Case Illustration by Lewis Blevins Jr., MD, Medical Director of the California Center for Pituitary Disorders
A 56-year-old man was referred to the California Center for Pituitary Disorders for acromegaly, which was suspected based on an enlarged femoral head detected during hip replacement surgery for degenerative arthritis. His IGF-1 level was elevated at 1361 ng/mL (the normal range is 81-225 ng/mL). MRI of the pituitary showed a 2-cm macroadenoma filling the sella and extending into the superior aspect of the right cavernous sinus. He underwent transsphenoidal surgery that removed approximately 70% of his tumor. The only residual tumor was located in the superior aspect of the right cavernous sinus (see image). His IGF-1 level fell to 904 ng/mL.
Successful outcomes following surgery for acromegaly depend not only on the expertise of the operating neurosurgeon, but also on the size and degree of invasiveness of the tumor. At our center remission rates after transsphenoidal surgery are 95% for patients with microadenomas producing growth hormone and 65% to 75% for patients with macroadenomas. Patients with significant amounts of tumor within the cavernous sinuses, such as in this patient, are often difficult to cure with surgery alone, but debulking procedures significantly improve biochemical and clinical indicators of disease. Our patient had some improvement in his arthralgias, less swelling in his hands and feet, and less sweating, but remained symptomatic after surgery.
We initiated treatment with lanreotide to normalize IGF-1 and control residual tumor. Our patient's IGF-1 level decreased but failed to normalize, and reached a nadir of 305 ng/mL after 6 months of treatment. Symptoms of acromegaly persisted. Somatostatin analogues control IGF-1 and growth hormone levels in 28% to 50% of patients. Successful treatment depends on the presence of somatostatin receptors on the surface membranes of the cells composing growth-hormone-secreting pituitary adenomas. Many patients are partial responders and benefit from either alternate therapy of addition of a second drug to control their disease.
Our patient elected to discontinue his somatostatin analog and to start a trial of pegvisomant (20 mg daily). His IGF-1 level fell rapidly to 197 ng/mL and his symptoms of growth hormone excess, with exception of his arthralgias, have resolved. He remains controlled on medical management without side effects. His residual tumor has not increased in size over a 5-year period of observation. Pegvisomant can achieve normalization of IGF-1 levels in up to 93% of patients. Cabergoline, a dopamine agonist that is another alternative to somatostatin analogs, normalizes IGF-1 levels in 20% to 40% of patients.
Despite excellent results achieved with these drugs, many patients continue to suffer from uncontrolled IGF-1 levels. In a recent unpublished survey of 124 patients participating in a support group for acromegaly, elevated IGF-1 levels were reported by 44% of those treated with surgery alone and 37% of those who had undergone surgery and were on medication at the time of the survey. Nearly 25% of all patients surveyed did not know the results of their IGF-1 testing. Regardless of the drug prescribed, it is essential that doses are aggressively titrated to maximum efficacy. Normalization of the IGF-1 level not only improves symptoms and prevents progression of disease complications, but has also been correlated with restoration of normal life expectancy and survival when compared to an age-matched, healthy population. Also, it is essential that patients know their IGF-1 levels so that they can participate in decisions regarding their treatment.