Endocrine Flashcards

Question

why is it important to recognise subclinical hyperthyroidism?

Answer 1

The importance in recognising subclinical hyperthyroidism lies in the potential effect on the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and ↑ the likelihood of dementia

Answer 2

Management • TSH levels often revert back to normal - therefore levels must be persistently low to warrant intervention • A reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission

Answer 3

Basics • Normal T3 – T4 • ↑TSH • No obvious symptoms

Answer 4

Significance • Risk of progressing to overt hypothyroidism is 2-5% per year (higher in men) • Risk ↑ by presence of thyroid autoantibodies

Answer 5

Treat if • TSH>10 • Thyroid autoantibodies positive • Other autoimmune disorder • Previous treatment of graves' disease

Answer 6

In European countries primary atrophic hypothyroidism is the most cause causes of hypothyroidism, whereas in North America Hashimoto's thyroiditis appears to account for the majority of cases. The reason for this discrepancy is unclear Hypothyroidism affects around 1-2% of women in the UK and is around 5-10 times more common in ♀s than ♂s.

Answer 7

1. primary atrophic hypothyroidism 2. Hashimoto's thyroiditis 3. After thyroidectomy or radioiodine treatment 4. Drug therapy (e.g. lithium, amiodarone or anti-thyroid drugs such as carbimazole) 5. Dietary iodine deficiency

Answer 8

• Most common cause in Europe • Autoimmune disease, associated with IDDM, Addison's or pernicious anemia • 5 times more common in women

Answer 9

1. From pituitary failure 2. Other associated conditions • Down's syndrome • Turner's syndrome • Coeliac disease

Answer 10

A TSH value between 0.5 to 2.5 mU/l is now considered preferable

Answer 11

• Initial starting dose of levothyroxine should be lower in elderly patients and those with ischemic heart disease (e.g. 25–50 mcg/day). • Following a change in thyroxine dose thyroid function tests should be checked after 6-8 weeks • The therapeutic goal is 'normalisation' of the thyroid stimulating hormone (TSH) level. As the majority 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. Dosage changes should of course also take account of symptoms • There is no evidence to support combination therapy with levothyroxine and liothyronine

Answer 12

• Hyperthyroidism: due to over treatment • ↓ bone mineral density • Worsening of angina • Atrial fibrillation

Answer 13

Steroid therapy is required prior to thyroxine

Answer 14

low/normal TSH low T4 common in inpatients, changes are reversible upon recovery from the systemic illness. Usually in hospitalized patients.

Answer 15

high TSH normal or high T4

Answer 16

low TSH, high T4

Answer 17

Pendred's Syndrome Autosomal recessive disorder of defective iodine uptake

Answer 18

Features: • Sensorineural deafness • Goitre • Euthyroid or mild hypothyroidism

Answer 19

• Pretibial myxedema: erythematous, edematous lesions above the lateral malleoli • Thyroid acropachy: clubbing • Scalp hair thinning • ↑ sweating Pruritus can occur in both hyper- and hypothyroidism

Answer 20

• Dry (anhydrosis), cold, yellowish skin • Non-pitting edema (e.g. Hands, face) • Dry, coarse scalp hair, loss of lateral aspect of eyebrows • Eczema • Xanthomata Pruritus can occur in both hyper- and hypothyroidism

Answer 21

Propylthiouracil is traditionally taught as the antithyroid drug of choice in pregnancy. This approach was supported by the 2007 Endocrine Society consensus guidelines. It also has the advantage of being excreted to a lesser extent than carbimazole in breast milk.

Answer 22

Pregnancy: Thyroid Problems in pregnancy there is ↑ in the levels of thyroxine-binding globulin (TBG). This causes ↑ in the levels of total thyroxine but does not affect the free thyroxine level

Answer 23

Thyrotoxicosis • Untreated thyrotoxicosis ↑ the risk of fetal loss, maternal heart failure and premature labour

Answer 24

• Graves' disease is the most common cause of thyrotoxicosis in pregnancy. It is also recognised that activation of the TSH receptor by HCG may also occur - often termed transient gestational hyperthyroidism. HCG levels will fall in second and third trimester

Answer 25

• Propylthiouracil has traditionally been the antithyroid drug of choice. This approach was supported by the 2007 endocrine society consensus guidelines • Maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism • Thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine risk of neonatal thyroid problems • Block-and-replace regimes should not be used in pregnancy • Radioiodine therapy is contraindicated

Answer 26

Key points • Thyroxine is safe during pregnancy • Serum thyroid stimulating hormone measured in each trimester and 6-8 weeks post-partum • Some women require an ↑ dose of thyroxine during pregnancy • Breast feeding is safe whilst on thyroxine

Answer 27

Papillary: 70% - Often young ♀s - excellent prognosis (associated with FAP) Follicular: 20% Spreads through blood vessels Medullary: 5% Cancer of parafollicular cells, secrete calcitonin, part of MEN-2 Anaplastic: 1% Not responsive to treatment, can cause pressure symptoms L ymphoma: Rare Associated with Hashimoto's and other autoimmune disorders Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones

Answer 28

Management of papillary and follicular cancer • Total thyroidectomy • Followed by radioiodine (I-131) to kill residual cells • Yearly thyroglobulin levels to detect early recurrent disease (only after total thyroid ablation)

Answer 29

Primary Hyperparathyroidism: In postgraduate exams primary hyperparathyroidism is stereotypically seen in elderly ♀s with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma

Answer 30

Features: 'Bones, stones, abdominal groans and psychic moans' • Polydipsia, polyuria • Peptic ulceration/constipation/pancreatitis • Bone pain/fracture • Renal stones • Depression • Hypertension

