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MALCOLM M. MARTIN, ARLINE L. A. MARTIN and KENNETH L. MOSSMAN

Abstract. The outcome of treatment in 3 groups of boys with constitutional delay in growth and development given monthly intramuscular injections of testosterone enanthate 200 mg (22 subjects) 100 mg (10 subjects) and 50 mg (12 subjects) was compared with the outcome in a control group (14 subjects) without treatment. The 4 groups were similar in chronological age, height, height age, bone age, height age/bone age ratio, pubertal development and had similar predicted adult heights. All treated subjects achieved an excellent growth response with growth velocities reflecting androgen dose. Bone age advanced commensurate with height age in all the treated groups and Δ height age/Δ bone age ratios at the end of therapy did not differ significantly. Nor was there a significant difference in the height prediction by the RWT method before and at the end of treatment. However, the year following treatment, growth velocities reversed so that those who received the largest steroid dose and had grown the fastest, decelerated the most and eventually ended up significantly shorter than their predicted adult height. In contrast the control group and those treated with smaller doses of testosterone achieved their predicted heights. The present study confirms that large doses of androgens compromise adult height and are contraindicated in the treatment of constitutional delay in growth and development. Testosterone enanthate 50 mg/mo did not affect predicted adult height adversely, but to the contrary, permitted it to be fully realised. The data caution against drawing conclusions based on changes observed during androgen therapy in the absence of extended follow-up.

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Martin Sonenberg and William L. Money

ABSTRACT

The effect of various reagents, which produce protein derivatives, on the biological activity of growth hormone has been studied. Various conditions which affect growth hormone stability have also been investigated. In general, it has been found that reaction of growth hormone with phenylisocyanate, nitrous acid or concentrated sulfuric acid, under the conditions specified, destroyed the biological activity. Reaction of growth hormone with thioglycolic acid, iodine, or acid methanol yielded growth hormone derivatives which were active or inactive, depending on the reaction conditions. Reaction with acid ethanol, formaldehyde, cysteine, sodium bisulfite, diisopropylfluorophosphate, urea or bromine had no effect on the growth-promoting activity of these preparations. Growth hormone was found to be rather stable in dilute and glacial acetic acid except when heated to a temperature of 94° C. The implications of these findings are discussed.

None of the growth hormone derivatives obtained in this study was able to inhibit the growth-promoting response induced by unmodified growth hormone preparations.

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Helen L Storr and Martin O Savage

Cushing's disease (CD) is the commonest form of ACTH-dependent Cushing's syndrome and is a rare clinical diagnosis in paediatric and adolescent patients. CD is caused by an ACTH-secreting pituitary corticotroph adenoma and is associated with significant morbidity in children; therefore, early diagnosis and treatment are critical for optimal therapeutic outcome. This review highlights the key clinical and biochemical features of paediatric CD and appraises current practices in diagnosis and management. A close liaison with adult endocrinology colleagues, particularly, for interpretation of investigations and definition of therapeutic strategy is strongly advised.

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G. Tolis, L. Kovacs, H. Friesen and J. B. Martin

ABSTRACT

Ten patients with active acromegaly were studied. In 9 plasma GH levels failed to suppress after glucose (OGTT), in 8 an increase in serum GH occurred after thyrotrophin releasing hormone (TRH). After L-Dopa, 4 patients showed no change in serum GH, 3 exhibited a decrease and in 3 an increase in serum hGH occurred. With a combined insulin (ITT) and arginine (ATT) test, 2 patients exhibited an increase in hGH, and in 6 no change occurred. Fasting serum GH concentration was less than 11 ng/ml in 5 patients. Basal prolactin (hPRL) levels were normal in all patients including two with galactorrhea. L-Dopa suppressed and TRH stimulated hPRL secretion in all, but the responses which were seen were subnormal. Hydrocortisone infusion in two acromegalics did not affect the prolactin induced increase after TRH but blunted the GH increase after TRH.