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Biomedical subjects

D Dewailly

Publications and source records attributed to D Dewailly.

At least 91 records · Page 5Linked to original sources

Recovery of ovulatory menstrual cycles under hydrocortisone in two amenorrheic women with isolated corticotropin deficiency.

Two amenorrheic women presenting clinical signs of adrenal insufficiency were shown to have isolated corticotropin deficiency (ICD). LH and FSH were normally responsive to GnRH. The occurrence of this disease during the postpartum and the presence of autoantibodies against corticotropic cells in one case may indicate that ICD was a sequela of an autoimmune hypophysitis. The presence of amenorrhea, while the gonadotroph was not damaged, and the reappearance of ovulatory menstrual cycles under the sole effect of hydrocortisone replacement therapy suggest that cortisol deficiency may by itself alter the gonadal function.

Adrenal Insufficiency↗

Long term treatment with the somatostatin analog SMS 201-995 in a patient with a thyrotropin- and growth hormone-secreting pituitary adenoma.

A patient with a mixed pituitary tumor secreting TSH and GH was treated, starting 3 months after partial adenomectomy, with the somatostatin analog SMS 201-995 for 8 months. Somatostatin itself inhibited TSH, GH, and alpha-subunit release by the tumor both in vivo and in vitro. Long term treatment with twice daily sc injections of SMS 201-995 resulted in decreased TSH secretion and lower serum thyroid hormone levels. However, euthyroidism was achieved only when the patient was treated with three daily 200-micrograms injections of SMS 201-995. After 30 weeks of SMS 201-995 therapy, TSH secretion increased, while GH secretion remained suppressed. After withdrawal for 6 months, SMS 201-995 (100 micrograms, sc, twice daily) again completely inhibited TSH secretion. SMS 201-995 did not alter the volume of the residual adenomatous tissue. We conclude that SMS 201-995 may be a valuable therapeutic agent for the management of patients with a thyrotroph adenoma. However, desensitization may occur during long term treatment.

Adenoma↗

[Selective control of different hypophysial secretions by long-lasting pharmacodynamic agents. Analogs of somatostatin and LHRH and long-lasting bromocriptine].

The biological activity of the natural somatostatin can be quantitatively and qualitatively altered by the substitution and/or the exclusion of some of its amino-acids. The most used synthetic analog, SMS 201-995, has a potent inhibiting effect on GH secretion, but is less effective on insulin and glucagon secretions. It is mainly used in Endocrinology for the treatment of acromegaly. It is also useful for inhibiting the inappropriate TSH secretion from a thyrotroph adenoma. The LH-RH agonists ast essentially by desensitizing the gonadotroph from the endogenous LH-RH. By sub-cutaneous, intra-muscular or nasal route, they allow to inhibit the gonadal functions in some hormone-dependent cancers and in true precocious puberty. More recently, they have been tested for the treatment of gonadotropic adenomas, where they may have sometimes a paradoxical effect. In combination with exogenous gonadotropins, they enhance the control of ovulation and are new valuable tools for IVF programs. Clinical studies with the LH-RH antagonists are just beginning. The long-acting bromocriptine affords a new alternative to the oral treatment of hyperprolactinaemia. Its suppressive effects lasts at least 35 days in normal subjects and 21 days in patients with macroprolactinomas.

Bromocriptine↗

Clinical and biological phenotypes in late-onset 21-hydroxylase deficiency.

We analyzed data from 20 patients with late-onset 21-hydroxylase deficiency (LOHD). Three clinical phenotypes could be distinguished among the 18 women. Seven (39%) presented with clinical features suggesting polycystic ovarian disease (PCOD). However, despite androgen levels similar to those of patients with typical PCOD, high serum LH to FSH ratios were not consistently found. Seven other women (39%) presented with isolated hirsutism, suggesting idiopathic hirsutism. The remaining 4 women (22%) had no manifestations of androgen excess and were considered to have the cryptic form of LOHD. Serum 17-hydroxyprogesterone (17-OHP) and androgen levels were similar in the 3 phenotypes, suggesting that the clinical expression of LOHD in women is modulated by individual factors, such as androgen sensitivity. The 2 men were detected by family study and were clinically normal. Since clinical diagnosis of LOHD is impossible, we concentrated on hormonal data with the aim of providing guidelines for the biological diagnosis of LOHD. Assay of basal serum 17-OHD at 0800 h in both sexes and in the early follicular phase in women was sufficient to establish the diagnosis of LOHD in most patients. If doubtful results are obtained, i.e. serum 17-OHP levels between 2 and 5 ng/ml, an ACTH test must be performed. Post-ACTH serum 17-OHP levels exceeding 10 ng/ml confirm the diagnosis of LOHD. Such results should avoid confusion with heterozygotes for 21-hydroxylase deficiency, whose frequency is high within the general population and may be even higher in patients with idiopathic hirsutism or PCOD.

17-alpha-Hydroxyprogesterone↗

Dopamine-secreting pheochromocytoma: an unrecognized entity? Classification of pheochromocytomas according to their type of secretion.

A pheochromocytoma that exclusively secretes dopamine (DA) rather than predominantly DA among a blend of catecholamines is as yet unreported. Of the 50 patients with pheochromocytoma who have undergone surgery, 32 underwent treatment within the last 5 years (when DA assay has been available). One half of these patients (15/32) exhibited DA secretion either in mixed catecholamines (12 patients) or exclusively (three patients). All three patients with exclusive DA-secreting tumors were normotensive. Without hypertension, the clinical investigation was a diagnostic challenge (unexplained cough or flank mass with inflammatory features). All three tumors were malignant and two were ectopic. Five of the 12 patients with mixed catecholamine-secreting tumors whose secretions included DA were hypertensive. Five other patients had flank mass and one had an unexplained cough. Tumors were rather large, and three of the tumors with mixed secretion were ectopic. Of the 12 patients, seven had tumors that were judged to be malignant. Three patients exhibited a dramatic decrease in blood pressure under alpha-blockade, which was not used in subsequent cases. Predominant or exclusive secretion of DA would explain the lack of hypertension due to its antiadrenergic action that inhibits the vasoconstrictive effects of other amines. Hypertension in patients with pheochromocytoma might depend on the ratio of DA/noradrenaline + adrenaline.

Adrenal Gland Neoplasms↗

Medical treatment of hyperprolactinemia.

The current treatment of choice for primary hyperprolactinemia is medical. This is true not only for idiopathic forms, but also for micro- and macroprolactinomas, which are the most frequent causes of this pathology. Although questioned by some authors, the slow evolution of the illness, the rarity of transformation of a microadenoma into a macroadenoma, and the possibility of spontaneous cure cause most authors to favor medical treatment, with which they observe both normalization of gonadal function and tumor regression. By retrospective analysis of 95 hyperprolactinemic patients (72 women and 23 men including 26 cases of suspected microadenoma and 44 macroadenomas) treated with 3 dopamine agonists (bromocriptine, metergoline and CU 32085) between 1975 and 1983, and with the help of large series published in the literature, we have tried to review the present knowledge of this subject. After a quick review of different medications, we will consider their prolactin-suppressing effects, their influences upon gonadal and gonadotropic functions, and their antitumoral action. More specific problems will then be discussed: side effects, resistance, possibility of cure, the evolution of the prolactinoma, the place of medical therapy relative to surgery, and contraception in association with dopaminergics.

Adenoma↗

Treatment of human hyperprolactinaemia with a new dopamine agonist: CU 32085 (mesulergin).

CU 38085 (mesulergin) was given at doses ranging from 0.5 to 5 mg/day to 37 patients with pathological hyperprolactinaemia of varying aetiology. The effectiveness of this drug on the suppression of hyperprolactinaemia and on the recovery of gonadal functions was equivalent to that of bromocriptine previously given to a different group of 83 hyperprolactinaemic patients. Tumour shrinkage during treatment with CU 32085 was ascertained in two cases of macroprolactinoma. Histological examination after adenomectomy revealed extensive peri-vascular fibrosis in both cases. In most patients, the efficient doses of CU 32085 were 5-fold lower than those of bromocriptine. After acute oral administration in 10 previously untreated patients, 0.5 mg of CU 32085 had a more prolonged suppressive effect on Prl levels than 2.5 mg of bromocriptine (approximately 18 vs 12 h). According to this, 0.5 mg CU 32085 once a day was sufficient to maintain Prl levels within the normal range in 16 patients. Side-effects were similar in nature and frequency to those induced by bromocriptine and seemed to be dose-dependent. They can be avoided by slowly increases of dose at initiation of treatment.

Administration, Oral↗

[Antidiuretic hormone levels (arginine-vasopressin) in cases of peripheral hypothyroidism. 26 cases].

Plasma arginine-vasopressin (AVP) levels were measured by radioimmunoassay in 26 untreated myxoedematous patients and 27 healthy subjects. In 22 patients, in spite low osmolality AVP values were not significantly different from those found in controls, but they were considerably increased in 4 patients with severe myxoedema and very low osmolality. Statistical analysis showed negative correlation between AVP values and osmolality in the patients. On the other hand, no correlation was found between AVP values and aldosterone or plasma renin activity values. These results suggest inappropriate secretion of antidiuretic hormone in myxoedema.

Aged↗

Investigative strategy of hyperandrogenism in women.

Investigative procedures in the assessment of female hyperandrogenism are reviewed. Based on their experience, the authors suggest an inexpensive investigative strategy in hyperandrogenic females consisting of the following: the first step depends upon the clinical symptoms--in cases of hirsutism with regular menstrual cycles, plasma testosterone (T) and plasma dehydroepiandrosterone sulfate (DHA-S) are assayed, and the basal body temperature chart is recorded. In cases of hirsutism with irregular or anovulatory menstrual cycles, in addition to T and DHA-S, plasma 17-hydroxyprogesterone and urinary-free cortisol are assayed. In case of anovulation without hirsutism, T and DHA-S are assayed, and the LHRH test is performed. The results of this first investigation allow to attribute to the woman one of the six following hormone profiles: (1) metabolic hyperadrenalism; (2) tumoral hyperandrogenism; (3) 21-hydroxylase defect; (4) nontumoral DHA-S increase; (5) nontumoral ovarian hyperandrogenism; (6) idiopathic hirsutism. The additional investigative procedures required in each of these groups are detailed.

Adrenal Hyperplasia, Congenital↗

Nuclear estradiol-binding sites in human breast cancer.

The binding of estradiol to nuclear fractions extracted from human breast carcinomatous tissue was demonstrated. The material, which was extracted with KCl, had an approximate molecular weight of 37,000 and bound estradiol with both high and low affinity (Kd congruent to 1 nM, type A receptors; Kd congruent to 30 nM, type B receptors) as calculated according to the method of Scatchard. Competition studies indicated that both components were specific for estradiol, and among the 134 tumors studied the receptors were found to be linked in almost all cases. Thirty-six % of the tumors were nuclear receptor positive. Cytoplasmic estradiol and progesterone receptors were also measured. Among the cytoplasmic tumors positive for cytoplasmic and progesterone receptors, 37% were devoid of both types of nuclear receptors; this may explain the failure of endocrine therapy in some cases. The determination of nuclear binding sites in human breast tumors appeared to be an interesting criterion for the assessment of estradiol-dependent cell growth.

Adenocarcinoma↗