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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.

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.

ObjectiveRelative corticosteroid insufficiency may be common in critically ill patients and is associated with a poor outcome; however, the response of the hypothalamic–pituitary–adrenal (HPA) axis in nursed patients is not known. Our aim was to evaluate the response of HPA axis to the severity of illness in non-critically ill nursed (NCIN) patients and the clinical outcome.Subjects and methodsFifty-six nursed patients who were divided into four groups (stroke, mild disease, sepsis and severe sepsis) as well as a control group (n=15) were studied. At admission (day 1), cortisol and ACTH were measured and a low-dose (1 μg) corticotrophin test was performed, followed 2 h later by a standard-dose (250 μg) corticotrophin test. Diurnal variation of cortisol was obtained on day 2. A second identical set of low-dose and standard-dose corticotrophin tests were performed on day 5 or 6 (recovery phase).ResultsIn patients with stroke and severe sepsis, cortisol had the highest values and its diurnal variation was abolished. Dissociation of ACTH and cortisol was found in all patients.The Δmax of cortisol after the 1-μg corticotrophin test did not differ among the groups, while after the 250-μg corticotrophin test, it was borderline higher in controls. The ratio of responders (Δmax of cortisol ≥9 μg/dl) to non-responders after 1- or 250-μg corticotrophin test did not differ among patients and controls. All patients had a good outcome without glucocorticoid treatment.ConclusionsDepending on the severity of illness, mild alterations in the HPA axis occurred. However, relative corticosteroid insufficiency was not confirmed in NCIN patients.

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.

Transient hyperglycemia is commonly observed in non-diabetic subjects during surgery. We undertook this study to investigate (1) insulin secretion pattern and glucose levels during elective surgery, and (2) the role of pre-operative fasting in the development of surgery-induced hyperglycemia.We examined 21 severely obese normal glucose tolerant patients, who underwent bariatric surgery. From the 21 operated subjects, 14 remained fasted while seven patients received 75 g glucose the preoperative night. They sampled at baseline and from the onset of operation frequently for 9 h thereafter, for measuring serum insulin and glucose.Hyperglycemia developed within 1 h from the onset of operation and lasted 9 h. The administration of 75 g glucose the preoperative night prevented surgery-induced hyperglycemia. Insulin profile analyzed by deconvolution analysis was similar between fasted patients and those who received 75 g glucose. Serum insulin was suppressed at the beginning of the surgery and reached baseline values 4 h thereafter.Hyperglycemia occurred within 1 h from the beginning of surgery and sustained for at least 9 h while insulin levels are suppressed or unaltered compared to baseline values in euglycemia. The administration of 75 g glucose the preoperative night prevents surgery-induced hyperglycemia without altering the profile of insulin secretion.

Background There has been limited research examining the efficacy of providing written information to cancer patients in southern and eastern European countries. This study investigated the impact of a booklet about chemotherapy on patient satisfaction, quality of life (QoL) and emotional distress, and assessed booklet use. Patients and methods A total of 145 Greek cancer outpatients prior to commencing chemotherapy completed a questionnaire and were randomized to receive (n = 72) or not receive (n = 73) the booklet. All patients completed the second questionnaire before the following cycle of chemotherapy. Results Baseline characteristics were well balanced between the two groups. Experimental group patients reported being significantly more satisfied with the information received and care overall than those in the control group, felt significantly more and better informed, and perceived the information received as being clearer and detailed. The intervention produced no benefits in terms of anxiety, depression or QoL. The booklet was read by almost all patients and to a great extent by significant others. The majority considered the booklet useful to read and helpful in recalling chemotherapy-related information. Conclusions The current results provide further evidence on the efficacy of information-giving interventions in societies where disclosure of information to cancer patients still remains controversial.

