Long-term remission following antithyroid drug withdrawal in patients with Graves' hyperthyroidism: parameters with prognostic value.

OBJECTIVE: To assess the predictive value of some clinical and biochemical parameters, and of the +49 A/G polymorphism of the CTLA-4 gene, for long-term remission following the withdrawal of antithyroid drugs before starting antithyroid drug therapy. STUDY DESIGN: Observational, prospective and longitudinal study. METHODS: Seventy-two patients (11 of whom were men) with newly diagnosed Graves' hyperthyroidism who had been attended consecutively at a University Clinic in a population with sufficient iodine intake were included in the study. EXCLUSION CRITERIA: patients under the age of 18, pregnant women and non-Caucasian patients. All subjects were treated following a well-defined protocol. Long-term remission was calculated at 12 and 36 months following withdrawal of the antithyroid drug. RESULTS: Thirty-six of the 72 study subjects experienced a remission of at least 12 months following withdrawal of methimazole, with no differences according to their age or sex. A comparison made between the remission rates seen in both groups yielded significant differences regarding the presence of Graves' orbitopathy, the duration of the treatment with methimazole and the absence of the CTLA-4 G/G genotype. In the univariate and multivariate analyses performed, only lower frequencies of Graves' orbitopathy and an absence of the CTLA-4 G/G genotype were considered independent predictors of long-term remission. CONCLUSIONS: The absence of Graves' orbitopathy and of the CTLA-4 G/G genotype are independent predictors of long-term remission following a first course of antithyroid drugs.

Eating disoders in type 2 diabetic people: Brief review.

BACKGROUND: Relationship between type 1 diabetes and Eating disorders is well-known, less information exists on the relationship between type 2 diabetes (T2DM) people and eating disorders. AIM: Review information on the prevalence and impact of type 2 diabetes and eating disorders comorbidity. METHODS: Search in Medline and PubMed relevant articles on the aforementioned co-morbidity. Review includes articles on epidemiological, clinical and therapeutics aspects. CONCLUSIONS: Disordered eating behaviours may affect around 40% of T2DM people, being the predominant clinical forms: Eating Disorders Non otherwise specified (EDNOS), Night Eating Syndrome (NES) and Binge Eating Disorder (BED), however, population-based estimates of T2DM and ED comorbidity are mandatory to determine the prevalence of ED in T2DM people. The association between both entities has a consequence which is an impairment of metabolic control, associated to increase risk of vascular complications and difficult body weight loss, basis of T2DM treatment.

Comparative study of cognitive-behavioral psychotherapy and nutritional support in patients with different types of eating disorders.

BACKGROUND AND OBJECTIVE: There are several psychological approaches to treat ED with efficacy being revealed by empirical research; however none of them are universally accepted. The objective was to compare response to Cognitive Behavioral Therapy in patients with different clinical forms of Eating Disorders. MATERIAL AND METHOD: Seventy-four patients diagnosed with eating disorders, 32 with Anorexia nervosa (AN), 19 with Bulimia nervosa (BN) and 23 with Eating disorders not otherwise specified (EDNOS) were included. This is a prospective and comparative study. Patients were treated by psychotherapy, nutritional treatment and pharmacotherapy. RESULTS: The recovery rates in the groups of patients with AN, BN and EDNOS were 14 (43.7%), 8 (42.1%), 10 (43.4%), respectively, p>0.05. The rates of improvement were 14 (43.7%), 10 (52.6%), 12 (52.1%) for AN, BN and EDNOS, respectively, p>0.05. Finally, the rate of patients who had poor outcome were 3 (9.3%), 1 (5.2%), and 1 (4.3%), p>0.05, for AN, BN, and EDNOS, respectively. Cox regression analysis showed that the age of disease onset and no use of psychotropic drugs predicted a good response in patients with ED. CONCLUSIONS: The treatment response to Cognitive Behavioral Therapy, nutritional support and psychotropic drugs in the majority of patients was favorable and similar in most patients with different types of Eating Disorders. Furthermore, a young age and no use of psychotropic drugs predict a favorable outcome in patients with ED.

