Search

The Hormonal assessment of Arterial Hypertension (HTA) is an important part of the balance of resistant hypertension. This assessment - going well beyond the search for primary hyperaldosteronism (PHA) - requires a rigorous methodology and a robust experience of the nursing team within a dedicated unit: the HTA Day Hospital. If all the conditions are met and the assessment carried out well, it will allow a significant profitability since in this resistant hypertensive population it will detect a particular mechanism or secondary hypertension in 70% of patients. Since the diagnosis of PHA is essentially biological, the proper execution of the various stages of the assessment is essential to its documentation., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Hormonal exposure in young women increases the risk of venous thromboembolic disease (VTE). Thrombophilia testing is often proposed in women of childbearing age before the initiation of contraception. However, the presence of a familial history of VTE has the potential to be more accurate than the presence of inherited thrombophilia., Objective: To demonstrate an association between the risk of VTE in young women with hormonal exposure (pregnancy or oral contraceptive use) and the presence of a previous episode of VTE in their first-degree relatives, according to whether or not a detectable inherited thrombophilia was present., Methods: We will perform a multicenter case-control cross-sectional study. The main risk factor is defined by the presence of a symptomatic VTE in young women with hormonal exposure. The principle variable is the presence of an objectively diagnosed episode of VTE in first-degree relatives. We will need to include 2,200 family members in 440 cases., Expected Results: We expect to improve understanding of the thrombotic risk in first-degree relatives of patients in hormonal context with or without a past history of VTE., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Occupational asthma (OA) is described as the most common respiratory disease in industrialized countries. A female predominance characterizes many populations of asthmatic workers. Differences in occupational exposures by gender as well as hormonal variations could affect OA in women., Purpose: To identify the socio-occupational and medical characteristics of OA in women compared to men and to investigate a possible hormonal influence on OA in women., Material and Methods: This is a retrospective study, based on medical records of out patients of the Department of Occupational Medicine during the period between 1st January 2009 and 30 June 2016 for OA completed by a phone call to collect missing data., Results: Over 222 cases of OA, a female predominance was noted (60.81%), which was predominantly in the textile sector (61.5%). Clinically, men had more exercise dyspnea and wheezing, whereas the association with rhinitis was significantly greater in women. The majority of women with asthma had irregular menstrual cycles (46.2%), they were multiparous in 54%, menopaused in 13% of cases with a mean age of menarche of 12±1.65 years. A worsening of OA was noted in 58% of women during their perimenstrual period, 75% during pregnancy and 14% of women when taking hormonal contraceptives. In asthmatic women, only the presence of non-specific bronchial hyperreactivity was significantly associated with menarche age (P=0.007)., Conclusion: Differences between men and women in OA with variability of symptoms during female genital life have been identified. Further studies to personalized care strategies for women need to be undertaken., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The 1-25-hydroxyvitamine D (1-25OHD) or calcitriol deficiency in chronic kidney disease (CKD) patients was associated with increases vascular calcification risk, nephrons reduction, bone deficit and cardiovascular mortality by atherosclerosis. The objective of this study was to investigate the pleiotropic effects of 200.000 IU (D 200 group) every 3 months versus 30.000 IU (D 30 group) every month dose vitamin D supplementation in stage 3 CKD patients. A cohort of 132 adult subjects was randomized into 2 groups according to dose vitamin D supplementation in deficient subjects (25OHD <50 nmol/L or <20 ng/mL). Serum 25OHD levels were assessed before and after 6 and 12 months of vitamin D supplementation. Patients were phenotyped for IRS according to NCEP/ATPIII. Glomerular filtration rate (GFR) by the MDRD formula. Insulin resistance was evaluated by the Homa-IR model. IRS clusters by Cobas Integra 400®. PTH, Cortisol and IGF-1 were determined by radioimmunologic methods. The 25OHD profile was analyzed by LC-MS/MS. Results showed that vitamin D supplementation increased serum 25OHD concentrations (>75 nmol/L or >30 ng/mL) in both groups; however, the supplementation benefits are more significant in D 30 group than in D 200 group. We noted a highlighted improvement of kidney function, an inhibition of GFR collaps, a safe reduction of proteinuria, a significant PTH and C-reactive protein (inflammation) levels attenuation, concomitantly with cortisolemia normalization and decreased IGF-1 depletion. Nevertheless, homocysteine and Lp(a) concentrations remain increased, not modulated by vitamin D treatment. This study shows that continuous low doses (30.000 IU every month) are recommended for intermittent high doses (200.000 IU every 3 months) vitamin D supplementation. Our study suggests that the serum 25OHD profile can be considered a reliable biomarker in the bioclinic CKD status to stage stabilization and inhibit its evolution.

