U. Cordes

Subcutaneous gonadotropin therapy in male patients with hypogonadotropic hypogonadism

OBJECTIVE The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism. DESIGN Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively. SETTING The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology. PATIENTS Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmanns syndrome in prepubertal or early pubertal stages. INTERVENTIONS Human chorionic gonadotropin and hMG were administered SC in individual dosages. MAIN OUTCOME MEASURES Increase of serum testosterone (T), testicular volume, semen volume, and sperm count were evaluated. RESULTS Normalization of serum T and complete sexual maturation was achieved in all patients. Spermatogenesis was induced in all but two patients. Seven patients showed normal findings in semen volume and sperm count, and two patients had semen quality close to normal. In five patients sperm count remained less than 10 x 10(6)/mL. CONCLUSIONS The results obtained by SC gonadotropin replacement prove this mode of administration to be effective in stimulating steroidogenesis and spermatogenesis in hypogonadotropic males.

Gonadotropin secretion in eugonadotropic human males and postmenopausal females under long-term application of a potent analog of gonadotropin-releasing hormone.

Long-acting analogs are of special interest in long-term treatment with gonadotropin-releasing hormone (GnRH). However, inhibitory effects of agonist analogs on gonadotropin secretion or on reproductive processes have been observed in rats as well as in human males. Since these inhibitory effects seem to be dose-related, we checked the findings for d-Leu 6 -des-Gly 10 -GnRH-ethylamide within the dose range proposed by us for treatment. In six eugonadotropic human males, a significant decrease of luteinizing hormone and follicle-stimulating hormone responsiveness to a standard dose of GnRH and significant decrease of testosterone basal secretion were observed after 2 and 4weeks of subcutaneous administration of 5μg of d-Leu 6 -des-Gly 10 -GnRH-ethylamide twice daily. In two eugonadotropic males, these effects could not be observed under pernasal administration of 50μg of the substance for 4weeks. In two postmenopausal women, subcutaneous long-term administration of 5μg of the substance produced a marked decrease of basal serum levels and decreased responsiveness of both gonadotropins within 2weeks of application. In one of the women, reversibility of the changes was tested 3months after treatment and could be confirmed. The findings are of great importance for therapeutic trials with d-Leu 6 -des-Gly 10 -GnRH-ethylamide and other GnRH analogs. They show that investigations are still necessary to find the optimal therapeutic regimens for this substance.

The effects of equal caloric amounts of xylitol, sucrose and starch on insulin requirements and blood glucose levels in insulin-dependent diabetics

SummaryXylitol has been suggested as a potentially useful sweetener in the diabetic diet. In 14 insulin-dependent diabetics a standard diabetic diet regimen was compared with diets in which starch was isocalorically exchanged in the breakfast meal by either 30 g xylitol or 30 g sucrose. Insulin requirement and blood glucose were measured using a glucose-controlled insulin infusion system. The results following breakfast with xylitol were similar to those after starch breakfasts. Sucrose, in contrast, induced a greater post-prandial rise in blood glucose levels despite counter-regulation by the glucose-controlled i infusion system. InsuUn requirement after sucrose significantly exceeded (p<0.01) that after xylitol or starch during the first 60 min and 2 h respectively. No short-term side effects of xylitol were found.

Evaluation of the clonidine-suppression test in the diagnosis of pheochromocytoma

SummaryIn this study we examined the preoperative value of the clonidine-suppression test in 15 patients with surgically proved pheochromocytomas. The result of the clonidine-suppression test was pathological (epinephrine plus norepinephrine above 500 ng/l 3 h after clonidine) in 10 of 15 patients (66%). These patients had relatively large tumors and higher basal norepinephrine plasma levels. Out of the 5 cases without a pathological clonidine test 4 had normal basal plasma catecholamine levels with the result that the clonidine test could not be properly applied and 1 case produced a false negative result. These 5 cases generally had smaller tumors and lower plasma catecholamine levels. Two of these cases had basally raised epinephrine values. The other three cases had either a paradoxical increase or a suspiciously low fall (less than 25%) in norepinephrine within the normal range. We conclude that the clonidine-suppression test is only reliable for the diagnosis of relatively large pheochromocytomas.