Factors influencing the outcome of patients with incidental papillary thyroid microcarcinoma.

Objective. To analyze some factors that could influence the outcome of patients with PTMC. Material and Methods. This is a longitudinal observational study. All patients diagnosed and treated for papillary thyroid microcarcinoma at the University Hospital of Vigo, between January 1994 and December 2003, were included in the present study. Demographic characteristics, tumour characteristics, TNM stage, rate of recurrence, and treatment with (131)I were the study variables. Results. Ninety-one patients (75 females) with an average age of 47.7 ± 13.4 years, range 19-81, were studied. Initial tumour staging was T1 in 90 patients and T4a in 1 case. Initial lymph node involvement was present in 4 cases (4.4%). We only found one case with distant metastases at diagnosis. Postsurgical evaluation of thyroid specimens revealed that 28 (30.7%) tumours were multifocal. The average size of the tumour was 0.44 ± 0.25 cm, range 0.1-1. Univariate analysis reveals a statistically significant association between tumour multifocality and postsurgical (131)I therapy with the recurrence rate. In the multivariate analysis only multifocality (P = 0.037, HR 5.7) was a significant risk factor for the recurrence rate. Conclusions. Our results indicate that tumour multifocality is an independent predictor of relapse but neither the tumour size nor postsurgical (131)I therapy.

[Endocrine disruptors and obesity: obesogens]. / Disruptores endocrinos y obesidad: obesógenos.

Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans.

High prevalence of eating disorders not otherwise specified in northwestern Spain: population-based study.

PURPOSE: To determine the incidence and prevalence of eating disorder and its clinical forms. METHODS: All new ED cases of both genders, ≥15 years old, diagnosed from January 2005 to December 2009 were included. All patients who suffered from ED in December 2009 were included in the prevalence study. This is a prospective, population-based study. Cumulative incidence rates and 20-year prevalence were calculated. RESULTS: The ED incidence was 14.1 (95% CI 11.4-16.1) cases per 100,000 inhabitants per year, for AN, BN and EDNOS 3.1 (95% CI 2.00-4.1), 4.4 (95% CI 3.0-8.00) and 6.5 (95% CI 4.8-7.9), respectively. The incidence of ED at the four age-intervals, 15-24, 25-34, 35-45 and >45 years, revealed that the 25-34-year interval had the highest incidence; moreover, new cases were observed even in the >45-year interval. The prevalence of ED was 82.8 (95% CI 69.4-94.5) per 100,000 inhabitants, being for AN, BN and EDNOS 18.6 (95% CI 12.5-24.4), 25.7 (95% CI 18.5-32.5) and 38.3 (95% CI 29.4-46.5), respectively. CONCLUSIONS: The incidence and prevalence of EDNOS are the highest in the ED cases; furthermore, new cases of ED are observed above the age of 45, which are remarkable data.

Disordered eating behaviors in type 1 diabetic patients.

Patients with type 1 diabetes mellitus are at high risk for disordered eating behaviors (DEB). Due to the fact that type 1 diabetes mellitus is one of the most common chronic illnesses of childhood and adolescence, the coexistence of eating disorders (ED) and diabetes often affects adolescents and young adults. Since weight management during this state of development can be especially difficult for those with type 1 diabetes, some diabetics may restrict or omit insulin, a condition known as diabulimia, as a form of weight control. It has been clearly shown that ED in type 1 diabetics are associated with impaired metabolic control, more frequent episodes of ketoacidosis and an earlier than expected onset of diabetes-related microvascular complications, particularly retinopathy. The management of these conditions requires a multidisciplinary team formed by an endocrinologist/diabetologist, a nurse educator, a nutritionist, a psychologist and, frequently, a psychiatrist. The treatment of type 1 diabetes patients with DEB and ED should have the following components: diabetes treatment, nutritional management and psychological therapy. A high index of suspicion of the presence of an eating disturbance, particularly among those patients with persistent poor metabolic control, repeated episodes of ketoacidosis and/or weight and shape concerns are recommended in the initial stage of diabetes treatment, especially in young women. Given the extent of the problem and the severe medical risk associated with it, more clinical and technological research aimed to improve its treatment is critical to the future health of this at-risk population.

