Elevated Thyroid-stimulating Hormone Research Articles

The Association Between Elevated Thyroid-Stimulating Hormone Levels and Prolonged Length of Stay Among Adult Diabetic Patients Hospitalized in Internal Medicine Departments: A Large Historical Cohort Study

Background/Objectives: Type 2 diabetes mellitus (DM2) and hypothyroidism are two of the most common endocrine disorders in clinical practice. Hospital length of stay (LOS) is a quality metric of the health systems. We evaluated the association between elevated thyroid-stimulating hormone (TSH) levels and prolonged LOS among all adult patients (age ≥ 18 years) with DM admitted to our Internal Medicine departments between 2014 and 2022. Methods: Data on patient characteristics, LOS, and in-hospital mortality were collected. A TSH level > 4.7 μIU/mL was considered as being elevated. A LOS > 75th percentile and in-hospital mortality were defined as being prolonged. Univariate and multivariable analyses were applied, and propensity score matching controlled for differences between patients with normal and those with elevated TSH levels. Results: Of the 19,066 study participants (median age 75.6 years, IQR 75.9–83.3), 1524 (7.9%) had elevated TSH levels, and prolonged LOS was significantly more common among them (before matching: 38.6% vs. 29.1%, p < 0.001; after matching: 38.7% vs. 32.6%, p = 0.001). After adjustment for potential confounders, elevated TSH levels were also associated with prolonged LOS (OR = 1.22, 95% CI 1.07–1.39, p = 0.002). Conclusions: Elevated TSH levels in diabetic patients hospitalized in Internal Medicine departments are associated with prolonged LOS, emphasizing the importance of identifying hypothyroidism among them.

CONGENITAL HYPOTHYROIDISM IN NEWBORN AND ASSOCIATION WITH SOCIODEMOGRAPHIC PARAMETERS AMONG NEONATE DELIVERED AT MILITARY HOSPITAL IN A CITY OF CENTRAL INDIA

Objectives: The present study aims to assess the incidence of congenital hypothyroidism (CH) among neonates in a tertiary care hospital in central India, examining its association with various sociodemographic parameters. Methods: This cross-sectional study, conducted between January and December 2022, included all live births at a tertiary care center in Jabalpur, Madhya Pradesh. Cord blood thyroid-stimulating hormone (TSH) levels were measured for all newborns as part of routine screening. Sociodemographic data, including maternal age, gestational age, birth order, and newborn sex, were collected. Universal sampling was employed, encompassing all consenting parents and their neonates. Results: Among 388 live births, TSH values ranged from 0.23 to 35.59 mIU/L, with a mean TSH of 8.76±5.92 mIU/L. Of the neonates, 95.9% had normal TSH levels, while 4.1% exhibited elevated levels. Subsequent follow-up identified CH in two neonates (5.2 per thousand live births). Analysis revealed no significant association between elevated TSH levels and maternal age or newborn sex. However, a significant association was observed with gestational age. Birth order also displayed significance, with the third birth order having a higher proportion of neonates with raised TSH levels. Conclusion: This study highlights the importance of CH screening in preventing long-term complications and the various sociodemographic factors linked to CH, such as maternal age, gestational age, and birth order.

Obesity-related subclinical hypothyroidism in childhood: Elevated triglycerides but not basal metabolicrate.

