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The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0 years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962–1.000) and recurrent disease (AUC 0.856, 95% CI 0.715–0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75 ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05 ng/ml, 77.8%, 85.5%, 36.8%, and 97%. The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

Objectives Data regarding thyroid cancer (TC) epidemiology in Greece in the last decade are scarce, so we investigated the trends in TC detection during 2007 to 2016. Methods We retrospectively studied 2040 pathology reports of total thyroidectomies performed at our institution from 2007 to 2016. Results A number of 478 cases of TC were identified in the studied decade. The overall incidence of TC among thyroidectomies rose over the years. The proportion of papillary T1 tumors among thyroidectomies increased in the second period of our study (2012‐2016), while that of papillary T2 to T4 tumors and other TC subtypes remained unchanged. Papillary T1 tumors represented 63.6% of all TC cases and 75.3% of them were low‐risk microcarcinomas (papillary thyroid microcarcinoma). The strategy of fine needle aspiration (FNA) prior to surgery in the management of thyroid nodules was adopted by more clinical endocrinologists in the area of Southwestern (SW) Greece in the second period of our study (2012‐2016:29.7% vs 2007‐2011:18.4%, P, A rise in thyroid cancer detection was observed in Southwestern Greece the decade 2007‐2016, concerning mainly small and low‐risk papillary tumours. The increasing use of FNA in the triage of thyroid nodules is the main cause for this rise.

The aim of this review is to provide relevant information regarding the impact of thyroid disease, starting from birth and mainly concerning hyperthyroidism and hypothyroidism, on reproduction. Hyperthyroidism occurs much less commonly in children than hypothyroidism, with Graves' disease (GD) being the most common cause of thyrotoxicosis in children. Children born with neonatal GD have no defects in the reproductive system that could be related to hyperthyroidism. Current treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine (RAI). In males, normal thyroid function seems important, at least in some parameters, for maintenance of semen quality via genomic or non-genomic mechanisms, either by locally acting on Sertoli cells, Leydig cells, or germ cells, or by affecting crosstalk between the HPT axis and the HPG axis. Sexual behavior may also be affected in thyroxic men, although many of these patients may have normal free testosterone levels. In women, menstrual irregularities are the most common reproduction-related symptoms in thyrotoxicosis, while this disorder is also associated with reduced fertility, although most women remain ovulatory. An increase in sex hormone-binding globulin (SHBG) and androgens, thyroid autoimmunity, and an impact on uterine oxidative stress are the main pathophysiological mechanisms which may influence female fertility. Thyroid hormones are responsible for normal growth and development during pre- and postnatal life, congenital hypothyroidism (CH) being the most common cause of neonatal thyroid disorders, affecting about one newborn infant in 3500. The reproductive tract appears to develop normally in cretins. Today, CH-screening programs allow for early identification and treatment, and, as a result, affected children now achieve normal or near-normal development. Hypothyroidism in males is associated with decreased libido or impotence. Although little is currently known about the effects of hypothyroidism on spermatogenesis and fertility, it has been established that sperm morphology and motility are mainly affected. In women of reproductive age, hypothyroidism results in changes in cycle length and amount of bleeding. Moreover, a negative effect on fertility and higher miscarriage rates has also been described.

Background A new liquid levothyroxine (LT4) dissolved in glycerol and water has recently been developed by a Greek pharmaceutical company (Uni-Pharma, Athens, Greece). Objectives To evaluate the therapeutic equivalence of this new liquid LT4 preparation versus the already existing tablet formulation of the same manufacturer, in order to obtain approval by the Greek National Organization for Medicines. Methods This was a prospective, randomized, cross-over phase III study. The study included 50 patients (9 men and 41 non-pregnant women, with a mean age of 42.5 ± 12.5 years), with documented overt primary hypothyroidism. All subjects were well controlled on substitution therapy with various LT4 formulations. None of the patients had known LT4 malabsorption. The patients were randomized into 2 groups (A and B). The individuals of group A initially received T4® tablets for 10 ± 2 weeks and subsequently switched to T4® drops (100 μg/mL solution) at the same dose for another 10 ± 2 weeks. In group B, the reverse procedure was followed. Total T3 (T3), free T4 (fT4), and TSH were measured in all participants at enrollment and at the end of each 10 ± 2-week trial period. Results Out of the 50 recruited patients, 6 were lost to follow-up and 5 were excluded due to non-compliance with the study protocol. In the 39 patients who completed the study, the serum TSH levels after 10 ± 2 weeks of treatment either with T4® tablets or with T4® drops did not differ (1.759 ± 1.104 vs. 2.076 ± 1.334 mIU/L, mean ± SD). Conclusions In hypothyroid patients, the new liquid LT4 preparation (T4® drops) is therapeutically equivalent to the tablet form (T4® tablets).

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from −36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) is a common and deleterious side effect of amiodarone use. There are two types of AIT, characterized by distinct pathogenic mechanisms and, hence, different treatments. Discriminating between type 1 (AIT1) and type 2 (AIT2) AIT is often very challenging. Beta-glucuronidase (β-G) is a lysosomal enzyme released into the extracellular fluid during inflammation. OBJECTIVES: To examine whether the determination of the plasma activity of β-G is useful in distinguishing AIT1 from AIT2. METHODS: The study included 67 subjects: 9 with AIT1, 9 with AIT2, 14 with hyperthyroidism due to Grave's disease or toxic multinodular goiter, 14 with subacute thyroiditis, and 21 euthyroid controls. Thyroid function tests and plasma β-G activity were determined in all participants, while thyrotoxic patients also underwent thyroid ultrasound/scintigraphy and urine iodine excretion assessment. RESULTS: Plasma β-G activity (expressed as mean ± SD in nmol 4-methylumbelliferone [4-MU]/mL plasma/h) in AIT2 was higher compared to AIT1 (2,263.6 ± 771 vs. 1,101.8 ± 201.9, p < 0.05) and similar to subacute thyroiditis (2,263.6 ± 771 vs. 2,083.2 ± 987.5, p = ns). β-G activity did not differ significantly between AIT1 and controls (1,101.8 ± 201.9 vs. 954.6 ± 248.6, p = ns). ROC curve analysis revealed that β-G activity had a high predictive value for destructive processes, namely AIT2 and subacute thyroiditis (AUC 0.846, 95% CI 0.748–0.943) and a cut-off value of 1,480.5 nmol 4-MU/mL plasma/h was able to discriminate between destructive and non-destructive thyroid conditions with 74% sensitivity and 82% specificity. CONCLUSION: In our study, plasma β-G activity performed well in distinguishing AIT1 from AIT2. Further studies are warranted to establish its usefulness as a discriminator between the two AIT types.

