Adult Growth Hormone Deficiency

Adult growth hormone deficiency is insufficient growth hormone secretion in adults, either persisting from childhood or acquired from pituitary disease (adenoma, surgery, radiotherapy, trauma, hypophysitis, postpartum necrosis).

It is uncommon, affecting roughly 2 to 3 for each 10,000 adults, and is nearly always accompanied by other pituitary deficiencies when acquired.

Features are increased visceral fat, reduced lean mass and bone density, dyslipidaemia, reduced exercise capacity and low mood, with raised cardiovascular risk.

Pathophysiology

Loss of the anabolic and metabolic effects of growth hormone and IGF-1 alters body composition, lipid handling and bone turnover.

Growth hormone also affects other hormones: it increases cortisol clearance and converts thyroxine to triiodothyronine. Starting replacement can unmask adrenal insufficiency and lower free thyroxine.

• Fatigue, reduced strength and exercise capacity, central adiposity, low mood and reduced quality of life.
• Dyslipidaemia and reduced bone density. No specific sign.

• Test only in patients with pituitary disease or childhood onset deficiency. With three or more other pituitary hormone deficits and a low IGF-1 (under the age- and sex adjusted range), no stimulation test is needed.
• Otherwise use a stimulation test with peak growth hormone cut offs: insulin tolerance test under 3 micrograms/L (contraindicated in ischaemic heart disease, epilepsy and untreated adrenal insufficiency); glucagon test under 3 micrograms/L (a lower cut off applies in obesity, assay dependent); macimorelin under 2.8 micrograms/L; growth hormone releasing hormone with arginine with body mass index specific cut offs (about 11, 8 and 4 micrograms/L for lean, overweight and obese).
• Childhood onset: retest after final height with growth hormone stopped for at least 1 month.
• Replace other deficits first and treat hypothyroidism and Cushing syndrome before testing.

Differential diagnosis.

• Obesity (blunted response), ageing and poorly controlled diabetes.
• Hypothyroidism, depression, chronic illness and anorexia nervosa.
• Cushing syndrome and drug effects.

• Daily somatropin by subcutaneous injection, starting low: about 0.1 to 0.2 mg daily over age 60, 0.2 to 0.3 mg daily at 30 to 60 years, and 0.4 to 0.5 mg daily under 30 years. Titrate by 0.1 to 0.2 mg every 1 to 2 months to IGF-1 in the upper half of the age adjusted reference range (not over +2 z-scores) and tolerability. Women on oral oestrogen need higher doses, or switch to transdermal oestrogen. Long acting weekly preparations (for example somapacitan) follow their own labelled dosing.
• Contraindications: active malignancy, benign intracranial hypertension and proliferative diabetic retinopathy. Defer in critical illness.
• Adverse effects: fluid retention, arthralgia, carpal tunnel syndrome, glucose intolerance and headache. Reduce the dose if these occur.
• Review hydrocortisone and levothyroxine doses after starting.

Special groups. Older adults: start at the lowest dose. Women on oral oestrogen: higher dose. Childhood onset: manage the transition in a joint clinic. Pregnancy: growth hormone is usually stopped at confirmed pregnancy.

Monitoring. IGF-1 every 2 to 3 months during titration, then yearly with glucose or HbA1c, lipids, weight and waist, and bone density every 2 to 3 years.

Referral and escalation. Endocrinology for all adults with suspected deficiency.