Normal Thyroid Research Articles

12387 Late New-onset Graves' Orbitopathy: 14 Years Post-radioactive Iodine Treatment Of Graves' Disease: Case Report

Abstract Disclosure: F.F. Altaleb: None. K. Alaybaa: None. N. Aljohani: None. Introduction: Graves' orbitopathy (GO) is an autoimmune condition affecting the orbit and retro-ocular tissues, often accompanied by hyperthyroidism associated with Graves' disease, but it is rarely observed in euthyroid or hypothyroid individuals. Radioactive iodine (RAI) therapy for Graves' disease and smoking are recognized risk factors for GO development and progression. Individuals who smoke and undergo RAI treatment are significantly more likely to experience ocular lesions and worsening of GO compared to non-smokers. The exacerbation of GO post RAI therapy is attributed to elevated levels of TSH receptor antibodies, which may persist for up to a year post-treatment. Our case presents a rare occurrence of severe new-onset GO manifesting 14 years after achieving prolonged euthyroid status and successful RAI treatment for Graves' disease, accompanied by persistent TSH receptor antibody positivity that is unlikely to be suppressed by long term levothyroxine therapy. Clinical case: A 55-year-old male who’s a smoker and previously diagnosed with Grave’s hyperthyroidism, received treatment with RAI ablation therapy 14 years ago. At the time of diagnosis, there were no symptoms or signs of GO, and no history of thyroid eye disease was detected. Following the RAI treatment, he developed hypothyroidism and was promptly started on a daily dosage of 100 mcg of levothyroxine.Upon ocular examination: Visual acuity: 20/30 in both eyes. Significant restriction in extraocular muscle movements, with reported diplopia and pain. Bilateral lid retraction, proptosis, right conjunctival chemosis, and injection of the bulbar conjunctiva and caruncle, as well as lagophthalmos, were evident. No relative afferent pupillary defect observed. Color vision: 3/15 in the right eye, 15/15 in the left eye. Intraocular pressure: 22 mmHg (right eye), 16 mmHg (left eye). Optic discs unremarkable. Proptosis measurements: 26 mm (right eye), 23 mm (left eye). Ophthalmopathy clinical activity score: 7.Our laboratory analysis indicated normal thyroid function test However, the TSH receptor antibody and TPO antibody returned positive.We initiated treatment with IV methylprednisolone at a dosage of 500 Mg weekly for a duration of 4 weeks. Additionally, we introduced local measures, along with selenium supplementation. Within a week of initiating treatment, the conjunctival chemosis resolved, and there was improvement in ocular movement, resulting in mild to moderate restriction in all directions of gaze. Conclusion: This case illustrates the unexpected development of GO in a patient who had been euthyroid and effectively cured of Grave's disease for a span of 14 years following RAI treatment. The presence of TSH receptor antibodies, which are likely unresponsive to suppression by levothyroxine, as well as smoking cigarette might have contributed to the late new onset of the disease. Presentation: 6/3/2024

7745 Hirsutism in young girls, Beyond PCOS

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively. USG abdomen & pelvis was normal.HOMA-IR was 4.1. Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2,acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen & pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm & clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes. Presentation: 6/3/2024