[Phenotype of the C634Y mutation in the RET proto-oncogene in MEN2A: report of a family]. / Fenotipo de la mutación C634Y del protooncogén RET en el MEN2A: a propósito de una familia.

BACKGROUND AND OBJECTIVES: Genetic testing of RET proto-oncogen allows an early diagnosis of Multiple Endocrine Neoplasia syndrome type 2 and establish a correlation between genotype and clinical manifestations. The purpose of this study was to demonstrate the benefits of an early diagnosis with genetic testing followed by prompt surgery on the cure of MTC versus a later diagnosis with serum calcitonin. PATIENTS AND METHOD: Retrospective descriptive study of 8 members of a MEN 2A family by C634Y mutation. We performed serum calcitonin screening until 1999 and subsequently RET genetic testing was obtained. Carriers underwent total thyroidectomy and periodic determination of calcitonin, urinary metanephrines, calcium, phosphorus and neck and abdominal imaging techniques. RESULTS: Five patients were diagnosed by calcitonin familial screening and all of them have high calcitonin by now. Three patients were diagnosed by genetic testing (an adult and two children) and they are free of disease. Calcitonin was closely monitored in children and they underwent surgery when it started to raise, at 6 and 10 years old respectively, finding nodular C-cell hyperplasia in both. Of 8 carriers 3 developed pheochromocytomas, bilateral and asynchronous, one-half had normal urinary metanephrines and two of them were simultaneous with MTC. No patient had biochemical data suggesting hyperparathyroidism although in one patient multiple parathyroid adenomas were found at thyroidectomy. CONCLUSIONS: RET genetic analysis has achieved an early diagnosis and treatment with no development of MTC in our patients, adjusting the time and type of surgery and allowing a genotype-phenotype correlation. It demonstrates how a genetic alteration is associated with a pathology that we can prevent and manage improving the prognosis of our patients.

Treatment of Graves' hyperthyroidism with thionamides-derived drugs: review.

Thionamide-derived antithyroid drugs (ATD) have been in use for over half a century and much is now known about their mechanism of action, pharmacokinetics and clinical pharmacology. Candidates for first option ATD therapy are young adults, without large goitre. The recommended initial dose for patients without big goitre and mild hyperthyroidism is 20 mg of MMI/CBZ. The recommended maintenance doses are 5-10 mg of MMI/CBZ. In cases of big goitre and/or severe hyperthyroidism the recommended initial dose is 30 to 40 mg/day. PTU use should be restricted to first trimester of pregnancy, doses should be as low as possible (150 to 200 mg/day) and then changing to MMI is recommended. Treatment Duration should be of 12-18 months. ATD plus thyroxine combination therapy have not advantage on ATD alone. ATD plus L-Thyroxine regimens should be used to avoid hypothyroidism when patients are with maintenance doses of ATD drugs in order to relax monitoring. In this case a low dose of T4 50-75 µg per day is used. Breast feeding women with hyperthyroidism can be treated with MMI/CBZ. ATD will not stop until serum stimulating TSH-receptors antibodies values are within the normal range. We are waiting for results of ongoing studies of biochemical and/or genetic markers that will permit us to predict the outcome of these patients after ATD treatment is stopped.

Time trends for thyroid cancer in northwestern Spain: true rise in the incidence of micro and larger forms of papillary thyroid carcinoma.

