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.

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).

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)

[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.

Dynamic thyroid stimulating hormone tests: do they still have a role?

Modern assays for TSH and for free thyroid hormones have significantly reduced the need for dynamic testing of the hypothalamo-pituitary-thyroid axis in patients with biochemical thyroid dysfunction. However, under certain conditions, such as isolated TSH deficiency, thyrotropinoma and thyroid hormone resistance, the TRH test remains an important adjunctive diagnostic tool. In recent years, the development of recombinant human TSH (rhTSH) has led to a new dynamic test of thyroglobulin (Tg) secretion as a marker of recurrent or metastatic thyroid cancer. RhTSH provides an alternative to thyroid hormone suppression treatment withdrawal in patients who cannot tolerate hypothyroidism and is the agent of choice in patients unable to mount a TSH response.

Trends in diagnostic and therapeutic criteria in Graves' disease in the last 10 years.

A questionnaire describing a typical clinical case of Graves' disease and 10 variations on it was mailed to 70 Spanish units of endocrinology with the aim of assessing the new diagnostic and therapeutic trends for hyperthyroidism caused by Graves' disease in Spain and to compare the results obtained from previous studies carried out in Europe and Spain 10 years previously. Responses indicated that thyrotrophin (98%) and free thyroxine (88%) were the most used tests in the in vitro diagnosis of Graves' disease with a significant decrease in the use of total thyroxine, total triiodothyronine, and thyroglobulin in comparison with the surveys conducted 10 years previously in Europe and Spain. The presence of antibodies against the thyrotrophin receptor was the most frequently used immune marker in the diagnosis (78%) and the new use of antithyroperoxidase antibodies (36%) in diagnosis is noteworthy. Antithyroid drugs remain the treatment of choice (98%). Surgery was used mainly for large size goitres (33%) and radioiodine for recurrences after medical (61%) or surgical (80%) treatment. In conclusion, the responses obtained from this questionnaire provide insight into current specialist diagnostic and therapeutic practices with respect to Graves' disease and which could be of value to non-specialist units of endocrinology.

Efectos de los anticonvulsivantes sobre la funcion tiroidea en niños epilépticos

Para evaluar el efecto de los anticonvulsivantes sobre la función tiroidea en los niños se realizó un estudio en el cual se incluyeron 75 pacientes que reciben drogas antiepilépticas. A todos los pacientes se les cuantificó los niveles séricos de tirotropina (TSH) y tiroxina (T4). Veintidos (29 por ciento) pacientes en total mostraron alteraciones de las pruebas tiroideas, 10 (13 por ciento) mostraron niveles elevados de TSH (7.5-87.5 mU/mL), 8 con niveles normales de T4, y 2 con T4 bajo 8 de los 10 reciben ácido valproico y 2 reciben fenobarbital con duración entre 1 y 5 años. Doce pacientes (16 por ciento) mostraron niveles bajos de T4 (4.01-5.5 mg/dL), con valores normales de TSH. Nueve de ellos reciben carbamazepina y 3 reciben fenobarbital con duración entre 0.5 y 5.5 años. En conclusión, los anticonvulsivantes pueden alterar la función tiroidea en niños. Es más frecuente con la carbamazepina, el ácido valproico y el fenobarbital

Pruebas de función tiroidea

Las pruebas de función tiroidea se han convertido en pruebas de rutina en los laboratorios clínicos, así como de común solicitud en las ordenes médicas, lo que hace necesario que los médicos tengan un dominio amplio y útil de las diferentes pruebas y técnicas que se utilizan para evaluar función tiroidea. La mejor comprensión de la fisiología y metabolismo de las hormonas T3 y T4, ha hecho que desde hace algunos años se venga haciendo énfasis en la mayor utilidad y especificidad de las fracciones libres, lo que ha mejorado el diagnóstico y seguimiento de los pacientes y ha llevado a una mejor utilización e interpretación del comportamiento de éstas en el paciente con una determinada enfermedad tiroidea. Se ha definido también la importancia de los anticuerpos, muy especificamente en las enfermedades tiroideas que tienen un componente autoinmune. Estas pruebas deben hacer parte de las pruebas de rutina solicitadas en la evaluación de los pacientes con afecciones tiroideas.