8183 An Unusual Cause of Fluctuating Thyroid Hormone Levels

Abstract Disclosure: V. Taqi: None. W. Akhter: None. J.L. Gilden: None. Background: Thyroid disease, especially congenital hypothyroidism is a common endocrine problem with an estimated global prevalence of 4.25%. Since every organ system is affected by thyroid hormones, untreated hypothyroidism can lead to profound adverse outcomes. Many drugs, hormones, and dietary supplements have been noted to affect the efficacy of thyroid hormones, yet there was always concern about the effect of the excessive growth of intestinal flora in the small intestine on thyroid supplement absorption. Drugs, malabsorption, celiac disease and increased excretion are common causes of fluctuating thyroid hormones. In this case, we present a young male patient with congenital hypothyroidism, who required fluctuating doses of levothyroxine due to abnormal thyroid hormone levels, despite compliance with proper administration, and dramatic improvement of thyroid hormone levels after starting probiotic therapy. Case : An 18-year-old Caucasian male with congenital hypothyroidism had been treated with varying doses of thyroid hormone replacement by a Pediatric Endocrine Center. Due to his recall that TSH=4.13 mIU/L and he was “tired of taking medication”, he stopped taking 125 mcg of levothyroxine. Four months later, TSH was > 200 mIU/L (nl=0.48-4.17). Levothyroxine 137 mcg was then started. However, 11 months later, TSH=14.2 mIU/L, Free T4=1.6 ng/dL (nl=1.03-1.64). He was then referred to our Endocrine Clinic. He denied symptoms of hypo or hyperthyroidism or other medical issues. His grandfather was known to have hypothyroidism and diabetes mellitus (details unknown). On exam: Wt. was 149 Ib, Ht= 67 Inch. VS: BP 98/46, P 69, R:16,temp: 97.9F, Physical exam showed normal findings without thyromegaly, but there was a delay in tendon reflexes. Laboratory-unremarkable CBC, CMP panels with normal thyroid antibodies, and Celiac titers. TSH initially improved from 14.2 to 8.4 mIU/L after increasing the thyroxine dosage from 137 to 150 mcg for 2 weeks, then to 175 mcg after 4 weeks, but TSH increased to 12.1 mIu/L, despite being compliant with medication and ensuring proper way of administration. He continued to deny symptoms of hypo or hyperthyroidism, or any other medical issues, including lactose intolerance or malabsorption. However, probiotics were then added to his regimen, and continuation of the current dose resulted in a suppressed TSH=0.15 mIU/L. The levothyroxine was then decreased to 150 mcg with continuation of probiotics. One month later, TSH was 1.31 mIU/L with Free T4 of 1.5 ng/dL. Conclusion : Common causes for fluctuating thyroid hormone levels include intestinal malabsorption, celiac disease, nephrotic syndrome, drugs, and food interaction. This case demonstrates that despite proper administration, fluctuating thyroid hormone levels can result from some uncommon causes, such as lactose intolerance, which can be unmasked by co-administration of probiotics. Presentation: 6/2/2024

8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None. Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring. Presentation: 6/3/2024

7986 Cardiovascular Risk Factors in Patients with Autoimmune Thyroiditis: Impact of Overweight and Obesity

Abstract Disclosure: C. Neves: None. J. Neves: None. L. Pereira: None. O. Sokhatska: None. J. Queirós: None. J. Delgado: None. Background: Autoimmune thyroiditis is one of the most common organ specific autoimmune disorders. Several studies suggest that patients with autoimmune thyroid may have an increased cardiovascular risk even among those with normal thyroid function. Our objective was to evaluate the cardiovascular risk factors in autoimmune thyroiditis according to body weight. Methods: We evaluated patients with autoimmune thyroiditis followed in outpatient clinic. We evaluated anthropometric parameters, glycemic profile, lipid, homocysteine, folic acid, B12 vitamin, high-sensitivity C reactive protein (hsCRP), thyroid function and thyroid autoimmunity. Participants were divided in groups according to body weight: normal weight [body mass index (BMI) 18.5-24.9 kg/m2], overweight (BMI 25.0-29.9 kg/m2) and obesity (BMI ≥30 kg/m2). Correlations were evaluated in the whole group and in subgroups of body weight. Statistical analysis was performed with the one-way ANOVA test and Pearson’s correlation test. Results: Within our sample of 354 patients had autoimmune thyroid, 93.8% were females, with a mean age of 46.7±16.3 years. One-hundred and three (37.6%) had normal weight, 128 (36.1%) had overweight and 91 (25.7%) had obesity. The mean TSH level of our population was 2.5±6.0 μUI/L. In our sample, TSH, FT4 and FT3 did not significantly differed between body weight groups. Comparing with normal weight, patients with obesity and overweight had higher fasting glucose (normal weight 92±13 mg/dL vs overweight 91±23 mg/dL vs 92±13 mg/dL, p= 0.004), higher LDL levels (normal weight 112.7±29.2 mg/dL vs overweight 130.1±29.4 mg/dL vs obesity 130.6±31.3mg/dL, p<0.001), higher triglycerides (normal weight 94.8 ± 43.0 mg/dL vs overweight 120.1 ± 79.0 mg/dL vs obesity 140.5 ± 80.4 mg/dL, p<0.001) and higher hsCRP levels (normal weight 0.3±0.5 mg/dL, overweight 0.4±0.5 mg/dL vs obesity 0.5±0.6 mg/dL, p=0.018). In the whole group, TSH was positively correlated with insulin (r=0.184, p=0.003), C-peptide (r=0.187, p=0.003) and HOMA-IR (r=0.178, p=0.004); anti-TG was negatively correlated with HDL (r= -0.147, p=0.006), and anti-TPO was positively correlated with LDL cholesterol (r=0.134, p=0.013) and with HOMA-IR (r= 0.126, p=0.039). In patients with normal weight anti-TG was negatively correlated with fasting glycemia (r=-0.204, p=0.046). In patients with overweight, anti-TG was positively correlated with hsCRP (r= 0.187, p= 0.043). In patients with obesity, TSH was positively correlated with C-peptide (r=0.280, p=0.020) and triglycerides (r=0.258, p= 0.016); and anti-TPO was correlated with fasting insulin levels (r=0.282, p=0.018). Conclusions: In patients with autoimmune thyroiditis, the interrelationships between thyroid function, autoimmunity, obesity, insulin resistance and lipid profile may contribute to the increased cardiovascular risk. Presentation: 6/3/2024

