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Biomedical subjects

D Dewailly

Publications and source records attributed to D Dewailly.

At least 19 recordsLinked to original sources
PubMed1992

Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis.

OBJECTIVES: To provide an up-to-date review of studies that have examined the physiological effects of insulin and insulin-like growth factor I (IGF-I) on ovarian growth, maturation, and steroid synthesis, their physiological role in puberty, and their pathophysiological role in polycystic ovarian syndrome (PCOS). To deduce from these data a hypothesis, explaining the pathogenetic connections between puberty and PCOS. DATA IDENTIFICATION: The most relevant studies related to this topic have been identified through a computerized bibliographic search (MEDLINE) and through manual scanning of what has been published during recent years in the most important journals in the field of reproductive endocrinology. RESULTS: Insulin and IGF-I stimulate ovarian growth and potentiate the actions of gonadotropins on ovarian steroid synthesis. Insulin also augments the bioactive concentrations of IGF-I and androgens through regulation of the synthesis of their respective binding proteins insulin-like growth factor-1 binding protein (IGFBP-1) and sex hormone-binding globulin (SHBG) in the liver. Insulin and IGF-I might also be able to increase the adrenal sensitivity to adrenocorticotropic hormone (ACTH). Insulin resistance with compensating hyperinsulinism is a common feature of PCOS. It is also a normal phenomenon during puberty. Polycystic ovarian syndrome often develops during puberty. Ultrasonographic investigations suggest that it is much more common during adolescence than generally assumed. Actually, there is a striking resemblance between the endocrine characteristics of puberty and some forms of PCOS. Both conditions are characterized by insulin resistance, hyperpulsatile gonadotropin secretion, hyperactive ovarian and adrenal androgen synthesis, and decreased levels of IGFBP-1 and SHBG. CONCLUSION: We propose the progressively increasing insulin levels and IGF-I activity during puberty as inducing factors in the development of PCOS in susceptible subjects.

Female↗
PubMed1992

Insulin resistance and polycystic ovarian syndrome.

Insulin resistance (IR) and polycystic ovarian syndrome (PCOS) appear as linked phenomena, although this is not easy to obviate in common forms of PCOS while it is evident in the rare cases of extreme IR and hyperinsulinism (HI). Experimental data indicate that insulin could interfere with the local insulin-like growth factor systems in ovaries, and presumably in adrenals and in the hypothalamic pituitary system. The female puberty system offers a physiological model to explain the gonadotropic action of insulin. In patients with IR, HI could induce a state of hyperpuberty, leading to the constitution of PCOS during adolescence.

Female↗
PubMed1992

Resistance to somatostatin (SRIH) analog therapy in acromegaly. Re-evaluation of the correlation between the SRIH receptor status of the pituitary tumor and the in vivo inhibition of GH secretion in response to SRIH analog.

The development of a long-acting somatostatin (SRIH) analog (octreotide, Sandoz) has been a major breakthrough in the treatment of acromegaly. However, in 20-30% of the patients, growth hormone (GH) plasma levels remain elevated (> 10 micrograms/l) despite treatment with octreotide. This raised the concept of resistance to SRIH analog therapy in acromegaly. Indeed, in vivo response to SRIH analogs varies greatly among acromegalic patients. According to the reviews in the literature and our own autoradiographic data, no direct correlation can be established between the GH response to octreotide and the number or affinity of the SRIH receptors located on the tumor. In our series a greater density of SRIH receptors is present on tumors from patients very sensitive to the SRIH agonist. A subset of patients resistant to octreotide could result from a very low density of SRIH receptor although this type of GH-secreting tumor constitutes certainly a rare case. A subset of GH-secreting pituitary tumors can be characterized by a mutation on the alpha subunit of the guanine nucleotide-dependent protein coupled to the stimulation of adenylate cyclase (G alpha s). This mutation results in a high basal adenylate cyclase activity and a low GHRH-stimulated activity. However, when the adenomas are separated according to their basal adenylate cyclase activity, SRIH is able to decrease cAMP levels in both types of tumor. In addition, in our series no direct correlation is observed between the SRIH inhibition of adenylate cyclase and the amount of SRIH-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Effects of the dopamine agonist CV 205-502 in human prolactinomas resistant to bromocriptine.

