Uso adecuado de las pruebas de laboratorio para la evaluación de la función tiroidea en pediatría / Appropriate use of laboratory tests for evaluation of thyroid function in pediatrics

Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects.

BACKGROUND: Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. OBJECTIVE AND METHODS: To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: "sars cov 2", "covid 19", "subacute thyroiditis", "atypical thyroiditis", "chronic thyroiditis", "hashimoto's thyroiditis", "graves' disease", "thyroid nodule", "differentiated thyroid cancer", "medullary thyroid cancer", "methimazole", "levothyroxine", "multikinase inhibitor", "remdesivir", "tocilizumab". Data were collected, analyzed, and discussed to answer the following clinical questions: "What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?"; "Could medical management of thyroid diseases influence the clinical course of COVID-19?"; "Does medical management of COVID-19 interfere with thyroid function?"; "Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?". RESULTS: SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. DISCUSSION: Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.

Trends in thyroid function testing, neck ultrasound, thyroid fine needle aspiration, and thyroidectomies in North-eastern Italy.

PURPOSE: Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid dysfunctions and diseases in Italy. METHODS: A population-based study was conducted in North-eastern Italy, including 11.7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo- or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region. RESULTS: Between 2010 and 2017 in North-eastern Italy, 24.5% of women and 9.8% of men received at least one TSH test yearly. In 2017, 7.1% of women and 1.5% of men were prescribed drugs for thyroid dysfunction, 94.6% of whom for hypothyroidism. Neck ultrasound examinations were performed yearly in 6.9% of women and 4.6% of men, with a nearly two-fold variation between areas. Thyroid FNA and thyroidectomies were three-fold more frequent in women (394 and 85 per 100,000) than in men (128 and 29 per 100,000) with a marked variation between areas. Both procedures decreased consistently after 2013. CONCLUSIONS: The results of this population-based study describe recent variations over time and between surrounding areas of indicators of 'diagnostic pressure' on thyroid in North-eastern Italy. These results emphasize the need to harmonize practices and to reduce some procedures (e.g., neck ultrasound and total thyroidectomies) in certain areas.

Marked Decrease Over Time in Conversion Surgery After Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma.

Background: Active surveillance for low-risk papillary microcarcinoma (PMC) of the thyroid is an accepted and safe management strategy. However, some patients undergo conversion surgery after the initiation of active surveillance for various reasons. We investigated the reasons for conversion surgery and whether and how they changed over time. Methods: We enrolled 2288 patients with PMC who underwent active surveillance. Of these, 162 (7.1%) underwent conversion surgery >12 months after initiating active surveillance due to disease progression (57 patients), patient preference (43 patients), physician preference (31 patients), other associated thyroid or parathyroid diseases (24 patients), and other reasons (7 patients). We analyzed cumulative conversion rates not only in the whole cohort but also in the first three major subsets based on the reasons for surgery. We also divided our whole cohort into two groups based on the period of active surveillance commencement: the first-half group (February 2005-November 2011; 561 patients) and the second-half group (December 2011-June 2017; 1727 patients). Results: The criteria for PMC progression did not differ between the first- and second-half groups. The proportion of female patients in the physician preference group was significantly higher than that in the disease progression and the patient preference groups. Tumor size at surgery was larger, and tumor volume-doubling rate was higher in the disease progression group than in the other two groups. Patients in the second-half group were significantly less likely to undergo conversion surgery than those in the first-half group. Furthermore, conversion surgery rates in the second-half group were significantly lower than those in the first-half group in the patient preference, physician preference, and disease progression groups. Conclusions: Patients with PMC in the second-half group were significantly less likely to undergo conversion surgery than those in the first-half group regardless of the reason. This is probably because data accumulation of favorable outcomes with active surveillance significantly contributed to physicians' confidence and patients' trust and understanding of this disease.

Trust your Endocrinologist - Report and Recommendations on the Ordering of Reverse T3 Testing.

