Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation.

In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by nonislet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations and graft function during 5 years post-IT. Twenty-four patients with type 1 diabetes, followed for 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity <50% (LOW purity) or ≥50% (HIGH purity). We also analyzed blood levels of carbohydrate antigen 19-9 (CA 19-9)-a biomarker of pancreatic ductal cells-and glucagon, before and after IT. At 5 years, mean hemoglobin A1c (HbA1c levels) (P = .01) and daily insulin requirements (P = .03) were lower in the LOW purity group. Insulin independence was more frequent in the LOW purity group (P < .05). CA19-9 and glucagon levels increased post-IT (P < .0001) and were inversely correlated with the degree of purity. Overall, our results suggest that nonislet cells have a beneficial effect on long-term islet graft function, possibly through ductal-to-endocrine cell differentiation. ClinicalTrial.gov NCT00446264 and NCT01123187.

Gastric bypass increases postprandial insulin and GLP-1 in nonobese minipigs.

BACKGROUND: Gastric bypass in obese patients induces a dramatic increase of postprandial insulin and glucagon-like peptide-1 (GLP-1) secretion, independently of weight loss. We explored postprandial insulin and GLP-1 secretion in nonobese minipigs before and after RYGB. METHODS: Lean adult Göttingen minipigs (n = 7) were submitted to an open gastric bypass surgery mimicking the clinical procedure in humans (30-cm(3) gastric pouch/150-cm alimentary limb/70-cm biliary limb). All animals were evaluated at baseline and then 10 and 30 days after surgery. At each time point, serum glucose, insulin, GLP-1 and D-xylose levels were measured 3 h after a standardized mixed meal. RESULTS: Weight remained stable during follow-up. Insulin and GLP-1 responses to the test meal were dramatically and similarly increased at 10 days and 1 month after RYGB. Maximal postprandial insulin and GLP-1 levels were 16.3 ± 1.7 mIU/l and 71.7 ± 16.5 pmol/l at baseline, 111.5 ± 38.9 mIU/l and 320.8 ± 84.0 pmol/l at 10 days and 96.6 ± 10.4 mIU/l and 297.3 ± 79.1 pmol/l at 1 month, respectively. D-Xylose absorption remained unchanged before and after surgery. CONCLUSIONS: RYGB induced a dramatic increase of postprandial insulin and GLP-1 secretion in nonobese minipigs. This preclinical model could help to understand the underlying metabolic effects of RYGB, focusing on the role of postsurgical anatomical rearrangement, especially duodenojejunal exclusion and ileal brake. This study supports the use of RYGB in diabetic nonobese patients in absence of obesity.

Metastatic melanoma: spontaneous occurrence of auto antibodies is a good prognosis factor in a prospective cohort.

BACKGROUND: Melanoma is an immunogenic tumour type frequently associated with spontaneous auto-immune manifestations such as spontaneous regression, vitiligo-like reactions or auto-immune retinopathy, which seem to be associated with better prognosis. OBJECTIVES: The aim of this prospective study was to evaluate the correlation between spontaneous autoimmunity and survival in patients with stage IV melanoma. METHODS: From 2007 to 2008, 103 patients were studied with antithyroid and antinuclear auto antibody assays performed every 6 months. Any detectable occurrence of a spontaneous self antibody (SpSA) at the upper detection limit, at least for one assay, was considered to be a biological marker of autoimmunity. RESULTS: Univariate and multivariate analyses confirmed significantly longer survival in the absence of known primary melanoma (P = 0.044) and in the presence of marker of biologic autoimmunity, independently of previous immunotherapy (P = 0.045). CONCLUSIONS: This prospective and comparative study is, to our knowledge, the first to report the frequency of SpSA in stage IV melanoma. Our results suggest that spontaneous autoimmunity, through a rupture of self-tolerance, is a good prognostic factor in a subgroup of patients with stage IV melanoma.

Predictive factors of change in BMD at 1 and 2 years in women with anorexia nervosa: a study of 146 cases.

