Remission of acromegaly caused by pituitary carcinoma after surgical excision of growth hormone-secreting metastasis detected by 111-indium pentetreotide scan.
GH-secreting carcinomas of the pituitary are extremely rare. We describe a 37-yr-old woman with refractory acromegaly 15 yr after transphenoidal surgery and radiotherapy, with no evidence of a recurrent pituitary mass. Scanning with 111-indium pentetreotide revealed an area of intense activity in the left neck. A 3.5 x 2.5-cm mass was excised from the neck after demonstrating an arterio-venous GH gradient of 7:1. GH levels (50 ng/mL) dropped to 0.8 ng/mL 3 h after surgery and remained normal. GH gene expression was demonstrated in the metastasis by Northern and Western blot analyses and by positive immunocytochemistry and immunoelectron microscopy. In vitro cultured cells responded to GHRH and TRH by increasing GH levels (P < 0.01). Medium GH was identical to authentic pituitary GH, as demonstrated by high pressure liquid chromatography. RT-PCR of hypothalamic hormone receptor messenger RNA in the mass revealed somatostatin receptor subtypes 2, 3, and 5 and GHRH, TRH, and dopamine receptor expression. No GH gene amplification, rearrangement, or gsp mutation was found. RB gene deletion and H-ras mutations, previously reported in PRL- and ACTH-secreting carcinomas, were not detected. In conclusion, clinical and molecular features of a GH-secreting pituitary carcinoma are presented. This metastatic lesion synthesized GH and expressed functional hypothalamic hormone receptors.
Greenman
Y
Y
Department of Medicine, Cedars Sinai Research Institute-University of California School of Medicine, Los Angeles, 90048, USA.
Woolf
P
P
Coniglio
J
J
O'Mara
R
R
Pei
L
L
Said
J W
JW
Melmed
S
S
D000172:Acromegaly / Q000209:etiology / Q000628:therapy*; D000328:Adult; D000704:Analysis of Variance; D001483:Base Sequence; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D017931:DNA Primers; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007205:Indium Radioisotopes; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy / Q000601:surgery*; D016133:Polymerase Chain Reaction; D011877:Radionuclide Imaging; D011986:Receptors, Somatotropin / Q000096:biosynthesis; D013004:Somatostatin / Q000031:analogs & derivatives*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D007205:Indium Radioisotopes; D011986:Receptors, Somatotropin; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C081788:pentetreotide