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Medical Management of Acromegaly Due to Ectopic Production of Growth Hormone-Releasing Hormone by a Carcinoid Tumor^*

Department of Medicine, Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center, University of California School of Medicine (S.M., F.H.Z., G.D.B.) Los Angeles, California 90048
Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine (T.D., L.A.F.) Cincinnati, Ohio 45267

Address all correspondence and requests for reprints to: Shlomo Melmed, M.D., Division of Endocrinology, Room 1735, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048.

A 59-yr-old woman with a disseminated carcinoid tumor was evaluated for acromegaly. She had previously undergone a hypophysectomy for acromegaly and an enlarged pituitary, with a reduction in her serum GH levels from 100 to 4 µg/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 µg/L) and insulin-like growth factor I (IGF-I; 528 µg/L) and plasma GHRH levels (12 µg/L; normal, <30 ng/L). Computed tomographic scan did not reveal pituitary enlargement. Metastatic carcinoid tissue in bone removed at biopsy contained GHRH (100 pg/mg tissue). High performance liquid chromatography of plasma GHRH revealed predominantly GHRH-(3-40)-OH, a biologically inactive GHRH metabolite, along with mature GHRH forms, while carcinoid tissue contained both GHRH-(1-40)-OH and GHRH-(1-44)-NH₂. Treatment with pergolide initially resulted in reduction in serum GH and IGF-I levels and amelioration of symptoms of acromegaly. However, after 14 months of pergolide therapy, serum GH levels increased despite administration of up to 1000 µg pergolide/day. Plasma GHRH levels remained elevated throughout the treatment period. Subsequent treatment with SMS 201–995, a long-acting somatostatin analog, for over 1 yr resulted in sustained reductions of ectopic GHRH secretion, GH hypersecretion, and IGF-I levels. Plasma GHRH levels correlated with simultaneously measured serum GH levels in response to acute SMS 201–995 administration. SMS 201–995 was an effective medical treatment for acromegaly caused by ectopic GHRH production in this patient.

^* This work was supported by NIH Grants DK-33802, DK-34824, and DK-30667 and Training Grant DK-07426 from the NIDDK.

Received December 28, 1987.

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