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RESUMEN Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune crónica que afecta a múltiples órganos y puede asociarse a otras patologías autoinmunes como la Enfermedad tiroidea autoiunme. El hipotiroidismo es la afectación más frecuente dentro de las patologías tiroideas. Objetivo: Determinar la presencia y las concentraciones en sangre de los anti TPO en pacientes con LES. Establecer si las concentraciones elevadas de anticuerpos anti TPO están relacionadas con mayor nivel de actividad lúpica medida por SLEDAI. Metodología: Estudio observacional de corte transversal, descriptivo con componente analítico. Muestreo no probabilístico a conveniencia de casos consecutivos. Población enfocada: Pacientes con LES que tengan o no enfermedad tiroidea conocida. Se incluyeron pacientes de ambos sexos mayores de 18 años con diagnóstico de LES según los criterios del ACR/EULAR, con duración de la enfermedad mayor a 12 meses. Resultados: Se incluyó a 54 pacientes con LES con un valor de la media de la edad de 37,40 ± 12,86 años, en los cuales se encontró una prevalencia de 20,37 % de pacientes con anti- TPO positivos. El valor de la media de las concentraciones de anti TPO en los pacientes que resultaron positivos fue de 58,9 mU/l. En relación al perfil tiroideo de los pacientes con anti TPO positivo, el 55 % de ellos tenían niveles de TSH elevados con un valor de la media de las concentraciones de la TSH de 27,48 ± 4,4 mnU/l. De los 11 pacientes con niveles de anti-TPO positivo y LES, el 45,45 % presentó concentraciones de las hormonas tiroideas compatibles con hipotiroidismo. Conclusión: Este estudio constató una prevalencia de coexistencia de LES y Enfermedad Tiroidea Autoinmune del 38,8%. Estos pacientes presentaban un perfil tiroideo comptible con hipotiroidismo en su mayoría. No se encontró relación entre tener anticuerpos anti-TPO positivos y la actividad del LES, así como tampoco con los demás indicadores de actividad. ABSTRACT Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs and can be associated with other autoimmune pathologies such as autoimmune thyroid disease (ATD). Hypothyroidism is the most common disorder within the thyroid disease spectrum. Objective: To determine the presence and serum levels of anti-TPO antibodies in patients with SLE and to establish whether high concentrations of anti-TPO antibodies are related to a higher score of disease activity measured by SLEDAI. Methodology: Observational, cross-sectional, descriptive study with an analytical component. Consecutive sampling was used to select patients. The target population was patients with or without known thyroid disease. Patients of both sexes, over 18 years of age, who satisfied ACR/EULAR classification criteria for SLE, with a disease duration greater than 12 months were included. Results: A total of 54 patients with SLE were included, with a mean age of 37.4±12.86 years. We found a 20.37% prevalence of anti-TPO antibody positivity. Mean anti-TPO level in patients who tested positive was 58.9 mIU/L. In relation to anti-TPO positive patients’ thyroid profile, 55% had elevated TSH with a mean serum level of 27.48±4.4 mIU/L. Out of 11 patients with positive anti-TPO levels, 45.45% had thyroid hormone levels compatible with hypothyroidism. Conclusion : This study found a prevalence of ATD in SLE of 38.8%. Most of these patients had a thyroid profile compatible with hypothyroidism. No relationship was found between positive anti-TPO antibodies and SLE activity, as well as with other SLE disease activity markers.

espanolResumen Se reporta un caso de endocrinopatia multiple constituido por tiroiditis linfocitica y feocromocitoma en un canino labrador hembra de 6 anos de edad con historia de sincopes, alopecia, descamacion, hiperpigmentacion e hiperqueratosis en cola y nariz, intolerancia al ejercicio, disnea, depresion leve; paraclinicamente mostro TSH elevada, T4 disminuida, hipercolesterolemia, hipertrigliceridemia; por electrocardiografia se diagnostico taquicardia supraventricular. Se trato con levotiroxina sodica via oral, con respuesta parcial; sin embargo, despues de varias semanas, la paciente fallecio subitamente. En la necropsia se evidencio una condicion corporal 4/5, alopecia axilar y abdominal, reduccion de tamano de las glandulas tiroides con infiltracion de tejido adiposo; en la medula adrenal se encontro una masa color amarilla; las arterias coronarias, basilares cerebrales y de las serosas gastrointestinales estaban engrosadas con material granular amarillento intramural y oclusion luminal; el miocardio mostro regiones blanquecinas difusas al azar. Microscopicamente se encontro una tiroiditis linfocitica multifocal con atrofia severa e infiltracion de tejido adiposo; aterosclerosis de las arterias de multiples organos con trombosis; infartos cronicos y agudos del miocardio, dermatosis atrofica y feocromocitoma. Este es el primer reporte de hipotiroidismo primario en nuestro medio con enfasis en patologia macro y microscopica, asi mismo es el primer caso en la literatura de endocrinopatia multiple constituida por tiroiditis linfocitica y feocromocitoma. EnglishAbstract A case report of multiple endocrinopathy consisting of lymphocytic thyroiditis and pheochromocytoma, in a 6-year-old female canine labrador with a history of syncope, alopecia, desquamation, hyperpigmentation and hyperkeratosis in the tail and nose, exercise intolerance, dyspnea, mild depression; Paraclinically, it showed elevated TSH, decreased T4, hypercholesterolemia, hypertriglyceridemia; supraventricular tachycardia was diagnosed by electrocardiography. It was treated with levothyroxine sodium orally, with partial response; however, after several weeks, the patient died suddenly. At necropsy, a 4/5 body condition was evident, axillary and abdominal alopecia, reduction of the size of the thyroid glands with infiltration of adipose tissue; a yellow colored mass was found in the adrenal medulla; the coronary, cerebral basilar, and gastrointestinal serous arteries were thickened with intramural yellowish granular material and luminal occlusion; the myocardium showed random fuzzy whitish regions. Microscopically, multifocal lymphocytic thyroiditis was found with severe atrophy and adipose tissue infiltration; atherosclerosis of the arteries of multiple organs with thrombosis; chronic and acute myocardial infarctions, atrophic dermatosis and pheochromocytoma. This is the first report of primary hypothyroidism in our setting with an emphasis on macro and microscopic pathology, as well as the first case in the literature of multiple endocrinopathy consisting of lymphocytic thyroiditis and pheochromocytoma. portuguesResumo Reporta-se um caso de endocrinopatia multiple constituido por tireoidite linfocitica e feocromocitoma num cao labrador de 6 anos de idade com sintomatologia de sincopes, alopecia, descamacao, hiperpigmentacao e hiperqueratose na cauda e nariz, intolerância ao exercicio e dispneia; paraclinicamente TSH aumentado, T4 diminuido, hipercolesterolemia, hipertrigliceridemia; eletrocardiograficamente diagnosticou-se taquicardia supraventricular; foi tratado com levotiroxina sodica oral, com resposta parcial; no entanto, depois de varias semanas, faleceu repentinamente. Na necropsia evidenciou-se alopecia axilar e abdominal, atrofia bilateral da tireoide; na medula adrenal um nodulo de cor amarela; as arterias coronarias, basilares cerebrais e das serosas gastrointestinais encontravam-se espessadas e irregulares. Microscopicamente, observou-se tireoidite linfocitica multifocal com atrofia grave e infiltracao gordurosa; aterosclerose multi-orgânica; infartos cronicos e agudos do miocardio, dermatose atrofica e, na medula adrenal, feocromocitoma; foi realizada imuno-histoquimica para classificacao dos linfocitos tireoidianos com imunocoloracao CD3 positiva e CD 79a negativa. Este e o primeiro relato de hipotireoidismo primario em nosso meio, com enfase na patologia macro e microscopica, assim mesmo e o primeiro caso na literatura de endocrinopatia multiple que consiste em tireoidite linfocitica e feocromocitoma, no qual foi realizada a imunoclassificacao dos linfocitos intratireoidianos.

