Normal TSH Levels Research Articles

Efficacy of levothyroxine monotherapy in achieving clinical euthyroidism and its impact on weight loss in women with hypothyroidism and obesity.

In light of research indicating that normal TSH levels do not necessarily reflect clinical euthyroidism in hypothyroid patients, and given the patient dissatisfaction with levothyroxine (LT4) monotherapy, we evaluate the response to weight loss treatment in patients with obesity and primary hypothyroidism who are euthyroid under LT4 therapy, with a focus on weight and metabolic parameters. The retrospective study included 138 subjects with obesity (BMI ≥ 30kg/m2), 69 women with hypothyroidism on levothyroxine, and 69 age- and BMI-matched women without thyroid disease. Secondary causes of obesity, medications that may affect thyroid functions and metabolic parameters, chronic and oncological disease, pregnancy, TSH outside the reference range, follow-up periods of less than one year, and bariatric surgery were the exclusion criteria. Patients' characteristics and metabolic responses to weight reduction treatment consisting of calorie restriction, moderate exercise, and metformin if needed were evaluated. TSH and fT4 levels were higher, and fT3 and T3/T4 ratios were lower all within the reference ranges in hypothyroid women. They were less insulin resistant. Both patient' groups experienced a significant decrease in body weight, BMI, and atherogenic index of plasma (AIP) during the follow-up (p = 0.001). Insulin resistance was not changed. The groups' body weight, BMI, HOMA-IR, and AIP changes were similar at the end of the study (p = 0.876, p = 0.850, p = 0.555, p = 0.293). The results suggest that achieving euthyroid status via levothyroxine monotherapy in hypothyroid women leads to weight loss responses comparable to those in women with normal thyroid. This supports the effectiveness of current hypothyroidism treatment strategies, emphasizing TSH level normalization, in achieving clinical euthyroidism concerning weight loss outcomes.

Prevalence of Autoimmune Thyroiditis Among Children with Type 1 Diabetes

A single-stage cross-sectional study was conducted on the basis of the National Center for Maternal Health in the Kyrgyz Republic, children aged 0 to 18 years were examined. To study the prevalence of autoimmune thyroid disease with type 1 diabetes mellitus to improve the compensation of carbohydrate metabolism in children and adolescents with type 1 diabetes. Autoimmune thyroiditis often accompanies and interferes with type 1 diabetes mellitus in children and adolescents. Thyroid dysfunction in children with type 1 diabetes mellitus can negatively affect various areas of metabolic control. This study included 60 children with type 1 diabetes mellitus and autoimmune thyroiditis, 24 of them girls (40.0%), 36 boys (60%). The average value of ±SD for their age at the time of examination was 11.6±4.1 years, ranging from 1 to 17 years. Of the children with type 1 diabetes mellitus who tested positive for antibodies to thyroid peroxidase, 30 children (50%) had obvious hypothyroidism. Of the thirty children with normal TSH levels, 4 children (13.3%) showed signs of subclinical hypothyroidism, while 26 children (86.7%) had euthyroidism.

7308 A Case of Thyroid Hormone Resistance Associated With a Novel Mutation in the THRA Gene

Abstract Disclosure: J.A. Siddiqui: None. M. Barbosa: None. V. Fettig: None. C.J. Romero: None. Introduction: Thyroid hormone resistance (THR) is a syndrome leading to decreased response of target organs to thyroid hormone. Normal thyroid hormone action is mediated by thyroid hormone nuclear receptors and is essential for normal development and metabolism. Two isoforms are encoded by the thyroid hormone receptor α and β genes (THRA and THRB). Mutations in THRB are commonly reported with limited cases of THRA mutations. We report a 15-month-old and her mother with a pathogenic variant in the THRα receptor leading to thyroid hormone resistance. CASE: A 15-month-old ex-39-week gestation female was born small for gestational age (birth weight: 2450 grams,3rd %ile and birth length: 17 inches,1st %ile). The newborn screen was normal. She presented with macroglossia, low tone and global developmental delay. She had severe constipation complicated by rectal prolapse that required surgical correction. There are multiple relatives (mother, maternal half-brother and maternal grandparents) with neurodevelopmental issues. The mother’s previous genetic evaluation was non-diagnostic. Mother reports a thyroid condition but without treatment. The patient was initially referred to genetics and whole exome sequencing revealed a heterozygous c.1205 T>C p. (L402P) variant in the THRα gene, which was maternally inherited and reported as a variant of uncertain significance. On physical exam, Heart rate was 112 bpm; height <1%ile (Z-score -3.22 SD), weight 3%ile (Z-score -1.89 SD). Patient has a wide anterior fontanelle (4x3 cm), macroglossia and delayed teeth eruption. Other exam findings: non-palpable thyroid and postaxial polydactyly on the 5th digit of the right toe. Thyroid hormone testing: normal TSH 1.829 uIU/mL, low total T4 4.4 mcg/dL, low Free T4 of 0.58 ng/dL and high free T3 of 4.24 pg/mL. Levothyroxine treatment was initiated(25 mcg daily). After 1 month treatment, TSH level was 0.23 uIU/mL, total T4 was 6.1 mcg/dL and low reverse T3 of 5.8 ng/dL. DISCUSSION: Thyroid hormone resistance due to THRα mutations are rare and under-recognized. The main clinical phenotype includes growth retardation, delayed development, decreased muscle tone, delayed tooth eruption and constipation. Unlike patients with THRβ mutations, the hypothalamus-pituitary-thyroid axis in patients with THRα mutations is minimally affected with a normal TSH level. Total T3 levels are elevated with slightly low total T4 and free T4:T3 ratio is low. Treatment with levothyroxine leads to suppressions of TSH levels, therefore confirming intact central T3 feedback loop. Reports, however, show minor clinical improvements with treatment; therefore further research is needed in these patients to explore more effective therapeutic options. We present a case of a novel congenital THRA mutation leading to a clinical phenotype consistent with THR. She continues care in our clinic with hopes to further study her mutation. Presentation: 6/2/2024

6415 Resistance to Thyroid Hormone -A Challenge to Manage

Abstract Disclosure: A. Altaf: None. F. Iqbal: None. E. Hamoudeh: None. C. Coyne: None. K. Anne: None. L. Buckley: None. Background: Resistance to thyroid hormone (RTH) or Refetoff syndrome was first introduced in 1967. It is an autosomal dominant or recessive genetic disease with a mutation in the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. The distinguishing biochemical feature of RTHβ is an elevated level of circulating free thyroid hormones with normal or high TSH concentration and decreased peripheral tissue response to thyroid hormone. Common signs and symptoms in patients with RTHβ are short stature, attention deficit disorder, and resting tachycardia and many patients might be asymptomatic. Case: We report a case of a 36-year-old patient with past medical history of congenital bilateral hearing loss, atrial fibrillation, CHF, and slow learning/comprehending who presented to the ER with shortness of breath and atrial fibrillation with tachycardia. Admission labs revealed elevated TSH 3.9, elevated fT4 3.28, and elevated TT3 205. He reported that for the past year, he has been on levothyroxine 50mcg for abnormal TSH. Levothyroxine was stopped and the patient was discharged on methimazole 10mg daily. Further workup revealed negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound with Doppler demonstrated a mildly hypervascular thyroid gland without evidence of nodules. Brain MRI was negative for any pituitary abnormalities. HAMA testing continued to show elevated TSH. Patient was followed by cardiology and due to continued atrial fibrillation, had multiple cardioversions and was managed on a beta blocker. Due to his atrial fibrillation, endocrinology service continued his methimazole till his genetic testing came positive for an autosomal dominant heterozygous pathogenic mutation in THRB c.1373 T>C (p. Val458Ala). His thyroid hormones and TSH continue to be elevated. Currently, he is not on thyroid medication and getting monitored. The need for multiple cardioversions for atrial fibrillation in this patient makes resistance to thyroid hormone management challenging. Discussion: Hyperthyroidism is commonly mistaken for RTH. However, the lack of TSH suppression should be further investigated. Most patients with RTHβ are adequately compensated by the increased endogenous supply of thyroid hormone showing increased serum fT3 and fT4 levels and normal or near normal TSH levels. Beta Blockers like atenolol cannot inhibit the conversion of T4 to T3 and can be used for RTHβ with tachycardia. Triiodothyroaceticacid (TRIAC) or dextrothyroxine (DT4) have also been used to treat thyrotoxicosis. In summary, treatment for RTHβ remains a challenge for clinicians, especially in patients with atrial fibrillation and many patients are misdiagnosed and managed as hyperthyroidism. Presentation: 6/3/2024

6784 A Case of Euthyroid Hyperthyroxinemia due to Thyroid Binding Globulin Excess Syndrome

Abstract Disclosure: A.S. Iyer: None. Background: Congenital thyroid binding globulin (TBG) excess is a rare phenomenon associated with elevated serum total T3 and total T4 concentrations but normal serum concentrations of free thyroid hormones, with clinically euthyroid patients. While TBG excess can be caused by pregnancy, estrogen-secreting tumors, and estrogen therapy, congenital TBG excess follows an X-linked pattern, with hemizygous males most affected, and heterozygous females showing a spectrum of disease due to random inactivation of one X chromosome. Clinical Case: A 39-year-old Caucasian female presented as a referral from the Gastroenterology clinic due to concern for thyroid resistance syndrome. Symptoms included chronic constipation (improving with Miralax®), gradual weight gain of 8 pounds in one year, fatigue, and palpitations. She reported that her total thyroid hormone levels have always been elevated, with other thyroid labs remaining within normal limits, along with family history of similar labs noted in her two sons, father, and paternal grandmother. Upon initial encounter, TSH was 1.637 (0.430-3.550 uIU/mL), total T4 15.4 (4.8-11.7 ug/dL), total T3 231 (80-200 ng/dL), free T4 0.97 (0.70-1.25 ng/dL), free T3 3.2 (1.7-3.7 pg/mL), and albumin 4.2 (3.5-5.0 g/dL). The patient was not on oral contraceptive pills and she denied any pregnancies in the last three years. Thyroid ultrasound showed a normal-appearing homogeneous thyroid gland with a small cyst with colloid and no cervical lymphadenopathy. Initial differential diagnosis included TBG excess syndrome versus familial dysalbuminemic hyperthyroxinemia. Permission was obtained from the patient to access one of her son’s medical records from age 8-weeks old when he was also evaluated for abnormal thyroid labs. TSH was 2.144 (0.350-6.500 uIU/mL), total T4 28.2 (5.0-12.0 ug/dL), free T4 1.55 (0.8-1.8 ng/dL), and free T3 4.0 pg/mL (no reference available). Thyroid binding globulin was found to be elevated at 81 (12-26 mcg/mL) in her son and found to be elevated to 78.0 (13.5-30.9 mcg/mL) in this patient, confirming a diagnosis of TBG excess syndrome. Conclusions: TBG excess syndrome should be considered in the differential of patients with high total T3 and total T4 levels with normal levels of free T3, free T4, and TSH, especially in individuals who have a known family history and who have minimal or nonspecific symptoms. Definitive diagnosis will make further testing and treatment unnecessary. However, if these patients develop hypo- or hyperthyroidism, then use of TSH and free levels of T4 and T3 is necessary to direct management and avoid confusion. Reference: Pappa, T., and S. Refetoff. “Thyroid hormone transport proteins: Thyroxine-binding globulin, transthyretin, and albumin.” Reference Module in Neuroscience and Biobehavioral Psychology, 2017, https://doi.org/10.1016/b978-0-12-809324-5.03494-5. Presentation: 6/2/2024

8534 Comorbid Autoimmune Thyroid Disease in a Parent-Child Pair with Resistance to Thyroid Hormone Beta

Abstract Disclosure: A.H. Smith: None. E. Grethen: None. Resistance to Thyroid Hormone Beta (RTHβ) is an inherited disorder caused by mutations in the gene encoding the thyroid hormone receptor beta protein, resulting in decreased binding affinity to triiodothyronine in certain tissues. An asymptomatic individual with RTHβ may demonstrate abnormalities in serologic evaluation of thyroid hormone markers. When other thyroid pathologies present with RTHβ, however, the diagnosis and management can quickly become complex. Below we discuss two cases, a parent-child pair, with different presentations of presumably the same RTHβ gene. Patient 1 is a 61-year-old male with a history of autoimmune thyroiditis several years ago, presenting for continuation of care; he has had levothyroxine doses gradually uptitrated to over 3 mcg/kg to normalize TSH despite persistently high free T4 levels. He also has a family history notable for six out of seven siblings with autoimmune thyroid disease. Patient 2 is a 44-year-old male who was evaluated for hypothyroidism and difficulty with levothyroxine titration. Prior to consultation, he underwent radioactive iodine ablation for presumed Grave’s disease, followed by total thyroidectomy due to persistent symptoms. Post-operatively, he required high doses of levothyroxine to maintain normal TSH levels; however T4 and T3 levels remained high. Both patients confirmed proper levothyroxine supplementation. Further analysis of both patients demonstrated mildly elevated TBG and normal alpha subunit. Patient 2 pursued genetic testing while patient 1 declined, revealing a heterozygous R320S mutation in the TR-beta protein. Further testing and genetic counseling were offered to other family members. Propranolol and levothyroxine supplementation were titrated accordingly; triiodothyronine administration was attempted but did not alleviate symptoms. These two cases demonstrate the increased risk of autoimmune thyroid disorders in patients with RTHβ and the unique challenges they pose in accurate diagnosis. Autoimmune thyroiditis in RTHβ, with goiter, elevated T4 and elevated T3 levels, can be easily confused with Grave’s disease, especially when TSH is suppressed during active thyroiditis. Timely diagnosis can aid in targeted management of sequelae, prevent ineffective treatments for comorbid conditions which may mimic other diseases, and provide anticipatory/preventive guidance for family members to help with screening. Presentation: 6/1/2024

8135 A Rare Case of Late Recurrence of Graves’ Disease Decades After Radioactive Iodine Therapy: Is it Really a Definitive Treatment?

