Epidemiology

Taken from the results of one study:^[1]

• The incidence of hypopituitarism is estimated to be 4·2 per 100,000 per year.
• The prevalence of hypopituitarism is estimated to be 45·5 per 100,000.

Causes

The most common cause of hypopituitarism is anterior pituitary tumours. The causes of hypopituitarism include:

• Pituitary tumours: for example, adenomas
• Non-pituitary tumours: craniopharyngiomas, meningiomas, gliomas, chordomas, ependymomas, metastases
• Infiltrative processes: sarcoidosis, histiocytosis X, haemochromatosis
• Infections: cerebral abscess, meningitis, encephalitis, tuberculosis, syphilis
• Ischaemia and infarction: subarachnoid haemorrhage, ischaemic stroke, Sheehan's syndrome (postpartum haemorrhage with anterior pituitary infarction), pituitary apoplexy (caused by an acute infarction of a pituitary adenoma)^[2]
• Empty sella syndrome: radiological diagnosis of absence of normal pituitary within the sella turcica. Usually benign and asymptomatic but may develop headaches and hypopituitarism.
• Iatrogenic: irradiation,^[3] neurosurgery, withholding previous chronic glucocorticoid replacement
• Head injury (may have occurred up to several years before)^[4]
• Congenital: Kallmann's syndrome (congenital hypogonadotropic hypogonadism with midline defects such as anosmia)^[5]
• Autoimmune: lymphocytic hypophysitis^[6]
• Pituitary hypoplasia or aplasia
• Genetic causes, eg PIT1, PROP1 gene mutations, septo-optic dysplasia
• Idiopathic causes

Presentation

• Presentation varies from asymptomatic to acute pituitary failure with acute collapse and coma, depending on the aetiology, rapidity of onset, and predominant hormones involved.
• Initially, a patient with any hormone deficiency may be asymptomatic.
• May present with endocrine dysfunction:
  • Adrenocorticotrophic hormone (ACTH) deficiency:
    • Chronic: fatigue, pallor, anorexia, weight loss
    • Acute: weakness, dizziness, nausea, vomiting, circulatory collapse, fever, shock
    • Children: delayed puberty, failure to thrive
    • Hypoglycaemia, hypotension, anaemia, lymphocytosis, eosinophilia, hyponatraemia
  • Thyroid-stimulating hormone (TSH) deficiency:
    • Tiredness, cold intolerance, constipation, hair loss, dry skin, hoarseness, cognitive slowing
    • Weight gain, bradycardia, hypotension
    • Children: retarded development, growth retardation
  • Gonadotropin deficiency:
    • Women: oligomenorrhoea, loss of libido, dyspareunia, infertility, osteoporosis
    • Men: loss of libido, impaired sexual function, mood impairment, loss of facial, scrotal, and body hair; decreased muscle mass, osteoporosis, anaemia
    • Children: delayed puberty
  • Growth hormone deficiency:
    • Decreased muscle mass and strength, visceral obesity, fatigue, decreased quality of life, impairment of attention and memory
    • Dyslipidaemia, premature atherosclerosis
    • Children: growth retardation
  • Antidiuretic hormone deficiency:
    • Polyuria, polydipsia
    • Decreased urine osmolality, hypernatraemia
  • May also present with features attributable to the underlying cause:
    • Space-occupying lesion: headaches or visual field deficits
    • Large lesions involving the hypothalamus: polydipsia and inappropriate secretion of antidiuretic hormone

Hypopituitary coma

• Usually occurs in a patient known to have hypopituitarism and often develops gradually but may occur suddenly due to pituitary apoplexy.
• May be triggered by infection, trauma, surgery, hypothermia or pituitary haemorrhage.
• Clinical features include hormone deficiencies, meningism, visual field defects, ophthalmoplegia, reduced consciousness, hypotension, hypothermia and hypoglycaemia.
• Treatment is required urgently in the form of intravenous hydrocortisone. Thyroid replacement (T₃) should only be started once hydrocortisone therapy has been given. Pituitary apoplexy requires urgent surgery.

Differential diagnosis

• Polyglandular autoimmune syndromes
• Pituitary adenoma

Investigations

• Blood glucose, renal function and electrolytes (disturbances of renal function, glucose and electrolytes are common).
• Hormonal assays:
  • Thyroid function tests, prolactin, gonadotrophins, testosterone, cortisol.
  • Measurement of gonadotrophins, TSH, growth hormone, glucose and cortisol following triple stimulation with gonadotrophin-releasing hormone, TRH (thyrotropin-releasing hormone) and insulin-induced hypoglycaemia.
• Cranial MRI scan should be performed to exclude tumours and other lesions of the sellar and parasellar region after hypopituitarism has been confirmed.^[1]

Associated diseases

Hypopituitarism is sometimes associated with diabetes mellitus, dyslipidaemia, cardiovascular disease and osteoporosis.^[1]

Screening and prevention^[1]

• After pituitary surgery, glucocorticoid replacement should be given to avoid undetected hypoadrenalism until deficits of ACTH and other pituitary hormones are excluded about four weeks after surgery.
• Following traumatic brain injury or subarachnoid haemorrhage, there is a high risk of hypopituitarism but symptoms are usually masked by the sequelae of brain injury. Endocrine assessment should be routinely performed, especially following moderate or severe head injury.

Management

• Acute resuscitation, including intravenous saline boluses,^[7] may be required.
• If hypopituitarism has been caused by a tumour, pituitary function may be restored after successful surgical or medical removal of the lesion.
• Medical care consists of hormone replacement as appropriate and treatment of the underlying cause.
• Glucocorticoids are required if the ACTH-adrenal axis is impaired, especially in acute presentations. Increased doses of glucocorticoids are required following any form of emotional or physical stress (eg during an infection) to prevent acute decompensation.^[7]
• Secondary hypothyroidism: thyroid hormone replacement.
• Gonadotropin deficiency: testosterone replacement for men and oestrogens, with or without progesterone, for women (combined oral contraceptive pill for premenopausal women).
• Growth hormone replacement for children.
• Surgical
  • In pituitary apoplexy, prompt surgical decompression may be life-saving.
  • Extirpate macroadenomas that do not respond to medical therapy.

Complications

• Morbidity is variable depending on the degree of hormone deficiency and the underlying cause.
• Susceptibility to infection is increased.

Prognosis

• Mortality is increased by a factor between 1.3 and 2.2 when compared with age-sex controls.^[8]
• If adequately replaced, prognosis in hypopituitarism is good. Prognosis is therefore usually dependent on the underlying cause.

Prevention

• Good obstetric care has reduced the incidence of postpartum hypopituitarism.
• Radiation therapy that minimises exposure to the pituitary reduces incidence and time of onset of hypopituitarism.
• Improved neurosurgery techniques reduce the likelihood of subsequent hypopituitarism.