Background Pregnant women, neonates, and school-age children are vulnerable to iodine deficiency. The iodine contents in the environment (drinking water and household salt for cooking) vary by geographical location in China. The aim of this study was to assess the iodine status in vulnerable groups from different geographical zones and analyze the iodine content in household salt and drinking water from these zones. Methods In coastal and inland regions of Zhejiang Province, China, samples of spot urine, drinking water, and household salt for cooking from both pregnant women and school-age children were determined for iodine concentration between 2017 and 2018. Thyroid-stimulating hormone (TSH) levels from neonates born between 2014 and 2015 were acquired from the Newborns Screening Information System. The iodine status of the vulnerable populations was assessed according to the criteria recommended by the World Health Organization. Results The median UIC of pregnant women was significantly lower in the coastal region (113.0 μg/L) than the inland region (134.9 μg/L; p 5 mIU/L) was significantly higher in the coastal region (15.8%) than the inland region (10.5%; p Conclusions In these two regions with low iodine contents in drinking water, both pregnant women and neonates were iodine-deficient, although school-age children were iodine-sufficient. Urgent efforts are needed to improve the iodine status of pregnant women and neonates.

Purpose Newborn screening (NBS) methods to detect congenital hypothyroidism (CH) vary regarding whether total thyroxine (T4), thyroid stimulating hormone (TSH), or both are measured. Neonates with low T4 and normal or low TSH (lowT4/TSH) may only be detected by T4-inclusive methods or age-dependent repeat screens. Premature neonates and those with pituitary-hypothalamic disorders frequently manifest lowT4/TSH. Methods This is a retrospective case-study of newborns who were screen-positive for lowT4/TSH in Alabama in 2009-2016 using a combined T4 and TSH method and 2 routine NBS. The clinical, laboratory, and final diagnosis after 3 years were determined. Results Over 8 years, 225 infants were referred to our institution for evaluation and treatment of CH. Twelve infants were screen-positive for lowT4/TSH by first or second NBS. Four of the 12 infants had permanent CH (30%): 2 with primary and 2 with central etiologies. One infant with moderately severe central CH was only detected by the routine second NBS. Six of 7 premature infants had elevated TSH on serum confirmation labs consistent with a delay in hypothalamic-pituitary maturation, yet 2 of these patients were later established to have permanent primary CH. While most cases of lowT4/TSH resolved by 3 years of age, several neonates had extended periods of moderate to severe hypothyroxinemia prior to detection and treatment. Conclusion One third of the infants with lowT4/TSH on NBS in this study had permanent CH. These results emphasize the importance of T4-based assay methods, subsequent (repeat) screens and long-term follow-up in the management of neonates with lowT4/TSH on newborn screen.

Introduction: Alterations in thyroid hormones during critical illness, known as non-thyroidal illness syndrome (NTIS), were suggested to have a prognostic value. However, paediatric data is limited. The aim of this study was to assess prevalence and prognostic value of NTIS among critically ill children. Materials and methods: A prospective observational study conducted on 70 critically ill children admitted into paediatric intensive care unit (PICU). Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were measured within 24 h of PICU admission. Primary outcome was 30-day mortality. Results: NTIS occurred in 62.9% of patients but it took several forms. The commonest pattern was low FT3 with normal FT4 and TSH (25.7% of patients). Combined decrease in FT3, FT4, and TSH levels occurred in 7.1% of patients. An unusual finding of elevated TSH was noted in three patients, which might be related to disease severity. Low FT4 was significantly more prevalent among non-survivors compared with survivors (50% versus 19.2%, P = .028). NTIS independently predicted mortality (OR = 3.91; 95% CI = 1.006–15.19; P = .0491). Concomitant decrease in FT3, FT4, and TSH was the best independent predictor of mortality (OR = 16.9; 95% CI = 1.40–203.04; P = .026). TSH was negatively correlated with length of PICU stay (rs = —0.35, P = .011). FT3 level was significantly lower among patients who received dopamine infusion compared with those who did not receive it (2.1 ± 0.66 versus 2.76 ± 0.91 pg/mL, P = .011). Conclusion: NTIS is common among critically ill children and appears to be associated with mortality and illness severity. Resumen: Introducción: Se ha sugerido que las alteraciones en las hormonas tiroideas ocurridas en pacientes con enfermedad crítica, fenómeno conocido como síndrome del enfermo eutiroideo (SEE), pueden tener valor pronóstico. No obstante, los datos en población pediátrica son escasos. El objetivo del estudio fue evaluar la prevalencia y el valor pronóstico del SEE en niños críticos. Materiales y métodos: Estudio prospectivo observacional en 70 niños críticos ingresados en la unidad de cuidados intensivos pediátricos (UCIP). Se determinaron los niveles de triyodotironina libre (T3L), tiroxina libre (T4L) y tirotropina (TSH) en las primeras 24 horas de ingreso. La variable de resultado principal fue la mortalidad a los 30 días. Resultados: Se observó SEE en el 62,9% de los pacientes, aunque adoptó formas diversas. El patrón más frecuente fue un nivel bajo de T3L con niveles normales de T4L y TSH (25,7% de los pacientes). La combinación de valores bajos de T3L, T4L, y TSH ocurrió en el 7,1% de los pacientes. Hubo un hallazgo inusual de TSH elevada en 3 pacientes que podría estar asociado a la gravedad de la enfermedad. Los valores bajos de T4L se observaron con una frecuencia significativamente mayor en pacientes fallecidos en comparación con supervivientes (50% versus 19,2%, p = 0,028). El SEE predijo la mortalidad de manera independiente (OR = 3,91; IC 95% = 10,06–15,19; p = 0,0491). La combinación de niveles bajos de T3L, T4L, y TSH fue el mejor factor pronóstico independiente de mortalidad (OR = 16,9; IC 95% = 1,40–203,04; p = 0,026). Se observó una correlación negativa entre la TSH y la duración de la estancia en la UCIP (rs = —0,35; p = 0,011). El valor de T3L fue significativamente menor en pacientes tratados con perfusión de dopamina, comparados con pacientes que no la recibieron (2,1 ± 0,66 versus 2,76 ± 0,91 pg/ml, p = 0,011). Conclusión: El SEE es común en niños críticos y parece estar asociado a la mortalidad y la gravedad de la enfermedad.

Introduction: TSH-secreting pituitary adenomas (TSH-sPAs) or thyrotropinomas are very rare forms of pituitary adenomas (PAs). Although several authors have presented single cases or case series on this occurrence, only few authors have indicated that hyperthyroidism heralded the pathogenesis of TSH-sPA. We also present a case of refractory transposing hyperthyroid disorder inducing TSH-sPA. Case Presentation: We present a 47-year-old woman with 20 years’ history hyperthyroidism and a visible anterior neck swelling with normal TSH. She was put on anti-thyroid medications that transposed her hyperthyroid state to hypothyroid state with elevated TSH and a pituitary adenoma (PA). The PA was surgically excised via transsphenoidal approach. Conclusion: Hyperthyroidism or anti-thyroid medications could be responsible for the trigger of a feedback mechanism that led to over-secretion of TSH and subsequently the development of PA.

Persistent elevation of thyroid-stimulating hormone (TSH) is common in endocrinology practice in patients undergoing replacement or suppression therapy with levothyroxine sodium (LT4). After examining the causes of this condition, LT4 absorption test is recommended. In this report, we wanted to share our results of LT4 absorption test in patients with elevated TSH levels. The files of patients who presented to our clinic between 2015 and 2018, whose TSH elevation continued despite high-dose LT4 therapy, and who underwent absorption test were reviewed retrospectively. Levothyroxine sodium absorption test was applied to five patients. Absorption test revealed LT4 malabsorption in two patients and pseudomalabsorption in the other three patients. When all published pseudomalabsorption cases were considered, it has been stated that at least 2.5 times increase in basal fT4 level may exclude malabsorption. The formula we used has been implemented by Cleveland Clinic since 2014. In cases where TSH normalization is not achieved despite high doses of LT4 therapy, LT4 absorption test is an easy test for administration and interpretation and prevents unnecessary medical treatments and examinations.

Background The aim of this study was to investigate the impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer. Methods Blood samples were collected on the first visit to our department and 14 days after embryo transfer. Women were divided into three groups based on D14 TSH levels, which were compared to basal TSH levels in groups with different clinical outcomes. TSH levels between pregnant and nonpregnant women were also compared. Results The clinical pregnancy rate in women with lower TSH levels 14 days after transfer was slightly but significantly lower (56%, P = 0.05) compared to those with higher TSH levels. Furthermore, TSH levels were significantly elevated 14 days after transfer compared to basal TSH levels in pregnant women and in women who successfully became pregnant (P Conclusions Elevated TSH levels 14 days after embryo transfer compared to basal TSH levels seem to play a protective role and predict favorable clinical outcomes under specific conditions.