Abstract Disclosure: K.S. Hill: None. R. Osman: None. Graves’ disease (GD) is the most common cause of hyperthyroidism in the US and worldwide. Radioactive iodine (RAI) therapy has excellent success rates in treatment of GD. Studies have demonstrated that RAI successfully treats GD with a single session in the majority of cases. Recurrence after RAI, if it occurs, is most commonly seen in the first year after RAI. However, this is rare particularly in patients who have developed evidence of successful treatment in the form of post-ablative hypothyroidism. Only a few case reports have demonstrated recurrence of GD more than 10 years after treatment of GD with RAI and development of post-ablative hypothyroidism. We report a case of GD recurrence approximately 30 years after ablation. A 69 y/o woman presented for evaluation of hyperthyroidism and newly discovered thyroid nodule. Her history was significant for GD with orbitopathy diagnosed in the early 1990s and treated with RAI. Following the ablation, she developed hypothyroidism and was managed for over 20 years on levothyroxine therapy. In recent years she began to develop symptoms of palpitations and heat intolerance with biochemical evidence of thyrotoxicosis despite reductions in her levothyroxine dose. She also developed recurrence of her orbitopathy, confirmed by ophthalmology. During this time, a neck CT incidentally described an atrophic thyroid gland with a 9 mm soft tissue nodule in the left thyroid bed. Follow up ultrasound showed a 1.1 cm nodule with increased vascularity in the left thyroid bed with an otherwise atrophic gland and no lymphadenopathy. Her levothyroxine was stopped for one month in preparation for a thyroid uptake scan, during which TSH increased to 15 mcU/mL. Scan showed overall severely decreased radioactive iodine uptake of the gland consistent with prior ablation although there was a faint uptake most focally conspicuous on the left side inferiorly. Thyroid stimulating immunoglobulin (TSI) was elevated at 1.35 IU/L (Ref 0.00-0.55). After discussion with the patient, the decision was made for surgical treatment with thyroidectomy. Pathology was benign. She was continued on her prior dose of levothyroxine 75 mcg daily however now with clinical and biochemical evidence of hypothyroidism requiring continued increase in levothyroxine dose to normalize TSH levels. GD is the most common cause of hyperthyroidism and RAI therapy is the most common definitive treatment for GD in the US. Recurrence of GD after ablative hypothyroidism is rare, particularly in the case of late recurrence decades after ablation. Only a few cases are reported in the literature, ours with the longest interval-to-relapse. Recurrence of orbitopathy may be the first clue. Our case highlights the need to continue to monitor clinically for recurrence of Graves’ disease long after RAI use. Presentation: 6/3/2024

Testing for a causal role of thyroid hormone measurements within the normal range on human metabolism and diseases: a systematic Mendelian randomization

Variation in thyroid function parameters within the normal range has been observationally associated with adverse health outcomes. Whether those associations reflect causal effects is largely unknown. We systematically tested associations between genetic differences in thyrotropin (TSH) and free thyroxine (FT4) within the normal range and more than 1100 diseases and more than 6000 molecular traits (metabolites and proteins) in three large population-based cohorts. This was performed by combining individual and summary level genetic data and using polygenic scores and Mendelian randomization (MR) methods. We performed a phenome-wide MR study in the OpenGWAS database covering thousands of complex phenotypes and diseases. Genetically predicted TSH or FT4 levels within the normal range were predominately associated with thyroid-related outcomes, like goitre. The few extra-thyroidal outcomes that were found to be associated with genetic liability towards high but normal TSH levels included atrial fibrillation (odds ratio=0.92, p-value=2.13×10-3), thyroid cancer (odds ratio=0.57, p-value=2.97×10-4), and specific biomarkers, such as sex hormone binding globulin (β=-0.046, p-value=1.33×10-6) and total cholesterol (β=0.027, p-value=5.80×10-3). In contrast to previous studies that have described the association with thyroid hormone levels and disease outcomes, our genetic approach finds little evidence of an association between genetic differences in thyroid function within the normal range and non-thyroidal phenotypes. The association described in previous studies may be explained by reverse causation and confounding. This research was funded by the Swiss National Science Foundation (P1BEP3_200041). The Fenland study (DOI 10.22025/2017.10.101.00001) is funded by the Medical Research Council (MC_UU_12015/1, MC_PC_13046 and MC_UU_00006/1). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC-UU_12015/1, MC_PC_13048 and MC_UU_00006/1).

Association of serum thyroid-stimulating hormone and bone mineral density in Chinese adults with normal thyroid function

PurposeThis study aims to investigate the association of serum TSH with BMD in Chinese adults with normal thyroid function.MethodsThese participants were divided into tertiles based on serum TSH levels. Linear regression model and multinomial logistic regression models were used to analyze the associations of continuous BMD and categorical BMD with serum TSH, respectively.ResultsIn women younger than 60 years, BMD decreased with the increase of TSH at normal level, while in women older than 60 years, BMD increased with the increase of TSH at normal level; besides, the BMD of women younger than 60 years old was significantly higher than that of women over 60 years old (156.05 ± 39.34 mg/cm3 vs. 86.95 ± 29.51 mg/cm3, P < 0.001). Linear regression results showed negative associations of BMD and normal TSH level in women with age younger than 60 years (β=-4.34, P < 0.001), but this inverse trend was observed in women over 60 years old (β = 2.04, P = 0.041). Both in men younger than 60 years and over 60 years old, BMD decreased with the increase of TSH at normal levels; besides, the BMD of men younger than 60 years was significantly higher than those over 60 years old (143.08 ± 32.76 mg/cm3 vs. 108.13 ± 31.99 mg/cm3, P < 0.001).ConclusionsThe results demonstrated an opposite trend in BMD at normal TSH levels in younger and elder females, that is, in females younger than 60 years, BMD decreased with the increase of TSH, which indicated that TSH might play a different role in younger and elder females. However, this trend was not significant in males.