The purpose is to consider the practical management of etiological work up in hypertension, beyond national or international recommendations, leading to consider the prior practice of hormonal assays or renal, renovascular or adrenal imaging. The ease of access to imaging, difficulties to meet the requirements to obtain reliable hormonal assays explain the use of first-line imaging in clinical practice. The renal and adrenal CT angiography provides diagnostic orientation without allowing a formal conclusion. Incidentaloma prevalence in the general population, increasing with age, underlines the limitations of a decision based only on imaging. The discovery of adrenal morphological abnormalities justifies the realization of hormonal assays to determine their causal relationship with hypertension. The aldosterone/PRA ratio, in standardized conditions, has the best diagnostic performance to screen for primary aldosteronism and is the pivotal test of the etiological diagnosis of hypertension. The identification of a subclinical Cushing should be considered in patients with adrenal morphological abnormalities, particularly in case of metabolic syndrome. The abdominal CTscan is initially recommended in the diagnosis of pheochromocytoma, but the recommende boichemical testing is urine metanephrines whose result will lead to search a pheochromocytoma or an extra-abdominal paraganglioma. Many drug interactions must be considered in order to interpret hormonal measurements and avoid erroneous diagnosis. Finally, a genetic context and the possibility of endocrine causes with normal abdominal CT scan should be considered: extra-abdominal paraganglioma, parathyroid adenoma and Cushing's disease with pituitary adenoma, requiring a multidisciplinary decision. The efficiency of imaging as first-line in the screening of secondary hypertension is relative and confrontation with hormone assays will be critical to the diagnostic and therapeutic management. In young women, hormonal measurements precede imaging in the etiological investigation of hypertension., (Copyright © 2016. Published by Elsevier Masson SAS.)

Imaging technological advances and widespread use of abdominal imaging have led to the identification of an increasing number of adrenal incidentalomas in the last decades. Causes of these adrenal masses are multiple, but the most common etiology is the non-functional adenoma. Although in most cases, these masses are benign and non-functional, clinicians have to perform biochemical testing for subclinical cushing's syndrome, pheochromocytoma or primary hyperaldosteronism. This screening is essential for their etiological diagnosis and therapeutic management. We report in this article the biological approach to detect secretory activity of adrenal incidentalomas and the diagnostic accuracy of the biochemical tests used.

Changes in endocrine functional status, including androgen deficiency in men, decreased GH and DHEA secretion (leading to loss of muscle and bone mass), thyroid dysfunction (especially hypothyroidism) are all much more common in older individuals. In this brief review we will focus on the knowledge of the mechanisms of each of these endocrine disorders progressing with age and analyse the effects of various hormonal replacement therapies on clinical outcomes in the elderly population. We will successively discuss the pituitary-thyroid axis (especially the diagnosis and treatment of hypothyroidism), the hypothalamo-pituitary axis (deficiency in GH-IGF1), the pituitary-adrenocortical function (reduction in DHEA and DHEAS) and the pituitary-gonadal axis in men (late onset hypogonadism).

A lot of studies published on the ten last years showed a decrease of fertility among HIV positive women. The present research aims to see if this decrease is linked to an ovarian failure, using AMH as principal marker of ovarian function. In this pilot study, 54 HIV-positive and 39 HIV-negative women were compared on the basis of their ovarian function, fecundity and possible ovarian failure. A blood sample was taken for hormonal titrations, HIV seropositivity, viral load and CD4 T cell count. An interview explored demographic characteristics, obstetrical and infectious history, and menstrual characteristics. This study was performed in Burkina Faso between January and February 2008. There is no significant difference after adjusting for age of AMH level between the two groups. However, in our study, 5.5% of HIV positive women had a premature menopause, which is a significant variation from the premature menopause rates of the African population, which is 1.4%. In conclusion, this study put the HIV impact on ovarian function into perspective but the high premature menopause rates could suggest an ovarian attack by the virus or the treatment.

