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What is Acromegaly?

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Acromegaly is an insidious disorder, due to chronic hypersecretion of growth hormone (GH) occurring in adulthood. GH hypersecretion prior to epiphyseal fusion results in gigantism. Elevated GH and/or insulin-like growth factor-1 (IGF-1) levels affect multiple organ systems resulting in acral and soft tissue growth, and metabolic dysfunction. Untreated acromegaly causes significant morbidity and mortality. Furthermore, mortality rates are twice the expected value, most commonly due to cardiovascular and respiratory complications. Control of GH hypersecretion lowers the morbidity and mortality associated with acromegaly. Ninety-fne percent of cases of acromegaly are caused by benign GH secreting pituitary adenomas; ectopic pituitary tumors and extrapituitary tumors (hypothalamus, pancreas, carcinoid, lung, ovary, breast) are found in a very small percentage of cases.

Treatment goals for patients harboring pituitary tumors include normalization of GH and IGF-1 levels, as well as removal of the adenoma with preservation of pituitary function and surrounding structures.

Therapeutic options include surgery, radiotherapy and drug therapy.

Approximately 30% of GH secreting pituitary adenomas are microadenomas (lOmm), resulting in persistence of GH hypersecretion postoperatively in half of the cases. Several patients, demonstrating postoperative “biochemical cure”, show recurrent tumor growth and increased GH levels when retested subsequently. Transsphenoidal pituitary tumor resection should be performed by surgeons experienced in this technique.

Radiotherapy is very effective in shrinking GH secreting pituitary tumors, but may take up to 20 years to lower GH levels and is associated with a high incidence of hypopituitarism. Data from longterm studies investigating the safety and efficacy of stereotactic radiosurgery (gamma knife) are not yet available.

Medical therapy includes dopamine agonists (DA), somatostatin analogs and GH antagonists. Only 15-20% of patients demonstrate GH suppression and 10% normalization of IGF-1 level on high doses of DA therapy. Somatostatin analogs normalize IGF-1 levels in 60% of patients. Somatostatin analogs are administered by subcutaneous injection in divided doses three to four tlmes daily. However, longacting somatostatin analog formulations administered intramuscularly once or twice a month will soon be available in the USA. Trovert, a pegylated analog of human growth hormone, functions as a growth hormone antagonist, displacing GH from hepatic receptors, thereby lowering circulating IGF- 1 levels. The safety and efficacy of a once daily subcutaneous injection of Trovert are currently being evaluated.

The addition of these long-acting and novel formulations to the treatment modalities for acromegaly greatly enhance therapeutic options.

References:

  1. Melmed S. Acromegaly. In: Melmed S., ed. The Pituitary. London Blackwell Science Inc., 1995: 413-442.
  2. Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK. 1994. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinology (Oxf) 41:95-102.
  3. Fahlbusch R, Honegger J, Schot W, Buchfelder M. 1994 Results of surgery in acromegaly. In: Wass JAH ed. Treating acromegaly. Bristol: Journal of Endocrinology; 49-54.
  4. Laws Jr. ER, Carpenter SM, Scheithauer BW, Randall RV. 1987 Long term results of transsphenoidal surgery for the management of acromegaly. In: Robbins R, Melmed S, eds. Acromegaly: a century of scientific and clinical progress. New York: Plenum Press; 241-248.
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  6. Jaffe CA, Barkan AL. 1992 Treatment of acromegaly with dopamine agonists. Endocrinol Metab Clin North Amer 21:713-735.
  7. Ezzat S, Snyder PJ, Young WF et al. 1992. Octreotide treatment of acromegaly: a randomized multicenter study. Ann Intern Med. 117:711-718.
  8. Newman C, Melmed S, Snyder, PJ et al. 1995. Safety and efficacy of long term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients-a clinical research center study. J Clin Endocrinol Metab 80:1768-2775.
  9. Sassolas G. 1995. Medical Therapy with somatostatin analogs for acromegaly. Eur J Endocrinol 133:675-677.
  10. Cheung NW, Taylor L, Boyages SC. 1997 An audit of long term octreotide therapy for acromegaly. Aust NZ J Med. 27: 12-18.
  11. Harris AG. 1996. Treatment of acromegaly. In: Daly AF, ed. Acromegaly and its managment. Philadelphia: Lippincott-Raven; 49-68.
  12. Flagstad AK, Halse J, Rakke S, et al. 1997 Sandostatin LAR in acromegalic patients; long term treatment. J Clin Endocrinol Metab 80:3601-3607.