Thyrotoxicosis in Partial Mola Hidatidosa

Thyrotoxicosis is a clinical condition associated with excessive thyroid hormone levels. Symptoms can range from asymptomatic to life-threatening due to thyroid storm. Thyrotoxicosis in hydatidiform moles is a rare condition but has a high mortality rate, so etiological studies are still needed for optimal management. Case Report: Patient Mrs. T, 25 years old Hindu, Balinese, 12 weeks pregnant (Gravida 1 Para 0 abortion 0), came to the obstetrics ER on September 24, 2023 with complaints of discharge from the birth canal since the morning, nausea (+), often shaking, easily tired and often sweaty. physical examination obtained blood pressure 100/60mmHg, pulse 78x/min, respiratory rate 20x/min, axillary temperature 36.80C oxygen saturation 99%. From obstetric examination, fundus uteri height ½ center, vaginal toucher vulva vagina within normal limits, portiono (-) fluxus (+), laboratory examination obtained HCG 387,392.8 mIU/m, FT4 31.05 pmol/L (N: 9-22), TSH &lt;0.01 uIU/mL (N: 0.4-4.2) ultrasound results describe honey comb appearance and histopathology results describe partial mola. Evacuation by curettage was performed, resulting in reduced serum ?-hCG levels and reduced thyroid hormone levels. Discussion: The patient was diagnosed with partial hydatidiform mole and thyrotoxicosis. Hydatidiform moles can cause thyrotoxicosis. This condition is caused by the structure of ?- hCG which resembles TSH so that it can activate TSH receptors. After evacuation of hydatidiform moles, normal TSH and FT4 levels will be obtained. Conclusion: The female patient with thyrotoxicosis due to hydatidiform moles had the moles evacuated, resulting in normal thyroid hormone levels.

Cytomorphological Profile of Graves' Disease and its Co-relation with anti-TPO Antibody

Objective: Thyroid diseases are major health problems in our society, which are manifested by alteration in hormone secretion, enlargement of the thyroid gland. FNAC plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost and with a diagnostic accuracy rate of 92%. This study was designed to cytomorphological profile of Graves’ disease and its co relation with anti TPO antibody. Materials and Methods: This is a prospective analytical study of fifty patients with clinically enlarged thyroid gland presenting at STG Hospital, Haldwani, Nainital during Oct 2019 to Oct 2022. FNAC smears of these patients were studied and correlated with cytomorphological findings of different types, grades of thyroiditis and hormone level of T4, T3 and T.S.H. Results: Females were mostly affected by thyroid diseases than males. Female patients were 39 (78%) and male patients were 11 (22%). In the present study, patients were in the age group of 13 to 74 years of age. High T3 levels were noted in 80% high T4 levels were found in 90%. Low TSH level was found in only 64%, normal TSH level found in 34% and 2% presented with high TSH level. 34 patients (68%) found high anti-thyroid peroxidase antibody titre &gt;34 U/ml. Cytomorphology revealed moderate to high cellularity in 88% cases, mild to moderate nuclear atypia in 86% and presence of marginal vacuoles in 82%. Lymphocytic infiltrate found in 24% cases and epithelioid cell granuloma in 14% cases. Conclusion: Thyroid cytology proves to be a reliable, simple, and cost-effective first-line diagnostic procedure with high patient acceptance and with rare, usually easily treated and not life-threatening complications. We recommend further studies with a larger population to validate our study. Keywords: Thyroiditis, Graves' Disease, Malignancy Goiter, Histopathology

IJCM_145A: A Clinico-Epidemiological Profile of Patients with Thyroid Disorders Admitted to Tertiary Care Hospitals in Mangalore

Background: Thyroid ailments are frequently encountered endocrine disorders next to diabetes. They arise either due to functional aberrations of the thyroid gland resulting in over or under secretion of thyroid hormone or due to structural anomalies. People have varied constitutional, non-specific manifestations that cause abnormal metabolic functioning of the thyroid gland. Objectives: 1. To describe the socio-demographic characteristics of patients with thyroid disorders. 2. To analyze the clinical features, laboratory findings, and clinical outcomes of these patients. Methodology: This hospital-based descriptive study was conducted at the Government Wenlock Hospital in Mangalore. The study included patients admitted with thyroid disorders in the last 2 years. Data extraction sheet was developed from patient medical records. The sheet comprised three sections: socio-demographic information, clinical features at admission, and investigations and outcomes. Results: Most of the patients (52.8%) belonged to the 20-40 age group, followed by 30.5% in the 40-60 age group. Females comprised 81.5% of the study population, males -18.5%. 74.8% had swelling, 3.2% had facial puffiness. 1.8% had weight gain, only 1.2% had weight loss .16.3% had other comorbid conditions. 31.5% had low TSH levels 49.3% had normal TSH levels, 64.5 % - normal T3 levels, 63.2% - normal T4 levels. Anaemia was reported in 15.2% o, while 7.2% developed oedema. 34.2% had multinodular goitre, 20.2% - hypothyroidism 9.5 % - hyperthyroidism and 11.1% - malignancy. Out of the total 97% recovered 1% died 1% had discharge against medical advice and 1 % got discharged on request. Conclusion: Majority were females in the 20-40 age group. Majority of them had swelling followed by facial puffiness. Most of them had normal TSH, T3 and T4 levels, anaemia and oedema was also reported in few. Majority had multinodular goitre followed by hypothyroidism, malignancy, and hyperthyroidism. Majority had recovered.