Morbidly obese subjects may present with abnormal thyroid function tests but the reported data are scarce. Therefore, we studied the thyroid parameters in 144 morbidly obese patients, 110 females and 34 males, to assess the prevalence of hypothyroidism. Eleven percent (11.8%) carried the diagnosis of hypothyroidism and were undergoing levothyroxine (LT4) replacement therapy, 7.7% had newly diagnosed subclinical hypothyroidism, 0.7% had subclinical hyperthyroidism and 7.7% were euthyroid with positive antibodies (anti-thyroid peroxidase antibodies [TPOAb]). From the 144 subjects, we selected a cohort of 78 euthyroid subjects with negative TPOAb, who did not receive LT4 replacement or suppression therapy (the experimental group) and compared them to 77 normal-weight euthyroid subjects, TPOA-negative, matched for age and gender who served as controls. The experimental group had higher serum levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and thyrotropin (TSH) compared to the control group. Serum TSH concentration was associated with fasting serum insulin levels and insulin resistance but not with serum leptin levels, body mass index (BMI), fat mass, and lean body mass. In conclusion, in morbidly obese individuals, the prevalence of overt and subclinical hypothyroidism was high (19.5%). The morbidly obese subjects have higher levels of T3, FT3, T4, and TSH, probably the result of the reset of their central thyrostat at higher level.

Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism.

Objective: Kallmann's Syndrome is a heritable disorder characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. A common pathogenesis for KS and schizophrenia had been proposed based on shared pathologies of these two disorders, although no such clinical associations have ever been reported. Method: We report a 35 year old man with schizophrenia and Kallmann's Syndrome. The patient presented with signs and symptoms of hypogonadism, severe hyposmia and normal endocrine functions of the anterior pituitary. Hyposmia has been attributed to the absence of the olfactory bulbs and tracts and atrophy of the olfactory gyri, but normal olfactory mucosa. The patient presented with paranoid schizophrenia with persecutory delusions, auditory hallucinations, thought disorder, depersonalization, and gradual but marked global deterioration. Results: Psychiatric evaluation revealed an entirely different psychopathological and personality profile between the patient and the six other Kallmann patients studied. Cycle sequencing analysis revealed a normal sequence of all 14 exons of the KAL gene. In conclusion, based on the presented case, Kallmann's Syndrome and schizophrenia represent a rare clinical association rather than a syndrome with a common pathogenesis, which if present should be confined to the olfactory dysfunction.

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

This study assessed the information needs of Greek cancer patients and examined whether awareness of diagnosis had any impact on patients. One hundred patients were interviewed about overall and specific information needs, satisfaction, emotional distress, and quality of life. Patients exhibited a great desire for information overall. The need to have more information was high especially regarding the aftermath of chemotherapy, prognosis, how chemotherapy worked, and diagnosis. Patients were more satisfied with care but less satisfied with the information received. Only 37% knew they had cancer, especially the younger, the better educated, and those with breast cancer. Awareness was not related to satisfaction, emotional distress, or quality of life. Our findings suggest that Greek cancer patients need more factual information about their condition and management. Greek oncologists may feel freer to inform their patients about the diagnosis and other issues following their judgement, rather than employing the policy of concealing the truth.

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.

To evaluate right ventricular function in patients with beta-thalassaemia major and congestive heart failure. Background In patients with beta-thalassaemia major a high incidence of cardiac involvement still exists despite improved prognosis with chelation therapy. Development of severe right heart failure is common and has been attributed to pulmonary hypertension secondary to lung haemochromatosis. However, the possibility of direct right ventricular myocardial involvement in the absence of significant pulmonary hypertension has not been adequately investigated.Twenty-nine consecutively screened patients with beta-thalassaemia major and congestive heart failure were investigated by Doppler echocardiography, right ventricular first-pass radionuclide examination and cardiac catheterization. Haemodynamic data were obtained both before and after volume loading. A control group of 39 patients with beta-thalassaemia major, free from cardiac disease, and matched for age, gender, body surface area and heart rate was used for comparison. A subset of the control thalassaemic group (n=15) underwent both radionuclide and haemodynamic assessment.The majority of patients were on non-optimal chelation therapy. Only two of 29 patients were found to have cor pulmonale. One other patient suffered from constrictive pericarditis. A restrictive filling pattern in both ventricles and left ventricular systolic dysfunction were evident in the other 26 patients. Pulmonary artery pressure (systolic, 33+/-8 vs 27+/-5 mmHg, P0.05) and pulmonary vascular resistance (114+/-56 vs 65+/-29 dynes. s. cm(-5), P0.01) were only mildly elevated in the heart failure group. After volume challenge, cardiac output remained unchanged although the increments of ventricular filling pressures were significant (Deltaright atrial: 4.8+/-2.2 mmHg, P0.05; Deltapulmonary capillary wedge: 5.6+/-2.9 mmHg, P0.05) and correlated with each other (r=0.69;P0.001) in heart failure patients, suggesting pericardial constraint and ventricular interaction. In these patients compared with the control thalassaemic group, a lower right ventricular ejection fraction (29%+/-9 vs 59%+/-6, P0.0001) without correlation with pulmonary artery pressures was found. Haemodynamically significant right ventricular dysfunction defined as mean right atrial pressure10 mmHg and ratio of mean right atrial-to-capillary wedge pressure0.8 was evident in 15 of the 26 patients (58%), all with severe symptoms, representing three fourths of the patients in functional class III and IV. Simultaneous pressure recordings in six of these 15 patients showed equalization of ventricular end-diastolic pressures within 5 mmHg.The majority of patients with beta-thalassaemia major and severe congestive heart failure demonstrated a unique haemodynamic pattern similar to that described in predominant right ventricular infarction, indicating severe right ventricular cardiomyopathy in addition to left ventricular dysfunction. The incidence of cor pulmonale as a cause of right heart failure seems to be much lower than previously hypothesized.