Studies on the associations between obesity-related subclinical hypothyroidism with basal metabolic rate and risk factors of cardiovascular disease in children and adolescents are scarce. Retrospective cohort study of children with obesity (n = 294) from the Uppsala Longitudinal Study of Childhood Obesity cohort. Differences in basal metabolic rate quantified by indirect calorimetry, and the cardiovascular risk factors; body mass index, blood lipids, fasting and 2 h oral glucose tolerance test glucose, glycated haemoglobin and insulin resistance, between subjects with and without subclinical hypothyroidism were investigated. The associations of baseline thyroid stimulating hormone (TSH) and ΔTSH with change in cardiovascular risk factors over time were assessed. Subjects with subclinical hypothyroidism had elevated triacylglycerides but no alterations in basal metabolic rate or other measured cardiovascular risk factors. ΔTSH was positively associated with Δtriacylglycerides, Δtotal-cholesterol and ΔLDL-cholesterol, independently of age, sex, Δbody mass index and ΔT4. In the subclinical hypothyroidism group, 92% of individuals normalised their TSH 0.9-2.9 years later. Children with obesity and subclinical hypothyroidism did not have an altered basal metabolic rate but elevated triacylglycerides. During the follow-up period, TSH changed in parallel with several blood lipids. Elevated TSH often normalised without pharmaceutical intervention within 3 years. The present study found that subclinical hypothyroidism in paediatric obesity is related to elevated triglycerides. The present study found that subclinical hypothyroidism is not associated to basal metabolic rate in paediatric obesity. TSH change over time correlated with the change in triglycerides and LDL and total cholesterol. Among subjects with subclinical hypothyroidism at baseline 92% normalised without pharmaceutical intervention within 3 years. This research adds to the knowledge of the longitudinal, natural course of elevated TSH in paediatric obesity which is expected to help to make informed decisions regarding follow-up and evaluation of this patient group.

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5′-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans

Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining in vivo and new approach methodologies (NAMs), in a weight of evidence approach.Data demonstrate a MOA of liver enzyme induction via nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight. Non-human relevance of the MOA was demonstrated in in vitro cross species assays in rat, dog and human hepatocytes. Increased gene expression and activity of cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were observed in rat and dog hepatocytes exposed to valifenalate, with increased T4 clearance and/or T4 glucuronidation/T4-UGT activity. Therefore, a causal relationship between increased liver enzyme induction and thyroid effects in dogs and rats is concluded. Rat hepatocytes were most sensitive, while valifenalate did not increase T4-UGT activity above 2-fold of vehicle control or T4 glucuronidation and T4 clearance in human hepatocytes. Consequently, valifenalate exposure in humans is unlikely to lead to decreased T4 levels, and subsequent thyroid and developmental neurotoxicity effects. Alternative human-relevant thyroid MOAs were excluded, i.e. inhibition of deiodinases (DIO), thyroperoxidase (TPO) or the sodium iodide symporter (NIS).Due to known species differences in thyroid homeostasis between humans and laboratory animals and, importantly, based on the presented data, this liver enzyme mediated MOA is considered not relevant for human hazard assessment.

Hyperthyroidism, hypothyroidism, thyroid stimulating hormone, and dementia risk: results from the NHANES 2011-2012 and Mendelian randomization analysis.

As the world ages, dementia places a heavy burden on society and the economy, but current methods of diagnosing dementia are still limited and there are no better therapies that target the causes of dementia. The purpose of this work is to explore the relationship between thyroid disease, thyroid stimulating hormone (TSH) concentrations, free tetraiodothyronine (FT4) concentrations and cognitive function. This study utilized cognitive function and thyroid data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to assess the relationship between different groups of TSH and FT4 concentrations and cognitive function using weighted logistic regression and restricted cubic spline (RCS), and then used two-sample Mendelian Randomization (MR) to assess the causal relationship between hyperthyroidism, hypothyroidism, TSH and FT4 concentrations with dementia. Our analysis of the 2011-2012 NHANES data showed that the individuals with low TSH concentrations had higher Alzheimer's Disease Word List Registry Consortium1 (CERAD1) and CERAD.delay.recall scores than individuals with high TSH concentrations, and individuals with low FT4 concentrations had higher CERAD3 and Animal Fluency Test scores than individuals with high FT4 concentrations. Our results also showed a non-linear relationship between serum TSH and FT4 concentrations and the Animal Fluency Test. The TSH concentrations within the range of 1.703 to 3.145 mIU/L exhibit a positive correlation with Animal Fluency Test, whereas concentrations outside this range are negatively correlated with Animal Fluency Test. The FT4 concentrations exhibited a positive correlation with Animal Fluency Test to the left of the FT4 concentrations inflection point (0.849 ng/L), whereas to the right of this inflection point, correlation was negative. MR analysis results further indicate that genetic predisposition to hyperthyroidism may be associated with a reduced risk of dementia and vascular dementia(VaD). Conversely, genetic predisposition to hypothyroidism appears to be linked with an increased risk of dementia and VaD. Additionally, genetic predisposition to elevated TSH concentrations may be correlated with a heightened risk of risk of Alzheimer's disease (AD). This study provides evidence of a nonlinear relationship between TSH and FT4 concentrations and cognitive function, with hyperthyroidism decreasing the risk of dementia and VaD, hypothyroidism increasing the risk of dementia and VaD, and elevated serum TSH concentrations increasing the risk of AD. Furthermore, prioritizing early detection, diagnosis, and treatment through the assessment of thyroid function in individuals at high risk for developing dementia is of paramount importance. This strategy has the potential to significantly contribute to the prevention and deceleration of dementia progression.

