TSH Measurements Research Articles

7067 A Pilot Study on Levothyroxine Administration- Understanding the Effects on Thyroid Hormone Levels and Patient Compliance Without Restrictions on Food or Time

Abstract Disclosure: R. Patel: None. K. Pandya: None. D. Olson: None. Background- Hypothyroidism is one of the most common treatable endocrinological disorders that can be managed by replacement therapy. In most cases, compliance is a major hindrance for maintenance medications to express the intended effect. Thus, prescribing medications in a more convenient way would make it easier for the patients to remember and hence amplify compliance. Traditional practice dictates thyroid replacement medication to be administered early in the morning on an empty stomach for optimum absorption. This mandates some patients to set an alarm clock for early morning to take their thyroid medication, which can not just be cumbersome but also increase the chances of having a fall and can alter sleep hygiene as well. We aimed to identify if allowing patients with a more lenient approach in medication timing can help increase compliance while still maintaining thyroid hormone levels with fewer side effects. Methods- As an initial single-arm pilot study, we retrospectively looked at thirteen patients from a single center, for whom patient preference was respected in allowing them to take thyroid replacement in conjunction with any other medication, food, coffee, or any combination of those, as long as it was consistently taken the same way and at the same time each day. In this study, the patient population ranged in age from 44 to 95, with a mean age of 77.38. Most of these patients had follow-ups for over a decade while their TSH levels were observed with minimum follow-up duration being 4 years. Results- On the serial measurement of TSH on this patient cohort, it was discovered that patients were still euthyroid, ranging from 0.36 to 5.28 with a mean of 2.654. This euthyroid state was achieved without requiring any frequent monitoring or extraordinarily high doses of thyroid supplement hormones compared to patients following traditional measures for the same. The highest dose required to achieve Euthyroid status was no more than 125 mcg once/day without any major hormonal fluctuations or adverse events during their treatment course. Thus, indicating that the proposed amendment to thyroid replacement instructions did not negatively impact thyroid function Conclusion- Hence, we propose a more lenient approach to taking Thyroids supplements allowing the patients to take them more conveniently and hence improving the compliance, improving overall outcomes. This can primarily be applied to the elderly population, minimising potential harm, i.e., falls, and other limitations in an attempt to take it consistently. However, this will be further investigated through a clinical trial to gather more comprehensive data on outcomes as well as identify any potential limitations of this concept. Presentation: 6/2/2024

Thyroid Hormone Replacement Dosing after Bariatric Surgery in Patients with Primary Hypothyroidism And Severe Obesity: Tehran Obesity Treatment Study.

Background: Obesity and hypothyroidism are common medical conditions that are associated with each other. Bariatric surgery (BS) is a common approach used to achieve substantial weight loss in obese patients. However, there is limited evidence regarding the need for postsurgery levothyroxine (LT4) dose adjustment in patients with hypothyroidism undergoing BS. Methods: This was a three-year prospective cohort study assessing postsurgery LT4 requirements with attention to body composition changes. The current study included 1030 patients with hypothyroidism, who underwent sleeve gastrectomy (SG) (n = 707, 88.3% women) or one anastomosis gastric bypass (OAGB) (n = 323, 92% women). Patients were followed for 36 months after surgery. A bioelectrical impedance analyzer was used for body composition assessment. LT4 requirements were assessed by generalized estimating equation (GEE) methods adjusted for weight as a time-varying covariate. Results: During the follow-up, TSH (mIU/L) and T4 (ng/dL) measurements did not significantly change in the OAGB group over time. However, in the SG group, TSH measurement decreased over time (ptrend = <0.001). In the third year of the follow-up, 56.1% and 33.3% of patients in the SG and OAGB groups experienced LT4 (μg/day) dose reduction, while 24.4% and 9.1% of the participants experienced LT4 dose increments, respectively. GEE analysis showed a significant increase in the LT4/fat mass (FM) (μg/kg) ratio after 36 months of follow-up compared with the baseline in both the SG [1.8 (1.5-2.2) to 2.7 (2.0-3.5), ptrend = 0.039)] and OAGB [1.7 (1.4-2.2) to 3.2 (2.7-4.8), ptrend = <0.001)] groups. Moreover, patients who underwent OAGB experienced greater LT4/FM (μg/kg) dose adjustments compared to those undergoing SG (pbetween = 0.060). In both groups, after the first year, the increase in LT4/FM (μg/kg) plateaued (pinteraction = 0.009). Conclusion: Most hypothyroid patients experienced either a reduction or no change in LT4 (μg/day) dosage after 36 months in both surgical groups. The LT4/FM (μg/kg) was significantly increased in patients undergoing either SG or OAGB with greater alterations in the latter. Further studies on larger populations and with longer duration of follow-up are needed to confirm our results.