Introdução: Os adenomas hipofisários são tumores caracterizados pela proliferação de células adeno-hipofisárias produtoras de hormônios tróficos. Dentre eles, os adenomas hipofisários produtores de TSH (TSHomas), neoplasias benignas pouco frequentes, que correspondem a menos do que 3% dos adenomas hipofisários. Método: Pesquisamos os termos TSHomas, tireotropinomas e adenomas pituitários secretores de TSH nas bases Pubmed, Lilacs e Scielo. Incluímos artigos publicados entre 2010 e 2020, sendo excluídos relatos de casos, artigos indisponíveis e que não tratavam sobre o tema. Resultados e discussão: Os TSHomas são tumores fibrosos, monoclonais, com incidência entre 0,015 a 0,03 casos/100.000 habitantes, que se manifestam por hipertireoidismo e sintomas causados por efeito de massa. São diagnosticados diante da elevação de TSH juntamente a hormônios tireoidianos, na presença de alterações neurorradiológicas. O tratamento de primeira escolha consiste na neurocirurgia transesfenoidal, sendo os análogos de somatostatina e a radioterapia alternativas para o manejo de pacientes em que a intervenção cirúrgica é desaconselhada. Conclusão: Os TSHomas são raros, contudo, precisam ser investigados diante da secreção inadequada de TSH.Palavras chave: Adenoma, Hormônios tireoidianos, Neoplasias hipofisárias, Síndrome da secreção inadequada de TSH, Hipertireoidismo centralABSTRACTIntroduction: Pituitary adenomas are tumors characterized by the proliferation of adenohypophysis cells that produce trophic hormones. Among them, TSH-producing pituitary adenomas (TSHomas), uncommon benign neoplasms, whichcorrespond to less than 3% of pituitary adenomas. Method: We searched for the terms TSHomas, thyrotropinomas and pituitary adenomas secreting TSH in the Pubmed, Lilacs and Scielo databases. We included articles published between 2010 and 2020, excluding case reports, articles that were unavailable and did not deal with the topic. Results and discussion: TSHomas are fibrous, monoclonal tumors, with an incidence of 0.015 to 0.03 cases / 100,000 inhabitants, which are manifested by hyperthyroidism and symptoms caused by a mass effect. They are diagnosed with elevated TSH along with thyroid hormones, in the presence of neuroradiological changes. The first-choice treatment consists of transsphenoidal neurosurgery, with somatostatin analogs and radiotherapy being alternatives for the management of patients in whom surgical intervention is not recommended. Conclusion: TSHomas are rare, however, they need to be investigated due to inadequate TSH secretion.Keywords: Adenoma, Thyroid hormones, Pituitary neoplasms, Inappropriate TSH secretion syndrome, Central hypothyroidism

Background. Georgia historically was a country with moderate to severe iodine deficiency and high prevalence of endemic goiter. A representative countrywide iodine survey conducted in Georgia in 2017 confirmed optimal iodine nutrition of the population with median UIC 298 mcg/L in SAC and 211 mcg/L in PW. Aim. The aim of this study was to assess status of iodine nutrition of population in Georgia. Methods. The assesement based on the proportion of neonatal Thyroid-Stimulating Hormone (TSH) levels >5mIU/L from 2009 to 2015 and compare these data with the results of direct assessment of iodine status made during the 2017 national survey. Results. From 2009 to 2015 the proportion of newborns with TSH >20 mIU/L decreased threefold: from 0.45 to 0.15%. This trend was observed in all regions of the country with significant difference between the capital city and Western in Eastern parts of the country. There has been also significant reduction of the prevalence of TSH >5 mIU/L in Georgia from 4.46% in 2009 to 3.5% in 2015. However, only in Tbilisi the frequency of elevated TSH was below 3% – the cutoff level for adequate iodine nutrition. In other regions (Western and Eastern Georgia) prevalence of TSH >5 mIU/L was 3.8% and 4.4% respectively that could be falsely interpreted as mild iodine deficiency. Conclusions. Although neonatal TSH is useful to detect moderate to severe iodine deficiency, it should be cautiously recommended for the evaluation of iodine status in iodine sufficient to mildly iodine deficient regions.

Objective. We retrospectively analyzed activated BAT visualization on FDG-PET/CT in patients with various conditions and TH levels to clarify the relationships between visualization of BAT on FDG-PET/CT and the effect of TH. Methods. Patients who underwent clinical FDG-PET/CT were reviewed and we categorized patients into 5 groups: (i) thyroid hormone withdrawal (THW) group; (ii) recombinant human thyrotropin (rhTSH) group; (iii) hypothyroidism group; (iv) hyperthyroidism group; and (v) BAT group. A total of sixty-two FDG-PET/CT imaging studies in fifty-nine patients were performed. To compare each group, gender; age; body weight; serum TSH, FT3, and FT4 levels; and outside temperature were evaluated. Results. No significant visualization of BAT was noted in any of the images in the THW, rhTSH, hypothyroidism, and hyperthyroidism groups. All patients in the BAT group were in a euthyroid state. When the BAT-negative and BAT-positive patient groups were compared, it was noted that the minimum and maximum temperature on the day of the PET study and maximum temperature of the one day before the PET study were significantly lower in BAT-positive group than in all those of other groups. Conclusions. Elevated TSH condition before RIT, hyperthyroidism, or hypothyroidism did not significantly impact BAT visualization of clinical FDG-PET/CT images.

The heavy metals pollution and related health issues were widely reported in e-waste sites, while the impacts of e-waste exposure on the essential trace elements have been neglected. The aim of this study was focused on the internal Cu, Fe, Mn and Zn levels in the residents from an e-waste site and the potential endocrine disrupting effects of these essential trace elements on the hypothalamic-pituitary-thyroid (HPT) axis. This was a cross-sectional study that 87 subjects were recruited from the e-waste site and 81 from the reference site. The results indicated that the e-waste exposed group had significantly lower Fe, Mn level when compared with the reference group (p

Background The incidence of congenital hypothyroidism (CH) differs significantly among different ethnicities and regions, and early differentiation of transient CH is important to avoid unnecessary prolonged treatment with L-T4. Objective To investigate the incidence of CH based on the newborn screening program in Guangxi Zhuang Autonomous Region, China, and to analyze the predictors that might allow for an early differentiation between permanent (P) and transient (T) CH. Design and methods Data from newborn screening program over a seven-year period (January 2009 to January 2016) at Guangxi Maternal and Child Health Hospital are analyzed. Blood samples were collected on filter paper between 3 and 7 days after birth, and TSH level was measured by time-resolved fluorescence assay. Individuals with increased TSH (TSH ≥ 8 IU/L) levels detected by newborn screening were recalled for further evaluation. Serum TSH, FT3 and FT4 were determined by electrochemiluminescence assay using venous blood samples. Diagnosis of CH is based on elevated TSH levels (>10 IU/L) and decreased FT4 levels (4 levels were diagnosed as hyperthyrotropinemia. Permanent or transient CH was determined by using the results of thyroid function tests after temporary withdrawal of L-T4 therapy at approximately 2–3 years of age. Results Among 1,238,340 infants in the newborn screening program, 14,443 individuals were recalled for reevaluation (re-call rate 1.18%), 911 and 731 individuals were subsequently determined to have hyperthyrotropinemia and CH respectively; thus, a prevalence of 1:1359 and 1:1694 for hyperthyrotropinemia and CH. Of the 731 patients with CH, 161 patients were diagnosed with permanent CH (PCH), and 159 patients were diagnosed with transient CH (TCH), the other 411 patients are too young to determine their subtypes. Patients with PCH required an increasing dose of L-T4 during the first few years, whereas patients with TCH required a decreased dose of L-T4. The TSH levels at diagnosis and the dose of L-T4 used were significantly higher in PCH cases than in transient cases. The FT4 levels at diagnosis were significantly lower in PCH cases than in TCH cases. The TSH levels at diagnosis, FT4 levels at diagnosis and L-T4 doses at 90 days were evaluated as predictors for differentiating PCH and TCH, and their accuracy at their respective optimal cutoffs were determined to be 60.6%, 66.7% and 93.9%, respectively. Conclusions The CH incidence in Guangxi Zhuang Autonomous Region is slightly higher (1:1694) compared to the worldwide levels (1/2000–1/4000). The PCH and TCH ratio is close to 1; thus, the estimated PCH incidence is 1/3388, which is similar to reported worldwide average incidence (1/3000). The L-T4 dose required at 90 days (>30 μg/day) has the highest predictive value for PCH. Earlier differentiation of PCH and TCH helps to determine appropriate treatment course.