Objective: To assess the reliability of thyroglobulin (Tg) as a marker of iodine status during pregnancy. Design: 299 women aged 30.5 ± 4.8 years (mean ± SD) were studied. Methods: In every subject, we measured urinary iodine concentration (UIC), serum thyrotropin (TSH), Tg, free thyroxine (fT4), Tg autoantibodies (TgAbs) and human chorionic gonadotropin (hCG) levels. We excluded samples with increased TgAbs from the analysis. Results: According to WHO criteria, the study population was iodine deficient in every trimester. Serum Tg levels did not differ during the three trimesters of pregnancy. Serum hCG levels fell significantly as pregnancies advanced. A weak, significantly negative correlation (limited to the 3rd trimester) was found between Tg and UIC (ρ = -0.187, p = 0.039). Serum fT4 decreased as pregnancies advanced and TSH increased. Serum fT4 was negatively correlated with TSH (ρ = -0.161, p = 0.006) and positively with hCG (ρ = +0.165, p = 0.005). The multiple regression equation of Tg based on hCG, TSH, UIC and trimester of pregnancy was significant but weak (F = 4.057, p = 0.003; R2 = 0.055), with hCG as a significant predictor Tg (p for log hCG = 0.041). Conclusions: Tg cannot be considered as a valid marker of iodine deficiency in pregnancy, at least in a mildly iodine-deficient environment. Further studies in a larger patient cohort with differences in iodine status, as well as studies on Tg changes after improving iodine status in pregnant women, are needed in order to corroborate these results.

OBJECTIVE: To evaluate the effect of prolonged intensive aerobic exercise and acute energy deficit (180 km ultra-marathon race) on serum leptin, adiponectin, resistin and visfatin levels and their association and interaction with serum cortisol and insulin levels in highly trained ultra-endurance runners. DESIGN: The study included 17 highly trained ultra-endurance male athletes (mean age 51.29±6.84 years and body mass index (BMI) 23.51±1.90) participating in the 5th Olympian Race held in Greece on May 2010. Anthropometric values were assessed; serum cortisol, insulin, leptin, adiponectin, resistin and visfatin levels were measured at baseline, post-exercise and ∼20 hours after the end of the race. RESULTS: All hormonal values of the post-exercise and recovery status were corrected for plasma volume changes. The estimated energy deficit during the ultra-endurance event was about 5000 Kcal. At the end of the race serum resistin levels were elevated (p

BACKGROUND The current trend in the management of low risk differentiated thyroid carcinoma is to follow less aggressive strategies. OBJECTIVE To assess the long-term morbidity and mortality outcomes of low-risk papillary thyroid carcinoma (PTC) patients undergoing minimal intervention. DESIGN We retrospectively analyzed 137 patients with low-risk PTC (stage I: n=77; stage II: n=60). Of these patients, 107 (Group 1) had macro-PTC and underwent near-total thyroidectomy and received postoperatively 50mCi RAI. The remaining 30 patients (Group 2) had micro-PTC (

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention. Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds. EUthyroid info:eu-repo/grantAgreement/EC/FP7/634453

Exercise challenges homeostasis and establishes a new dynamic equilibrium. Elite Rhythmic Gymnasts (RG's) begin exercise at an early age, undergo physical and psychological stress, and adopt negative energy balance to retain a lean physique. The aim of the present study was to evaluate the effect of negative energy balance, acute and chronic exercise on salivary adiponectin, resistin and visfatin levels and their interaction with salivary cortisol, and insulin levels in elite RG's. This study is unique in character, as all variables were assessed on the field of competition. The study included 51 elite RG's participating in "Kalamata 2010 World Cup" in Kalamata, Greece on April 2010. Twenty-seven healthy age-matched girls were used as controls. Anthropometric values were assessed; baseline and post exercise salivary cortisol, insulin, adiponectin, resistin, and visfatin levels were measured. Comparisons regarding hormonal features between RG's and controls were adjusted for BMI and body fat percentage. Salivary adiponectin levels were higher (p0.05) and visfatin lower (p=0.094) in RG's compared with controls, while no significant changes were observed regarding salivary cortisol, insulin, and resistin levels. In elite RG's acute intensive anaerobic exercise led to increased salivary insulin levels (p0.001), reduced salivary adiponectin (p0.001) and visfatin levels (p0.05), and no changes in salivary resistin levels. Moreover, diurnal variation of salivary cortisol was lost. In elite RG's salivary adiponectin is upregulated and salivary visfatin is downregulated after chronic intensive exercise and negative energy balance, while both salivary adiponectin and visfatin levels are suppressed after short term intensive anaerobic exercise.

The aim of this study was to determine the impact of intensive training on adult final height in elite female rhythmic and artistic gymnasts. The study included 215 rhythmic gymnasts (RG) and 113 artistic gymnasts (AG). AG were below the 50th percentile, while RG were taller than average. Final adult height was lower than target height in AG, while in RG, it exceeded target height. AG started training earlier than RG (p

Suppressive or replacement doses of levothyroxine (LT4) are affected by the rate and extent of the active ingredient absorbed, as well as by the lean body mass. Obesity has reached epidemic proportions worldwide and is related with many comorbidities. The aim of this study was to determine the pharmacokinetic parameters of LT4 in severely obese individuals and compared them with similar data in lean control subjects.We studied 62 euthyroid subjects who had negative tests for anti-thyroid peroxidise antibodies (Ab-TPO). Thirty eight of these subjects were severely obese but otherwise healthy (severe obese subjects [SOS] group). Twenty-four were healthy control subjects (control group), with a body mass index of 23.3 ± 1.7 kg/m(2). Subjects received 600 μg oral sodium LT4 after an overnight fast. Serum triiodothyronine (T3), T4, and thyroid-stimulating hormone were measured at baseline. Serum T4 and T3 was measured 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours after LT4 administration.Baseline serum T4 and thyroid-stimulating hormone concentrations were higher in the SOS group than in the control group; serum T3 was similar in the two groups. The corrected area under the curve and the maximum T4 concentration after LT4 administration were lower, whereas the time to maximum concentration from the baseline was higher in SOS than in the control group. The estimated plasma volume was higher in the SOS than in the control group. Mean serum T3 levels increased gradually during the four hours after LT4 administration in the control group. In contrast, they decreased gradually in the SOS group.Severely obese individuals may need higher LT4 suppressive or replacement doses than normal-weight individuals due, among other factors, to impaired LT4 pharmacokinetic parameters. The latter could be attributed to their higher plasma volume and/or to delayed gastrointestinal LT4 absorption. T4 conversion to T3 might be defective in severe obesity.

