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ABSTRACT: Cushing's disease causes considerable morbidity and mortality, including cardiovascular, metabolic, respiratory and psychiatric complications, bone demineralization and increased susceptibility to infections. Metabolic complications include a high prevalence of impaired glucose tolerance, fasting hyperglycaemia and diabetes. Although pituitary surgery is the gold-standard treatment, other treatment strategies such as radiotherapy and medical therapy to reduce cortisol synthesis may be proposed in the event of recurrence or failure, or when surgery is not an option. Bilateral adrenalectomy can also be considered. One of the medical treatments used in Cushing's disease is the somatostatin analogue pasireotide, which acts on adrenocorticotropic hormone (ACTH) secretion by the pituitary. Its efficacy in reducing urinary free cortisol, plasma cortisol and ACTH, and in improving the clinical signs of the disease has been demonstrated. Its observed adverse effects are similar to the known effects of first-generation somatostatin analogues, although disturbances of carbohydrate metabolism are more frequent and more severe with pasireotide. The aim of the present review was to summarize the epidemiology and pathophysiology of the disturbances of glucose metabolism that arise in Cushing's disease, and to propose recommendations for detecting and monitoring glucose abnormalities and for managing pasireotide-induced hyperglycaemia.
Diabetes & Metabolism 12/2012; · 2.41 Impact Factor
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P Chanson,
J Bertherat,
A Beckers,
H Bihan,
T Brue,
P Caron,
O Chabre,
M Cogne, C Cortet-Rudelli,
B Delemer,
H Dufour,
R Gaillard,
M Gueydan,
I Morange,
J-C Souberbielle,
A Tabarin
Annales d Endocrinologie 05/2009; 70(2):92-106. · 0.74 Impact Factor
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ABSTRACT: TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.
Annales d Endocrinologie 07/2008; 69(3):244-8. · 0.74 Impact Factor
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ABSTRACT: There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the reference morphological examination. In clinical practice, it is usually performed very early, following the discovery of increased plasma concentrations of PRL. This approach is warranted for marked increase in PRL in the absence of drugs with hyperprolactinemic effects (>10 x upper limit of normal) since a diagnosis of PRL adenoma is extremely likely under such circumstances. When hyperprolactinemia is moderate, which is the most common finding in practice, all etiologies are possible in theory and it is important to follow a rational diagnostic plan (history-taking to identify use of any drugs with hyperprolactinemic effects paying attention to renal and hepatic history, investigation for endocrine diseases occasionally associated with hyperprolactinemia such as hypothyroidism or polycystic ovary syndrome (PCOS), confirmation of hyperprolactinemia by a second assay when the initial level is less than five times the upper normal limit, pregnancy testing for women of childbearing age) in order to rule out all non-tumoral causes of hyperprolactinemia before proceeding with imaging. Absence of any consequences of hyperprolactinemia on gonadic function or the existence of a concomitant disease that could account for the clinical signs, demonstration of wide variations in PRL from one assay to another in a single patient could prompt screening for macroprolactinemia before MRI is ordered. Macroprolactinoma could also occur in the case of normal or doubtful MRI or discrepancy in response to medical or surgical treatment. T1- and T2-weighted coronal sections (with or without T1 after gadolinium injection) are generally sufficient for diagnosis of microprolactinoma. Dynamic tests may be useful if MRI is normal or unclear. Gadolinium injection with sagittal and axial sections is essential for examination of large lesions. In this case, when the increase of PRL is moderate (<150 mg/ml), a non-lactotropic lesion may be suspected without misdiagnosing a hook effect. Careful analysis of the images allows differentiation between tumoral lesions and pituitary hyperplasia.
Annales d Endocrinologie 07/2007; 68(2-3):98-105. · 0.74 Impact Factor
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ABSTRACT: To emphasize the difficulties to distinguish between uterine agenesis and extreme uterine hypotrophy in the context of primary amenorrhoea with delayed puberty.