This study aims to explore the correlation between serum 25-hydroxyvitamin D and thyroid hormones during the second trimester. In total, 277 pregnant women at 13-28 weeks of gestation were enrolled. According to the level of thyrotropic-stimulating hormone, they were divided into a reduced TSH group, a normal TSH group and an elevated TSH group. In this study, we found that the prevalence of vitamin D deficiency was as high as 94.58%. The 25-hydroxyvitamin D level in the reduced TSH group was lower than that in the normal thyroid function group (p = .0005), and the 25-hydroxyvitamin D level in the elevated TSH group was higher than that in normal TSH group (p=.0339). A positive correlation was observed between 25-hydroxyvitamin D and thyrotropic-stimulating hormone (r = 0.3034, p = .0000). Furthermore, 25-hydroxyvitamin D was negatively correlated with the free thyroxine level (r = -0.1286, p = .0323) as well as the free triiodothyronine level (r = 0.1247, p = .0380). These data suggest that the relationships between 25-hydroxyvitamin D and thyroid parameters were characterized during the second trimester. Pregnant women in the second-trimester who are diagnosed with transient hyperthyroidism should be evaluated for the possibility of vitamin D deficiency.

Background: To analyze predictive factors suggesting transient congenital hypothyroidism (TCH) compared to permanent congenital hypothyroidism (PCH) or transient thyroid function test (TFT) abnormalities among children who had positive screening results at our centers over the past decade. Methods: A retrospective chart review of 105 subjects who presented elevated TSH levels on a newborn screening test (NST) was done. TCH was defined when a trial-off therapy was successful, and PCH was defined when a trial failed or when the subject was kept on medication beyond 3 years of age. A transient TFT abnormality was defined when follow-up TFTs were normalized without levothyroxine (LT4) therapy. Results: Congenital hypothyroidism (CH) was diagnosed in 75.2% (TCH 35.2% and PCH 40.0%) of all subjects; the others (24.8%) showed transient TFT abnormalities. Initial NST-TSH levels (optimal cutoff point, 31.0 mu IU/mL), the LT4 dose at 2 years of age (4.1 mu g/kg/day), and the maximal LT4 dose (50 mu g/day) merged as significant predictive factors discriminating between TCH and PCH. The initial serum level of free T4 (1.06 ng/dL) and not TSH (27.2 mu IU/mL) was the only discriminating factor between transient TFT abnormalities and TCH. Conclusion: Earlier re-evaluation might be possible when a patient's initial NST-TSH levels and maximal or 2-year LT4 doses are low, as both are important predictors of successful trial-off therapy in CH patients. When the initial serum level of free T4 is above the average value in neonates with mildly elevated TSH levels, TFTs may be more likely to normalize on their own. Copyright (C) 2017, Taiwan Pediatric Association-. Published by Elsevier Taiwan LLC. This-is an open access article under the CC BY-NC-ND license

Wprowadzenie: Pacjenci z wrodzoną niedoczynnością tarczycy (congenital hypothyroidism - CH) mają większe niż w populacji ogólnej ryzyko wystąpienia innych pozatarczycowych, wrodzonych nieprawidłowości. Nieprawidłowości te dotyczą głównie narządów i układów, w których prawidłowy rozwój i funkcjonowanie zaangażowane są geny odpowiedzialne również za prawidłowy przebieg organogenezy i syntezy hormonów gruczołu tarczowego. Cel pracy: Ocena częstości występowania innych wad towarzyszących CH, z uwzględnieniem możliwych przyczyn tej zależności i roli badań genetycznych. Materiał i metody: Do badania zostały włączone 54 noworodki objęte badaniem przesiewowym w kierunku CH w latach 2010-2017 w województwie małopolskim. Przeprowadzono dokładną retrospektywną analizę dokumentacji medycznej tych pacjentów. Wyniki: W grupie badanej u 20 z 54 pacjentów (37%) stwierdzono obecność współtowarzyszących CH, wrodzonych nieprawidłowości innych narządów. U 10 (18,5%) potwierdzono obecność wady serca, u 5 (9,25%) stwierdzono nieprawidłowe objawy ze strony układu oddechowego, u 7 (12,96%) stwierdzono nieprawidłowe objawy ze strony układu pokarmowego, u 5 (9,25%) rozpoznano nieprawidłowości ze strony układu moczowo-płciowego, u 3 (5,55%) stwierdzono nieprawidłowości ze strony układu nerwowego, u 6 (11,1%) rozpoznano nieprawidłowości ze strony układu mięśniowo-szkieletowego. Wnioski: Analiza uzyskanych danych i aktualnego piśmiennictwa wskazują, że największą rolę w powstawaniu pozatarczycowych nieprawidłowości u pacjentów z CH mogą mieć czynniki genetyczne. Zasadna wydaje się identyfikacja mutacji, która doprowadziła do CH. Znając mutacje mogące odpowiadać za wady współtowarzyszące CH, można by objąć pacjentów z CH odpowiednimi badaniami skriningowymi, mającymi na celu ich wczesne zdiagnozowanie, a w efekcie - odpowiednie, natychmiastowe leczenie. Introduction: Patients with congenital hypothyroidism (CH) can have an increased risk of occurrence of extrathyroidal defects compared to the general population, which could influence their development. The abnormalities occur mainly in organ systems whose development and function is dependent on genes that are also responsible for proper organogenesis of the thyroid gland and thyroid hormone synthesis. Aim of the study: The aim of the study was to evaluate the frequency of extrathyroidal defects in CH patients, taking into consideration the cause of this co-occurrence and the role of genetic tests. Material and methods: The study included 54 newborns with positive screening test for CH based on elevated TSH level, in the years 2010-2017, from South-Eastern Poland. The data was retrieved retrospectively from patients’ medical records. Results: Twenty of 54 newborns with CH (37%) had congenital defects of other organs. In 10 (18.5%) cardiac defects were found, in 5 (9.25%) abnormal symptoms of the respiratory system, 7 (12.96%) had abnormalities of the gastrointestinal system, five (9.25%) had genitourinary abnormalities, 3 (5.55%) had abnormalities of the nervous system, and 6 (11.1%) had musculoskeletal abnormalities. Conclusions: The analysis of our data and current literature suggests that genetic factors play the most important role in the development of extrathyroidal abnormalities in newborns with CH. Identifying the mutation causing CH, the potential defects that can accompany newborns with CH, screening could be offered for these patients in order to obtain an earlier diagnosis and implement early and appropriate treatment.

A 74-year-old asymptomatic Japanese man with suspected thyroid dysfunction was referred to our hospital. He had an elevated TSH (53.8 mIU/L; reference interval: 0.5-5.0) despite a free T4 (FT4) level (1.4 ng/dL; reference interval: 0.9-1.6). Further analysis revealed macro-TSH. A notable finding was that a 500-μg TRH stimulation test revealed a blunted free T3 (FT3) response despite a prolonged TSH response. Macro-TSH typically presents with inappropriately marked elevation of serum TSH levels compared with other thyroid hormones, as exhibited in our case. However, the level of TSH elevation that might differentiate macro-TSH from subclinical hypothyroidism is poorly known. We retrospectively analyzed 8,183 concurrent measurements of TSH and FT4 in individuals previously examined in our hospital to define the cut-off value for screening cases of inappropriate TSH elevation. FT4 values were rounded off to one decimal place, and the 97.5th percentile of TSH against each FT4 value was calculated. The data of our patient and that of 30 cases of macro-TSH extracted from the English literature were then assessed. When the approximate curve obtained from the 97.5th percentile of TSH values was defined as the cut-off value [Log10TSH = 0.700 + 1.549/{1 + (FT4/0.844)6.854}], 25 of the 31 (80.6%) macro-TSH cases were identified. In conclusion, we report for the first time a case of macro-TSH demonstrating an abnormal FT3 response to TRH. A cut-off value of TSH adjusted to the FT4 level may be a good method of screening for inappropriate TSH elevation (or inappropriate hyperthyrotropinemia) including those caused by macro-TSH.