Answer 31

Associations • Hypertension • Multiple endocrine neoplasia: MEN I and II

Answer 32

Investigations • Raised calcium, low phosphate • PTH may be raised or normal • Technetium-MIBI subtraction scan

Answer 33

Treatment • IV Fluids • Total parathyroidectomy • Bisphosphonates

Answer 34

Primary hypoparathyroidism • ↓ PTH secretion • E.g. Secondary to thyroid surgery • Low calcium, high phosphate • Treat with alfacalcidol

Answer 35

• Target cells being insensitive to PTH • In type I pseudohypoparathyroidism there is a complete receptor defect whereas in type II the cell receptor is intact. • Due to abnormality in a G protein • Autosomal dominant fashion • Associated with low IQ, short stature, shortened 4th and 5th metacarpals • Low calcium, high phosphate, high PTH • Diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause ↑ in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are ↑ whilst in pseudohypoparathyroidism type II only cAMP rises.

Answer 36

Pseudopseudohypoparathyroidism • Similar phenotype to pseudohypoparathyroidism but normal biochemistry

Answer 37

Causes of Cranial DI • Idiopathic • Post head injury • Pituitary surgery • Craniopharyngiomas • Histiocytosis X

Answer 38

DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)

Answer 39

Causes of nephrogenic DI • Genetic (primary) • Electrolytes: hypercalcemia, Hypokalemia • Drugs: demeclocycline, lithium • Tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis

Answer 40

Investigation • High plasma osmolarity, low urine osmolarity • Water deprivation test

Answer 41

If the patient is symptomatic: • Fasting glucose ≥7.0 mmol/l • Random glucose ≥11.1 mmol/l (or after 75g oral glucose tolerance test) If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions. Impaired fasting glucose (IFG): fasting glucose 6.1 - 7.0 mmol/l implies impaired fasting glucose Impaired glucose tolerance (IGT): fasting plasma glucose < 7.0 and OGTT 2-hour 7.8 - 11.1

Answer 42

If the patient is symptomatic: • Fasting glucose ≥7.0 mmol/l • Random glucose ≥11.1 mmol/l (or after 75g oral glucose tolerance test) If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions. Impaired fasting glucose (IFG): fasting glucose 6.1 - 7.0 mmol/l implies impaired fasting glucose Impaired glucose tolerance (IGT): fasting plasma glucose < 7.0 and OGTT 2-hour 7.8 - 11.1 a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes) in patients without symptoms, the test must be repeated to confirm the diagnosis it should be remembered that misleading HbA1c results can be caused by increased red cell turnover

Answer 43

Common adverse effects • Hypoglycaemic episodes (more common with long acting preparations such as chlorpropamide) • ↑ appetite and weight gain Rarer adverse effects • Syndrome of inappropriate ADH secretion • Bone marrow suppression • Liver damage (cholestatic) • Photosensitivity • Peripheral neuropathy • Sulfonylureas should be avoided in breast feeding and pregnancy

Answer 44

Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. Mechanism of action • ↑ Insulin sensitivity • ↓ hepatic gluconeogenesis • May also ↓ gastrointestinal absorption of carbohydrates

Answer 45

Unlike sulphonylureas it does not cause hypoglycemia and weight gain and is therefore first-line if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease

Answer 46

Adverse effects • Gastrointestinal upsets are common (nausea, anorexia, diarrhea), intolerable in 20% • ↓ vitamin B12 absorption - rarely a clinical problem • Lactic acidosis* with severe liver disease or renal failure • High dose (>2gm) interferes with enterohepatic circulation of bile salt → diarrhea. Gastrointestinal side-effects are more likely to occur if metformin is not slowly titrated up. The BNF advises leaving at least 1 week before increasing the dose. If a patient is intolerant to standard metformin then modified release preparations should be tried

Answer 47

• Chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 μmol/l and stopping metformin if > 150 μmol/l • Do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis) • Alcohol abuse is a relative contraindication • Stop 2 days before general anaesthetic, restart when renal function normal • Stop prior to IV contrast e.g. Angiography, restart when renal function normal

Answer 48

Thiazolidinediones are a new class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and ↓ peripheral insulin resistance Peroxisome Proliferator-Activated Receptor Gamma (PPAR-gamma receptor) is an intracellular nuclear receptor. Its natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function

Answer 49

Adverse effects • Weight gain • Liver impairment: monitor LFTs • Fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is ↑ if the patient also takes insulin • Recent studies have indicated an ↑ risk of fractures • Rosiglitazone is not recommended for use in patients with ischemic heart disease or peripheral arterial disease. The risk of complications may be ↑ if rosiglitazone is combined with insuli

Answer 50

NICE guidance on thiazolidinediones • Only continue if there is a reduction of > 0.5 percentage points in HbA1c in 6 months

Answer 51

a hormone released by the small intestine in response to an oral glucose load In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be ↓ in T2DM. Increasing GLP-1 levels, either by the administration of an analogue or inhibiting its breakdown, is therefore the target of two recent classes of drug

Answer 52

• ↑ insulin secretion and inhibit glucagon secretion • Licensed for use in T2DM • Must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal • May be combined with metformin, a sulfonylurea or a thiazolidinedione • Typically results in weight loss • Major adverse effect is nausea and vomiting • The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide: o increased risk of severe pancreatitis o increased risk of renal impairment

Answer 53

• ↑ insulin secretion and inhibit glucagon secretion • Licensed for use in T2DM • Must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal • May be combined with metformin, a sulfonylurea or a thiazolidinedione • Typically results in weight loss • Major adverse effect is nausea and vomiting • The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide: o increased risk of severe pancreatitis o increased risk of renal impairment