In 21 patients with prolactinomas resistant to bromocriptine, we studied the effects of CV 205-502 on PRL hypersecretion and tumor mass, as assessed by consecutive computed tomography examinations. Cell culture studies were performed in 9 of such tumors. In 11 patients (group I; 52%) with a mean baseline plasma PRL level of 468 +/- 160 micrograms/L (+/- SE), normal PRL values were achieved after 1-6 months of treatment with 0.1-0.5 mg/day CV 205-502. Tumor size was reduced by 25% or more in 6 of 11 patients. In group II (n = 10), PRL levels (948 +/- 538 micrograms/L at baseline) were reduced by 48% after treatment with 0.1 mg/day CV 205-502. A progressive increase in the daily dose up to 0.5 mg did not further improve the partial reduction of PRL. No reduction in tumor size was observed in this group. The cell culture studies showed that 1) a brief exposure to both drugs provoked PRL suppression lasting 3 days; 2) in group I, CV 205-502 suppressed PRL release more efficiently than bromocriptine, with a maximal inhibition of 72% at 10(-9) mol/L; and 3) in group II, CV 205-502 only achieved a 26% inhibition of PRL release at 10(-8) mol/L, superimposable to that of bromocriptine. These data indicate that in at least half of such adenomas resistant to bromocriptine, CV 205-502, probably due to its higher affinity toward the D2 dopamine receptor, can overcome such resistance.

Adult↗
PubMed1992

[Glycoprotein hormones, glycosylation and biological activity].

Glycoprotein hormones LH, FSH, TSH and hCG are heterodimeric molecules: each contains two subunits, a common alpha and a unique beta subunit. Each subunit bears one or two Asparagine linked carbohydrate moieties which have a biantennary complex-type or hybrid-type structure. Different technical methods as deglycosylation or molecular biology techniques have been used to study the role of carbohydrate residues in hormonal bioactivity. The carbohydrate chains are not directly involved in receptor binding events but their mechanisms of action is not fully understood. Two hypotheses are frequently emphasised: a conformational role or an involvement in the coupling of the receptor-adenylate cyclase system. At the post receptor level carbohydrate chains modulate the bioactivity in two ways: a global regulation following an all-or-none mode and slight one. The removal of the carbohydrate moieties leads to a loss of the in vitro hormonal activity. The results observed are dependent of the deglycosylation techniques and the bioactivity tests used. Hormone's deglycosylation reduces their capacity of production of cAMP and, to a lesser extent, their steroidogenic power. Deglycosylated hormones are antagonists to negative hormones although deglycosylated hCG has some agonist properties in vivo. Microheterogeneity of the glycoprotein hormones is due to slight variations in sialic acid and/or sulfate content. Glycoprotein hormones exist as several isoforms which differ in biological potency. Alkaline isoforms (less sialylated ones) are the most biologically active in vitro but have a short half live in vivo; acid isoforms are less active in vitro but have a longer circulatory half live. The polymorphism of glycoprotein hormones is a highly regulated process.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗
PubMed1992

[Insulin resistance and polycystic ovary syndrome].

The causes and consequences of the insulin resistance that accompanies the polycystic ovary Syndrome (PCOS) are still controversial. The hyperandrogenism does not appear any more as a causal factor but on the contrary is likely to be a consequence, via the ovarian effects of hyperinsulinism. These are still not clearly understood in their molecular aspects, but their reality is undoubtful in view of some clinical studies which showed an improvement following by the reduction of hyperinsulinism. Therefore, the aetiopathogenic role of the insulin resistance in PCOS becomes more and more obvious but it cannot be split from the likely implication of the intra-ovarian growth factors, and more especially the IGF 1 which could act synergistically with it. Moreover, the presence of LH seems to be still a pre-requisite to the ovarian action of insulin. The therapeutical incidences of these hypothesis are obvious and should improve in the next future the medical management of PCOS.

