[Metabolic rhabdomyolysis during statin therapy]. / Rhabdomyolyse métabolique au cours d'un traitement par statine.

The occurrence of rhabdomyolysis during statin treatment for dyslipidemia is a well-known side effect. However, the differential diagnosis of rhabdomyolysis is large. We report on a patient treated with statin who presented a rhabdomyolysis. The persistence of laboratory abnormalities allowed to discover a metabolic rhabdomyolysis, namely a carnitine palmitoyltransférase II deficiency. The diagnosis of the genetic abnormality allows to modify the therapeutic care.

Reduced fibre size, capillary supply and mitochondrial activity in constitutional thinness' skeletal muscle.

AIM: Constitutional thinness (CT) is a rare condition of natural low body weight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison with a normal BMI control group. METHODS: Ten CT women (BMI < 17.5 kg/m2 ) and 10 female controls (BMI: 18.5-25 kg/m2 ) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibres pattern, capillarity, enzymes activities and transcriptomics. RESULTS: Constitutional thinness displayed similar energy balance metabolic and hormonal profile to controls. Constitutional thinness presented with lower mean area of all the skeletal muscular fibres (-24%, P = .01) and percentage of slow-twitch type I fibres (-25%, P = .02, respectively). Significant downregulation of the mRNA expression of several mitochondrial-related genes and triglycerides metabolism was found along with low cytochrome c oxidase (COX) activity and capillary network in type I fibres. Pre- and post-mitochondrial respiratory chain enzymes levels were found similar to controls. Transcriptomics also revealed downregulation of cytoskeletal-related genes. CONCLUSION: Diminished type I fibres, decreased mitochondrial and metabolic activity suggested by these results are discordant with normal resting metabolic rate of CT subjects. Downregulated genes related to cytoskeletal proteins and myocyte differentiation could account for CT's resistance to weight gain.

Drug treatment of hyperprolactinemia.

Medical treatment of hyperprolactinemia is based upon use of dopamine agonists (DA): bromocriptine, lisuride, quinagolide and cabergoline. In over 80% of cases, these drugs induce normal prolactinemia and ovulatory cycles. In resistant cases, the DA should be changed. Tolerance may occasionally be poor, particularly with bromocriptine, which appears less well-tolerated than quinagolide and than cabergoline above all. In the event of intolerance to a given DA, another should be tried. In patients with macroprolactinoma treated with DA, MRI monitoring should be carried out after 3 months of treatment to verify tumor size reduction, then after 1 year, yearly for the next 5 years and once every 5 years if adenoma size is stable. In cases of microprolactinoma, control under treatment is pointless. MRI may be performed after 1 year and then after 5 years. Once normal prolactin levels have been achieved, attempts may be made to stop the treatment. When a prolonged treatment is interrupted, especially with cabergoline, progressive increase in serum prolactin and return of hyperprolactinemia symptoms are seen in only around 20-30% of cases, particularly when residual adenoma exists after prolonged treatment. Nevertheless, prolactin levels should continue to be monitored after discontinuation of DA, possibly with MRI monitoring, since prolactin levels may rise again after a number of months or years. When normal prolactin levels have been achieved with DA, another solution consists in reducing the dose or dosing frequency of DA in steps to the lowest effective dose consistent with maintenance of normal prolactin levels and stable adenoma size. For drug-induced hyperprolactinemia, where the causative medication cannot be withdrawn, it is often pointless and possibly even dangerous to administer a DA. It is therefore necessary to check for absence of pituitary adenoma and where necessary, begin treatment with sex steroids so as to ensure satisfactory impregnation with sex steroids and avoid osteoporosis. For macroprolactinoma, the first-line treatment is drug therapy with DA. At present, there is no evidence to suggest that prior treatment with DA can modify the outcome of surgery. With microprolactinoma, DA treatment offers a good first-line therapeutic option but surgery may also be useful. DAs for microprolactinoma may be withdrawn after menopause.

Clinical characterization of familial isolated pituitary adenomas.

CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases. CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

[Retrospective study of anorexia nervosa: reduced mortality and stable recovery rates]. / Diminution de la mortalité et stabilité du taux de guérison dans le suivi de l'anorexie mentale.

OBJECTIVES: Anorexia nervosa is an eating disorder that combines malnutrition, amenorrhea, and distorted body image. To learn more about the course of this disease we undertook a retrospective study of girls diagnosed with anorexia nervosa in the Saint Etienne Endocrinology Department between 1979 and 2004. METHODS: Patients were diagnosed according to DSMIV criteria. Data collected to complete the Morgan-Russell outcome assessment schedule included chronology of illness, patients' morphological features, anorexia type, treatment choice, patient's gynecological history, and social status. RESULTS: The study included 206 cases. The average follow-up period was 8.3 +/- 5.3 years. Defining recovery as stable BMI>17.5 kg/m2 for at least one year and recovery of normal menstruation, full recovery was observed in 55.8% and partial recovery in 25.7%, while 18.5% remained chronically ill. Early onset (i.e., during adolescence) was associated with good prognosis, and advanced emaciation and delayed or insufficient medical care with poor prognosis. CONCLUSIONS: The seriousness of this disease is due more to the incidence of cases that become chronic than to the mortality rate. Prediction of severity would be improved by taking into account underlying personality traits, such as addictive tendencies and depression.

Surgical management of hyperthyroidism.

AIMS: Hyperthyroidism includes several clinical and histopathological situations. Surgery is commonly indicated after failure of medical treatment. The aim of this study was to analyze the indications and complications of surgery as well as endocrine results. MATERIALS AND METHODS: Patients operated on for hyperthyroidism between 2004 and 2012 were included in a retrospective study. Total thyroidectomy was performed for Graves' disease, toxic multinodular goiter and amiodarone-associated thyrotoxicosis; patients with toxic nodule underwent hemithyroidectomy. Pathologic analysis assessed surgical specimens; postoperative complications and resolution of hyperthyroidism were noted. RESULTS: Two hundred patients from 15 to 83 years old were included. One hundred and eighty-eight underwent primary surgery and 12 were re-operated for recurrent goiter (6 with subtotal thyroidectomy for multinodular goiter 25 years previously; 6 with hemithyroidectomy for solitary nodule 15 years previously). Eighty-two patients suffered from toxic multinodular goiter, 78 from Graves' disease, 35 from solitary toxic nodules and 5 from amiodarone-associated thyrotoxicosis. Fourteen papillary carcinomas (including 11 papillary microcarcinomas) and 34 healthy parathyroid glands (17%) were identified in the pathological specimens. Postoperative complications comprised 4% permanent recurrent laryngeal nerve palsy (1 year follow-up), 9% hematoma requiring surgical revision, and 3% definitive hypocalcemia. Normalization of thyroid hormone levels was observed in 198 patients. Two recurrences occurred due to incomplete resection (1 case of Graves' disease and 1 intrathoracic toxic goiter that occurred respectively 18 and 5 months after resection). Postoperative complications were more frequent in multinodular goiter (23%) than in Graves' disease (13%) (ns: P>0.05). CONCLUSION: Surgical management of hyperthyroidism enables good endocrinal control if surgery is complete. Patients need to be fully informed of all possible postoperative complications that could occur, especially vocal ones. Long-term follow-up is necessary to detect recurrence, which can occur more than 20 years after partial thyroidectomy surgery. Surgery allows early diagnosis of 12.5% of papillary carcinomas.

Beta-lipotropin and cortisol responses to an intravenous infusion dexamethasone suppression test in Cushing's syndrome and obesity.