Is thyroid function associated with polycystic ovary syndrome? A bidirectional Mendelian randomization study.

Some observational studies have suggested the association between thyroid function and polycystic ovary syndrome (PCOS). However, it remains to be determined whether these associations are causal or not. The aim of this study was to investigate the underlying causal association between different thyroid function status and PCOS. Bidirectional Mendelian randomization (MR) analysis was conducted to explore the impact of different thyroid function statuses on PCOS. The study included 10,074 individuals with PCOS and 103,164 controls for the primary analysis, with validation analysis repeated in the FinnGen R9 and EstBB PCOS cohorts. Female-specific thyroid function GWAS data were obtained from European population, including Hyperthyroidism (22,383 cases and 54,288 controls) and Hypothyroidism (27,383 cases and 54,288 controls) from the UK Biobank, and TSH (54,288 cases and 72,167 controls) and FT4 (49,269 cases and 72,167 controls) within the reference range from the ThyroidOmics Consortium. Inverse variance weighting (IVW) was chosen as the principal method, and sensitivity analysis was conducted to test for the presence of horizontal pleiotropy or heterogeneity. The IVW analysis indicated nominal significance between normal TSH levels and PCOS after adjusted for age and BMI [OR (95% CI) = 0.78(0.62,0.97), P = 0.029], suggesting that maintaining normal TSH levels might act as a protective factor against the pathogenesis of PCOS. Besides, in order to increase the statistical power, we pooled PCOS GWAS above together by meta-analysis and found PCOS contributed to the occurrence of hyperthyroidism [OR(95%CI) = 1.37(0.73,2.57), P = 0.012]. However, no causal relationship was found after Bonferroni correction (P-value < 0.0031). Although the MR analysis didn't indicate genetic causal association between thyroid function and PCOS after Bonferroni correction. Further efforts are needed to interpret the potential causal relationship between thyroid function and PCOS in different age and BMI subgroup.

Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers.

Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH. In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively. Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4-4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04-3.7), low hCG (<median, OR: 2.1, 95% CI: 1.40-3.16), obesity (BMI > 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04-1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation. Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

O-11 A rare cause of thyroid cancer - Li Fraumeni 2 syndrome

Abstract Introduction Thyroid cancer often originates from follicular cells, and papillary thyroid cancer (PTC) is the most common type. There is a familial predisposition in some cases of thyroid cancer. However, a minority of cases have thyroid cancer syndrome (e.g., familial polyposis, MEN 2, or Cowden syndrome). Many known genetic susceptibility genes are RET/PTC, BRAF, RAS, TERT, and TP53. We want to present a case of Li Fraumeni type 2 syndrome as a rare cause of thyroid cancer. Clinical Case A 69-year-old female patient with a history of PTC is admitted to the endocrinology department for follow-up. In 1976, this patient had a thyroid lobectomy, but the pathology result is unknown, and she takes 75 mcg of levothyroxine daily. In 1999, she was diagnosed with rectal cancer. The patient had a completion thyroidectomy in 2002, and the pathology was compatible with PTC. In 2014, she was diagnosed with right breast noninvasive ductal cancer. Cases of cancer were also quite common in her family history. The results of laboratory tests revealed normal TSH levels with negative thyroglobulin and anti-thyroglobulin levels. Neck ultrasonography showed no rest gland and pathological LAP. We requested genetic analysis (55 genes) for familial cancer syndromes. As a result of the analysis, 2 genes were found to be heterozygous. The c.599T&amp;gt;c heterozygous variant in the CHEK 2 gene was found (Figure 1). It was evaluated as pathogenic in the database review. Another heterozygous mutation in the BRIP1 gene, which was evaluated as a VUS also detected. Conclusion The CHEK 2 gene is a DNA-repairing protein kinase at position 22.q12.1. It is responsible for TP53 stabilization, genome maintenance, and apoptosis. CHEK2 phosphorylates p53 in response to DNA damage, leading to cell cycle arrest and stabilization (Figure 2). The mutation(CHEK 2 c.599T&amp;gt;c) we detected in this case has been considered possibly pathogenic in the academic databases. There are reported CHEK 2 c.599T&amp;gt;c cases on the CLINVAR site; the first report is from 2013. Classic Li-Fraumeni syndrome is a rare autosomal dominant syndrome caused by TP53 gene mutation. The chromosome location on classical Li fraumeni is 17p13.1. Li-Fraumeni type 2 develops due to the CHEK 2 gene mutation on chromosome 22q12.1. The results of a mutation of the CHEK2 gene are breast cancer, prostate cancer, PTC, colon cancer, kidney cancer, adrenocortical cancer, lung cancer, and rare cases of myelodysplastic syndromes. There are no data on thyroid-specific mortality in carriers of the CHEK2 mutations, and it is not yet known whether thyroid cancer in this population is more aggressive or has a better outcome.The familial syndromes should also be considered if PTC is detected in breast, colon, and prostate cancer patients. Studies on Li-Fraumeni type 2 syndrome are scarce, and considering the prevalence in European countries, further investigations of this syndrome and screening in patients with multiple cancers in the family should be warranted.Figure 1.Genetic sequencing image of the case