Identification and determination of the urinary metabolite of iodotyrosine invivo

BackgroundCongenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models. MethodGas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results. ResultsWe identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice. ConclusionOur findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

6983 Pembrolizimab Induced Hypophysitis: Uncommon Side Effect Leading To Late Diagnosis

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. A. Shridar: None. R. Kaur: None. O. Chaudhary: None. M.S. Zubair: None. Background: Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy inducing remission in various malignancies. Associated immune-related adverse effects (irAEs) have been recorded but cases of concomitant hypophysitis and thyroiditis are rare. Clinical case: The patient is a 41-year-old male with a past medical history significant for metastatic melanoma of the left calf, status post sentinel lymph node biopsy and left inguinal lymph node dissection, treated with pembrolizumab for one year. He initially presented with a severe headache that was preceded by two months of fatigue and impaired concentration. CT and MRI head were both unremarkable while lab work was significant for cortisol 0.2 ug/dL and adrenocorticotropic hormone (ACTH) 1.1 pmol/L. A full hormone panel was ordered which showed normal insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Free testosterone was at the lower end of normal. Prolactin was elevated at 27.3 ng/mL. The thyroid function tests showed primary hypothyroidism with elevated thyroid stimulating hormone (TSH) at 109 uIU/mL, low T4 at 1.5 ug/dL, and low free T4 at 0.4 ng/dL. There were no signs or symptoms of posterior pituitary dysfunction. The patient was diagnosed with hypophysitis and started on hydrocortisone 20 mg once daily along with levothyroxine 175 mcg once daily. DEXA scan showed normal bone mineral density. Subsequently, the patient presented to our care and reported symptom improvement after taking the prescribed medication however he continued to develop fatigue by the end of the day. Therefore, hydrocortisone prescription was switched to 15 mg in the morning and 10 mg at noon. A repeat thyroid function panel, sex hormone binding globulin, and LH were ordered, to be followed up at the patient's next visit. The patient was also advised to wear a medical alert bracelet at all times moving forward. Conclusion: Due to non-specific symptoms at onset, hypophysitis can be undiagnosed or misdiagnosed therefore it is important to have a high clinical suspicion with patients on PD-1 inhibitors presenting with such symptoms. It is also imperative to order a full set of hormones as this patient had concomitant primary hypothyroidism. Presentation: 6/1/2024

