Endocrinology

Question 1

Describe the pathophysiology, investigation and management of thyroid eye disease

Answer 1

Typically associated with Grave’s, but patients can be euthyroid, hypothyroid or hyperthyroid at presentation

Can be worsened by treatment, particularly radioiodine

Retro-orbital inflammation and lymphocyte infiltration results in swelling of the orbit

Eye discomfort, diplopia, exophthalmos, proptosis, lid retraction

Diagnose clinically

Treat hyper or hypothyroidism, avoid smoking, artificial tears, treat other symptoms

In later disease, high dose steroid may be used and surgery may be required

Question 2

Describe symptoms of diabetes

Answer 2

• Glycosuria - Depletion of Energy Stores
  
  • Tiredness, Weakness, Weight Loss, Difficulty Concentrating, Irritability
• Glycosuria - Osmotic Diuresis
  
  • Polyuria, Polydipsia, Dry Mucous Membranes, Reduced Skin Turgor, Postural Hypotension
• Glucose Shifts - Swollen Ocular Lenses
  
  • Blurred Vision
• Ketone Production
  
  • Nausea, Vomiting, Abdominal Pain, Heavy/Rapid Breathing, Acetone Breath, Drowsiness, Coma
• Depletion of Energy Stores
  
  • Weakness, Polyphagia, Weight Loss, Growth Retardation in Young
• Complications
  
  • Macrovascular, Microvascular, Neuropathy, Infection

Question 3

Define diabetes

Answer 3

“a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, protein and fat metabolism resulting from defects in insulin secretion, insulin action, or both”

Question 4

Describe the clinical effects of vitamin D deficiency

Answer 4

Can be due to poor sunlight exposure, malabsorption, gastrectomy, renal disease or enzyme-inducing drugs

Can result in osteomalacia in adulthood

Failure to ossify bones in adulthood as a result of Vit D deficiency

Presents insidiously with bone pain, proximal myopathy and hypocalcaemia

Characterised by low calcium, low phosphate, high ALP, low Vit D, elevated PTH

Treat with vitamin D replacement (cholecalciferol or alfacalcidol)

Question 5

Describe Latent Autoimmune Diabetes of Adulthood

Answer 5

Age of onset >25yrs

Obesity is rare

Insulin usually required within months or years of diagnosis

Polygenic inheritance

GAD antibodies

Question 6

Describe the pathophysiology, investigation and management of hyperprolactinaemia

Answer 6

Can be caused by prolactin-releasing pituitary tumours

Clinical features include galactorrhoea, headaches, mass effect, visual field defects, amenorrhoea, erectile dysfunction

Diagnose with serum prolactin (usually >6000) and pituitary MRI

Remaining pituitary function should also be tested (gonadal and thyroid hormones)

Treat with dopamine agonists (e.g. cabergoline, bromocriptine) as dopamine has a negative feedback mechanism on prolactin secretion

Surgery only indicated if medical therapy fails

Question 7

Describe Whipple’s triad

Answer 7

collection of three criteria that suggest a patient’s symptoms result from hypoglycemia that may indicate insulinoma

1. Low Plasma Glucose
2. Symptoms Consistent with Hypoglycaemia
3. Relief of Symptoms when Glucose is Raised to Normal

Question 8

Describe the treatment of hypoglycaemia

Answer 8

Question 9

Describe the pathophysiology, investigation and management of hyperthyroidism

Answer 9

Most commonly due to an autoimmune disease (Grave’s)

Symptoms include diarrhoea, weight loss, sweats, heat intolerance, palpitations, tremor

Signs include tachycardia, AF, lid lag, lid retraction, goitre, bruit, thyroid eye disease, pretibial myxoedema, thyroid acropachy

Investigate with TSH (suppressed) and Free T4 (elevated)

May also consider thyroid auto-antibodies and iodine uptake scan

Manage with beta-blockers and ‘block and replace’ with carbimazole and levothyroxine simultaneously

