Common Pitfalls in the Interpretation of Endocrine Tests.

Endocrine tests are the cornerstone of diagnosing multiple diseases that primary care physicians are frequently faced with. Some of these tests can be affected by situations that affect the proper interpretation, leading to incorrect diagnoses and unnecessary treatment, such as the interference of biotin with thyroid function test, falsely elevated prolactin values in presence of macroprolactinemia or falsely normal due to the "hook effect" in macroprolactinomas. Recognizing these situations is essential for the clinician to make an adequate interpretation of these tests as well as an accurate diagnosis that guarantees the best outcomes for the patient.

Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro.

OBJECTIVES: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. SUBJECTS AND METHODS: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 µg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 µg/L. RESULTS: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. CONCLUSIONS: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro

ABSTRACT Objectives: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Subjects and methods: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. Results: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. Conclusions: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Newborn Screening in the US May Miss Mild Persistent Hypothyroidism.

OBJECTIVE: To determine if newborn screening (NBS) programs for congenital hypothyroidism in the US use thyroid-stimulating hormone (TSH) cutoffs that are age adjusted to account for the physiologic 4-fold reduction in TSH concentrations over the first few days of life. STUDY DESIGN: All NBS programs in the US were contacted and asked to provide information on their NBS protocols, TSH cutoffs, and whether these cutoffs were age adjusted. RESULTS: Of 51 NBS programs, 28 request a repeat specimen if the initial eluted serum TSH concentration is mildly increased (between the cutoff and a median upper limit of 50 mU/L), whereas 14 programs perform a routine second screen in all infants. Although these specimens are typically collected between 1 week and 1 month of life, 16 of the 28 programs with a discretionary second test and 8 of 14 programs with a routine second test do not have age-adjusted TSH cutoffs after the first 48 hours of life. CONCLUSIONS: There is variation in NBS practices for screening for congenital hypothyroidism across the US, and many programs do not adjust the TSH cutoff beyond the first 2 days of life. Samples are processed when received from older infants, often to retest borderline initial results. This approach will miss congenital hypothyroidism in infants with persistent mild TSH elevations. We recommend that all NBS programs provide age-adjusted TSH cutoffs, and suggest developing a standard approach to screening for congenital hypothyroidism in the US.

Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes?

Serum thyroid stimulating hormone (TSH) levels increase with age. This elevation has been associated with better outcomes in very elderly subjects; however, little is known about the relationship between TSH below the lower limit of the reference range and health-related outcomes. Here, we investigated the association between cognitive impairment or depressive symptoms and low-normal serum TSH (<1.0 µIU/mL, in the reference range) in elderly subjects and whether the use of methimazole in subjects without dementia but with low-normal TSH could affect cognition or depressive symptoms. From 293 healthy adults ≥65 years old with normal TSH included in the sectional phase, only subjects without dementia were prospectively analyzed: 1) TSH ≥1.0 µIU/mL (observation; untreated); 2) TSH <1.0 µIU/mL (observation; untreated); and 3) TSH <1.0 µIU/mL (methimazole therapy). Cognition was assessed, using the Mini Mental State Examination (MMSE) and depressive symptoms (at MMSE ≥ 13) by the Geriatric Depression Scale (GDS). Age >80 years was the sole independent factor associated with dementia (OR=2.89; confidence interval [CI] 1.72-4.86; p<0.01). Prospectively, 93 completed follow-up, with 7.5% (7) receiving methimazole intervention. Untreated subjects with lower TSH showed the greatest declines in MMSE scores during follow-up that was not observed in those with serum TSH ≥1.0 µIU/mL. Lower MMSE score reductions were associated with elderly subjects receiving methimazole. There were no significant changes in depressive symptoms and GDS scores among those with serum TSH <1.0 µIU/mL. In this study, low-normal TSH was not associated with higher prevalence of dementia. However, in elderly subjects without dementia, low TSH was associated with worsening cognition.

The clinical use of thyroid function tests.

Laboratory tests are essential for accurate diagnosis and cost-effective management of thyroid disorders. When the clinical suspicion is strong, hormonal levels just confirms the diagnosis. However, in most patients, symptoms are subtle and unspecific, so that only biochemical tests can detect the disorder. The objective of this article is to do a critical analysis of the appropriate use of the most important thyroid function tests, including serum concentrations of thyrotropin (TSH), thyroid hormones and antithyroid antibodies. Through a survey in the MedLine database, we discuss the major pitfalls and interferences related to daily use of these tests and recommendations are presented to optimize the use of these diagnostic tools in clinical practice.

The influence of body mass index and low-grade systemic inflammation on thyroid hormone abnormalities in patients with type 2 diabetes.

