Approach
Clinical examination can provide important clues to the aetiology and duration of hypopituitarism. Diagnosis is based on biochemical confirmation of hormone deficits. Each hormone has to be tested separately and there is a variable pattern of hormone deficiency among patients.
History and examination
The clinical manifestations of hypopituitarism are variable and dependent on the duration and degree of hormone deficiencies.
Acute severe hypopituitarism
May occur with pituitary apoplexy. This may present with headache, nausea, vomiting, fatigue, weakness, dizziness, and circulatory collapse secondary to acute loss of adrenocorticotrophic hormone (ACTH) and thus subsequent cortisol deficiency.
Patients with moderate to severe traumatic brain injury are at risk of traumatic hypopituitarism.[46]
Chronic hypopituitarism
Presentation varies with age of onset.
Faltering growth, short stature, delayed dentition, delayed puberty, obesity, and sequelae of hypoglycaemia are signs of hypopituitarism in children.
In adults, pituitary tumours may present with clinical features relating to space-occupying lesions: headaches, cranial nerve palsies, temporal lobe epilepsy, and cerebrospinal fluid rhinorrhoea.[56] Functional pituitary tumours can produce a complex picture of combined hormonal excess and deficiencies (such as acromegaly in the presence of a growth hormone-secreting adenoma, or oligomenorrhoea in a woman with a prolactin-secreting pituitary adenoma), alongside signs and symptoms of mass effect from the tumour.[4]
Clinical presentations of chronic hypopituitarism in adults may include:[3][4][47][57]
Failure to lactate postpartum; may indicate prolactin deficiency, and the possible development of Sheehan syndrome.
Obesity, reduced lean body and bone mass, reduced exercise capacity, fatigue, reduced wellbeing, long-term insulin resistance, increased cardiovascular risk, and reduced quality of life; can result from growth hormone deficiency.
Erectile dysfunction, reduced fertility, reduced bone and muscle mass, loss of facial and body hair, gynaecomastia, and testicular atrophy; potential features of gonadotrophin (follicle-stimulating hormone and luteinising hormone) deficiency in men.
Amenorrhoea, oligomenorrhoea, infertility, hypoactive sexual desire disorder, breast atrophy, hot flushes, osteoporosis, and premature atherosclerosis (long-term); gonadotrophin deficiency in women.
Anorexia, weight loss, nausea, myalgias, hypoglycaemia, pallor, and loss of axillary and pubic hair in women; ACTH deficiency. Secondary chronic ACTH deficiency does not cause hypotension or hyperpigmentation, which may be present in primary adrenal insufficiency.
Weight gain, cold intolerance, fatigue, dry skin, hoarseness, constipation, bradycardia, and delayed relaxation of reflexes; hypothyroidism.
Diabetes insipidus with nocturia, polyuria, and polydipsia usually suggests a hypothalamic or hypothalamic-pituitary stalk disorder. Antidiuretic hormone (ADH) deficiency is rarely seen as a primary feature of pituitary disease, except in tumours that extend superiorly, affecting the synthesis of ADH, but is commonly seen as a presenting manifestation of pituitary metastases, granulomatous disease, and germ cell tumours. Diabetes insipidus may be masked by coexisting ACTH deficiency and may be unmasked by glucocorticoid replacement.
Mild hyperprolactinaemia due to lactotroph disinhibition from mass lesions; commonly coexists with hypopituitarism and may present as galactorrhoea.
Investigations
The knowledge that the patient has a lesion known to cause hypopituitarism - namely, a sellar or parasellar mass - is sufficient reason to test for hypopituitarism, even in the absence of symptoms and signs.
The endocrine assessment of a patient with suspected hypopituitarism usually involves measurement of basal anterior pituitary hormones and their respective target gland hormone levels.[3][47]
ACTH: cortisol
Thyroid-stimulating hormone (TSH): free thyroxine (T4) and TSH
Follicle-stimulating hormone (FSH)/luteinising hormone (LH): FSH/LH, estradiol (females), testosterone (males)
Prolactin: prolactin (PRL)
Growth hormone: insulin-like growth factor-1.
Serum electrolytes and serum and urine osmolarity should be performed as part of the initial evaluation to exclude potential complications.[3] Hyponatraemia is present in ACTH and thyroid-stimulating hormone deficiencies.[57] Hypernatraemia suggests diabetes insipidus.
A low early morning cortisol level in the setting of an inappropriately low ACTH level suggests ACTH deficiency. Dynamic testing with tetracosactide stimulation test and insulin tolerance test may be required in some patients at risk of panhypopituitarism to comprehensively assess the ACTH-adrenal axis and growth hormone secretory reserves.
Tetracosactide stimulation test should be performed initially. Limitations include false-negative tests in partial or acute pituitary insufficiency as there has not been adequate time for the adrenal gland to atrophy.
Metyrapone testing of the adrenal axis, in the hospital setting, is an alternative option, but is limited because of difficulty in acquiring metyrapone.
Insulin tolerance test is the definitive test for adrenal reserve. It is relatively contraindicated in children, older adults, and patients with cardiovascular, cerebrovascular, or seizure disorders, or untreated hypothyroidism or hypoadrenalism, because of the danger of hypoglycaemia.[3][58][59]
Patients with clinical symptoms or biochemical evidence for diabetes insipidus should have a water deprivation test performed.[47] Caution should be taken when performing a water deprivation test in older adults due to the risk of dehydration.[59]
Examination of visual fields
Essential to rule out visual field deficits and should be supported by either Goldmann or computer-assisted perimetry.[4][60] The most sensitive clinical test for visual deficits is loss of red/white appreciation in the superior upper outer quadrants when the optic chiasm is being compressed from below by a sellar mass.
Imaging studies
Imaging of the pituitary fossa is indicated when there is biochemical evidence of hypopituitarism and clinical evidence of visual field defects.
Magnetic resonance imaging (MRI) of the sella, using a dedicated pituitary protocol, is preferred.[4] MRI offers higher resolution than a computed tomography (CT) scan and is able to demonstrate microadenomas as small as 3 mm in diameter.[61][62] CT may, however, be used in patients with contraindications to MRI.[4][63]
The normal high-intensity posterior pituitary signal seen on T1-weighted MRI is absent in the majority of patients with diabetes insipidus.[3]
CT pituitary scan is performed if craniopharyngioma is suspected; it is superior to MRI in the detection of calcification (classically seen with craniopharyngiomas).
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