Introducción: se carece de guías clínicas claras para la solicitud de pruebas tiroideas en pacientes hospitalizados. Se evaluó el nivel de pertinencia y tipos de perfil solicitados en pacientes hospitalizados en el Hospital Universitario de San Vicente Fundación. Métodos: estudio retrospectivo en pacientes mayores de 14 años, no gestantes, hospitalizados en el Hospital Universitario de San Vicente Fundación. Se evaluaron 351 registros en el sistema de historia clínica, se definieron seis grupos de pertinencia, las categorías 1 a 4 se consideraron como pertinente, y la 5 y 6 como solicitudes de pruebas no pertinentes. Se registraron variables demográficas y clínicas. Las variables estadísticas cuantitativas fueron evaluadas con la prueba U Mann-Whitney, las variables cualitativas con chi2 Pearson y Estadístico de Fisher. Resultados: se obtuvieron valores normales en 67% de las TSH medidas, en 80% de las T4 y el 53% de las T3. La anormalidad más frecuente de la TSH fue elevación en 24%, para la T4 libre fue su reducción en 11.5% y para la T3 elevación en 27%. Se encontró TSH ≤ 0.1 en 3.5% y ≥ 20 en 3.9%. De los 60 pacientes con TSH elevada el 75% están entre 5 y 9.99 mUI/mL. La T4L ≤ de 0.7 ng/dL fue 11.5% y ≥ 1.48 en 8.6%. El 95% de las T4L medidas en la categoría no pertinente fueron normales. Conclusiones: se debe mejorar la pertinencia de solicitud de pruebas tiroideas en hospitalización. Se propone abordaje inicial solo con TSH

Background: The levothyroxine absorption test for evaluation of pseudomalabsorption in patients with primary hypothyroid is not standardised. An individual in whom a workup for malabsorption is warranted remains undefined. Methods: Twenty-five euthyroid, 25 newly diagnosed hypothyroid, 25 treated hypothyroid with normalised TSH, and 25 hypothyroid subjects with elevated TSH despite adequate dose of levothyroxine for more than 6 months, and 10 euthyroid subjects with true malabsorption were administered levothyroxine (10 μg/kg or maximum 600 μg) to study its absorption profile by measuring free T4 level at hourly intervals for 5 h. Results: Free T4 peaked at 3 h with marginal insignificant decline at 4 h in all groups. The increments of free T4 (between baseline and 3 h) of the four groups (except malabsorption) were not statistically different. The mean increment of free T4 in true malabsorption was 0.39 ng/dL (95% CI: 0.29–0.52) and it was 0.78 ng/dL (95% CI: 0.73–0.85) (10.4 pmol/L) for other groups combined together. The cut off of free T4 increment at 3 h from baseline above 0.40 ng/dL had a sensitivity of 97% and specificity of 80% (AUC 0.904, p < 0.001) to exclude true malabsorption. Conclusion: Subjects with elevated TSH on adequate dose of LT4 can be reliably diagnosed to be non-adherent to treatment with levothyroxine absorption test. The incremental value above 0.40 ng/dL (5.14 pmol/L) at 3 h may be useful to identify individuals where workup of malabsorption is unwarranted.

Pitfalls in hormonal assays are commonly seen in clinical practice and may lead to erroneous clinical impressions and treatments. In this article, we address common laboratory pitfalls encountered during evaluation of patients with real or presumed endocrine disorders including high dose hook effect and falsely normal prolactin in cases of macroprolactinomas, macroprolactinemia and falsely elevated prolactin, macrothyrotropinemia and falsely elevated TSH, heterophile antibodies leading to false elevation of hormonal concentration, biotin interference with different hormonal assays, cross-reactivity of steroid hormones immunoassays, and others. We describe the mechanisms of such laboratory pitfalls, review clinical scenarios in which they might occur, and discuss the ways to resolve such conundrums. The aim of this article is to present a learning material for the endocrine trainees and practitioners.

Case: A 30-yr-old pregnant woman presented with hypothyroidism at 19 weeks. She had been diagnosed with hypothyroidism 15 years ago and was treated with L-T4. She was told 1-1/2 yr ago that her thyroid levels had normalized and L-T4 was discontinued. Shortly thereafter she became pregnant. Labs then included TSH-37 mU/L (NL: 0.358-3.74) and Free T4 (FT4)-0.52 ng/dL (NL: 0.76-1.46) with elevated Anti-Peroxidase and Anti-Thyroglobulin antibody levels. She was started on L-T4, 25 mcg/d. During the pregnancy, her FT4 levels (0.52 - 1.27) were commensurate with her associated L-T4 dosages (25 - 150 mcg/day), consistent with a mid-FT4 level in accord with her calculated Ideal Body Weight dosage of 94 mcg/day. Likewise, her TSH levels (37 - 1.13) were inversely commensurate with her FT4 levels and L-T4 dosages. She delivered a normal baby, and since has been treated with L-T4, 150-175 mcg/d, and remained clinically euthyroid. Because of renal failure (GFR-36.3) with Type I Renal Tubular Acidosis, she was started on a urine alkalizing agent, sodium citrate/citric acid (SC/CA), 20 mg orally every 6 hrs. Since delivery, the patient’s FT4 levels have been very erratic and non-commensurate with her L-T4 dosages. In the past 14 mos. she has been on L-T4 dosages of 150-175 mcg/d (aver: 172 mcg/d). Her FT4 levels (ranging from 0.17 to 1.51 [aver: 0.89]), however, have continued to correlate very closely with her TSH levels (0.397 to 373 [aver: 68.7]). Notably, her four highest TSH levels were 373, 177, 134 and 122. She credibly insists on full compliance with her L-T4 therapy, never taking the medication within an hour of having breakfast or taking her other medications, which included ferrous sulfate and SC/CA. Interestingly, the highest TSH level recorded before starting SC/CA was only 24.9, associated with a low FT4 level of 0.66. Discussion: Evaluation focused on (1) the high levels of TSH, and (2) the postpartum lack of correlation of her FT4 levels and her L-T4 dosages. Regarding the former, extensive thyrotroph hyperplasia was not evident on pituitary MRI (though not ruling out lesser hyperplasia) and very high TSH levels are occasionally observed in patients hypothyroid for years. Resistance to Thyroid Hormone and TSH-producing pituitary adenoma were not likely in view of the close correlation of her TSH and FT4 levels, and her occasional near-normal TSH and FT4 levels. Human Anti-Mouse Antibodies (HAMA) and Macro-TSH were ruled out by assay. TSH Receptor Resistance to TSH could not be ruled out for lack of available assays and genetic analysis. Her normal absorption of L-T4 during pregnancy argues against chronic intrinsic malabsorption. Conclusion: Malabsorption of L-T4 relating to drug interference from ferrous sulfate and/or GI alkalinization from use of SC/CA, in a patient with thyrotroph hyperplasia from long-term Hashimoto’s hypothyroidism would appear to be the most likely, though complex, explanation.

Introduction Patients with persistently abnormal thyroid function tests despite increasing thyroid hormone supplementation should be investigated for several clinically important causes. We present an interesting such case in which widely fluctuating TSH measurements were caused by assay-interfering heterophile antibodies. Clinical Case A 57-year-old female with primary hypothyroidism was referred to our clinic for widely fluctuating TSH levels despite adjustment of levothyroxine dose. Indeed, her TSH levels over the previous year were as high as 24.56 μIU/ml (reference range 0.27-4.20) with normal or even elevated Free T4 (up to 1.64 ng/dl, reference range 0.70-1.48), but with no symptoms of hypo- or hyperthyroidism. Laboratory assessment at our institution revealed a TSH of 0.13 µIU/ml without change in the dose of levothyroxine since the prior measurement. It was assumed that the patient had trouble with medication compliance. Over the subsequent year, serial thyroid function tests (TFTs) done at an outside institution showed TSH elevated between 18-28 µIU/ml with elevated free T4 levels. Multiple possibilities were considered as the cause of discordant TFTs including poor compliance (although she denied missing any levothyroxine doses), thyroid hormone resistance syndrome, TSH producing tumor, interference from biotin supplementation and antibody interference. Upon further review, a pattern was evident in the TFTs, with marked elevations in TSH levels noted when labs were done locally, but normal or low TSH levels when done at our institution, raising the suspicion of interfering antibodies. The majority of commercially available TSH assays use an automated chemiluminescence system with two-site sandwich antibody assay. Antibodies including heterophile antibodies (human anti-mouse monoclonal antibodies or HAMAs), autoantibodies and rheumatoid factors can interfere with immunoassays. HAMAs are the most common cause of interference. Clinical laboratory personnel can employ several techniques to investigate potential antibody interference. In our case, the clinical pathologist ran the TSH assay with dilution analysis at our institution and showed a linear pattern, indicating no interference. However, a dilutional analysis of this same sample at the outside lab did not demonstrate dilutional linearity confirming the presence of an interfering antibody. Thus, the TSH values obtained at the outside institution were erroneous. The patient’s actual TSH was low at 0.21 µIU/ml, hence solving mystery of her discordant TFTs. Conclusion Interfering antibodies such as HAMAs should be suspected whenever thyroid function tests done at different laboratories conflict with each other, conflict with the clinical picture, or form an unusual pattern. Reference: N Bolstad et al. Best Pract Res Clin Endocrinol Metab. 2013; 27(5):647-61

