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Examines the prevalence of serum hepatitis C virus antibodies in patients with Hashimoto's thyroiditis. Assessment on thyroid function using standard radioimmunoassay; Detection of receptor antibodies for thyroid stimulating hormone using radioreceptor assay; Use of laser nephelometry in immunoglobulin assays.

The thallium-technetium subtraction technique, proposed originally by Ferlin and co-workers, is now widely used to localize parathyroid adenoma. We report here the case of a hypercalcemic woman, referred to our ward with the biologically assessed diagnosis of primary hyperparathyroidism. Thallium-technetium subtraction scintigraphy not only successfully localized the parathyroid adenoma but also revealed the existence of an autonomous nodule of the thyroid, which was not suspected. It has previously been shown that this method can localize parathyroid adenoma in cases of cold thyroid nodule. This report shows that this is also true in the case of hot thyroid nodule. No observations of concomitant parathyroid adenoma and autonomous nodule of the thyroid have been reported (at least during the two past decades). Is this association casual or has it never been noticed? Further examinations can be performed with thallium when a hot thyroid nodule is found in a hypercalcemic patient. [ABSTRACT FROM AUTHOR]

Compares the distribution of the R131/H131 isoforms in patients of French Caucasian origin who had autoimmune disorders. Difference in the distribution of the three genotypes when patients with systemic lupus erythematosus (SLE) were compared with healthy controls; Association of the R131 FcgammaRIIA allele with SLE in French Caucasian patients.

Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.

We report the case of a 42-year-old woman who presented with multiple pulmonary nodules. Surgical resection of 3 nodules revealed differentiated thyroid carcinoma. Thyroid and neck ultrasound was normal. A review of her history revealed that this patient underwent an ovarian cyst resection 15 years ago. Reexamination of pathology samples, with the help of immunohistochemical markers, concluded to a struma ovarii. Pelvic ultrasound was normal; F-18 FDG PET scan was negative. She had total thyroidectomy, with negative histology, followed by first I-131 therapy (3.9 GBq). Thyroglobuline (Tg) was elevated (3230 microg/L in hypothyroidism). The whole-body scan showed multiple foci of pulmonary I-131 uptake, a bone metastasis of third rib, and I-131 uptake in an abdominal para-aortic lymph node. At second I-131 therapy (3.8 GBq), Tg level had decreased to 14 microg/L and there was a decrease in the number of pulmonary nodular I-131 uptake, and resolution of the bone and para-aortic lymph node metastasis. At third I-131 therapy (4.9 GBq), thyroglobuline was undetectable and the whole-body scan showed no I-131 uptake. Struma ovarii is a rare ovarian tumor mostly benign. Metastasis of malignant struma ovarii are rare. Most frequent localizations are liver and peritoneum. Treatment of the malignant struma ovarii implies ovarian surgical resection, total thyroidectomy, and I-131 therapy.

Context and Objectives: Fluorodihydroxyphenylalanine-(18F) (FDOPA) positron emission tomography (PET) is a recent imaging modality used to localize endocrine tumors. This study was conducted to evaluate the impact of FDOPA-PET on the management of patients referred for carcinoid or noncarcinoid digestive tumors and the clinical relevance of the treatment decisions based on this examination., Methods and Patients: Between March 2002 and December 2006, 101 FDOPA-PET examinations were performed in 78 adult patients for follow-up of histologically documented carcinoid tumor of the ileum (23 patients) or noncarcinoid digestive tumor (26 patients) or to screen for occult digestive endocrine tumors (29 patients). More than one FDOPA-PET examination was performed in 12 patients. The impact of FDOPA PET was evaluated on a per-patient basis by means of a questionnaire completed by the referring physician, and the relevance of the treatment decision was assessed on the basis of follow-up data., Results: The survey response rate was 91% (71 of 78). The overall impact rate of FDOPA-PET on patient management was 25% (18 of 71). The greatest impact was observed for carcinoid tumors (50%: 11 of 22) and was clinically relevant in every case, followed by occult endocrine tumors (16%: four of 25), and was clinically relevant in three of the four cases, and noncarcinoid tumors (13%: 3 of 22), clinically relevant in only one case., Conclusion: FDOPA-PET appears to be a major tool for the management of carcinoid tumors with excellent diagnostic performances and induced relevant changes in patient management. FDOPA-PET was less sensitive and less useful for the management of noncarcinoid tumors.