The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol in elite artistic gymnasts (AGs).The study included 239 AGs (142 females-97 males) who participated in the European Championship of Gymnastics in 2006 and 81 adolescents (40 females-41 males), matched for age, as controls. All athletes participated voluntarily in all or parts of the study, providing samples or data for each of the variables measured. Height, weight, body fat, lean body mass (LBM), bone age and Tanner stage of puberty were assessed and data concerning the time of thelarche, adrenarche and menarche as well as, the onset and the intensity (hours per week) of training were obtained.Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. From controls, the saliva samples were collected in the morning. Cortisol concentrations were measured using a chemiluminescence method. Acute stress was assessed using a questionnaire designed for the study.No difference was found between morning and afternoon salivary cortisol levels in both male and female AGs (females: AM: 15.45±7.45nmol/l vs PM: 15.73±9.38nmol/l; males: AM: 10.21±5.52nmol/l vs PM: 9.93±13.8nmol/l, p0.05). Female AGs presented higher levels of morning salivary cortisol than female controls (p0.05). Both male and female AGs had higher degree of psychological stress in comparison with controls (p0.001, p0.013, respectively). Female AGs had higher morning and afternoon salivary cortisol levels (p0.01, p0.01, respectively) and higher degree of stress (p0.003) than males.In elite AGs the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AGs presented higher levels of morning salivary cortisol and psychological stress compared to both male AGs and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.

Genetic potential for growth can be fully expressed only under favorable environmental conditions. Although moderate physical activity has beneficial effects on growth, excessive physical training may negatively affect it. Sports favoring restricted energy availability, in the presence of high energy expenditure, are of particular concern. In gymnastics, a different pattern in skeletal maturation and linear growth was observed, resulting in an attenuation of growth potential in artistic gymnasts (AG), more pronounced in males than in females. In female rhythmic gymnasts (RG), the genetic predisposition to growth was preserved owing to a late catchup growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented so far. Intensive physical training and negative energy balance alter the hypothalamic pituitary set point at puberty, prolong the prepubertal stage, and delay pubertal development and menarche in a variety of sports. In elite RG and AG, prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, following the bone maturation rather than the chronological age.

Bone mass (BM) and skeletal size are similar in prepubertal girls and boys and double between the onset of puberty and early adult life. Sex steroids are responsible for the maturation in human skeleton, as well as for the sexual dimorphism, observed after the onset of puberty. Physical activity in childhood is critical for maximizing bone growth and thus for preventing osteoporosis during older age. Therefore, it constitutes the most effective prevention strategy available. In athletes, high-impact loading activities have been shown to improve BM, whereas in sports requiring a lean somatotype (therefore leading to a negative energy balance), the delay in skeletal maturation and pubertal development predisposes athletes to osteopenia and osteoporosis. Although the early onset of training, the continuous intensive exercise and its long duration attenuate bone acquisition, the excess mechanical load to which these athletes are exposed from a young age exerts beneficial effects on bone formation that lead to a positive net-effect on BM.

Objective To evaluate basal metabolic rate (BMR) in women with PCOS and to determine its association with insulin resistance (IR). Design Prospective assessment of BMR in women with PCOS. Setting Outpatient clinic of the Division of Reproductive Endocrinology. Patient(s) The study included 91 Greek women with PCOS and biochemical hyperandrogenemia, with mean age 24.03 ± 0.55 years and mean body mass index (BMI) 26.67 ± 0.69 kg/m 2 , and 48 matched regularly menstruating women, with mean age 26.33 ± 0.93 years and mean BMI 23.35 ± 0.85 kg/m 2 , as control subjects. Intervention(s) Assessment of BMR by indirect calorimetry, IR by HOMA and QUICKI indices, fasting insulin, and fasting glucose/insulin ratio. Main Outcome Measure(s) Reduced BMR in PCOS with or without IR. Result(s) Adjusted BMR was 1,868 ± 41 kcal/day in the control group, 1,445.57 ± 76 in all PCOS women, 1,590 ± 130 in PCOS women without IR and 1,116 ± 106 in PCOS women with IR. Adjusted BMR showed a statistically significant difference between women with PCOS and control subjects, with lowest values in the group of PCOS women with IR, even after adjusting all groups for age and BMI. Conclusion(s) Women with PCOS, particularly those with IR, present a significantly decreased BMR.

Nontoxic nodular goiter (NTNG) is common in endemic goiter regions. Thyroxine (T4) is often used to treat NTNG. There is little information regarding T4 treatment in regions that have recently become iodine sufficient. We studied the effect of T4 treatment on thyroid function tests in southwestern Greece (SWG), a recently iodine-sufficient area.We studied 827 residents of SWG (group A) to determine goiter prevalence, thyroid function, and urinary iodine concentration (UIC). Group B: 385 consecutive patients with thyroid dysfunction. Of these, 89 had NTNG and followed for 10 years on T4 treatment, and 296 had hyperthyroidism. Group C: 29 patients with NTNG, treated with triiodothyronine (T3) 50 mug/day and followed for 6 months. Measurements included serum T4 and 24-hour radioactive iodine uptake (RAIU) before and at the end of T3 administration.The median UIC in group A was 114 microg/L. In group B (89 patients), the incidence of newly diagnosed hyperthyroidism was 5-7% per year with a cumulative percentage of 33% at the 10th year. The initial thyrotropin (TSH) was lower (0.78 +/- 0.51 mIU/L) in those who developed thyrotoxicosis compared to those who remained euthyroid (1.17 +/- 0.74 mIU/L) (p0.05). In 296 thyrotoxic patients, the incidence of autoimmune hyperthyroidism and toxic multi-nodular goiter (TMNG) was similar. In group C, 10/29 patients remained euthyroid and the 24-hour RAIU decreased by 49% during T3 treatment. Similarly, serum T4 decreased by 49%. In the remaining patients who developed hyperthyroidism, 24-hour RAIU and T4 were decreased by 19% and 22%, respectively.In SWG, a recently iodine-sufficient region, the risk of developing hyperthyroidism in patients with NTNG after administration of 100-150 microg T4 is relatively high in those whose serum TSH before T4 treatment is in the lower normal range. Therefore, T4 treatment should be avoided in these patients.