8208 Unexpected And Significant Rise In TSH In The Setting Of Relugolix Use

Abstract Disclosure: A.Y. Groysman: None. A. Poloju: None. P. Majety: None. T. Abraham: None. Background: Relugolix is a gonadotropin-releasing hormone antagonist used as androgen deprivation therapy for metastatic and nonmetastatic castration-resistant prostate cancer that was FDA-approved in December 2020. Common side effects include hot flashes, increased glucose and triglycerides, and decreased hemoglobin. We report a case of Relugolix interference with the absorption of levothyroxine, which has not been reported in the literature. Case: A 79-year-old white man with high-risk, Gleason 9 prostate cancer and Hashimoto’s hypothyroidism presented for evaluation of elevated thyroid stimulating hormone (TSH) level- 52.87 mIU/L (0.28-4.10 mIU/L). He did not have cold intolerance, constipation, fatigue, or weight gain. He was diagnosed with hypothyroidism in 1998 and was on a stable dose of levothyroxine 88mcg daily from 2016 until the time of this presentation. He is adherent and reports following a routine of having breakfast with coffee soon after taking levothyroxine for many years. In June 2022, his TSH was 4.48 mIU/L. In July 2022, he started taking Relugolix along with levothyroxine. Following this, his TSH levels increased to 30.08 mIU/L (FT4: 0.67 ng/dL), 35.43 mIU/L (FT4: 0.57 ng/dL), 52.87 mIU/L (FT4: 0.48 ng/dL) on 2/24/23, 3/3/23, and 3/14/23, respectively. No new medications were reported. His other medications were atorvastatin, tamsulosin, and vitamin D, which he took at night. He did not take calcium or biotin supplements. He had gradual weight gain (8 lbs) over the last 9 months. Levothyroxine dose was increased from 88 to 125 mcg daily and he was instructed to separate Relugolix from levothyroxine so he started taking Relugolix at bedtime. Repeat TSH was low at 0.12 mIU/L. The levothyroxine dose was eventually titrated back to 88 mcg daily and TSH was 5.2 (appropriate for age). Conclusion: Several medications are known to interfere with the absorption of levothyroxine. Our case suggests that Relugolix may be one of them. The significant rise in TSH and levothyroxine requirements months after starting Relugolix and the ability to return to the previous dose of levothyroxine only by separating Relugolix from levothyroxine strongly suggests that there is an interference between these medications that has not been reported. Presentation: 6/2/2024

7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy

Abstract Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None. Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine &amp;lt;0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function. Presentation: 6/2/2024

8141 A Rare Case of Follicular Adenoma with Osseous Metaplasia and Mature Bone Formation- Is Surveillance Important?

Abstract Disclosure: K. Madani: None. Y. Al-Khazraji: None. D.H. Sacoto: None. G.K. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None. Osseous metaplasia and mature bone formation (MBF) are common in malignant thyroid and parathyroid tumors. It is very unusual to have MBF in a benign tumor-like follicular adenoma, as in the case we describe. We found only twelve such cases reported in the literature, and none addressed the cancer risk or need for surveillance for the development of potential malignancy. Thus, further studies are required to investigate the need for surveillance in patients not undergoing excision and in those with remnant thyroid tissue post-removal of the adenoma for recurrence. A 43-year-old female with history of hyperlipidemia and hypothyroidism had an incidental finding of midline neck mass during the evaluation of a left upper extremity lipoma. Ultrasound of the neck showed two nodules in the Left (L) thyroid lobe: a complex nodule measured 2.2 x 1.2 x 2.1 cm and a calcified nodule measuring 1.5 x 0.8 x 0.6 cm. MRI of the neck revealed a 1.9 cm heterogeneously enhancing nodule in the mid to lower pole of the L thyroid lobe. The patient had symptoms suggestive of compression, such as dysphagia, odynophagia, and hoarseness; thus, left hemothyroidectomy was performed. Tissue biopsy was notable for follicular adenoma with osseous metaplasia and mature bone formation. The patient remained clinically and biochemically euthyroid, with only mildly elevated thyrotropin level, and treatment with levothyroxine 25 mcg once daily was initiated. On post-surgical follow-up, there was a lack of data to support close monitoring modality and strategy for the remnant thyroid lobe and neck nodal compartments. We concluded with the patient to follow up in a clinical visit for a physical exam of the neck and to obtain a follow-up sonogram at an interval of six months, in addition to monitoring TSH levels to guide hypothyroidism therapy. Osseous metaplasia has not been established as a premalignant condition, but in certain tissues like the esophagus, metaplasia is a risk factor for malignant conversion, for instance, in Barrett’s esophagus leading to esophageal adenocarcinoma. Moreover, MBF in thyroid tissue has been attributed to the activity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2), which are linked with mitogenesis and tumorigenesis. Thus, the question arises if post-excision surveillance is required in patients with a history of osseous metaplasia in remnant thyroid tissue post-lobectomy or partial thyroidectomy. At this point, more epidemiological data on similar cases may help us understand the true risk of this clinical scenario, in order to develop a reasonable approach for surveillance. Presentation: 6/3/2024

Clinical values of preoperative red blood cell distribution width and platelet parameters in patients with papillary thyroid carcinoma.