Laboratory testing for markers of thyroid function is essential for the diagnosis of thyroid disease, yet, the landscape of thyroid function testing is complex and inappropriate test orders are common. Reverse T3 (rT3) is frequently seen on thyroid function testing menus as a marker of nonthyroidal illness. However, the diagnostic utility of rT3 for this indication is questionable, and testing of rT3 is not recommended by any professional practice guidelines. We reviewed a set of rT3 orders at our institution, and identified that 11 of 20 orders appeared inappropriate with respect to clinical context. These orders were less likely to have been placed at the recommendation of an endocrinologist relative to appropriate orders. We recommend that all providers refer to professional guidelines for thyroid function testing, and consult with an endocrinologist for appropriate usage of esoteric or non-standard thyroid function tests.

Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight. METHODS: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496. FINDINGS: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT4]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (pinteraction=0·10). Each 1 SD increase in FT4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second. INTERPRETATION: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy. FUNDING: Netherlands Organization for Scientific Research (grant 401.16.020).

Thyroid disrupting chemicals and developmental neurotoxicity - New tools and approaches to evaluate hormone action.

It is well documented that thyroid hormone (TH) action is critical for normal brain development and is mediated by both nuclear and extranuclear pathways. Given this dependence, the impact of environmental endocrine disrupting chemicals that interfere with thyroid signaling is a major concern with direct implications for children's health. However, identifying thyroid disrupting chemicals in vivo is primarily reliant on serum thyroxine (T4) measurements within greater developmental and reproductive toxicity assessments. These studies do not examine known TH-dependent phenotypes in parallel, which complicates chemical evaluation. Additionally, there exist no recommendations regarding what degree of serum T4 dysfunction is adverse, and little consideration is given to quantifying TH action within the developing brain. This review summarizes current testing strategies in rodent models and discusses new approaches for evaluating the developmental neurotoxicity of thyroid disrupting chemicals. This includes assays to identify adverse cellular effects of the brain by both immunohistochemistry and gene expression, which would compliment serum T4 measures. While additional experiments are needed to test the full utility of these approaches, incorporation of these cellular and molecular assays could enhance chemical evaluation in the regulatory arena.

Evaluation of Prevalence of Changes in Thyroid Functional Tests in Mole Hydatiforme

Introduction: Mole hydatiforme is the most common type of gestational trophoblast disease (GTI) and the aim of this study, is evaluation the frequency of changes in thyroid function test in mole hydatidiform patients. Materials and Methods: In this retrospective study, 63 patients with mole hydatidiform who reffering to gynecolgy ward of Ali ibn Abitaleb Hospital in Zahedan from April 2016 to March 2017, were studied. Information such as age, gravidity and laboratory findings inclluding thyroid function test (TFT) and the presence or absence of clinical sympltoms were recorded in the information forms and analyzed by SPSS software. Results: In this study, 63 patients with mole hydatidiform were studied. The mean age of the patients was 26.6 ± 7.7 years. The most common clinical manifestations of hyperthyroidism in patients with mole hydatidorme was tachycardia (39.7%). There was no relationschip between age and gravidity with the hyperthyroid simptoms and thyroid function test. Conclusion: Overall, the results of this study showed ttat 67% of patients with mole hydatidiform hay reduced TSH and more than 50% of cases hay increased free T3 and T4. There was no relationship between maternal age and gravidity with changes in thyroid functional test (AU)

Long-term Methimazole Therapy in Juvenile Graves' Disease: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Recent studies show that long-term (LT) antithyroid drugs reduce relapse of hyperthyroidism in patients with Graves' disease. Our objective was to evaluate the effectiveness and safety of LT methimazole treatment and to compare remission rates in Graves' disease patients after LT and short-term (ST) therapy. METHODS: In this randomized, parallel group trial, 66 consecutive patients with untreated juvenile Graves' hyperthyroidism were enrolled. After a median 22 months of methimazole treatment, 56 patients were randomly assigned to either continue low-dose methimazole treatment (n = 24, LT group) or to discontinue treatment (n = 24, ST group). Twenty-four patients in LT group completed 96 to 120 months of methimazole treatment. Patients in both groups were managed for 48 months after discontinuation of treatment. RESULTS: Except for 3 cases of cutaneous reactions, no other adverse events were observed throughout 120 months of methimazole therapy. Serum free thyroxine, triiodothyronine, thyrotropin, and thyrotropin receptor antibody remained normal, and the required daily dosage of methimazole was gradually decreased from 5.17 ± 1.05 mg at 22 months to 3.5 ± 1.3 mg between 96 and 120 months of treatment (P < .001). Hyperthyroidism was cured in 92% and 88% of LT patients and in 46% and 33% of ST patients, 1 and 4 years after methimazole withdrawal, respectively. CONCLUSIONS: LT methimazole treatment of 96 to 120 months is safe and effective for treatment of juvenile Graves' disease. The four-year cure rate of hyperthyroidism with LT methimazole treatment is almost 3 times more than that of ST methimazole treatment.