Answer 54

NICE guidelines on the use of Exenatide if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if: 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

Answer 55

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors (e.g. Vildagliptin, sitagliptin) • Oral preparation • Trials show that the drugs are relatively well tolerated with no ↑ incidence of hypoglycemia • Do not cause weight gain

Answer 56

NICE Guidelines on DPP-4 Inhibitors • Continue DPP-4 inhibitor only if there is ↓ of > 0.5 percentage points in HbA1c in 6 months • NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione

Answer 57

• 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 use of foods marketed specifically at people with diabetes • Initial target weight loss in an overweight person is 5-10%

Answer 58

Lifestyle 48 mmol/mol (6.5%) Lifestyle + metformin 48 mmol/mol (6.5%) Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) 53 mmol/mol (7.0%)

Answer 59

This is area which has changed in 2015 individual targets should be agreed with patients to encourage motivation HbA1c should be checked every 3-6 months until stable, then 6 monthly NICE encourage us to consider relaxing targets on 'a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes' in 2015 the guidelines changed so HbA1c targets are now dependent on treatment

Answer 60

Same as non-diabetics clinic BP HBPM/ABPM Age < 80 years 140/90 mmHg 135/85 mmHg Age > 80 years 150/90 mmHg 145/85 mmHg) • ACE inhibitors are first-line

Answer 61

metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list: sulfonylurea gliptin pioglitazone SGLT-2 inhibitor if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered: metformin + gliptin + sulfonylurea metformin + pioglitazone + sulfonylurea metformin + sulfonylurea + SGLT-2 inhibitor metformin + pioglitazone + SGLT-2 inhibitor OR insulin therapy should be considered

Answer 62

if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions, consider one of the following: sulfonylurea gliptin pioglitazone if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used: gliptin + pioglitazone gliptin + sulfonylurea pioglitazone + sulfonylurea if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy

Answer 63

following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on • If serum cholesterol target is not reached consider increasing simvastatin to 80mg HS. • If target still not reached consider using a more effective statin (e.g. Atorvastatin) or adding ezetimibe • Target total cholesterol is < 4.0 mmol/l

Answer 64

Starting insulin • Usually commenced if HbA1c > 7.5% • NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bed-time or twice daily according to need

Answer 65

• Aspirin to all patients > 50 years and to younger patients with other significant risk factors

Answer 66

• If serum triglyceride levels are > 4.5 mmol/l prescribe fenofibrate

Answer 67

• First-line: oral duloxetine. Oral amitriptyline if duloxetine is contraindicated. • Second-line treatment: if first-line treatment was with duloxetine, switch to amitriptyline or pregabalin, or combine with pregabalin. If first-line treatment was with amitriptyline, switch to or combine with pregabalin • Other options: pain management clinic, tramadol (not other strong opioids), topical lidocaine for localised pain if patients unable to take oral medication • Consider capsaicin ointment (red pepper extract) local application

Answer 68

Gastroparesis • Symptoms include erratic blood glucose control, bloating and vomiting • Management options include metoclopramide, domperidone or erythromycin

Answer 69

↑ Insulin with ↓ C-Peptide level points to a diagnosis of insulin abuse C-Peptide level ↑ with Sulfonylurea abuse

Answer 70

Causes • Insulinoma - ↑ ratio of proinsulin to insulin • Self-administration of insulin/sulphonylureas • Liver failure • Addison's disease • Alcohol Other possible causes in children • Nesidioblastosis - β cell hyperplasia

Answer 71

Glycosylated hemoglobin (HbA1c) is the most widely used measure of long-term glycaemic control in DM. HbA1c is produced by the glycosylation of hemoglobin at a rate proportional to the glucose concentration. The level of HbA1c therefore is dependent on • Red blood cell lifespan • Average blood glucose concentration HbA1c is generally thought to reflect the blood glucose over the previous '2-3 months' although there is some evidence it is weighed more strongly to glucose levels of the past 2-4 week

Answer 72

1. Glucose > 33.3 mmol/l 2. pH > 7.30 3. Serum bicarbonate > 15 mmol/l 4. Serum osmolality > 320 mosmol/kg 5. Traces of ketones may be present in urines

Answer 73

Pathophysiology -Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium -Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood. -Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.

Answer 74

General: fatigue, lethargy, nausea and vomiting Neurological: altered level of consciousness, headaches, papilloedema, weakness Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis) Cardiovascular: dehydration, hypotension, tachycardia

Answer 75

1. Normalise the osmolality (gradually) 2. Replace fluid and electrolyte losses 3. Normalise blood glucose (gradually)

Answer 76

Intravenous (IV) 0.9% sodium chloride solution is the first line fluid for restoring total body fluid -If the serum osmolarity is not declining despite positive balance with 0.9% sodium chloride, then the fluid should be switched to 0.45% sodium chloride solution which is more hypotonic relative to the HHS patients serum osmolarity -IV fluid replacement should aim to achieve a positive balance of 3-6 litres by 12 hours and the remaining replacement of estimated fluid losses within the next 12 hours.

Answer 77

If significant ketonaemia is present (3β-hydroxy butyrate is more than 1 mmol/L) this indicates relative hypoinsulinaemia and insulin should be started at time zero (e.g. mixed DKA / HHS picture). The recommended insulin dose is a fixed rate intravenous insulin infusion given at 0.05 units per kg per hour. If significant ketonaemia is not present (3β-hydroxy butyrate is less than 1 mmol/L) then do NOT start insulin.