Previous reports highlight the role of systemic inflammation in the genesis of non-thyroidal illness syndrome and type 2 diabetes mellitus (T2DM). Our objective was to assess whether body mass index and the low-grade systemic inflammation would be associated with changes in thyroid hormone metabolism in patients with type 2 diabetes. This was a cross-sectional study of 104 subjects; 52 patients with type 2 diabetes and 52 in a control group, paired by age, gender and body mass index. We measured total (T) and free (F) thyroxine (T4) and triiodothyronine (T3), reverse T3 (rT3), the ratios FT3/rT3, FT3/FT4 and FT4/rT3, clinical parameters (age, gender, diabetes duration and complications, body mass index, waist circumference, hypertension, HbA1c), and high sensitivity C-reactive protein. Patients with DM presented lower levels of TT4 (p=0.006), TT3 (p<0.001) and FT3 (p<0.001) and higher of FT4 (p<0.001), waist circumference (p=0.047) and C-reactive protein (p<0.001). Body mass index was inversely correlated with FT4 (p=0.036) and TT3 (p=0.008). C-reactive protein was positively correlated with rT3 (p=0.001) and inversely with FT4/rT3 (p<0.001) and FT3/rT3 (p=0.014). Body mass index was an independent predictor for FT4 (B=-0.011, p=0.029) and TT3 levels (B=-1.118, p=0.003). Inflammation predicted the FT4/rT3 ratio (B=-0.190, p<0.001). C-reactive protein (B=0.235, p<0.001) and body mass index (B=-0.008, p=0.047) were independent predictors for rT3. In conclusion, type 2 diabetes was associated with a low T3 state. Body mass index and the low-grade systemic inflammation are related to the non-thyroidal illness syndrome in these patients, possibly by altering the activity of peripheral deiodinases.

Utilização dos testes de função tireoidiana na prática clínica / The clinical use of thyroid function tests

Exames laboratoriais são fundamentais para o diagnóstico acurado e o monitoramento custo-efetivo das disfunções tireoidianas. Quando há alta suspeita clínica, as dosagens hormonais apenas confirmam o diagnóstico. No entanto, na maioria dos pacientes, a sintomatologia é sutil e inespecífica, de forma que apenas testes bioquímicos podem detectar o transtorno. O objetivo deste artigo é fazer uma análise crítica do uso apropriado dos principais testes de função tireoidiana, entre eles a dosagem sérica do hormônio estimulante da tireoide (TSH), dos hormônios tireoidianos e dos anticorpos antitireoidianos. Mediante um levantamento na base de dados do MedLine, são discutidas as principais armadilhas e interferências relacionadas ao uso cotidiano desses testes e apresentadas recomendações para otimizar a utilização dessas ferramentas diagnósticas na prática clínica.

Laboratory tests are essential for accurate diagnosis and cost-effective management of thyroid disorders. When the clinical suspicion is strong, hormonal levels just confirms the diagnosis. However, in most patients, symptoms are subtle and unspecific, so that only biochemical tests can detect the disorder. The objective of this article is to do a critical analysis of the appropriate use of the most important thyroid function tests, including serum concentrations of thyrotropin (TSH), thyroid hormones and antithyroid antibodies. Through a survey in the MedLine database, we discuss the major pitfalls and interferences related to daily use of these tests and recommendations are presented to optimize the use of these diagnostic tools in clinical practice.

Clinical monitoring guidelines for congenital hypothyroidism: laboratory outcome data in the first year of life.

OBJECTIVE: To examine whether current recommendations for thyroid status monitoring in children with congenital hypothyroidism (CH) (monthly in the first 6 months and every 3-4 months subsequently) are adequate, or whether monthly monitoring is necessary throughout the first year. STUDY DESIGN: We reviewed charts of 70 children with CH for initial thyroid-stimulating hormone (TSH), frequency of follow-up, dose changes, and thyroxine (T(4)) and TSH levels in the first year. Need for monthly monitoring was determined on the basis of guidelines to maintain T(4)/free T(4) in the upper half of the normal range and rapidly normalize TSH. RESULTS: Monthly monitoring was justified in 75% in the first 6 months and 36% in the next 6 months. Children requiring monthly monitoring in the second 6 months had higher baseline TSH (P = .02) and lower T(4) (P = .01) than those not requiring monthly monitoring. Thyroid dysgenesis, starting levothyroxine dose, sex, and ethnicity did not predict requirement for monthly monitoring. Thirty percent of children in the first and second 6 months had ≥1 high TSH level, with a T(4)/free T(4) not in the upper half of the normal range. CONCLUSION: More than a third of children with CH require monthly monitoring between 6 to 12 months on the basis of study criteria. Current monitoring guidelines may need to be reexamined.

Thyroid uptake and scintigraphy using 99mTc pertechnetate: standardization in normal individuals.

CONTEXT: Thyroid uptake and scintigraphy using 99mTc-pertechnetate has proven to be more advantageous than with 131I-iodide, since the images have better quality, the procedure is faster and the patient is submitted to a lower radiation dose. OBJECTIVE: The purpose of this study was to standardize a simple and fast methodology for performing thyroid uptake and scintigraphy and to determine the normal values for 99mTc- pertechnetate uptake. TYPE OF STUDY: Prospective, non-randomized. SETTING: Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas State University. PARTICIPANTS: The study consisted of 47 normal individuals, 30 women and 17 men, with ages ranging from 19 to 61 years (mean of 33 years). PROCEDURES: The laboratory assessment of thyroid function consisted of serum dosages of ultra-sensitive thyroxin and thyrotrophin. Twenty minutes after an intravenous injection of 10 mCi (370 MBq) of 99mTc-pertechnetate, the images were obtained on a computerized scintillation camera equipped with a low-energy high-resolution parallel hole collimator. RESULTS: All the individuals were euthyroid both on clinical and laboratory evaluation. The baseline thyroid 99mTc-pertechnetate uptake ranged from 0.4 to 1.7%. The uptake values obtained in these normal individuals showed that 95% presented a thyroid uptake that ranged from 0.4 to 1.5% of the injected dose. CONCLUSION: The assessment of thyroid structure and function using 99mTc-pertechnetate is a simple, fast and efficient method, which could easily become a part of the routine studies in nuclear medicine laboratories.

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.