The prevalence of thyroid carcinoma is increasing, and papillary thyroid carcinoma (PTC) is the most frequent subtype. More and more attention is being concentrated on the association between inflammation indicators and malignant tumors. The aim of the present study was to analyze whether the preoperative red blood cell distribution width (RDW) and platelet parameters, including mean platelet volume (MPV) and platelet distribution width (PDW), can be applied to distinguish between patients with PTC or papillary thyroid microcarcinoma (PTMC) and healthy controls, and to explore the associations with clinicopathological characteristics. The study retrospectively compared the RDW, MPV and PDW values of 780 patients with PTC or PTMC against a healthy control group. Receiver operating characteristic (ROC) curves were conducted to determine diagnostic accuracy. Furthermore, the clinicopathological features of the patients with PTC or PTMC were compared between higher and lower platelet parameter groups based on the RDW, MPV and PDW values. Significantly higher preoperative RDW, MPV and PDW values were found in patients with PTC or PTMC compared with those of the healthy group. ROC curve analysis showed that the area under the curve (AUC) plus 95% confidence interval (95% CI) values of RDW, MPV and PDW were 0.808 (0.780-0.835), 0.771 (0.743-0.799) and 0.711 (0.681-0.742), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835-0.881) for the patients with PTC. For the patients with PTMC, RDW, MPV and PDW had AUC (95% CI) values of 0.812 (0.783-0.840), 0.779 (0.749-0.808) and 0.718 (0.685-0.751), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835-0.881). A higher RDW was significantly associated with being female, deeper tumor infiltration, and normal FT3 and FT4 levels. A higher PDW was significantly associated with elevated thyrotropin receptor antibody levels. In conclusion, as convenient and available inflammation indicators, RDW, PDW and MPV have diagnostic ability and can distinguish between patients with PTC or PTMC and healthy controls. In addition, the combined application of RDW and MPV can improve the diagnostic power. The values of RDW and MPV were associated with clinicopathological characteristics. To the best of our knowledge, this is the first study to prove the usefulness of preoperative RDW combined with MPV in diagnosing patients with PTC or PTMC.

Thyroxine Replacement Therapy during Ramadan Fasting: A Narrative Review

Abstract Introduction Ramadan fasting-induced changes in eating and sleeping patterns pose a risk of influencing thyroid hormone levels. There is a recognition of the potential impact of fasting and feasting on levothyroxine (L-T4) absorption. Materials and Methods A narrative, nonsystematic literature review from two major medical online databases (PubMed and Google Scholar) from their inception to the search day (February 22, 2024). A relevant combined search term was used. The retrieved literature is narrated in a concise account. Results There is a relationship between metabolism and thyroid-stimulating hormone (TSH). This relationship contributes to transient metabolic disturbances that influence the pharmacodynamics and pharmacokinetics of various drugs, adding complexity to the management of hypothyroidism during Ramadan fasting. Several observational studies have studied the changes in thyroid function levels during unmodified L-T4 regimens. Experimental trials explored the impact on body weight, well-being, and thyroid functions when the timing of L-T4 administration changes. Findings are far from homogeneous due to different study protocols. A recent meta-analysis demonstrated a significant post-Ramadan increase in TSH levels among euthyroid patients. L-T4 timing points, encompassing pre-Iftar, post-Iftar, and pre-Suhoor, are associated with elevated TSH levels after Ramadan fasting. The emphasis on individualized L-T4 regimens during Ramadan fasting is underscored, with recommendations for patients to refrain from food for at least 3 hours before and 30 minutes after L-T4 intake to ensure optimal compliance by most experts. The association between adherence to L-T4 during Ramadan fasting and maintaining euthyroid status is highlighted, encouraging patients to follow prescribed regimens diligently. Modified dosing frequencies, such as weekly regimens, exhibit promising results, especially in patients grappling with compliance issues. Proactive consultations with physicians before Ramadan are needed to review the latest thyroid function test and make possible dose adjustments. Conclusion Managing hypothyroidism during Ramadan necessitates an understanding of medication timing, food-drug interactions, and prior regimens. Adherence, facilitated by flexibility, plays a critical role in achieving euthyroid status.