Among adolescents who consulted with our center because of primary amenorrhoea, from 1997 to 2005, three patients were referred for a suspicion of Mayer-Rokitansky-Kuster-Hauser Syndrome, after ultrasonography had failed to visualize the uterus. The 3 patients underwent endocrine and genetic evaluations. Transabdominal ultrasonography and MRI performed pelvic examination. Patients were placed under estrogen treatment.
Endocrine evaluation indicated primary ovarian failure for patient 1, and hypogonadotrophic hypogonadism for patients 2 and 3. Karyotype was 46,XX in all patients. Initial pelvic ultrasonography revealed the absence of uterus. MRI allowed visualizing prepubertal uterus for patient 1, a hypotrophic uterus for patient 3 and concluded to uterine agenesis for patient 2. In all cases estradiol substitutive therapy induced uterine growth and confirmed retrospectively the diagnosis of extreme uterine hypotrophy.
Pelvic ultrasonography can be misleading in the evaluation of primary amenorrhoea. No visualization of uterus on ultrasonography can occur in the context of delayed puberty and should not induce a premature diagnosis of Mayer-Rokitansky-Kuster-Hauser syndrome. Indeed, such a diagnosis has therapeutic, reproductive and psychological consequences.
Gynécologie Obstétrique & Fertilité 12/2006; 34(11):1029-35. · 0.52 Impact Factor
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ABSTRACT: We report two sisters with profound insulin resistance associated with a novel heterozygous missense mutation in exon 19 (His1130Arg) of the insulin receptor gene. The eldest was seen after puberty at age 15 and she presented a severe form of polycystic ovary syndrome (PCOS) with biological hyperandrogenism (HA) mimicking a virilizing tumour. However, she has been able to ovulate under clomiphene citrate (CC) and to achieve two uneventful pregnancies. The patient had no glucose tolerance abnormality during pregnancies. The outcome of pregnancy was good except for a low birthweight. The youngest sister was seen earlier in life (at age 11) before puberty. First, she developed polycystic ovaries (PCO), seen under ultrasound scan, and later also developed full PCOS. This second finding gave us the opportunity to observe that PCO developed before and at the beginning of puberty despite low LH levels. We postulate that the development of PCO was the consequence of an LH-independent intra-ovarian HA likely induced by the severe hyperinsulinism in the context of genetic abnormalities.
Human Reproduction 06/2006; 21(5):1274-8. · 4.47 Impact Factor
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ABSTRACT: The effectiveness of biological investigations aiming at discriminating isolated hypogonadotropic hypogonadism (IHH) from constitutional delayed puberty (CDP) in male patients is still controversial. We revisited the diagnostic power of the basal serum testosterone level, the Triptorelin test and the human chorionic gonadotropin (hCG) test in a cohort of 33 boys with delayed puberty.
Boys were aged 14.2 to 26.2 Years at referral. A 5-Year-long clinical follow-up after the initial study allowed confirmation of the diagnosis. At the end of the follow-up period, IHH was found in 13 patients while the other 20 had normal spontaneous pubertal development (CDP).
At referral, a basal morning testosterone level >1.7 nmol/l was observed in 55% of patients with CDP exclusively (predictive positive value (PPV)=100%; predictive negative value (PNV)=59%). For CDP, the PPV of the LH peak 3 h after Triptorelin was 100% by setting the upper threshold at 14 IU/l and the PNV was 72%. However, no lower threshold could discriminate IHH from CDP in the remaining patients with an LH peak 3 h after Triptorelin <14 IU/l. In CDP patients, the PPV of the serum testosterone increment after hCG stimulation (deltaT/hCG) was 100% for values >9 nmol/l (PNV=72%). In IHH patients, the PPV of deltaT/hCG was 100% for values <3 nmol/l (PNV=82%). Only 29% of the studied population had a deltaT/hCG between these lower and upper thresholds and therefore could not have been classified initially.
(i) Dynamic testing for the diagnosis of delayed puberty is useful only when the basal testosterone level is lower than 1.7 nmol/l; (ii) in that case, the hCG test has better discriminating power than the Triptorelin test and appears as the best cost-effective investigation. It prevents useless and expensive investigations in about one-half of CDP patients with a basal morning testosterone level lower than 1.7 nmol/l.
