False-positive iodine-131 whole-body scan findings in patients with differentiated thyroid carcinoma: report of 11 cases and review of the literature

BACKGROUND: Iodine-131 (I-131) whole-body scan (WBS) plays an important role in the management of patients with differentiated thyroid carcinoma (DTC), to detect normal thyroid remnants and recurrent or metastatic disease. A focus of I-131 accumulation outside the thyroid bed and the areas of physiological uptake is strongly suggestive of a distant functioning metastasis. However, many false-positive I-131 WBS findings have been reported in the literature. PATIENT FINDINGS: We describe a series of 11 personal cases of patients with DTC, collected from 1992 to 2011, in whom diagnostic or post-treatment WBS showed false-positive retention of I-131 in various locations. SUMMARY: False-positive accumulations of I-131 on WBS may be classified according to the underlying pathophysiological mechanisms: external and internal contaminations by body secretions, ectopic normal thyroid and gastric tissues, inflammatory and infectious diseases, benign and malignant tumors, cysts and effusions of serous cavities, thymic uptake, and other non classified causes. CONCLUSIONS: Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments

Thyroxine Therapy in Euthyroid Patients Does Not Affect Body Composition or Muscular Function

OBJECTIVE:The main objective of the study was to evaluate the effects of small increments in thyroxine (T4) levels following levothyroxine (L-T4) administration on the body composition of women patients. The secondary objective was to assess the effect of the therapy on energy expenditure and muscular function. METHODS: The prospective, randomized study consisted of a 12-month follow-up of 37 women with thyroid nodules. The patients were divided into two groups for comparison, one treated with L-T4 (20 women) and the other untreated (17 women). L-T4 dose was individually adjusted to obtain a serum thyroid-stimulating hormone in the lower portion of the normal range. Multiple tests, including bioelectrical impedance analysis, dual-energy X-ray absorptiometry, air displacement plethysmography, measurement of waist circumference, and skinfold anthropometry, were used to investigate the muscular, fat, and water compartments; energy expenditure and muscular function were assessed by cycle ergometry. RESULTS: There were no significant differences in body composition, heart rate, energy metabolism, or muscular function between the group of women treated with L-T4 and the untreated group. CONCLUSION: The controlled increase of circulating T4 does not appear to modify the body composition or muscular function in women patients

Structural evolution of G-protein-coupled receptors: a sequence space approach

Class A G-protein-coupled receptors (GPCRs) provide a fascinating example of evolutionary success. In this review, we discuss how metric multidimensional scaling (MDS), a multivariate analysis method, complements traditional tree-based phylogenetic methods and helps decipher the mechanisms that drove the evolution of class A GPCRs. MDS provides low-dimensional representations of a distance matrix. Applied to a multiple sequence alignment, MDS represents the sequences in a Euclidean space as points whose interdistances are as close as possible to the distances in the alignment (the so-called sequence space). We detail how to perform the MDS analysis of a multiple sequence alignment and how to analyze and interpret the resulting sequence space. We also show that the projection of supplementary data (a property of the MDS method) can be used to straightforwardly monitor the evolutionary drift of specific subfamilies. The sequence space of class A GPCRs reveals the key role of mutations at the level of the TM2 and TM5 proline residues in the evolution of class A GPCRs

A Child with Resistance to Thyroid Hormone without Thyroid Hormone Receptor Gene Mutation: A 20-Year Follow-Up

We report here the 20-year follow-up study of a male subject diagnosed at 15 months of age as a sporadic case of pituitary resistance to thyroid hormone on the combination of clinical hyperthyroidism, elevated serum thyroid hormone (TH) levels and inappropriate thyrotropin (TSH). On d-thyroxine (D-T4) therapy from 30 months of age to 12.5 years, hyperactivity and hyperthyroid signs and symptoms as well as growth abnormalities improved, serum l-thyroxine (L-T4) enantiomer normalized, and basal and stimulated TSH decreased significantly without complete suppression. After 8 years off D-T4, at 20 years of age, clinical status was normal despite persisting high TH levels and inappropriate TSH. Evolution of serum markers of TH action and echocardiography measurements followed up from 15 months to 20 years of age either in basal condition or on triiodothyronine (T3), as well as the sequential determination of bone mineral density suggest differences in the tissue responses to T3: normal in bone with a high remodelling rate, heterogeneity for various hepatic markers, and decreased at heart level. No mutations were found in the coding sequence of TRβ1, TRβ2, TRα1, RXRγ, SMRT, NCoR1, and NCoA1. In this patient the putative long-term effects of the persisting high bone resorption are unknown

Hypochloremia and hyponatremia as the initial presentation of cystic fibrosis in three adults

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Most diagnoses of CF are made during infancy or childhood, and are based on respiratory or digestive involvement. Initial extracellular dehydration leading to the diagnosis of CF is usual in infants but has only exceptionally been reported in adults. We describe three new adult cases of CF initially presenting with depletive hyponatremia and hypochloremia following exposure to heat. At first consultation, these patients had no symptoms suggestive of CF. One patient presented with a seizure induced by hyponatremia. The two other patients were siblings carrying a novel c.4434insA mutation in exon 24 of CFTR. Acute dehydration is a very rare initial manifestation of CF but may be life-threatening. The possibility of CF should not be ignored in cases of depletive hyponatremia, hypochloremia or hypokalemic metabolic alkalosis, even in otherwise healthy patients

An elevated level of TSH might be predictive of differentiated thyroid cancer

Suppression therapy of thyreostimulin (TSH) using thyroid hormones improves survival of subjects operated for differentiated thyroid cancer. The TSH level might be different depending on the type of nodule. The objective of this study was to compare retrospectively the TSH level between two groups of subjects who underwent total thyroidectomy for a nodule, matched on sex, ethnicity, age and biological method of TSH measurement, one whose final histology was benign and one malignant. There was no significant difference between the two groups in terms of age, sex, family history of thyroid disease or thyroid autoimmunity. The subjects, whose final histology was malignant, had a mean TSH level significantly higher than subjects with benign disease (1.55 mU/l versus 0.96 mU/l, P=0.003). Cancer risk was greater when the TSH was in the upper tertile of normal range. There was no correlation between the risk of thyroid cancer and age, sex, family history of thyroid disease, or menopausal status. The relative risk of having thyroid carcinoma was higher when the margins of nodules were blurred or in the presence of microcalcifications. These data confirm a trend toward baseline values of TSH higher in subjects with a thyroid-differentiated cancer. However, we could not define a preoperative threshold that would reliably determine the malignant or benign nature of the nodule

In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

BACKGROUND: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p\u27-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p\u27-DDT exposure and reproductive abnormalities. OBJECTIVES: To investigate the putative effects of p,p\u27-DDT on the human follitropin receptor (FSHR) function. METHODS AND RESULTS: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p\u27-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p\u27-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p\u27-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p\u27-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p\u27-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p\u27-DDT was dependent on the FSHR. In addition, p,p\u27-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p\u27-DDT and potentiation of the FSHR response to FSH by p,p\u27-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p\u27-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p\u27-DDT and 16a into the FSHR transmembrane bundle. CONCLUSION:p,p\u27-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptor