Evaluation of the usefulness of antymüllerian hormone and inhibin B as markers of ovarian activity in patients with Turner syndrome - preliminary results.

INTRODUCTION: Spontaneous puberty occurs in 30% of patients with Turner Syndrome. Its absence is an indication for hormone replacement therapy (HRT). No reliable markers of spontaneous puberty have been defined to date. AIM OF THE STUDY: To evaluate the usefulness of antymüllerian hormone (AMH) and inhibin B assessment in predicting ovarian function and spontaneous puberty in girls with TS. MATERIAL AND METHODS: The study included 35 TS patients treated with human recombinant growth hormone (rhGH). Gonadal axis function parameters (LH, FSH and estradiol) were evaluated at the age of physiological puberty (10-12 years, mean 10.5 years), before introduction of HRT. Ad-ditionally AMH and inhibin B levels were assessed. In follow up patients were divided into 2 groups: with (SP) and without (WP) spontaneous puberty. Spontaneous puberty was defined as Tanner stage 2 or higher breast development. RESULTS: WP patients were observed until the mean age of 16y. SP occurred in 16 patients (mean age 10 years). Patients with SP presented with significantly lower mean FSH level (1.14-91.1 mIU/ml, mean mIU/ml 24.5 vs. 7.7-196.4 mIU/ml, mean 66.5 mIU/ml, p = 0.002), higher mean estradiol (10.5-68.8 pg/ml, mean 28.4 pg/ml vs. 6.1-26.0 pg/ml, mean 14.9 pg/ml, p = 0.005), AMH (0.0-3.11 ng/ml, mean 0.8 ng/ml vs. 0.0-0.002 ng/ml, mean 0.003 ng/ml, p = 0.001) and inhibin B (0.0-110.0 pg/ml, mean 29.1 pg/ml vs. 0.0-11.0 pg/ml, mean 1.06 pg/ml, p = 0.026) levels. In three SP patients without elevated FSH level (FSH < 35 mIU/ml) we found zero concen-tration levels of AMH and inhibin B. SP patients had mosaic (non 45,X) karyotype in 87.5% and WP patients only in 47%. CONCLUSIONS: AMH and inhibin B assessment may be a valuable complement to the diagnosis of ovarian function in patients with TS. Low levels of these parameters may indicate a risk of ovarian failure even in patients with spontaneous puberty and without hypergonadotropic hy-pogonadism.

Distinguishing between post-trauma pituitary stalk disruption and genetic pituitary stalk interruption syndrome - case presentation and literature overview.

INTRODUCTION: The diagnosis of post-trauma pituitary stalk transection, which is often life-threatening condition, is frequently delayed. In medical litera-ture still exist conflicting data concerning distinguishing this pathology with genetic developmental pituitary stalk interruption syndrome (PSIS). CASE PRESENTATION: We present a case of patient with post-trauma pituitary stalk transection resulting in combined life-threatening pituitary hormone defi-ciency (CPHD) and typical MRI picture: atrophic not visible stalk and posterior pituitary and hypotrophic anterior pituitary with most typical for this disorders hyperintense signal of distal regenerating axon of hypothalamus (pseudo posterior lobe) at median eminence with not visible posterior pituitary. This latter finding is often confused with ectopic posterior lobe in genetically determined PSIS. CONCLUSIONS: MRI image together with medical history of the head trauma and its strict temporal relation with transient diabetes insipidus and the occurrence of CPHD signs, as well as the lack of extrapituitary midline defects differentiate posttraumatic pituitary stalk transection syndrome (PSTS) from genetic PSIS. In every case of severe traumatic head injury hormonal evaluation and MRI of hypothalamic-pituitary axis should be performed.

The impact of thyroid function on the occurrence of metabolic syndrome in obese children and adolescents.

INTRODUCTION: Thyroid axis abnormalities are common in obese patients. Their contribution in the development of metabolic obesity complications remains unclear. AIM OF STUDY: To assess the influence of thyroid axis dysfunction on the occurrence of metabolic obesity complications. MATERIAL AND METHODS: A cross-sectional review of the thyroid function in 100 obese patients (59 girls and 41 boys, mean age 13.5 years) with alimentary obe-sity (mean standardised body mass index [BMI SDS] in boys 4.175 and girls 4.723) complicated by metabolic syndrome (MS) diag-nosed on the basis of the IDF 2006 criteria (MS, 25 patients) and uncomplicated (75 patients). TSH, fT4, fT3 thyroid peroxidase anti-bodies (TPOAb), and thyroglobulin antibodies (TGAb) were assessed in a single fasting blood sample. RESULTS: There was no case of overt thyroid disease within the whole analysed group. There were no significant differences in mean TSH, fT4, and fT3 levels in patients with and without MS (2.7 µIU/ml vs. 3.0 µIU/ml, 14.5 vs. 14.0 pmol/l, and 5.6 vs. 6.2, respectively; p > 0.05). In the MS group only two patients (8%) presented with a TSH level above the upper limit of the normal range; in the group without MS elevated TSH was noticed in 18 (24%) patients. The maximal value of TSH (10.44 µIU/ml) was noticed in one boy without MS. Positive TPOAb and/or TGAb were present in 11% of all patients: two patients (8%) with MS and nine (12%) without MS. CONCLUSIONS: Isolated increased TSH level is common in obese adolescents, although there is no correlation between TSH, fT3, and fT4 levels and BMI SDS value. Isolated increased TSH level is not associated with the occurrence of MS in obese adolescents. The occurrence of asymptomatic autoimmune thyroiditis (AITD) in obese adolescents is more common than in the general population.

