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. The clinical manifestations of hypopituitarism are variable and dependent on the duration and degree of hormone deficiencies, as well as the age of onset.
Acute
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.[31]
Chronic
Children
Faltering growth, short stature, delayed dentition, delayed puberty, obesity, and sequelae of hypoglycaemia are signs of hypopituitarism in children.
Adults
Pituitary tumours may present with clinical features relating to space-occupying lesions: headaches, cranial nerve palsies, temporal lobe epilepsy, and cerebrospinal fluid rhinorrhoea.[7] Functional pituitary tumours can produce a complex picture of combined hormonal excess and deficiencies, such as a prolactinoma resulting in galactorrhoea, or excessive growth hormone resulting in acromegaly and subsequent hypothyroidism, hypogonadism, or hypoadrenalism, from mass effect of the tumour.
Failure to lactate postpartum may indicate prolactin deficiency and the possible development of Sheehan syndrome.
Growth hormone deficiency causes 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.[44]
Gonadotrophin (follicle-stimulating hormone and luteinising hormone) deficiency in men may result in erectile dysfunction, reduced fertility, reduced bone and muscle mass, loss of facial and body hair, gynaecomastia, and testicular atrophy.[45]
In women, gonadotrophin deficiency may present with amenorrhoea, oligomenorrhoea, infertility, hypoactive sexual desire disorder, breast atrophy, hot flushes, osteoporosis, and premature atherosclerosis (long-term).[46]
A combination of symptoms and two low fasting morning testosterone levels is necessary to establish a diagnosis of late-onset hypogonadism.[45]
ACTH deficiency causes anorexia, weight loss, nausea, myalgias, hypoglycaemia, pallor, and loss of axillary and pubic hair in women. Acute ACTH deficiency can cause significant hypotension; however, secondary chronic ACTH deficiency does not cause hypotension or hyperpigmentation, which may be present in primary adrenal insufficiency.[47]
Hypothyroidism may present with weight gain, cold intolerance, fatigue, dry skin, hoarseness, constipation, bradycardia, and delayed relaxation of reflexes.
The presence of 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.
Examination of visual fields clinically is essential to rule out visual field deficits and should be supported by either Goldmann or computer-assisted perimetry. 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.
Investigations
The knowledge that the patient has a lesion known to cause hypopituitarism - namely, a sellar or parasellar mass - is by itself 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 (ACTH, cortisol, thyroid-stimulating hormone, free thyroxine [T4], free triiodothyronine [T3], follicle-stimulating hormone, luteinising hormone, estradiol, testosterone, and prolactin). Growth hormone levels are not typically measured directly as growth hormone secretion is pulsatile. Insulin-like growth factor-1 represents a better overall integrated measure of growth hormone secretion.
Serum electrolytes and serum and urine osmolarity should be performed as part of the initial evaluation.[32] Hyponatraemia is present in ACTH and thyroid-stimulating hormone deficiencies.[47] 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 cosyntropin-syntropin/tetracosactide stimulation test and insulin tolerance test may be required in some patients at risk of panhypopituitarism to assess the ACTH-adrenal axis and growth hormone secretory reserves comprehensively.
Cosyntropin/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.[48]
Patients with clinical symptoms or biochemical evidence for diabetes insipidus should have a water deprivation test performed.[32]
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) is the technique of choice, as it offers higher resolution than a computed tomography (CT) scan and is able to demonstrate microadenomas as small as 3 mm in diameter.[49] The normal high-intensity posterior pituitary signal seen on T1-weighted MRI is absent in more than 95% of patients with diabetes insipidus. CT pituitary scan is performed if craniopharyngioma is suspected, as it is superior to MRI in the detection of calcification (classically seen with craniopharyngiomas).
Use of this content is subject to our disclaimer