Answer 78

The low-insulin condition in DKA stimulate → lipolysis → production of ketone bodies, β- hydroxybutyrate and acetoacetate, which can be used as metabolic fuel

Answer 79

British joint diabetes society Key points glucose > 11 mmol/l or known diabetes mellitus pH < 7.3 bicarbonate < 15 mmol/l ketones > 3 mmol/l or urine ketones ++ on dipstick American diabetes assoc Key points glucose > 13.8 mmol/l pH < 7.30 serum bicarbonate <18 mmol/l anion gap > 10 ketonaemia

Answer 80

fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially. -insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started -correction of hypokalaemia -long-acting insulin should be continued, short-acting insulin should be stopped

Answer 81

• Gastric stasis • Cerebral edema • Thromboembolism • Acute respiratory distress syndrome • Acute renal failure

Answer 82

Pregnancy: Diabetes Mellitus Diabetes mellitus may be a pre-existing problem or develop during pregnancy, gestational diabetes. It complicates around 1 in 40 pregnancies

Answer 83

Risk factors for gestational diabetes • BMI of > 30 kg/m2 • Previous macrosomic baby weighing 4.5 kg or above. • Previous gestational diabetes • First-degree relative with diabetes • Family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle Eastern)

Answer 84

Screening for gestational diabetes • If a women has had gestational diabetes previously an oral glucose tolerance test (OGTT) should be performed at 16-18 weeks and at 28 weeks if the first test is normal • Women with any of the other risk factors should be offered an OGTT at 24–28 weeks

Answer 85

Management • Weight loss for women with BMI of > 27 kg/m2 • Stop oral hypoglycaemic agents, apart from metformin*, and commence insulin • Folic acid 5 mg/day from pre-conception to 12 weeks gestation • Detailed anomaly scan at 18-20 weeks including 4-chamber view of the heart and outflow tracts • Tight glycaemic control ↓ complication rates • Treat retinopathy as can worsen during pregnancy

Answer 86

Women who develop gestational diabetes should stop taking hypoglycaemic medication following delivery. A fasting glucose should be checked at the 6 week postnatal check

Answer 87

Type 1 Diabetes Mellitus is caused by autoimmune destruction of the β-cells of the pancreas. Identical twins show a genetic concordance of 40%. It is associated with HLA-DR3 and DR4. It is inherited in a polygenic fashion

Answer 88

Type 1 DM Pathophysiology: • Autoimmune disease • Antibodies against β cells of pancreas • HLA DR4 > HLA DR3 • Various antibodies such as islet-associated antigen (IAA) antibody and glutamic acid decarboxylase (GAD) antibody are detected in patients who later go on to develop type 1 DM - their prognostic significance is not yet clear

Answer 89

Adhesive capsulitis (frozen shoulder) is strongly associated with diabetes type-I with as many as 40% of patients developing this problem at some stage

Answer 90

Type 2 diabetes mellitus is thought to be caused by a relative deficiency of insulin and the phenomenon of insulin resistance. Age, obesity and ethnicity are important aetiological factors. There is almost 100% concordance in identical twins and no HLA associations

Answer 91

Maturity-Onset Diabetes Of The Young (MODY) is characterized by the development of type 2 diabetes mellitus in patients < 25 years old. It is typically inherited as an autosomal dominant condition. Over six different genetic mutations have so far been identified as leading to MODY. Ketosis is not a feature at presentation. Usually there is a strong family history

Answer 92

MODY 3 • 60% of cases • Due to a defect in the HNF-1 α gene (Hepatocyte Nuclear Factor). MODY 2 • 20% of cases • Due to a defect in the glucokinase gene MODY 1 • <10% • Due to defect in HNF-4 α gene.

Answer 93

Specific rules • If on insulin then can hold HGV license if: there has not been any severe hypoglycaemic event in the previous 12 months the driver has full hypoglycaemic awareness the driver must show adequate control of the condition by regular blood glucose monitoring*, at least twice daily and at times relevant to driving the driver must demonstrate an understanding of the risks of hypoglycaemia here are no other debarring complications of diabetes • If on insulin then patient can drive a car as long as they have hypoglycaemic awareness and no relevant visual impairment • If on tablets, exenatide or gliptin no need to notify DVLA • If diet controlled alone and no relevant complications (e.g. Maculopathy) then no requirement to inform DVLA

Answer 94

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

Answer 95

Features • Of hypoglycemia: 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

Answer 96

Diagnosis • Supervised, prolonged fasting (up to 72 hours) • CT pancreas

Answer 97

Basics • Used in investigation of hypopituitarism • IV insulin given, GH and cortisol levels measured • With normal pituitary function GH and cortisol should rise nsulin stress tests are also occasionally used to differentiate Cushing's from pseudo-Cushing

Answer 98

Contraindications • Epilepsy • Ischemic heart disease • Adrenal insufficiency

Answer 99

Cushing's disease (pituitary tumor) is the most common, non-iatrogenic, cause of Cushing's syndrome

Answer 100

ACTH dependent causes • Cushing's disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia • Ectopic ACTH production (5-10%): e.g. Small cell lung cancer Small cell lung cancer accounts 50-75% of case of ectopic ACTH

Answer 101

ACTH independent causes • Iatrogenic: steroids • Adrenal adenoma (5-10%) • Adrenal carcinoma (rare) • Carney complex: syndrome including cardiac myxoma • Micronodular adrenal dysplasia (very rare)

Answer 102

Pseudo-Cushing's • Mimics Cushing's • Often due to alcohol excess or severe depression • Causes false positive dexamethasone suppression test or 24 hr urinary free cortisol • Insulin stress test may be used to differentiate

Answer 103

The two most commonly used tests are: overnight dexamethasone suppression test (most sensitive) 24 hr urinary free cortisol

