Dimitrios T. Papadimitriou

Low TSH levels are not associated with osteoporosis in childhood

INTRODUCTION A recent study on TSH receptor (TSHR) null mice suggested that skeletal loss occurring in hyperthyroidism is caused by the low TSH rather than high thyroid hormone levels. The aim of this study was to examine whether low TSH results in osteoporosis in the human. SUBJECTS AND METHODS We determined bone mineral density (BMD) and markers of bone metabolism in two male siblings aged 9.8 and 6.8 years with isolated TSH deficiency, due to a mutation of the TSH beta-subunit gene. BMD was measured in the lumbar spine (L1-L4) by dual-energy X-ray absorptiometry. Laboratory investigation included the determination of serum calcium, phosphate, 25-hydroxy-vitamin D, parathyroid hormone concentrations, and urine calcium (Ca)/creatinine (Cr) ratio. Osteoblast activity was measured by serum bone alkaline phosphatase and osteocalcin levels, and osteoclast activity by urine cross-linked amino-terminal, carboxy-terminal telopeptides of type I collagen and deoxypyridinoline concentrations. RESULTS BMD of both patients was within the normal range for age and sex; z-scores were -0.55 and -0.23 for patients 1 and 2 respectively. Serum calcium, phosphate, urine Ca/Cr ratio, and specific markers of bone metabolism were also within normal range. CONCLUSION In childhood, chronic extremely low TSH levels, in the face of normal thyroid hormone levels, are not related to bone loss.

Mineralocorticoid deficiency in post-operative cerebral salt wasting.

Acute hyponatremia, following neurosurgery, results from inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW). CSW is due to abnormally high atrial or brain natriuretic peptides (ANP, BNP), which block all stimulators of zona glomerulosa steroidogenesis, resulting in mineralocorticoid deficiency. A 3 year-old girl presented CSW at day 4, after resection of craniopharyngioma and hypophysectomy. Hyponatremia, hyperkalemia and high natriuresis occurred on day 8, with low renin and aldosterone and elevated BNP 120.3 ng/ml (undetectable before surgery). Fludrocortisone 100 microg/day controlled natriuresis and restored electrolytes within 24 hours. A 5 year-old boy presented CSW at day 6 after partial resection of optic glioma. Fludocortisone 100 microg/day restored electrolytes within 8 hours. ANP was elevated, 60.6 ng/l, aldosterone and renin were low. Fludrocortisone supplementation should be considered in CSW, as excessive natriuresis is controlled, and electrolytes are easily restored, avoiding life-threatening complications of this complex disorder.

Prevalence of overweight and obesity in young Greek men.

We determined the prevalence of overweight and obesity in young Greek men in 2006 and examined variations related to their place of residence and educational level. Body height and weight were measured in 2568 conscripts of the Greek army, aged 19–26 years. The calculated body mass index (BMI, kg m−2) was correlated to their socio‐demographic characteristics, i.e. level of education and place of residence (urban or rural). Overweight and obesity were defined according to the World Health Organization classification. Mean BMI (standard deviation) of the conscripts was 24.7 (4.2). The prevalence of overweight (30 > BMI ≥ 25 kg m−2) was 28.5% and correlated positively with a higher educational level, whereas the prevalence of obesity (BMI ≥ 30 kg m−2) was 10.4% and correlated positively with a lower educational level. Our data were compared with those of similar studies performed in the years 1969: BMI 23.8 (1.4) (P < 0.0001) and 1990: BMI 23.8 (2.9) (P < 0.0001), showing a positive secular trend for BMI in Greek conscripts in the last 16 years. In conclusion, we documented an alarmingly high prevalence of overweight and obesity among young Greek men.

Timing of Pubertal Onset in Girls: Evidence for Non-Gaussian Distribution

CONTEXT The timing of the onset of puberty is considered to approximate a normal distribution. However, because many more girls present with early than late puberty, we hypothesized that the distribution of the timing of the onset of puberty in girls might have changed. OBJECTIVE/SUBJECTS: The objective of the study was to examine the distribution of the timing of the onset of puberty in normal Greek girls. DESIGN Onset of puberty, i.e. breast development (B2), was studied longitudinally in 311 prepubertal schoolgirls aged 6.4-8.2 yr until the onset of puberty. We also studied cross-sectionally 126 girls, 6-14 yr old. SETTING Clinical examinations took place in the school setting. RESULTS In the longitudinal study, median of the distribution of age at B2 was 10.0 yr (with the 25th and 75th centiles being 9.2 and 10.6 yr, respectively). Skewness was -0.45 (P=0.001), suggesting a negatively skewed distribution. In the cross-sectional study, 126 subjects were found at B2. The median of the age distribution at B2 was 10.1 yr (with the 25th and 75th centiles being 9.7 and 11.2 years, respectively). Skewness was -0.44 (P=0.03), suggesting a negatively skewed distribution. CONCLUSIONS A non-Gaussian distribution of the age at the onset of puberty in girls was documented. The currently used cutoff ages for precocious and delayed puberty may not be applicable to modern children; therefore, up-to-date studies on pubertal maturation are much needed.