May require radio-iodine or thyroidectomy

Question 10

Describe the normal physiological role and regulation of calcium

Answer 10

Functions include muscle contraction, membrane stabilisation, bone growth and remodelling, enzyme co-factor, secondary signalling messenger, hormone secretion

Most calcium is found in the skeleton, some intracellularly and some extracellularly (free or albumin-bound)

Regulated chiefly by parathyroid hormone, which raises blood calcium by increasing reabsorption at the renal distal tubule; increasing osteoclast activity; and increasing Vit D synthesis which increases calcium absorption from the gut

Question 11

Describe the pathophysiology, investigation and management of Kallmann’s syndrome

Answer 11

A cause of primary hypogonadotropic hypogonadism

Most common form of isolated gonadotropin-releasing hormone deficiency

Due to a failure of cell migration of GnRH cells to the hypothalamus from the olfactory placode

Associated with anosmia and colour blindness

May have micropenis and cryptorchidism

Familial with variable penetration (X-Linked, Autosomal Dominant or Autosomal Recessive)

Diagnosed with clinical exam (usually due to delayed puberty) and hormone profile (LH, FSH, GnRH)

Treat with testosterone

Question 12

Describe the pathophysiology, investigation and management of hypothyroidism

Answer 12

Common primary autoimmune causes include Hashimoto’s Thyroiditis (destruction of lymphocytic and plasma cell infiltration)

Other primary causes include iodine deficiency or post-thyroidectomy

Secondary hypothyroidism arises due to hypopituitarism (low TSH)

Causes fatigue, cold intolerance, weight gain, constipation, menorrhagia, bradycardia, dry skin/hair, goitre

Diagnosed with high TSH and low T4

Manage with levothyroxine replacement

Question 13

Define gestational diabetes

Answer 13

Carbohydrate intolerance with onset, or diagnosis, during pregnancy

Risk factors include high body mass index, previous macrosomic baby or gestational diabetes, or family history of, or ethnic prevalence of, diabetes

All women with risk factors should have an OGTT at 24 to 28 weeks

Internationally agreed criteria for gestational diabetes using 75 g OGTT:

Fasting venous plasma glucose ≥ 5.1 mmol/l, or

One hour value ≥ 10 mmol/l, or

Two hours after OGTT ≥ 8.5 mmol/l

Question 14

State causes of amenorrhoea

Answer 14

• Primary
  
  • Chromosomal or Genetic Abnormalities (e.g. Turners)
  • Problems with Hypothalamus or Pituitary
• Secondary
  
  • Pregnancy
  • Menopause
  • Chemotherapy
  • Certain Medications
  • PCOS
  • Thyroid Problems

Question 15

Describe the pathophysiology and management of Diabetic Ketoacidosis

Answer 15

Absolute insulin deficiency results in activation of the ketone pathway, used in starvation states

This results in acetone (ketone) production, which along with profound hyperglycaemia can be life-threatening

Presents with osmotic symptoms, weight loss, breathlessness, abdominal pain, leg cramps, N&V, confusion

Characterised by a Metabolic Acidosis, Hyperglycaemia and Urinary/Plasma Ketones

Manage with IV fluids, insulin and assess need for potassium

Follow national DKA pathway

Question 16

Describe the pathophysiology and management of Hyperglycemic Hyperosmolar State

Answer 16

Occurs in a relative insulin deficiency

No ketoacidosis

More insidious onset

Marked dehydration and hyperglycaemia

Rehydrate with saline and give insulin if glucose does not fall with fluids alone

LMWH prophylaxis and consider K+

Question 17

Describe insulinoma

Answer 17

A rare neuroendocrine tumour, often benign

Presents as fasting hypoglycaemia with Whipple’s triad

Test with IV insulin and measure c-peptide (should normally be suppressed but this will not happen in insulinoma)

