Flashcards in Endocrine Deck (216)
What is acromegaly?
Constellation of signs and symptoms caused by hypersecretion of GH in adults (Excess GH before puberty results in gigantism)
What is the aetiology of acromegaly?
- Most cases are a result of GH-secreting pituitary adenoma
- Rarely: Excess GHRH causing somatotroph hyperplasia from hypothalamic ganglioneuroma, bronchial carcinoid or pancreatic tumours
What is the epidemiology of acromegaly?
- Age at diagnosis: 40-50
What are the presenting symptoms of acromegaly?
- Very gradual progression of symptoms over many years
- May complain of rings and shoes becoming tight
- Increased sweating, headache, carpal tunnel syndrome
- Symptoms of hypopituitarism (hypogonadism, hypothyroidism, hypoadrenalism) Visual disturbances (caused by optic chiasmm compression
- Hyperprolactinaemia (irregular periods, reduced libido, impotence)
What are the signs of acromegaly on examination?
- Hands: Enlarged spade-like hands with thick greasy skin. Signs of carpal tunnel syndrome. Premature oesteoarthritis (which also affects other large joints, temporomandibular joint)
- Face: Prominent eyebrow ridge (frontal bossing) and cheeks, broad nose bridge, prominent nasolabial folds, thick lips, increased gap between teeth, large tongue, progathism, husky resonant voice (thickening vocal cords)
- Visual field loss: Bitemporal superior quadrantanopia progressing to bitemporal hemianopia (caused by pituitary tumour compressing the optic chiasm)
- Neck: Multi-nodular goitre
- Feet: enlarged
What are the investigations for acromegaly?
- Serum IGF-1: GH stimulates liver IGF-1 secretion
- Oral glucose tolerance test: Failure of suppression of GH after 75h oral glucose load (false positive results seen in anorexia nervosa, Wilson's disease, opiate addiction
- Pituitary function tests: 9am cortisol, free T4 and TSH, LH, FSH, testosterone (in men) and prolactin (to test for hypopituitarism
- MRI of the brain: to image the pituitary tumour and effect on the optic chiasm
How is acromegaly managed?
- Surgical: Trans-spenoidal hypophysectomy is the only curative treatment
- Radiotherapy: Adjunctive treatment to surgery
- Medical: If surgery is contra-indicated or reduced
- SC somatostatin analogues (octreotide, lanreotide) Side effects: abdo pain, steatorrhoea glucose intolerance, gallstones, irritation at injection site
- Oral dopamine agonists (bromocriptine, cabergoline) SE: nausea, vomiting, constipation, postural hypotension (raised dose gradually and take it during meals) psychosis
- GH antagonist (pegvisomant)
- Monitor: GH and IGF1 levels can be used to monitor disease control. Pituitary function tests, echocardiography, regular colonoscopy and blood glucose
What are the possible complications of acromegaly?
- CVS: cardiomyopathy, hypertension
- Respiratory: Obstructive sleep apnoea
- GI: colonic polyps
- Reproductive: Hyperprolactinaemia
- Metabolic: Hypercalcaemia, Hyperphosphataemia, renal stones, diabetes mellitus, Hypertriglyceridaemia
- Psychological: Depression, psychosis (resulting from dopamine agonist therapy)
- Complications of surgery: Nasoseptal perforation, hypopituitarism, adenoma recurrence, CSF leak, infection (meninges, sphenoid sinus)
What is the prognosis for acromegaly?
Good with early diagnosis and treatment, although physical changes are irreversible
What is adrenal insufficiency?
Deficiency of the adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)
What is the aetiology of adrenal insufficiency?
- Primary (Addison's disease): Autoimmune
- Infections: Tuberculosis, meningococcal septicaemia (Waterhouse-Friderischen syndrome), CMV (HIV patients), histoplasmosis
- Infiltration: Metastasis (e.g. lung, breast, melanoma), lymphoma, amyloidosis
- Infarction: Secondary to thrombophilia
- Inherited: Adrenoleukodystrophy, ACTH receptor mutation
- Surgical: After bilateral adrenalectomy
- Secondary: Pituitary or hypothalamic disease
- Iatrogenic: Sudden cessation of long-term steroid therapy
What is the epidemiology of adrenal insufficiency?
Most common cause is iatrogenic
- Primary causes are rare
What are the presenting symptoms of adrenal insufficiency?
- Chronic presentation: Non-specific symptoms such as dizziness, anorexia, weight loss, diarrhoea, vomiting, abdominal pain, lethargy, weakness, depression
- Acute presentation (Addisonian crisis): Acute adrenal insufficiency with major haemodynamic collapse often precipitated by stress (e.g. infection or surgery)
What are the signs of adrenal insufficiency on examination?
- Postural hypotension
- Increased pigmentation: Generalised but more noticeable on buccal mucosa, scars, skin creases, nail, pressure points (resulting from melanocytes being stimulated by raised ACTH level)
- Loss of body hair in women (androgen deficiency)
- Associated autoimmune conditions: e.g. vitiligo
- Addisonian crisis: Hypotensive shock, tachycardia, pale, cold, clammy, oliguria
What are the investigations for adrenal insufficiency?
- Confirm the diagnosis: 9am serum cortisol less than 100nmol/L is diagnostic of adrenal insufficiency.
