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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 the pituitary hormones. Hypopituitarism is usually chronic and lifelong, unless successful surgery or medical treatment of the underlying disorder can restore pituitary function.
Taken from the results of one study:
- The incidence of hypopituitarism is estimated to be 4·2 per 100,000 per year.
- The prevalence of hypopituitarism is estimated to be 29-45 per 100,000.
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).
- 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).
- Congenital: Kallmann's syndrome (congenital hypogonadotropic hypogonadism with midline defects such as anosmia).
- Autoimmune: lymphocytic hypophysitis.
- Pituitary hypoplasia or aplasia.
- Genetic causes - eg, PIT1, PROP1 gene mutations, septo-optic dysplasia.
- Idiopathic causes.
- 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:
- Adrenal insufficiency and Addison's disease.
- 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:
- See also the separate Hypothyroidism article.
- Tiredness, cold intolerance, constipation, hair loss, dry skin, hoarseness, cognitive slowing.
- Weight gain, bradycardia, hypotension.
- Children: delayed development, growth restriction and intellectual impairment.
- Gonadotrophin 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:
- Short stature.
- Decreased muscle mass and strength, visceral obesity, fatigue, decreased quality of life, impairment of attention and memory.
- Dyslipidaemia, premature atherosclerosis.
- Children: growth restriction.
- 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.
- 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.
- Blood glucose, renal function and electrolytes (disturbances of renal function, glucose and electrolytes are common).
- Hormonal assays:
- TFTs, prolactin, gonadotrophins, testosterone, cortisol.
- Measurement of gonadotrophins, TSH, growth hormone, glucose and cortisol following triple stimulation with gonadotrophin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH) and insulin-induced hypoglycaemia.
- Pituitary function tests.
- Cranial MRI scan should be performed to exclude tumours and other lesions of the sellar and parasellar region after hypopituitarism has been confirmed.
Screening and prevention
- 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.
- Acute pituitary failure may require resuscitation, including intravenous fluids.
- 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.
- Secondary hypothyroidism: thyroid hormone replacement.
- Gonadotrophin deficiency: testosterone replacement; oestrogens, with or without progesterone, for women (combined oral contraceptive pill for premenopausal women). Dehydroepiandrosterone may be prescribed also. It is a precursor hormone, so has little biological effect on its own, but has powerful effects when converted into other hormones such as testosterone and estradiol.
- Growth hormone replacement.
- Management of diabetes insipidus.
- In pituitary apoplexy, prompt surgical decompression may be life-saving.
- Removal of macroadenomas that do not respond to medical therapy.
- Morbidity is variable depending on the degree of hormone deficiency and the underlying cause.
- Susceptibility to infection is increased.
- Although an increased mortality rate in hypopituitary patients is well documented, the actual cause of the increased mortality is not clear.
- If relevant hormones are 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 minimises exposure to the pituitary gland reduces incidence and time of onset of hypopituitarism.
- Improved neurosurgical techniques reduce the likelihood of subsequent hypopituitarism.
Further reading and references
Brain tumours (primary) and brain metastases in adults; NICE Guideline (July 2018)
Human growth hormone (somatropin) for the treatment of growth failure in children; NICE Technology Appraisal Guidance, May 2010
Regal M, Paramo C, Sierra SM, et al; Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001 Dec55(6):735-40.
Hypogonadotropic hypogonadism 2 with or without anosmia, HH2; Online Mendelian Inheritance in Man (OMIM)
Molitch ME; Diagnosis and Treatment of Pituitary Adenomas: A Review. JAMA. 2017 Feb 7317(5):516-524. doi: 10.1001/jama.2016.19699.
Brain and central nervous system cancers - recognition and referral; NICE CKS, November 2015 (UK access only)
Weiss RE; Hypopituitarism: Emergencies. last updated April 2015.
Higham CE, Johannsson G, Shalet SM; Hypopituitarism. Lancet. 2016 Mar 31. pii: S0140-6736(16)30053-8. doi: 10.1016/S0140-6736(16)30053-8.
Shared Care Guidelines: Paediatric use of Recombinant human Growth Hormone (r-hGH, Somatropin); British Society for Paediatric Endocrinology and Diabetes (July 2015)
Capatina C, Inder W, Karavitaki N, et al; Management of endocrine disease: pituitary tumour apoplexy. Eur J Endocrinol. 2015 May172(5):R179-90. doi: 10.1530/EJE-14-0794. Epub 2014 Dec 1.