An i.v. infusion dexamethasone (Dex) test was used to investigate the ACTH feedback response in 9 normal subjects, 12 obese patients, and 11 patients with Cushing's syndrome. Dex phosphate was infused iv for 4 h, starting at 1100 h (1 mg/h). Plasma concentrations of beta-lipotropin (beta LPH) and cortisol were measured every 20 min between 0900 and 1600 h, then every 2 h until midnight and at 0900 h the next day. In normal subjects and obese patients, plasma beta LPH and cortisol concentrations fell rapidly to less than 40 ng/liter and 3 micrograms/dl, respectively, at the end of Dex infusion. Subsequent values remained low through 0900 h the next day. In 7 patients with Cushing's disease, basal plasma beta LPH and cortisol concentrations declined by greater than 50% during the Dex infusion. In these patients, rapid escape from suppression occurred between 1600 and 2400 h; by 0900 h the following day, beta LPH and cortisol levels were higher than 100 ng/liter and 10 micrograms/dl, respectively. In 3 patients with adrenal tumors, beta LPH concentrations were low, and cortisol concentrations did not decline during the Dex infusion. In 1 patient with ectopic ACTH secretion, beta LPH concentrations were high and were not suppressed by the Dex infusion. We conclude that the iv infusion Dex suppression test can distinguish patients with Cushing's syndrome from normal or obese subjects and can aid in the etiological diagnosis of Cushing's syndrome.

Hypercorticism blunts circadian variations of osteocalcin regardless of nutritional status.

Anorexia nervosa (AN) and Cushing's syndrome (CS) are both responsible for osteoporosis. The mechanisms leading to osteoporosis in AN include hypogonadism, nutritional depletion, and in some cases hypercorticism. Osteocalcin circulating level is a serum marker of osteoblastic activity that follows a circadian rhythm (OCR). Serum osteocalcin is decreased in both CS and AN and can be increased with treatment. In this study we analyzed the influence of combined cortisol and nutritional status on osteocalcin levels and its circadian rhythm in these two different models of hypercorticism, one nutritionally replete (CS) and one nutritionally deplete (AN), and we evaluated the effects of their treatment (surgical cure and weight gain, respectively). Before treatment, osteocalcin levels were lower in CS (n = 16) and AN (n = 42) than in controls and in the AN patient subgroup with hypercorticism (n = 13) compared to those without (n = 29). OCR was absent in CS and in AN patients with hypercorticism, whereas their circadian cortisol cycle was maintained. In CS, successful surgical treatment increased osteocalcin levels (n = 5) and restored OCR. In AN, weight gain (n = 13) induced a significant decrease in cortisol levels in hypercortisolic AN patients, and restored normal osteocalcin levels and OCR. In conclusion, we found that hypercorticism was associated with a decrease in osteocalcin levels in nutritionally replete or deplete patients and that OCR was more affected by cortisol levels than by cortisol cycle.

Twenty-four hour melatonin secretory pattern in men with idiopathic hemochromatosis.

In idiopathic hemochromatosis, iron deposits in endocrine tissue can be associated with hormonal disorders including hypogonadism. We have studied the functional status of the pineal gland in this disease in relation to gonadotrophin levels and cortisol rhythm. Plasma melatonin, luteinizing hormone (LH) and cortisol concentrations were measured by radioimmunoassay every 20 min over a 24 hr period in nine men with idiopathic hemochromatosis aged 36 to 66 years. In six patients a circadian melatonin rhythm was present. The 24 hr means were in the normal range in three patients, and varied below the control values in two patients and above the control values in one patient. These variations seemed unrelated to gonadotrophin status. In the three other patients no plasma melatonin rhythm was observed; two patients with gonadotrophin insufficiency had low melatonin levels, and one with normal gonadotrophin function had high melatonin concentrations. In all cases, the plasma cortisol rhythm was normal. We concluded that the circadian melatonin rhythmicity can be disturbed in some cases of idiopathic hemochromatosis without relationship to the cortisol rhythm and associated endocrine disorders.

Sex steroid-binding protein in nonendocrine diseases.

