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Maria Bückström, Kerstin Hall and Vicki Sara

Abstract. Somatomedin levels in cerebrospinal fluid (CSF) were determined in patients with acromegaly, pituitary deficiency, prolactinoma, and Cushing's disease by radioimmunoassay (RIA) for insulin-like growth factor 1 (IGF-1) and for IGF-2 as well as a radioreceptor assay (RRA) with adult human brain plasma membranes and IGF-2 as ligand. The mean value of RIA-IGF-2 (31 ± 1.6 ng/ml) predominated over that of RIA-IGF-1 (5.8 ± 0.3 ng/ml), but 10 times higher levels were found by RRA-IGF-2. Patients with acromegaly were not found to have higher values than those with GH deficiency even after corrections were made for possible leakage across the blood-CSF barrier. No correlations were found between CSF somatomedin levels determined by different techniques and immunoreactive IGF-1 or GH in the peripheral circulation except for a positive correlation between CSF RIA-IGF-2 and serum IGF-1 in patients with acromegaly. These findings suggest that somatomedins in CSF consist primarily of IGF-2-like peptides which are derived from production within the central nervous system or pituitary gland rather than from transport across the blood-CSF barrier.

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Maria C Thorén, Inga-Lena Wivall-Helleryd, Werner F Blum and Kerstin E Hall

Thorén MC, Wivall-Helleryd I-L. Blum WF, Hall KE. Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency. Eur J Endocrinol 1994;131:33–40. ISSN 0804–4643

Insulin-like growth factor I (IGF-I) circulates bound to specific binding proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We administered recombinant IGF-I (40 μg/kg body wt, from Kabi Pharmacia) in a morning dose (08.00 h) for seven consecutive days to six patients (21–47 years) with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood sampling was performed on days 1 and 7, otherwise morning samples were drawn. The mean serum total IGF-I was maximal 3–4 h after the injection. A higher peak and basal value (p < 0.05) was observed on day 7 when compared to that observed on day 1. The concentrations were 237 vs 190 μg/l and 43 vs 22 μg/l. The mean free IGF-I increased concomitantly to 17 and 20 μg/l after 2–3 h on days 1 and 7. After 4 h, IGF-II was decreased (p <0.05) from 340 to 291 μg/l on day 1 and from 341 to 252 μg/l on day 7. The IGF-I area under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the patient with the highest IGFBP-3 level obtained IGF-I levels above 100 μg/l for 24 h. In spite of unchanged glucose levels, there was a modest suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were fasting. A small decline of mean potassium concentrations was found 2–6 h after the injection on day 1. During a week with daily injections, the morning serum IGF-I increased slightly in comparison to basal levels but no significant change in morning values of IGFBP-1, -2, -3, glucose and insulin were observed. Serum urea, creatinine, cholesterol and free fatty acid decreased significantly, indicating metabolic effects of IGF-I. Thus IGF-I has metabolic effects in doses not leading to hypoglycemia. To achieve a normal diurnal IGF-I level, recombinant IGF-I should be administered two or three times per 24 h in subjects with subnormal IGFBP-3 levels.

Marja Thorén, Department of Endocrinology and Diabetology, Karolinska Hospital, S-171 76 Stockholm, Sweden

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Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout J Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen and Evi Nagler

Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association – European Dialysis and Transplant Association (ERA–EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.

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Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout J Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen and Evi Nagler