Fidaa Ibrahim

A very high incidence of low 25 hydroxy-vitamin D serum concentration in a French population of patients with primary hyperparathyroidism

Since the demonstration that vitamin D status might influence the clinical and biological expression of primary hyperparathyroidism (PHPT), a serum 25-hydroxy vitamin D (25-OHD) concentration of 50 nmol/l has been considered by an expert panel as the minimum level to be maintained in asymptomatic PHPT patients. Two yr after this recommendation, we aimed to evaluate the frequency of serum 25-OHD concentrations below this threshold in PHPT patients. In the present study, serum 25-OHD, second- and third-generation PTH, calcium, phosphate, magnesium, albumin and creatinine were measured in 72 out 145 consecutive PHPT patients operated on in our Endocrine Surgery Department, in whom blood samples were available before as well as two days after surgical intervention. Before surgery, the frequency of serum 25-OHD levels <50 nmol/l ranged from 91.5 to 100% whatever the classification used to identify patients: whole group, symptomatic vs asymptomatic, patients with calcium levels >3 vs >3 mmol/l. 25-OHD concentrations correlated negatively with the weight of adenoma, PTH levels, and total calcium concentrations measured before surgery. Pre-operative PTH levels, whatever the assay used, and total calcium concentrations were positively and significantly correlated. Two days post-surgery, 13 patients were moderately hypocalcemic. Neither pre-surgery 25-OHD nor PTH, calcium or phosphorus level or adenoma weight were predictive of post-operative hypocalcemia. The dramatic frequency of low 25-OHD concentrations in our PHPT patients demonstrates that the above-mentioned recommendation is far from being applied in France despite evidence of worsening expression of PHPT with decreasing 25-OHD serum levels.

Plasma 11-deoxycorticosterone (DOC) and mineralocorticoid receptor testicular expression during rainbow trout Oncorhynchus mykiss spermiation: implication with 17alpha, 20beta-dihydroxyprogesterone on the milt fluidity?

BackgroundIn rainbow trout (Oncorhynchus mykiss), the endocrine control of spermiation is not fully understood. Besides 11ketotestosterone (11KT) and 17alpha, 20beta-dihydroxyprogesterone (MIS), the potential physiological ligand of the mineralocorticoid receptor (MR) 11-deoxycorticosterone (DOC), is a credible candidate in O. mykiss spermiation regulation as spermiation is accompanied with changes in aqueous and ionic flows.MethodsIn this study, we investigated potential roles of DOC during spermiation 1) by describing changes in blood plasma DOC level, MR mRNA abundance during the reproductive cycle and MR localization in the reproductive tract 2) by investigating and comparing the effects of DOC (10 mg/kg) and MIS (5 mg/kg) supplementations on sperm parameters 3) by measuring the in vitro effect of DOC on testis MIS production.ResultsThe plasma concentration of DOC increased rapidly at the end of the reproductive cycle to reach levels that were 10–50 fold higher in mature males than in immature fish. MR mRNA relative abundance was lower in maturing testes when compared to immature testes, but increased rapidly during the spermiation period, immediately after the plasma rise in DOC. At this stage, immunohistochemistry localized MR protein to cells situated at the periphery of the seminiferous tubules and in the efferent ducts. Neither DOC nor MIS had significant effects on the mean sperm volume, although MIS treatment significantly increased the percentage of males producing milt. However, a significant reduction in the spermatocrit was observed when DOC and MIS were administrated together. Finally, we detected an inhibitory effect of DOC on testis MIS production in vitro.ConclusionThese results are in agreement with potential roles of DOC and MR during spermiation and support the hypothesis that DOC and MIS mechanisms of action are linked during this reproductive stage, maybe controlling milt fluidity. They also confirm that in O. mykiss MIS is involved in spermiation induction.

β- and α-Cell Dysfunctions in Africans With Ketosis-Prone Atypical Diabetes During Near-Normoglycemic Remission

OBJECTIVE Ketosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission. RESEARCH DESIGN AND METHODS We characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping. RESULTS Early insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin. CONCLUSIONS Patients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.