Quercetin and Thyroid.

Quercetin is the most abundant flavonoid present in fruits and vegetables. For its antiproliferative, antiviral, anti-inflammatory and antioxidants activities, it is an active ingredient of several herbal remedies and is available as a nutraceutical. Experimental studies performed in vitro have demonstrated that quercetin inhibits growth and function in normal thyroid cells and may act as a thyroid disruptor. These effects have also been confirmed in vivo using rodent models. Some studies have reported the ability of quercetin to interfere with the metabolism of thyroid hormones, since it inhibits the 5'-deiodinase type 1 (D1) activity in the thyroid, as well as in the liver. Besides the effects on normal thyroid cells, several experiments performed in vitro have shown a potential therapeutic role of quercetin in thyroid cancer. Indeed, quercetin inhibits the growth, the adhesion and the migration of thyroid cancer cells, and it also has redifferentiation properties in some thyroid cancer cell lines. In conclusion, these data suggest that, although its effects can be of benefit in hyperthyroidism and thyroid cancer, caution is required in the use of high doses of quercetin due to its anti-thyroid properties. Further in vivo studies are certainly needed to confirm these hypotheses.

Neutrophil elastase specific fluorescent probe for early diagnosis of thyroiditis via serum sample testing and fluorescence imaging

Autoimmune thyroid diseases (AITD) often interfere with early detection due to asymptomatic symptoms and normal thyroid function in routine tests. Developing early diagnostic tools is crucial for timely and accurate treatment, potentially reducing complications and improving patient outcomes. In this study, we developed Ox-NE, a novel fluorescent probe designed for the specific detection and quantification of neutrophil elastase (NE), a key biomarker of inflammation. Unlike the traditional probes, Ox-NE utilizes a unique mechanism that minimizes background fluorescence and enhances photostability, offering rapid, non-invasive, and apparent diagnostic capabilities. Ox-NE had a low limit of detection (LOD) of 1.54 μg/mL and exhibited high sensitivity and specificity with strong anti-interference properties. Through in vitro experiments, Ox-NE could accurately detect elevated NE levels in the serum of thyroiditis patients. Additionally, it could differentiate between normal thyroid cells, inflamed thyroid cells, and thyroid cancer cells. It also effectively facilitated the screening of sivelestat, a therapeutic agent for thyroiditis. Successful fluorescence imaging in mouse models further confirmed the potential of Ox-NE in advancing thyroid disease diagnostics.

Subclinical Hyperthyroidism Enhances Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women.

Metformin treatment decreases elevated concentrations of anterior pituitary hormones. The aim of this prospective, cohort study was to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function. The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55-3 g daily). Plasma glucose, insulin, thyroid-stimulating hormone (TSH), total and free thyroid hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin-like growth factor-1 (IGF-1) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1-IR], and glycated hemoglobin [HbA1c]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA1c in response to metformin treatment. Although metformin decreased HOMA1-IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (-50 ± 20% vs -30 ± 15%). Similar relationships were observed for FSH (-43 ± 21% vs -21 ± 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 ± 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF-1. The obtained results indicate that hyperthyroidism enhances the gonadotropin-lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic-pituitary-thyroid axis in case of its overactivity.

Overexpression of NR1D1 portends disease recurrence in thyroid cancer.

Dysregulation of circadian rhythms has been linked to cancer susceptibility. Thyroid cancer cells demonstrate altered circadian oscillations in endogenous clock transcripts. Our previous research identified NR1D1, a component of the circadian clock, as one of the recurrence-associated genes in papillary thyroid cancer. The objective of this study was to investigate the expression pattern of NR1D1 in thyroid cancer and explore its prognostic and translational implications. We assessed NR1D1 expression using immunohistochemical analysis and examined its correlation with clinicopathological parameters. In vitro and in vivo experiments were performed to elucidate the oncogenic roles of NR1D1 and potential mechanisms. Nuclear NR1D1 expression was present in thyroid follicular epithelial-derived cancers, whereas normal thyroid tissue and benign nodular goiter showed no detectable NR1D1 immunoreactivity. Patients with high expression of NR1D1 had more advanced disease stages, extrathyroidal extension, lymphovascular invasion, and shorter recurrence-free survival compared to those with low levels of NR1D1. Through gain- and loss-of-function studies, we demonstrated that NR1D1 modulation affected the growth of organoids, resistance to anoikis, and the invasive and migratory capacity of thyroid cancer cells. The invasion-promoting effect of NR1D1 was regulated by the β-catenin/ZEB1 axis. Moreover, the overexpression of NR1D1 accelerated xenograft growth and lung metastasis in vivo. NR1D1 is overexpressed in malignant thyroid tumors and has prognostic significance. Our findings suggest therapeutic potential in targeting NR1D1 for thyroid cancer.

Histone 3 and 4 acetylation patterns in nodular goiter and well-differentiated thyroid tumors compared with normal thyroid tissue

Histone 3 and 4 acetylation patterns in nodular goiter and well-differentiated thyroid tumors compared with normal thyroid tissue

Meta-Analytical and Meta-Regression Evaluation of Subclinical Hyperthyroidism's Effect on Male Reproductive Health: Hormonal and Seminal Perspectives.

Subclinical hyperthyroidism (SCH) is a subtle thyroid dysfunction marked by decreased serum thyroid-stimulating hormone (TSH) levels while maintaining a normal thyroid hormone profile. Despite its mild nature, SCH can significantly impact various physiological functions, including male reproductive health. However, the effects of SCH on reproductive hormones and semen quality are less understood compared to overt thyroid disorders. This study employed extensive search methods across various databases from January 2000 to February 2024 to explore the relationship between SCH and Hormonal and Seminal Perspectives. Effect sizes, estimated using the standardized mean difference (SMD) and pooled with a Random-effect model, provided significant insights from 748 participants. Included studies adhered to the following criteria: Patients (male individuals with SCH), Intervention (assessment of reproductive hormones and semen quality), Comparison (SCH patients versus healthy controls), and Outcome (changes in reproductive factors). Significant alterations in reproductive hormones were observed in SCH patients, including reduced LH levels (SMD = - 0.20; p = 0.007), elevated FSH levels (SMD = 0.25; p = 0.002), and stable testosterone levels (SMD = - 0.05; p = 0.50). Regarding thyroid profile, SCH was associated with increased FT3 (SMD = 0.15; p < 0.001) and FT4 (SMD = 0.08; p = 0.002) levels, along with decreased TSH levels (SMD = - 2.00; p < 0.001). Adverse effects on semen quality were also observed. These findings underscore the need to incorporate thyroid health assessments in the evaluation of male infertility, recognizing the impact of minor thyroid hormone deviations on reproductive outcomes.