Objective: The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-alpha (HNF1A) gene mutation., Research Design and Methods: We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes., Results: Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10(-4)). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03)., Conclusions: These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors.

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of (131)I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and (131)I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative (131)I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive (131)I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of (131)I. The bone metastases in the remaining eight patients were discovered on the post-surgery (131)I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to (131)I therapy, with (131)I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused (131)I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite (131)I therapy. Post-surgical (131)I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by (131)I therapy.

Background: Stimulation testing in the first year following thyroid ablation has important prognostic value in thyroid cancer patients. Recombinant human TSH (rhTSH) is better tolerated than thyroid hormone withdrawal but provides only transient stimulation so that the TSH threshold of 30 mIU x l(-1) which defines adequate testing during thyroid hormone withdrawal is not appropriate for rhTSH stimulation. We looked at rhTSH levels after a standard two intramuscular injections of 0.9 mg rhTSH., Methods: Plasma rhTSH levels were measured 24 h after the second injection in 143 consecutive patients., Results: rhTSH levels showed large inter-patient variation (range: 44-240; mean+/-SD: 131+/-48). There was a strong inverse correlation between TSH levels and body weight (P<0.001). Levels lower than 80 mIU x l(-1) (corresponding to 1 SD below average) were recorded in 24 patients (16.8%). These patients had an average body weight of 79.7 kg, as compared to 67.9 kg for those patients with TSH levels higher than 80 mIU x l(-1). A withdrawal test in the first year after thyroid ablation was available in 64 patients. Only one patient (1.6%) had inadequate endogenous TSH stimulation, and there was no dependence of endogenous plasma TSH levels upon weight., Conclusion: Contrary to endogenous stimulation, TSH levels after rhTSH injection vary with body weight. The dosage of rhTSH may need to be adapted in patients with more than 80 kg body weight.

Purpose: Recurrences are frequent in thyroid cancer patients and long-term follow-up is therefore necessary. We evaluated the yield of rhTSH stimulation in three groups of patients, classified according to the UICC/TNM risk stratification and the results of first follow-up testing., Methods: The study population comprised 129 patients referred for rhTSH testing. All had undergone first follow-up testing after thyroid hormone withdrawal (off-T4) within 1 year of 131I ablation. Negative first follow-up testing was defined as Tg <2 ng/ml and no neck uptake on 131I diagnostic whole-body scan. Seventy-five patients had stage I thyroid cancer and negative first follow-up testing (group A), 19 had stage I disease and positive first follow-up testing (group B), and 35 had stage II-IV disease (group C). RhTSH stimulation was performed an average of 6 years after first follow-up testing., Results: 131I diagnostic scanning after rhTSH was negative in all 75 group A patients. Only one group A patient had detectable Tg after rhTSH injection (1.5 ng/ml), but Tg had also been detected at baseline in this patient (1.45 ng/ml). Given the absence of a response to stimulation, suggesting an interference, Tg was reassessed with a different technique and proved to be undetectable (<0.1 ng/ml). Stimulation with rhTSH in group B showed residual Tg in seven patients and residual 131I uptake in the thyroid bed in two patients, but none of these patients had signs of disease progression. Five group C patients (14%) had a positive rhTSH test result, and this was suggestive of disease progression in at least two cases., Conclusion: The first follow-up testing is essential for prognostic classification after 131I ablation of thyroid cancer. In stage I patients, undetectable Tg and negative 131I scan 1 year after ablation define a large population of subjects who have a very low risk of recurrence and who do not require further stimulation tests. In contrast, periodic rhTSH stimulation tests appear useful in higher-risk patients.

Objective: The American consensus statement on patients with low-risk thyroid cancer, published in 2003, suggests repeat (131)I therapy if the thyroglobulin value is elevated at first follow-up. We evaluated this strategy in our practice., Methods: Among 407 patients with thyroid cancer who had total thyroidectomy and (131)I ablation between January 2000 and December 2003, 12 patients with stage I thyroid cancer (any tumour (T), any node (N), metastasis (M)0 if < 45 years or T1, N0, M0 if > 45 years), were re-treated on the basis of their thyroglobulin level at first follow-up. Mean patient age was 32.8 years. None of them had a T4 tumour. Thyroglobulin levels after thyroid hormone withdrawal 'off-T4' ranged between 4.5 and 251 ng/ml (median 8). One to four courses of 3.7 GBq (131)I were given., Results: Three patients had a negative (131)I therapy scan and an uneventful course. Two patients had slight residual uptake only in the thyroid bed and negative ultrasound examination. Four patients had isolated (131)I uptake in the mediastinal region. No abnormalities were found on complementary mediastinal imaging. This finding was interpreted as benign (131)I thymic uptake. The last three patients also had mediastinal thymic uptake associated with a slight thyroid bed uptake. One patient had a gradual increase in the thyroglobulin level, and underwent resection of nonfunctioning neck lymph nodes. Thyroglobulin levels declined in all other patients., Conclusions: No distant lesions were found in a group of young 'low-risk' thyroid cancer patients given empirical (131)I therapy for residual thyroglobulin. When blind (131)I therapy shows no uptake, or uptake limited to the thymus, (131)I therapy should not be repeated. The authors also briefly discuss the hypothesis that enhanced thymus might be a source of benign thyroglobulin secretion.

FDG PET can detect thyroid cancer in patients referred for exploration of a different cancer. Because of its lack of specificity, however, this modality is not indicated for examination of thyroid nodules: ultrasonography and fine needle biopsy with cytology allow histological diagnosis, which can be completed by iodine-123 scintigraphy when an autonomous nodule is suspected. No information is currently available about the utility of FDG PET in preoperative staging. In follow-up of patients undergoing thyroidectomy for adenocarcinoma, FDG PET is useful for detecting recurrence in cases where serum thyroglobulin levels rise and iodine-131 scintigraphy is negative: surgical resection may be appropriate. Nonetheless FDG PET should be performed more widely and earlier: the initial presence of foci positive for FDG is a major predictor of shorter survival, and most cancer lesions take up either iodine or FDG. In follow-up of medullary carcinoma, FDG PET detects residual tissue better than any other scintigraphic procedures, especially when serum levels of CEA (carcinoembryonic antigen) are rising rapidly. FDOPA PET seems to have better sensitivity than FDG-PET and may be useful in occult recurrence, as three case reports indicate.

Hypothesis: Completion pancreatectomy in patients with pancreatic leakage associated with postoperative peritonitis after pancreaticoduodenectomy is a viable salvage procedure., Design: Retrospective analysis from a cohort of consecutive patients admitted between January 1, 1989, and December 31, 1999, for postoperative peritonitis originating from pancreaticojejunostomy leakage., Setting: Tertiary referral center with surgical intensive care unit specializing in the treatment of intra-abdominal sepsis., Patients: Eight consecutive patients with postoperative peritonitis originating from pancreaticojejunostomy after pancreaticoduodenectomy, with a mean Acute Physiology and Chronic Health Evaluation II score of 18.6. We excluded patients with pancreatic fistulas or abscesses amenable to percutaneous drainage or other conservative treatment., Intervention: Completion pancreatectomy., Main Outcome Measures: Mortality, morbidity, and long-term outcome, which was assessed by interview., Results: Three patients died in the postoperative period: 2 required early reoperation during the postoperative period and died of hemorrhage and sepsis, and 1 died of multiorgan failure without reoperation. Recurrence of carcinoma was responsible for late death of 2 other patients., Conclusions: Postoperative peritonitis after pancreaticoduodenectomy still has high mortality; however, completion pancreatectomy may represent the only means to achieve source control of infection in cases of postoperative peritonitis.