Image with CT/MRI and endoscopic USS

Manage with excision

Question 18

Describe the pharmacology of SGLT-2 inhibitors

Answer 18

e.g. Empagliflozin, Canagliflozin

Inhibits sodium-glucose co-transporter in the renal tubules

Blocks glucose reabsorption and promotes loss of glucose in the urine

Question 19

Describe the pharmacology of Pioglitazone

Answer 19

Acts on PPAR receptors to increase peripheral insulin sensitivity

SE include hypoglycaemia, fractures, oedema

Question 20

Describe the pathophysiology, investigation and management of Phaeochromocytoma

Answer 20

Rare catecholamine-producing tumours arising from sympathetic paraganglia cells (collections of chromaffin cells) in the adrenal medulla

Often associated with hard to control hypertension

Episodes of headache, palpitations, pallor and sweating

Also associated with tremor, anxiety, nausea, vomiting, chest and abdominal pain

Diagnose with at least two 24 hour urinary catecholamines, CT abdomen and MIGB scan (chromaffin seeking analogue)

Medical management with alpha-blockade (phenoxybenzamine) first, then with beta blocker (bisoprolol) if tachycardic

Followed by surgical resection

Question 21

Compare and contrast type 1 and type 2 diabetes

Answer 21

Type 1 - Immune pathogenesis with severe insulin deficiency

Type 2 - Combination of insulin resistance and insulin deficiency

Question 22

State important causes of hypercalcaemia

Answer 22

• PTH-Mediated (i.e. Elevated/Normal PTH)
  
  • Primary Hyperparathyroidism
  • Familial Syndromes (MEN-1, MEN-2)
  • Familial Hypocalciuric Hypercalcaemia
• PTH-Independent (i.e. Undetectable PTH)
  
  • Malignancy
  • Granulomatous Disorders
  • Drugs (thiazides, lithium, calcium supplements)
  • Adrenal Insufficiency
  • Milk-Alkali Syndrome
  • Immobilisation

Question 23

State signs and symptoms of hypercalcaemia

Answer 23

May be asymptomatic if mild

Symptoms more common when calcium >3mmol/L

Muscle Weakness, Bone Pain, Osteoporosis

Anorexia, Nausea, Constipation, Pancreatitis

Confusion, Depression, Fatigue, Coma

Shortened QTc, Bradycardia, Hypertension

Polyuria, Nephrogenic DI, Stones

Question 24

Describe testosterone replacement therapy, its advantages and disadvantages

Answer 24

Can be given orally, IM or topically

Best option for androgen replacement in deficiency

Side effects include mood issues (aggression/behaviour changes), libido issues, increased haematocrit, acne, sweating, gynaecomastia

Testosterone is a drug of abuse in sports

Question 25

List causes of Secondary Diabetes

Answer 25

Genetic defects of beta-cell function Genetic defects in insulin action Disease of exocrine pancreas (pancreatitis, carcinoma, CF, haemochromatosis) Endocrinopathies (acromegaly, cushings) Immunosuppressive Agents (glucocorticoids, tacrolimus, ciclosporin) Anti-Psychotics (clozapine) Genetic Syndromes Associated with DM (Down's, Turner's, Kleinfelter's)

Question 26

Define hypoglycaemia and describe symptoms

Answer 26

Insulin-Treated DM - \<4mmol/L Normal People - \<2.8mmol/L Autonomic - Sweating, Palpitations, Shaking, Hunger Neuroglycopenic - Confusion, Drowsiness, Visual Disturbance Nausea + Headache

Question 27

Describe causes of hirsutism

Answer 27

Male pattern hair growth in women Causes are familial, idiopathic or due to increased androgen secretion by the ovary (e.g. PCOS, ovarian cancer), adrenal (e.g. CAH, Cushing's, cancer) or drugs (e.g. Steroids) Manage with oestrogens (combine contraceptive pill), metformin Clomifene can be used for infertility