Thyroid function monitoring during pregnancy in euthyroid women with thyroid autoimmunity.

Thyroid autoimmunity (TAI) may be present in 1-17% of pregnant women. Monitoring of thyroid function in euthyroid pregnant women positive for anti-thyroperoxidase antibodies (TPOAb+) is recommended. To determine the prevalence and possible clinical and biological risk factors of biochemical progression (rise in serum thyroid-stimulating hormone (TSH) > 2.5 mU/L) at second blood sampling during pregnancy, in euthyroid women (TSH ≤ 2.5 mU/L) according to their TPOAb status. This study included demographic and biological data from two previously published cohorts (n = 274 women from August 1996 to May 1997 Copenhagen cohort, and n = 66 women from January 2013 to December 2014 Brussels cohort) having at least two measurements of TSH and free thyroxine (FT4) and at least one of TPOAb during spontaneously achieved singleton pregnancies. The majority of women studied did not show biochemical progression. Only 4.2% progressed, significantly more frequently among TPOAb+ women, as compared to TPOAb- group (9.4 vs 2.7%, P = 0.015). No rise in serum TSH > 4 mU/L at 2nd sampling was observed. Higher baseline TSH levels were associated with biochemical progression in both TPOAb+ (P = 0.05) and TPOAb- women (P < 0.001), whereas maternal age, BMI, multiparity, smoking, FT4, and TPOAb concentrations were not significantly different between women with and without progression. Only a minority of euthyroid women with thyroid autoimmunity presented biochemical progression and none with a TSH > 4 mU/L. Larger studies are needed to better target the subset of women who would benefit most from repeated thyroid function monitoring during pregnancy.

Hipotiroidismo

Hypothyroidism is one of the most prevalent endocrine diseases in routine clinical practice. The most common etiology worldwide is iodine deficiency. In countries with sufficient iodine intake, it is Hashimoto's thyroiditis. In this sense, it is important to take an adequate case history and physical examination for a diagnosis, although confirmation is determined by biochemical analysis. The universal screening protocol consists of the initial TSH measurement and, in case of abnormal values, FT4 measurement. The normal limits for TSH are controversial and continue to be the subject of debate today. They have associated conditioning factors such as pregnancy or the normal limit in the older adult population. Replacement therapy is not always indicated, but when it is, oral levothyroxine is the treatment of choice.

Indicaciones e interpretación de pruebas complementarias analíticas en la patología tiroidea

Analytical tests are crucial for the screening, diagnosis, treatment, and follow-up on thyroid disease. Universal thyroid function screening is not recommended at present; its determination may be indicated based on the patient's specific symptoms and situations. An isolated TSH measurement is currently considered the standard for screening and the aposteriori determination of free T4 and T3 is indicated depending on the result. Likewise, the determination of antibodies is essential for the diagnosis of autoimmune thyroid dysfunction. Common errors in interpretation include the presence of non-thyroidal disease, immunoassay interference, or certain drugs. This protocol provides practical guidelines for interpreting and using tests in thyroid disease, highlighting key diagnostic considerations.

Maternal thyroid function in early pregnancy and offspring school performance and neurodevelopmental disorders.