UNLABELLED: Bone mineral density (BMD; measured by DXA) changes were observed at all sites at 1 year in 146 patients with anorexia nervosa. Four independent factors accounted for the variation in BMD at the spine: duration of anorexia, bone-specific alkaline phosphatase (BAP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and triiodothyronine (T3). No change in BMD was observed from 1 to 2 years during follow-up. INTRODUCTION: The purpose of this study was to assess changes in BMD at 1 and 2 years in anorexia nervosa patients, and to explore the relationships between change in BMD and various clinical and biological parameters measured at the first visit. METHODS: BMD was measured in anorexia nervosa patients at inclusion, at 1-year follow-up (n = 146) and at 2-year follow-up (n = 89). RESULTS: Bone loss was observed at all sites at 1 year. When multivariate analyses were performed, four independent factors accounted for the variation in BMD at the spine: duration of anorexia nervosa, BAP, ICTP, and T3. At the total hip site, leptin level was the main factor accounting for the variation in BMD. Strong correlations were also observed between weight at 1 year and change in BMD at 2 years. At the 2-year follow-up, no significant change in BMD was observed at the spine or femoral neck. In patients who were no longer amenorrheic at 1 year, a significant improvement in BMD at 2 years was observed at the total hip (+1.2%, p = 0.02) and femoral neck (+3.7%, p = 0.02). Similarly, in patients with a body mass index >17 kg/m(2) at 1 year, an improvement in BMD at the total hip at 2 years was observed (+3%, p = 0.02) CONCLUSION: Bone loss in anorexia nervosa patients occurs at an early stage, and the factors influencing such are different at the spine and hip.

Guidelines of the French society of endocrinology for the management of thyroid nodules.

The present document is a follow-up of the clinical practice guidelines of the French Society of Endocrinology, which were established for the use of its members and made available to scientific communities and physicians. Based on a critical analysis of data from the literature, consensuses and guidelines that have already been published internationally, it constitutes an update of the report on the diagnostic management of thyroid nodules that was proposed in France, in 1995, under the auspices of the French National Agency for Medical Evaluation (l'Agence nationale d'évaluation médicale). The current guidelines were deliberated beforehand by a number of physicians that are recognised for their expertise on the subject, coming from the specialities of endocrinology (the French Thyroid Research Group) and surgery (the French Association for Endocrine Surgery), as well as representatives from the fields of biology, ultrasonography, cytology and nuclear medicine. The guidelines were presented and submitted for the opinion of the members of the Society at its annual conference, which was held in Nice from 7-10 October 2009. The amended document was posted on the website of the Society and benefited from additional remarks of its members. The final version that is presented here was not subjected to methodological validation. It does not claim to be universal in its scope and will need to be revised in concert with progress made in technical and developmental concepts. It constitutes a document that the Society deems useful for distribution concerning the management of thyroid nodules, which is current, efficient and cost effective.

Hypercalcitonemia revealing a somatostatinoma.

Somatostatinoma are rare well-differentiated endocrine tumors with malignant behavior arising from the pancreas and duodenum. They are defined by somatostatin positive immunostaining of the majority of tumor cells. The main clinical features are diabetes, diarrhea and biliary lithiasis related to somatostatin production. Somatostatinoma secreting both calcitonin and somatostatin may be unrecognized as a small number of such observations have been published. We report the case of a 57- year-old woman referred for weight loss, diarrhea and worsening diabetes. Computer tomography scan revealed multiple hypervascular liver lesions suggestive of metastases. High plasma calcitonin level was evidenced, with normal chromogranin-A value, and high plasma somatostatin results lately communicated. Calcitonin secretion of extra-thyroidal origin was suspected leading to the identification of a pancreatic mass by further multiphase CT. The patient underwent left pancreatectomy with surgical hepatic resection. Histological and immunostaining studies confirmed definitive diagnosis of somatostatinoma secreting both somatostatin and calcitonin. Plasma calcitonin should be measured in the assessment of duodeno-pancreatic endocrine neoplasm. Calcitonin determination is available, more reproducible than other specific pancreatic endocrine markers and could be effective for diagnosis and follow-up of such foregut-derived endocrine neoplasia.

Chromogranin A assay in clinical practice.

Chromogranins belong to the family of secretory chromogranin and secretogranin proteins. They are found in secretory vesicles throughout the neuroendocrine system. Chromogranin A (CgA) is the main component. CgA acts as a prohormone submitted to processes of degradation through which active peptides are generated. CgA has auto, para and endocrine functions. It is widely used as an immunohistochemical marker. Despite the lack of international standardization, and the lack of an accurate definition of the diagnostic cut-off levels, some CgA assays are reliable. Numerous studies have suggested that CgA determination may be of interest for the diagnosis and the follow-up of various endocrine tumors. Plasma levels of this general marker are proportional to tumor mass. The localization of the primitive tumor, the presence of associated hormonal secretions and possible renal failure and/or hypergastrinemia must be taken into consideration for proper interpretation of CgA levels. New clinical indications are emerging for the evaluation of stress in intensive care units and the assessment of cardiovascular risk. New assays estimating the concentration of active peptides are under development.