Implementation of thyroid function tests algorithms by clinical laboratories: A four-year experience of good clinical and diagnostic practice in a tertiary hospital in Greece.

INTRODUCTION: Thyroid Function Tests (TFTs) are among the most commontly ordered tests. Significant overuse of TFTs can occur when instead of using a single TSH test to screen for thyroid disease a full panel (TSH plus FT4 and FT3) is ordered. The aim of our study was to evaluate the effectiveness of the application of a scientifically-established laboratory-controlled algorithm for TFTs to physician's orders for inpatients and to address potential pitfalls of such an approach. MATERIALS AND METHODS: We collected and analyzed Laboratory Information System data of the TFTs performed between April 2009 and March 2016 in a 739-bed tertiary teaching hospital. Between April 2013 and March 2016, we applied a laboratory controlled algorithm for inpatient TFT assays after TSH and did not perform further tests, unless a justified bypass was requested by the treating physician. RESULTS: Algorithm application led to significant reductions of TFTs executed per TSH ordered. Compared to the four years preceding the intervention, executed FT4/TSH tests decreased from 93 to 18%, FT3/TSH from 92 to 18%, anti-TG/TSH from 18 to 4% and anti-TPO/TSH from 11 to 3%. Simultaneously, FT4, FT3, anti-TG, and anti-TPO tests ordered in outpatients also displayed a significant gradual decrease. CONCLUSIONS: Hospital-based laboratories can safely apply a generally accepted TFTs algorithm on physician's orders without any compromise in diagnostic/therapeutic accuracy, thus achieving significant direct cost-reduction and increased physician awareness on current TFT ordering practices. Such an approach, combined with collaboration with ordering physicians, can safeguard patients from the consequences of low-value care practices.

Hypothyroidism and Iodine Deficiency in Children on Chronic Parenteral Nutrition.

BACKGROUND AND OBJECTIVES: Iodine is an essential trace element for maintenance of normal thyroid function. Normal thyroid function is a prerequisite for neurocognitive development and growth in children. In the United States, iodine is not routinely added as a trace element in parenteral nutrition (PN). Our objective was to determine the prevalence of iodine deficiency and hypothyroidism in children on chronic PN. METHODS: This was a cross-sectional study of children <17 years of age and using PN for >6 months at a tertiary children's hospital. Primary outcomes were spot urine iodine concentration (UIC), serum thyrotropin, and free thyroxine levels. RESULTS: Twenty-seven patients were identified (74% male). The median age at screening was 48 months (range: 7-213 months). The median duration on PN was 27 months (range: 11-77 months). Seventeen out of 20 patients (85%) were iodine deficient (spot UIC <100 µg/L), whereas 11 out of 20 patients (55%) were severely iodine deficient (spot UIC <20 µg/L). The prevalence of acquired hypothyroidism (elevated thyrotropin, low free thyroxine, and UIC <100 µg/L) was 33% (n = 8). None of the children with hypothyroidism screened for autoimmune thyroiditis had positive test results. There was no statistically significant association between duration of PN use and development of iodine deficiency (P = .08) or hypothyroidism (P = .96). CONCLUSIONS: Children on chronic PN are at risk for developing iodine deficiency and resultant hypothyroidism; hence, these children should be screened for these outcomes. Further studies are needed to define the temporal onset of iodine deficiency and timing to thyroid dysfunction related to PN.

Plasma free thyroxine in the upper quartile is associated with an increased incidence of major cardiovascular events in older men that do not have thyroid dysfunction according to conventional criteria.