Interrelationships Between Plasma Norepinephrine and Blood Pressure Response to Norepinephrine in Normotension and Hypertension

Slightly to moderately increased plasma norepinephrine levels thought to reflect increased sympathetic tone have been observed in a proportion of patients with essential hypertension (1–3). However, some authors have also reported on normal- plasma norepinephrine levels in essential hypertension (4, 5).

Sympathetic Nervous Activity, Noradrenaline Reactivity, and Blood Pressure Control

Slightly to moderately increased plasma noradrenaline levels thought to reflect increased sympathetic tone have been observed in a proportion of patients with essential hypertension [1, 2, 3]. However, some authors have also reported on normal plasma noradrenaline levels in essential hypertension [4, 5].

The Influence of Penbutolol and Placebo on Blood Sugar Levels and Insulin Consumption in the Glucose-Controlled Insulin Infusion System (" Artificial Endocrine Pancreas")

SummaryThe aim of the study was to investigate the influence of 40 mg of the beta-blocker penbutolol (BetapressinTM; Hoechst Ltd., Frankfurt/ Main) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes (IDDM) patients. The patients were treated with penbutolol and placebo for a period of three days, and then were examined with the help of the glucose-controlled insulin infusion system.The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo, nor could any changes be measured in these parameters when measured after food intake.After a submaximal exercise load on the bicycle ergometer (1 watt per kg body weight) following an evening meal, no difference could be observed between penbutolol and placebo in the above-mentioned parameters. The same was also true for hormonal parameters as STH, ACTH, cortisol, and catecholamines.These findings demonstrated that medication of penbutolol over a three-day period has no influence on the baseline blood sugar profile and insulin consumption or on insulin consumption after food intake during rest and physical exercise.

Knochenveränderungen bei Akromegalie

An 2 7 Frauen und 11 Mannern mit Akromegalie wurde die Knochendichte in Single-Photonenabsorptionstechnik am proximalen (uberwiegend Kompakta) und distalen (uberwiegend Spongiosa) Mespunkt des Unterarms untersucht. Die Knochendichte lag dabei am proximalen Mespunkt im zu erwartenden Altersnormbereich, am distalen Mespunkt war sie deutlich erhoht (p < 0,001). Die mit quantitativer Computertomographie gemessene Spongiosa der Lendenwirbelsaule fanden wir uber das Alter hinaus vermindert. Als Ausdruck eines gesteigerten Knochenabbaus fanden wir das Hydroxyprolin im Urin erhoht, wahrend sich das Osteocalcin als Marker der Osteoblastenaktivitat invers dazu verhielt.

Development and application of insulin infusion profiles for therapy of type I diabetics with portable insulin infusion systems

We studied the insulin requirements of seven insulin-dependent diabetics applying a glucose controlled insulin infusion system. The data were transformed into individually programmed and rectangular profiles. The MAGE, a measure of blood sugar fluctuations, was significantly lower when individually programmed step profiles were used (P less than 0.005) than it was when rectangular profiles were applied: 57.7 +/- 24.8 mg/dl vs 89.0 +/- 42.9 mg/dl. The average of measured blood glucose levels was significantly lower in individually programmed infusion profiles (P less than 0.025). The combination of individually programmed profiles and preprandial insulin bolus significantly reduced the postprandial blood glucose level and increase (P less than 0.001). Our investigations suggest that individually programmed insulin infusion profiles are able to smooth blood glucose fluctuations. When combined with an initial insulin bolus they may lead to a reduced insulin consumption after meals.

Die Entwicklung von Insulininfusionsprofilen zur Therapie insulinpflichtiger Diabetiker mit tragbaren Insulininfusionssystemen

Wir analysieren den Insulinbedarf von 7 insulinpflichtigen Diabetikem am glukosekontrollierten Insulininfusionssystem und ubertrugen die dabei gewonnenen Daten auf ein portables Insulininfusionsgerat, bei dem individuell Insulinabgabeproflle programmiert werden konnen, bzw. ein System mit einfachen Rechteckprofllen. Unsere Untersuchungen ergaben, das mit individuell erstellten Insulininfusionsprofilen eine bessere Glattung der Blutzuckerspiegel zu erreichen ist. Bei Berucksichtigung der kephalen Phase der Insulinsekretion kann offenbar sogar Insulin eingespart werden. We studied the insulin requirement of 7 insulin-dependent diabetics using a glucose-controlled insulin infusion system. The data established by our investigation were then translated, to an individually programmable insulin infusion system developed by ourselves, and also to a system employing simple rectangular profiles.