The aim of the present study was to examine the effects of chronic iodide administration in pharmacological doses on thyroid function in children with a history of transient congenital hypothyroidism (TCH). We hypothesized that such children may carry a previously undisclosed intrinsic intrathyroidal defect, rendering them susceptible to TCH. We administered for this 60-65 mg iodide daily for 60 d in 13 individuals with TCH (group A), 8 of their siblings (group B), 8 healthy controls (group C), and 11 normal adults (group D). Thyroid function was evaluated by measuring serum T(3), T(4), free T(3), free T(4), TSH, and thyroglobulin concentrations and autoantibodies against thyroid peroxidase and thyroglobulin at baseline at 15, 30, and 60 d during iodide administration, and 2 months after iodide withdrawal. Hyperthyrotropinemia greater than 4.2 mU/liter but not higher than 10 mU/liter with normal thyroid hormone concentrations was observed in one of the TCH group and in two of the group B siblings. During iodide administration, hyperthyrotropinemia was observed in 8 of 13 (62%) adolescents in group A, 4 of 7 (57%) in group B, and 6 of 8 (75%) in group C. None of the 11 adults (group D) developed hyperthyrotropinemia during iodide administration. Serum T(4) and free T(4) concentrations were decreased in all groups when compared with baseline values. The magnitude of the decrease of serum T(4) was identical in all groups (0.7-0.8 microg/dl). Thyroid enlargement was observed in all subjects and was more pronounced in children. There were no cases of subclinical and/or overt hyperthyroidism. After iodine withdrawal, serum TSH decreased in all groups and returned to baseline levels, as well as the thyroid volume. In conclusion, the hypothalamic-pituitary-thyroid axis of adolescents with TCH responds to pharmacological doses of iodide similarly to that observed in normal children. The hyperthyrotropinemia observed in the adolescents exposed to iodides may reflect incipient transient hypothyroidism or simply a brisk TSH response to a small serum T(4) decrease. Whatever the mechanism, chronic use of excessive quantities of iodide should be avoided until the end of puberty.

We studied 129 female rhythmic gymnasts (RG) and 142 female artistic gymnasts (AG) who participated in the 1999 Gymnastics World Championship for RG in Osaka, Japan, and the 1999 and 2001 Gymnastics World Championships for AG in Tianjin, China (n 48), and Ghent, Belgium (n 94), respectively. RG were taller than average, with a mean height SD score above the 50th percentile, whereas AG were relatively short, with a mean height SD score below the 50th percentile. Both RG and AG followed their respective reported target height SD score, which was above the 50th percentile for the RG and below the 50th percentile for the AG. The RG followed a growth pattern that was higher than their reported target height, whereas AG exhibited a negative growth pattern. RG and AG weighed less than the population mean, with the mean weight for age below the 50th percentile for both groups. RG were taller than AG (t 17.15; P < 0.001), with a higher reported target height SD score (t 6.44; P < 0.001), a greater height-reported target height (t 2.74; P < 0.001), and a lower mean body fat (t 11.83; P < 0.001) and body mass index (t 10.73; P < 0.001) than AG. AG started their training at an earlier age than RG (t 4.13; P < 0.001). Using multiple regression analysis, actual height SD score was independently influenced positively by weight SD score for both RG (b 0.421; t 4.317; P < 0.001) and AG (b 1.404; t 16.514; P

The two traditional methods for the assessment of iodine deficiency in a given area are the estimation of urinary excretion of iodine, and the prevalence of goiter. In field studies, the estimation of urinary iodine excretion (UIE) in random urine specimens provides an adequate assessment of a population's iodine nutrition. The recommended method is the classic one, based on Sandell-Kolthoff reaction (Method A). Recently, a new semi-quantitative method has been introduced (rapid urinary iodide test [RUIT]). We performed a field study in a developing country (Azerbaijan) in order to compare the classic Method A to RUIT. The study included 942 schoolchildren, to whom UIE was estimated by RUIT. Comparing the two methods, (n = 260), the sensitivity of RUIT using as gold standard Method A, was 96% and the specificity was 61%. The correlation between median values UIE estimated by RUIT and by Method A was excellent (r = 0.98, p < 0.001). An agreement in iodine deficiency classification according to the World Health Organization-United Nations Children's Fund-International Council for the Control of Iodine-Deficiency Disorders (WHO-UNICEF-ICCIDD) between the two methods was observed in eight of nine areas. In conclusion, RUIT is a suitable method for UIE estimation in field studies of suspected iodine deficiency. The test is relatively inexpensive, easy to perform, and does not require sophisticated instruments.

OBJECTIVE: Adequate dietary iodine intake is necessary for normal thyroid gland function at all times, and most particularly during pregnancy. Increased iodine loss is cited, among other factors, as responsible for the increased iodine demand in this period. Our aim was to compare renal iodine excretion between women during all three pregnancy trimesters with that of their spouses and thereby to estimate the iodine intake in an a large sample of pregnant women in urban areas in Greece. DESIGN: Four hundred twenty-four healthy pregnant women were included prospectively (residents of Athens n=218, residents of Patras n=206). The spouses of 177 of these women following the same diet were also studied. Determinations included serum FT4, TSH and aTPO and urinary iodine excretion (UIE). RESULTS: No difference was found either in median UIE throughout pregnancy or between the UIE of the pregnant women and their spouses during the trimesters. Throughout pregnancy, mild iodine deficiency was noted and was classified as mild in 60%, moderate in 30% and severe in 10% of the women studied. Users of iodized salt had significantly higher median UIE compared with non-users. Serum FT4 levels decreased and TSH increased as pregnancy progressed. CONCLUSIONS: Our study indicates that renal iodine excretion is not increased during pregnancy. This finding needs to be confirmed by further investigation in other populations with different iodine intakes. Thus, increased iodine requirements in pregnancy are possibly due to extra-renal causes. The population of pregnant women in Greek urban areas is mildly-and often moderately and severely-iodopenic and needs to be treated accordingly.