European Journal of Endocrinology 07/2003; 149(1):23-9. · 3.42 Impact Factor
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ABSTRACT: This study revisited the ultrasonographic diagnostic criteria of polycystic ovary syndrome (PCOS) and studied the relationship between the major hormonal and metabolic features of PCOS and the follicle number per ovary (FNPO).
This prospective study included 214 women with PCOS compared with 112 women with normal ovaries. Main clinical, biological and ultrasonographic markers of PCOS were assessed during the early follicular phase.
The mean FNPO of follicles 2-5 mm in size was significantly higher in polycystic ovaries than in controls, while it was similar within the 6-9 mm range. Setting the threshold at 12 for the 2-9 mm FNPO offered the best compromise between specificity (99%) and sensitivity (75%). Within the 2-5 mm follicular range, we found significant positive relationships between the FNPO and androgens. The FNPO within the 6-9 mm range was significantly and negatively related to body mass index and fasting insulin serum level.
We propose to modify the definition of polycystic ovaries by adding the presence of > or =12 follicles measuring 2-9 mm in diameter (mean of both ovaries). Also, our findings strengthen the hypothesis that the intra-ovarian hyperandrogenism promotes excessive early follicular growth and that further progression cannot proceed normally because of hyperinsulinism and/or other metabolic influence linked to obesity.
Human Reproduction 03/2003; 18(3):598-603. · 4.47 Impact Factor
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ABSTRACT: The authors present the clinical aspects and changes of the pituitary gland and adenomas in pregnant women by MRI. A number of physiological morphologic changes are seen during pregnancy. Moreover, the hormonal milieu affects patients with adenomas which could evolve leading to severe complications as hypertrophy, necrosis, and hemorrhage. An increase in the volume and T1 hyperintensity of the anterior pituitary, is normally seen. These changes are explained by an increase in lactotrops and prolactin production. Tumoral complications are more frequent with macroadenomas, and are suggestive of a sellar mass or apoplexy. Nevertheless, other differential diagnoses must be suggested in pregnancy and post-partum including hypophysitis and Sheehan syndrome.
Journal de Radiologie 04/2002; 83(3):329-35. · 0.42 Impact Factor
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ABSTRACT: OBJECTIVE: To explore the abnormalities of serum inhibin isoform concentrations in a large group of patients with polycystic ovary syndrome (PCOS) and to evaluate the influence of body mass index (BMI), age, LH, and androgens on serum inhibin levels. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENT(s): Forty-one women with PCOS were compared with 24 healthy women. INTERVENTION(s): Blood sampling was performed in the early follicular phase in patients and in control women. MAIN OUTCOME MEASURE(s): Serum levels of inhibin A, inhibin B, alpha-inhibin, pro-alphaC (alpha-inhibin precursor proteins), LH, FSH, E(2), T, and androstenedione (A) were assessed in all subjects. RESULT(s): Serum alpha-inhibin levels together with LH, T, and A levels were significantly increased in women with PCOS. Serum inhibin A levels were lower in patients with PCOS than controls (median +/- SD: 7.35 +/- 2.9 vs. 9.4 +/- 4.7 pg/mL), pro-alphaC levels were higher (264 +/- 136.7 vs. 127 +/- 81.5 pg/mL), and inhibin B levels did not differ between the groups (110.5 +/- 51.5 vs. 108 +/- 47.5 pg/mL). Simple regression analysis showed that inhibin A and B levels were negatively correlated with BMI in patients with PCOS (r = -0.43 and r27 kg/m(2)) displayed significantly lower inhibin A and inhibin B levels and a higher pro-alphaC-inhibin A ratio than nonobese patients with PCOS (BMI </=27 kg/m(2)). In this last subgroup, the mean inhibin B level was significantly higher than in controls (median +/- SD: 144 +/- 53.5 vs. 108 +/- 47.5 pg/mL). Partial regression analysis, after controlling for age and BMI, demonstrated that in patients with PCOS, pro-alphaC levels were positively and independently correlated with LH and A levels. CONCLUSION(s): Among women with PCOS, the trend toward an excess serum inhibin B level is observed exclusively in nonobese patients. The higher pro-alphaC levels and the lower inhibin A levels might reflect a defect in the processing of inhibins specific to polycystic ovaries. In addition, our data suggest that pro-alphaC originates from the theca-interstitial cells and could participate in control of the androgen production by these cells.