Androgens↗
PubMed1992

A long-acting repeatable form of bromocriptine as long-term treatment of prolactin-secreting macroadenomas: a multicenter study.

OBJECTIVE: To assess the efficacy and tolerability of monthly injections of the long-acting repeatable bromocriptine in patients with macroprolactinomas. DESIGN: Open and prospective trial. SETTING: This multicenter trial was carried out in seven university hospitals. PATIENTS: Forty-two patients with prolactin (PRL)-secreting macroadenomas. INTERVENTIONS: Fifty to 200 mg of the drug were administered intragluteally every 28 days for 6 to 24 months. MAIN OUTCOME MEASURES: The efficacy was assessed by repetitive plasma PRL measurements, visual field determinations, and computed tomography scan examinations. RESULTS: After the first 50-mg injection, the mean percentage decrease of PRL levels was 71% from baseline on day 14; between days 1 and 28, PRL levels were suppressed to normal in nine cases, and a clear tumor shrinkage was documented in 21% of the patients. Normalization of PRL secretion was obtained in 62%, and a clear-cut reduction in tumor size in 50% of the patients after 6 months of treatment. CONCLUSIONS: The long-acting repeatable form of bromocriptine was a well tolerated and quickly effective treatment in most of these patients with macroprolactinomas.

Adenoma↗
PubMed1991

Polycystic ovarian disease: contribution of vaginal endosonography and reassessment of ultrasonic diagnosis.

OBJECTIVE: We evaluated the superiority of vaginal ultrasonography (US) on the abdominal US for the diagnosis of polycystic ovarian disease (PCOD). DESIGN: The US pattern of ovaries was prospectively investigated by abdominal US and, whenever possible, by vaginal US. SETTING: Primary care, institutional. PATIENTS: One hundred forty-four women in whom PCOD was suspected on endocrine grounds and 62 other patients presenting with primary hyperprolactinemia (n = 23) or hypothalamic anovulation (n = 39). MAIN OUTCOME MEASURE: Vaginal US allowed a better analysis of the ovarian stroma. RESULTS: The external ovarian features of PCOD were observed by both routes in less than one third of the 144 patients with PCOD. The internal ovarian features of PCOD were much more frequently observed by vaginal US than by abdominal US (polycystic pattern: 66.7% versus 38.1%, P less than 0.05; increased ovarian stroma: 57.1% versus 4.8%, P less than 0.001). In the 62 patients without PCOD, US features of PCOD were observed in less than 10% of them, except for the uterine width/ovarian length ratio less than 1 and the polycystic pattern (abdominal US: 17% and 34%; vaginal US: 11% and 50%, respectively). CONCLUSIONS: An increased ovarian stroma seems to be the most sensitive and specific US sign of PCOD, providing that it can be investigated by vaginal US.

Abdomen↗
PubMed1991

[Short-term effect of delayed-action injectable bromocriptine in macroprolactinoma. French multicenter study].

In this prospective multicenter trial, 61 patients presenting with a macroprolactinoma were studied over a 1 month-period following a single 50 mg intragluteal injection of the long-acting repeatable (L.A.R.) form of bromocriptine. The effects of the drug were evaluated mainly by repetitive plasma prolactin measurements on days 1, 3, 7, 14 and 28 after injection, and by repeated visual-field and computed tomography scanning examinations. Normalization of PRL levels was obtained in 23% of patients during the first month following injection. In 6 patients (9.8%), PRL values remained within normal range on day 28 after injection. In these latter patients, PRL levels were significantly lower than in the patients whose PRL values were not normal on day 28 (312 +/- 111 vs 2454 +/- 484 ng/ml [m +/- SEM]). The mean lowest PRL levels were achieved on day 3. The mean percent maximal decrease in PRL levels ranged between 70 and 72% from days 3 to 14 but constantly remained below 50% in 6 patients. An improvement in visual field was observed by day 7 in 45% of patients presenting initially with visual field defects. In particular, in half of the patients with bilateral quadranopsia or hemianopsia, such visual impairments had disappeared after 1 month of treatment. Computed tomography scanning examinations showed in 11% of the patients a more than 20% reduction in tumor mass by day 7 following injection. On day 28, the percent reduction in tumor size was 20-40% in 28% and above 40% in 10% of the patients. Most adverse effects (digestive symptoms, dizziness, postural hypotension) were observed during the first 24 hours of treatment. Local and systemic tolerability was in general good. In macroprolactinoma patients, a single 50 mg injection of bromocriptine LAR was thus able to achieve in the short-term a clear cut reduction in tumor size in 2/5 patients and normalization of PRL levels in 1/10 of patients. A study of the effects of monthly administration of bromocriptine LAR is currently under progress to assess the long-term efficacy of this drug.