Two middle aged Caucasian women with no previous history of thyroid or any other disease developed typical subacute thyroiditis (SAT) with minimal thyroidal radioactive iodine uptake. A few months after restoration of euthyroidism and discontinuation of corticosteroid therapy, they developed mild hyperthyroidism due to Graves’ disease (GD), as judged by the increased diffuse thyroidal radioactive iodine uptake. Both of them were genetically predisposed to the above diseases since they had the certain HLA haplotypes for SAT and GD. Also they developed anti- thyroglobulin antibodies during the period of GD. We hypothesize that genetic background and the increased load of Tg or other autoantigens released from the distracted damaged thyroid gland due to SAT triggered the development of GD a few months later.

The goal of this study was to assess the prevalence of iodine deficiency (ID) in Azerbaijan after the discontinuation of an iodine prophylaxis program by assessing the prevalence of goiter, iodine intake, and thyroid function. The study included 942 schoolchildren (475 boys and 467 girls) ages 8-14 years, from 13 distinct regions. The survey included the following: (1) clinical evaluation; (2) assessment of thyroid volume both by ultrasound and by palpation; (3) determination of iodide in a morning urine specimen using the classic Sandel-Kolthoff reaction in 347 schoolchildren; (4) determinations of thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and anti-thyroid peroxidase (TPO) in serum (n = 165) and TSH in whole blood spotted on filter paper (n = 942). The prevalence of goiter for the whole country was determined by ultrasound (US) to be 86% and by palpation 66%, reaching 100% in the mountainous regions of Caucasus. The median urinary iodine excretion (UIE) was 54 microg/L, reaching level of 26 and 39 microg/L in the Caucasus region. In conclusion, according to the World Health Organization (WHO) classification, Azerbaijan now has mild to moderate ID (median UIE, 54 microg/L) and in the mountainous regions with severe ID. The high prevalence of goiter and the low UIE emphasizes the need for urgent medical reintervention. An iodination program is now implemented by our team in the mountainous regions under the auspice of the government of Azerbaijan.

Rhythmic gymnasts performing under conditions of high intensity are exposed to particularly high levels of psychological stress and intense physical training, factors that can contribute to the observed delay in skeletal maturation and pubertal development, and alter optimal growth. The study was conducted in the field, during the International, European, and World Rhythmic Sports Gymnastics Championships of the years 1997-2000, and included 104 elite female rhythmic gymnasts, aged 12-23 yr. The study included height and weight measurements, estimation of body fat and skeletal maturation, and registration of parental height. Height, weight, target height, and predicted adult height were expressed as the SD score of the mean height and weight for age, according to Tanner's standards. Gymnasts were taller and thinner than average for age, with height velocity SD score for each age group above the 50th percentile for all age groups (n = 140, mean = 1.9 +/- 2.5). Interestingly, although height velocity in normal girls comes to an end by the age of 15, in our examined rhythmic gymnasts it continues up to the age of 18. There was a delay of skeletal maturation of 1.8 yr (n = 72, r = 0.730, P < 0.001), compensated by an acceleration of height velocity toward the end of puberty. The final adult height was identical to the estimated predicted height at first evaluation, and significantly higher than the genetically determined target height (n = 35, r = 0.58, P < 0.001), denoting that genetic predisposition to final height is not only achieved, but even exceeded. Using multiple regression analysis, target height was the only independent parameter that has been proven to influence positively the height velocity SD score (b = 0.233, t = 2.215, P = 0.029), denoting that genetic predisposition remains the main driving force for the observed efficient catch up growth. In conclusion, the elite rhythmic gymnasts compensate for their loss of pubertal growth spurt by a late acceleration of linear growth. Despite the delay in skeletal maturation, genetic predisposition of growth is not only preserved, but even exceeded.

Iodine is an essential element for thyroid hormone synthesis. The thyroid gland has the capacity and holds the machinery to handle the iodine efficiently when the availability of iodine becomes scarce, as well as when iodine is available in excessive quantities. The latter situation is handled by the thyroid by acutely inhibiting the organification of iodine, the so-called acute Wolff-Chaikoff effect, by a mechanism not well understood 52 years after the original description. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones. The acute Wolff-Chaikoff effect lasts for few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns. This is achieved by decreasing the intrathyroidal inorganic iodine concentration by down regulation of the sodium iodine symporter (NIS) and therefore permits the TPO-H202 system to resume normal activity. However, in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues. Iodide-induced hypothyroidism has also been observed in patients with a history of postpartum thyroiditis, in euthyroid patients after a previous episode of subacute thyroiditis, and in patients treated with recombinant interferon-alpha who developed transient thyroid dysfunction during interferon-a treatment. The hypothyroidism is transient and thyroid function returns to normal in 2 to 3 weeks after iodide withdrawal, but transient T4 replacement therapy may be required in some patients. The patients who develop transient iodine-induced hypothyroidism must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

The absorption of levothyroxine (LT4) is affected by many factors. Bariatric surgery is recommended in severely obese patients. The aim of this study was to determine the consequences of bariatric surgery on LT4 pharmacokinetic parameters, and to identify the regions of the gastrointestinal tract where LT4 is absorbed in patients with severe obesity before and after surgery.We studied 32 severely obese nonhypothyroid patients who underwent sleeve gastrectomy (SG; n=10), Roux-en-Y gastric bypass (RYGBP; n=7), or biliopancreatic diversion with long limbs (BPD-LL; n=15). Before surgery, from 8:00 a.m., blood samples were collected before and every 30 minutes after the oral administration of a solution of 600 μg of LT4. The same procedure was repeated 35 days after surgery. We estimated the pharmacokinetic parameters of LT4 before and after surgery, including the area under the curve (AUC), the peak thyroxine concentration (Cmax), and the time to peak thyroxine concentration (Tmax).Following surgery, in the SG group, the mean AUC was higher than it was before surgery (18.97±6.01 vs. 25.048±6.47 [μg/dL]·h; p0.01), whereas the values of Cmax and Tmax were similar to those before surgery. In the RYGBP group, mean AUC, Cmax, and Tmax were similar before and after surgery. In the BPD-LL group, mean AUC and Cmax were higher after surgery than before (14.18±5.64 vs. 25.51±9.1 [μg/dL]·h, p0.001; 5.62±1.34 vs. 8.16±2.57 μg/dL, p0.001, respectively), whereas Tmax was similar.The pharmacokinetic parameters of LT4 absorption are improved following SG and BPD-LL types of bariatric procedures. We conclude that the stomach, the duodenum, and the upper part of the jejunum are not sites for LT4 absorption, because in the above-mentioned bariatric procedures these are bypassed or removed.

