Somatostatin Analogues

Somatostatin analogues are long-acting peptides that inhibit hormone secretion. They control acromegaly and carcinoid syndrome, have antiproliferative effect in neuroendocrine tumours, and are used in variceal bleeding, high-output fistulas, chylous leaks, dumping and refractory secretory diarrhoea.

Mechanism. They bind somatostatin receptors. Octreotide and lanreotide act mainly on subtype 2 (and 5), suppressing growth hormone, IGF-1 and gut hormones. Pasireotide binds subtypes 1, 2, 3 and 5, giving added ACTH suppression in Cushing disease. They also reduce splanchnic blood flow and gut motility and secretion.

Pharmacokinetics. Octreotide immediate release has a half-life of about 2 hours (subcutaneous) and is given 2 to 3 times daily or by infusion. Depot forms (octreotide long acting, lanreotide) release over 4 weeks. Hepatic clearance, with reduced clearance in cirrhosis and kidney failure.

Octreotide. Subcutaneous 50 to 100 micrograms two to three times daily, up to 1.5 mg daily. Long acting depot 20 mg intramuscularly every 4 weeks (10 to 30 mg).

Lanreotide. 60 to 120 mg deep subcutaneous every 4 weeks (up to 120 mg every 6 to 8 weeks when controlled).

Pasireotide. Subcutaneous 0.3 to 0.9 mg twice daily or long acting 10 to 40 mg monthly (Cushing disease and acromegaly). It causes hyperglycaemia in about 60 to 70%.

Oral agents. Oral non-peptide somatostatin receptor agonists are emerging; confirm status locally.

• Acromegaly: first-line medical therapy; normalises IGF-1 in 50 to 60%. Used before surgery to shrink tumour in selected patients and after surgery if disease persists.
• Neuroendocrine tumour and carcinoid syndrome: symptoms (flushing, diarrhoea) and antiproliferative effect.
• Variceal bleeding: octreotide 50 micrograms intravenous bolus, then 50 micrograms/h for 2 to 5 days, with endoscopy.
• Sulphonylurea-induced hypoglycaemia: octreotide 50 micrograms subcutaneously every 6 hours after glucose.
• Other: pancreatic or enterocutaneous fistula, chylous leak, VIPoma, dumping syndrome, secretory diarrhoea (including in HIV).

Special groups. Pregnancy: avoid unless essential. Breastfeeding: avoid. Children: specialist use. Older adults: bradycardia and conduction defects. Kidney impairment: in dialysis start octreotide depot at 10 mg. Liver impairment: cirrhosis requires a start of 10 mg depot or lanreotide 60 mg.

Adverse effects. Diarrhoea, abdominal pain and steatorrhoea, gallstones and biliary sludge (20 to 30% with long use), bradycardia and conduction block, glucose changes (hyperglycaemia or hypoglycaemia), injection site pain, hypothyroidism, vitamin B12 deficiency.

Interactions. Reduced ciclosporin absorption. Bromocriptine exposure rises. Beta blockers and calcium channel blockers add bradycardia. Insulin and sulphonylurea doses may need reduction.

Monitoring. IGF-1 and growth hormone every 3 to 6 months, glucose (more intensely with pasireotide), gallbladder ultrasound at baseline and with symptoms, ECG at baseline, thyroid function, and B12 in long-term use.

Referral and escalation. Uncontrolled acromegaly on maximum dose, symptomatic bradycardia, gallstone complications, or marked hyperglycaemia.