Somatotropin and growth hormone antagonists

Somatotropin and growth hormone antagonists

Growth hormone (GH) replacement

Recombinant GH (somatotropin, peptide sequence identical to human pituitary growth hormone 1) is licensed to treat gonadal dysgenesis (of Turner syndrome) and GH deficiency (including growth failure in children- see NICE guidance TA188 in the UK). It is administered by s.c. injection and is available in injection devices and needle-free autoinjectors.

 

Modulation of GH activity

GH activity can be altered by the administration of somatostatin analogues or GH receptor antagonists.

Somatostatin analogues

In normal physiology somatostatin acts to inhibit production of several hormones, including GH and some gut hormones and controls release of hormones from the pancreas. Pharmacological analogues mimic somatostatin's effects in particular indications. In carcinoid tumours these drugs are used to inhibit secretory activity and reduce carcinoid syndrome symptoms such as flushing and diarrhea.

  • lanreotide is licensed to treat acromegaly, neuroendocrine tumours and thyroid tumours. Lanreotide can be used to manage unresectable advanced or metastatic gastroenteropancreatic neuroendocrine tumours of midgut, pancreatic or unknown origin where hindgut sites of origin have been excluded.
  • octreotide is licensed for symptomatic relief from carcinoid tumour related effects, for short-term treatment of acromegaly before surgery, or for longer-term treatment of tumours inadequately controlled by other treatment or post-radiotherapy whilst it takes full effect. In palliative medicine octreotide is licensed to reduce intestinal secretions and vomiting caused by bowel obstruction.
  • pasireotide is licensed to treat Cushing's disease in patients for whom surgery is inappropriate or has failed. This drug is used less often than lanreotide and octreotide.

 

GH receptor antagonist

GH receptor antagonists compete with endogenous GH for the receptor and inhibit proper GH signal transduction. One of the effects of GH receptor antagonism is a reduction in IGF-1 production and secretion, and disruption of the GH/IGF-1 axis.

  • pegvisomant is a peptidic GH receptor antagonist licensed in the UK to treat acromegaly in patients with inadequate response to surgery and/or radiation and to treatment with somatostatin analogues. The peptide is conjugated with polyethylene glycol (PEGylated) to increase its circulating half-life.