In humans, sex steroid-binding protein (SBP) is a protein from the liver which binds with high affinity sex steroid hormones. The plasma concentration of SBP is regulated in part by hormonal factors. It has been shown that estrogens and/or thyroid hormones increase the production of SBP by hepatoma cell lines. It is therefore assumed that the increase in SBP levels in patients given oral estrogens or thyroid hormones is the consequence of a direct stimulation of the liver production of SBP by these hormones. The effects of androgen, progestagen and glucocorticoid hormones are unclear or still a matter of controversy. Moreover, the regulation of the metabolic clearance rate of SBP and the influence of nonhormonal factors on the production of SBP are still speculative. Changes in SBP have been described in a few nonendocrine diseases. A slight hormonal dysfunction may be either the primary or the sole cause of the changes in SBP occurring in these diseases. As an example, elevated SBP levels have been reported in men with liver cirrhosis together with testicular hypofunction and increased estrogen levels. It is therefore difficult to demonstrate that the increase in SBP is due to the liver dysfunction rather than to the endocrinological side effects of cirrhosis. The aim of this review is to present some aspects of the nonhormonal regulation of SBP. There is accumulating evidence in the literature for a relation between SBP levels and body weight and fat distribution, energy balance, diet and physical activity, and lipid metabolism. Therefore, it is tempting to propose that SBP is an index which reflects the status of endocrine, metabolic and nutritional functions. Measurement of SBP may be considered of interest in the light of previous epidemiological studies and the preventive approach to diseases such as hormone dependent tumors, cardiovascular diseases and osteoporosis.

Screening for diabetic retinopathy in France.

Ocular complications of diabetes, particularly retinopathy, are the major cause of blindness in the working age population in industrialised nations. Laser photocoagulation has shown definite results in reducing visual morbidity with many more likely to benefit if diagnosed early enough. Institution of an efficient screening programme aimed at detecting patients at risk when they can still be effectively treated has been recognised as an urgent priority worldwide. In France, a signatory to the Saint Vincent's Declaration, an analysis of the national healthcare database reveals a gross inadequacy in the current extent of screening for diabetic retinopathy. The possible causative factors have been analysed and the necessary corrective measures, some of which are already under way, have been discussed. Ideally, screening by ophthalmologists at recommended intervals have been advised by national and professional health care associations. This has not been feasible owing to the lack of organised planning and serious manpower deficit caused by a progressive decline in the number of ophthalmologists. Recently, the need for an efficient, widely-available and user-friendly screening tool has led to the evaluation of multifield fundus photography in real time using digital nonmydriatic camera in comparison with more established methods of detecting diabetic retinopathy. Lastly, the future possibility of involving in France non-ophthalmologists like endocrinologists or general practitioner or non medical profession like orthoptists after proper training to meet the necessary manpower shortage has been addressed. Optimal use of telemedicine along with establishment of preferential reference channels for newly discovered cases of sight-threatening cases of retinopathy are public health priority necessary to give to the screening of diabetic retinopathy its full efficiency.

Combination of autoantibody markers and risk for development of type 1 diabetes: results from a large french cohort of family members.

BACKGROUND: The aims of the study were to characterize the relatives at high risk of progression to diabetes and to determine whether rate of progression to diabetes varied according to age, specific combination of antibodies and genetic markers of susceptibility. METHODS: Family members of type 1 diabetic patients were examined through a large medical network for the presence of specific antibodies to beta cell constituents and high risk DQB1 alleles. Antibodies to insulin, GAD and IA-2 as well as ICA were examined in 4,044 family members recruited in a large prospective family study in the Rhone-Alpes region (the GRADI study). Among them, 3,951 non diabetic first degree relatives have been tested on a median of 2.2 occasions and were followed for up to 16 years. RESULTS: Presence of antibodies to GAD (3.6%), IA-2 (4.9%), insulin (2.2%) and ICA at titers equal or above 20JDF units (1.1%) were noticed at the first determination and prevalence increased among ICA positive relatives versus ICA negative relatives. All combinations of markers resulted in specificities above 90%. The positive predictive value of antibodies was dependent on the number of positive antibodies. Combination of antibodies to GAD and IA-2 or GAD and IAA had higher predictive values and sensitivities than ICA titers above 20 JDF units. Additional positivity of IAA increased the predictive value but reduced the sensitivity of the screening procedure. Using a combi GAD/IA-2 assay increased the sensitivity of the screening up to 87.8% but reduced the predictive value to 13.8%. CONCLUSIONS: These data confirm in a large French cohort of first degree relatives of type 1 diabetic patients that combinations of antibodies to beta cell constituents can replace ICA in the first screening procedure. We report that combi GAD/IA-2 assay is well suited for screening purposes. However, time to diabetes in antibody positive relatives appears to be more heterogeneous to what has been described. The importance of genetic markers needs further evaluation.

Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience.

OBJECTIVE: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter. RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation. RESULTS: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study. CONCLUSION: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

Efficacy of low doses of radioiodine in the treatment of autonomous thyroid nodules: importance of dose/area ratio.

Radioiodine (131I) represents an interesting alternative to surgery in the treatment of autonomously functioning thyroid nodules (AFTN), but leads to a significant incidence of hypothyroidism when high doses are used. Over 4 years, we have treated 40 patients (hyperthyroid [Plummer's disease]: 6, single hot nodules with undetectable thyrotropin [TSH] and normal serum free thyroxine [FT4]: 34), 34 single hot nodules with undetectable thyrotropin TSH and normal serum free thyroxine [FT4] with 131I. The dose level was neither related to the concentration of FT4 nor to the iodine uptake on thyroid scintigram. Retrospectively we measured the nodule's area on the scan and calculated the dose/area ratio (DAR). Three months after treatment, 30 patients were euthyroid, 9 were still hyperthyroid, and 1 was hypothyroid. The mean DAR of the euthyroid patients was twofold higher than for the hyperthyroid subjects (1.4 +/- 0.8 vs. 0.7 +/- 0.3 mCi/cm2; p = .003) and one-half the DAR for the hypothyroid patient (2.82 mCi/cm2). Twenty of the 30 euthyroid patients had received a dose higher than 1 mCi/cm2 and 7 of 9 hyperthyroid patients had received a dose lower than 1 mCi/cm2. (chi2 = 12.9; p = .02). The initial values of T4, TSH, and dose level of patients who were euthyroid or hyperthyroid at 3 months were not different. These data suggest that the efficacy of 131I for treating AFTN depends on the DAR, rather than the initial T4 value or the 131I uptake. A DAR between 1 and 1.5 mCi/cm2 seems to be optimal and avoids hypothyroidism.

Are depression and denutrition good predictors of dexamethasone suppression test (DST) in anorexia nervosa?

This study was conducted to investigate the corticotropic axis in anorexia nervosa. In 93 female inpatients who met DSM-III-R criteria for anorexia nervosa, subsample (n = 64) with DSM-III criteria was also considered. Using stepwise regression analysis, this study examined the relationship between independent variables ie, age, body mass index, scores on depression scales and postdexamethasone serum cortisol, considered as a dependent variable. In patients who met DSM-III criteria, 16.7% of the variance of serum cortisol can be explained. The main predictors are depressive retardation, emaciation and age. Using stepwise logistic regression the main categorical predictors of the test suppression vs non suppression are of the same nature. The condition of realisation of DST are discussed.

[Disorders of noradrenergic pathways in anorexia nervosa. Results]. / A propos de la perturbation de la voie noradrénergique dans l'anorexie mentale. Quelques résultats.

Twelve patients suffering from mental anorexia were examined on clinical and biological grounds, based on the hypothesis of the functional depression of the noradrenergic track. The initial values of MHPG and of catecholamines were below normal. The quantitative results for depression and retardation were lessened significantly under beta-stimulant treatment. Only glucuro-conjugate MHPG excretion increased significantly, but the MHPG values were much lower than normal at the end of the treatment. The correlations between biochemical and behavioural parameters were worth noticing as far as the retardation scale was concerned. The present study shows the advantage of the dexamethasone suppression test and of the response of TSH under TRH.

[TeBG and thyrotoxicosis in the hot thyroid nodule]. / TeBG et thyrotoxicose dans le nodule chaud thyroïdien.