Thyroid hormones are critical for neural development, and during the first trimester of pregnancy the fetus relies fully on maternal thyroid hormone production. To investigate the associations between maternal thyroid hormone levels in the first trimester with the child's school performance, risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). From the Copenhagen Primary Care Laboratory Pregnancy Database information on first trimester TSH and fT4 measurements in mothers of children born in 2000-2014 were linked with information on the child's standardized test scores in school, ADHD (patient record diagnoses and medication) and ASD (patient record diagnoses) until end of 2018. Associations of TSH and fT4 with the outcomes were individually assessed by linear mixed models and Cox regression models. The analyses were stratified by preexisting maternal thyroid disorders. TSH measurements were available for 17,909 mother-child dyads. Among those with children born in 2000-2009, 6,126 had a standardized school test score and were analyzed for the association between maternal thyroid hormone levels and child's school performance, and no support for an association was found. The association between thyroid hormone levels and child's risk of ADHD and ASD were analyzed for the 17,909 dyads and with no support for an association between thyroid hormone levels and these neurodevelopmental disorders. Stratification by preexisting maternal thyroid disorders did not affect the results. We found no evidence for associations between first trimester maternal thyroid hormone levels and child's school performance, or risk of ADHD or ASD.

Subclinical Hypothyroidism as a Possible Cause of Herpes Zoster Reactivation

Background: Hypothyroidism was considered as a predisposing factor for herpes zoster (HZ) infection. Thus, Thyroxine deficiency may be a risk factor for varicella zoster virus reactivation. The aim of this study was to test if thyroid hormone supplementation will ameliorate the clinical course of HZ infection.&#x0D; Methodology: This was a prospective cohort conducted on 60 herpes zoster infected patients, who had a subclinical hypothyroidism. Serum TSH and FT4 measurements were made by using electrochemiluminescence immunoassay. All patients were divided into two groups. Group A included 30 patients who were treated with Eltroxin 25 µg daily for 3 months. Group B included 30 patients who took placebo. All were submitted to cutaneous examination (e.g., rash and new lesions). Any complications were documented. Pain was assessed before and after treatment, and any pain-controlling medications were registered. The primary endpoints were time to achieve complete pain cessation, time to cessation of the formation of the new lesions, and time to &gt; 50% crusting/healed lesions. Secondary outcome included time to 100% crusting/healed lesions, time to complete absence of moderate to excruciating pain, time to first pain-free period, and time to absence of abnormal sensations.&#x0D; Results: Both groups were comparable regarding patient age, gender, chronic medical diseases, and characteristics of herpes zoster rash. Ophthalmic zoster was reported in 6.7% and 10% of groups A and B respectively. However, group A (Eltroxin supported) had much better and rapid and rash healing of pain than group B. Finally, zoster-related complications were significantly lower in group A than group B.&#x0D; Conclusions: Subclinical hypothyroidism is associated with HZ reactivation process, so hypothyroid medical treatments are effective in this case.

CRITERIA FOR ULTRASOUND SUSPICION OF THYROID NODULE

A thyroid nodule is a formation well differentiated from the rest of the thyroid. It represents the most frequent thyroidpathology, and the majority of these nodules are benign. Assessment of patients with thyroid nodules includes history,clinical examination, TSH measurement and thyroid ultrasound.In this article, we will detail the criteria for suspicion, including the place of ultrasound in the evaluation of thyroidnodules, based on the EU-TIRADS criteria

Standardisation and harmonisation of thyroid-stimulating hormone measurements: historical, current, and future perspectives.

Thyroid-stimulating hormone (TSH) is an important clinical marker in the diagnosis and management of thyroid disease. TSH measurements are reported in milli-International Units per Litre (mIU/L), traceable to a World Health Organisation (WHO) reference material. There is a wide variety of commercial immunoassays for TSH measurements available, which have historically been poorly harmonised due to a lack of commutability of the WHO reference materials with patient samples. This led to the recent development of a serum-based reference panel for TSH, traceable to the WHO reference material, available via the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC), aimed at harmonisation of TSH immunoassays. This report describes recent developments in the TSH reference system, including establishment of the4th WHO International Standard for TSH, and aims to clarify the relationship between the available reference materials and their intended uses. This 4th WHO IS is widely available and defines the unit of TSH activity, therefore its continued existence is of paramount importance, however it continues to show a lack of commutability with patient in many TSH immunoassays. This makes the C-STFT TSH panel, albeit available in restricted numbers, a critical resource to ensure better TSH assay harmonisation.