Adult↗
PubMed1990

[Gonadotropic adenoma. Clinical and hormonal characteristics].

The main clinical and hormonal features of gonadotropin secreting adenomas (GSA) are reviewed through the literature and our personal data. There is still no agreement about their definition and frequency. The most classical clinical presentation is that of men aged 50 years or more, bearing a large pituitary adenoma, the only biological expression of which is a moderately elevated serum FSH level. Female cases are less recognised and are underestimated because the serum LH and/or FSH elevated levels are not informative in menopausal women. The assay of the alpha subunit may help in these cases. In premenopausal women, few of them having been described so far, the GSA may be revealed by an amenorrhea-galactorrhea syndrome with a mild hyperprolactinaemia which may result from different mechanisms. The absence of gonadal hyperactivity, and, conversely, the frequent hypogonadism associated with GSA lead the clinician to raise some questions: are all GSA able to secret gonadotropins? How is the bioactivity of the LH and/or FSH secreted by GSA? How reliable are the radioimmunoassays routinely used for measurement of LH and FSH in patient's serum? Furthermore, therapeutical management of GSA is still impaired by the lack of documented medical treatments which could control their growth and prevent their recurrence.

Adenoma↗
PubMed1989

Adrenocorticotropin and cortisol responses to ovine corticotropin-releasing factor in alcohol dependence disorder. Preliminary report.

A 100-micrograms bolus of synthetic ovine corticotropin-releasing factor was administered intravenously to 10 nondepressed inpatients suffering from an alcohol dependence disorder. The test was performed during withdrawal and after 4 weeks of abstinence. During withdrawal, the plasma cortisol responses of alcoholic patients and 7 control subjects were similar, except for an earlier decrease of cortisol in the former group. However, after 4 weeks of abstinence, the cortisol response was significantly lower in alcoholic patients than in controls. These abnormalities observed during discontinuance of alcohol consumption may reflect adaptive mechanisms of the hypothalamic-pituitary-adrenal activity which may be previously altered by chronic alcohol intoxication.

Adrenal Cortex↗
PubMed1988

Screening heterozygotes for 21-hydroxylase deficiency among hirsute women: lack of utility of the adrenocorticotropin hormone test.

Heterozygosity for 21-hydroxylase deficiency (21-OHD) was investigated in 174 adult hirsute women by using the sum of the incremental responses of serum 17 alpha-hydroxyprogesterone (17 alpha-OHP) and progesterone (P) (delta 17 alpha-OHP + P), 60 minutes after a 0.25 mg intravenous (IV) bolus of synthetic adrenocorticotropic hormone (ACTH). The distribution of 17 alpha-OHP + P in hirsute women was bimodal, allowing two subgroups to be distinguished. In one subgroup including 137 patients, the mode was similar to controls and all values were lower than 3 ng/ml. Thirty-seven (21%) patients constituted another subgroup with values higher than 3 ng/ml and could a priori have been considered as heterozygotes for 21-OHD. However, human leukocyte antigen genotyping provided no conclusive evidence that this subgroup included exclusively heterozygotes for the 21-OHD.

17-alpha-Hydroxyprogesterone↗
PubMed1988

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↗
PubMed1988

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↗