Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor.
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 micrograms/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 micrograms/L) and insulin-like growth factor I (IGF-I; 528 micrograms/L) and plasma GHRH levels (12 micrograms/L; normal, less than 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 micrograms 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.
D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology; D001859:Bone Neoplasms / Q000556:secondary; D002276:Carcinoid Tumor / Q000032:analysis / Q000150:complications* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D006729:Hormones, Ectopic / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D015282:Octreotide; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D006729:Hormones, Ectopic; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone; D015282:Octreotide