Overweight and obesity decreased in Greek schoolchildren from 2009 to 2012 during the early phase of the economic crisis

We examined the weight status of Greek schoolchildren from November 2009 to May 2012, shortly before, and during the early years, of the Greek economic crisis.

Greek young men grow taller.

Aim: To examine whether a secular trend for greater height is still observed in young Greek men.

Characteristics of the short children referred to an academic paediatric endocrine clinic in Greece

Aim:  To describe the characteristics of short children in relation to gender and the various diagnoses.

The Big Vitamin D Mistake

Since 2006, type 1 diabetes in Finland has plateaued and then decreased after the authorities’ decision to fortify dietary milk products with cholecalciferol. The role of vitamin D in innate and adaptive immunity is critical. A statistical error in the estimation of the recommended dietary allowance (RDA) for vitamin D was recently discovered; in a correct analysis of the data used by the Institute of Medicine, it was found that 8895 IU/d was needed for 97.5% of individuals to achieve values ≥50 nmol/L. Another study confirmed that 6201 IU/d was needed to achieve 75 nmol/L and 9122 IU/d was needed to reach 100 nmol/L. The largest meta-analysis ever conducted of studies published between 1966 and 2013 showed that 25-hydroxyvitamin D levels <75 nmol/L may be too low for safety and associated with higher all-cause mortality, demolishing the previously presumed U-shape curve of mortality associated with vitamin D levels. Since all-disease mortality is reduced to 1.0 with serum vitamin D levels ≥100 nmol/L, we call public health authorities to consider designating as the RDA at least three-fourths of the levels proposed by the Endocrine Society Expert Committee as safe upper tolerable daily intake doses. This could lead to a recommendation of 1000 IU for children <1 year on enriched formula and 1500 IU for breastfed children older than 6 months, 3000 IU for children >1 year of age, and around 8000 IU for young adults and thereafter. Actions are urgently needed to protect the global population from vitamin D deficiency.

L-Dopa Is a Potent Stimulator of Cortisol in Short Children

Aims: In this study, we evaluated the diagnostic usefulness of oral L-dopa as a stimulatory agent for cortisol. Methods: In 27 short children that were evaluated for possible growth hormone deficiency (GHD), the levels of serum GH and cortisol were determined after oral L-dopa administration and after i.m. glucagon administration. We defined cortisol concentrations >18 μg/dl (496 nmol/l) as adequate response. Peak GH concentration <10 ng/ml in both tests defined GHD. Results: Twenty-five out of the 27 children (93%) studied showed a normal cortisol response, i.e. a peak serum cortisol >18 μg/dl in the L-dopa test, whereas 19 children (70%) had a normal cortisol response after stimulation with glucagon. In the children with normal cortisol response in both tests, the mean peak serum cortisol concentration was 28.7 (SD 1.59) after L-dopa and 26.65 (SD 1.26) μg/dl after glucagon administration. There was no statistically significant difference in peak serum cortisol response to L-dopa between GH-deficient and GH-sufficient children [25.90 (SD 4.9) vs. 29.87 (SD 9.9) μg/dl, respectively]. Conclusions: These results clearly suggest that L-dopa administration is a potent stimulus for cortisol secretion at least in short children.

L-Dopa Stimulates Cortisol Secretion through Adrenocorticotropic Hormone Release in Short Children

Background/Aims: We recently showed that L-Dopa administration is a potent stimulator of cortisol secretion in children with short stature. Herein, we examined whether adrenocorticotropic hormone (ACTH) is implicated in the mechanism by which cortisol is stimulated during the L-Dopa test. Methods: Nineteen children with short stature who fulfilled the auxological criteria for growth hormone (GH) deficiency and had a subnormal GH response to glucagon stimulation underwent a second GH stimulation test (L-Dopa test). Serum GH, cortisol and plasma ACTH were determined at baseline and every 30 min up to 120 min after oral L-Dopa administration. Peak values of GH >10 ng/ml, cortisol >18 μg/dl and ACTH >52 pg/ml were considered as normal response. Results: Normal response rates were 10.5% (2/19) for GH, 94.7% (18/19) for cortisol and 68.4% (13/19) for ACTH. Among the children with a normal response in ACTH, its concentration increased from a basal value (mean ± standard deviation) of 23.3 ± 9.6 to 290.3 ± 221 pg/ml, almost always 90-120 min after L-Dopa administration. Mean peak cortisol was 36.2 ± 9.1 μg/dl, and it peaked almost simultaneously with ACTH. Conclusion: Our data suggest a stimulatory effect of the dopaminergic system on the hypothalamic-pituitary-adrenal axis.