Objectives: The outcome of dysthyroidism and the presence of antithyroid antibodies in patients with chronic hepatitis C virus (HCV) infection receiving interferon-alpha therapy is clearly established. However, the prevalence and the specificity of antithyroid antibodies in HCV patients before interferon-alpha therapy remain controversial. The aim of the present study is to clarify within a large population of HCV patients the prevalence of antithyroid antibodies before interferon-alpha therapy and to determine whether their immunodominant antigen is the same as described in autoimmune thyroiditis., Methods: Sera from 99 patients with chronic hepatitis C before (n = 99) and after (n = 37) interferon-alpha treatment were investigated for the presence of antimicrosomal and antithyroperoxidase antibodies assessed by indirect immunofluorescence and ELISA, respectively. Dot blotting on human thyroid lysate was designed to further characterize these autoantibodies. Data were compared to those obtained with sera of patients with autoimmune thyroiditis (n = 75) and healthy subjects (n = 96)., Results: In HCV patients, antimicrosomal antibodies were found with a higher proportion before interferon-alpha therapy (12.1%) than after therapy (8%). Thyroperoxidase constitutes the main antigen in only 4% before treatment, a prevalence similar to that observed in healthy controls., Conclusions: The prevalence of antithyroid antibodies is low in patients with chronic hepatitis C before interferon-alpha therapy. Thyroperoxidase may not be their main target. Further studies are required to determine whether HCV infection leads to a breakdown of tolerance to a thyroid self-protein other than thyroperoxidase.

The ligand immunofunctional assay for plasma insulin-like growth factor (IGF) binding protein (IGFBP)-3 developed in our laboratory provides for specific measurement of intact, as opposed to proteolyzed, IGFBP-3. IGFBP-bound IGFs are dissociated and separated by acid pH ultrafiltration; thereafter, intact and proteolyzed IGFBP-3 are captured by a monoclonal antibody in a solid-phase assay and incubated with (125)I-IGF-I, which detects the intact protein but not its proteolytic fragments. This assay was combined with assays for IGF-I (RIA of the ultrafiltrate) and total IGFBP-3 (immunoradiometric assay) to quantify the percentage of proteolyzed IGFBP-3 (percent proteolyzed IGFBP-3) and to calculate the IGF-I/intact IGFBP-3 ratio as an index of the fraction of exchangeable IGF-I bound to IGFBP-3. This fraction represents most of the IGF-I that is bioavailable. Because GH and insulin control the hepatic production and plasma concentrations of IGF-I and IGFBP-3, we set out to determine whether variations in the secretion of the two hormones are involved in the regulation of IGFBP-3 proteolysis. The study included adult populations of 36 healthy subjects, 23 hypopituitary patients untreated with GH, 43 acromegalics (13 untreated), 42 insulin-treated type 1 diabetics [insulin-dependent diabetes mellitus (IDDM)] patients, and 50 type 2 diabetics [non-IDDM (NIDDM)] patients, 22 of whom were insulin-treated and the remaining 28 treated with sulfonylurea and/or metformin). Unlike IGF-I and (to a lesser extent) total IGFBP-3 levels, which decline with age, percent proteolyzed IGFBP-3 seemed relatively stable. In healthy adults, the mean +/- SEM was 29.4 +/- 1.9 for subjects less than 45 yr old and was slightly (but not significantly) lower, 25.7 +/- 3, for those of more than 45 yr. There was no difference between male and female subjects. In GH-deficient patients, despite severely depressed IGF-I levels, percent proteolyzed IGFBP-3 and IGF-I/intact IGFBP-3 ratios were within the normal range. Among acromegalics, percent proteolyzed IGFBP-3 was elevated: 36.6 +/- 3.3 for patients of less than 45 yr, 33.3 +/- 3.2 for patients of more than 45 yr (P = 0.02 vs. healthy subjects). Consequently, the effects of excessive IGF-I synthesis are exacerbated by the enlarged exchangeable fraction of IGFBP-3-bound IGF-I. There was no significant difference in percent proteolyzed IGFBP-3 between GH-deficient patients before and after GH treatment or between treated and untreated acromegalics. In IDDM patients, the means for percent proteolyzed IGFBP-3 were higher than those in healthy adults: 36.7 +/- 3.7 (P = 0.03) and 31.3 +/- 3.3 for subjects of less than 45 and more than 45 yr, respectively. In NIDDM patients, all of whom were more than 45 yr old, the means were 35.2 +/- 2.5 (P = 0.02) for insulin-treated patients and 33 +/- 2.5 for the group treated orally. Among the diabetics, increased IGFBP-3 proteolysis resulted in an IGF-I/intact IGFBP-3 ratio that was normal for IDDM patients of less than 45 yr and above normal (P = 0.01) for the others. Percentage proteolyzed IGFBP-3 and the IGF-I/intact IGFBP-3 ratio were inversely related to body mass index in IDDM patients (r = -0.42, P = 0.008; and r = -0.31, P = 0.05, respectively) and to percentage glycosylated hemoglobin in all insulin-treated diabetics (r = -0.25, P = 0.05; and r = -0.33, P = 0.008, respectively). There was also an inverse relationship between IGF-I/intact IGFBP-3 ratios and IGFBP-1 levels in healthy adults (r = -0.39, P = 0.03) and orally treated NIDDM patients (r = -0.37, P = 0.05). Percentage proteolyzed IGFBP-3 was positively correlated to total IGFBP-3 in healthy adults (r = 0.65, P = 0.0001) and in all the groups of patients. It was negatively correlated to IGF-I/total IGFBP-3 in healthy subjects (r = -0.40, P = 0.02) and diabetics (r = -0.30, P = 0.005). This suggests an autoregulatory mechanism controlling the bioavailability of IGFBP-3-bound IGF-I in the 140-kDa complexes. In the pathological conditions studied here, regulation of IGF-I bioavailability by limited proteolysis of IGFBP-3 contributes toward an appropriate adaptation to insulin deficiency and/or resistance but not to disturbances of GH secretion.

