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RJM Ross and SL Chew

Growth hormone (GH) resistance is defined biochemically by the finding of high GH and low IGF-I levels. It may be primary, as in Laron's syndrome (GH receptor mutations), or acquired (Table 1) (1). Acquired resistance is found in conditions that have in common malnutrition and net protein catabolism. There is evidence to suggest that GH resistance is permissive to protein catabolism and that its reversal may improve the nutritional state of some patients. In this review we discuss the clinical problem, its molecular basis and the possibility of therapeutic intervention with GH and/or IGF-I.

The clinical problem

Trauma, sepsis, surgery and organ failure are all associated with an increased catabolic rate. When prolonged, this results in malnutrition, muscle weakness, delayed wound healing and immunosuppression (2). Loss of body protein still occurs in these patients groups despite intense nutritional support (3). In many patients nutritional state is the most important predictor

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CW le Roux, PJ Jenkins, SL Chew, C Camacho-Hubner, AB Grossman, GM Besser and JP Monson

OBJECTIVE: Epidemiological studies have shown an increased risk for prostate carcinoma in men with serum IGF-I in the upper part of the age-related reference range. Recombinant human GH (rhGH) is widely used in patients with GH deficiency, usually raising the serum IGF-I levels into the normal range: safety surveillance is therefore mandatory, with particular regard to neoplasia. The aim was to examine whether rhGH replacement in hypopituitary adults is associated with changes in serum prostate-specific antigen (PSA) as a surrogate marker of changes in prostatic growth. DESIGN AND METHODS: A prospective longitudinal study was used with a median follow-up of 22 (range 2.5-32) months, in which 41 men aged over 50 years with adult onset hypopituitarism and GH deficiency during rhGH replacement were examined. Serum PSA and IGF-I were measured at baseline and at latest follow-up. RESULTS: Mean serum PSA remained unchanged during rhGH replacement, with a median follow-up of 2 years. No correlation was found between the individual changes in serum IGF-I and changes in serum PSA. CONCLUSIONS: These data are reassuring thus far regarding the safety of GH replacement in relation to the prostate in this patient group.

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RJM Ross, SL Chew, L Perry, K Erskine, S Medbak and F Afshar

Ross RJM, Chew SL, Perry L, Erskine K, Medbak S, Afshar F. Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery. Eur J Endocrinol 1995;132:722–6. ISSN 0804–4643

The diagnosis of Cushing's Disease during pregnancy is complex because the biochemical features are obscured by changes in the normal hypothalamo-pituitary-adrenal axis that occur during gestation. To date, treatment has not been successful and there is a high incidence of maternal and fetal complications. We report the case of a 24-year-old woman with Cushing's disease who presented during her 16th week of pregnancy. Diagnosis was confirmed by the finding of elevated serum and urinary free cortisol levels with loss of the normal circadian rhythm of serum cortisol. Cortisol levels failed to suppress after a low-dose dexamethasone test but suppressed after a high-dose test. There was an exaggerated serum cortisol and plasma adrenocorticotrophin (ACTH) response to corticotrophinreleasing hormone (CRH). Magnetic resonance (MR) scanning demonstrated a pituitary tumour and cure was effected by transsphenoidal surgery where tumour immunostaining for ACTH was removed. Postoperatively the patient made an uncomplicated recovery; serum cortisol and plasma ACTH levels were undetectable at 9 days following surgery and recovery of the hypothalamo-pituitary axis occurred at 99 days after surgery. Caesarean section was performed at 38 weeks of pregnancy and a healthy but small female infant was delivered. This case illustrates the biochemical features of Cushing's disease during pregnancy and is the first report of the use of CRH testing and MR scanning in this clinical situation. The cure by surgery and successful outcome for mother and infant, with preservation of normal anterior pituitary function, suggest that transsphenoidal surgery may be the treatment of choice.

RJM Ross, Dept of Endocrinology, St Bartholomew's Hospital, London ECIA 7BE, UK