BACKGROUND: Thyroid cancer incidence is increasing throughout the world. Most studies attribute this rise entirely to the increase in papillary carcinoma, the most common thyroid malignancy in iodine-sufficient areas. A variety of nonetiological factors such as changes in clinical practice may affect the incidence of thyroid cancer and some researchers have suggested that this rise is only apparent due to an increase in diagnostic activity. Since data on the epidemiology of thyroid cancer in Spain are scarce, the main goal of this study was to analyze changes in thyroid cancer presentation, incidence, and prevalence in Vigo (northwestern Spain) between 1978 and 2001, and to investigate the relationship between the incidence rates and trends in tumor size and thyroid surgery. METHODS: In this descriptive epidemiologic study, an analysis was carried out on new thyroid cancer cases obtained from the Pathology Registry of the University Hospital of Vigo (500,000 inhabitants). Trends in age, sex, thyroid surgery, histological type, tumor size, and incidence rates were calculated. The prevalence of thyroid cancer was determined in three cross-sectional surveys. RESULTS: The rate of population undergoing thyroid surgery significantly increased over time. Out of 322 new primary thyroid cancers, papillary thyroid cancer (PTC) was the predominant type (76%). The age-standardized incidence rate shows a significant increase in females: 1.56 per 100,000 year (1978 to 1985) to 3.83 (1986 to 1993) and 8.23 (1994 to 2001); and in males: 0.33, 1.19, and 2.65, respectively. PTC was mainly responsible for this pattern and was the result of both the increase in micropapillary thyroid carcinoma (MPTC) incidence and in PTC measuring more than 1 cm. Besides MPTC cases, no significant variations were observed in tumor size over time. CONCLUSIONS: In northwestern Spain, the incidence of thyroid cancer is increasing. These data should be taken into account when planning health resources for these patients. Our results may reflect the contribution that other factors, besides increased diagnostic activity, have made to the rise in thyroid cancer incidence in our region. Additional studies are needed to explain the rise in PTC incidence throughout the world and to search for potential risk factors that are currently unrecognized.

Acromegaloidism with normal growth hormone secretion associated with X-tetrasomy.

We reported a case of a 26-year-old female who was referred to our clinic with the diagnosis of possible acromegaly. She was born from a term pregnancy by forceps delivery. The patient was diagnosed as having hip luxation at one month and spoke her first word at 15 months. She had been diagnosed at the age of 9 years old as having perinatal encephalopathy with intellectual and motor affectation. Since this period of time she has undergone an insidious change in her appearance, mainly comprising progressive coarsening of the face. For this reason she was submitted to our clinic with presumed acromegaly. Dynamic tests of growth hormone secretion ruled out such a diagnosis. The Patient was considered as having "acromegaloidism", a term used for patients whom manifest clinical features of acromegaly but do not present a demonstrable growth hormone hypersecretion. Subsequently cytogenetic evaluation revealed an infrequent chromosome pattern: X-Tetrasomy. In the present article a differential diagnosis of acromegaloidism and the potential role of genes present on X-chromosome involved in human growth such as SHOX gene are discussed. Overdosification of SHOX gene might explain tall stature of girls with X-tetrasomy. Our observation suggested that X-tetrasomy should be considered in the differential diagnosis of acromegaloidism. Furthermore, this may lead to the identification of new genes in the X-chromosome that are important for growth of facial structures.

[Assessment of the value of monitoring of PTH levels in the standard surgical management of patients with primary hyperparathyroidism]. / Valor de la monitorización intraoperatoria de las concentraciones séricas de paratirina en el tratamiento quirúrgico convencional del hiperparatiroidismo primario.

BACKGROUND AND OBJECTIVE: We decided to evaluate the predictive value of the intra-operative monitoring of PTH concentrations for the standard surgical management of primary hyperparathyroidism (PHP). PATIENTS AND METHOD: 23 patients with PHP were included. RESULTS: When serum PTH values either at anaesthesia induction or at visualization-manipulation of the gland were compared with those values at ten minutes post-excision, we observed 20 cases which were true positive, 1 true negative and 2 false negative. By contrast, when the highest PTH pre-excision value was compared with the PTH value at ten minutes post-excision, false negatives results were eliminated. CONCLUSION: Monitoring of PTH levels during conventional treatment of primary hyperparathyroidism has a good predictive value.