Objective Thyroid hormone, requiring adequate maternal iodine intake, is critical for neurodevelopment in utero. Perchlorate and, less so, thiocyanate decrease uptake of iodine into the thyroid gland by competitively inhibiting the sodium/iodide symporter (NIS). It remains unclear whether environmental perchlorate exposure adversely affects thyroid function in first-trimester pregnant women. Design Cross-sectional. Patients 134 pregnant women from Athens, Greece, at mean ± SD 10·9 ± 2·3 weeks' gestation. Measurements Urinary iodide, perchlorate, and thiocyanate and thyroid function tests were measured. Results The median urinary iodide was 120 μg/l. Urinary perchlorate levels were detectable in all women: median (range) 4·1 (0·2–118·5) μg/l. Serum thyroperoxidase antibodies (TPO Ab) were detectable in 16% of women. Using Spearman's rank correlation analyses, there was no correlation between urinary perchlorate concentrations and serum TSH, although inverse correlations were seen between urine perchlorate and free T3 and free T4 values. In univariate analyses, urine thiocyanate was positively correlated with serum TSH, but was not associated with serum free T3 or free T4. Urine perchlorate was positively correlated with gestational age. In multivariate analyses adjusting for urinary iodide concentrations, urine thiocyanate, gestational age, maternal age and TPO Ab titres, urine perchlorate was not a significant predictor of thyroid function. Conclusions Low-level perchlorate and thiocyanate exposure is ubiquitous, but, in adjusted analyses, is not associated with alterations in thyroid function tests among mildly iodine-deficient Greek women in the first trimester of pregnancy.

OBJECTIVE Elite male artistic gymnasts (AG) are exposed to high levels of physical and psychological stress during adolescence and experience a significant late maturation in both linear growth and pubertal development. The aim of the present study was to determine the impact of intensive physical training on the adult final height in elite male AG. METHODS This study is unique in character, as all variables were measured on the field of competition. The study was prospective and longitudinal; however, the current analysis of data is cross-sectional. Data from 86 elite male AG were obtained during the gymnastics competitions of European and World Championships. Clinical evaluation included height and weight measurements, as well as assessment of pubic hair and genital development according to Tanner's stages of pubertal development. The laboratory investigation included determination of skeletal maturation. All athletes completed a questionnaire that included questions on personal (onset and intensity of training, number of competitions per year) and family data (paternal and maternal heights). RESULTS Male AG were below the 50th percentile for both final height and weight. Elite male AG had final height standard deviation score (SDS) lower than their genetic predisposition. Final height SDS was correlated positively with target height SDS (r = 0.430, p < 0.001) and weight SDS (r = 0.477, p < 0.001) and negatively to the intensity of training (r = -0.252, p = 0.022). The main factors influencing final height, by multiple regression analysis were weight SDS (p < 0.001) and target height SDS (p = 0.003). CONCLUSION In elite maleAG, final height falls short of genetic predisposition, still well within normal limits. Considering medical and psychological risks in general, and based on the results of this research project, the International Federation of Gymnastics has increased the age limit for participants in international gymnastics competitions by 1 year.

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p

OBJECTIVE: To evaluate the rate of complications and the risk factors in relation to the extent of surgery in patients undergoing thyroidectomy in a tertiary university center. DESIGN: Data were collected retrospectively from 2,043 consecutive patients who underwent thyroid surgery for various thyroid diseases at the University Hospital of Patras, Greece, between January 1996 and December 2007. recurrent laryngeal nerve palsy (rLNP) and hypoparathyroidism were set as the primary end points, while hematoma and wound infection were set as the secondary endpoints. rESULTS: Total, near-total and subtotal thyroidectomy was performed in 1,149, 777 and 117 patients, respectively. Transient rLNP occurred in 34 (1.6%) and permanent in 19 (0.9%) patients. Multivariate logistic regression analysis showed that extended resection (Or-odds ratio-1.6), Graves’ disease (Or 2.7), thyroiditis (Or 2.1), recurrent goiter (Or 2.3) and thyroid malignancy (Or 1.7) were all independent risk factors for transient rLNP, whereas Graves’ disease (Or 2.2) and recurrent goiter (Or 1.7) emerged as independent risk factors for permanent rLNP. The rates of transient and permanent hypoparathyroidism were 27.8% and 4.8%, respectively. Multivariate analysis for transient hypoparathyroidism revealed that the extent of surgical resection (Or 2.2), Graves’ disease (Or 2.1), recurrent goiter (Or 1.7), female gender (Or 1.5) and specimen weight (Or 1.6) were independent predictors. However, the extent of surgical resection (Or 2.7), Graves’ disease (Or 1.8), recurrent goiter (Or 1.5) and malignant disease (Or 1.5) were independent risk factors for permanent hypoparathy roidism. Postoperative wound infection and hematoma occurred in 6 (0.3%) and 27 (1.3%) patients, respectively. No correlation was observed between wound infection or postoperative hemorrhage and the extent of surgery. CONCLUSIONS: Despite the higher morbidity, total thyroidectomy is emerging as an attractive surgical option even for benign thyroid disease due to the risk of subclinical (occult) malignancy, the possibility of goiter relapse as well as of the increased risk of complications following reoperation.

Bone mass (BM) and skeletal size are similar in prepubertal girls and boys and double between the onset of puberty and early adult life. Sex steroids are responsible for the maturation in human skeleton, as well as for the sexual dimorphism, observed after the onset of puberty. Physical activity in childhood is critical for maximizing bone growth and thus for preventing osteoporosis during older age. Therefore, it constitutes the most effective prevention strategy available. In athletes, high-impact loading activities have been shown to improve BM, whereas in sports requiring a lean somatotype (therefore leading to a negative energy balance), the delay in skeletal maturation and pubertal development predisposes athletes to osteopenia and osteoporosis. Although the early onset of training, the continuous intensive exercise and its long duration attenuate bone acquisition, the excess mechanical load to which these athletes are exposed from a young age exerts beneficial effects on bone formation that lead to a positive net-effect on BM.

Iodine deficiency (ID) is still a major universal health problem. Iodine deficiency disorders (IDDs) affect people of all ages, among whom the most vulnerable are children and adolescents. The aim of the present study was to assess the long-term effects on growth and pubertal development of correcting severe ID in areas of Azerbaijan between 1999 and 2000.Iodized oil was administered orally to 293,000 children, aged 6-16 years. Among those, 364 children were randomly selected and were examined 1 year before the administration of iodized oil (Group I-neg, iodine negative) and 295 children (Group I-Rx, iodine treated) were examined 4 years (Group I-R x 4, iodine treated 4 years later; n = 173) or 5 years (Group I-R x 5, iodine treated 5 years later; n = 122) after the last dose of iodide.In Group I-neg the median urine iodine concentration (UIC) (mcg/L) was 36 (mean: 36.272 +/- 11.036) and increased significantly (p0.001) in Group I-R x 4: 188 (mean: 230.969 +/- 155.818) and in Group I-R x 5: 175 (mean: 201.176 +/- 130.369). The prevalence of goiter was 99% in Group I-neg and 2% in Group I-R x 4. Children in Group I-Rx had a greater standard deviation score (SDS) for height (-0.1364 +/- 1.279, n = 294) than children in Group I-neg (-0.5019 +/- 1.17, n = 363) (p0.001, t = -3.817), which was more significant for boys. SDS for weight was similar in both groups (Group I-neg: -0.17 +/- 0.78, n = 363; Group I-Rx: -0.115 +/- 0.917, n = 294). The rate of puberty development as judged by the development of breast and pubic hair was normalized in both sexes after the correction of ID.Our results demonstrate that long-term correction of severe ID leads to sustained improvement of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.

Objective To evaluate the association of an activating single-nucleotide polymorphism (SNP) at position −71 of the promoter of 17β-hydroxysteroid dehydrogenase type 5 gene (−71A/G HSD17B5 SNP) and polycystic ovary syndrome (PCOS) in a well characterized cohort of caucasian PCOS women with biochemical hyperandrogenemia. Design The PCOS patients and unrelated healthy control subjects were genotyped for the −71A/G HSD17B5 SNP. The acquired genotypic data was tested for association with PCOS and other quantitative phenotypic traits of the syndrome in PCOS patients. Setting Subjects were recruited from the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, at the University Hospital of Patras, Greece. Genotyping and biochemical determinations took place at the Laboratory of Molecular Endrocinology, University of Patras Medical School, Rion, Greece. Patient(s) Participants comprised 150 caucasian Greek PCOS women with biochemical hyperandrogenism and chronic anovulation and polycystic ovarian morphology on ultrasound and 51 healthy control subjects. Main Outcome Measure(s) HSD17B5 genotype, serum testosterone, serum androstenedione. Result(s) No association of the −71A/G HSD17B5 SNP with PCOS was detected. However, the −71G HSD17B5 variant was associated with increased serum testosterone levels and decreased androstenedione/testosterone ratio. Conclusion(s) The −71G HSD17B5 variant is not a major component of the molecular pathogenetic mechanisms of PCOS, although it might contribute to the severity of hyperandrogenemia in women with PCOS and biochemical hyperandrogenism.

Fibroids or leiomyomas or myomas of the uterus are the most common benign gynecologic disease, while fibroadenomas of the breast are most frequently seen in young women, usually within 20 years after puberty. Multiple tumors in one or both breasts are found in 10-15% of patients. Single thyroid nodules are much more common in women than in men, and their prevalence increases with age. The aim of the present study was to determine cross-sectionally the incidence of solitary thyroid nodules and fibroadenomas of the breast in women with uterine fibroids. In women with uterine adenomas, the frequency of fibroadenomas of the breast was 65% and of thyroid nodules was 38.7%, while in women with a normal uterus, the frequency was 35% and 20%, respectively. Therefore, women with uterine fibroids have an increased incidence of thyroid nodules (t = 4.68, p = 0.030) and of fibroadenomas of the breast (t = 11.74, p = 0.001).

Context: In animals, acute iodine administration results in acute intrathyroidal inhibition of iodinations followed by escape of the inhibition if the excessive iodine intake continues. In humans, the intrathyroidal nonhormonal and hormonal iodine concentration after exposure to large doses of iodine for a relatively long period of time is not known. Objective: To determine whether, in human thyroid, administration of large doses of iodine for a relatively long time results in alterations of intrathyroidal hormonal (HI) T4 and T3 and total iodine (TI) content, as well as whether changes in serum concentration of thyroid hormones and TSH would occur after iodine administration or discontinuation. Design: In 33 euthyroid patients with single thyroid nodule or hyperparathyroidism, Lugol solution (80 mg iodine) was administered for 15 d before operation. Groups of six to eight patients underwent operation 0, 5, 10, and 15 d after iodine withdrawal. TI, HI in a sample of thyroid tissue, and serum concentration of T4, T3, and TSH were measured. In 21 normal euthyroid subjects who did not undergo operation, a similar protocol was used and serial blood measurements were taken. Main Outcome Measure: Intrathyroidal TI, HI, and serum thyroid hormone and TSH measurements were the main outcome measure. Results: Intrathyroidal HI content and serum T4 and T3 were unchanged during and after iodine discontinuation. TI was increased during iodine administration and returned to control values 5 d after discontinuation of iodine. The ratio of HI/TI was decreased and returned to control values 15 d after the iodine was discontinued. Serum TSH was increased during iodine administration and returned to control values 10 d after iodine withdrawal. Conclusions: In humans, administration of iodine for a relatively long period of time was accompanied by increased intrathyroidal TI, but no changes in HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.

Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and acts through the thyrotropin receptor (TSHR) located on the surface membrane of thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the absence of TSH have been found in toxic adenomas and in hot nodules of multinodular goiters. Clinically and histologically heterogeneous nodules can share common gain-of-function mutations. Mutation prevalence varies greatly and is inversely related to iodine intake of the population. We report a Greek patient presenting with subclinical hyperthyroidism due to a fast-growing autonomous hyperplastic nodule in a long-standing multinodular goiter. Direct DNA sequencing showed that the hot nodule harbored a somatic heterozygous activating TSHR mutation: substitution of glutamine for leucine in the third transmembrane helix. This mutation (L512Q) was recently described in two solitary toxic adenomas. This report expands the spectrum of mutations shared by dissimilar hot nodules, supporting a common mechanism for nonautoimmune thyroid autonomy. The identification of the L512Q substitution demonstrates that gain-of-function TSHR mutations are encountered in Greece, although iodine deficiency has been significantly corrected over the last three decades.