[New assays of TSH-receptor antibodies: analytical and clinical performances in the diagnosis of Graves' disease]. / Nouveaux dosages des anticorps anti-récepteur de la TSH : performances analytiques et cliniques dans le diagnostic de la maladie de Basedow.

Graves' disease autoimmunity is attributable to the presence of serum antibodies (Ab) directed against the TSH receptor (TSHR) measured by a second generation (2G) assay using the human TRAK (hTRAK) with a high sensitivity in the diagnosis of Graves' disease. In this study, we have compared both analytical and clinical performances of hTRAK with those of five new methods using a porcine TSHR: two 2G methods and three assays using the monoclonal M22 directed against the TSHR pocket. We showed a bad reproducibility of these new methods with inter assay CVs higher than 10%. High clinical sensitivity and specificity that appeared similar to those of the hTRAK and next to 100% were observed except for a 2G method that failed to detect five Graves' patients. All these new methods should be avoided since they display a high variability despite their calibration against the same International Standard 90/672. The TRAKh using a human TSHR should be still used for a correct interpretation of results in the follow-up of Graves' disease.

Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay.

BACKGROUND: We compared the clinical performances of two new M22-based assays for TSH-receptor antibody (TRAb) with those of the human TRAb assay (hTRAK) in Graves' disease patients at the end of treatment. PATIENTS AND METHODS: Sera were obtained from 128 Graves' patients treated for 18 months with antithyroid drugs. Sixty-six remained in remission and sixty-two had relapse of hyperthyroidism in a 3-year follow-up after discontinuing treatment. TRAbs were measured using two M22-based methods (electrochemiluminescence using the Cobas or ELISA using the Medizym TRAb clone) and with the hTRAK. RESULTS: At T18, the results were significantly higher by the Cobas assay (median: 2.7 IU/L, range: 1.1-18.5 IU/L) or lower by ELISA (median: 0.56 IU/L, range: 0.22-14.8 IU/L) than those obtained for the hTRAK (median: 1.5 IU/L, range: 0.9-9.8 IU/L). The use of cut-off limits at 1.9 IU/L, 3.2 IU/L and 0.94 IU/L gave similar and higher prevalences of TRAb-positive patients in the group of relapse as compared to the remission group. However, some patients remained misclassified in each remission or relapse group. CONCLUSIONS: The M22-based TRAb assays did not improve the predictive value of relapse obtained with the hTRAK measured at the end of treatment. High inter-method variability requires assay harmonization for correct interpretation of results.

Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8.

CONTEXT: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T(3) levels. Lack of MCT8 transport of T(3) in neurons could explain the neurological phenotype. OBJECTIVE: Our objective was to determine whether the high T(3) levels could also contribute to some critical features observed in these patients. RESULTS: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T(3) (FT(3)) level (11.3 pmol/liter), without FT(4) and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT(4)) was tested. After PTU (200 mg/d), serum FT(4) was undetectable, FT(3) was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT(4) doses (100 microg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT(4) was normal (16.4 pmol/liter), and FT(3) was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter. CONCLUSIONS: 1) When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T(3) levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT(4) could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.

Does the RET variant G691S influence the features of sporadic medullary thyroid carcinoma?

OBJECTIVE: The RET (rearranged during transfection) proto-oncogene G691S variant is over-represented in the germline of patients with sporadic medullary thyroid carcinoma (sMTC) vs. normal controls but so far is not associated with any medical or pathological features of the tumour. The aim of our study was to assess the influence of this variant on the age of onset, clinical, biological and pathological features of sMTC. DESIGN AND PATIENTS: One hundred patients with histologically proven MTC, for whom the germline genetic analysis of RET was negative and medical records were available, were included in the study. RESULTS: Patients with the heterozygous GS variant or the homozygous SS variant (n = 36) were on average 8.0 years younger than patients with the wild-type GG variant (n = 64, mean age 43.9 vs. 51.9 years, P < 0.01). The former group did not differ from the wild-type group in terms of MTC size, prevalence of C-cell hyperplasia (CCH) or papillary thyroid carcinoma (PTC). However, the prevalence of an increased preoperative basal calcitonin (bCT) level (> 1000 pg/ml) was 2.75-fold higher in the patients with the GS or SS variant than in those with the wild-type variant (P < 0.001). The proportion of patients with lymph node metastases was also higher in the former group (P < 0.05). Multivariate analysis confirmed that the presence of the RET variant is independently associated with higher preoperative bCT values (P = 0.011). CONCLUSIONS: Our data demonstrate that the RET G691S variant could modulate the age of onset of sMTC as demonstrated previously for familial tumours. Moreover, this variant is an independent predictor of a higher basal calcitonin synthesis rate in patients with sMTC.

