A 50-year-old man comes to the office following transsphenoidal resection of a growth hormone–secreting pituitary adenoma. Three months ago, the patient was diagnosed with acromegaly. MRI of the pituitary showed a 14-mm sellar mass pressing on the optic chiasm and extending into the right cavernous sinus. The surgeon was able to only partially resect the pituitary mass because of the extension into the right cavernous sinus. Medical therapy for acromegaly with octreotide is planned. Which of the following changes are likely to occur following octreotide treatment in this patient?
Acromegaly is characterized by the excessive secretion of growth hormone (GH), usually due to a somatotroph pituitary adenoma. The actions of GH are mediated primarily by insulin-like growth factor-1 (IGF-1) from the liver; classic manifestations include bony enlargement of the hands and skull (eg, frontal bossing, jaw malocclusion), arthropathy, cardiomyopathy, and skin thickening. In most cases, initial treatment includes transsphenoidal resection of the tumor. However, if the tumor is unresectable or incompletely resected, the phenotypic manifestations may progress. For these patients, additional medical therapy is indicated.
Octreotide is a long-acting octapeptide somatostatin analogue that has an altered amino acid sequence in the non–receptor binding domain, which makes it more resistant to degradation than native somatostatin. Like somatostatin, octreotide has a broad range of antisecretory actions mediated by membrane receptors. In patients with acromegaly, it inhibits GH secretion and subsequently reduces IGF-1 release, which can mitigate many of the clinical manifestations of the disease. It also exerts an anti-proliferative effect on somatotroph cells and helps reduce residual adenoma size in many patients (Choice E).
(Choices B and D) Pegvisomant is a competitive inhibitor of GH that blocks the binding of GH to its receptor. This drug reduces GH-induced IGF-1 secretion and the subsequent downstream effects but does not alter GH secretion. Adenoma size may remain stable or increase somewhat.
(Choice C) Medical treatment (eg, octreotide) is indicated for patients with incompletely resected somatotroph adenomas because, without treatment, the residual tissue will likely continue to grow and secrete GH, inducing a rise in IGF-1 levels.
Educational objective:
Acromegaly is usually treated with resection of the somatotroph pituitary adenoma, but additional medical therapy is needed for patients with residual tumor. Octreotide is a long-acting somatostatin analogue that inhibits growth hormone secretion and, subsequently, insulin-like growth factor-1 release. It also reduces residual adenoma size in many patients.