Introduction: Testicular biopsies are diagnostic and therapeutic tools involved in male infertility care. However, this surgery is invasive and not systematically successful. We studied the preoperative clinical and hormonal factors allowing to predict the obtaining of sperm cells., Patients and Methods: A retrospective study was conducted on 209 patients who all had a testicular biopsy for procreation medically assisted (PMA). The studied criteria were: the age at the time of the surgery, the male cause of the infertility, the testicular volume, the tobacco smoking exposure, the concentrations of estradiol, FSH, LH, prolactin, and testosterone. The comparison of both groups (successful biopsy versus failed biopsy) was made in bivariate analysis then in multivariate analysis., Results: The testicular volume average and the cause were the two only factors which had a real influence on the negativity of the biopsy. In it was added in bivariate analysis a statistically significant correlation of the smoking exposure and the FSH with the failed biopsy., Discussion: The existence of these factors, and their accumulation, was strongly predictive of a failure of the biopsy. However, we found germ cells in patients exposed to the studied factors, letting think that it is systematically necessary to propose the surgery at the risk of a limited profit., (Copyright © 2012. Published by Elsevier Masson SAS.)

Turner's syndrome is characterized by an ovarian failure, which occurs in most cases before puberty and leads to infertility. In vitro fertilization with oocyte donation has dramatically transformed the prognosis of infertility of these women. However, in the same time, it has become obvious that pregnancies in Turner's syndrome are at very high risk of possible sudden death because of a specific risk for cardiovascular complications involving aortic root dissection. We report the case of a serious cardiac failure occurred during a twin pregnancy obtained by oocyte donation in a 39-year-old patient with Turner's syndrome. Pregnancy outcome was hopefully favourable thanks to a foetal extraction at 27 weeks of amenorrhoea. If the most reported cases of maternal deaths in patients with Turner's syndrome are associated with an aortic root dissection, our observation is characterized by a full normal cardiologic assessment before the pregnancy and by the absence of aortic root dilatation during pregnancy. This case also illustrates the very high risk of pregnancy in women with Turner's syndrome and the importance of a multidisciplinary care by professionals informed and been used to this obstetric practice.

The clinical pertinence of laboratory tests is conditioned by the use of well-documented databases on biological variability. Knowledge of these variations in the pediatric and adolescent population is well established. On the other hand, the situation is not so obvious for the elderly population. This population is generally not homogeneous and well-defined physiological variations are scarce. The observed variations generally reflect infraclinical or chronic illnesses. Interindividual variation is generally higher in the elderly population than in younger subjects. Thus, it would be more judicious to classify older persons as a function of their functional performance. This raises the issue of the proper definition of "good health" during the aging process. The criteria usually used for young adults should be revisited. The relationship with age is in fact variable from one assay to another: sometimes low, non significant or on contrary extremely wide. Well-adapted reference intervals are a prerequisite to proper interpretation of laboratory data in the elderly population. In some instances however, reference limits may be unsuitable, e.g. when the biological variability is too large, reference limits used for younger adults should be applied, while in other cases, traditional reference limits must be applied for decision-making limits.

Antiphospholipid syndrome (APS) is an acquired thrombotic disorder. It mainly occurs with systemic disease or as a primary disorder. All organs may be involved by thrombosis, but to date the most common endocrine manifestation is chronic adrenal insufficiency. Very few cases of hypopituitarism with primary APS have been reported. We report the case of a 27-year-old woman, victim of a stroke leading to double vision and intracranial hypertension. Magnetic resonance imaging showed a macro-adenoma with hemorrhage of a suprasellar lesion. Hormone assessment showed hyper prolactinemia with positive anticardiolipin antibody. Our case is the second reported associating APS with apoplexy. We discuss the clinical, biological and radiological features observed in our case. We conclude that APS should be searched for whenever a history of adenoma with apoplexy is found associated with recurrent thrombosis.