Hyperthyroidism in thyroid carcinoma originating in struma ovarii.

Thyroid carcinoma originating in Struma Ovarii (SO) is a rare thyroid ectopic cancer that accounts for 0.01% of all ovarian malignancies and is associated with hyperthyroidism in less than 15% of cases. In a 44-year-old patient with pelvic pain, the CT scan revealed a solid-cystic formation in the ovarium. A left oophorectomy was performed and showed a borderline serous tumor and papillary thyroid carcinoma ('thyroid carcinoma originating in Struma Ovarii') measuring 10 cm. Thyroid function was assessed, and hyperthyroidism was diagnosed. Surgical complementation and a pelvic re-approach were performed. The histological findings showed a papillary thyroid carcinoma in the uterine serosa and the right adnexa. Thyroid function was re-evaluated, and despite normal thyroid function, the TRAb test remained positive. The patient underwent total thyroidectomy and radioiodine therapy (RIT), after which the TRAb test became negative. During 3 years of follow-up, no evidence of tumor was observed. In our case of thyroid carcinoma originating in SO, hyperthyroidism was treated with ovarian surgery, total thyroidectomy, and RIT. It is worth noting that thyroid function was normalized after ovarian surgery, but the TRAb test only became negative after total thyroidectomy. We hope to draw attention to the importance of evaluating thyroid function in patients with SO and treating high-risk SO patients with RIT after total thyroidectomy to achieve disease remission. Struma ovarii can cause hyperthyroidism. Thyroid carcinoma can originate in Struma Ovarii. Differentiated thyroid carcinoma and hyperthyroidism originating in Struma Ovarii are rare conditions.

Prevalence of abnormal thyroid function test in adults attending primary care setting in the year 2022 in the Kingdom of Bahrain

ABSTRACT Background: Thyroid disease is known to be one of the most common endocrine diseases globally and has serious health implications if left untreated. Objective: This study aimed to gain a better understanding of common thyroid diseases and to explore the associated risk factors in the Kingdom of Bahrain. Methods: A case-control study was carried out after obtaining all thyroid stimulating hormone (TSH) results done in a primary healthcare setting from January 1, 2022 to December 31, 2022 from the Health Information Department. In total, 500 participants were randomly selected from each group: the abnormal thyroid test group (cases) and the normal thyroid test group (controls). Participants were interviewed using a structured list of associated risk factors with the following sections: sociodemographic characteristics, comorbidities, family history of thyroid disease, BMI, previous radiation therapy, and certain medications. Results: The prevalence of abnormal thyroid tests was found to be 11%. Cases were categorized into four groups: hyperthyroidism (26.4%), hypothyroidism (64.6%), hyperthyroidism (4.5%), and subclinical hypothyroidism 13 (4.5%). The results showed significant differences between case and control in the following risk factors: female sex, increasing age, BMI, dyslipidemia, family history of thyroid disease, and previous radiation therapy (P = &lt;0.05). Conclusion: In summary, the high prevalence of abnormal thyroid results highlights the need for an organized national screening program for individuals at average risk for developing thyroid disease.

TGFBR3 inhibits progression of papillary thyroid cancer by inhibiting PI3K/AKT pathway and EMT.

Transforming growth factor beta receptor III (TGFBR3) has been shown to play a tumor suppressive role in a variety of cancers. However, its role in papillary thyroid cancer (PTC) remains unknown. TGFBR3 expression levels in PTC were analyzed utilizing TCGA and GEO database. Edu, wounding healing and Transwell assays were used to evaluate cell proliferation, migration and invasion. Transcriptome sequencing, qRT-PCR and Western blotting were used to detect the underlying mechanism of TGFBR3 in PTC progression. This study demonstrated that TGFBR3 expression was significantly down-regulated in PTC compared to normal thyroid tissues. Low expression of TGFBR3 was associated with poor prognosis of patients with PTC. Furthermore, TGFBR3 expression positively correlated with thyroid differentiation score. In investigating the biological impact of TGFBR3 over-expression in PTC cell lines, we found that the proliferation, migration and invasion of PTC cells were significantly inhibited in response to TGFBR3 overexpression. Moreover, we also demonstrated that overexpression of TGFBR3 inhibited PI3K/AKT pathway and epithelial mesenchymal transformation processes. Lastly, TGFBR3 expression was found to be involved in tumor immune infiltration, highlighting its potential influence on immune dynamics within the tumor microenvironment in PTC. TGFBR3 plays a tumor suppressive role in PTC progression by inhibiting PI3K/AKT pathway and EMT.

