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Martin Sonenberg and William L. Money


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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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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Cristina L Ronchi, Matthias Kroiss, Silviu Sbiera, Timo Deutschbein, and Martin Fassnacht

Adrenocortical carcinoma (ACC) is not only a rare and heterogeneous disease but also one of the most aggressive endocrine tumors. Despite significant advances in the last decade, its pathogenesis is still only incompletely understood and overall therapeutic means are unsatisfactory. Herein, we provide our personal view of the currently available treatment options and suggest the following research efforts that we consider timely and necessary to improve therapy: i) for better outcome in localized ACCs, surgery should be restricted to experienced centers, which should then collaborate closely to address the key surgical questions (e.g. best approach and extent of surgery) in a multicenter manner. ii) For the development of better systemic therapies, it is crucial to elucidate the exact molecular mechanisms of action of mitotane. iii) A prospective trial is needed to address the role of cytotoxic drugs in the adjuvant setting in aggressive ACCs (e.g. mitotane vs mitotane+cisplatin). iv) For metastatic ACCs, new regimens should be investigated as first-line therapy. v) Several other issues (e.g. the role of radiotherapy and salvage therapies) might be answered – at least in a first step – by large retrospective multicenter studies. In conclusion, although it is unrealistic to expect that the majority of ACCs can be cured within the next decade, international collaborative efforts (including multiple translational and clinical studies) should allow significant improvement of clinical outcome of this disease. To this end, it might be reasonable to expand the European Network for the Study of Adrenal Tumors (ENSAT) to a truly worldwide international network – INSAT.

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Jan Born, Ina Ditschuneit, Martin Schreiber, Christoph Dodt, and Horst L Fehm

Born J, Ditschuneit I, Schreiber M, Dodt C, Fehm HL. Effects of age and gender on pituitary-adrenocortical responsiveness in humans. Eur J Endocrinol 1995;132:705–11. ISSN 0804–4643

This study compared plasma concentrations of adrenocorticotropin (ACTH) and cortisol in young men (N = 10, mean age 24.4 years), young women (N = 10, mean age 25.4 years), old men (N = 8, mean age 81.6 years) and old women (N = 8. mean age 83.5 years) under basal resting conditions and after stimulation with either human corticotropin-releasing hormone (hCRH, 100 μg iv) or a combined injection of hCRH (100 μg and arginine vasopressin (VP, 0.5 IU iv). Basal secretion of cortisol did not differ among groups, but basal concentrations of ACTH were diminished in young women (p < 0.01), indicating an enhanced adrenal sensitivity to ACTH in these subjects. Pituitary responses to hCRH did not differ between young men and women. However, responses to hCRH/VP were stronger in the young females (p < 0.01), suggesting an enhanced pituitary responsiveness to the augmenting effect of VP on ACTH release in this group. Pituitary-adrenal secretory responses were greater in old than in young men after sole injection of hCRH (p < 0.05) and even more so after combined injection of hCRH/VP (p < 0.01). In old women, pituitary-adrenal secretory responses were also greater than in young women (p < 0.05). But, in particular for responses to hCRH/VP, these effects were less distinct than within the men. Results indicate an enhancing effect of age on pituitary responsiveness to the hypothalamic secretagogues hCRH and VP, modulated by the subject's gender.

Jan Born, Klinische Forschergruppe, Klinische Neuroendokrinologie, Medizinische Universität zu Lübeck, Haus 23 a, Ratzeburger Allee 160, 23538 Lübeck, Germany