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.

An early diagnosis of sepsis in patients with diabetic ketoacidosis and hyperosmolar non-ketotic coma is crucial and could save lives. We studied serum C-reactive protein and interleukin-6 to find out how useful these might be for identifying sepsis.Sixty one diabetic patients with ketoacidosis or hyperosmolar non-ketotic coma were enrolled. Patients with signs and symptoms of systemic inflammatory response syndrome were identified. Acute-phase reactants, including C-reactive protein and interleukin-6, the main cytokine responsible for the induction of acute-phase proteins, were measured on admission and when patients had clinically improved and were euglycaemic.A total of 49 out of 61 patients with diabetic ketoacidosis or hyperosmosis had signs of systemic inflammatory response syndrome. Another 27 patients had systemic inflammatory response syndrome and no signs of infection and 22 patients had systemic inflammatory response syndrome due to proven infection. We detected a significant increase in serum C-reactive protein and interleukin-6 values in patients infected compared with patients not infected with systemic inflammatory response syndrome SIRS. Patients who finally died had much higher levels of these proteins, while there was a prompt reduction of serum C-reactive protein and interleukin-6 early during remission.Diabetic ketoacidosis and hyperosmolar non-ketotic coma can often cause a clinical syndrome resembling systemic inflammatory response syndrome. Determination of serum C-reactive protein and interleukin-6 levels is a useful way of excluding an underlying infection early on as well as confirming and monitoring sepsis.

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.

The presence of medial arterial calcification (MAC), often referred to as Moncheberg's sclerosis, was sought in patients with long-standing diabetes mellitus. One hundred patients aged 22-50 years were initially divided into two groups, those with neuropathy and those without. As expected, the incidence of MAC was significantly higher in the neuropathy group (40% vs 20%) . When the patients were divided into two groups, those with MAC and those without, it appeared that the incidence of MAC was very high in patients who had microalbuminuria (57% vs 13%) and particularly when microalbuminuria was combined with neuropathy (40% vs 7%). It is concluded that microalbuminuria is a strong predicting factor of medial arterial sclerosis independent of neuropathy.

The aim of our study was to determine the prevalence of thyroid dysfunction and autoimmune abnormalities in rheumatoid arthritis (RA) and to further investigate the possible association between D-penicillamine and autoimmune thyroiditis. For this purpose, one hundred and one unselected consecutive patients with RA and 70 age and sex matched controls were studied prospectively. Evaluation included a complete history and physical examination with special attention to symptoms suggestive of thyroid pathology, routine laboratory and serologic immune profile, plus determination of serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), antibodies to thyroid peroxidase (AbTPO) and TSH receptor antibodies (TRAB). Serum thyroxine binding globulin (TBG) was measured in all subjects with high thyroid hormone levels, whereas free T3 and T4 concentrations were determined in all individuals with abnormal T3, T4, TSH or TBG. Six patients with hyperhyroidism, 3 with hypothyroidism and 1 with the euthyroid hyperthyroxinemia (EH) syndrome were found, whereas four of the controls had hyperthyroidism. Thirteen patients and 6 controls had high AbTPO levels whereas no one had high TRAB. No association was detected between thyroid abnormalities and any serologic RA finding. Furthermore, no correlation between thyroid dysfunction and elevated AbTPO's was found. A relatively high prevalence of thyroid dysfunction (9,9%) and subclinical autoimmune thyroiditis (12,9%), the latter indicated by elevated AbTPO's, was found in our RA patients. These figures were higher than those in the control group (5,7% and 8,6% respectively), but the difference did not reach statistical significance. Of further interest may be our finding that, despite anecdotal reports blaming D-penicillamine for cases of autoimmune thyroiditis, the incidence of the latter was similar among recipients and nonrecipients of the drug. Similarly, TRAB were not detected in any patient treated with D-penicillamine.

