S. Ezzat et al., SOMATOTROPH HYPERPLASIA WITHOUT PITUITARY-ADENOMA ASSOCIATED WITH A LONG-STANDING GROWTH HORMONE-RELEASING HORMONE-PRODUCING BRONCHIAL CARCINOID, The Journal of clinical endocrinology and metabolism, 78(3), 1994, pp. 555-560
Acromegaly is most often associated with a pituitary somatotroph adeno
ma. While multiple lines of evidence suggest an intrinsic somatic cell
defect in adenoma formation, the role of hypothalamic hormones in pit
uitary tumorigenesis remains unclear. We describe the functional and m
orphological features of the pituitary of a patient with a longstandin
g ectopic GH-releasing hormone (GHRH)-producing tumor and acromegaly.
This 28-yr-old woman with a documented 10-yr history of a disseminated
bronchial carcinoid was evaluated for clinical features of acromegaly
. Elevated serum GH (88 mu g/L) was not suppressed after glucose inges
tion and was paradoxically stimulated by TRH, but did not respond to G
HRH or GnRH administration. Serum insulin-like growth factor-1 (730 mu
g/L; normal, <333 mu g/L), insulin-like growth factor-binding protein
-3 (9.5 mg/L; normal, 2-4.2 mg/L), and GHRH (26.1 mu g/L; normal, <20
ng/L) were elevated. Magnetic resonance imaging revealed a diffusely e
nlarged pituitary gland. Octreotide treatment for 4 months resulted in
suboptimal clinical and biochemical responses. Examination of the tra
nssphenoidally resected pituitary by light microscopy revealed diffuse
somatotroph hyperplasia, with intact reticulin network and preservati
on of the acinar architecture. Electron microscopy showed active somat
otrophs interspersed with other cell types. In situ hybridization reve
aled very strong positivity for GH mRNA, whereas fewer cells contained
GHRH and somatostatin mRNA signals. Dispersed pituitary cells secrete
d GH into culture medium. GH release was stimulated by GHRH and GHRH p
lus TRH, but-not by TRH alone; GH was suppressed by octreotide in vitr
o. We conclude that sustained exposure to ectopic GHRH leads to somato
troph hyperplasia, but, at least in this case, was not sufficient for
adenomatous transformation.