Liver Biochemical Abnormalities in Adolescent Patients with Turner Syndrome

Objective: Elevated liver function tests (LFTs) are common in adult Turner syndrome (TS) patients. Data regarding children and adolescents are lacking. To investigate the prevalence of abnormal LFTs in children and adolescents with TS during several years of observation; to evaluate the potential impact of increased body mass index (BMI) and sex hormone replacement therapy (HRT) on LFTs. Methods: The analysis included 100 girls with TS, aged 4-16 years, all of whom were receiving recombinant human growth hormone therapy. A longitudinal study was conducted which included 81 patients. Results: Mean BMI-standard deviation (SD) score of the subjects was 0.63 (SD: 1.53). Forty-four were being treated with HRT. Elevated LFTs were found in 34% of the patients overall (32% not receiving HRT vs 36% on HRT). The relative risk of increased LFTs was not higher in obese vs normal weight [odds ratio (OR): 0.2; 95% confidence interval (CI): 0.1-0.36, p=0.38 vs OR: 0.16; 95% CI: 0.08-0.3, p=0.1]. HRT did not increase the risk of abnormal LFTs activity (OR: 0.8; 95% CI: 0.5-1.2, p=0.37 vs OR: 0.7; 95% CI: 0.4-1.1, p=0.27). During the follow-up period (mean±SD=4.31±0.82 years), no patient developed overt liver disease. There was no significant increase nor decrease of abnormal LFT frequency in the subsequent years of follow up. Conclusion: Constantly elevated LFTs in TS are common in children and adolescents with TS. However the causes and clinical significance remain unclear. This study suggests that obesity and HRT do not increase the risk of elevated LFTs.

Secondary Adrenal Insufficiency due to Intra-articular Glucocorticoid Injections.

BACKGROUND: The most common cause of hypothalamic-pituitary-adrenal axis suppression is systemic glucocorticoids administration. CASE CHARACTERISTICS: A 14-year-old boy with juvenile idiopathic arthritis receiving repeated intra-articular steroids for last 3 years developed fever, fatigue, nausea and abdominal pain. Stimulation with low-dose Synathen revealed low adrenal reserve, suggesting secondary adrenal insufficiency. OUTCOME: Temporary hydrocortisone substitution therapy improved condition. MESSAGE: Intra-articular steroids may cause potentially life-threatening suppression of the hypothalamic-pituitary-adrenal axis.

Adjusting insulin doses in patients with type 1 diabetes who use insulin pump and continuous glucose monitoring: Variations among countries and physicians.

AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.

Shall we diagnose metabolic syndrome in adolescents?

BACKGROUND: The clinical value of the diagnosis of metabolic syndrome (MS) in children and adolescents remains unclear. The aim of the present study was to assess the occurrence of metabolic complications, other than included in 2007 IDF MS definition, in obese children and adolescents METHODS: The study included 75 (33 boys) obese adolescents (mean age 13.9 years, mean BMI SDS 4.49). Classical (fasting glucose, TGL, HDL, blood pressure) and non classical (insulin resistance [HOMA-IR], creatinine, AST, ALT, uric acid, fibrinogen, liver US and 24h BP profile) risk factors were compared between groups with and without MS. 15(8 boys) met the 2007 IDF criteria for MS. RESULTS: Patients with MS presented with significantly lower: BMI SDS (4.2 vs. 5.8, p=0.02), mean 24h SBP (0.8 vs. 1.0, p=0.03), and uric acid level (352.1 vs. 414.0, p=0.01). In both groups a significant percentage of abnormal results of 24hABPM (up to 42.9 and 57.6%), insulin resistance (85.7 % and 61.1%), non alcoholic fatty liver disease (57.4 % and 38.9 %) and hyperuricemia (69.2 % and 55.3%) was observed. CONCLUSION: Recognizing the metabolic syndrome in adolescents does not provide any additional clinical benefits. It seems that in every obese child a wide, personalized diagnostic work-up should be performed.

Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results.

PURPOSE: The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). METHODS: In 14 TS (mean age 13.8), LE (17ß-estradiol, 62.5 µg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17ß-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. RESULTS: There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17ß-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 µIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. CONCLUSION: Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.