Systematic review of thyroid function in NKX2-1-related disorders: Screening and diagnosis.

NKX2-1-related disorders (NKX2-1-RD) are rare conditions affecting lung, thyroid, and brain development, primarily caused by pathogenic variants or deletions in the NKX2-1 gene. Congenital hypothyroidism (CH) is a common endocrine manifestation, leading to irreversible intellectual disability if left untreated. The aim was to evaluate the current evidence for the use of screening and diagnostic techniques for endocrine alterations in patients with NKX2-1-RD. This systematic review was reported following the PRISMA guidelines. Two separate research questions in PICO format were addressed to cover initial screening and diagnosis procedures for endocrine diseases in patients with NKX2-1-RD. Eligibility criteria focused on patients with genetic confirmation of the disease and hypothyroidism. Various databases were searched, and data were extracted and assessed independently by two reviewers. Out of 1012 potentially relevant studies, 46 were included, for a total of 113 patients. CH was the most frequent endocrine alteration (45% of patients). Neonatal screening was reported in only 21% of patients based on blood TSH measurements. TSH thresholds varied widely across studies, making hypothyroidism detection ranges difficult to establish. Diagnostic tests using serum TSH were used to diagnose hypothyroidism or confirm its presence. 35% of patients were diagnosed at neonatal age, and 42% at adult age. Other hormonal dysfunctions identified due to clinical signs, such as anterior pituitary deficiencies, were detected later in life. Thyroid scintigraphy and ultrasonography allowed for the description of the thyroid gland in 30% of cases of hypothyroidism. Phenotypic variability was observed in individuals with the same variants, making genotype-phenotype correlations challenging. This review highlights the need for standardized protocols in endocrine screening for NKX2-1-RD, emphasizing the importance of consistent methodology and hormone threshold levels. Variability in NKX2-1 gene variants further complicates diagnostic efforts. Future research should concentrate on optimizing early screening protocols and diagnostic strategies.

Allan-Herndon-Dudley syndrome in Hong Kong: Implication for newborn screening

BackgroundAllan-Herndon-Dudley syndrome (MCT 8 deficiency) is an X-linked recessive condition caused by hemizygous pathogenic variants in SLC16A2 encoding the monocarboxylate transporter 8 (MCT8). Patients present with global developmental delay and neurological impairment, and abnormal serum thyroid function tests. The drug, 3,3′,5 triiodothyroacetic acid (TRIAC), was recently demonstrated to improve the endocrinological profile. Improvement in diagnostic approach is key to earlier start of treatment. Patient findingsWe described four Chinese patients with MCT8 deficiency undergoing different diagnostic odysseys. Their initial presentation included global developmental delay and dystonia. Patient 2 also had epilepsy. Patients 1 and 2 presented with two novel variants: (1)hemizygous NM_006517.4(SLC16A2):c.1170 + 2 T > A; p.(?), and (2)hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17) respectively. Patients 3 and 4 were biological brothers harboring hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17), which was first reported in 2004. We obtained the measurement of triiodothyronine (T3) and reverse T3 (rT3) from dried blood spot samples collected on Day 1 of life from Patient 1 and studied the biomarkers (rT3 and T3/rT3 ratio) proposed by Iwayama et al. for the detection of MCT8 deficiency at birth. Our data verified the significantly reduced rT3 level in Patient 1, compared with healthy newborns, although low T3 level and comparable T3/rT3 ratio with controls were detected. SummaryPatients with MCT8 deficiency often undergo diagnostic odysseys. An early diagnosis could be missed by a normal newborn thyroid function screening result based on biochemical measurement of TSH and/or T4/fT4. Early detection of rT3 is key to improving current diagnostic approach. ConclusionWe recommend that full thyroid function profile (TSH, T4/fT4, T3/fT3, rT3) be considered early for all pediatric patients presenting with unexplained developmental delay and/or dystonia. The potential inclusion of rT3 measurement in newborn screening may prove promising.