Thyrotoxicosis revealing metastases of unrecognized thyroid cancer: a report on two cases.

We report two cases of thyrotoxicosis-revealing functional metastases of a follicular carcinoma that extended to the bones, liver and kidneys in one case and to the lungs in the other. Both patients had undergone surgical intervention for a thyroid nodule more than 15 years before the diagnosis of thyrotoxicosis and metastatic dissemination. In both the cases, the carcinoma was not recognized by the pathologist after the first surgical intervention, but was finally diagnosed several years later due to the occurrence of thyrotoxicosis. Iodine-131 therapy was effective at suppressing the thyrotoxicosis in both the patients. The effectiveness on the metastatic extension was very different for each patient: in the first case, the patient died a few years later without any control of the metastatic tissue. For the second patient, the metastases disappeared a few months after radioiodine treatment, with the patient still in remission more than 10 years later. The physiopathology and the evolution of these two cases are discussed with the data available in the literature.

Calcitonin levels do not decrease with weaning in chronic alcoholism.

OBJECTIVE: Alcohol might increase calcitonin but this assertion is mainly based on the acute effect of the drug in small animals and humans. The aim of this study was to investigate the effect of chronic alcoholic intoxication on plasma calcitonin (CT) levels. DESIGN: 20 smoking male subjects admitted to be weaned from chronic daily alcohol consumption >100 g were included after informed consent. Blood was sampled upon admission (T0) and after 5 (T5) and 21 (T21) days of alcohol weaning to measure mean erythrocyte volume, gamma-glutamyltransferase (GGT), calcium, gastrin, and CT levels. The control group consisted of 30 male subjects with daily alcohol consumption <20 g. MAIN OUTCOME: The characteristics of the alcohol group were as follows (mean +/- SD): age 41.2 +/- 13 years old; mean erythrocyte volume: 96.0 +/- 4.2 microm(3) (N: 85-95); calcium level: 94.7 +/- 3.7 mg/L (N: 85-105); gastrinemia: 59.3 +/- 14.9 ng/mL (N: <120). At T0 and T21, three alcoholic subjects had CT levels above 10 pg/mL, usually considered as the normal cut-off value. There was no correlation between CT and the different biochemical parameters at T0, T5, and T21. There was no difference between CT levels at the different stages in the alcohol group (T0: 6.4 +/- 3.6 pg/mL; T5: 6.5 +/- 5.3 pg/mL; T21: 8.4 +/- 5.6), although GGT significantly decreased with weaning duration (T0: 248 +/- 354 IU/L; T5: 211 +/- 290 IU/L; T21: 79 +/- 90 IU/L; ANOVA, p <0.05). But a significant difference was found between mean CT levels in the alcohol group and in the control group (3.1 +/- 0.7 pg/mL, p <0.0001). CONCLUSIONS: This study suggests that mean CT levels of chronically alcoholic smoking male subjects are higher than those of an age- and sex-matched control group. However, most alcoholic patients exhibited CT levels <10 pg/mL. No decrease in CT levels was noted over a short period of alcohol weaning. As CT measurement is currently recommended in thyroid nodule assessment, this finding may be important to know how to decipher borderline values of CT.

[Usefulness of procalcitonin for the diagnosis of acute pyelonephritis in children]. / Apport du dosage de la procalcitonine pour le diagnostic de pyélonéphrite aiguë de l'enfant.

BACKGROUND: Acute pyelonephritis can induce parenchymal scarring. The aim of this study was to evaluate the usefulness of procalcitonin (PCT) to predict renal involvement in febrile children with urinary tract infection (UTI). METHODS: In a prospective study serum PCT was measured and compared with others commonly used inflammatory markers in children admitted to the emergency unit with acute pyelonephritis. Renal parenchymal involvement was assessed by a (99 m)Tc-labeled dimercaptosuccinic acid (DMSA) renal scar performed in the first 3 days after the admission. RESULTS: Among 42 enrolled patients, 19 (45%) had acute renal involvement (Group A) ; 23 (55%) (Group B) had normal DMSA scan (n = 16), or old scarring (n = 4) or various anomalies related to uropathy (n = 3). In group A, the mean PCT level was significantly higher than in the group B (5.4 ng/ml, vs 0.4 ng /ml, p < 10(-5)). In these 2 groups, mean C reactive protein (CRP) levels were 99.1 mg/l and 44.6 mg/l respectively (p < 0.001). For a level of serum PCT > or = 0.5 ng/ml, the sensitivity and specificity to predict the renal involvement were 100% and 87% respectively; for a level> or= 20 mg/l CRP had a sensitivity of 94% but a specificity of 30%. CONCLUSION: Serum PCT levels were significantly increased in febrile children with UTI when acute renal parenchymal involvement was present. PCT seems a better marker than CRP for the prediction of patients at risk of renal lesions.