BACKGROUND: The aim of this study was to assess the association of plasma free thyroxine (FT4) and serum thyroid stimulating hormone (TSH) concentrations with the past diagnosis of cardiovascular disease and incidence of new cardiovascular events in older men with no known thyroid disease. METHODS: This study involved a cohort of community-recruited older men without known thyroid disease. Plasma FT4 and serum TSH were measured by immunoassay. Past cardiovascular disease diagnosis was defined through questionnaire data. The incidence of major cardiovascular events were assessed using the Western Australian Data Linkage System. The associations of plasma FT4 and serum TSH with the past diagnosis of cardiovascular disease and the incidence of new major cardiovascular events (cardiovascular death, myocardial infarction or stroke) were examined using logistic regression and Cox proportional hazard analyses. RESULTS: 3712 men were followed for a mean of 9.5years. Men with plasma FT4 in the upper quartile, compared to other men, were more likely to have been previously diagnosed with cardiovascular disease but this association did not persist after adjustment for other risk factors. Men with plasma FT4 in the upper quartile, compared to other men, had an increased incidence of major cardiovascular events (adjusted hazard ratio, HR, 1.15, 95% CI 1.00-1.31) and myocardial infarction alone (adjusted HR 1.29, 95% CI 1.06-1.54). CONCLUSION: This study suggests that older men with higher levels of plasma FT4 not meeting current criteria for the diagnosis of hyperthyroidism are at increased risk of major cardiovascular events.

Early thyroxine treatment in Down syndrome and thyroid function later in life.

OBJECTIVE: The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis. METHODS: We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis. RESULTS: TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L; P = 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) (P = 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower (P < 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group. CONCLUSION: Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia.

Electronic Detection of Delayed Test Result Follow-Up in Patients with Hypothyroidism.

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: 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. KEY RESULTS: 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%). CONCLUSIONS: 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.

Disfunción tiroidea y lipídica asociada a bexaroteno en el linfoma cutáneo de células T / Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma

Fundamento y objetivo: El bexaroteno es un rexinoide sintético selectivo del receptor X aprobado para el tratamiento sistémico del linfoma cutáneo de células T. Durante el tratamiento es muy frecuente la aparición de hipotiroidismo e hiperlipidemia mixta grave, siendo ambos efectos adversos reversibles y dependientes de la dosis. La elevación del colesterol LDL y los triglicéridos (hasta unos niveles aumentados que incluso se han asociado a pancreatitis en algunos casos) está ampliamente descrita (al igual que sucede con otros retinoides), siendo el descenso del colesterol HDL menos conocido. Revisamos nuestra experiencia con el uso de bexaroteno. Material y métodos: Se presenta una serie de 3 casos de pacientes tratados con bexaroteno en los que, además de sufrir los efectos adversos bien conocidos, se observó un grave descenso del colesterol HDL. Resultados: Los 3 pacientes estudiados presentaron complicaciones metabólicas en forma de hipotiroidismo central e hiperlipidemia mixta grave, con especial énfasis en el marcado descenso que experimentaron nuestros pacientes (descenso medio > 83%) en las cifras de colesterol HDL. El tratamiento hipolipidemiante y hormonal sustitutivo con levotiroxina dio lugar a una mejoría de los parámetros, sin llegar a alcanzarse los objetivos. Conclusiones: El bexaroteno produce, como efectos secundarios predecibles, una hiperlipidemia mixta grave con descenso marcado de los niveles de colesterol HDL e hipotiroidismo central, los cuales son reversibles y dependientes de la dosis. Se incluye una reflexión sobre los posibles mecanismos etológicos e implicaciones de este fenómeno (AU)

Background and objective: Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. Material and methods: We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. Results: The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease > 83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. Conclusions: Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included (AU)

[Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers]. / Avancées dans les dosages de thyroglobuline et leur impact dans la prise en charge des cancers différenciés de la thyroïde.

Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia.

Standardization of FT4 and harmonization of TSH measurements - a request for input from endocrinologists and other physicians.

Given the prevalence of thyroid disorders and the subtle signs and symptoms that may accompany subclinical disease, reliable laboratory testing for serum TSH and free thyroid hormones is important for both primary care physicians and endocrinologists. The laboratory community has recognized the need for standardization of thyroid function tests to achieve comparability of measurement results between methods. This applies in particular to tests for free T4 (FT4), which may be considered controversial in terms of clinical and analytical validity. However, variability is also observed with TSH testing - a fact which has not been emphasized in ongoing discussions regarding lowering the upper limit of normal and/or common decision limits to start treatment for hypothyroidism. In response to this need, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee for Standardization of Thyroid Function Tests worked over the years towards the goal of standardization of FT4 and TSH testing.