Answer 104

Cortisol following low-dose dexamethasone: low Cortisol following high-dose dexamethasone: low ACTH: normal

Answer 105

Cortisol following low-dose dexamethasone: unequiv. Cortisol following high-dose dexamethasone: unequiv. ACTH: low

Answer 106

Cortisol following low-dose dexamethasone: unequiv. Cortisol following high-dose dexamethasone: low ACTH: high

Answer 107

Cortisol following low-dose dexamethasone: uneiquiv Cortisol following high-dose dexamethasone: unequiv ACTH: high

Answer 108

High-dose dexamethasone suppression test • If pituitary source then cortisol suppressed • If ectopic/adrenal then no change in cortisol

Answer 109

CRH (corticotrophin-releasing hormone) stimulation • If pituitary source then cortisol rises • If ectopic/adrenal then no change in cortisol

Answer 110

Liddle's Syndrome is an autosomal dominant disorder that mimics hyperaldosteronism, resulting in Hypokalemia associated with hypertension. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium, leading to hypokalemia and alkalosis. ↓ rennin - ↓ aldesterone

Answer 111

Treatment is with either amiloride or triamterene

Answer 112

Gitelman’s Syndrome: defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule Little minded people (Liddle) would’ve HTN but gentlemen would not develop HTN Features • Hypokalemia • Hypomagnesemia • Hypocalciuria • Metabolic alkalosis • Normotension ↑ rennin - ↑ aldesterone

Answer 113

Bartter's Syndrome is an inherited cause (usually autosomal recessive) of severe Hypokalemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter in the ascending loop of Henle. It should be noted that is associated with normotension (unlike other endocrine causes of Hypokalemia such as Conn's, Cushing's and Liddle's syndrome which are associated with hypertension)

Answer 114

Features: • Usually presents in childhood, e.g. Failure to thrive • Polyuria, polydipsia • Renal stones, nephrocalcinosis is commom • W eakness ↑ rennin - ↑ aldesterone

Answer 115

bartter's syndrome

Answer 116

Primary Hyperaldosteronism: primary hyperaldosteronism was previously thought to be most commonly caused by an adrenal adenoma, termed Conn's Syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in 70% of cases.

Answer 117

Features • Hypertension • Hypokalemia (e.g. Muscle weakness) • Alkalosis • Hypernatremia • Not related to posture

Answer 118

the 2016 Endocrine Society recommend that a plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone) following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess Adrenal Venous Sampling (AVS) can be done to identify the gland secreting excess hormone in primary hyperaldosteronism

Answer 119

Sodium restrict adrenal adenoma: surgery bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone

Answer 120

Addison's Disease: autoimmune destruction of the adrenal glands is the commonest cause of hypoadrenalism in the UK, accounting for 80% of cases

Answer 121

Features • Lethargy, weakness, anorexia, nausea & vomiting, weight loss • Hyperpigmentation, vitiligo, loss of pubic hair in women • Crisis: collapse, shock, pyrexia Typical history of Addison's: abdominal pain and vomiting. Patients may have a history of other autoimmune conditions such as thyroid disorders. Steroids should be given as soon as possible

Answer 122

•Tuberculosis •Metastases (e.g. Bronchial Carcinoma) •Meningococcal septicemia (Waterhouse-Friderichsen Syndrome) •HIV •Antiphospholipid Syndrome •Severe illness

Answer 123

•Pituitary disorders (e.g. Tumours, Irradiation, Infiltration) •Drugs: ACE-I – Heparin – Lead poisoning

Answer 124

3. Exogenous glucocorticoid therapy

Answer 125

Pseudohypoaldosteronism: due to primary aldosterone resistance (rare, but may occur due to Spirnolactone)

Answer 126

Dehydroepiandrosterone is the most abundant circulating adrenal steroid. Adrenal glands are the main source of DHEA in ♀s - loss of functioning adrenal tissue as in Addison's disease may result in symptoms secondary to androgen deficiency, such as loss of libido. Research is ongoing as to whether routine replacement of DHEA is beneficial

Answer 127

Hyponatremia and high potassium in a patient with lethargy is highly suggestive of Addison's

Answer 128

The short synacthen test is the best test to diagnose Addison's disease Investigations: in a patient with suspected Addison's disease the definite investigation is a short ACTH test. Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated If an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful: > 500 nmol/l makes Addison's very unlikely < 100 nmol/l is definitely abnormal 100-500 nmol/l should prompt a ACTH stimulation test to be performed

Answer 129

Associated electrolyte abnormalities • Hyperkalemia • Hyper-Renin • Hypo-Aldosterone • Hyponatremia • Hypoglycemia • Metabolic acidosis (Hypo pH)

Answer 130

Criteria: • Normal Renal, Normal Adrenal and Normal Thyorid • Hyponatremia <135 mEq/L • Hypotonic plasma - POsm <270 mOsm/kg. • Inappropriately ↑ urine osmolality • Urine sodium >20 mEq/L (inappropriate natriuresis) • Maintained hypervolemia • Suppression of renin-angiotensin system (RAS) • No equal concentration of atrial natriuretic peptide • ↓BUN • Normal S.Creatinine • ↓ uric acid • ↓ albumin • Normal Acid-Base, K+ balance

Answer 131

1. Malignancy • Especially small cell lung cancer • Also: pancreas, prostate 2. Neurological • Stroke • Subarachnoid hemorrhage • Subdural hemorrhage • Meningitis/encephalitis/abscess 3. Infections • TB • Pneumonia 4. Drugs • Sulfonylureas • SSRIs, tricyclics • Carbamazepine • Vincristine • Cyclophosphamide 5. Other causes • Positive end-expiratory pressure (PEEP) • Porphyrias

Answer 132

Treatment: • Demeclocycline

Answer 133

Pheochromocytoma: is a rare catecholamine secreting neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue. It secretes excessive amounts of catecholamines, usually adrenaline if in the adrenal gland (not extra-adrenal) and noradrenaline.