THU397 Homeostatic Regulation Of 1,25-dihydroxyvitamin D: Critical Role Of 24-hydroxylation (CYP24A1)

Abstract Disclosure: Z. Shahidzadeh Yazdi: None. E.A. Streeten: Grant Recipient; Self; Regeneron Pharmaceuticals. H.B. Whitlatch: Grant Recipient; Self; Regeneron Pharmaceuticals. M.E. Montasser: Grant Recipient; Self; Regeneron Pharmaceuticals. A.L. Beitelshees: None. S.I. Taylor: Consulting Fee; Self; Ionis Pharmaceuticals Inc. The VITAL study raised substantial questions whether current Endocrine Society guidelines provide optimal criteria to identify patients whose bone health would benefit from vitamin D (VitD) supplements. We investigated the impact of VitD supplements on levels of VitD metabolites and other biomarkers in the context of studying interactions between VitD and canagliflozin. 11 healthy Amish participants with 25-hydroxyvitamin-D (25(OH)D) levels ≤20 ng/mL were recruited in the context of our ongoing pharmacogenomic study of canagliflozin. RESULTS: VitD supplements increased mean levels of 25(OH)D from 16.5±1.6 ng/mL to 44.3±5.5 ng/mL (p=0.0006) and 24,25(OH)2D from 1.0±0.1 ng/mL to 4.3±0.6 ng/mL (p=0.0002). Mean levels of 1,25(OH)2D and PTH were unchanged: 43.8±3.6 vs. 44.9±4.1 pg/mL for 1,25(OH)2D and 47.5±4.8 vs. 48.4±5.1 pg/mL for PTH. We applied mathematical modeling, which suggested that regulation of 24-hydroxylation was the principal mechanism responsible for maintaining 1,25(OH)2D levels within a narrow range in our mildly VitD deficient research participants [25(OH)D levels: 10-20 ng/mL]. When 25(OH)D levels were low (&amp;lt;20 ng/mL), 24-hydroxylation was maximally suppressed. Low levels of 24-hydroxylase activity tend to sustain levels of 1,25(OH)2D by decreasing its rate of metabolic clearance. VitD supplementation induced 24-hydroxylase activity by ∼5-fold – reaching a plateau when 25(OH)D levels &amp;gt;60 ng/mL. As suggested in the literature (JCY Tang et al, Sci Rep, 9:6974, 2019), we calculated ratios of 1,25(OH)2D/24,25(OH)2D as an index for the homeostatic response to VitD status. When we plotted the 1,25(OH)2D/24,25(OH)2D ratio as a function of 25(OH)D/1,25(OH)2D, we observed an extremely high degree of correlation (Spearman correlation coefficient of -0.94; p=10-10). DISCUSSION: Clinical assessment of thyroid status provides a highly relevant historical precedent. 50 years ago, thyroid status was assessed by measurement of total serum thyroxine (T4) levels. Diagnostic accuracy was greatly improved when total T4 was replaced by laboratory measurement of either free T4 or TSH (an index of the homeostatic response to thyroid status). Current clinical guidelines recommend assessment of VitD status by measuring total levels of 25(OH)D, which unfortunately are confounded by inter-individual variation in levels of VitD binding proteins (VDBP). We anticipate that diagnostic accuracy would be greatly enhanced if clinicians replaced measurement of total 25(OH)D by laboratory measurements that are not affected by variation in levels of VDBP. By analogy to the approach to clinical assessment of thyroid status, we recommend consideration of VDBP-independent indices of VitD status including 25(OH)D/1,25(OH)2D as an index of VitD stores and 1,25(OH)2D/24,25(OH)2D as an index for the body’s homeostatic response to VitD status. Presentation: Thursday, June 15, 2023