Fertility and Sterility 05/2000; 73(5):972-7. · 3.56 Impact Factor
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J M Kuhn,
S Arlot,
H Lefebvre,
P Caron, C Cortet-Rudelli,
F Archambaud,
P Chanson,
A Tabarin,
M I Goth,
J Blumberg,
F Catus,
S Ispas,
P Beck-Peccoz
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ABSTRACT: Somatostatin analogs have been shown to be effective for the treatment of TSH-secreting pituitary adenomas. However, their use in this indication is limited by the fact that available analogs require several daily sc injections. The present study was performed to evaluate the effects of a slow release formulation of the somatostatin analog lanreotide (SR-L) on both hormone secretion and tumor size and to assess the tolerance in a series of thyrotropinomas treated for 6 months. Eighteen patients with hyperthyroidism related to a TSH-secreting pituitary adenoma, evidenced by pituitary magnetic resonance imaging, were studied. After a basal assessment, each patient received 30 mg SR-L, im, every 14 days for 1 month. Then, according to the free T3 (fT3) plasma level measured, 9 of 18 patients were injected twice monthly, and 7 of 18 patients received SR-L every 10 days for 5 additional months. One patient was dismissed from the study in month 1 of the study for side-effects and another in month 3 for noncompliance to the protocol. Clinical and biological evaluations (plasma TSH, free alpha-subunit, fT4, fT3, and lanreotide levels) were performed before and in months 1, 3, and 6 of treatment. Pituitary magnetic resonance imaging and gallbladder ultrasonography were performed both at entry and at the end of the study. Clinical signs of hyperthyroidism improved within 1 month in all 16 evaluable patients. Mean (+/- SEM) plasma lanreotide levels reached 1.11 +/- 0.43 and 1.69 +/- 0.65 ng/mL in month 3 using 2 and 3 injections/month, respectively, then remained stable until the end of the study. During therapy, the plasma TSH level decreased from 2.72 +/- 0.32 to 1.89 +/-0.27 mU/L (P < 0.01), with parallel significant changes in free alpha-subunit. During the same period, plasma fT4 and fT3 levels decreased from 37.9 +/- 2.9 to 19.7 +/- 2.3 pmol/L (P < 0.01) and from 14.6 +/- 1.1 to 8.3 +/- 0.8 pmol/L (P < 0.01), respectively. No statistically significant change in mean adenoma size was observed after 6 months of treatment. Side-effects, including pain at the injection point, abdominal cramps, and diarrhea, were mild and transient and did not lead to interruption of the treatment. No gallstones occurred during the study. SR-L appears to be able to suppress clinical signs of hyperthyroidism in our series of patients with TSH-secreting pituitary adenomas. The analog also reduces plasma TSH and thyroid hormone levels, which were normalized in 13 of 16 cases. The effect was maintained throughout the treatment using 2 or 3 SR-L injections monthly without any problem of tolerance. We conclude that SR-L is a safe and effective treatment of thyrotropinomas and avoids the drawbacks of the modes of administration of other somatostatin analogs, given three times daily.