Tight Junctions and Cancer: Targeting Claudin-1 and Claudin-4 in Thyroid Pathologies.

Purpose: Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. Methods: The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Results: Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79-35, p = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. Conclusions: The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.

Comparative Analysis of Metastatic Thyroid Carcinoma versus Ectopic Thyroid Carcinoma in Lateral Neck Masses without Identifiable Primary Thyroid Carcinoma

Background/Objectives: Thyroid carcinoma, presenting as a lateral neck mass without an identifiable primary tumor within the thyroid, poses a diagnostic challenge. This comparative analysis aimed to explore the differences between metastatic thyroid carcinoma and ectopic thyroid carcinoma, as both present with a lateral neck mass without evidence of primary thyroid carcinoma. Methods: Searches were conducted for studies on thyroid carcinoma in the lateral neck without evidence of primary thyroid carcinoma. A total of 39 patients were identified from 32 reported studies. Results: Metastatic and ectopic thyroid carcinomas were found in 11 and 28 patients, respectively. Metastatic thyroid carcinoma is characterized by evidence of spontaneous primary tumor regression within the thyroid and commonly associated with multiple lymph node metastases in central and lateral neck compartments. Ectopic thyroid carcinoma is more commonly diagnosed in younger patients and is frequently identified in branchial cleft cysts. The coexistence of normal thyroid tissue adjacent to the ectopic thyroid carcinoma was confirmed, and patients with ectopic thyroid carcinoma exhibited significantly higher rates of second-stage thyroidectomy or neck dissection. When complete surgical excision was considered adequate, excision alone was chosen for patients with ectopic thyroid carcinoma. Conclusions: Identifying these differences is valuable for the differential diagnosis and development of treatment strategies for metastatic and ectopic thyroid carcinomas in lateral neck masses without evidence of primary thyroid tumor.

Prevalence of Hypothyroidism in Children with Transfusion Dependent Thalassemia Patient Attending in A Tertiary Care Hospital of Bangladesh

Background: Blood transfusions and iron chelation are standard treatments for β-thalassemia major and Hb E-Beta-Thalassemia. However, repeated transfusions raise body iron levels, leading to secondary hemosiderosis and complications in the heart, endocrine system, and liver. Thyroid dysfunction results from gland infiltration, chronic hypoxia, free radical damage, and iron overload. This study aimed to find out the prevalence of hypothyroidism in transfusion-dependent thalassemic children attending Bangladesh Shishu Hospital &amp; Institute. Methods: A descriptive cross-sectional study was conducted at the Thalassemia Centre, Department of Hematology and Oncology, Bangladesh Shishu Hospital &amp; Institute, from December 2019 to November 2020. The study included 140 children with thalassemia, aged 5 to 16 years, who were receiving blood transfusions. Data were collected using a structured questionnaire with participant consent. Statistical analysis was performed using SPSS version 23.0. Results: In this study, hypothyroidism was observed in 26.2% of patients, with 23.5% having subclinical and 2.9% overt hypothyroidism. In most of the patients (n=85), aged 11-16 years, 58.3% had normal thyroid function, 36.5% had subclinical, and 4.7% had overt hypothyroidism, which was statistically significant (p&lt;0.05). Of the 91 patients with hemoglobin levels below 11.5 g/dL, 85.7% had normal thyroid function, 13.2% had subclinical hypothyroidism, and 1.1% had overt hypothyroidism, also significant (p&lt;0.05). In the group with ferritin levels of 1200-2000 ng/mL, 78.1% had normal thyroid function, 18.8% had subclinical hypothyroidism, and 3.1% had overt hypothyroidism, which was not statistically significant (p&gt;0.05). Conclusion: Subclinical hypothyroidism is commonly seen in thalassemia patients aged 5 to 16 years who undergo regular blood transfusions. Regular physical exams and thyroid function assessments are crucial to detect overt hypothyroidism early. Timely hormone replacement can