Inborn errors of metabolism (IEM) are rare diseases, most often inherited as an autosomal recessive disorder. They may be associated with endocrine dysfunction, the most frequent of them being disorders of carbohydrate metabolism (hypoglycemia, diabetes). The endocrinologist might be led to screen these complications in a patient whose diagnosis has been done during childhood. In some rare cases, he should evoke the diagnosis in front of an endocrine disorder most often associated to a multisystemic involvement. This spreading field is new, not yet very well known in adulthood. Long-term consequences of IEM on fertility and bone metabolism are still poorly understood. Diagnosis orientation relies on a few specific lab investigations encompassing blood lactate, free fatty acids and 3-hydroxy-butyrate, ammoniemia, carnitine and acylcarnitines, aminoacid and urinary organic chromatography. Hyperinsulinism, glycogenosis, fatty acid ss-oxydation, carnitine cycle and glycosylation (CDG syndrome) disorders, fructose intolerance, tyrosinemia, organic aciduria may explain hypoglycemia. These diagnosis should be evoked in front of unexplained adult hypoglycemia. Diabetes is related to iron overload, mitochondriopathy and thiamine sensitive diabetes. Clinical spectrum of some forms of IEM switch from hypoglycemia in childhood to diabetes in adulthood. Mitochondriopathies can be associated to all types of endocrine disorders, the most frequent being diabetes and dysthyroidism. Hypothyroidism is encountered in mitochondriopathies, cystinosis and primary hyperoxaluria. Hypogonadism is almost constant in galactosemia, frequent in CDG syndromes, cystinosis and iron overload. Most of the time, a specialized advice is required, which is one of the mission of reference centres.

The hormonal exploration of menometrorrhagia concerns only the patients throughout their reproductive life, it is not indicated outside this period. In first intention at the woman in age to procreate, will be realized a determination of hCG, an inescapable determination to eliminate a pregnancy and a measure of serum TSH in the case of personal or family history for the screening of subclinical hypothyroidism. Further investigations can be carried out in second-based signs of appeal under the differential diagnosis of polycystic ovary syndrome (PCOS), as a measure serum prolactin, 17-hydroxyprogesterone and total testosterone and not bound to its binding protein the SHBG.

Fragile X syndrome is associated with expansion of a CGG triplet repeat in the FMR1 gene, which abolishes production of the FMRP protein. This abnormality is expressed as a number of neuro-endocrine disorders (the adrenal axis, macroorchidism) and the emergence of significant behavioural stress. Here, we report on the hormonal status of a young adult with fragile X syndrome, with a focus on catecholamine and cortisol changes during a submaximal treadmill test. The patient showed abnormally high epinephrine and norepinephrine concentrations. During a submaximal incremental test, cortisol levels were higher than the laboratory reference range. Although the submaximal incremental test has a significant "stressful" effect, this young adult was able to complete the entire protocol without any maladaptive behaviour or withdrawal.

Intrahepatic cholestasis of pregnancy is the most common liver disorder unique to pregnancy in women without hypertension. The cause of intrahepatic cholestasis of pregnancy is still under discussion but genetic and hormonal factors are predominant. The main symptom is skin pruritus, associated with increase in serum transaminase activities and bile acid concentrations. Intrahepatic cholestasis of pregnancy carries a risk for the pregnancy because of preterm delivery and sudden intrauterine fetal death. Ursodeoxycholic acid (usually 1000mg per day or 15mg/kg per day) is currently the most effective pharmacologic treatment. Ursodeoxycholic acid reduces pruritus, transaminases and bile acid levels and probably prematurity without adverse effects. Obstetric management is still under debate. The majority of authors recommend active management with elective delivery usually before or at 38 weeks of gestation according the severity of cholestasis. Prospective controlled studies are required to confirm the benefit of ursodeoxycholic acid treatment on fetal outcome and to clarify the obstetrical management near term.

Growth hormone (GH) together with cortisol are two important counter-regulatory hormones maintaining normal glycemia. Hyperinsulinemic hypoglycemia is a disorder of this counter-regulation described in neonates. We report here a rare case of reversible dissociated hypopituitarism secondary to an insulinoma in a 38-year-old man referred for investigation of hypoglycemic episodes. Hormonal investigations were in favour of dissociated anterior pituitary failure, with growth hormone and corticotroph deficiency. The hypothalamic-pituitary MRI was normal. The fasting test argued in favour of a hyperinsulinemic hypoglycemia. The abdominal scan and the endoscopic ultrasound showed a mass within the tail of the pancreas. Distal pancreatectomy was performed. Histology disclosed an insulinoma. On follow-up, no hypoglycemic episodes recurred and cortisol and GH response to induced hypoglycemia was normal. Our clinical case shows that hyperinsulinemia and hypoglycemia in patients with insulinoma can give rise to functional growth hormone and corticotrophin deficiency. The pathophysiological mechanism of this defective counter-regulation remains to be clarified; some studies suggest it could be related to hyperinsulinemia-induced decreased in CRF secretion and GHRH pulse.