[131 iodine for the treatment of benign goiters]. / L'iode 131 comme traitement des goitres bénins.

INTRODUCTION: In order to evaluate the efficacy of 131 Iodine on goitre volume and on thyroid function, we studied a cohort of patients exhibiting a multinodular and toxic or non toxic goitre. METHODS: This retrospective study was conducted at the Marc Linquette clinic in Lille, in collaboration with the department of nuclear medicine. Thirty-eight patients treated with 131 Iodine were included from 1995 to 2001. Clinical examination and serum analyses including TSH, free T4 and T3, anti-thyroid peroxidase and anti-thyroglobulin antibodies and TSH-receptor antibodies measurements were conducted on inclusion and then at 3, 6, 12 and 72 months. The activity of 131 Iodine corresponded to a standard dose or was calculated according to Marinelli's method. We excluded patients who had not undergone assessment at the above-mentioned time schedules. RESULTS: The treatment was indicated in 30 patients presenting with a non compressive but toxic goitre, in 5 patients with a toxic compressive goitre and in 3 patients with a compressive but non-toxic goitre. Surgery had been excluded for all these patients because of their age, their cardiac status or because they had refused surgery after failure with prior partial thyroidectomy or medical treatment. Among the toxic goitres, TSH levels were low and T3 and T4 increased in 17 patients. In the 18 others, hyperthyroidism was manifested by an isolated decrease of TSH. The thyroid volume before treatment, assessed in 20 patients, was of 18 to 135 cm3 (mean: 53 cm3). Treatment consisted in administration of radioactivity of 3 to 30 mCi in 30 patients and standard activity of 20 to 25 mCi in 8. Functional efficacy with reduction in hyperthyroidism was noted after 3 months, and corrected in nearly all patients after 1 year, and morphological efficacy, with a mean decrease of 33.5% in the size of the goitres. No supplementary surgery was required, notably for the initially compressed goitres. Immediate and long term tolerance was satisfactory. CONCLUSION: Metabolic 131Iodine radiotherapy is effective for the functional and morphological treatment of goitres with good tolerance and few side effects. 131 Iodine is a reasonable alternative in cases with absolute or relative contraindication for surgery.

Thyroid carcinomas involving follicular and parafollicular C cells: seventeen cases with characterization of RET oncogenic activation.

Recent studies have focused on the occurrence of concomitant medullary-papillary thyroid carcinomas (MTC-PTC). The aims of this report were to compare the frequency of occult PTC in a population with MTC versus a control population that had undergone thyroidectomies and to check whether differences could be related to particular phenotype or genotype. To achieve these goals, we determined the frequency of occult PTC among patients operated for MTC (n = 82) or undergoing total thyroidectomy mainly for goiter and/or nodules (n = 7313) between 1994-2001. We then examined the clinical, histologic, and genetic characteristics (using a bio-chemical family inquiry and screening for RET germline mutations) of patients with associated PTC-MTC. Results show a significantly higher frequency of occult PTC in MTC (14.7%) than in total thyroidectomy (6.8%; p < 0.01). Seventeen cases of MTC or bilateral C-cell hyperplasia (CCH) and separate occult PTC were identified from 16 different families. Although common RET mutations providing evidence of familial forms of MTC were identified in only 3 of 16 families, clinical and histologic features usually seen in inherited forms of MTC such as young age of occurrence, bilateral CCH or associated case in family were found in 11 of the remaining 14 patients. In conclusion, results suggest that the association of MTC-PTC is not only a coincidence. Surprisingly, 11 of 17 MTC-PTC patients exhibited clinical, histologic, and/or family features usually encountered in familial forms despite the fact that no RET defect were present. This suggests the possible involvement of another gene or uncommon abnormality of RET gene.