Association between thyroid function and prognosis of severe COVID-19 among patients with SARS-CoV-2 infection: a retrospective cohort study in China.

This study aims to examine the thyroid hormone profile and its association with severe coronavirus disease 2019 (COVID-19) in patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This retrospective cohort study enrolled patients admitted to a tertiary hospital due to SARS-CoV-2 infection between February 18 and May 18, 2022. Clinical data were collected retrospectively from the electronic medical record system. Based on the thyroid function, patients were divided into five groups: normal, non-thyroid illness syndrome (NTIS), hypothyroidism, thyrotoxicosis, and unclassified. The association between thyroid function and severe COVID-19 was detected using multivariable logistic regression and restricted cubic splines analysis. This study included 3,161 patients, with 7.7% of them developing severe COVID-19. 44.9% of the patients had normal thyroid function, 36.5% had NTIS, 6.7% had hypothyroidism, and 1.0% had thyrotoxicosis on admission. After adjusting for age, sex, and relevant clinical characteristics, NTIS and hypothyroidism were associated with increased risks of severe COVID-19 (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.59-3.56 and OR 2.29, 95% CI 1.23-4.26, respectively), compared to normal thyroid function group. Among patients with NTIS or hypothyroidism, higher levels of total triiodothyronine (TT3) are associated with lower risks of severe COVID-19 (OR 0.73, 95% CI 0.64-0.82, for every 0.1nmol/L increase in TT3 level). Thyroid hormone profiles of NTIS or hypothyroidism are associated with increased risks of severe COVID-19. The decreased level of TT3 correlated with the increased risk of severe COVID-19 in patients with NTIS or hypothyroidism.

2D Shear Wave Elastography of Normal Thyroid Gland in Nepalese Population

Ultrasonography (USG) is modality of choice for normal, diffuse or nodular thyroid diseases. Two dimensional shear wave elastography (2D-SWE) is the latest innovation in USG techniques that allows real-time quantitative assessment of tissue stiffness using acoustic radiation force impulse (ARFI) induced by ultrafast focused US beam sequence (up to 20,000Hz) to record the propagation of the shear waves in real time and displays a map that represents the local elasticity values of tissues in real-time and in a quantitative manner without any compression of the organ. At times, there are difficulties in differentiating normal thyroid gland from diffuse thyroid disease based solely on gray scale USG for which 2D-SWE can be an adjunct. This study aims to establish 2D-SWE parameters for normal thyroid gland in Nepalese population. A cross sectional descriptive study was carried out with 2D SWE on all euthyroid patients with normal thyroid gland on B-mode USG at Department of Radiology, Nepal Medical College Teaching Hospital between December 2021 and November 2022. Tissue stiffness of normal thyroid gland was recorded and tabulated in terms of SMV units (m/s) according age and gender. Out of 100 subjects ( 52 females and 48 males) the youngest was 16 year female and oldest was 68 year female with mean age of 37.07 year (S.D = 11.58). Minimum mean velocity of 1.78 m/s was seen in 36 year old male and maximum of 3.40 m/s in 26 year old female. Mean of mean velocity was 2.36 m/s with (S.D= 0.34). Linear positive correlation was seen between shear wave velocities and age with no statistically significant difference between genders. This study had the most number of normal subjects (100) with almost equal gender distribution (52 females and 48 males) compared to previous studies in known literature. This study also analyzed correlation of shear wave velocity with age unlike other studies. Statistically significant correlation was seen between age and velocities in males only and also in mean velocities between age group 21-40 and 41-60 years (p-value= 0.037).

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.