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The Implication of Somatotroph Adenoma Phenotype to Somatostatin Analog Responsiveness in Acromegaly

Department of Medicine, Mount Sinai Hospital (S.B., S.E.) and St. Michael’s Hospital (G.L.B.); Department of Pathology, University Health Network (S.L.A.) and St. Michael’s Hospital (K.K.); Department of Laboratory Medicine and Pathobiology (S.L.A., K.K.) and Department of Medicine, Ontario Cancer Institute and the Freeman Centre for Endocrine Oncology (S.B., S.L.A., S.E.), Toronto, Ontario, Canada M5G-1X5

Address all correspondence and requests for reprints to: Dr. Shereen Ezzat, Mount Sinai Hospital, 600 University Avenue, Room 437, Toronto, Ontario, Canada M5G 1X5. E-mail: sezzat{at}mtsinai.on.ca.

Context: Persistently elevated GH and IGF-I levels are associated with increased mortality. Their response to somatostatin analogs (SSA) is variable.

Objective: The objective of this study was to examine the significance of somatotroph adenoma type on response to SSA.

Design: This study was a retrospective examination of postoperatively treated acromegalic patients with the SSA octreotide.

Setting: The study was performed at a university-affiliated tertiary care center.

Patients: Forty patients with acromegaly were studied.

Main Outcome Measures: Normalization of IGF-I levels and GH responses were the main outcome measures.

Results: Univariate analysis revealed that responders were more likely to have densely granulated somatotroph adenomas (80% vs. 43.8%; P = 0.024), to be older (51.3 vs. 38.2 yr; P < 0.003), to have smaller tumors (stage 3; 78.6% vs. 35.7%; P = 0.022), to have lower baseline IGF-I (453 vs. 716 µg/liter; P < 0.001) and GH levels (2.7 vs. 7.8 µg/liter; P < 0.05), and to require a lower maximum dose of SSA (24 vs. 31 mg every 4 wk; P = 0.013). Multivariate analysis confirmed that a densely granulated adenoma was the strongest predictor of complete response [adjusted odds ratio (OR), 58.41; 95% confidence interval (CI), 1.24–1000.00; P = 0.04] compared with other covariates, including older age at time of diagnosis (OR, 1.15/yr; 95% CI, 1.01–1.31; P = 0.03), and tumor stage of 3 or less (OR, 29.77; 95% CI, 1.01–885.45; P < 0.05).

Conclusions: Somatotroph tumor type represents a strong clinical predictor of response to SSA treatment and will help to identify patients who warrant more vigilant management of their disease.

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