Question 28

State differential diagnoses for non-diabetes hypoglycaemia

Answer 28

Drugs Critical Illness (hepatic/renal/cardiac failure, sepsis) Hormone Deficiency (e.g. Cortisol) Non-Islet Cell Tumour Endogenous Hyperinsulinism (Insulinoma, Functional Islet Cell Disorders, Insullin Autoimmune Hypoglycaemia) Accidental, Surreptitious, Malicious Hypoglycaemia

Question 29

Describe the rationale for Continuous Subcutaneous Insulin Infusion treatment

Answer 29

Can potentially provide significant improvement in glycaemic control and quality of life for some people with T1DM Potentially make it easier to achieve glucose control with less danger of severe and incapacitating hypoglycaemia Complications include reactions, infections at cannula site, tube blockage, pump malfunction

Question 30

Describe the different insulin regimens available

Answer 30

Insulin is a peptide, so cannot be given orally Can be given as a once-daily basal, twice daily mix or basal-bolus therapy Insulin pens are more convenient, accurate, discrete and less painful than conventional vial and syringes

Question 31

Describe the pathophysiology, investigation and management of Primary Gondal Disease

Answer 31

PGD is due to testicular failure Causes include chromosomal defects (e.g. Kleinfelters), cryptorchidism or adult leydig cell/seminiferous tubule failure (due to trauma, chemotherapy, radiotherapy or multi-system disorders) Characterised by low testosterone, high/normal LH and FSH and normal prolactin Manage with testosterone replacement

Question 32

State the WHO diagnostic criteria for diabetes

Answer 32

Fasting Plasma Glucose \>/= 7mmol/L Random Plasma Glucose \>/= 11.1mmol/L One Abnormal Value if Symptomatic Two Abnormal Values if Asymptomatic Should not be diagnosed on the basis of HbA1c or glycosuria alone

Question 33

Describe the pathogenesis of type 1 and type 2 diabetes mellitus

Answer 33

* Type 1 DM * Chronic, progressive metabolic disorder characterised by hyperglycaemia and the absence of insulin secretion * Type 1 diabetes results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans * Occurs in genetically susceptible subjects and is probably by one or more environmental agents * Type 2 DM * Chronic, progressive metabolic disorder characterised by hyperglycaemia, insulin resistance and relative impairment of insulin deficiency * Common with a prevalence that rises markedly with increasing levels of obesity * Most likely arises through a complex interaction among many genes and environmental factors

Question 34

Describe the pathophysiology, clinical features, investigation and management of Polycystic Ovarian Syndrome

Answer 34

See figure for Pathophysiology Presents with hirsutism, acne, male-pattern hair loss, acanthosis nigricans, obesity Lifestyle modification - diet, exercise, weight loss Oestrogen (combined oral contraceptive) Metformin (reduces glucose intolerance and hyperinsulinaemia) Clomifene (selective oestrogen receptor modulator) Gonadotropin therapy

Question 35

Describe the pathophysiology, investigation and management of acromegaly

Answer 35

Hypersecretion of growth hormone, most commonly due to a pituitary tumour GH stimulates bone and soft tissue growth through increased secretion of insulin-like growth factor Features include sweats and headaches, altered facial features (coarse features, macroglossia, frontal bossing, protruding jaw), spade-like hands, increased foot size, visual impairment, cardiomyopathy, increased inter-dental spaces Diagnose with GH measurements with OGTT (glucose should suppress GH) Measure IGF-1 and then Pituitary MRI First line treatment is surgery May require medical therapy such as somatostatin analogues, dopamine agonists or GH receptor antagonists Radiotherapy may be used for residual tumour or if ongoing symptoms

Question 36

Describe MODY

Answer 36

Maturity Onset Diabetes of the Young 1-2% of all DM Caused by a change in a single gene (monogenic) Autosomal dominant Main features include \<25yrs onset, runs in families from one generation to next, managed by diet, OHAs and insulin

Question 37

Describe the pathophysiology, investigation and management of Primary Hyperaldosteronism