Standard monitoring of controlled ovarian hyperstimulation (COH) includes hormone assays (estradiol, LH, progesterone) and regular pelvic ultrasound examination. We report a randomized study on an attempt to simplify monitoring of COH. Ultrasound monitoring of the cycle alone did not affect pregnancy rates and did not increase the risks of OHSS. These results encourage the future simplification of stimulation protocols.

The polycystic ovary syndrome (PCOS) is the most frequent cause of hyperandrogenism and anovulation in adult women as well as in adolescent girls. Since 2003 the diagnosis of PCOS has been based on the association of hyperandrogenism, oligoanovulation and polycystic ovary (PCO) morphology at ultrasound (at least 2 items out of 3). In adolescents however, PCOS features may be difficult to distinguish from the symptoms of the end of puberty. Moreover, transvaginal ultrasound examination is seldom possible, and it is difficult to get precise imaging of the ovaries by abdominal route. However, the diagnosis of PCOS in a hyperandrogenic and/or oligomenorrheic adolescent requires on the strict application of the Rotterdam criteria, as in adult women. Priority should be given to clinical features whereas pelvic ultrasound must be considered as optional. Few hormonal assays will serve mainly to make the differential diagnosis, in addition to clinical findings. Once established, the diagnosis of PCOS in an adolescent girl must lead to the detection of the metabolic syndrome by means of simple investigations. This will allow early prevention of its complications.

To study the effects of microgravity on the mechanisms involved in the regulation of body hydrous status, total body water (TBW), plasma volume (PV), and its main regulating hormones (plasma renin, aldosterone, atrial natriuretic peptide (ANP), anti-diuretic hormone (ADH)) were determined, by isotopic dilution, Dill and Costill's formula, and radio-immunologic dosages, in 9 male subjects submitted to a 90-d head-down bed rest (HDBR). ADH was determined in 24 h urinary collection as well as osmolality, sodium, and potassium. Body mass decreased (-2.8 +/- 0.8 kg) as well as TBW(-7.2% +/- 0.9%, i.e., -2.6 +/- 0.7 kg) and PV (-4.7% +/- 1.8%). Renin and aldosterone were enhanced (+109.0% +/- 15.4% and +87.2% +/- 38.9%, respectively). Simultaneously, we observed a decrease in ANP (-33.2% +/- 20.4%). Other variables, including ADH, were not affected by HDBR. Body mass and TBW decrease (and consequently lean body mass) are associated with muscle atrophy. Renin, aldostrerone, and ANP modifications are well explained by the decrease in PV, which was not enough to induce ADH changes. It suggests that in man, the main regulatory factor for ADH secretion is osmolality, when PV is modestly and progressively decreased without arterial pressure modification, which was the case in the present protocol.

Post-partum pituitary necrosis (Sheehan's syndrome) is a rare complication of the post-partum haemorrhage. The diagnosis can be erratic and often delayed. We report the case of a patient who had headaches and meningitis signs few hours after a post-partum haemorrhage. Magnetic Resonance Imaging (MRI) performed at day 2 showed a specific hypophysitis. The onset of asthenia, loss of weight, polyuro-polydipsy, persistent amenorrhoea and absence of lactation led to hormonal investigation. This permitted to diagnose global antehypopituitarism associated with diabetes insipidus. Progressive pituitary atrophy due to necrosis was found using MRI follow-up over 1 year. Our report summarises pathophysiological features of Sheehan's syndrome and early clinical and biological signs are discussed. MRI of the sellar region may be useful to early suspect the diagnosis.

There is increasing interest in the subject of hormone changes in the aging male, which is likely to become particularly important with the expected growth in the population of men over 50. The main concerns at present are androgen decline in the aging male (ADAM), or partial androgen deficiency of the aging male (PADAM), commonly known as the andropause. Although there have been advances in our knowledge of androgen deficiency in the aging male, it is still incomplete, sometimes confusing, and some aspects of androgen replacement therapy remain controversial. The International Society for the Study of the Aging Male (ISSAM) therefore felt it was a good time to review the current situation by publishing a series of practical and official guidelines concerning the diagnosis, treatment and monitoring of late-onset hypogonadism in males. The aim of this study is to present the French translation of these recent international guidelines, and to comment on them.

