History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors for hypopituitarism include pituitary tumours, apoplexy, surgery, or radiation; genetic predisposition such as mutations of the PROP1 gene that cause familial hormone deficiencies; and hypothalamic disease.

history of traumatic brain injury

Hypopituitarism as a consequence of traumatic brain injury is increasingly recognised.[11][12]​​

Deficiency of one or more pituitary hormones may follow a traumatic brain injury and is especially prevalent in younger populations.[44][45][46]

headaches

Often develop due to raised intracranial pressure from a space-occupying lesion in the sellar or parasellar region.

In patients who develop a sudden severe headache, the possibility of pituitary apoplexy needs to be considered.

faltering growth or short stature

Growth hormone deficiency in children.

infertility

Gonadotrophin deficiency.

hypoglycaemia

Adrenal insufficiency.

amenorrhoea/oligomenorrhoea

Suggests gonadotrophin deficiency and occurs early in the sequence of pituitary hormone loss. Patients can also present with prolactin excess causing functional suppression of the pituitary gonadal axis.

galactorrhoea

Seen in patients with elevated prolactin levels from stalk effect or a prolactinoma.

May be spontaneous or expressible.

delayed puberty

Absence of facial and body hair, gynaecomastia, and small undeveloped testes due to gonadotrophin deficiency in childhood.

uncommon

family history of pituitary hormone deficiencies

Family members may have required multiple hormone replacement therapies from childhood.

hypotension

Acute adrenal insufficiency.

visual field defects

Patients will complain of difficulty seeing into the periphery, sometimes described as tunnel vision.

ophthalmoplegia

Associated with cranial nerve invasion or impingement by a sellar or parasellar process. Patients characteristically complain of diplopia.

Other diagnostic factors

common

cardiovascular events

Attributable to relative insulin resistance and chronic growth hormone deficiency (leading to obesity, hyperlipidaemia, and hypertension).[7]

cold intolerance

Thyroid hormone deficiency.

weight gain

Thyroid hormone deficiency.

erectile dysfunction and reduced libido

Seen in males with low testosterone from hypogonadotrophic hypogonadism.

nausea

Adrenal insufficiency.

vomiting

Adrenal insufficiency.

fatigue

Adrenal insufficiency.

weakness

Adrenal insufficiency.

dizziness

Adrenal insufficiency.

constipation

Thyroid hormone deficiency results in reduced gastrointestinal motility.

dry skin

Thyroid hormone deficiency.

delayed relaxation of reflexes

Thyroid hormone deficiency.

uncommon

hypoactive sexual desire

Gonadotrophin deficiency.

hot flushes

Gonadotrophin deficiency.

nocturia and polyuria

Antidiuretic hormone insufficiency leading to diabetes insipidus.

breast atrophy

Gonadotrophin deficiency.

reduced bone and muscle mass

Due to gonadotrophin deficiency in both sexes. Osteoporosis may present as an atraumatic fracture or as an incidental finding on radiological tests.

loss of axillary and pubic hair

Chronic cases of adrenal insufficiency.

Risk factors

strong

pituitary tumour

Typical clinical syndrome such as acromegaly, resulting from hypersecretion of one or more anterior pituitary hormones. Alternatively, they may present more insidiously with mass effect, with tumour expansion leading to compression of surrounding structures.[13]

Craniopharyngiomas arise in Rathke's pouch and may be cystic or solid and are commonly calcified. They commonly present with growth hormone deficiency and diabetes insipidus, with or without visual field defects.[15]

pituitary apoplexy

Denotes the sudden haemorrhagic destruction of a pre-existing pituitary adenoma. It presents with the sudden onset of an excruciating headache, visual disturbance, or ophthalmoplegia due to cranial nerve palsies (III, IV, VI).[48]

pituitary surgery

The risk of new hypopituitarism after pituitary adenoma surgery varies from approximately 5% to 25%.[42][43]​​ Aetiology and surgeon experience inform risk.

Prompt postoperative assessment of pituitary function should be performed following surgery for pituitary adenomas.[49]

cranial radiation

In patients with pituitary adenoma, radiotherapy is associated with new or worsening pituitary hormone deficits at 5 years in 30% to 50% and 10% to 40% of patients treated with conventional radiotherapy and stereotactic radiosurgery, respectively.[41]

The degree of hormonal deficits caused by radiotherapy is related to the age of exposure of the patient, the radiation dose received, and the time elapsed since the radiation exposure to the hypothalamic-pituitary axis.[50][51][52]

traumatic brain injury

Deficiency of one or more pituitary hormones may follow a traumatic brain injury and is especially prevalent in younger populations.[44][45]​​[46]​​

A head injury can lead to pituitary dysfunction, regardless of the severity of the injury, and timing of presentation can vary from immediately after the injury to months afterwards.[53]

genetic predisposition

May be of either pituitary or hypothalamic origin. Congenital deficiencies may be of isolated hormones or multiple pituitary hormones.[37]

Transcription factor defects including Pit-1, PROP1, HESX1, LHX3, and LHX4 are associated with multiple hormone deficiencies and varying degrees of inherited hypopituitarism.[38][39]​​ Mutations in the PROP1 gene are the most common cause of familial and sporadic congenital pituitary hormone deficiencies.

Mutations in the TBX19 gene (also known as TPIT) cause isolated adrenocorticotrophic hormone (ACTH) deficiency.[40]

hypothalamic disease

Unlike diseases that affect the pituitary directly, hypothalamic conditions can also diminish secretion of vasopressin and cause diabetes insipidus (DI). Typically, pituitary lesions alone do not cause DI, because some vasopressin-producing neurons terminate in the median eminence.

Mass lesions such as craniopharyngiomas, malignant tumours, and metastasis; hypothalamic radiation; and infiltrative lesions such as sarcoidosis and more commonly Langerhans cell histiocytosis X have been associated with the development of DI.

weak

inflammatory disorders

Lymphocytic hypophysitis commonly results in adrenocorticotrophic hormone and thyroid-stimulating hormone deficiency; however, diabetes insipidus and hyperprolactinaemia have also been described.

Hereditary haemochromatosis commonly results in gonadotrophin deficiency.

severe postpartum haemorrhage (Sheehan syndrome)

Infarction of the pituitary after substantial blood loss with hypotension during childbirth.[22][23]

Anterior pituitary hormone deficits may be single or multiple depending on the degree of necrosis. Classically, it is associated with inability to lactate post delivery.[54]

empty sella syndrome

Characterised by the herniation of the subarachnoid space within the sella turcica.

Primary empty sella excludes any history of previous pituitary pathology, and is considered to be idiopathic. Secondary empty sella may occur following: pituitary tumour treatment (e.g., neurosurgery, radiotherapy, or pharmacotherapy); spontaneous necrosis (ischaemia or haemorrhage); or an infectious process.[55]

tuberculous meningitis

May cause hypopituitarism years after the original infection.

syphilis

May cause hypopituitarism in congenital syphilis and adult infection.

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