Growth Hormone-Secreting Pituitary Adenoma

Growth hormone secreting pituitary adenoma is a somatotroph tumour causing acromegaly in adults (gigantism if growth hormone excess begins before epiphyseal closure).

Incidence is about 3 to 4 for each million people each year, and diagnosis is usually at 40 to 60 years after a delay of 5 to 10 years. Tumours are densely or sparsely granulated, the latter being larger and less responsive to somatostatin analogues.

GNAS (gsp) variants occur in about 40% of tumours. AIP variants, MEN1 and Carney complex are rarer genetic causes.

Pathophysiology.

Excess growth hormone stimulates hepatic insulin like growth factor 1. Together they cause soft tissue and bone overgrowth, insulin resistance, sodium retention and cardiac hypertrophy.

Mortality is raised by cardiovascular, respiratory and neoplastic disease, and normalising IGF-1 lowers it.

• Enlarged hands and feet (ring and shoe size), coarse facial features, prognathism, macroglossia, sweating, skin tags, carpal tunnel syndrome and arthropathy.
• Headache, visual field loss, snoring or obstructive sleep apnoea, hypertension, cardiomyopathy, glucose intolerance, goitre and colonic polyps.
• Hypogonadism, hyperprolactinaemia and other pituitary deficits.

Red flags.

• Heart failure or severe sleep apnoea.
• Visual loss or apoplexy.

• Age- and sex adjusted IGF-1 (raised). If raised or equivocal, a 75 g oral glucose tolerance test: growth hormone not suppressed to under 1 microgram/L (0.4 microgram/L with ultrasensitive assays).
• Prolactin, pituitary MRI with contrast, visual fields, and the other pituitary axes.
• Complications: HbA1c or oral glucose tolerance test, echocardiogram, sleep study, lipids, blood pressure, thyroid ultrasound if goitre, and colonoscopy at diagnosis in adults.

Differential diagnosis.

• Physiological growth hormone rises (puberty, pregnancy, fasting, anorexia nervosa, poorly controlled diabetes, liver or kidney failure).
• Ectopic growth hormone releasing hormone production (pancreatic neuroendocrine tumour, carcinoid).
• McCune-Albright syndrome and pachydermoperiostosis.
• Hypothyroidism and other causes of coarse features.

• Transsphenoidal surgery is first line for resectable tumours. Remission: IGF-1 within the age- and sex adjusted reference range and random growth hormone under 1 microgram/L (or nadir under 0.4 microgram/L on a glucose test).
• Medical therapy: octreotide long acting 20 mg intramuscularly every 4 weeks (range 10 to 40 mg); lanreotide 90 to 120 mg deep subcutaneous every 4 weeks; pasireotide long acting 40 mg intramuscularly every 4 weeks (up to 60 mg, raises glucose); pegvisomant 10 mg subcutaneously daily after a loading dose (40 mg in some labels, 80 mg in others), titrated by 5 mg every 4 to 6 weeks to a maximum of 30 mg daily with liver tests and IGF-1; cabergoline 0.5 to 3 mg weekly for mild IGF-1 excess.
• Stereotactic radiotherapy for residual disease. Replace pituitary hormone deficits.
• Treat hypertension, diabetes, sleep apnoea (continuous positive airway pressure), heart failure and arthropathy.

Special groups. Pregnancy: stop somatostatin analogues and cabergoline when pregnancy is confirmed, check visual fields each trimester, and note that placental growth hormone raises IGF-1.

Monitoring. IGF-1 and growth hormone 12 weeks after surgery and every 3 months after starting drugs, then yearly. MRI at 3 to 6 months, then yearly. Glucose, echocardiogram and repeat colonoscopy by findings.

Referral and escalation. Pituitary multidisciplinary team; urgent review for visual loss or heart failure.