Hypothyroidism is characterized by increased thyrotropin (TSH) levels and reduced free thyroid hormone fractions while, subclinical hypothyroidism (sHT) by elevated serum TSH in the face of normal thyroid hormones. The high frequency of hypothyroidism among the general population in Western Countries made levothyroxine (LT4) one of the 10 most prescribed drugs. However, circulating TSH has been demonstrated to increase with aging, regardless the existence of an actual thyroid disease. Thus, when confronting an increase in circulating TSH levels in the elderly, especially in the oldest old, it is important to carry an appropriate diagnostic path, comprehensive of clinical picture as well as laboratory and imaging techniques. In the current review, we summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly-therapy. The treatment of choice for hypothyroid patients is hormone replacement with LT4 but, it is important to consider multiple factors before commencing the therapy, from the age dependent TSH increase to the presence of an actual thyroid disease and comorbidities. When treatment is necessary, a tailored therapy should be chosen, considering poly-pharmacy and frailty. A careful follow-up and treatment re-assessment should be always considered to avoid the risk of over-treatment. It is important to stress the need of educating the patient for a correct administration of LT4, particularly when poly-therapy is in place, and the importance of a tailored therapeutic approach and follow-up, to avoid overtreatment.

Calcium carbonate was previously shown to interfere with l-thyroxine absorption. To estimate the magnitude of tablet l-thyroxine malabsorption caused by calcium carbonate, with resulting increase in serum thyrotropin (TSH), we performed a cohort study in a referral care center. Fifty postmenopausal hypothyroid l-thyroxine-treated women (age 71.7 ± 5.1 years) who added calcium supplementation (600–1000 mg/day) were considered. They were taking l-thyroxine 45–60 min before breakfast (setting 1). After 4.4 ± 2.0 years from initiation of l-thyroxine therapy, they took calcium supplemaentation within 2 h after l-thyroxine taking (setting 2) for 2.3 ± 1.1 years. Hence, we recommended postponing calcium intake 6–8 h after l-thyroxine (setting 3). We evaluated TSH levels, the prevalence of women with elevated TSH (>4.12 mU/L), total cholesterolemia, fasting glycemia, blood pressure, and the prevalence of hypercholesterolemia, hyperglycemia, and hypertension. TSH levels were 3.33 ± 1.93 mU/L versus 1.93 ± 0.51 or 2.16 ± 0.54 comparing setting 2 with setting 1 or 3 (P

Background: Elevated free thyroxine could be primary or secondary, endogenous or exogenous and often presents with symptoms of hyperthyroidism. Thyroxine levels are low in hypothyroidism, where the individual requires exogenous supplementation to maintain a euthyroid state. However, thyroxine levels may be elevated in a hypothyroid patient because of over-supplementation/over-suppression with exogenous agent(s) or secondary to other pathologies and rarely, laboratory error or assay interference may cause alteration in the levels of the thyroid hormones. Case report: A 44-year-old man with well controlled hypothyroidism was referred for assessment of markedly elevated TSH and free thyroxine levels with low free T3. Clinically the patient was hypothyroid with symptoms of fatigue and weight gain of 30 pounds over the past 3-months and the TSH levels were consistent with marked hypothyroidism. However, free thyrxoine was markedly elevated, opposite of what to be expected. A systematic evaluation, presented here, was helpful in the diagnosis of pseudohyperthyroxinemia secondary to assay interferences in a timely fashion, avoiding unnecessary further investigations. Conclusions: Interference in immunoassays is an important clinical problem that is underestimated and can have important clinical consequences. It is important to recognize the possibility of such interferences early in the diagnostic process and to implement protocols to identify these whenever possible, in a timely fashion, to prevent untoward consequences. Vigilance by both the clinician and the laboratory staff is important.

ObjectiveConsumers may choose soya foods as healthful alternatives to animal products, but concern has arisen that eating large amounts of soya may adversely affect thyroid function. The present study aimed to examine the association between soya food consumption and serum thyroid-stimulating hormone (TSH) concentrations in North American churchgoers belonging to the Seventh-day Adventist denomination that encourages vegetarianism.DesignParticipants completed six repeated 24 h dietary recalls within a 6-month period. Soya protein and soya isoflavone intakes were estimated, and their relationships to TSH concentrations measured at the end of 6 months were calculated using logistic regression analyses.SettingCalibration sub-study of the Adventist Health Study-2.SubjectsWomen (n 548) and men (n 295) who were not taking thyroid medications.ResultsIn men, age and urinary iodine concentrations were associated with high serum TSH concentrations (>5 mIU/l), while among women White ethnicity was associated with high TSH. In multivariate models adjusted for age, ethnicity and urinary iodine, soya isoflavone and protein intakes were not associated with high TSH in men. In women higher soya isoflavone consumption was associated with higher TSH, with an adjusted odds ratio (highest v. lowest quintile) of 4·17 (95 % CI 1·73, 10·06). Likewise, women with high consumption of soya protein (midpoint of highest quintile, 11 g/d) v. low consumption (midpoint of lowest quintile, 0 g/d) carried increased odds of high TSH (OR=2·69; 95 % CI 1·34, 5·30).ConclusionsIn women high consumption of soya was associated with elevated TSH concentrations. No associations between soya intake and TSH were found in men.

BACKGROUND Mild or borderline congenital hypothyroidism [often referred to as mild neonatal hyperthyrotropinemia (MNH)] is characterized by an abnormal newborn screen (NBS), followed by mildly elevated TSH and normal FT4 on confirmatory testing. This condition is increasingly observed, but data regarding optimal management are limited. OBJECTIVE Examine the use of routine technetium thyroid scanning (TS) in the management of MNH. METHODS Retrospective study of infants with MNH between 2000 and 2011. We assessed the clinical course of infants with MNH according to TS results; as a comparator, infants with classic congenital hypothyroidism (CH) were analysed in parallel. RESULTS We identified 69 infants (52% boys) with MNH and 164 (34% boys) with classic CH. TS results were divided into four subgroups: no uptake in 7% of MNH vs 24% of classic CH (P

Anorexia nervosa (AN) is typically associated with altered thyroid function tests, notably a low total and free T3, and lower, but within normal range, free T4 and TSH. A 16-year-old girl with a four-year history of AN presented with elevated TSH that fluctuated with changes in weight. TSH was within normal limits (1.7–3.64 mIU/L) following periods of weight loss and elevated with weight gain (5.9–21.66 mIU/L). Antithyroperoxidase antibodies were markedly elevated, suggesting chronic Hashimoto's thyroiditis. Of note, the elevated TSH that would be expected in Hashimoto's thyroiditis was blunted by weight loss associated with AN. Physicians should be aware that AN may contribute to masking thyroid abnormalities in Hashimoto's thyroiditis. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:932–935).

The indications for levothyroxine replacement therapy for subclinical hypothyroidism (SH) remain a subject of debate, especially when prescribed for older adults. The results of the recent TRUST trial indicate that levothyroxine does not improve clinical symptom scores among elderly patients with SH. While there is much concern regarding the dilemma of introducing or withholding levothyroxine, less attention may be paid to the differential diagnosis of an elevated TSH level, which is the prerequisite for diagnosing SH. Herein, we review these issues facing endocrinologists and internists/generalists either in practice or in training. When a patient presents abnormal thyroid test results compatible with SH, a series of issues need to be addressed before the implementation of replacement therapy is considered: first, an isolated TSH elevation not linked to a primary thyroid pathology should be excluded; second, the persistent nature of the patient’s TSH elevation and SH profile should be verified; third, SH symptoms and potential complications relevant for the specific patient should be documented; fourth, expectations from levothyroxine substitution therapy for SH in the specific patient should be clarified. Only then can the decision be made whether levothyroxine substitution should be introduced or not.