Answer 37

Excess production of aldosterone, independent of the RAS system, causing sodium and water retention and reduced renin release Mostly caused by a solitary aldosterone-producing adenoma (Conn's syndrome) Other causes include bilateral adrenocortical hyperplasia or adrenal carcinoma Often asymptomatic, may have hypokalaemia, weakness, cramps, paresthesia, polyuria, polydipsia, hypertension Investigations include a raised aldosterone and aldosterone:renin ratio and suppressed renin Confirm with a saline suppression test (2L saline over 4 hours followed by a 4h aldosterone \>270pmol/L is highly suspicious) Manage with MR antagonists or amiloride Surgical management with unilateral laparoscopic adrenalectomy (only if adrenal adenoma)

Question 38

Describe the pathophysiology, investigation and management of Congenital Adrenal Hyperplasia

Answer 38

Autosomal recessive disorder Deficiency in 21-alpha-hydroxylase Results in steroidogenic defects including aldosterone and cortisol deficiency This means more pregnenolone is converted to the androgen DHEA Can result in ambiguous genitalia (female) and adrenal crisis and early virilisation (males) Managed with mineralocorticoid and glucocorticoid replacement

Question 39

Describe the pathophysiology, investigation and management of Kleinfelters

Answer 39

Most common genetic cause of male hypogonadism XXY Manifests clinically at puberty High LH and FSH, but seminiferous tubules regress and Leydig cells do not function normally Wide clinical variation, including delayed puberty, suboptimal genital development, reduced secondary sexual characteristics, gynaecomastia, azoospermia and behavioural issues Manage with androgen replacement, psychological support and fertility counselling

Question 40

Describe the pharmacology of DPP4 inhibitors

Answer 40

e.g. Sitagliptin Blocks the action of DPP4, which destroys the enzyme incretin Increased incretin levels inhibit glucagon, which increases insulin secretion

Question 41

Describe the pathophysiology, investigation and treatment of Cushing's Syndrome/Disease

Answer 41

Cushing's syndrome is the clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms Causes include exogenous steroid use, and a pituitary adenoma (specifically known as Cushing's disease) Symptoms include weight gain, mood change (depression, lethargy, irritability), proximal myopathy, gonadal dysfunction, acne Signs include central obesity, moon face, buffalo hump, skin/muscle atrophy, bruises, abdominal striae, hypertension, hyperglycaemia Investigate with MRI for pituitary mass, raised plasma cortisol, 24hr urinary free cortisol and dexamethasone suppression test (give dexamethasone at night and measure cortisol in the morning, should normally be suppressed but will not be in Cushing's) Manage by stopping offending medication, surgical removal of pituitary adenoma or adrenalectomy

Question 42

Describe the pathophysiology, investigation and management of adrenal insufficiency

Answer 42

Primary adrenal insufficiency (Addison's disease) is rare and characterised by destruction of the adrenal cortex leads to glucocorticoid and mineralocorticoid deficiency Causes include autoimmunity, adrenal TB, lymphoma, opportunistic infection Symptoms include anorexia, weight loss, fatigue, lethargy, dizziness, hypotension, hyperkalaemia, abdominal pain, vomiting, diarrhoea, skin and mucous membrane pigmentation Investigations include; Biochemistry - hyponatraemia, hyperkalaemia and hypoglycaemia High ACTH levels Adrenal auto-antibodies Renin (high) and aldosterone (low) levels Short Synacthen Test - Measure plasma cortisol before and 30 minutes after IV ACTH injection. In normal situations, ACTH should increase cortisol levels. A normal result is a baseline of \>250nmol/L and post-ACTH of \>480. In Addison's, there would be minimal cortisol response after ACTH injection

Question 43

Describe the pathophysiology and management of thyroid carcinoma

Answer 43

Papillary, Follicular, Medullary, Lymphoma or Anaplastic Manage with thyroidectomy with or without radiotherapy