Purpose: To compare the effects of patient-controlled analgesia (PCA), with or without a background infusion of morphine on postoperative pain relief and stress response after cardiac anesthesia., Methods: With University Ethics approval, 35 consenting adults undergoing elective open-heart surgery were randomly assigned preoperatively in a double-blind fashion to receive either morphine PCA alone (Group I, n = 15) or morphine PCA plus a continuous basal infusion (Group II, n = 14) for 44 hr postoperatively. Pain scores with visual analogue scale (VAS) at rest, deep inspiration and with cough, sedation scores, stress hormone levels [cortisol, adrenocorticotropin (ACTH) and growth hormone (GH)] and morphine consumption were assessed, and serum morphine levels were measured at four, 20, 28 and 44 hr after surgery. Adverse effects including nausea, vomiting, constipation, urinary retention and pruritus were noted. Total blood, fluid requirements, drainage and urinary output were recorded., Results: Postoperative morphine consumption at 44 hr was less in Group I (29.43 +/- 12.57 mg) than in Group II (50.14 +/- 16.44 mg), P = 0.0006. There was no significant difference between groups in VAS scores, GH levels, blood levels of morphine and adverse effects. While VAS scores, ACTH and GH levels decreased significantly in both groups, plasma cortisol levels increased significantly in Group I only at four hours. In Group II, ACTH and cortisol were higher at four and 44 hr respectively., Conclusion: PCA with morphine effectively controlled postoperative pain after cardiac surgery. The addition of a background infusion of morphine did not enhance analgesia and increased morphine consumption.

Purpose: Stress response to surgery is modulated by several factors, including magnitude of the injury, type of procedure (e.g., laparoscopy vs laparotomy) and type of anesthesia. Our purpose was to compare intra- and postoperative hormonal changes during isoflurane vs sevoflurane anesthesia, in a clinical model of well defined operative stress (laparoscopic pelvic surgery)., Method: In this prospective randomized clinical study, 20 women requiring laparoscopic pelvic surgery for benign ovarian cysts received either a standard isoflurane plus fentanyl (Group A) or sevoflurane plus fentanyl anesthesia (Group B). Blood samples were collected preoperatively, 30 min after the beginning of surgery, at the end of surgery after extubation, and two and four hours after the end of surgery. Intra- and postoperative plasma levels of norepinephrine, epinephrine, adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and prolactin (PRL) were measured., Results: Catecholamine levels and postoperative pain were similar in both groups. Nonetheless, in comparison to Group A, Group B showed a significant decrease of ACTH, cortisol and GH levels (A vs B at the end of surgery: ACTH 160 +/- 45 vs 100 +/- 40 pg.mL(-1); cortisol 45 +/- 8 vs 23 +/- 7 microg.dL(-1); GH 3 +/- 2 vs 0.8 +/- 0.4 ng.mL(-1); P < 0.001 for all), but enhanced PRL levels (A vs B, at 30 min after the beginning of surgery: 139 +/- 54 vs 185 +/- 22 ng.mL(-1); at the end of surgery: 100 +/- 27 vs 141 +/- 45 ng.mL(-1); P < 0.001 for both)., Conclusions: In the clinical setting of low stress laparoscopic surgery, the type of volatile anesthetic significantly affected the stress response; the changes associated with sevoflurane suggested a more favourable metabolic and immune response compared to isoflurane.

A 78-year old man developed an acute intracranial hypertension followed by central left facial palsy. CT Scan and MRI revealed an ischemia within the right lenticulostriate arteries territory and a hemorrhagic infarction of a pituitary adenoma without extrinsic carotid artery compression. Neuroophthalmologic examination and hormonal screening were normal. Though pituitary apoplexy and stroke might represent a fortuitous association, several mechanisms underlying such clinical picture are advanced.

