Recurrent acromegaly resulting from ectopic growth hormone gene expression by a metastatic pancreatic tumor.
BACKGROUND
Acromegaly is usually the result of a pituitary growth hormone (GH)-cell adenoma or is more rarely due to ectopic secretion of GH-releasing hormone (GHRH). The authors previously described a more unusual form of acromegaly secondary to ectopic GH synthesis by a pancreatic islet cell tumor.


METHODS
One year after tumor resection and transient disease remission, multiple abdominal metastases were identified with accompanying elevated levels of circulating GH and insulin-like growth factor-1 (IGF-1). Serial 24-hour GH sampling was performed before and after intravenous GHRH or thyrotropin releasing hormone (TRH) administration during treatment with bromocriptine; treatment with the somatostatin (SRIF) analogue octreotide; or no treatment. RNA from abdominal tumor tissue was extracted and subjected to Northern gel electrophoresis and GH hybridization analysis.


RESULTS
Neither GHRH nor TRH resulted in stimulation of the elevated GH levels. Bromocriptine and octreotide did not suppress GH secretion but attenuated the thyroid stimulating hormone (TSH) response to TRH administration. Octreotide (as much as 1500 micrograms/d) was clinically, biochemically, and radiographically ineffective. GH-secreting abdominal tumor tissue expressed a 0.9-kb mRNA transcript consistent with the size of authentic human GH mRNA.


CONCLUSIONS
The natural history and ectopic nature of a GH-producing pancreatic carcinoma has been documented, with biochemical remission occurring after initial tumor resection, with autonomous GH hypersecretion after tumor recurrence, and with RNA analysis demonstrating ectopic activation of GH gene transcription.
Ezzat
S
S
Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center-University of California, School of Medicine, Los Angeles 90048.
Ezrin
C
C
Yamashita
S
S
Melmed
S
S
D000172:Acromegaly / Q000097:blood* / Q000209:etiology; D001971:Bromocriptine / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D013006:Growth Hormone / Q000096:biosynthesis* / Q000235:genetics; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000150:complications; D011388:Prolactin / Q000097:blood; D012008:Recurrence; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage
D001971:Bromocriptine; D013973:Thyrotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D015282:Octreotide