Alteraciones endocrinológicas en el síndrome de Down / Endocrine disorders in Down’s syndrome

La prevalencia de alteraciones endocrinológicas, generalmente de origen autoinmune, es muy elevada en las personas con síndrome de Down. Por ello, durante toda la vida se debe vigilar la función tiroidea. Es especialmente frecuente el hipotiroidismo, especialmente en su forma subclínica. La delgada línea que separa el hipotiroidismo subclínico del verdadero hace difícil la indicación terapéutica. También la diabetes es más frecuente que en la población general, ocasionalmente asociada a hipotiroidismo (AU)

The prevalence of endocrine disorders, generally of autoimmune origin, is very high in persons with Down’s syndrome. Therefore, the thyroid function should be monitored during the entire lifetime. Hypothyroidism, particularly the subclinical form, is especially common. The thin line separating subclinical hypothyroidism from true hypothyroidism makes the therapeutic indication difficult. Diabetes is also more frequent than in the general population, occasionally associated to hypothyroidism (AU)

Orders for thyroid function tests - changes over 10 years.

In the BEACH (Bettering the Evaluation and Care of Health) program, between 2001-02 and 2010-11, general practice orders for thyroid function tests increased by 51%.

Evaluación de la eficacia y del impacto clínico de la PET- 18F-FDG en el diagnóstico de recurrencia del carcinoma medular de tiroides con calcitonina elevada y pruebas de imagen negativas / Evaluation of efficacy and clinical impact of 18F-FDG-PET in the diagnosis of recurrent medullary thyroid cancer with increased calcitonin and negative imaging test

Objetivo. Evaluar la eficacia y el impacto clínico de la PET-FDG en el diagnóstico de sospecha de recurrencia de carcinoma medular de tiroides (CMT), en pacientes con calcitonina elevada y pruebas de imagen negativas. Material y métodos. Estudiamos retrospectivamente a 31 pacientes consecutivos de febrero de 2001 a octubre de 2007; 17 mujeres y 14 hombres con una edad media de 56,2 años (rango: 26-88), diagnóstico anatomopatológico de carcinoma medular de tiroides y sospecha de recurrencia por elevación patológica de calcitonina y pruebas de imagen negativas. A todos los pacientes se les realizó PET/PET-TAC corporal 60min post-inyección intravenosa de 333-434 MBq de 18F-FDG. Los resultados se confirmaron mediante anatomía patológica en el 45,2% de los pacientes y por seguimiento clínico/radiológico en el 54,8% durante un período de seguimiento medio de 4 años (rango: 16 m-8 años). Resultados. Se obtuvo una sensibilidad del 88%, especificidad del 84,6%, valor predictivo positivo del 88%, valor predictivo negativo del 84,6% y exactitud diagnóstica del 87%. Los resultados de la PET-FDG modificaron la actitud terapéutica en 14 casos (45,2%). Se compararon las medias de los valores de calcitonina entre PET positivos para enfermedad y negativos, mediante la prueba de la «t» de Student no encontrando diferencia significativa (p=0,3). Conclusiones. La PET-18F-FDG es la prueba idónea para el diagnóstico de recurrencia oculta en CMT con calcitonina elevada y técnicas de imagen negativas, con elevado impacto clínico facilitando el manejo terapéutico de los pacientes con recurrencia de CMT, debiendo ser incluida en el algoritmo diagnóstico de estos pacientes(AU)

Aim. To evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test. Material and methods. We performed a retrospective study of 31 consecutive cases from february 2001 to october 2007 of 17 women and 14 men, mean age 56.2 years (range: 26-88), with anatomical-pathology diagnosis of medullary thyroid cancer and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All of the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60minutes after intravenous injection of 333-434 MBq of 18F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 m-8 years). Results. Sensitivity was 88%, specificity 84.6%, positive predictive value 88%, negative predictive value 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's «t» test between positive PET studies for the disease and negative ones. No significant differences were found (P=.3). Conclusions. In patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients(AU)