Growth hormone (GH) peaks versus areas under the curve in the diagnosis of adult GH deficiency: analysis of the variables provided by the GHRH + GHRP-6 test.

BACKGROUND: The diagnosis of growth hormone deficiency (GHD) relies on provocative tests of GH reserve. The aim in these tests is to obtain an objective, biochemical-based, measure of gland function, but clinicians and researchers rely on the GH peak, as a surrogate of the 24-hour pituitary secretion. However, on a mathematical basis the area under the secretory curve (AUC) should be more valid for this evaluation. OBJECTIVES: To validate which variable provided by a provocative test of GH secretion is mathematically more robust for supporting the clinical diagnosis. Adult normal subjects and GHD patients were challenged with the combined stimulus GHRH + GHRP-6. The diagnostic efficacy of the GH peak, and the AUC were compared by the receiver operating characteristic (ROC) curve methodology. PATIENTS AND METHODS: 146 patients with GH deficiency due to organic pituitary disease and 184 healthy subjects were administered GHRH 1 microg/Kg iv, plus GHRP-6 1 microg/Kg iv, and GH was determined. Four variables were studied: (a) the GH peak; (b) the "standard" AUC, (c) the "stimulated" AUC and (d) the basal value, used as internal control. RESULTS: Under ROC curve analysis, the basal variable was devoid of diagnostic capability, while the other variables performed strikingly well, the ROC curve area for the GH peak was 0.9997; and for the AUC 0.9993, with no statistical differences. CONCLUSIONS: The variables provided by measuring the GH peak and the area under the curve were similarly effective for diagnosis, although on clinical grounds, the peak was more convenient as needed no calculation. If results for other test were similar the time-honored method of measuring the GH peak could be considered mathematically validated.

Altered GH elimination kinetics in type 1 diabetes mellitus can explain the elevation in circulating levels: bicompartmental approach.

Type 1 diabetes mellitus (DM 1) is associated with elevated circulating GH concentrations. Because these high GH levels could be explained either by an augmented pituitary secretion and/or delayed elimination clearance or distribution, we sought to evaluate GH pharmacokinetics to propose a model that better explains the elimination kinetics in patients with DM 1 and assess possible differences with normal volunteers that could justify elevation in GH circulating levels in these patients. A multicompartmental analysis was applied to serum GH concentrations measured at different times for 150 min in six patients with DM 1 and six age-, sex-, and body mass index-matched normal subjects after the administration of an iv bolus of recombinant human GH (200 microg), previous suppression of endogenous GH release with octreotide. The best fitting to the GH disappearance profiles was obtained with the biexponential equation in both groups. From it, we propose a bicompartmental model to explain GH kinetics in normal and diabetic patients. The mean transit time in both compartments and the mean residence time in patients with DM 1 were more than twice the values from control group. So in DM 1 elevated circulating GH concentrations are, at least partially, caused by a delayed GH plasmatic clearance. The DM 1 patients included in this study had a normal renal function; thus, our results agree with the hypothesis that DM 1 constitutes a GH-insensitivity state because a reduced GH clearance by its receptor-mediated mechanism might explain the delayed GH elimination kinetics shown in patients with DM 1. However, the possibility of additional factors contributing to the slowed GH removal from circulation is not completely excluded.

[Iodine deficiency in pregnant and fertile women in an area of normal iodine intake]. / Déficit de yodo en gestantes y mujeres en edad fértil pertenecientes a un área con consumo normal de yodo.

BACKGROUND: Our purpose was to evaluate the efficacy of a iodine prophylaxis campaign in pregnant women. PATIENTS AND METHOD: Eighty-one pregnant and 29 fertile women were enrolled. The urine iodine concentration was determined. RESULTS: The median urine concentration of iodine was similar in both groups [pregnant women: 113.3 g/l; non-pregnant women: 99.1 g/l]. 67.9% pregnant women and 51.7% non-pregnant women had urine concentrations of iodine lower than the normal range. CONCLUSIONS: Our results suggest that the ongoing iodine prophylaxis campaign in our community is not effective in the adult population.