Answer 134

Features are typically episodic hypertension (around 90% of cases, may be sustained) headaches palpitations sweating anxiety

Answer 135

• Familial 10% • Bilateral in 10% • Malignant in 10% • Extra-adrenal in 10% (most common site = organ of zuckerkandl, adjacent to the bifurcation of the aorta)

Answer 136

24hr urinary collection of catecholamines is preferred to one of vanillylmandelic acid as it has a higher sensitivity. Three 24 hour collections are needed as some patients have intermittently raised levels

Answer 137

Surgery is the definitive management. The patient must be pre-stabilized with medical management: PHEochromocytoma - give PHEnoxybenzamine before beta-blockers • α-blocker (e.g. Phenoxybenzamine), given before a • β-blocker (e.g. Propranolol)

Answer 138

• Cushing's syndrome • Conn's syndrome (primary hyperaldosteronismm) • Liddle's syndrome • 11-β-hydroxylase deficiency* • Carbenoxolone (anti-ulcer drug) • High liquorice intake

Answer 139

• Diuretics • GI loss (e.g. diarrhea, vomiting) • Renal tubular acidosis (type 1 and 2**) • Bartter's syndrome • Gitelman syndrome

Answer 140

• Zona Glomerulosa (on outside): mineralocorticoids, mainly Aldosterone • Zona Fasciculata (middle): glucocorticoids, mainly Cortisol • Zona Reticularis (on inside): androgens, mainly Dehydroepiandrosterone

Answer 141

Insulin, TRH and LHRH are given to the patient following that the serum glucose, cortisol, growth hormone, TSH, LH and FSH levels are recorded at regular intervals. Prolactin levels are also sometimes measured* A normal dynamic pituitary function test has the following characteristics: • GH level rises > 20mu/l • Cortisol level rises > 550 mmol/l • TSH level rises by > 2 mu/l from baseline level • LH and FSH should double *dopamine antagonist tests using metoclopramide may also be used in the investigation of hyperprolactinemia. A normal response is at least a two-fold rise in prolactin. A blunted prolactin response suggests a prolactinoma

Answer 142

Growth hormone (GH) is an anabolic hormone secreted by the somatotroph cells of the anterior lobe of the pituitary gland.

Answer 143

Mechanism of action • Acts on a transmembrane receptor for growth • Binding of GH to the receptor leads to receptor dimerization • Acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily secreted by the liver

Answer 144

Conditions associated with GH disorders • Excess GH: acromegaly • GH deficiency: resulting in short stature

Answer 145

Acromegaly there is excess growth hormone secondary to a pituitary adenoma in over 95% of cases. A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.

Answer 146

Features • Coarse, oily skin , large tongue, prognathism, interdental spaces • Spade-like hands, ↑ in shoe size • Sweating due to 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

Answer 147

Complications • Hypertension • Diabetes (>10%) • Cardiomyopathy • Colorectal cancer

Answer 148

Acromegaly is associated with systemic rather than pulmonary hypertension.

Answer 149

Investigations: Growth hormone (GH) levels vary during the day and are therefore not diagnostic. Serum IGF-1 levels have now overtaken the oral glucose tolerance test (OGTT) with serial GH measurements as the first-line test. The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.

Answer 150

Oral glucose tolerance test • In normal patients GH is suppressed to < 2 mu/L with hyperglycemia • In acromegaly there is no suppression of GH • May also demonstrate impaired glucose tolerance which is associated with acromegaly A pituitary MRI may demonstrate a pituitary tumour

Answer 151

Cushing: Overnight Dexamethasone Test Cushing- vs. Pseudo-cushing: Insulin Stress Test Addison: Short Synacthen Test Pheochromocytoma: 24H Urinary Catecholamines Acromegaly: Oral Glucose Tolerance Test

Answer 152

Management: Trans-sphenoidal surgery is first-line treatment for acromegaly in the majority of patients Dopamine agonists • For example bromocriptine. • The first effective medical treatment for acromegaly, however now superseded by somatostatin analogues • Effective only in a minority of patients Somatostatin analogue • For example octreotide • Effective in 50-70% of patients • May be used as an adjunct as it helps to control cardiometabolic risk factors prior to surgery. Pegvisomant • GH receptor antagonist - prevents dimerization of the GH receptor • Once daily S/C administration • Very effective - ↓ IGF-1 levels in 90% of patients to normal • Doesn't ↓ tumour volume therefore surgery still needed if mass effect External irradiation is sometimes used for older patients or following failed surgical/medical treatment

Answer 153

Features of excess prolactin • Men: impotence, loss of libido, galactorrhoea • Women: amenorrhoea, galactorrhoea

Answer 154

Prolactin is secreted by the anterior pituitary gland with release being controlled by a wide variety of physiological factors. Dopamine acts as the primary prolactin releasing inhibitor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea

Answer 155

Prolactin is unique amongst the pituitary hormones in being tonically (continuous) inhibited by the hypothalamus

Answer 156

Causes of raised prolactin • Prolactinoma • Pregnancy • Estrogens • Physiological: stress, exercise, sleep • Acromegaly: 1/3 of patients • Polycystic ovarian syndrome • PRIMARY HYPOTHYROIDISM (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)

Answer 157

• Metoclopramide, domperidone • Phenothiazines • Haloperidol • Very rare: SSRIs, opioids

Answer 158

Prolactinomas are unusual as medical therapy is first line, even if visual field defects are present. The main indications for surgery are tumours resistant to dopamine agonists

Answer 159

Gynaecomastia describes an abnormal amount of breast tissue in ♂s and is usually caused by ↑ estrogen:androgen ratio.