Background: Rheumatoid arthritis and insulin-dependent diabetes mellitus are both autoimmune disorders of unknown etiology. We report the case of a patient who developed the two diseases simultaneously., Case Report: A 64-year-old man with no remarkable medical history developed insulin-dependent diabetes disclosed by ketoacidosis that occurred 3 weeks after onset of a bilateral symmetrical polyarthritic syndrome characteristic of rheumatoid arthritis., Discussion: These two disorders share common susceptibility of subjects with MHC class II molecules HLA DRB1*04. Immunological studies have also shown a common Th1 type cytokine-secretion pattern in both diseases. Epidemiological studies have not however clearly demonstrated a link between them.

Background: Automated electrophoresis combined with enzymatic cholesterol staining might improve routine assessment of LDL- and HDL-cholesterol (LDLC and HDLC), as an alternative to the Friedewald equation and precipitation. A new method (Hydrasys; SEBIA) that adapts the cholesterol esterase/cholesterol oxidase reaction within urea-free gels was evaluated., Methods: Fresh sera from 725 subjects (512 dyslipidemics) were analyzed by electrophoresis, in parallel with sequential ultracentrifugation, beta-quantification, calculation, and precipitation., Results: Electrophoresis was linear up to 4 g/L cholesterol, with a detection limit of 0.042 g/L cholesterol/band. Within-run, between-run, between-batch, and between-operator imprecision (CVs) were 1.6%, 2.0%, 1.5%, and 2.7% for LDLC, and 3.9%, 4.3%, 5.5%, and 4.9% for HDLC, and remained unchanged up to 6.3 g/L plasma triglycerides (TGs). Precision decreased with very low HDLC (<0.25 g/L). Serum storage for 3-7 days at +4 or -80 degrees C did not interfere significantly with the assay. Agreement with beta-quantification was stable for LDLC up to 5.07 g/L (r = 0.94), even at TG concentrations >4 g/L (r = 0.91). Bias (2.88% +/- 12%) and total error (7.84%) were unchanged at TG concentrations up to 18.5 g/L. Electrophoresis predicted National Cholesterol Education Program cut-points with <0.04 g/L error, exactly and appropriately classified 79% and 96% of the subjects, and divided by 2.4 (all subjects) and 5.8 (TGs >1.5 g/L) the percentage of subjects underestimated by calculation. One-half of the patients with TGs >4 g/L had LDLC >1.30 g/L. For HDLC, correlation was better with precipitation (r = 0.87) than ultracentrifugation (r = 0.76). Error (-0.10% +/- 26%) increased when HDLC decreased (<0.35 g/L). Direct assessment of the LDLC/HDLC ratio detected 45% more high-risk subjects than the calculation/precipitation combination., Conclusions: Electrophoresis provides reliable quantification of LDLC, improving precision, accuracy, and concordance over calculation, particularly with increasing plasma TGs. Implementation of methods to detect low cholesterol concentrations could extend the applications for HDLC assessment.