Associative Learning in Subclinical Hypothyroidism at Different Ranges of Thyroid Stimulating Hormone: A Cambridge Neuropsychological Test Automated Battery (CANTAB) Study of Visual Paired Association Learning Task.

Associative learning deficits are constantly found in subclinical hypothyroidism (SCH). Despite achieving normal thyroid stimulating hormone (TSH) levels, a considerable number of patients undergoing levothyroxine (LT-4) treatment frequently complain about memory retrieval. The Paired Association Learning (PAL) task involves computerised testing on the CANTAB- Cambridge Neuropsychological Test Automated Battery, also considered a screening tool for Alzheimer's disease (AD). This study aimed to investigate the impact of different levels of TSH on visual associative learning in SCH and determine if these impairments were reversed with LT-4. A total of 134 participants were included in this cross-sectional study. Group 1: 35 healthy controls; patients with SCH (Group 2: 33 newly identified cases; Group 3: 32 patients on LT-4 with elevated TSH; Group 4: 34 euthyroid but on LT-4). A thyroid profile and a neuropsychological clinical assessment were done. The visual PAL task was performed on CANTAB. PAL was significantly impaired (p = <0.05) in all 3 patient groups as compared to Group 1. The PAL total errors (adjusted) scores were significantly higher in Groups 2 and 3, indicating that associative learning is definitely impaired in SCH, reaching levels previously seen in patients with AD. Our findings encourage screening for visual associative learning or memory retrieval in patients with SCH. The study present has established a more reasonable threshold of TSH 2.5mIU/L to encourage examination of associative learning and the initiation of LT-4 in SCH. Poor PAL task performance in patients with SCH may have significant implications in clinical settings for suspecting AD.

Pathological correlation between eosinophils and thyroid nodules based on medical image testing

Thyroid nodule is a common thyroid disease, but the study of its pathology and pathogenesis is still limited. As a non-invasive diagnostic method, medical image examination is of great value to study the pathological correlation of thyroid nodules. The purpose of this study was to investigate the expression of eosinophils in medical image examination and the pathological correlation between eosinophils and thyroid nodules. The study analyzed the pathological reports of a group of patients with thyroid nodules examined by medical images and performed corresponding imaging scans or examinations. The imaging data is processed, including image reconstruction, data transmission and other steps, to generate images that can be diagnosed by doctors. Thyroid function and parameters of leukocyte were collected and compared.The serum levels of TT4 and fT4 were observed lower in G2 group, while thyroid stimulating hormone (TSH) was higher compared to G1 group before surgery. Compared to G2 group, eosinophils count and percentage were lower in G1group (p < 0.05) post-surgery and lower ratio of eosinophils count with lymphocyte count (ELR) were observed in G1 group patients (p < 0.05).Elevated TSH is closely related to malignant TN per surgery, while lower ELR suggesting that TN removed thoroughly. Relevant cut-off values required further study to guide the diagnosis, treatment and follow-up of TN.

Causal role of thyroid function in functional outcome after ischemic stroke: A Mendelian randomization study

BackgroundPrevious observational studies have suggested that thyroid function may be associated with functional outcome after ischemic stroke (IS). Nevertheless, the causal relationship remains unclear. This study aimed to explore the causal effect of thyroid function [thyroid-stimulating hormone (TSH), free thyroxine (FT4), hyperthyroidism, and hypothyroidism] on functional outcome (based on the modified Rankin scale) after IS by two-sample Mendelian randomization (MR) analysis. MethodsInverse variance weighted (IVW) was the primary method for evaluating causal associations. In addition, six additional MR methods (MR-Egger regression, weighted median, maximum likelihood, simple mode, weighted mode, and MR-PRESSO) were employed to supplement IVW. Furthermore, various sensitivity tests were conducted to assess the reliability: (i) Cochrane's Q test for assessing heterogeneity; (ii) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; (iii) leave-one-out sensitivity test for determining stability. ResultsThe results of IVW indicated that elevated TSH levels significantly improved functional outcome after IS (OR = 0.74, 95 % CI: 0.57-0.97, P = 0.028). In addition, six additional MR methods suggested parallel results. However, no causal effect of FT4, hyperthyroidism, and hypothyroidism on functional outcome after IS was identified. In addition, sensitivity tests demonstrated the reliability of the MR analyses, suggesting that the MR analysis was not influenced by significant heterogeneity and horizontal pleiotropy. ConclusionsOur MR study supported that elevated TSH levels might improve functional outcome after IS. Therefore, regular monitoring and maintenance of stable TSH levels may benefit patients recovering from IS.