Answer 160

Causes of gynaecomastia • Physiological: normal in puberty • Syndromes with androgen deficiency: kallman's, klinefelter's • Testicular failure: e.g. Mumps • Testicular cancer e.g. Seminoma secreting HCG • Liver disease • Ectopic tumour secretion • HYPERTHYROIDISM NOT HYPOTHYROIDISM • Hemodialysis

Answer 161

Drug causes of gynaecomastia • Spironolactone (most common drug cause) • Cimetidine • Digoxin • Cannabis • Finasteride • GnRH agonists e.g. goserelin, buserelin • Estrogens, anabolic steroids Very rare drug causes of gynaecomastia • Tricyclics • Isoniazid • Calcium channel blockers • Heroin • Busulfan • Methyldopa

Answer 162

SIGN recommend using criteria similar to those from the American Heart Association. For a diagnosis of metabolic syndrome at least 3 of the following should be identified: • Elevated waist circumference: men > 102 cm, women > 88 cm • Elevated triglycerides: > 1.7 mmol/l • ↓ HDL: < 1.03 mmol/l in ♂s and < 1.29 mmol/l in ♀s • Raised blood pressure: > 130/85 mmHg, or active treatment of hypertension • Raised fasting plasma glucose > 5.6 mmol/l, or previously diagnosed type 2 diabetes Other associated features include: • Raised uric acid levels (Hyperuricemia) • Non-alcoholic fatty liver disease • Polycystic ovarian syndrome

Answer 163

NICE have defined criteria for the use of orlistat. It should only be prescribed as part of an overall plan for managing obesity in adults who have: • BMI of 28 kg/m2 or more with associated risk factors, or • BMI of 30 kg/ m2 or more • Continued weight loss e.g. 5% at 3 months • Orlistat is normally used for < 1 year

Answer 164

Orlistat is a pancreatic lipase inhibitor used in the management of obesity. Adverse effects include faecal urgency/incontinence and flatulence. A lower dose version is now available without prescription ('Alli').

Answer 165

Obesity - NICE bariatric referral cut-offs • With risk factors (T2DM, BP etc): > 35 kg/m2 • no risk factors: > 40 kg/m2

Answer 166

Obesity hormones • Leptin ↓ appetite • Ghrelin ↑ appetite • Thyroxine ↑ appetite but not in obese pt.

Answer 167

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 to ↓ appetite. More adipose tissue (e.g. in obesity) results in high leptin levels. Leptin stimulates the release of melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH). Low levels of leptin stimulates the release of neuropeptide Y (NPY)

Answer 168

Ghrelin Where as leptin induces satiety, ghrelin stimulates hunger. It is produced mainly by the fundus of the stomach and the pancreas. Ghrelin levels ↑ before meals and ↓ after meals

Answer 169

Glycaemic index (GI) describes the capacity of a food to raise blood glucose in normal glucose-tolerant individuals. Foods with a high GI may be associated with ↑ risk of obesity and the post-prandial hyperglycemia associated with such foods may also ↑ the risk of T2DM

Answer 170

White rice (87), baked potato (85), white bread (70), corn flakes, rice krispies, watermelon, croissants, extruded breakfast cereals, straight glucose (100)

Answer 171

Couscous (65), boiled new potato (62), digestive biscuit (59), basmati rice (58), whole wheat products, sweet potato, table sugar, most white rices (e.g. jasmine)

Answer 172

Fruit and vegetables (except potatoes, watermelon), peanuts, grainy breads, pasta, legumes/pulses, milk, products extremely low in carbohydrates (fish, eggs, meat, some cheeses, nuts, cooking oil), brown rice

Answer 173

Hypercholesterolemia rather than hypertriglyceridemia: nephrotic syndrome, cholestasis, hypothyroidism

Answer 174

• Diabetes Mellitus (types 1 and 2) • Obesity • Alcohol • Chronic renal failure • Drugs: thiazides, non-selective β-blockers, unopposed estrogen • Liver disease

Answer 175

Overview • Rare cause of mixed hyperlipidemia (raised cholesterol and triglyceride levels) • Also known as Fredrickson type III hyperlipidemia, broad-β disease and dysbetalipoproteinemia • Associated with APO-E2 homozygosity • High incidence of ischemic heart disease and peripheral vascular disease • Thought to be caused by impaired removal of intermediate density lipoprotein from the circulation by the liver

Answer 176

Features • Y ellow palmar creases • Palmer xanthomas • Tuberous xanthomas

Answer 177

Management • Fibrates are first line treatment

Answer 178

Familial hypercholesterolemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the hepatic proteins involved in clearance of LDL-cholesterol from the circulation

Answer 179

Clinical diagnosis is now based on the Simon Broome criteria: • In adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus: • For definite FH: tendon xanthoma in patient or 1st or 2nd degree relatives or DNA-based evidence of FH • For possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels

Answer 180

Management • The use of CVD risk estimation using standard tables is not appropriate in FH as they do not accurately reflect the risk of CVD • Referral to a specialist lipid clinic is usually required • The maximum dose of potent statins are usually required • First-degree relatives have a 50% chance of having the disorder and should therefore be offered screening • Statins should be discontinued in women 3 months before conception due to the risk of congenital defects

