Hypopituitarism

Inadequate production of one or more pituitary hormone as a result of damage to the pituitary gland and/or hypothalamus

Aetiology

• Pituitary tumours - nonfunctioning pituitary macroadenomas are the most common cause of hypopituitarism amoung adults

• Other local brain tumours - astrocytomas, meningiomas, gliomas, clival chordoma

• Iatrogenic - surgery or radiation

• Secondary metastatic lesions - lung, breast

• Traumatic brain injury

• Vascaular diseases - polyarteitis

• Subarachnoid haemorrhage

• Hypothalamic diseases - syphilis, meningitis

• Autoimmune - Sheenan (post pregnancy)

• Granulomatous inflammation - sarcoidosis, histiocytosis X tuberberculosis, meneingitis

• Infarction/haemorrhage

Pathophysiology

• Hypopituitarism becomes symptomatic when more than 80% of pituitary cells are damaged

Consequences of hypofunction

• ↓ GH → growth failure

• ↓ TSH → secondary hypothyroidism

• ↓ LH/FSH → hypogonadism

• ↓ ACTH → hypoadrenal

• ↓ prolactin → unknown

• ↓ ADH → diabetes insipidus

Panhypopituitarism

• Refers to deficiency of all anterior pituitary hormones

• It is most commonly caused by pituitary tumours, surgery or radiotherapy

Clinical presentation

• Variable - depend on the specific hormone deficiency, age of onset, the rate at which hypopituirarism develops, and the underlying cause of hypopituitarism

• As well as hormonal effects, intra/parasellar masses (e.g. pituitary macroadenomas, craniopharyngiomas) can present with headaches and visual field defects (bitemporal hemianopia)

Anterior hypopituitarism

• Secondary hypothyroidism, hypoadrenalism, hypogonadism and GH deficiency lead to tiredness and general malaise, and reduced quality of life

• Hypothyroidism causes weight gain, slowness of thought and action, dry skin, cold intolerance, constipation and potentially bradycardia and hyperthermia

• Hypoadrenalism causes mild hypotension, hyponatreamia and CV collapse (during severe intercurrent stressful illness)

• Hypogonadism leads to loss of libido, loss of secondary sexual hair, amenorrhoea and erectile disfunction, and eventually osteoporosis

• Hypoprolactinaemia may cause galactorrhoea and hypogonadism, including amenorrhoea

• Weight gain (due to hypothyroidism), or weight loss in severe combined deficiency

• Longstanding panhypopituitarism gives the classic picture of pallor with hairlessness ('alabaster skin')

• GH deficiency in children leads to growth retardation

Posterior hypopituitarism

• Diabetes insipidus - polyuria, polydipsia

Investigations

• Each axis of the hypothalamo-pituitary system requires separate investigation

• The presence of normal gonadal function (ovulatory menstruation or normal libido/ erections) suggests that multiple defects of the anterior pituitary are unlikely

Basal tests

• LH, FSH, oestradiol/testosterone

• IGF-1

• Prolactin

• TSH, free T4, T3

• ACTH, cortisol

• Plasma/urine osmolality

Common dynamic tests

• Growth - insulin tolerance test, glucagon test

• HP-adrenal - insulin tolerance test, short ACTH stimulation test

• Water deprivation test

Imaging

• If a pituitary hormone deficiency is identified, perform cranial imaging (preferably MRI) to identify pituitary adenomas

Management

• Principle of treatment is hormone replacement and treatment of underlying cause

Hormone replacement

• Levothyroxine

• Hydrocortisone

• Cortisol is the most important hormone to replace because its deficiency can make patients the most unwell and often presents with an 'Addisonian' type clinical picture

• Desmospray (nasal) or desmopressin tablets for ADH

• Needs to be given in children for growth

• May be considered in adults to improve work capacity and psychological well-being
• Decreases abdominal fat, increases muscle mass, strength, excercise, capacity and stamina, improves cardiac function, decreases cholesterol, increases LDL, increases bone density

• Daily SC injection

• HRT/oest/prog pill for female

• Testosterone for males - sustanon (IM every 3-4 weeks) or skin gel (testogel, tostral) or nebido (prolonged IM injection 10-14 weeks)

Underlying cause

• Depends on cause

• Transphenoidal resection in cases of pituitary macroadenomas