Adult growth hormone deficiency is characterized by changes in body composition: increase in total fat, decrease in lean mass and osteopenia, with a fall in Bone Mineral Content (BMC) and in Bone Mineral density (BMD) leading to a rise in risk of fracture. We have analyzed the changes in body composition in 21 adults treated from 9 to 78 months, by dual X-RAY absorptiometry (DEXA). We've demonstrated a gain in bone mass and density, particularly of axial skeleton; a latence of minimum 12 months has been necessary to objective these changes. The balance of fat and lean mass has been poorly modified by treatment except for the lean mass of the trunk, which is significantly increased. We think that the usual doses of rGH, based on IGF-1 level, are perhaps underestimated.

Fibromyalgia is a syndrome characterized by chronic musculoskeletal pain and fatigue without biological detectable disturbances. The mechanisms of this disease are unknown. It has been postulated that it can be the consequence of a chronic stress mediated mainly through the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system. These fields have been extensively studied. Results were scattered and non convincing. A reduction of growth hormone and IGF-1 levels described in a third of patients has led to a double blind random clinical trial with biogenetic growth hormone. Results were equivocal . Other hormonal systems are grossly normals and circadian rhythms are unaltered. Despite some arguments in favour of a CRH neurons hyperactivity, these results are not able to consolide a particular physiopathological mechanism and to argument for a new therapeutic approach. Many of the abnormalities may be the consequence of psychological disturbances.

Perrault's syndrome is an autosomal recessive ovarian dysgenesis associated with sensorineural deafness. We report two cases in sisters issuing from consanguinous parents. Aged 16 and 21 years, both patients present the two cardinal symptoms of the syndrome. Magnetic resonance imaging in the second sister showed high intensity signals in the periventricular and subcortical white substance and in the central ovale, suggestive of cerebral leucodystrophy. This element may be one of a wide spectrum of neurological symptoms found in Perrault's syndrome. The discovery of the causal genes may allow better understanding of the biomolecular mechanisms involved in gonad and sensorineural differentiation.

It is commonly believed that a normal cortisol response to exogenous ACTH (synacthen test) reliably indicates, with the exception of states of acute ACTH deprivation, the integrity of hypothalamic-pituitary-adrenocortical function. Published evidence has shown that the synacthen test is not sensitive enough to reveal partial ACTH deficiency leading to a subnormal ACTH response to stress. We report a patient who maintained a normal response to exogenous ACTH stimulation despite symptomatic chronic ACTH deficiency in unstressed conditions. A normal cortisol response in the synacthen test does not therefore exclude the possibility of clinically relevant ACTH deficiency.

Biological rhythms spread over a wide range of frequencies: circadian, ultradian and infradian. Circannual rhythms belong to this latter domain as their period average one year +/- 2 months. The seasonal rhythms in man of melatonin, prolactin, hormones of bone metabolism, ACTH and HCG are here reviewed and the questions raised by their characterization - including methodological problems - their origin and their incidence on health and diseases.

This review presents the characteristics of biological rhythms and of their components. A number of points dealing with the specific needs in experimental protocols - e.g. in a circadian study - are here discussed. Last, examples in human physiopathology are given, which emphasize the need to take into account biological rhythms in health and disease.

Pharmacology can contribute in four ways to our understanding and to the management of resistant depression: 1) Dosage: some antidepressants have an inverted-U dose-response curve, i.e. the response disappears when dosage is increased. In man, dose-response relationships are not well established because the curves are obtained with groups of patients and they reflect an overall mean rather than the reality of each individual patient. 2) Secondary regulatory adaptive mechanism such as: down regulation of beta, 5-HT2, alpha-2 receptors--increased reactivity of 5-HT1A, alpha-1 and dopaminergic systems. Defective development of these mechanisms is thought to originate resistance in certain cases, which could therefore be corrected more or less specifically by adding thyroid hormone, lithium, an alpha-2 agonist or even by switching to a 5-HT1A agonist or a dopaminergic drug. 3) Biological resistance factors: it has been shown in the rat that hypothyroidism, diabetes, weight loss cause a decrease in beta-adrenergic system reactivity, and therefore a resistance to noradrenergic antidepressants. 4) Co-prescription: the efficacy of noradrenergic antidepressants is known to involve the activation of beta-adrenergic receptors. Animal studies have shown that the co-prescription of a beta-blocker nullifies this efficacy. Benzodiazepines decrease serotonergic and noradrenergic neuronal activity: animal studies have shown that they antagonize most antidepressants. What happens in depressed humans who are often co-prescribed these drugs? I would like to share with you a few data from experimental pharmacology which may help us to think differently, not when faced to a patient with resistant depression, but when confronted with the failure of a well conducted antidepressant treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors make a synthesis of studies about circadian rhythms in depression and of hypothesis to explain them. They successively study trials on the phases, on the average levels, on the amplitude of rhythms. They conclude the most significant troubles are, shortening of latency on paradoxical sleep for phases, slump of melatonin levels, blunded amplitude of every parameter. Among possible explanations, they present and discuss a trouble of oscillators, a decrease of sensitivity to external synchronizers and a trouble in rhythm coupling.