Plasma 11β-hydroxy-4-androstene-3,17-dione: comparison of a time-resolved fluoroimmunoassay using a biotinylated tracer with a radioimmunoassay using a tritiated tracer

The plasma concentration of 11beta-hydroxy-4-androstene-3,17-dione (11beta) is very high in 21-hydroxylase deficiency, Cushings syndrome, and hyperandrogenism of adrenal origin, and very low in congenital 11-hydroxylase deficiency and adrenal insufficiency. Thus, when plasma 4-androstenedione is elevated, it is useful to measure the plasma 11beta level in order to determine the adrenal or ovarian origin of the hyperandrogenism. To eliminate disadvantages related to the 11beta radioimmunoassay (RIA), which uses a tritiated tracer, as well as the high cost associated with scintillation proximity assay (SPA), we developed a non-isotopic 11beta assay that utilizes an 11beta-biotin conjugate synthesized in our laboratory to measure time-resolved fluorescence after addition of streptavidin-europium to microtitration wells. The analytical qualities of this assay are very similar to those of the radioimmunoassay using a tritiated tracer, and an extraction step followed by celite chromatography (which separates 11beta from interfering plasma steroids) prior to a final radioimmuno-competition step. The correlation coefficient between 11beta levels measured by time-resolved plasma 11beta fluoroimmunoassay (TR-FIA) and RIA was 0.965.Finally, the TR-FIA technique was more sensitive and of greater precision than the RIA method.

Zinc transporter 8 autoantibodies assessment in daily practice

OBJECTIVES Zinc transporter 8 (ZnT8) is specifically expressed in the pancreatic β-cell and is more restricted in its tissue distribution than other auto-antigens as glutamic acid decarboxylase 65 (GAD65) and insulinoma-associated antigen-2 (IA2). ZnT8 autoantibodies (ZnT8A) assessment allows identifying rapid progression to clinical onset of the disease. We evaluated the prevalence of ZnT8A in adults of different ethnic and phenotypic groups and analyzed its potential utility as additional marker of autoimmunity in daily practice. METHODS ZnT8A, GADA and IA2A were assessed using enzyme-linked immune-sorbent assay (ELISA) in 160 controls and 216 diabetic subjects. 105 were of type 1 diabetes (T1D), 17 had Latent Autoimmune Diabetes of Adults (LADA), 38 were type 2 diabetic (T2D) and 56 had ketosis-prone diabetes (KPD). 82 patients were newly diagnosed cases. RESULTS ZnT8A were detected in 1% of controls and were not found in any of our 38 T2D subjects or 56 KPD subjects. In contrast, ZnT8A were detected in 18% of LADA subjects and in 38% of T1D subjects. A slight difference of percentage of ZnT8A positivity was found among our T1D ethnic groups. ZnT8A were positive in 41% of patients positive for GADA and 67% of patients positive for IA2A. The percentage of stratification achieved 91% when GADA, IA2A and ZnT8A were assessed simultaneously. CONCLUSIONS Results obtained for ZnT8A measurement using ELISA were consistent with previous data. Such investigation could improve the risk stratification and would be integrated in our daily practice.

Sex Difference In the Effect of Fetal Exposure to Maternal Diabetes on Insulin Secretion

Abstract We previously showed that fetal exposure to maternal type 1 diabetes (T1D) is associated with altered glucose-stimulated insulin secretion in adult offspring. Here, we investigated whether this β-cell defect displays a sex dimorphism. Twenty-nine adult nondiabetic offspring of T1D mothers (ODMs) were compared with 29 nondiabetic offspring of T1D fathers. We measured early insulin secretion in response to oral glucose and insulin secretion rate in response to intravenous glucose ramping. Insulin sensitivity and body composition were assessed by a euglycemic, hyperinsulinemic clamp and dual-energy X-ray absorptiometry, respectively. In response to oral glucose, male and female ODMs displayed a reduced insulin secretion. In contrast, in response to graded intravenous glucose infusion, only female ODMs (not males) exhibited decreased insulin secretion. There was no defect in response to combined intravenous arginine and glucose, suggesting that male and female ODMs exhibit a functional β-cell defect rather than a reduced β-cell mass. In conclusion, fetal exposure to maternal diabetes predisposes to β-cell dysfunction in adult male and female offspring. This β-cell defect is characterized by a sexual dimorphism following intravenous glucose stimulation.