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Regulation of vasopressin secretion in a patient with chronic hypernatraemia

Simon Smitz and Jean-Jacques Legros

Abstract. A patient with the chronic hypernatraemia syndrome is described. Using a sensitive and specific radioimmunoassay, the plasma arginine-vasopressin (AVP) level was measured under various conditions.

With an unrestricted diet, the plasma AVP level was inappropriately low for the degree of plasma hyperosmolality (0.9 pmol/l and 302 mOsm/kg, respectively).

After chronic water loading, plasma osmolality was 271 mOsm/kg, plasma AVP level 1.5 pmol/l, and the urine remained hypertonic with respect to the plasma.

During hypertonic saline infusion, plasma osmolality increased from 271 to 294 mOsm/kg without a concomitant increase in the plasma AVP concentration. After sc injection of apomorphine and after haemodynamic stimulation, the plasma AVP concentration increased from 0.8 to 36 pmol/l and from 1.2 to 6.3 pmol/I, respectively. These data demonstrate a selective deficiency in the osmoregulation of the AVP secretion. The observed neuroendocrine abnormalities may be linked to a congenital malformation of the brain.

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Identification of vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate secretion of antidiuretic hormone and an oat cell carcinoma

Simon Smitz, Jean-Jacques Legros, Paul Franchimont, and Marc le Maire

Abstract. In this study we have identified and characterized several vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion and oat cell carcinoma of the lung. Immunoreactive plasma vasopressin was measured after gel filtration (Sephadex G-25) or C-18 cartridge extraction using two different region-specific antisera: AS1 and AS2. Antiserum AS1 is more specifically directed towards the antigenic site of the hexapeptidic ring of arginine-vasopressin (AVP), whereas AS2 is more specifically directed towards the C-terminal region of AVP. Unexpectedly, the Sephadex G-25 gel filtration elution profile of the immunoreactive vasopressin was very heterogeneous, indicating the presence of several molecular species. After extraction of total AVP and AVP-like peptides of this plasma, an unusual AS1/AS2 ratio of immunoreactivity was observed, suggesting the presence of vasopressin-like peptides which differ from AVP in the C-terminus.

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Impact of GH replacement therapy on sleep in adult patients with GH deficiency of pituitary origin

Lisa L Morselli, Arlet Nedeltcheva, Rachel Leproult, Karine Spiegel, Enio Martino, Jean-Jacques Legros, Roy E Weiss, Jean Mockel, Eve Van Cauter, and Georges Copinschi

Objectives

We previously reported that adult patients with GH deficiency (GHD) due to a confirmed or likely pituitary defect, compared with healthy controls individually matched for age, gender, and BMI, have more slow-wave sleep (SWS) and higher delta activity (a marker of SWS intensity). Here, we examined the impact of recombinant human GH (rhGH) therapy, compared with placebo, on objective sleep quality in a subset of patients from the same cohort.

Design

Single-blind, randomized, crossover design study.

Methods

Fourteen patients with untreated GHD of confirmed or likely pituitary origin, aged 22–74 years, participated in the study. Patients with associated hormonal deficiencies were on appropriate replacement therapy. Polygraphic sleep recordings, with bedtimes individually tailored to habitual sleep times, were performed after 4 months on rhGH or placebo.

Results

Valid data were obtained in 13 patients. At the end of the rhGH treatment period, patients had a shorter sleep period time than at the end of the placebo period (479±11 vs 431±19 min respectively; P=0.005), primarily due to an earlier wake-up time, and a decrease in the intensity of SWS (delta activity) (559±125 vs 794±219 μV2 respectively; P=0.048).

Conclusions

Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients. The decrease in delta activity associated with rhGH treatment adds further evidence to the hypothesis that the excess of high-intensity SWS observed in untreated pituitary GHD patients is likely to result from overactivity of the hypothalamic GHRH system due to the lack of negative feedback inhibition by GH.

Free access

Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study

Jean-Jacques Legros, Eric J H Meuleman, Jolanda M H Elbers, T B Paul Geurts, Marion J G H Kaspers, Pierre M G Bouloux, and for the Study 43203 Investigators

Objective

To investigate the effects of oral testosterone undecanoate (TU) on symptoms associated with late-onset hypogonadism (LOH).

Design

Multicenter, randomized, double-blind, placebo-controlled.

Methods

The study was performed in 14 study centers in seven European countries. Men ≥50 years (n=322) with symptoms of hypogonadism and testosterone deficiency (calculated free testosterone <0.26 nmol/l) were randomized and treated for 12 months with placebo or oral TU 80, 160 or 240 mg/day. Primary outcome was the total score on the Aging Males' Symptoms (AMS) rating scale after six months of treatment.

Results

Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU resulted in an improved total AMS score at month 6, but differences between groups were not statistically significant. There was greater improvement in subjects <60 years when compared with subjects ≥60 years (P=0.001), but baseline testosterone level had no influence on treatment response. The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 (P=0.008) and 12 (P=0.012) compared with placebo, but not with 80 and 240 mg/day. Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates.

Conclusions

In one of the largest placebo-controlled studies of testosterone therapy in LOH, oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo, except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day.