Journal of Clinical Endocrinology & Metabolism 04/2000; 85(4):1487-91. · 6.50 Impact Factor
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Journal of endocrinological investigation 11/1998; 21(9):636-40. · 1.57 Impact Factor
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ABSTRACT: To date, only one study has demonstrated increased serum inhibin levels in women with polycystic ovary syndrome (PCOS). Moreover, no relationship between serum inhibin and either FSH or androgen levels has been noted. This lack of data could be due to 1) the heterogeneity of PCOS and the small sample size of previous studies, and/or 2) the complexity of circulating inhibin molecular forms, which hinders the precise evaluation of bioactive inhibin. In the present study, alpha-inhibin levels were assayed in the serum of 61 healthy women and 72 PCOS patients by means of an alpha-alpha enzyme-linked immunosorbent assay. Serum alpha-inhibin levels together with LH and androstenedione (A) levels were significantly increased in PCOS women (mean +/- SD, 1.45 +/- 0.55 vs. 0.94 +/- 0.36 U/mL in controls; P < 0.001). Moreover, simple and partial regression analysis demonstrated that serum A levels were positively and independently correlated to serum alpha-inhibin (r = 0.32; P < 0.01) and LH levels (r = 0.48; P < 0.001) in PCOS. The respective influences of alpha-inhibin and LH on A variability were 20% and 80%, as determined by multiple regression analysis. In conclusion, in agreement with recent in vitro data, our in vivo results argue for a role of inhibin in the hyperandrogenism of PCOS together with, but independently from, that of LH. Further studies are needed to determine whether this effect is produced by inhibin A and/or B.
Journal of Clinical Endocrinology & Metabolism 06/1997; 82(6):1939-43. · 6.50 Impact Factor
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ABSTRACT: A deficiency of 21-hydroxylase activity is one of the most commonly inherited genetic disorders in man, with heterozygosity for CYP21 mutations affecting approximately 1 in 60 of the non-Jewish Caucasian population. We have hypothesized that heterozygosity for CYP21 mutations in women increases their risk of developing clinically evident hyperandrogenism, and that this risk is related to the severity of the mutation of CYP21 and/or the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation. To test these hypotheses, we studied 38 obligate carriers for 21-hydroxylase deficiency (i.e. mothers of children with congenital adrenal hyperplasia or nonclassic congenital adreanl hyperplasia), comparing them to 27 weight-, parity-, and age-matched controls. Premenopausal carriers, not receiving hormonal treatment (n = 27), had higher mean total and free testosterone [T; 2.02 +/- 0.55 vs. 1.56 +/- 0.65 nmol/L (P < 0.007) and 0.018 +/- 0.007 vs. 0.012 +/- 0.006 nmol/L (P < 0.007), respectively] and lower mean sex hormone-binding globulin (214 +/- 62 vs. 277 +/- 129 nmol/L; P < 0.03) levels compared to controls. There was no difference in the mean basal levels of dehydroepiandrosterone sulfate, androstenedione (A4), or 17-OHP between carriers and controls. As expected, carriers exhibited higher stimulated and net increment 17-OHP levels than controls [21.1 +/- 27.1 vs. 6.2 +/- 3.1 nmol/L (P < 0.01) and 19.0 +/- 26.5 vs. 4.4 +/- 2.8 nmol/L (P < 0.009), respectively]. However, no difference was observed in the response of A4 to ACTH-(1-24) stimulation. Of the 27 carriers studied biochemically, 2 (7.4%) had a stimulated 17-OHP value between 30.3-60.6 nmol/L, and 1 (3.7%) had a 17-OHP level above 60.6 nmol/L, suggestive of nonclassic adrenal hyperplasia. Of all carriers studied genetically (n = 36), 50.0% (18 of 36) had 1, 33% (12 of 36) had 2, and 16.7% (6 of 36) had 3 or more mutations. In 27.8% (10 of 36) of carriers, the mutations were contiguous, consistent with a large gene conversion. All 38 carriers were examined for historical and physical features of hyperandrogenism. Hirsutism was defined as a Ferriman-Gallwey score of 6 or more, menstrual/ovulatory dysfunction as a history of menstrual cycles of more than 35-day, and hyperandrogenemia as total or free T, A4, and/or dehydroepiandrosterone sulfate levels above the upper 95th percentile of control values. Further, defining functional androgen excess (FAE) as the presence of at least 2 of the 3 hyperandrogenic features, 4 of 38 (10.5%) of carriers appeared to be affected (95% confidence interval, 2.9-24.8%). Assuming an expected prevalence rate of FAE in the general population of 5-20%, the frequency of FAE among our carriers was not significantly higher than expected. In conclusion, heterozygosity for CYP21 mutations does not appear to increase the risk of clinically evident hyperandrogenism, although carrying the defect was associated with higher mean and free T levels. Finally, due to the low frequency of androgen excess in our heterozygote population, we were unable to correlate the severity of the CYP21 mutation and/or the 17-OHP response to ACTH stimulation with the presence of the phenotype.