Post total pancreatectomy diabetes is a clearly defined form of unstable diabetes, requiring low doses of insulin, with frequent and severe hypoglycemic events. This is due to both deficiency of pancreatic glucagon, hormone of primary importance for hepatic gluconeogenesis and glycogenolysis, and exocrine failure. The management of this form of diabetes is difficult, involving exact correction of malabsorption and low doses of insulin. Whenever possible, partial pancreatectomy should therefore to be preferred. After partial pancreatectomy, the likelihood of diabetes depends on the volume of the remaining pancreas, the type of resection and above all the preexisting pancreatic status. Prevention of postoperative hyperglycemia could minimize the risk of long-term diabetes. Pancreatic cancer is a particular case: the onset of diabetes could be a manifestation of occult pancreatic cancer and glucose metabolism may improve after tumour excision with preservation of some pancreatic tissue.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases.

Bartter's syndrome, sometimes a familial autosomal recessive condition, is characterized by hypokalaemia with normal kaliuresis, hyperreninaemia with secondary hyperaldosteronism, vascular resistance to angiotensin and overproduction of prostaglandins by the kidneys. This syndrome is rare but sometimes envisaged in patients with unexplained hypokalaemia, the main difficulty being to exclude intoxication with diuretics which is very similar in all respects. Its physiopathology is unknown, and the various hypotheses put forward since it was first described (vascular insensitiveness to angiotensin, defect of sodium or chloride reabsorption, excess of atrial natriuretic factor, general abnormality of membrane permeability) were unable to demonstrate their primary character, each disorder described seeming, subsequently, secondary to another. For this reason, treatment is difficult and disappointing, but although the hypokalaemia is sometimes worrying, Bartter's syndrome is usually a benign condition.

We report the case of a 62-year old woman in euthyroidism who presented with a thyroid cancer located within a hot nodule. The nodule was partially extinctive, and the triiodothyronine test showed incomplete suppression. Fine needle cytology showed no malignant cells. Systematic lobectomy was performed, and the diagnosis of cancer was made at pathology. This rare situation does not mean that all non-toxic hot nodules must be removed, but if surgery is decided an extemporaneous histological examination is mandatory. Besides, such cases provide an additional argument in favour of surgery or treatment of toxic adenomas.

The authors report their experience of segmental pancreatic autotransplantation in dogs. The most reliable model seems to be: segmental heterotopic pancreas transplantation with bladder diversion of the exocrine secretion and spleno-splenic arterio-venous fistula allowing monitoring of the exocrine secretion and a reduction in the thrombosis rate.

Systematic assays of glycosylated haemoglobin were performed to verify that pregnant women with glycosuria and normal fasting blood glucose and glucose tolerance tests had no disturbances in glycoregulation . Glycosylated haemoglobin levels were measured in 25 glycosuric women on the second (n = 11) or third (n = 14) trimester of pregnancy and compared with those of 81 non-glycosuric women of similar weight and gestational age. On the third trimester, glycosylated haemoglobin levels were significantly higher in glycosuric women of normal weight than in controls (5.85% versus 5.08%; p less than 0.01). They were also significantly higher in obese glycosuric women than in controls of the same weight (6.71% versus 5.3%; p less than 0.001) and exceeded normal limits. These results should encourage better detection (by glucose tolerance test) and better supervision of women with "renal" diabetes.

The serum concentrations of the different forms of circulating testosterone, total testosterone, free testosterone and non-sex-hormone binding globulin bound testosterone (albumin bound + free fractions) which is considered as the bioavailable hormone, were measured in 15 hyperthyroid women before and after anti-thyroid drug therapy and in 15 age-matched healthy women. Sex-hormone binding globulin and albumin were quantified. Total testosterone was significantly higher in hyperthyroid women before treatment, whereas free testosterone and non sex-hormone binding globulin bound testosterone were significantly decreased. After recovery, all the parameters returned to the normal range. In hyperthyroid patients, the variations in the different fractions of testosterone can be related to the rise of sex-hormone binding globulin. These variations could be explained by the displacement of the equilibrium defined by the binding equation.