Adult Growth Hormone Deficiency
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Direct answer
Adult growth hormone deficiency is a syndrome of reduced GH secretion, most often from pituitary tumours, their treatment or cranial injury, that produces increased fat mass, reduced lean mass and poor quality of life. Diagnosis needs a low IGF-1 together with a subnormal GH response to a provocative test, classically the insulin tolerance test. Replacement is considered only once deficiency is confirmed and glucocorticoid replacement is already in place.
What you must remember
- Causes: pituitary adenoma or craniopharyngioma, pituitary surgery or radiotherapy, traumatic brain injury and subarachnoid haemorrhage.
- Clinical picture: increased central fat, reduced exercise capacity, dyslipidaemia, low bone density and reduced quality of life.
- IGF-1 screen: a low age-adjusted IGF-1 supports deficiency, but malnutrition, liver disease, hypothyroidism, uncontrolled diabetes and oral oestrogen all lower it.
- Insulin tolerance test: induces hypoglycaemia, and a peak GH below about 3 ng/mL indicates deficiency, though cut-offs vary by assay.
- Contraindications to insulin tolerance test: ischaemic heart disease, seizure disorder and untreated adrenal insufficiency.
- Alternative tests: GHRH-arginine, glucagon stimulation and the oral macimorelin test are used when the insulin tolerance test is unsuitable.
- Replacement: recombinant GH is started at a low dose in confirmed deficiency and titrated to IGF-1 in the upper normal range for age.
- Adverse effects: fluid retention, oedema, arthralgia, carpal tunnel syndrome and insulin resistance.
Confirming AGHD step by step
Adult GH deficiency is confirmed in a fixed order, and the pituitary's other axes are secured before growth hormone is tested or given. The steps below reflect how the diagnosis and treatment are sequenced in practice.
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Establish the clinical suspicion. Take a history of head injury, cranial irradiation, pituitary surgery or subarachnoid haemorrhage, and look for central obesity and reduced exercise capacity.
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Secure the other pituitary axes first. Check cortisol and thyroid status and establish replacement where needed, because GH increases cortisol clearance and can unmask adrenal insufficiency.
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Measure IGF-1 as a screen. A low value supports deficiency but is not diagnostic, so interpret it against age, nutrition, liver function, thyroid status and oestrogen exposure.
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Perform a provocative test. Use the insulin tolerance test where it is safe, and choose a GHRH-arginine or glucagon test when it is contraindicated or hypoglycaemia cannot be achieved.
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Start and titrate replacement. Begin at a low dose and titrate to IGF-1 in the upper normal range for age, while monitoring glucose, fluid retention, lipids and bone health.
Where the exam tries to catch you
Growth hormone questions usually test the sequence of replacement, the limits of IGF-1, or the safety of the insulin tolerance test.
- Trap: starting GH before steroid replacement in hypopituitarism. Correct: GH increases cortisol clearance and can unmask adrenal insufficiency, so glucocorticoid replacement is established first.
- Trap: diagnosing adult GH deficiency from a low IGF-1 alone. Correct: IGF-1 is lowered by malnutrition, liver disease, hypothyroidism and oral oestrogen, so a provocative test is usually needed, the exception being structural pituitary disease with three or more other hormone deficiencies.
- Trap: performing an insulin tolerance test in a patient with seizures or ischaemic heart disease. Correct: the test induces deep hypoglycaemia, so it is contraindicated in these conditions and an alternative test is used.
Frequently asked questions
Why is the insulin tolerance test used to diagnose adult growth hormone deficiency?
The insulin tolerance test induces hypoglycaemia, a strong physiological stimulus for GH release, and then measures the GH response. It is regarded as the reference provocative test in many guidelines. Because it causes deep hypoglycaemia, it must be supervised and avoided in ischaemic heart disease and seizure disorders.
What GH cut-off is used to define a subnormal response in adults?
A peak GH below about 3 ng/mL on the insulin tolerance test is taken as deficiency in adults, although cut-offs vary with the assay and the test used. The laboratory and guideline cut-offs in use should always be checked before a diagnosis is made. A single low IGF-1 value never establishes the diagnosis.
Why must glucocorticoid replacement be started before growth hormone?
Growth hormone increases cortisol clearance, so starting it in a patient with untreated central adrenal insufficiency can unmask a dangerous deficiency. Glucocorticoid replacement is therefore established and stable before GH therapy begins. This sequence is a standard safety rule in hypopituitarism.
Which features of adult growth hormone deficiency support starting replacement?
Increased central fat, reduced lean mass, dyslipidaemia, low bone density and poor exercise capacity are the main features that support replacement. Reduced quality of life is an important patient-reported measure in the decision. Replacement is started only after deficiency is confirmed by testing.