FRI435 A Grave Case Of Gynecomastia

Abstract Disclosure: S. Seltzer: None. A. illiams: None. T. Kader: None. Background: Gynecomastia is a common endocrinology referral. Our team saw a patient in the clinic with an unusual presentation. Clinical Case: A 28 year old male presented with worsening painful gynecomastia affecting one breast initially but eventually progressing to both breasts. His secondary concern was a 40lb weight loss and new onset tremor. He declined hypogonadal symptoms, palpitations, or new testicular growth. Exam revealed a resting pulse of 120 b.p.m., a palpable goiter, visible tremor, hyperdynamic heart sounds and bilateral tender gynecomastia. Labs revealed normal FSH, LH and hCG, high total testosterone (TT), thyroxine (T4) and triiodothyronine (T3) with positive thyroid receptor antibodies. Methimazole and beta blockade were started. He did develop an episode of atrial fibrillation requiring admission. Due to medication intolerance and patient preference the decision was made for total thyroidectomy. Three months post-surgery there was complete resolution of hyperthyroidism and gynecomastia.The differential for true gynecomastia is broad. The initial diagnostic approach includes a thorough history and physical exam followed by measuring serum testosterone (T), LH, hCG and estradiol (E2). Increased LH and low T indicates hypogonadism. Normal values may suggest an idiopathic cause. Elevated hCG warrants testicular imaging and if negative, chest and abdominal imaging to rule out extragonadal germ cell tumors. Elevated total T and LH should prompt measurement of TSH and T4 and if normal androgen resistance should be suspected. Elevated E2 and low/low normal LH should prompt testicular imaging and if normal an adrenal CT to rule out an adrenal neoplasm. If LH and T are low, prolactin should be measured as well as dedicated pituitary imaging.Any state which induces an increased E to T ratio may cause gynecomastia. The true pathophysiology in hyperthyroidism driving the increased sex hormone binding globulin (SHBG) production is unknown. It is postulated that this increase is driven by increased transcription and translation of hepatocyte nuclear factor-4ɑ secondary to elevated T41. SHBG more readily binds androgens than estrogens leading to a relative decrease in free T (FT). The lower FT levels result in negative feedback to the pituitary gland which causes increases in LH resulting in production of androgens, estradiol and peripheral aromatases. The increase in peripheral aromatization of testosterone leads to further elevation of the free estrogen levels. Conclusion: Hyperthyroidism should always be in the differential of gynecomastia as in our case the presentation may be atypical.

The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels.

To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease. Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4corr), baseline TSH (TSH0) and relative or absolute TSH increase (TSHfold, TSHabsolute). Patients diagnosed with CH (n=39) show comparable TSH0 (p-value 0.824) but lower T4corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4corr, the CH diagnosis was rejected based on a high TSHfold. In these cases, a spontaneous increase and mean normalization in T4corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy. The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results.

GlycA as a Novel Biomarker of Systemic Inflammation in Hypothyroidism.

