Hypopituitarism

Hypopituitarism is the inability of the pituitary gland to provide sufficient hormones, due to an inability of the pituitary gland to produce hormones or due to an insufficient supply of hypothalamic-releasing hormones. Symptoms depend on the degree of hormone depletion and the rapidity of onset. Hypopituitarism is usually a mixture of several hormonal deficiencies but rarely involves all of the pituitary hormones. Hypopituitarism is usually chronic and lifelong, unless successful surgery or medical treatment of the underlying disorder can restore pituitary function.¹

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.

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

• Pituitary tumours: e.g. 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, neurosurgery, withholding previous chronic glucocorticoid replacement
• Head injury (may have occurred up to several years before)³
• Congenital: Kallmann's syndrome (congenital hypogonadotropic hypogonadism with midline defects such as anosmia)⁴
• Autoimmune: lymphocytic hypophysitis⁵
• Pituitary hypoplasia or aplasia
• Genetic causes, e.g. PIT1, PROP1 gene mutations, septo-optic dysplasia
• Idiopathic causes

• Presentation varies from asymptomatic to acute collapse, 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:
  • 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
  • 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, polyuria
  • 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

• Usually occurs in a patient known to have hypopituitarism and often develops gradually but may occur suddenly due to pituitary apoplexy.
• Sudden onset will lead to haemorrhage and meningism and may be difficult to distinguish from a subarachnoid haemorrhage. Other features at presentation include 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.

• Polyglandular autoimmune syndromes
• Pituitary adenoma

• Blood glucose, renal function and electrolytes
• Hormonal assays: T4, TSH, prolactin, gonadotrophins, testosterone, cortisol. Measurement of gonadotrophins, TSH, growth hormone, glucose and cortisol following triple stimulation with gonadotrophin-releasing hormone, TRH and insulin-induced hypoglycaemia.
• Cranial MRI should be performed to exclude tumours and other lesions of the sellar and parasellar region after hypopituitarism has been confirmed.¹

Hypopituitarism is sometimes associated with diabetes mellitus, dyslipidaemia, cardiovascular complications and osteoporosis.¹

• After pituitary surgery, glucocorticoid replacement should be given to avoid undetected hypoadrenalism until deficits of ACTH and other pituitary hormones are excluded about 4 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.

• 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 such as following acute obstetric haemorrhage.
• Secondary hypothyroidism: thyroid hormone replacement.
• Gonadotropin deficiency: testosterone replacement for men and oestrogens, with or without progesterone, for women (combined oral contraceptive pill for pre-menopausal 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.

• Morbidity is variable depending on the degree of hormone deficiency and the underlying cause.

• Mortality is increased by a factor between 1.3 and 2.2 when compared to age-sex controls.⁶
• If adequately replaced, prognosis in hypopituitarism is good. Prognosis is therefore usually dependent on the underlying cause.

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