Brief hyperventilation is occasionally accompanied by repolarization abnormalities in subjects without apparent heart disease. However, the effect of prolonged hyperventilation on repolarization abnormalities is not clearly defined. We analysed the repolarization abnormalities induced by prolonged hyperventilation, correlated with hyperventilation induced haemodynamic changes and exercise test results and assessed the effect on them of age, gender, smoking and hypertension. Prolonged hyperventilation (overbreathing at least 30 respirations/min for 5 min and 10 min recovery) was performed in 474 healthy volunteers (269 men, 205 women) 42.6 +/- 13.5 years old. The electrocardiogram was analysed for transient ST depression or T-wave inversion. Repolarization abnormalities were observed in 72 subjects, 47 men (17.5%) and 25 women (12.2%). Age, gender, smoking and hypertension did not influence the overall incidence of repolarization abnormalities. ST depression was more frequently observed in women (4.4 vs 0.7%, P < 0.01), while T wave inversion from negative to positive was more frequent in men (8.9 vs 2.4%, P < 0.006). All subjects with ST depression were non-smokers (4.1% of the non-smokers, P < 0.003 compared to smokers). Repolarization abnormalities occurred usually (80.5%), but not exclusively, within the first hyperventilation minute. Subjects with repolarization abnormalities developed higher heart rate change with hyperventilation than those without repolarization abnormalities (29.2 +/- 13.1 vs 24.2 +/- 12.7, P < 0.002). A positive exercise test was observed in 45.4% of subjects with hyperventilation induced ST depression but only in 13.1% of subjects with T-wave changes, P < 0.02. Repolarization abnormalities are not uncommon during prolonged hyperventilation. Hear rate change affects the occurrence of repolarization abnormalities, while gender and smoking influence the type of repolarization abnormalities. ST depression but not T-wave inversion during hyperventilation is associated with a positive exercise test. Increased understanding about hyperventilation-induced repolarization abnormalities could affect use of the method in the clinic, either as a provocation test or as a complement to the interpretation of the exercise test.

Hyperventilation is well known to affect the electrocardiogram (ECG) in subjects without heart disease and produce spasm in patients with variant angina. The autonomic nervous system is thought to play a significant role in these effects. However, the normal hemodynamic response to hyperventilation is not well defined. We subjected 369 healthy volunteers (200 men, 169 women) to prolonged hyperventilation (30 respirations for 5 min and 10 min recovery) under continuous ECG monitoring and to exercise testing. Heart rate (HR), systolic and diastolic blood pressures (SBP, DBP) and rate-pressure product were recorded. Hyperventilation resulted in an immediate (within the first min), significant increase in HR by 27.4%, a further small increase at min 2 of hyperventilation, and a subsequent small decrease in HR at mins 3-5. An immediate drop of HR by 20.1% was observed with discontinuation of hyperventilation. Apart from a slightly higher HR increase in men, a similar pattern of HR changes was found in both genders. On multivariate analysis, younger age, absence of smoking, and male gender were associated with a higher HR increase with hyperventilation (p < 0.0001, p < 0.0001, and p < 0.001, respectively). SBP and DBP increased with hyperventilation, with their highest value at min 5 of hyperventilation and a subsequent drop to baseline levels. Age and gender did not affect the degree and pattern of BP changes. Absence of smoking and the presence of hypertension were associated with a higher SBP with hyperventilation (p < 0.003 and p < 0.007). The rate-pressure product increased by 43.6% with hyperventilation, a change that was only 19.1% of the respective rate-pressure product observed with exercise. Hyperventilation results in significant HR and BP increases, changes that are influenced by age, gender, smoking, and hypertension. Our study could serve as a standard for comparison of the hyperventilation effects in different disease states.