Sustained Euthyroidism during Thionamide Antithyroid Drug Treatment: Comparison of Short- and Long-term Methimazole Therapy

Background: Extended low serum thyrotropin (TSH) levels may increase the risk of cardiovascular events in patients with hyperthyroidism. Objectives: This study aimed to compare the time spent with sustained normal TSH concentration following short- and long-term methimazole treatment. Methods: A total of 258 patients with Graves’ hyperthyroidism completed 18 - 24 months of methimazole therapy and were randomized to discontinue treatment (n = 128, short-term group) or continue an additional 36 - 102 months of methimazole therapy (n = 130, long-term group). Clinical and laboratory evaluations were performed every 6 months for 132 months after randomization. Results: There was no difference in serum-free thyroxine, triiodothyronine, and TSH concentrations between the 2 groups at the time of randomization. Of 128 patients in the short-term group, 5 left in follow-up, 2 became hypothyroid, 67 (54%) had a relapse of hyperthyroidism, and only 54 (44%) were euthyroid at the end of the study. Among 130 patients on the long-term methimazole therapy, 4 were left in follow-up, 24 developed hyperthyroidism, 4 developed hypothyroidism, and 98 (78%) were euthyroid 132 months post-randomization. Total time spent on euthyroidism was 90.4% ± 8.1% of the study period in the short-term and 95.8% ± 7.0% in the long-term treatment groups (P &lt; 0.001). The lowest time spent in euthyroidism (74.6% ± 6.4% of the study period) belonged to 29 (24%) patients in the short-term group under levothyroxine therapy because of fluctuation in serum TSH. Patients in both groups with hyperthyroidism relapse who chose methimazole therapy spent &gt;90% of the study time in euthyroidism. Conclusions: In patients with Graves' hyperthyroidism, sustained normal serum TSH levels were more common in the long term as compared to the short-term methimazole treatment.

Implementation of Review Technique and Critical Path Method on Academic Programs am&lt;!-- ============== --&gt; &lt;journal_article publication_type='full_text'&gt; &lt;titles&gt; &lt;title&gt;“Comparison of Thyroid Uptake by Tc – 99m Pertechnetate and Iodine – 131 for Euthyroid &amp; Hypothyroid Patients”

Euthyroidism is defined as normal functioning thyroid gland that occurs with normal serum levels of TSH and T4. Lower than normal T4 levels usually mean its hypothyroidism. This thyroid condition can be treated with radioactive therapy using uptake studies by Iodine-131 and Tc-99m. Oral administration of I-131 has been a commonly accepted procedure for treatment of benign and malignant conditions of the thyroid since the 1940s. However, thyroid uptake using Tc-99m has proven to be more advantageous than with I-131, since the procedure is faster, short half-life (only 6 hours), short retention in the gland, no beta (-) radiation thus providing low dose to the thyroid gland (10000 times less than that of I-131) and the images have better quality for its gamma photon of 140keV. So the aim of this study was to make a comparison between I-131 and Tc-99m for performing thyroid uptake and to correlate them for both euthyroid and hypothyroid patients and hence to standardize a simple and fast method for performing thyroid uptake. This study was made for 87 patients (58 females and 29 males) with ages ranging from 14 to 75 years (mean of 39.2 years) were done with both I-131 and Tc-99m. The type of patients was euthyroid, hyperthyroid and hypothyroid. The correlation and comparison between I-131 and Tc-99m was studied for euthyroid and hypothyroid patients. From this study out of 87 patients 32 were found euthyroid, 12 were hypothyroid and others were hyperthyroid. Out of 32 euthyroid patients 26 patients were positive with both Tc-99m and I-131. 6 patients had negative results with Tc-99m and positive results with I-131. Out of 12 hypothyroid patients 10 patients were positive with both Tc-99m and I-131. 2 patients had negative results with Tc-99m and positive results with I-131. A statistically significant correlation was found between I-131 and Tc-99m data for euthyroid patients (r = 0.49, p-value = 0.005). But for hypothyroid patients (r = 0.56, p value = 0.058) which indicates statistically not significant correlation. Considering I-131 imaging as the gold-standard procedure, Tc-99m had a good correlation with I-131 for the detection of euthyroidism but not for the hypothyroidism. So, the consideration of thyroid structure and function using Tc-99m is a simple, fast, better and efficient method for euthyroid patients according to its advantages over I-131 and also for the good quality correlation of this study. To show better correlation for hypothyroidism; further study should be needed with more patients.