Radiological evolution of pituitary hyperplasia in primary hypothyroidism and its differentiation from nonfunctioning pituitary adenoma coexisting with primary hypothyroidism.

In a patient with elevated thyroid stimulating hormone (TSH, >50 µIU/ml) with sellar mass, it is crucial to differentiate isolated pituitary hyperplasia (IPH) from primary hypothyroidism coexisting with nonfunctioning pituitary adenoma (PHCNFPA) pre-operatively to avoid unwarranted surgery in the former condition. Here, we describe patients having pituitary mass/enlargement with markedly elevated TSH (>50 µIU/ml) and attempt to find the differentiating features between IPH and PHCNFPA. This is a retrospective study conducted at a tertiary care center. Case records of patients presenting between January 2020 and December 2022 with elevated TSH (>50 µIU/ml) for whom magnetic resonance imaging (MRI) of the sella was available were reviewed. Demographic details, symptomatology, clinical examination findings, thyroid function tests, data on pituitary hormonal excess and deficiencies, MRI findings, and details regarding levothyroxine supplementation were noted. Based on the final diagnosis, the patients were categorized into two groups: PHCNFPA and IPH. Five and 11 patients were diagnosed with PHCNFPA and IPH, respectively. The median (IQR) age at presentation of patients with PHCNFPA was significantly higher than that of IPH patients [37 (28-60.5) vs. 21 (10-21.5) years, p: 0.002]. A longer duration of hypothyroid symptoms was noted in the IPH group whereas visual field defects and corticotropin deficiency were more frequent and the pituitary lesion size was greater in PHCNFPA. Thyroid function tests were not different between the two groups. The pituitary enlargement in IPH was initially an increase in pituitary height that progressed to symmetrical nipple-, dome- or tent-shaped enlargement. Besides this characteristic enlargement pattern, isointense appearance on T1-weighted and T2-weighted images, homogeneous contrast enhancement, and prompt regression of pituitary lesion with levothyroxine replacement were characteristic of IPH whereas heterogeneous enhancement, cystic/hemorrhagic change, and ≥Knosp III invasion were characteristic of PHCNFPA. Peripheral rim enhancement and Knosp I-II parasellar extension were not uncommon in patients with IPH and did not distinguish it from PHCNFPA. The present study reports the radiological evolution of IPH and a unique series of PHCNFPA along with the distinguishing characteristics between them.

Impact of Some Natural and Artificial Sweeteners Consumption on Different Hormonal Levels and Inflammatory Cytokines in Male Rats: In Vivo and In Silico Studies.

Substituting sugar with noncaloric sweeteners prevents overweight and diabetes development. They come in two types: artificial, like aspartame and sucralose, and natural, such as sorbitol. This research aimed to assess the effects of sucrose and these sweeteners on nutritional parameters, hematological parameters, hormones, and anti- and pro-inflammatory cytokines in male rats. Thirty rats had been separated into five groups. The results showed the highest significant increase in body weight gain, total food intake, and feed efficiency noticed in the aspartame group followed by sucralose, sucrose, and sorbitol, respectively. In contrast to RBCs and platelets, all sweeteners significantly reduced the hemoglobin level, Hct %, and WBC count. The aspartame group showed the highest decline in glycoproteins, steroids, and T3, and T4 hormones and a dramatic elevation in thyroid stimulating hormone, eicosanoid, and amine hormones compared with the control group. A vigorous elevation in anti- and proinflammatory cytokine levels was observed in the aspartame group, followed by sucralose, sucrose, and sorbitol groups. Aspartame has the highest docking scores when studying the interactions of sweeteners and a target protein associated with hormones or cytokines using in silico molecular docking, with the best absorption, distribution, metabolism, elimination, and toxicity properties compared to the remaining sweeteners.

Lipoprotein-Associated Phospholipase A2 and hs-CRP are Correlated with Anti-TPO Antibodies in Jordanian Non-Pregnant Women with Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis (HT) is an autoimmune disorder characterized by elevated thyroid-stimulating hormone (TSH) levels. This research investigates the complex interaction between HT and cardiovascular risk in adult Jordanian non-pregnant women aged 20-50. Through a study involving 50 HT subjects and 40 healthy subjects, the levels of lipoprotein-associated phospholipase A2 (PLA2), high sensitivity C-reactive protein (hs-CRP), and anti-thyroid peroxidase (anti-TPO) antibodies were compared using ELISA methods and enzymatic colorimetric assays for lipid profiles. The results revealed significantly higher serum levels of hs-CRP, PLA2, and Anti-TPO in Hashimoto's patients, coupled with elevated cholesterol, triglyceride, and low-density lipoprotein (LDL) levels. Conversely, reduced levels of high-density lipoprotein (HDL) were observed in Hashimoto’s patients compared to healthy subjects. The study establishes a noteworthy correlation between thyroid autoimmunity, thyroid disease, PLA2, hs-CRP, and lipid profile, underscoring an increased cardiovascular risk in individuals with Hashimoto’s thyroiditis. The findings emphasize the prevalence of Anti-TPO antibodies in adult Jordanian non-pregnant women with Hashimoto’s thyroiditis.

Hypothyroidism and Its Impact on Menstrual Irregularities in Reproductive-Age Women: A Comprehensive Analysis at a Tertiary Care Center.

Hypothyroidism is known to affect a wide range of physiological systems, including menstrual function, in women of reproductive age. This study aims to comprehensively analyze the association between hypothyroidism and menstrual irregularities in women attending a tertiary care center. The study included 120 women aged 18-45 who presented with menstrual abnormalities. Convenience sampling was used to select participants from the outpatient department of obstetrics and gynecology. Thyroid function tests were conducted in the hospital's biochemistry laboratory, including assessments of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid peroxidase antibodies (TPOAb). The study aimed to determine the prevalence of hypothyroidism and its association with various menstrual irregularities, such as oligomenorrhea, polymenorrhea, menorrhagia, and amenorrhea. Data analysis was performed using SPSS software, applying descriptive statistics, Pearson correlation for continuous variables, and Chi-square tests for categorical variables. A significance level of p<0.05 was set for the analyses. The mean age of the participants was 33.1 years (SD ± 7.2). The distribution of menstrual irregularities was 60 (50%) oligomenorrhea, 24 (20%) polymenorrhea, 24 (20%) menorrhagia, and 12 (10%) amenorrhea. Elevated TSH levels (>4.0 mIU/L) were observed in 42 (35%) of the participants, low FT4 levels (<0.8 ng/dL) in 18 (15%), low FT3 levels (<2.5 pg/mL) in 12 (10%), and elevated TPOAb levels (>55 IU/mL) in 24 (20%). A significant association was found between elevated TSH levels and oligomenorrhea (66 (55%), p<0.05) and between reduced FT4 levels and menorrhagia (78 (65%), p<0.05). Additionally, elevated TPOAb levels were significantly associated with amenorrhea (60 (50%), p<0.05). The correlation analysis showed a moderately positive correlation between TSH levels and the severity of menstrual irregularities (r=0.35, p<0.01). Subclinical hypothyroidism was detected in 25% of the participants, while 15% had clinical hypothyroidism. This study underscores a notable link between hypothyroidism and menstrual irregularities in women of reproductive age. The results highlight the necessity of routine thyroid function screenings for women experiencing menstrual abnormalities, facilitating precise diagnosis and suitable treatment.