A patient with severe thyrotoxicosis developed the typical electrocardiographic (ECG) evolution of a non-q myocardial infarction. This occurred without evidence of myocardial necrosis and in the absence of coronary artery disease. Treatment with beta blockers resolved the ECG changes despite the persistence of the thyrotoxic state.

BACKGROUND: Stimulated hyperinsulinaemia is observed in some patients with syndrome X, defined as angina, positive stress test and normal coronary arteriography, and may be involved in the pathogenesis of the syndrome. An increased sympathetic response to exercise may also be pathogenetically involved. However, the diagnostic value of hyperinsulinaemia as a marker of this syndrome has not been defined. METHODS: We determined blood glucose and immunoreactive insulin during fasting, at 60 and 120 min after a glucose load of 75g in 21 patients (eight men, 13 women, 53.9 +/- 7.1 years old) with syndrome X and in 21 healthy volunteers matched to the patients for age, sex and body mass index (eight men, 13 women, 51.6 +/- 9.3 years old). Insulin values were related to the rate-pressure product increase at first exercise stage. RESULTS: The glucose values as well as the insulin values during fasting were similar in syndrome X patients and in controls. However, significantly higher insulin values (mU/l) were observed at 60 (P < 0.01) and 120 min (P < 0.005) in syndrome X patients (median 75.5 and 52, range 43-290 and 6.1-212, respectively) than in controls (median 47.5 and 24.5, range 8-195.6 and 5.2-164, respectively). A considerable overlap of insulin values, however, was observed between the two groups, with abnormal values even during fasting. For a specificity of 95%, an abnormal insulin value had a sensitivity of between 19 and 24% and a diagnostic accuracy of 57-60%. A significant positive correlation was found between insulin levels after the glucose load and the rate-pressure product increment with exercise (60 min, r = 0.60; 120 min, r = 0.65). CONCLUSION: Hyperinsulinaemia may be pathogenetically involved in syndrome X patients, in close relation to the higher sympathetic drive that characterizes this syndrome. However, the wide range of insulin values, frequently overlapping with normal values, limits the usefulness of this abnormality as a marker of the syndrome.

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.

The purpose of this study was to assess whether the administration of recombinant human erythropoietin (rHuEPO) would correct anemia and improve the quality of life (QOL) in cancer patients receiving chemotherapy. One hundred twenty-two patients with hemoglobin/=11.0 g/dl were randomized to receive rHuEPO 10,000 U three times weekly (n = 61) or no additional treatment (n = 61). Response was assessed by measuring changes in hemoglobin level and QOL. QOL was evaluated before each cycle of chemotherapy at baseline, Week 4, and Week 12 using two separate self-report questionnaires. The analyses indicated that the rHuEPO-treated patients experienced significantly less fatigue (P0.05) than their control group counterparts, and reported significantly higher scores on energy level (P0.05), ability to perform daily activities (P0.01), and overall QOL (P0.05). The overall change in hemoglobin level was significantly greater in the rHuEPO group than in the control group (1.7 g/dl versus 0.3 g/dl, P0.001). rHuEPO effectively corrects anemia and significantly improves QOL in patients with solid tumors receiving chemotherapy.

To develop a test of pituitary-thyroid responsiveness to thyrotropin-releasing hormone that would obviate the need for measuring serum thyrotropin, we determined serum thyrotropin, thyroxine, and tri-iodothyronine concentrations before and at frequent intervals after the intramuscular administration of 2 mg of thyrotropin-releasing hormone in normal subjects and in patients with a variety of thyroid disorders. In specimens obtained four and five hours after administration of the hormone to normal subjects, serum thyroxine concentration increased 2.4 plus or minus 0.7 mug per 100 ml (mean plus or minus S.D.) over base-line values, the magnitude of increase being greater than 1.5 mug per 100 ml in 32 of 34 subjects. Serum thyroxine concentrations after administration of thyrotropin-releasing hormone did not increase in 11 hyperthyroid patients. Of 13 with hypothyroidism, increases in 12 were 0 to 0.7 mug per 100 ml; in one the increment was 1.2 mug per 100 ml. Measurement of the serum thyroxine response to intramuscular thyrotropin-releasing hormone will usually suffice to determine the integrity of the hypothalamic-pituitary-thyroid complex.