A Study Estimating the Serum TSH Levels in First Trimester Pregnant Women

Background Pregnancy is a physiological condition among women. Pregnancy brings about major changes in the hormonal levels. Thyroid stimulating hormone is a hormone produced by anterior pituitary. TSH provides the most common sensitive index to reliably detect thyroid function abnormalities.ObjectiveThe goal of this study was to estimate the levels of serum TSH at first trimester in pregnant women in the department of Biochemistry St. Johnrsquos Medical College amp Hospital and compare with the biological reference intervals as established in the laboratory. Methodology This retrospective study was conducted from January to December 2021 in the department of Biochemistry St. Johnrsquos Medical College amp Hospital. Lab data review of pregnant women has been analysed for serum TSH. The study included 228 pregnant women in their first trimester aged between 20 and 35 years. Serum TSH levels were measured using the ABBOTT ARCHITECT CI8200 through Chemiluminometric Immunoassay. The collected data underwent analysis and comparison to derive descriptive statistics.Result A total of 228 pregnant women in the first trimester fulfilling the inclusion criteria were included. Maternal age of the study population was 20-35 years. Among the pregnant women 12 5.3 women showed low values for TSH lt0.35 microIUMl 11 4.8 women showed higher values for TSH gt4.94 microIUmL and 205 89.9 showed normal TSH levels during first trimester. In this study the mean TSH level in pregnant women was found to be 1.94plusmn1.50 microIUmL. The median TSH levels was 1.51 microIUmL 2.5th and 97.5th percentiles P2.5-P97.5 0.23-5.86 microIUmL.Conclusion The observed connection between aberrant TSH serum levels during the first trimester and adverse pregnancy outcomes underscores the necessity for proactive screening. Identifying pregnant women with elevated or reduced TSH levels early on holds significant potential for preventing complications. The incorporation of such screening protocols can yield a range of benefits including timely interventions and enhanced management strategies to mitigate adverse outcomes. Our research contributes to the growing body of evidence supporting TSH screening during early pregnancy emphasizing its pivotal role in safeguarding maternal and foetal health.

Pretibial Myxedema in a Hypothyroid Patient with Grave’s Disease: A Case Report

Pretibial myxedema, a rare dermatological manifestation primarily associated with Graves' disease, presents as nonpitting edema, nodular, or plaque-like lesions on the lower legs due to accumulation of hyaluronic acid. We present the case of a 42-year-old woman with a history of Graves' disease who developed dark plaques and indurated skin lesions on her shins, extending to the dorsal feet. Diagnosed with Grave’s disease 20 years prior, she underwent subtotal thyroidectomy following antithyroid treatment. Pretibial myxedema developed one-year post-thyroidectomy and was managed with systemic glucocorticoids. She later received iodine-131 therapy, which led to hypothyroidism, and started to admit thyroid hormone replacement. The thyroid function test revealed normal TSH levels and increased TRAbs. Histopathology of skin lesions showed mucopolysaccharide deposition and increased collagen confirming myxedema. This case highlights the rare elephantiasis form of pretibial myxedema and underscores the importance of recognizing characteristic skin lesions in patients with hypothyroidism.

The Impact of Hypothyroidism on Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention

Introduction: Hypothyroidism either subclinical (SCH) or overt is independently associated with an increased risk of coronary artery disease (CAD). The combined effects of SCH and overt hypothyroidism on clinical outcomes after percutaneous coronary intervention (PCI) are largely unknown. Aim: The aim of the study is to assess the impact of subclinical and overt hypothyroidism among patients presenting with CAD undergoing PCI. Materials and Methods: A total of 102 patients who were referred to the Madras Medical Mission Hospital for PCI from September 2020 to March 2021 were enrolled in the study. These patients were categorized into three groups. Each group has 34 patients and was followed for one year. Group 1: Patients with normal TSH levels (TSH-0.45 -5mlU/Liter) and euthyroid at T3, T4 levels. Group 2: Patients with subclinical hypothyroidism with elevated TSH levels (TSH=5-15mlU/liter) and normal thyroid with T3, T4 levels. Group 3: Patients with a family history of overt hypothyroidism or high TSH levels(&lt;15mlU/liter) and low T3 and T4 levels [16]. Results: We applied ANOVA to find the PCI outcomes. A p-value of &lt;0.05 was accepted as significant. Age (p-0.03), recent myocardial infarction (p-0.04), diabetes mellitus (p&lt;0.001), HbA1C (p-0.012), and systolic blood pressure (p-0.04) were found to be significant. Post-PCI bleeding complications (p&lt;0.001) during one month, six months, and one-year follow-up were the main observation of the study. Conclusion: The prior history of DM and elevated HbA1c levels observed in the overt hypothyroid group indicate that DM was one of the key factors associated with overt hypothyroidism. Despite the fact that PCI was safe for patients with hypothyroidism, the risk of early post-PCI bleeding was of concern.