title: Somatostatin and Thyrotrophin-Releasing Hormone Response and Receptor Status of a Thyrotrophin-Secreting Pituitary Adenoma: Clinical and in vitro Studies.
abstract: Abstract We have described a patient with a thyrotrophin-secreting pituitary adenoma and correlated a detailed physiological and anatomical investigation of the surgically resected tumour with its in vivo regulation. Thyrotrophin secretion was inhibited by circulating thyroid hormones, dopaminergic agonists and the somatostatin analogue SMS 201-995 but could not be stimulated by thyrotrophin-releasing hormone or further inhibited by exogenous triiodothyronine. Prolonged treatment with SMS 201-995 caused tumour shrinkage as shown by successive computed tomography scans but was accompanied by tumour desensitization and the development of diabetes mellitus. This is the first thyrotroph adenoma in which somatostatin receptors have been directly demonstrated and shown to completely block thyrotrophin-releasing hormone-induced inositol phospholipid accumulation when occupied. In addition, preincubation with triiodothyronine significantly inhibited thyrotrophin-releasing hormone-induced inositol phospholipid turnover in dispersed pituitary cells indicating that in this tumour, circulating thyroid hormones were exerting feedback inhibition at the level of the pituitary either by reducing the number of thyrotrophin-releasing hormone receptors and/or their coupling to second messenger pathways. In keeping with this hypothesis, the acute reduction in intrapituitary triiodothyronine by sodium ipodate in vivo had no effect on peripheral thyrotrophin over 6 h suggesting that the onset of the effect of triiodothyronine withdrawal on thyrotrophin secretion was suitably delayed. The importance of the inositol phospholipid second messenger pathway in transducing the secretory response in this tumour was further corroborated by electrophysiological studies which demonstrated thyrotrophin-releasing hormone-induced changes in K(+) currents which are dependent on intracellular Ca(2+) ions, presumably mobilized via the inositol phospholipids. In addition to thyrotrophin and alpha subunit, growth hormone mRNA and growth hormone were found throughout the tumour as were two populations of cells distinguished electron microscopically by the size of their secretory granules. Although acromegalic features are not unusual in thyrotroph adenomas, our patient showed no evidence of inappropriate growth hormone secretion during surgery or in response to pre- or post-operative insulin stress tests.
authors.affiliation: Medical Unit, Charing Cross and Westminster Medical School, Westminster Hospital, Page Street, London SW1P 2AP, UK.
authors.forename: A
authors.initials: A
authors.lastname: Levy
authors.forename: D J
authors.initials: DJ
authors.lastname: Eckland
authors.forename: A M
authors.initials: AM
authors.lastname: Gurney
authors.forename: J C
authors.initials: JC
authors.lastname: Reubi
authors.forename: R
authors.initials: R
authors.lastname: Doshi
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman