[Coronary embolism in hyperthyroidism].
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Biomedical subjects
Publications and source records attributed to L M Wolf.
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The occurrence of serotonin in the human adrenal gland was demonstrated both by immuno-histochemical and biochemical approaches. Using specific polyclonal antibodies to serotonin, the presence of numerous immunoreactive cells was revealed by means of the peroxidase-antiperoxidase technique. These cells exhibited the morphological characteristics of mast cells. Combination of high performance liquid chromatography and electrochemical detection showed the presence of substantial amounts of both serotonin and its metabolite 5-hydroxyindolacetic acid in adrenocortical extracts. The role of serotonin in the regulation of steroidogenesis from human adrenocortical slices was studied in vitro using a perifusion system technique coupled to a specific radioimmunoassay for cortisol. Graded doses of serotonin (from 10(-8) M to 3 x 10(-7) M) increased cortisol production in a dose-dependent manner. Prolonged exposure of adrenal fragments to serotonin (10(-7) M) induced a biphasic response, i.e. a rapid and transient increase in cortisol secretion followed by a plateau phase, suggesting the existence of a desensitization phenomenon. The stimulatory effect of serotonin (10(-7) M) was not altered during infusion of the serotonin1 and/or serotonin2 receptor antagonists methysergide (10(-6) M) and ketanserin (10(-6) M), respectively. In contrast, ICS 205 930 (10(-6) M), a non-selective serotonin3/serotonin4 antagonist, totally abolished the response of adrenal slices to serotonin (10(-7) M). The benzamide derivative zacopride, considered as a serotonin4 agonist, induced a robust stimulation of cortisol secretion. In addition, the corticotropic effects of serotonin (10(-7) M) and zacopride (10(-6) M) were not additive. Incubation of adrenocortical fragments with zacopride (10(-6) M) or serotonin (10(-6) M) caused a significant increase in cAMP formation. Taken together, these data suggest that serotonin, locally released by intra-adrenal mast-like cells, may act as a paracrine factor to stimulate cortisol secretion in man. Our results also indicate that serotonin-induced corticosteroid production is mediated through activation of a serotonin4 receptor subtype positively coupled to adenylate cyclase.
Changes in blood glucose homeostasis induced by the new somatostatin analogue BIM 23014 (BIM) were studied. Eight normal men (study 1) received either vehicle or 1000, 2000 and 3000 micrograms BIM as a 24 h s.c. infusion. Blood glucose, plasma insulin, C-peptide, glucagon and growth hormone (GH) were measured before treatment and then hourly for 24 h. In five normal men (study 2) an oral glucose tolerance test (OGTT) was performed during vehicle infusion and then on days 1 and 7 of a continuous s.c. infusion of 2000 micrograms BIM daily for 7 days. The same biological parameters as in study 1 were measured before OGTT and then twice-hourly for 5 h. Dose-dependent and transient glucose intolerance was observed in the first half of study 1. Except for glucagon, BIM significantly (P < 0.01) reduced plasma insulin, C-peptide and GH levels. In study 2 BIM infusion induced glucose intolerance and a drop in plasma insulin and C-peptide on day 1 which disappeared on day 7 of infusion. Higher on day 7 than on day 1, plasma GH secretion was significantly (P < 0.01) reduced throughout BIM infusion. In contrast plasma glucagon levels were not modified at any time. Side-effects were abdominal cramps and diarrhoea which were observed in most subjects when increasing BIM daily dose. In conclusion, BIM infusion induced transient changes in glucose homeostasis and insulin secretion in normal men. By contrast, plasma GH levels remained reduced throughout the treatment. BIM appears to be a useful tool to selectively inhibit GH secretion.
The mechanism of oligospermia with high level of follicle stimulating hormone (FSH) and normal levels of luteinizing hormone (LH) and testosterone is subject to controversy: pituitary origin with slowing down of LH pulses, or primary gonadal deficiency? We studied 23 men presenting with this hormonal profile. Compared with a control population, these men had decreased mean testosteronaemia, increased mean LH level, both at baseline and under LHRH, and increased area under the LH pulsatility curve. A positive correlation was found between LH and FSH plasma levels. These data are in favour of a primary gonadal deficiency, and we therefore expected to find an increased frequency and amplitude of LH pulses. In fact, the frequency was normal and the amplitude increased in one half of these men, while the frequency was reduced and the amplitude also increased in the other half. There was no difference in plasma FSH levels between these two groups. Pulsed administration of LHRH restored physiological stimulation, but it did not result in normalisation of the FSH/LH ratio and cannot be regarded as a suitable treatment. It would therefore seem that the mechanism of oligospermia with isolated high FSH level is an abnormal feedback of gonadal peptides and steroids.
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A geneological study made it possible to establish a link between two medullary thyroid carcinoma families from Normandy totalling 9 sick subjects, and a probable link with a third family. The study contributed to the diagnosis of multiple endocrine neoplasia type IIa, whereas the condition had been diagnosed for 6 years as familial medullary thyroid carcinoma, without phaechromocytoma. Group in these two families together increased the number of subjects tested, thereby facilitating genetic link analysis and enabling the link with markers of the disease on chromosome 10 to be asserted. The genetic study can now be used to detect individuals at risk, and with regular laboratory tests the diagnosis will be made at the "precancerous" stage. A genealogical study going back to the family-founding couple will increase the population which will benefit from screening in this region north of Rouen.
In order to study the function of the hypothalamic-pituitary-testicular axis in men referring for severe oligospermia, the hormonal pattern of 57 oligospermic men was compared to those of 19 healthy volunteers. Fourteen patients had plasma gonadotrophin levels in the normal range contrasting with low plasma testosterone (T) levels. An hyperprolactinemia was found in 2 of these men who were treated with bromocriptine. A dramatic increase in sperm count was obtained on month 9 to 12 of the therapy and 5 pregnancies were obtained. Two men with hypogonadotrophic hypogonadism and azoospermia were treated with gonadotrophins. Such a treatment induced a desquamation of immature germinal cells in the sperm on month 6 and the maturation et spermatozoa on month 18. By contrast to the latter patients, 8 men had a decrease in plasma T levels without clinical signs of hypoandrogenism. The spermocytogram showed numerous immature germinal cells. On month 7 of a treatment using gonadotrophins, the sperm count rose and 4 pregnancies were obtained after 3 to 12 months of therapy. In 2 patients an isolated FSH deficiency was suspected on the basis of undetectable FSH levels unresponsive to the infusion of GnRH. These patients were treated with hMG. This treatment induced a sharp increase in sperm count on month 6. Forty-three patients had an increase in either LH and/or FSH: 24 men had plasma testosterone and LH levels in the normal ranges, contrasting with an increase in plasma FSH level. In such men, the mean of testosterone level was significantly (p less than 0.001) lower than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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The sella turcica was investigated systematically by radiotomography in 19 patients with either idiopathic hirsutism (6 cases) or hirsutism associated with hypomenorrhea (13 cases), without hyperandrogenism. Morphological abnormalities of the sella were noted in 9 cases, but these radiological abnormalities were also observed in 5 out of 19 women without hirsutism studied at the same time, and these images should therefore be interpreted very prudently. Only two patients had associated sella anomalies and raised LH levels, which could suggest, but not confirm the presence of an LH micro-adenoma.
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A very through ocular examination was made in 48 hypertensive patients treated for 18 months with acebutolol in a daily dose of between 400 and 2400 mg. Abnormal symptoms in the form of a prickling sensation were seen in two cases. Microscopic punctate lesions of the conjunctive were seen in 9 subjects, either with the Bengal Pink or fluorescein tests. These very slight microscopic lesions were found in general only in the region of the palpebral slits, a zone normaly exposed to microtrauma, which decreases the value of this finding. The results of a Schirmer test were considered to be abnormal in six patients. These ocular abnormalities were generally mild and it could not be shown conclusively that they were related to treatment with acebutolol. Ocular surveillance, with examinations repeated every six months, indicated the absence of any harmful effect on the eye of prolonged used of acebutolol in the treatment of hypertension.
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