thyroxine therapy hyperthyroidism: due to over treatment reduced bone mineral density worsening of angina atrial fibrillation

Question 70

Hyperthyroidism in Pregnancy

Answer 70

In pregnant woman who develop hyperthyroidism in the first trimester, propylthiouracil is preferred over carbimazole due to lower risk of foetal malformation

Question 71

Sulphonylureas

Answer 71

Sulphonylureas may cause syndrome of inappropriate ADH

Question 72

T2DM

Answer 72

TD2M: if a triple combination of drugs has failed to reduce HbA1c then switching one of the drugs for a GLP-1 mimetic is recommended, particularly if the BMI > 35

Question 73

False Negative Renin Aldosterone ratio

Answer 73

Medications that can cause false negative renin:aldosterone ratio results are the following: Angiotensin-converting enzyme inhibitors (e.g. ramipril or lisinopril). Angiotensin receptor blockers (e.g. losartan). Direct renin inhibitors (e.g aliskiren). Aldosterone antagonists (e.g. spironolactone or eplerenone).

Question 74

Primary Hyperaldosteronism

Answer 74

Cause: Bilateral Idiopathic Adrenal Hyperplasia Investigation: Renin Aldosterone ratio High resolution CT Abdomen Adrenal vein sampling Management adrenal adenoma: surgery (laparoscopic adrenalectomy) bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone

Question 75

DPP-4 inhibitors

Answer 75

Dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown.

Question 76

Acromegaly

Answer 76

Features coarse facial appearance, spade-like hands, increase in shoe size large tongue, prognathism, interdental spaces excessive sweating and oily skin: caused by sweat gland hypertrophy features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia raised prolactin in 1/3 of cases → galactorrhoea 6% of patients have MEN-1 Complications hypertension diabetes (>10%) cardiomyopathy colorectal cancer

Question 77

Riedel's thyroiditis

Answer 77

Riedel's thyroiditis is a rare cause of hypothyroidism characterised by dense fibrous tissue replacing the normal thyroid parenchyma. On examination a hard, fixed, painless goitre is noted. It is usually seen in middle-aged women. It is associated with retroperitoneal fibrosis.

Question 78

Sulfonylureas

Answer 78

Sulfonylureas - bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.

Question 79

Insulinoma

Answer 79

An insulinoma is a neuroendocrine tumour deriving mainly from pancreatic Islets of Langerhans cells Basics most common pancreatic endocrine tumour 10% malignant, 10% multiple of patients with multiple tumours, 50% have MEN-1 Features of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc rapid weight gain may be seen high insulin, raised proinsulin:insulin ratio high C-peptide Diagnosis - Supervised, prolonged fasting (up to 72 hours) - CT pancreas Management - surgery - Diazoxide and somatostatin if patients are not candidates for surgery