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  • Author: Jos H Thijssen x
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Hans P. F. Koppeschaar, Ronald J. M. Croughs, Johanna W. van 't Verlaat, Martin J. Hendriks, Cor J. M. Arts, Jos H. H. Thijssen and Frits Schwarz

Abstract. Transfrontal hypophysectomy was performed in a patient with Cushing's disease and gross enlargement of the pituitary. Despite some reduction of cortisol production active Cushing's syndrome remained due to the presence of a tumour remnant. Medical treatment with the GABA-transaminase inhibitor sodium valproate induced hypocorticism necessitating corticosteroid substitution therapy. Nine months after sodium valproate withdrawal hypercorticism was documented. Re-institution of sodium valproate treatment induced hypocorticism again.

As sodium valproate is known to induce a decrease of plasma ACTH in Nelson's syndrome, it is proposed that large tumours present at the time of diagnosis and those appearing after adrenalectomy may represent the spectrum of a single disorder. A prospective trial to study the effects of sodium valproate and other neurotransmitter modulating agents on the size and endocrine function of ACTH secreting macroadenomas is urgently needed.

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Corné A Roelen, Hans P Koppeschaar, Wouter R de Vries, Pierre M Zelissen, Yvonne E Snel, Manorath E Doerga, Jos H Thijssen and Rien A Blankenstein

Roelen CA, Koppeschaar HP, de Vries WR, Zelissen PM, Snel YE, Doerga ME, Thijssen JH, Blankenstein RA. High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency. Eur J Endocrinol 1996;135:82–6. ISSN 0804–4643

The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements.

HPF Koppeschaar, Department of Endocrinology, University Hospital Utrecht, HPL00.407, PO Box 85500, 3508 GA Utrecht, The Netherlands