- Identify the level of defect ACTH: Raised in primary disease, decreased in secondary. Long Synacthen test
- Identify the cause: Autoantibodies (against 21-hydroxylase). Abdominal CT or MRI. Other tests e.g. adrenal biopsy for microscopy, culture, PCR, depending on the suspected causes
- Investigations in 'Addisonian crisis': FBC
How is adrenal insufficiency managed?
- Addisonian crisis: Rapid IV fluid rehydration. 50ml of 50% dextrose to correct hypoglycaemia. IV 200mg hydrocortisone bolus followed by 100mg 6 hourly (until BP stable). Treat the precipitating cause (e.g. antibiotics for infection). Monitor temperature, pulse, respiratory rate, BP, sat 02 and urine output
- Chronic: Replacement of glucocorticoids with hydrocortisone (three times/day) and mineralocorticoids with fludrocortisone. Hydrocortisone dosage needs to be increased during acute illness or stress. If associated with hypothyroidism, give hydrocortisone before thyroxine (to avoid precipitating Addisonian crisis)
- Advice: Steroid warning card, Medic-alert bracelet, emergency hydrocortisone ampoule, patient education
What are the possible complications of adrenal insufficiency?
Death during Addisonian crisis
What is the prognosis of adrenal insufficiency?
- Adrenal function rarely recovers, but normal life expectancy can be expected if treated
- Type I (autosomal recessive disorder caused by mutation in the AIRE gene which encodes a nuclear transcription factor): Addison's disease, chronic mucocutaneous candidiasis, hypoparathyroidism
- Type II: Addison's disease, diabetes mellitus Type I, hypothyroidism, hypogonadism
What is carcinoid syndrome?
Constellation of symptoms caused by systemic release of humoral factors (biogenic amines, polypeptides, prostaglandins) from carcinoid tumours
What is the aetiology of carcinoid syndrome?
- Carcinoid tumours are slow growing neuroendocrine tumours mostly derived from serotonin-producing enterochromaffin cells
- They produce secretory products such as serotonin, histamine, tachykinins, kallikrein and prostaglandin
- May be classified into fore-,mid-, hind-gut tumours, 75-80% tumours include appendix and rectum, where they are often benign and non-secretory
- Also found in other parts of large intestine, stomach, thymus, bronchus and other organs
- Hormones released into the portal circulation are metabolised in the liver
- Thus symptoms typically do not appear until there are hepatic metastases (resulting in the secretion of tumour products into the hepatic veins) or release into the systemic circulation from bronchial or extensive retroperitoneal tumours
What is the epidemiology of carcinoid syndrome?
- Asymptomatic carcinoid tumours are more common and may be an incidental finding after rectal biopsy or appendectomy
- 10% of patients with multiple endocrine neoplasia (MEN) type 1 have carcinoid tumours
What are the presenting symptoms of carcinoid syndrome?
- Paroxysmal flushing
- Crampy abdominal pain
What are the signs of carcinoid syndrome on examination?
- Facial flushing, telangiectasia, wheeze
- Right sided heart murmurs: tricuspid stenosis, regurgitation or pulmonary stenosis
- Nodular hepatomegaly in cases of metastatic disease
- Carcinoid crisis: Profound flushing, bronchospasm, tachycardia and fluctuating blood pressure
What are the investigations for carcinoid syndrome?
- 24h urine collection: 5-HIAA levels (a metabolite of serotonin, false positive with high intake of certain fruit/drugs e.g. bananas and avocados, caffeine, paracetamol
- Blood: Plasma chromogranin A & B, fasting gut hormones
- CT or MRI scan: To localises the tumour
- Radioisotope scan: Radiolabelled somatostatin analogue (e.g. indum-111 octreotide) helps localise tumour
- Investigations for MEN-1
What is Cushing's syndrome?
Syndrome associated with chronic inappropriate elevation of free circulating cortisol
What is the aetiology of Cushing's syndrome?
ACTH dependent (80%)
- Excess ACTH secreted from a pituitary adenoma: Cushing's disease (80%)
- ACTH secreted from an ectopic source e.g. small-cell lung carcinomas, pulmonary carcinoid tumours (20%)
ACTH independent (20%)
- Excess cortisol secreted from a benign adrenal adenoma (60%)
- Excess cortisol secreted from an adrenal carcinoma (40%)
Rare: ACTH-independent micro- or macronodular adrenal hyperplasia
What is the epidemiology of Cushing's syndrome?
Endogenous Cushing's syndrome is more common in females
- Peak incidence is 20-40 years
What are the presenting symptoms of Cushing's syndrome?
- Increasing weight and fatigue
- Muscle weakness, myalgia, thin skin, easy bruising, poor wound healing, fractures (resulting from osteoporosis)
- Hirsutism, acne, frontal balding. Oligo- or amenorrhoea, depression or psychosis
What are the signs of Cushing's syndrome on examination?
- Facial fullness, facial plethora, interscapular fat pad
- Proximal muscle weakness, thin skin, bruises
- Central obesity, pink/purple striae on abdomen, breast, thighs
- Kyphosis (due to vertebral fracture). Poorly healing wounds.
- Hirsutism, acne, frontal balding
- Hypertension. Ankle oedema (Salt and water retention a result of mineralocorticoid effect of excess cortisol)
- Pigmentation in ACTH dependent cases