The binding capacity of serum TeBG (testosterone-estradiol binding globulin), the plasma concentrations of thyroid hormones and the TSH response to TRF (200 micrograms i.v.) have been measured in female patients with a solitary autonomously functioning thyroid nodule (n = 26) or with a cold thyroid nodule (n = 20). It was found that TeBG was higher than the upper limit for normal (1.77 micrograms/dl) in the patients (n = 10) with increased serum concentrations of thyroid hormones and in 5 patients among 16 with normal thyroid hormone levels. After surgical removal of the nodule, the increased TeBG levels fell down within the normal, while the response of TSH to TRF which was suppressed before surgery, was recovered. In patients with a cold nodule, the administration of dl-Thyroxine (200-300 micrograms/daily) suppressed the response of TSH to TRF and increased slightly TeBG from 0.97 +/- 0.08 to 1.29 +/- 0.10 micrograms/dl (p less than 0.05) with a value higher than 1.77 micrograms/dl in 5. These data suggested that the pituitary secretion of TSH and the liver production of TeBG have a different threshold of sensitivity to thyroid hormones action. It is proposed that the measure of TeBG is a tool for the diagnosis of thyrotoxicosis in patients with autonomous thyroid nodules.

[Effect of estrogens on the value of serum thyroglobulin]. / Influence des oestrogènes sur la valeur de la thyroglobuline sérique.

Serum thyroglobulin (TG) is considered as a useful index of differentiated thyroid carcinoma evolution. Previous studies have suggested that TG levels might be dependent upon oestrogens. Here TG levels were determined in volunteers , free of any thyroid disease, divided into 5 groups according to estrogen level. Results (mean +/- s.d.) indicated that Tg levels in men group A (n = 9): 6,6 +/- 2,8 ng/ml in women undergoing oestroprogestagen treatment group B (n = 10) 3,7 +/- 1,5 ng/ml; in women free of oestroprogestaten treatment group C (n = 10): 5,9 +/- 4,0 ng/ml; in pregnant women group D (n = 40): 4,6 +/- 2,7 ng/ml, and in parturient women group E (n = 4): 7,2 +/- 2,2 ng/ml; were not correlated to estrogen levels. However, in a group where thyroid gland was not carefully examined i.c. a "blood doners group", a difference (p less than 0,005) was found between women (29 +/- 15) and men (14 +/- 9). Sex and estrogen levels there fore do not influence the TG index which as a result can be used in the monitoring of thyroid carcinoma in pregnant women.

[Contribution of chemiluminescence for determination of low value TSH in patients with dysthyroidism during negative TRH test]. / Apport de la chimiluminescence au dosage de valeurs basses de TSH chez des patients souffrant de dysthyroïdie lors de test à la TRH non répondant.

TSH values performed by immunoradiometric method were compared with chemiluminescent method in 28 hyperthyroid patients with negative TRH-test. This last method gives a better sensitivity (0.020 mUI/L vs. 0.050 mUI/L) and reproducibility (5% V.C. vs. 40%). The measure of undetectable TSH by immunoradiometric assay becomes possible with chemiluminescence. Due to this increase of sensitivity, the TRH-test needs to be reconsidered and allows to discriminate various degrees of TSH suppression.

[Study of variations of osteocalcin concentrations in function of collection, assay method and its nyctohemeral rhythm]. / Etude des variations de concentrations de l'ostéocalcine en fonction du mode de prélèvement, de la méthode de dosage et de son cycle nycthéméral.

Osteocalcin or bone GLA protein (BGP) can be used as well as a peripheral marker of the action of hormones on osteoblast. In the present study, we report our clinical and biological results in three different conditions: the kits used for determination, the time and the hour of withdrawal. We used 4 different radioimmunoassay kits: two kits (Elsa-os-nat (cis), Osca-test (Henning)) detect intact osteocalcin molecules only and the two others (Elsa-osteo(cis), Ostk-PR(cis)) detect intact osteocalcin molecules and osteocalcin fragments. Time between collection and assay is important: we observed a diminution of osteocalcin level which can be due to the degradation of intact molecules, of 25% to 49% (depending on the kit used). The clinical profile was studied with circadian rhythm. We observed a variation of osteocalcin level in 30% of circadian rhythm according to the hour of collection sample. In conclusion, we have seen two differents situations at risk of wrong interpretation due to low level BGP: inadequate serum collection or single blood collection instead of circadian cycle.