Background: GlycA is a novel glycoprotein biomarker of systemic inflammation and cardiovascular risk. Our objective was to assess the levels of GlycA in individuals with hypothyroidism. We also explored whether levothyroxine (LT4)-treated patients had different levels of GlycA, with attention to thyrotropin (TSH) levels. Methods: We performed a cross-sectional analysis, using baseline data from the ELSA-Brasil cohort study. We included only participants with serum TSH and GlycA levels measurements, using magnetic resonance spectroscopy (n = 4745). We excluded individuals with endogenous hyperthyroidism and those using drugs impacting thyroid function. Participants not taking LT4 and whose serum TSH was 0.4-4.0 mIU/L were classified as euthyroid (EU) and those with elevated TSH as undiagnosed hypothyroidism (UH). For those on LT4 (n = 345), adequacy of treatment was defined as TSH within the reference range. Those with TSH <0.4 mIU/L were considered over-treated (OT), and those >4.0 mIU/L, under-treated (UT). Both (UT+OT) were considered inadequately treated (IT). Group comparisons were performed by Kruskal-Wallis, adjusted Chi-square, and the post hoc Dunn test. Additional subgroup analysis were performed in patients with circulating thyroperoxidase antibodies (TPO-Ab+). Respective multivariable analyses were performed to evaluate the relationship between thyroid-related variables and GlycA levels (Generalized Linear Model), as well as an abnormal GlycA (>400 μmol/L; Logistic Binary Regression). Results: The prevalence rate of UH was 9.8% (467/4745) and, among those on LT4, only 61.7% (213/345) were adequately treated (AT). GlycA levels were higher in IT in comparison to EU (429 vs. 410 μmol/L, p < 0.01) but did not differ between UH (413 μmol/L) and euthyroidism. However, the subgroup analysis of those TPO-Ab+ showed that not only those with IT, but also those with UH, had higher levels of GlycA in comparison to euthyroidism (423 and 424 vs. 402 μmol/L, p = 0.04). This association between higher levels of GlycA and IT was maintained even in multivariable analysis (odds ratio 1.53, confidence interval 1.03 to 2.31) Lower levels of GlycA were detected in AT (405 μmol/L,) compared with OT (432 μmol/L, 0.04) and UT (423 μmol/L, p = 0.02). Conclusions: Patients with IT, both OT and UT, had higher GlycA levels, which may be associated with low-grade systemic inflammation and, possibly, increased cardiovascular risk.

Thyroid and Pregnancy

Abstract Hormonal changes and metabolic needs during pregnancy result in profound changes in biochemical parameters of thyroid function, especially if there is preexsisting autoimmune thyroid disease (AITD). Normal thyroid function is important in order to ensure the best outcome. Many changes in the functioning of the thyroid gland occur during pregnancy, and some diseases of thyroid gland can affect both mother and fetus. Hypothyroidism is the most serious disorder that occurs during pregnancy and can go unnoticed as a „non-specific” problem. Hypothyroidism arises from the reduced ability of the gland to adapt to the increased needs during pregnancy. Mild thyroid dysfunction of mothers in the first trimester, which does not threaten during the pregnancy, can damage the psychomotor development of the child. Measurement of TSH is the most practical, simple and cost-effective screening test for thyroid dysfunction. It is necessary to apply the trimester-specific TSH reference values to correctly interpreted thyroid function during pregnancy. The presence of TPOAb is confirmation of existence of AITD, and predicts increased risk of developing subclinical hypothyroidism (SH). Preconceptional education and adequate diagnosis and treatment of thyroid dysfunction in early pregnancy are of great importance, in order to prevent complications during pregnancy and offspring. Current data indicate an increase in pregnancy loss, gestational diabetes, gestational hypertension, pre-eclampsia and preterm delivery in women with SH in pregnancy. The control of thyroid disease reduce complications of pregnancy.

A mathematical algorithm to harmonize measurements for thyroid-stimulating hormone between instruments

BackgroundThyroid-stimulating hormone (TSH) is measured differently between diagnostic units using different devices, which makes cross-comparisons challenging. Here, we have developed a mathematical algorithm to harmonize TSH measurements between 2 instruments, the Abbott ISR2000 and the Siemens ADVIA Centaur XP. MethodsApplying the principle of the maximum allowable error between the standard curve and real signal values, the minimum number of comparison samples required for TSH hormone detection was calculated for both instruments. Next, a mathematical algorithm describing the relationship between TSH standard curves from both instruments was established. The algorithm was then tested on sample measurements from both instruments, with signals transformed to Siemens ADVIA Centuar XP-type data. Finally, test results were assessed where the relative error was <half of the total allowable error (1/2 TEa). ResultsBefore conversion, the mean percentage error between the TSH results of samples measured on both instruments was 23.20% (>1/2 TEa). After algorithmic transformation, the average percentage error was reduced to 7.93% (<1/2 TEa). ConclusionsOur algorithm enables TSH measurements across different instruments to be comparable, and provides a method to harmonize TSH data between laboratories that utilize different instrumentation.