Answer 181

Primary prevention: a systematic strategy should be used to identify people aged 40-74 who are likely to be at high risk of cardiovascular disease (CVD), defined as a 10-year risk of 20% or greater. The 1991 Framingham equations are still recommended to assess 10-year CVD risk. It is however recommended that adjustments are made in the following situations: • First-degree relative with a history of premature coronary heart disease (defined as < 55 years in ♂s and < 65 years in ♀s) - ↑ risk by 1.5 times if one relative affected or up to 2.0 times if more than one relative affected • South asian ethnicity - ↑ risk by 1.4 times

Answer 182

Along with lifestyle changes drug treatment should be considered for patients with a 10-year CVD risk of 20% or greater • Simvastatin 40mg on is the first line treatment • There is no target level for total or LDL cholesterol for primary prevention • Liver function tests should be check at baseline, within 3 months and at 12 months but not again unless clinically indicated Secondary prevention • All patients with CVD should be taking a statin in the absence of any contraindication • NICE recommend increasing to simvastatin 80 mg if a total cholesterol of less than 4 mmol/litre or an LDL cholesterol of less than 2 mmol/litre is not attained

Answer 183

In prolonged cholestasis features include: ↑ serum cholesterol, moderate ↑ in triglyceride, serum is not lipaemic, ↓ HDL levels. Clinical features include: palmar xanthomas; tuberous xanthomas (particularly on extensor surfaces); tendinous xanthomas are rare. Xanthomas usually only occur if cholestasis has persisted for more than 3 months sometimes fat deposits may involve bone and peripheral nerves.

Answer 184

The presence of tendon xanthomata and ↑LDL, ↑T.chol ≡ HDL meet the diagnostic criteria for familial hypercholesterolemia.

Answer 185

• Remnant hyperlipidemia • May less commonly be seen in familial hypercholesterolemia

Answer 186

Eruptive xanthoma are due to high triglyceride levels and present as multiple red/yellow vesicles on the extensor surfaces (e.g. elbows, knees)

Answer 187

Causes of eruptive xanthoma • Familial hypertriglyceridemia • Lipoprotein lipase deficiency

Answer 188

Tendon xanthoma, tuberous xanthoma, xanthelasma • Familial hypercholesterolemia • Remnant hyperlipidemia

Answer 189

Management of xanthelasma, options include: • Surgical excision • Topical trichloroacetic acid • Laser therapy • Electrodesiccation

Answer 190

Flushing, diarrhea, bronchospasm, tricuspid stenosis, pellagra → carcinoid with liver mets diagnosis: urinary 5-HIAA

Answer 191

• Usually occurs when metastases are present in the liver and release serotonin into the systemic circulation • May also occur with lung carcinoid as mediators are not 'cleared' by the liver

Answer 192

Features • Flushing (often earliest symptom) • Diarrhea • Bronchospasm • Hypotension • Right heart valvular stenosis (left heart can be affected in bronchial carcinoid) • ACTH and GHRH may also be secreted resulting in, for example, cushing's syndrome • Pellagra can rarely develop as dietary tryptophan is diverted to serotonin by the tumour

Answer 193

Investigation • Urinary 5-HIAA • Plasma chromogranin A y

Answer 194

Management • Somatostatin analogues e.g. Octreotide • Diarrhea: cyproheptadine may help

Answer 195

There are two distinct types of autoimmune polyendocrinopathy syndrome (APS), with type 2 (sometimes referred to as Schmidt's syndrome) being much more common.

Answer 196

APS1 is 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 Vitiligo can occur in both types

Answer 197

APS2 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 (Hypothyroid) Vitiligo can occur in both types

Answer 198

Primary HYPOparathyroidism is usually the first endocrine manifestation of type 1 autoimmune POLYendocrinopathy syndrome. While (MEN) → hyperparathyroidism is a common finding

Answer 199

Werner's Syndrom Mnemonic 'three P's': • Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia • Pituitary (70%) • Pancreas (50%, e.g gastrinoma) • Also: adrenal and thyroid Presentation → hypercalcemia

Answer 200

Sipple syndrome • Pheochromocytoma 95% • Medullary thyroid CA 70% • Parathyroid (60%) RET oncogene

Answer 201

• Medullary thyroid cancer • PHEOCHROMOCYTOMA • Marfanoid body habitus • Neuromas • Intestinal polyps (identified histologically as ganglioneromas are usually asymptomatic) RET oncogene

Answer 202

The high incidence of parathyroid tumours and hypercalcemia make serum calcium a useful indicator of MEN type 1 in suspected individuals

Answer 203

Androgen Insensitivity Syndrome: is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome

Answer 204

Features • 'Primary amennorhoea' • Undescended testes causing groin swellings • Breast development may occur as a result of conversion of testosterone to oestradiol

Answer 205

Diagnosis • Buccal smear or chromosomal analysis to reveal 46XY genotype

Answer 206

Management • Counselling - raise child as female • Bilateral orchidectomy (increased risk of testicular cancer due to undescended testes) • Estrogen therapy

Answer 207

group of autosomal recessive disorders affect adrenal steroid biosynthesis in response to resultant low cortisol levels the anterior pituitary secretes high levels of ACTH ACTH stimulates the production of adrenal androgens that may virilize a female infant

Answer 208

Cause 21-hydroxylase deficiency (90%) 11-beta hydroxylase deficiency (5%) 17-hydroxylase deficiency (very rare)

Answer 209

unexplained deterioration in vision awareness of change in intensity or quality of colour vision in one or both eyes history of eye suddenly 'popping out' (globe subluxation) obvious corneal opacity cornea still visible when the eyelids are closed disc swelling

Answer 210

Causes • Hypothyroidism • Acromegaly • Amyloidosis • Duchenne muscular dystrophy • Mucopolysaccharidosis (e.g. Hurler syndrome)