Mahmoud Choucair

Hypovitaminosis D in healthy schoolchildren.

Background. Vitamin D is essential for skeletal growth, but there are currently no guidelines for vitamin D supplementation after infancy. This study investigates vitamin D insufficiency in healthy children. Methods. Children ages 10 to 16 years from 3 private schools in Beirut, Lebanon, with differing socioeconomic status (SES) were studied: 169 in the spring of 1999 and 177 in the following fall; 83 students participated in both study phases. They had a physical examination, answered a dietary questionnaire, and blood was drawn for calciotropic hormones and indices of bone turnover. Results. Overall, 52% of the students were vitamin D-insufficient; the proportion of insufficiency was 65% in the winter and 40% at the end of the summer. During both seasons, girls had lower vitamin D levels than did boys; those who followed the dress code of covered head, arms, and legs had the lowest levels. Students in the mid-SES school had lower 25-hydroxyvitamin D (25-OHD) levels than did the ones from the high-SES school. After adjusting for confounders, gender, SES, and body mass index remained the significant predictors of vitamin D levels in both seasons (R 2 = 0.53, for spring and 0.28 for fall). There was a significant inverse correlation between 25-OHD levels and parathyroid hormone levels that was best fitted by a curvilinear model (R 2 = 0.19). Conclusion. Even in a sunny country, hypovitaminosis D is common in schoolchildren, more so in the winter. Girls, especially those with a lower SES, are at particular risk. The inverse changes in parathyroid hormone suggest that insufficient vitamin D levels may deleteriously affect skeletal metabolism in healthy adolescents. Vitamin D insufficiency may be prevalent in many other countries where supplementation of milk with vitamin D is not mandatory. Our results call to a reconsideration of vitamin D supplementation in high-risk adolescents to further optimize skeletal health. vitamin D insufficiency, bone metabolism, nutrition, gender, socioeconomic status.

Low calcium and vitamin D intake in healthy children and adolescents and their correlates.

Background: Optimal dietary calcium and possibly vitamin D intake throughout childhood and adolescence may enhance bone mineral accrual. Little data on the intake of these nutrients in Mediterranean countries exist, and predictors of their suboptimal intake are not well defined.Objective: To evaluate systematically the effect of gender, lifestyle factors, and socioeconomic status on mean calcium and vitamin D intake in healthy school children and adolescents from Lebanon.Design: A total of 385 students aged 10–16 y were selected from four public and four private schools between Fall 1999 and Spring 2000. Information on calcium and vitamin D intake, through a semiquantitative food frequency questionnaire that was validated against a 7-day daily record, and on socioeconomic and lifestyle factors were obtained.Results: Only 12% of the students met the adequate intake (AI) recommendation of 1300 mg of calcium/day, and only 16% met the AI recommendation of 200 IU of vitamin D/day. Boys had a significantly higher mean daily calcium intake than girls. Socioeconomic status as assessed by childrens pocket money was a predictor of higher calcium and vitamin D intake. Eating breakfast and physical activity were other correlates of daily calcium and vitamin D intake.Conclusions: Only a minority of students in our study met the AI for calcium and vitamin D. Gender, lifestyle factors, and socioeconomic status were significant predictors of calcium and vitamin D intake. Our findings have important implications regarding the institution of dietary public health strategies to promote skeletal health in Mediterranean countries during a critical time for bone mass accrual.

Disruption of POF1B Binding to Nonmuscle Actin Filaments Is Associated with Premature Ovarian Failure

Premature ovarian failure (POF) is characterized by elevated gonadotropins and amenorrhea in women aged <40 years. In a Lebanese family with five sisters who received the diagnosis of POF, we established linkage to the long arm of the X chromosome (between Xq21.1 and Xq21.3.3), using whole-genome SNP typing and homozygosity-by-descent mapping. By sequencing one candidate gene within that region, POF1B, we identified a point mutation localized in exon 10. This substitution of a nucleotide (G-->A), at position 1123, results in an arginine-->glutamine mutation of the protein sequence at position 329 (mutation R329Q). All the affected family members were homozygous for the mutation, whereas the unaffected members were heterozygous. Because POF1B shares high homology with the tail portion of the human myosin, we assessed the ability of both wild-type and mutant POF1B proteins to bind nonmuscle actin filaments in vitro. We found that the capacity of the mutant protein to bind nonmuscle actin filaments was diminished fourfold compared with the wild type, suggesting a function of POF1B in germ-cell division. Our study suggests that a homozygous point mutation in POF1B influences the pathogenesis of POF by altering POF1B binding to nonmuscle actin filaments.