The genetic potentials for growth can be fully expressed only under favourable environmental conditions. Excessive physical training may negatively affect growth, especially during puberty. Sports that require a strict control of energy input in the presence of a high energy output are of particular concern. In gymnastics, a different pattern in skeletal maturation was observed, leading to an attenuation of growth potential ins Artistic Gymnasts (AG), more pronounced in males than in females, whereas in female Rhythmic Gymnasts (RG) the genetic predisposition to growth was preserved because of a late catch-up growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented. Intensive physical training and negative energy balance modify the hypothalamic pituitary set point at puberty, prolong the prepubertal stage and delay pubertal development and menarche in a variety of sports. In elite RG and AG the prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, paralleling the bone age rather than the chronological age. Bone formation, and, consequently, BMD are enhanced by physical activity. In athletes, high-impact loading activities have been shown to improve BMD, while in sports requiring a lean somatotype, the delay in skeletal maturation and pubertal development, resulting from hypoestrogenemia, predisposes athletes to osteopenia. In AG, an increase in bone density is observed using the bone age as denominator.

Elite gymnasts are subjected to intense training, which may alter pubertal development.The objective of the investigation was to study the impact of gymnastics on pubertal development in rhythmic (RGs) and artistic gymnasts (AGs).Evaluation of somatometric parameters, pubertal stage, and intensity of training in the competition field were studied.The study was conducted at European and world championships of years 1997-2004.Subjects included 433 elite RGs and 427 AGs, aged 11-23 yr.There were no interventions.Mean chronological and bone ages of each pubertal stage and their relation to the intensity of training were measured.AGs and RGs showed a delay in skeletal maturation (Delta age-bone age, 2.13 and 1.28, respectively; P0.001). AGs were subjected to higher levels of physical training. Thelarche occurred at 12.9 yr for RGs and 13.2 yr for AGs (P = 0.003) and pubarche at 12.5 and 12.9 yr, respectively (P = 0.002). Puberty was delayed but normally progressed. AGs entered each pubertal stage later than RGs. The delay was influenced by the amount of energy output. Menarcheal age was 14.6 yr for RGs and 14.9 yr for AGs. Menarche was influenced in AGs by bone age (b = 0.333; t = 2.521; P = 0.020), pubarche (b = 0.322; t = 2.401; P = 0.026), and body fat (b = -0.458; t = -3.412; P = 0.003) and in RGs by bone age (b = 0.378; t = 3.689; P0.001) and pubarche (b = 0.525; t = 6.017; P0.001).In RGs and AGs, pubertal development was shifted to a later age, maintaining a normal rate of progression, which followed the bone age. AGs, who were exposed to a greater and more sustained energy output than RGs, presented a more pronounced delay in both skeletal maturation and pubertal development.

Steroids determination in saliva offers several advantages. The collection of saliva is a noninvasive, less stressful technique than blood withdrawal and reflects the circulating unbound fractions. The suitability of saliva for 17-hydroxyprogesterone and cortisol determinations has been documented in healthy subjects as well as in diseases like Congenital Adrenal Hyperplasia and Cushing syndrome. The aim of the study was to compare the influence of different collection methods on the results of 17-hydroxyprogesterone measurement in saliva collected by different ways, using commercially available RIAs developed for plasma. 17-hydroxyprogesterone was determined in 64 healthy adult volunteers (30 males, 34 females) in serum (Group SE) and in saliva collected before meals at 8-10 p.m. by directly spitting into a plastic tube (Group SP), using a cotton swab (Group SA) and using a polyester swab Salivette (Group SB). We used a commercially available direct radioimmunoassay without separation technique. The 17-hydroxyprogesterone mean values (ng/ml) were 1.16+/-1.3 (Group SE), 0.056+/-0.046 (Group SP), 0.089+/-0.048 (Group SA) and 0.058+/-0.049 (Group SB). The detection limit was 0.010 ng/ml. The correlations between the values in serum (Group SE) and in saliva were: r=0.77, p0.05 (Group SP); r=0.62, p0.05 (Group SA); r=0.70, p0.05 (Group SB). The saliva values corresponding to the serum cut-off point of 3 ng/ml upper limit of normal values were in ng/ml 0.13 (Group SP), 0.16 (Group SA) and 0.11 (Group SB). In conclusion, 17-hydroxyprogesterone determinations in saliva using commercially available RIAs primarily developed for serum, is a reliable and easy to perform procedure. The three different methods of saliva collection showed 17-hydroxyprogesterone concentrations to have good agreement.

We studied 262 athletes who were 13-23 yr old. There were 93 male and 169 female artistic gymnasts (AG). This study is unique in character, because all variables were measured on the field of competition (24th European Championship). Male AG had a higher height SD score than female (P < 0.001), with a higher reported target height SD score (P < 0.001), a higher predicted final height (P = 0.007), a lower Delta height - target height (P < 0.001), a less delayed bone age (P < 0.001), a greater body mass index (BMI) (P < 0.001), a lower mean body fat (P

Physical exercise enhances bone acquisition during adolescence. The aim of the study was to evaluate the influence of intensive physical exercise on bone acquisition in adolescent elite artistic gymnasts. The study included 262 athletes (93 males and 169 females, aged 13-23 yr) participating in the 24th European Championship held in Greece. Bone age compared with chronological age was delayed by 2 yr for females (n = 120) and 1 yr for males (n = 68). For both sexes, the growth chart of bone mineral density (BMD) followed a normal pattern when estimated according to bone age rather than chronological age. For females, BMD was positively correlated with bone age, chronological age, height, body weight, body mass index, body fat, lean body mass, and with age of onset of training, and negatively with duration of exercise and intensity of training (P values range from0.05 to0.0001). Multiple regression analysis revealed that age of onset of training was the major parameter attenuating the effect of exercise on BMD (P0.001). The latter was related to the stage of puberty (P0.05). For males, BMD was correlated positively with bone age, height, body weight, and lean body mass (P values range from0.01 to 0.0001). Multiple regression analysis revealed that the more powerful factor influencing BMD was weight (P0.01). In conclusion, bone acquisition in adolescents under intensive physical training follows the normal pattern only when estimated according to bone age. The age of onset, the duration, and the intensity of exercise attenuate the bone acquisition, at least in female artistic gymnasts.