Hypopituitarism

Hypopituitarism

·        Causes: hypophysectomy, pituitary irradiation, adenoma (either functional or non-functional), other intracranial tumours, Sheehan‟s Syndrome (pituitary necrosis after post-partum haemorrhage), TB

·        Check symptoms of:

o  Gonadal and GH (® bone strength): early to fail

o  Thyroid: intermediate to fail

o  Adrenal: last to go. 

o  Also look for PRL (need a little for LH peak to happen), vasopressin, space occupying lesions (test visual fields and for Oculmotor palsy)

o  ADH/Oxytocin only fail completely if hypothalamic tumour or major suprasellar extension

·        Symptoms: insidious onset, afternoon tiredness, pallor, anorexia, ¯libido (can be due to many illnesses to and ­PRL), impotence, amenorrhoea, no menarche by 16, headache, depression, hypothyroidism, reduced body hair in males (due to hypogonadism – is also normal in older age – but not front baldness

that‟s due to androgens), intolerance of intercurrent illness and postural hypotension (hypocortisone),

·        mild fluid retention (myxoedema and ¯cortisol ® water retention), mild anaemia, pallor (yellow of myxoedema, and anaemia), also marked behavioural changes

·        Signs: breast atrophy, small testes, ¯muscle to fat ratio, ¯hair, thin flaky wrinkled skin, postural hypotension, visual field defect

·        Differentials: depression, dementia, subdural bleed (although more acute), slowly progressive tumour

·        The age of presentation makes a difference:

o  Prepubertal failure slows growth, delays puberty

o  Post-pubertal failure reduces gonadal activity

o  Post-menopausal women: High FSH and LH would be normal. If FSH within normal range then ® very sensitive test of early pituitary failure (if menopausal should normally be high) 

o  Craniopharyngiomas are the commonest cause of pituitary failure in children, but can be found at any age

·        Types of lesion:

o  Mostly hypopituitarism comes from non-functioning pituitary adenomas (adenomata)

o  But also craniopharyngioma, GH or prolactin secreting tumours

o  Most other causes are rare: pituitary apoplexy (a pituitary haemorrhage, mostly into a pre-existing tumour) and pituitary infarction (occasionally during delivery)

·        Sites of tumour extension from the fossa

o  Suprasellar affects optic nerve

o  Parasellar affects III, IV and VI nerves

o  Infrasellar shows xray changes

·        Tests:

o  CT/MRI, visual fields, basal T4, TSH and PRL, U&E (hyponatraemia), FBC (normochromic normocytic anaemia) 

o  Triple stimulation test (unless heart disease or epilepsy): As inpatient with iv access, inject insulin, TRH and GnRH. Look for ­GH, ­Cortisol (due to ­ACTH), ­TSH, ­PRL (due to ­TRH)

o  LH and FSH insufficient on their own, without checking testosterone as well (may be ¯ due to   Â­testosterone).  Also LH & FSH tests are not sensitive enough to distinguish low from low-normal

o  Cortisol too variable to be a useful check of pituitary

o  Very high PRL indicates a prolactinoma, which can cause pan-hypopituitarism 

o   An overnight Metyrapone test - give Metyrapone orally at midnight and measure plasma cortisol and its biosynthetic precursor at 8.30am. Metyrapone blocks the synthesis of cortisol leading to a build-up of 11-deoxycortisol and reduced negative cortisol feedback ® a raised ACTH. Cortisol, ACTH and 11-deoxycortisol all remain low in hypopituitarism or long-standing suppression of the HP adrenal axis by drugs

o   Assessing severity:

§  Gonadal: Males – testosterone, LH and FSH.  Females: menstrual history, LH and FSH

§  Thyroid: fT4 and TSH

§  Adrenal: Short Synacthen test (false negatives possible) or urine free cortisol (not sensitive)

§  Growth Hormone: simple sample (after 10 am) or IGF1

§  Vasopressin: overnight urine concentration (osmolality)

·        Treatment: Hydrocortisone and thyroxine. Maybe GH. Testosterone in men, Oestrogen for pre-menopausal women