[Genetically-driven or supposed genetic-related insulinomas in adults: validation of the surgical strategy proposed by the A.F.C.E./G.E.N.E.M]. / Les insulinomes de l'adulte d'origine génétique supposée. Validation de la stratégie chirurgicale de l'A.F.C.E./G.E.N.E.M. Vers une simplification de l'imagerie pré-opératoire et des dosages per-opératoires.

Between 1971 and 2002, 80 patients underwent surgery for insulinoma at the Department of General and Endocrine Surgery of the Lille University Hospitals. The present report deals with 13 patients with proven multiple endocrine neoplasia type I (MEN I) or supposed genetic-related insulinomas. This entity differs from spontaneous insulinoma by the presence of multiple foci in the pancreas. Enucleation is not advised in this setting due to the strong likelihood of persistence or recurrence. Various studies suggest different strategies for preoperative localization and surgical approach. We analyzed retrospectively the surgical strategy proposed by the A.F.C.E. and G.E.N.E.M. The purpose of this study was to validate the strategy, integrate the contribution of genotypic diagnosis, simplify preoperative imaging studies, and re-evaluate the value of intraoperative baseline secretin-stimulated insulin measurements. We recommend preoperative endoscopic ultrasonography of the pancreatic head only and routine left pancreatectomy with enucleation of cephalic tumors under intraoperative hormone monitoring. Preoperative invasive localization studies are proposed only if the endoscopic ultrasonography is negative for the pancreatic head. Intraoperative secretin stimulation test can be useful in difficult cases, especially with concurrent nesidioblastosis or in case of secondary surgery. All but one of the 13 patients achieved long-term cure with this strategy.

Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis.

The role of estrogen deficiency in male osteoporosis is still under discussion. One hundred five subjects, 65 of them suffering from osteoporosis (mean age, 53.9 years) and 40 age-matched controls were studied. Osteoporosis was defined by a T score < -2.5 in the lumbar spine or at the femoral neck. Forty-one (63.1%) of the subjects had a history of low-energy fractures, involving vertebrae in 33 cases (50.8%). Osteoporosis was considered to be idiopathic in 33 subjects (50.8%) for whom no etiology could be found. We measured levels of total estradiol (pg/ml, with a detection threshold of 4 pg/ml), total testosterone (ng/ml), and their carrier protein, that is, sex hormone-binding globulin (SHBG, pmol/ml). Various markers of bone remodeling were also measured. Two of them provide an estimate of bone formation-osteocalcin (OC) and bone alkaline phosphatase (BAP). Two others evaluate bone resorption-procollagen type I C-terminal telopeptide (ICTP) and serum C-telopeptide of type I collagen (sCTX). There was no significant difference in estradiol levels between controls and osteroporosis patients. We did not find any significant correlation between estradiol levels and spinal bone mineral density (BMD) (r = 0.15, P > 0.05), and the relationship between estradiol levels and BMD at the femoral neck was weak (r = 0.25, P < 0.05). On the other hand, SHBG was significantly higher in the osteoporotic patients than in controls (P < 0.01). This difference persisted after adjustment for body mass index (BMI) and after exclusion of patients with a condition known to increase SHBG levels. Moreover, this carrier protein was negatively correlated with BMD at the femoral neck (r = -0.37, P < 0.01) and at the lumbar spine (r = -0.27, P < 0.05). SHBG also correlates strongly with sCTX (r = 0.37, P < 0.01). Finally, logistic regression analysis showed that serum SHBG concentration was significantly associated with the presence of fractures; the odds ratio of having a fracture was 2.04 [95% confidence interval (CI) 1.2-3.4, P < 0.01] for each increase of 1 standard deviation (SD) in the patient's SHBG level. The stronger relationship was nearly the same for the whole group and for patients with idiopathic osteoporosis. This study therefore suggests that SHBG may play a key role in male patients with idiopathic or secondary osteoporosis. It shows that serum SHBG concentration is increased in middle-aged men with osteoporosis and is correlated with hip, spine BMD, and sCTX levels. Finally, our findings are in agreement with previous studies which suggest that serum SHBG is a new biological marker of fracture risk in men.

[Proposed reference values for nine methods for measurement of free thyroxin]. / Proposition de valeurs de référence pour neuf techniques de dosage de la thyroxine libre dans le sérum.

In connection with a comparative study of nine kits for the measurement of free thyroxin, we determined reference values in a adult control group of 81 women and 73 men. The correlations observed between the kits are associated with very large differences in the results obtained. The reference ranges are more or less broad according to the kits, but narrower than those offered by the manufacturers.