A multidisciplinary study was conducted in 8 patients with neurological Human African Trypanosomiasis. The sleep-wake cycle followed an ultradian pattern which was more pronounced in patients with more severe symptoms. The EEG trace was consistently interrupted by numerous cyclic activation patterns with K complexes, rapid low amplitude elements and slow high voltage elements. Circadian rhythmicity was also disturbed in other physiological (rectal temperature), immunological (interleukins) or hormonal (cortisol, prolactin) variables, the disturbance being greater in severely hit patients.

Forty male patients with a prolactinoma were studied. The majority of tumors were large. Eight (20%) were microadenomas. Loss of libido and sexual impotence, the most frequent symptoms, were found in 82,5% of cases. Gynecomastia with galactorrhea was noted in six cases. Seven patients had hypopituitarism and nine visual field defects. Prolactin levels ranged from 30 to 7,000 ng/ml. The mean baseline prolactin value was higher in the group of invasive adenomas or enclosed adenomas with a suprasellar expansion. The LH-RH test, performed on twenty-eight patients, showed an abnormal response in 80% of the cases.

The authors have studied daily hormone monitoring (Estradiol 17B, FSH, LH, Progesterone) and ultrasound (the size of the follicles and the number of the follicles) in 17 inductions using Clomiphene and 16 using HMG and HCG in cases mainly of dysovulation, but also of anovulation, in women who had previously been treated by induction that had failed. They establish the difference in the results obtained as far as (Estradiol 17B concerned, as far as the number of follicle that were stimulated or the size of the pre-ovulatory follicle, according to whether Clomiphene or sequential HMG-HCG had been used as a method of induction. They analyse the liability of the criteria for screening by plasma levels and by ultrasound and the correlation between these two parameters.

The hormone state of development in the late preovulatory phase is described in its relationship to the start of the LH surge which occurs 37-39 hours before ovulation. No precise relationship has been found between the oestradiol (E2) peak in the plasma and that which occurs before ovulation. All the same, the succession of hormone events that have been observed in 77 spontaneous cycles is the following: the level of E2 suddenly rises between 35 and 30 hours before the ovulatory discharge and this rise is immediately followed by a rise in the level of LH. Then the plasma concentration of 17-hydroxyprogesterone (17-OHP) increases 5 hours before the LH surge. In the preovulatory follicle 5 hours after the start of the LH surge, a drop in the level of E2 and a rise in the level of progesterone is noted. Concentrations of androgens only lessen in the last 12 hours before ovulation whereas the level of 17-OHP stays stable. We have thus been able to work out the sequence of plasma hormone phenomena that occur in determining whether a preovulatory gonadotrophic surge will occur. We have described the hormone levels in follicular fluid immediately before spontaneous ovulation. These findings will be able to serve as a reference to evaluate the quality of the late preovulatory phase in abnormal cycles or in cycles that have been induced.

The hormonal response to repeated lactic acid anaerobic exercise was investigated in 6 young male adults. The exercise protocol consisted of 3 one-minute bouts of voluntary maximal effort, each bout being separated from the subsequent one by a two-minute rest period. Venous blood samples were obtained at rest and at the end of each of the 3 work bouts, as well as following 15 minutes of recovery. A marked increase in plasma catecholamine concentrations was observed in response to the repeated exercise bouts, the rise being more important for the adrenaline (x 22) than the noradrenaline (x 10) concentrations. A progressive increase in plasma somatotropin hormone was observed between the first and the last venous sampling. Moreover, a delayed rise in plasma cortisol, insulin, prolactin, and androstenedione was also observed. Hormonal concentrations of LH, FSH, DHEA-SO4, testosterone, SHBG and testosterone/SHBG ratio were not modified in response to the type of exercise.