Journal of Clinical Endocrinology & Metabolism 03/1997; 82(2):479-85. · 6.50 Impact Factor
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ABSTRACT: Some technical improvements have allowed to minimize the frequency of severe complications following fractionated pituitary conventional radiotherapy, without altering its efficiency. "Conformational" radiotherapy is currently under development, aiming at the best fitting of the tumor borders to the irradiation zone, by the means of stereotactic imaging. More recently, radiosurgery has been proposed for pituitary adenomas. It consists in a single high radiation dose to the tumor, by the means of either cobalt minibeams (Gamma Unit) or photon beams from a linear particle accelerator. These techniques require the use of a stereotactic frame and precise 3D imaging in order to tightly superimpose the target volume to the reference isodose. They must not be viewed as an alternative to conventional radiotherapy. They can be applied only to small lesions (less than 20 mm in their maximal axis) which are distant (> 5 mm) from the optic chiasma and nerves. Their efficiency is similar to the one of fractionated conventional radiotherapy, with a shorter response time. In conclusion, radiotherapy can be used safely for pituitary adenomas. It remains however a second line treatment, when surgery has been incomplete and when a simple, effective and inexpensive medical treatment is not possible.
Annales d Endocrinologie 02/1997; 58(1):21-9. · 0.74 Impact Factor
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ABSTRACT: A deficiency of 21-hydroxylase activity is one of the most commonly inherited genetic disorders in man, with heterozygosity for CYP21 mutations affecting approximately 1 in 60 of the non-Jewish Cauca- sian population. We have hypothesized that heterozygosity for CYP21 mutations in women increases their risk of developing clinically ev- ident hyperandrogenism, and that this risk is related to the severity of the mutation of CYP21 and/or the 17-hydroxyprogesterone (17- OHP) response to ACTH stimulation. To test these hypotheses, we studied 38 obligate carriers for 21-hydroxylase deficiency (i.e. mothers of children with congenital adrenal hyperplasia or nonclassic con- genital adreanl hyperplasia), comparing them to 27 weight-, parity-, and age-matched controls. Premenopausal carriers, not receiving hor- monal treatment (n 5 27), had higher mean total and free testosterone (T; 2.02 6 0.55 vs. 1.56 6 0.65 nmol/L (P , 0.007) and 0.018 6 0.007 vs. 0.012 6 0.006 nmol/L (P , 0.007), respectively) and lower mean sex hormone-binding globulin (214 6 62 vs. 277 6 129 nmol/L; P , 0.03) levels compared to controls. There was no difference in the mean basal levels of dehydroepiandrosterone sulfate, androstenedione (A4), or 17-OHP between carriers and controls. As expected, carriers ex- hibited higher stimulated and net increment 17-OHP levels than controls (21.1 6 27.1 vs. 6.2 6 3.1 nmol/L (P , 0.01) and 19.0 6 26.5 vs. 4.4 6 2.8 nmol/L (P , 0.009), respectively). However, no difference was observed in the response of A4 to ACTH-(1-24) stimulation. Of the 27 carriers studied biochemically, 2 (7.4%) had a stimulated 17- OHP value between 30.3- 60.6 nmol/L, and 1 (3.7%) had a 17-OHP level above 60.6 nmol/L, suggestive of nonclassic adrenal hyperplasia. Of all carriers studied genetically (n 5 36), 50.0% (18 of 36) had 1, 33% (12 of 36) had 2, and 16.7% (6 of 36) had 3 or more mutations. In 27.8% (10 of 36) of carriers, the mutations were contiguous, consistent with a large gene conversion. All 38 carriers were examined for historical and physical features of hyperandrogenism. Hirsutism was defined as a Ferriman-Gallwey score of 6 or more, menstrual/ovulatory dysfunc- tion as a history of menstrual cycles of more than 35-day, and hy- perandrogenemia as total or free T, A4, and/or dehydroepiandros- terone sulfate levels above the upper 95th percentile of control values. Further, defining functional androgen excess (FAE) as the presence of at least 2 of the 3 hyperandrogenic features, 4 of 38 (10.5%) of carriers appeared to be affected (95% confidence interval, 2.9 -24.8%). Assuming an expected prevalence rate of FAE in the general popu- lation of 5-20%, the frequency of FAE among our carriers was not significantly higher than expected. In conclusion, heterozygosity for CYP21 mutations does not appear to increase the risk of clinically evident hyperandrogenism, although carrying the defect was associated with higher mean and free T levels. Finally, due to the low frequency of androgen excess in our hetero- zygote population, we were unable to correlate the severity of the CYP21 mutation and/or the 17-OHP response to ACTH stimulation with the presence of the phenotype. (J Clin Endocrinol Metab 82: 479 - 485, 1997)
Journal of Clinical Endocrinology & Metabolism - J CLIN ENDOCRINOL METAB. 01/1997; 82(2):479-485.
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Fertility and Sterility - FERT STERIL. 01/1997; 68.
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ABSTRACT: The expression of the pituitary-specific transcription factor Pit-1 gene was analyzed in a series of 30 human lactotroph and somatotroph pituitary tumors. Northern blot analysis failed to reveal any quantitative differences in Pit-1 gene expression between somatotroph and lactotroph tumors, and reverse transcription-PCR analysis showed similar patterns of Pit-1 isoforms expression in both populations of tumors. The expression of the D2 receptor gene was subsequently analyzed in the same adenomas. In the prolactinomas, which presented with a variable sensitivity to dopamine agonist treatment, the intensity of the D2 receptor transcripts (2.8 kilobases) was variable and was related to the sensitivity to the dopamine agonist treatment. Notably, the individual D2 receptor messenger ribonucleic acid (mRNA) levels were highly correlated to the Pit-1 mRNA levels measured in the same tumors (r = 0.90; P < 0.0001). In the GH-secreting tumors, a significant expression of the D2 receptor gene was evidenced by Northern blot in all mixed somato-lactotroph adenomas and in some of the pure somatotroph adenomas; again, a positive correlation was found between D2 mRNA and Pit-1 mRNA levels (r = 0.68; P < 0.01). These results suggest the existence of mechanisms responsible for a coordinate control of Pit-1 and D2 receptor genes that remain to be determined.
Journal of Clinical Endocrinology & Metabolism 09/1996; 81(9):3390-6. · 6.50 Impact Factor
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ABSTRACT: Since the advent of immunohistochemical and cell culture techniques, the role of gonadotroph adenomas in hypophyseal disorders appears more important than formerly. A large part of "nonfunctional" adenomas in fact correspond to gonadotroph adenomas in vitro. These adenomas raise many clinical and biological questions since their presentation is not univocal. In addition, diagnosis of these adenomas is important since their spontaneous development leads to neuro-opthalmological complications, which presently are still too often the revealing manifestations of these adenomas.
La Revue du praticien 07/1996; 46(12):1498-1503.
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ABSTRACT: Polycystic Ovary Syndrome (PCOS) results from endocrine, paracrine and autocrine dysfunction, affecting thecal and granulosa cells. The circulating insulin/IGF system is often dysregulated in PCOS. It could influence the local IGFs/IGF-BPs system, when granulosa, and more putatively thecal cells depend on. It is a new field of research about the physiopathology of PCOS, lying on clinical grounds. However, its practical interest is still limited.
Contraception, fertilité, sexualité (1992) 11/1994; 22(10):615-7.