Objective: To discuss the approach to the isolated finding of an elevated thyrotropin (TSH) level on routine biochemical screening of a depressed patient. Method: A focused literature review as well as discussion of published clinical guidelines and the formulation of a rational clinical approach. Results: Screening for thyroid dysfunction is part of the routine assessment of the depressed patient. It is not uncommon for such patients to have an isolated elevation of TSH levels with nor laboratory or clinical features of thyroid disease. There is often misunderstanding about how to deal with this isolated laboratory finding which can lead to unnecessary investigation and treatment. Conclusions: A rational approach to evaluation and management of an isolated elevated TSH level is suggested.

Background: This study was done to evaluate the role of thyroid function i.e., free T3, free T4 and thyroid stimulating hormone (TSH) in relation to the occurrence of acne vulgaris.Methods: A total of 50 patients clinically diagnosed with acne vulgaris were subjected to a thyroid function test and results were evaluated.Results: While all the 50 patients had normal free T3 and free T4 levels, 9 (18%) of the 50 patients displayed an elevated TSH level. Gender distribution among the patients with elevated TSH learned more towards the male population with 6 patients while there were only 3 female patients with elevated TSH.Conclusions: There have been few studies regarding the role of thyroid function in acne vulgaris in relation to free T3, free T4 and TSH, though the presence of thyroid antibodies have been highlighted in quite a few studies. This study has shown the insignificance of thyroid function in acne vulgaris thus accentuating the negative.

Delays in following up abnormal test results are a common problem in outpatient settings. Surveillance systems that use trigger tools to identify delayed follow-up can help reduce missed opportunities in care. To develop and test an electronic health record (EHR)-based trigger algorithm to identify instances of delayed follow-up of abnormal thyroid-stimulating hormone (TSH) results in patients being treated for hypothyroidism. We developed an algorithm using structured EHR data to identify patients with hypothyroidism who had delayed follow-up (>60 days) after an abnormal TSH. We then retrospectively applied the algorithm to a large EHR data warehouse within the Department of Veterans Affairs (VA), on patient records from two large VA networks for the period from January 1, 2011, to December 31, 2011. Identified records were reviewed to confirm the presence of delays in follow-up. During the study period, 645,555 patients were seen in the outpatient setting within the two networks. Of 293,554 patients with at least one TSH test result, the trigger identified 1250 patients on treatment for hypothyroidism with elevated TSH. Of these patients, 271 were flagged as potentially having delayed follow-up of their test result. Chart reviews confirmed delays in 163 of the 271 flagged patients (PPV = 60.1%). An automated trigger algorithm applied to records in a large EHR data warehouse identified patients with hypothyroidism with potential delays in thyroid function test results follow-up. Future prospective application of the TSH trigger algorithm can be used by clinical teams as a surveillance and quality improvement technique to monitor and improve follow-up.

The upper limit of normal TSH has been revised from 5 mIU/L to 2.5 mIU/L. We sought to evaluate IVF patients and the association between abnormal TSH and early pregnancy loss.A retrospective study of patients who had TSH levels measured within the 2 weeks prior to their fresh autologous IVF cycles (2002-2014). Cohorts were stratified by oocyte age (35, [35-38), [38-41), [41-43) and ≥43 years), and TSH level [(0-0.5], (0.5-2.5], (2.5-5], and (5-23) mIU/L]. Patients were followed until pregnancy loss or delivery. Model was assessed by chi-square of ANOVA with significance at p 0.05.TSH was abnormally elevated (5 mIU/L), mildly elevated ((2.5-5] mIU/L) or suppressed (≤0.5 mIU/L) in 46, 317 and 65 of the 1201 total cycles, respectively. Treatment resulted in 630 pregnancies, 524 clinical pregnancies and 409 deliveries. Pregnancy loss rates were increased in patients ≥38 yo (p 0.001) but not [35-38) yo (p = 0.40) compared with those35 yo. Early pregnancy loss rate was not associated with TSH level (p 0.30) compared with euthyroid patients after adjusting for oocyte age.Early pregnancy loss rate in IVF patients appears to have no relation to recent TSH levels.

OBJECTIVE The aim of this study was to assess the performance of the revised New Zealand (NZ) newborn screening TSH cut-offs for congenital hypothyroidism (CHT). METHODS Screening data over 24 months were obtained from the NZ newborn metabolic screening programme, which utilizes a 2-tier system of direct clinical referral for infants with markedly elevated TSH, and second samples from those with mild TSH elevation. We evaluated the impact of a reduced TSH threshold (50 to 30 mIU/l blood) for direct notification and a lower cut-off (15 to 8 mIU/l blood) applied to second samples and babies older than 14 days. RESULTS In 2013 and 2014, 117 528 infants underwent newborn screening for CHT. Fifty-two CHT cases were identified by screening (47 general newborn population, five repeat testing in low-birth-weight infants) and one case was missed. Thirty-two infants with screening TSH ≥30 mIU/l were directly referred at a median of 9 days (5-14) and 15 with TSH 15-29 mIU/l were referred after a second sample at a median of 20 days (9-52, P

Background: In thyroid-stimulating-hormone (TSH)-based newborn congenital hypothyroidism (CH) screening programs, the optimal screening-TSH cutoff level is critical to ensuring that true cases of CH are not missed. Screening-TSH results can also be used to predict the likelihood of CH and guide appropriate clinical management. The purpose of this study is to evaluate the predictive value of various screening-TSH levels in predicting a diagnosis of CH in the Ontario Newborn Screening Program (ONSP). Methods: The initial screening and follow-up data of 444,744 full term infants born in Ontario, Canada from April 1, 2006 to March 31, 2010 were analyzed. Confirmed CH cases were based on local endocrinologists' report and initiation of thyroxine treatment. Results: There were a total of 541 positive screening tests (~1/822 live births) of which 296 were true positives (~1:1,500 live births). Subjects were further subdivided based on screening-TSH and positive predictive values (PPV) were calculated. Twenty four percent in the 17-19.9 mIU/L range were true positives. In the 17-30 mIU/L range, 29 % were true positives with a significantly higher PPV for those sampled after (43 %) rather than before (25 %) 28 h of age (p < 0.02). Seventy three percent of neonates with an initial screening-TSH of ≥ 30 mIU/L and 97 % of those with ≥ 40 mIU/L were later confirmed to have CH. Conclusions: Infants with modestly elevated screening positive TSH levels between 17 and 19.9 mIU/L have a significant risk (24 %) of having CH. The very high frequency of true positives in term newborns with initial TSH values ≥ 30mIU/L suggests that this group should be referred directly to a pediatric endocrinologist in an effort to expedite further assessment and treatment. Screen positives with a modestly elevated TSH values (17-19.9 mIU/L) need to be examined in more detail with extended follow-up data to determine if they have transient or permanent CH.

Subclinical hypothyroidism first of all is a laboratory finding, defined by elevated TSH and normal peripheral thyroxine concentrations. The first steps are to verify the condition and to clarify whether the patient has underlying thyroid disease or other comorbidities. Results of recent studies on subclinical hypothyroidism are reassuring. No consistent association has been demonstrated between mildly elevated TSH levels (5-10 mIU / l) and cardiovascular events, mortality, fracture risk or cognitive impairment. In contrast TSH levels between 5-10 mIU / l may even confer lower mortality in the elderly and may hence be protective. These data strongly suggest that the long-time controversy on definition of normal upper TSH levels should take a more conservative turn. Thus, diagnosis of subclinical hypothyroidism should be handled cautiously. Individualized treatment decision is recommended if TSH levels are only mildly elevated and less than 8-10 mIU / l. In case of autoimmune thyroiditis or previous thyroid therapy (surgery, radioiodine treatment) the risk of progression to overt hypothyroidism has to be considered and there is no doubt that the latter should be avoided.

This study was designed to investigate the relationship between Systemic Lupus Erythematosus (SLE) and autoimmune thyroiditis disease. Forty one SLE patients diagnosed by latex agglutination test with twenty age and sex matched controls were included in this study. Results revealed that twenty one (51%) of SLE patients had antithyroglobuline antibody and ten of the SLE had elevated TSH. These results suggests that there was an association between SLE and autoimmune thyroiditis.