Chronic diphenylhydantoin (DPH) administration (5 mg x 100 g body wt-1 x day-1) to the normal rat is associated with a decrease in the serum thyroxine (T4) and triiodothyronine (T3) concentrations without an appropriate rise in the serum thyrotropin (TSH) concentration, suggesting a possible direct effect of DPH on TSH secretion. To further study this possibility, DPH was administered chronically to thyroidectomized, hypothyroid rats. In the hypothyroid rats treated chronically with DPH, serum TSH did not increase, pituitary TSH content was significantly decreased, and the serum TSH response to thyrotropin-releasing hormone (TRH) was decreased compared to that of diluent-treated, hypothyroid rats. Hypothalamic TRH content was similar in DPH and diluent-treated rats. These findings suggest that DPH suppresses pituitary TSH secretion, probably as a thyroid hormone agonist. The effect of a single large dose of DPH (20 mg/100 g body wt) administered to thyroidectomized rats also decreased serum tSH but, in contrast to the findings in chronically treated rats, hypothalamic TRH and pituitary TSH content and the serum TSH responses to TRH were increased. These differences may be due to the acute inhibitory effect of a large dose of DPH on hypothalamic TRH release. Furthermore, because the effect of thyroid hormone on regulating pituitary TSH synthesis and release is dose and time dependent, the effect of DPH as a thyroid hormone agonist on pituitary TSH dynamics may also be variable.

The degree of exophthalmos and the width of the palpebral fissure were studied serially in 58 previously thyrotoxic patients, who were divided into 6 treatment groups: 1. guanethidine eye drops; 2. oral thyroxine; 3. guanethidine eye drops and oral thyroxine; 4. guanethidine and prednisolone eye drops; 5. napththazoline nitrate 0.1% and zine sulfate 0.5% eye drops; and 6. metronidazole orally. Exophthalmos increased significantly in the first and third group, and the palpebral fissure decreased in the first group. It was concluded that guanethidine eye drops should be given when there is marked lid retraction with minimal exophtalmos; that prednisolone eye drops are not indicated in endocrine exophthalmos; and that the combination of guanethidine eye drops with oral thyroxine in different dosages is worth further study.

The pattern of thyrotropin secretion was analyzed in seven euthyroid women, before and after withdrawal of long-term thyroid hormone, by serial measurements of thyroid 131l uptake, serum thyroxine, tri-iodothyronine, and thyrotropin concentrations, and the response to thyrotropin-releasing hormone. During exogenous hormone administration, 131l uptake was suppressed, and serum thyrotropin concentrations before and after administration of thyrotropin-releasing hormone were undetectable. After withdrawal of exogenous hormone, thyrotropin secretory function was transiently impaired, as indicated by undetectable basal thyrotropin concentrations together with absence of response to thyrotropin-releasing hormone, and subsequently by normal values of basal thyrotropin concentration and normal responses to releasing hormone while serum thyroxine and tri-iodothyronine concentrations were subnormal. Decreased thyrotropin reserve persisted for two to five weeks. Detectable values of serum thyrotropin (less than 1.2 muU per milliliter) and a normal 131l uptake usually occurred concurrently in two to three weeks. Serum thyroxine concentration returned to normal at least four weeks after hormone withdrawal.

The administration of iodide to pregnant and nursing rats induces hypothyroidism in the term fetus and neonatal rat through age 10 days as indicated by an increase in the serum concentration of thyroid-stimulating hormone and a decrease in the serum of thyroxine and triiodothyronine. Thyroid function returned to normal from age 18 through 60 days in spite of continued iodide administration, strongly suggesting that resistance to the inhibitory effect of iodide on thyroid hormone synthesis is developed at approximately 18 days of age. This perinatal rat model can be used to study the mechanisms responsible for iodide-induced hypothyroidism and goiter in human newborns whose mothers received iodide-containing medications during pregnancy.

The chronic use of methadone or heroin results in various abnormalities in the transport and peripheral metabolism of thyroxine (T4). An increase in the thyroxine-binding capacity of the t...

Excerpt To the editor: Bilateral adrenal hemorrhage with resultant acute adrenal insufficiency has been recognized as a fatal complication of anticoagulant therapy (1, 2). Only rarely has this medi...

Excerpt A multitude of thyroid function tests are now available to the clinician to aid in the diagnosis of thyroid disease. Unfortunately, the laboratory test that is requested may not be appropri...