Ameliorating Effect of Ashwagandha (Withania Somnifera) Extract on Hippocampus and Growth Plate Changes Associated With Propylthiouracil Induced Hypothyroidism in Juvenile Rats

Background: Hypothyroidism is a decrease in the production of the thyroid hormones and leads to gland dysfunction. Ashwagandha extract was used as an ayurvedic treatment and supposed to be as antihypothyroidism agent. Objectives: to investigate the impact of ashwagandha (Ash) extract on propylthiouracil (PTU)-induced hypothyroidism in rats. Subjects and Methods: The rats were divided into three groups, control group, PTU (hypothyroid) group (6mg/kg/day by oral route), PTU (6mg/kg/day by oral route) +Ash (50mg/kg/day by oral route) treated group. All treatment continued for 30 days. At the end of experiment, measurement of serum T3, T4 and TSH was performed. Thyroid gland, right sided tibia and dentate gyrus region of hippocampus were examined using histological, histochemical and immunohistochemical studies. All measurements were statistically analyzed. Results: Decrease in serum T3 and T4 and congestion of the blood capillaries, follicular distortion, and vacuolar degeneration of some follicular cells were exhibited in thyroid gland of hypothyroid group. Histological changes in growth plate cartilage in the form of decrease of matrix deposition and plate thickness were detected. Dentate gyrus showed distorted granule cell layer. Immunohistochemically, low expression of the GFAP was expressed in astrocytes. PTU+Ash treated group showed improvement of the previous changes. Conclusion: Administration of ashwagandha with PTU displayed protective effect on the thyroid gland and its associated histological changes in growth plate cartilage and dentate gyrus. Higher doses of ashwagandha should be used for extrapolation if it may give better results than the used dose.

Unexplained Hyperthyrotropinemia: A Biochemical and Clinical Challenge.

A raised serum TSH in the absence of a clear etiology, or "unexplained hyperthyrotropinemia" (UH), can be challenging for clinicians. The aim of the present study was to evaluate potential strategies aimed at a clinical and biochemical characterization of UH patients. We compared 36 patients with UH with a control group of 14 patients with chronic autoimmune thyroiditis (CAT) and subclinical hypothyroidism. The two groups were compared in terms of the following: (i) the rate of normalization of TSH after repeating with another assay; (ii) the rate of normalization of TSH over time with the same assay; (iii) the reduction in TSH after precipitation with polyethilenglycole (PEG); and (iv) free thyroxine (FT4) levels. Similar TSH levels were observed in UH [5.65 (5.21-6.37)] and CAT [5.62 (5.17-8.50)] (p = 0.489). TSH measurement with another assay method showed a normal TSH value in 41.9% of UH vs. 46.1% of CAT patients (p = 0.797). After repeating the TSH measurement in time with the same assay method, an increased TSH value was confirmed in all cases, in both groups (0% in the UH group vs. 0% in the CAT group, p = 1.000). TSH recovery after PEG precipitation was similar in the two groups (% precipitable post-PEG: 68.75 ± 3.14 in UH vs. 68.67 ± 7.18 in CAT, p = 0.960). FT4 levels were similar in the two groups (FT4 1.02 ± 0.20 ng/dl in UH vs. 1.00 ± 0.20 ng/dl in CAT, p = 0.789). The results do not support the concept that laboratory interferences are more frequent in UH patients, suggesting that patients with UH should be managed in the same way as patients with CAT until proven otherwise.

Impact of preconception thyrotrophin on obstetric outcomes in the fertile population

IntroductionThere is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy.Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester.In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested.Although this is a different population, these «optimal» TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. ObjectivesDetermine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women. Materials and methodsRetrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18–40 years, euthyroid (TSH 0.5–4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5–2.4 mU/l (optimal) and TSH 2.5–4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. ResultsWe found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. ConclusionOur results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.