Hypothyroidism, overt or subclinical, is associated with adverse outcomes for pregnant women and their offspring. Knowledge of current national thyroid testing rates and positivity during pregnancy is limited.The aim of the study was to estimate thyroid testing rate and positivity during pregnancy and postpartum, including testing and positivity rates of thyroperoxidase antibody (TPO Ab) and free T(4) tests in pregnant women with elevated TSH levels (hypothyroid), and in pregnant women having TSH within range (euthyroid).Records from a large, national sample of pregnant women screened from June 2005 through May 2008 were examined.The study included 502,036 pregnant women, for whom gestational age information was available.Testing rates and the prevalence of hypothyroidism during pregnancy and postpartum were measured using assay-specific, trimester-specific reference intervals. Screening and positivity rates of TPO Ab and free T(4) tests were also measured.Of women ages 18 to 40 yr, 23% (117,892 of 502,036) were tested for gestational hypothyroidism (defined as both subclinical and overt hypothyroidism). Of these, 15.5% (18,291 of 117,892) tested positive for gestational hypothyroidism. Twenty-four percent (22,650 of 93,312) of women with TSH within range and 33% (6,072 of 18,291) of women with elevated TSH were also tested for gestational hypothyroxinemia. Gestational hypothyroxinemia was seen in 0.2% (47 of 22,650) of the tested women with TSH within range and was seen in 2.4% (144 of 6,072) of the tested women having elevated TSH; 0.3% (276 of 93,312) of women with TSH within range received a TPO Ab test, and of these, 15% (41 of 276) tested positive; 0.66% (120 of 18,291) of women with elevated TSH received a TPO Ab test, and of these, 65% (78 of 120) tested positive. Only 20.7% (1873 of 9063) of hypothyroid women received thyroid screening within 6 months postpartum; of these, 11.5% (215 of 1873) were diagnosed with postpartum hypothyroidism.Gestational hypothyroidism is more common than generally acknowledged. Testing is not common, and test selection is variable. There is a low rate of postpartum follow-up.

Objective To describe a patient who developed a thyrotropin (TSH)-Secreting adenoma in the setting of primary hypothyroidism. Methods We report the clinical, laboratory, and radiologic findings of a patient with a history of primary hypothyroidism who presented with headache, a bitemporal visual field deficit, and elevated TSH despite long-term levothyroxine therapy. We discuss the diagnostic challenges of this case and review the relevant literature. Results A 54-yearold woman with a history of primary hypothyroidism presented with a 3-year history of headache and a week of worsening vision. Imaging revealed a heterogeneous sellar mass elevating the optic chiasm. Her serum TSH was 46.5 mIU/L and free thyroxine concentration was 0.1 ng/dL. The differential diagnosis included pituitary hyperplasia and a TSH-secreting adenoma in a patient with primary hypothyroidism. The pathologic characteristics of the tumor were consistent with the latter. Conclusion In a patient with an elevated TSH concentration and a previous diagnosis of hypothyroidism, it is important to consider other entities besides medication noncompliance. TSH-secreting adenomas can also cause elevated levels of TSH. (Endocr Pract. 2011;17: e135-e139)

The diagnosis of subclinical hypothyroidism--serum TSH levels above and T(4) levels within the laboratory reference ranges--depends critically on the upper limit of the TSH reference interval. Calls have been made to lower the current upper TSH reference limit of 4.0 mU/l to 2.5 mU/l to exclude patients with occult hypothyroidism. However, data from population studies do not indicate that the distribution of TSH is altered owing to inclusion of such individuals. The opposite suggestion has also been put forward; the TSH upper reference limit is often too low, especially in the elderly, in women and in white individuals, which may lead to unnecessary or even harmful therapy. Studies in elderly individuals have shown that although aging may be associated with increased TSH levels, paradoxically, overt hypothyroidism in this population may be associated with a less robust TSH response than in young individuals. This Review highlights the interindividual and intraindividual variability of TSH levels and discusses the current controversy that surrounds the appropriateness of reference ranges defined on the basis of age, race, sex and amount of iodine intake. Moreover, the current evidence on lowering or increasing the upper limit of the TSH reference interval is reviewed and the need to individualize levothyroxine treatment in patients with elevated TSH levels is discussed.

OBJECTIVE: The levothyroxine withdrawal (L-T4) for some weeks results in prolonged exposure to elevated TSH. In contrast, administration of recombinant human TSH (rhTSH) promotes a short period of hyperthyrotropinemia. The objective of this study was to compare the area under the curve (AUC) of TSH obtained after L-T4 withdrawal versus administration of rhTSH. METHODS: Thirty patients received 0.9 mg rhTSH for two consecutive days, and 64 were prepared by L-T4 withdrawal for four weeks, with the latter being reintroduced 48 hour after 131I. Measurement of TSH were performed before the first rhTSH ampoule; immediately before and seven and 14 days after 131I; before L-T4 withdrawal; and, weekly, up to two months after 131I. RESULTS: The AUC obtained after rhTSH was 4.6 times smaller than that obtained after L-T4 withdrawal (532 versus 2,423 mIU/L per day). It should be emphasized that, on average, in the latter group, 58.5% of the AUC corresponded to the period after reintroduction of hormone therapy. CONCLUSIONS: Surprising difference in the TSH AUC was demonstrated between rhTSH administration versus L-T4 withdrawal. OBJETIVO: A suspensão de levotiroxina (L-T4) por algumas semanas resulta em exposição prolongada ao TSH elevado. Em contraste, a administração do TSH recombinante (rhTSH) promove um curto período de hipertirotropinemia. O objetivo deste estudo foi comparar a área sob a curva (do inglês "area under the curve", AUC) do TSH obtida após suspensão da L-T4 versus a administração do rhTSH. MÉTODOS: Trinta pacientes receberam 0,9 mg de rhTSH por dois dias consecutivos, e 64 foram preparados com suspensão da L-T4 por quatro semanas, com reintrodução dessa terapia 48 horas após o radioiodo. As medidas de TSH foram realizadas antes da primeira ampola de rhTSH; imediatamente antes e sete e 14 dias após o 131I; antes da suspensão da L-T4; e, semanalmente, até dois meses após o 131I. RESULTADOS: A AUC do TSH obtida após rhTSH foi 4,6 vezes menor do que a alcançada após suspensão da L-T4 (532 versus 2.423 mUI/L ao dia). Enfatiza-se que, em média, no último grupo, 58,5% da AUC correspondeu ao período após a reintrodução da terapia hormonal. CONCLUSÕES: Surpreendente diferença na AUC do TSH foi demonstrada entre a administração do rhTSH versus suspensão da L-T4.

Objective To determine the thyroid status of Basenji dogs in Australia. Methods Jugular or cephalic venipuncture blood samples were taken from 113 Basenji, comprising 47 males, 5 castrates, 48 entire and 13 spayed bitches, and sent on ice in plain and EDTA tubes to a single laboratory to determine haematocrit and serum concentrations of total thyroid hormone (thyroxine, TT4), thyroid-stimulating hormone (TSH) and cholesterol. In a subgroup of 8 dogs with abnormal elevated TSH concentrations and subnormal TT4 concentrations, 5 were further examined by dynamic endocrine testing using recombinant human (rh) TSH (54 µg). Results Ages ranged from 1 to 14 years and weight range was 6.5 to 14.0 kg. TT4 concentrations (nmol/L) ranged from 2 to 27, with a median of 13 and a mean ± SD of 13.0 ± 5.7. Importantly, 85/113 (75%) of TT4 values were lower than the normal laboratory reference range (17–37). TSH concentrations (ng/mL) ranged from 0.05 to 5.37, with a median of 0.16 and a mean ± SD of 0.3 ± 0.6. Conclusions Basenji have a similar reference range for serum TSH, but a considerably lower reference range for TT4 (2–27 nmol/L) than most breeds and crossbreds, resembling the sight hounds in this respect. Given the difficulty of accurately measuring TT4 concentrations that are so low, concomitant serial TSH determinations are essential to properly asses thyroid function. Taken alone, TT4 determinations are only of use when the value is within the reference range, in which case a diagnosis of hypothyroidism is likely excluded.

A follicular thyroid carcinoma was suspected in a 62-year-old woman after the fifth goitre excision for non-neoplastic inappropriate thyrotropin secretion. Small-follicular adenoma could not be excluded histologically. After an attempt at thyrotropin suppression with L-thyroxine, triiodothyronine, D-thyroxine with L-thyroxine, and bromocriptine had failed, lasting if partial decrease in the maximally elevated TSH levels was achieved with triiodothyroacetic acid (TRIAC). One of the patient's three daughters also has non-neoplastic inappropriate thyrotropin secretion and has had two goitre excisions. It is most likely a familial form of inappropriate TSH secretion.