Effect of gender, puberty, and vitamin D status on biochemical markers of bone remodedeling

Peak bone mass, a determinant of osteoporosis at older ages, is affected by genetic, nutritional, lifestyle, and hormonal factors. Adolescence is a critical time for peak bone mass accrual, and boys achieve a higher peak bone mass than girls. We have reported vitamin D insufficiency in adolescents in our population, but its impact on bone remodeling is unclear. We systematically evaluated the impact of puberty, gender, and vitamin D status on biochemical markers of bone remodeling. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), C-terminal telopeptide of type I collagen crosslinks (S-CTX), and 25 OH vitamin D were measured in 172 healthy students from private schools in the fall of 1999: There were 92 girls and 80 boys, age 10-17 years. In girls, all markers of bone turnover changed significantly with pubertal stage, were maximal at midpuberty, and decreased toward adult levels by Tanner stage V. Conversely in boys, these markers increased during early pubertal stages but had not normalized by Tanner stage V. Levels of all biochemical markers were significantly higher in boys compared to girls even after adjustment for age, body weight, and Tanner stage, P < 0.0001. In the subgroup of girls, those with vitamin D insufficiency, serum levels of BAP and S-CTX were highest. However, in multiple regression analyses, gender was the only consistent correlate of all three markers of bone remodeling. In conclusion, after adjusting for age, weight, and Tanner stages, changes in bone remodeling markers were most powerfully affected by gender. The latter may have important implications on gender differences in peak bone mass.

Persistent Effect of Vitamin D Supplementation on Musculoskeletal Parameters in Adolescents One Year After Trial Completion.

We showed a beneficial effect of vitamin D supplementation on musculoskeletal parameters in adolescent girls in a 1‐year, randomized, double‐blinded placebo‐controlled trial (RCT). Our objective for this study was to investigate the residual effect of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD), at the lumbar spine and hip, lean mass, and height, 1 year after trial completion. We performed post hoc analyses in 167 adolescents, 86 girls and 81 boys, age 13.9 ± 2 years, who received vitamin D or placebo during the trial, and continued into the follow‐up trial. Musculoskeletal parameters were measured at baseline, 12 months (intervention), and 24 months (follow‐up). ANOVA and t tests were used to compare results between the placebo group and the merged vitamin D arms (200 or 2000 IU/day), by gender. Baseline characteristics were comparable between treatment groups at entry into the extension. Girls who had received vitamin D during the trial, had significantly larger hip BMC increments compared to those assigned to placebo, at 24 months compared to study entry, but not 24 compared to 12 months, which persisted in adjusted analyses. There were no significant differences in bone mass changes between treatment groups in boys, at 24 months compared to 12 months or to baseline. The beneficial effect of vitamin D supplementation on hip bone mass, achieved in girls during the trial, persisted 1 year after trial completion. These net cumulative increments, 1 year after discontinuation of supplementation, may have important implications on optimizing peak bone mass accretion in adolescent girls.

Activating BRAF Mutations Detected in Mixed Hürthle Cell Carcinoma and Multifocal Papillary Carcinoma of the Thyroid Gland: Report of an Unusual Case and Review of the Literature.

Despite the increase in the incidence of thyroid carcinomas, the occurrence of collision tumors in the thyroid remains a rare event. We present the case of a 69-year-old female who presented to the emergency department with a chief complaint of painful neck swelling. Imaging revealed a large right hemithyroid mass and a left hemithyroid nodule. Fine needle aspiration of the lesions and subsequent total thyroidectomy revealed a Hürthle cell carcinoma in the right lobe and bilateral multicentric papillary carcinoma foci, including 2 foci with a classical pattern and 1 encapsulated follicular variant in the isthmus. BRAF gene mutation analysis revealed V600E gene mutation in the classical variants of papillary carcinoma and in the Hürthle cell carcinoma. The focus of follicular variant of papillary carcinoma in the isthmus and a sample from normal thyroid tissue did not harbor BRAF mutations. This case is remarkable in being an unusual report of a follicular Hürthle cell carcinoma harboring the BRAF V600E mutation and occurring in collision with multifocal papillary carcinoma. Documentation of such cases is important as it helps better understand the pathogenesis, clinical behavior, and radiologic findings of such rare lesions and to determine the optimal treatment modalities.

An unusual case of autonomous hyperparathyroidism in a patient with X-linked hypophosphatemic rickets and Kallmann syndrome.

We are reporting an unusual patient who presented to our medical center at 18 years of age for evaluation of disabling bilateral lower extremity deformity and delayed puberty. Extensive clinical, laboratory, and radiologic evaluation confirmed the coexistence of 2 X-linked inherited disorders, X-linked hypophosphatemic rickets (XLH) and Kallmann syndrome (KS). Treatment with oral phosphate and calcitriol along with intramuscular testosterone injections was initiated. Despite a dramatic response, the course of treatment was complicated by secondary hyperparathyroidism and, 13 years later, by the development of an autonomous parathyroid adenoma that was surgically resected. Furthermore, the coexistence of XLH and KS has not been reported before. We believe that the proximity of the KAL-1 gene (Xp 22.3), involved in the pathogenesis of KS, to the phosphate regulating endopeptidase on the X chromosome gene (Xp 22.1–22.2), involved in XLH, might be responsible for this association.