Elevated Thyroid Peroxidase Antibodies Research Articles

Sex differences and risk factors of self-reported suicide attempts in middle-aged Chinese Han patients with first-episode drug-naïve anxious depression: a large-scale cross-sectional study.

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

Association of thyroid peroxidase antibody with the RNF213 p.R4810K variant in ischemic stroke/transient ischemic attack

Background and aimsRNF213 is a susceptibility gene for moyamoya disease and vasospastic angina, with a second hit considered necessary for their development. Elevated thyroid peroxidase antibody (TPO-Ab) levels have been observed in both diseases, suggesting a possible role of TPO-Ab as a second hit for developing RNF213-related vasculopathy. We investigated the association of TPO-Ab levels with RNF213-related ischemic stroke (IS)/transient ischemic attack (TIA), other than moyamoya disease. MethodsFrom the National Cerebral and Cardiovascular Center Genome Registry, a multicenter, prospective, observational study, we enrolled patients with IS/TIA who were admitted within 1 week of onset. Patients with IS/TIA due to definite moyamoya disease or hemorrhagic stroke were excluded. Participants underwent genotyping for RNF213 p. R4810K, and baseline characteristics and TPO-Ab levels were compared between RNF213 p. R4810K variant carriers and non-carriers. ResultsIn total, 2090 IS/TIA patients were analyzed [733 women (35.1%); median age 74 (interquartile range, 63–81) years, baseline NIHSS score 3 (2–6)], and 85 (4.1%) of them carried the variant. Median TPO-Ab levels were significantly higher in variant carriers (8.5 IU/mL vs. 2.1 IU/mL, p < 0.01), who also showed a higher frequency of elevated TPO-Ab levels (>16 IU/mL) (27.1% vs. 4.4%). In the multivariate analysis, presence of the RNF213 p. R4810K variant (adjusted odds ratio, 12.42; 95% confidential interval, 6.23–24.75) was significantly associated with elevated TPO-Ab levels. ConclusionsElevated TPO-Ab levels may be significantly associated with presence of the RNF213 p. R4810K variant in IS/TIA patients. Thus, TPO-Ab may inherently modify IS/TIA development in RNF213 p. R4810K variant carriers.

Long-term effect of a large dose of iodinated contrast in patients with mild thyroid dysfunction: a prospective cohort study.

More than 75 million procedures with intravascular iodine-based contrast media (ICM) are performed worldwide every year, and some patients undergoing these procedures do not have normal thyroid function. The long-term effects of ICM in patients with mild thyroid dysfunction (TD) are unclear. This prospective cohort study was conducted in China. Patients with stable angina pectoris with total triiodothyronine (TT3) reduction, normal thyroid-stimulating hormone, and reverse triiodothyronine (rT3) were enrolled and divided into high-dose (≥100 mL ICM) and low-dose groups (<100 mL ICM). We dynamically investigated the trends in thyroid function, rT3, and thyroid antibodies 1 year after ICM exposure. A total of 154 patients completed 6 months of follow-up and 149 completed 1 year of follow-up. Thyroglobulin antibody (TGAB) levels were elevated in 41 (26.6%) patients before ICM exposure, 11 (7.1%) of whom also had elevated thyroid peroxidase antibody levels. Transient subclinical TD occurred 6 months after ICM exposure; 75.5% of post-operative TD occurred in the high-dose group. One patient developed severe hypothyroidism with myxedema, requiring drug intervention 1 year after ICM exposure. The level of rT3 showed no statistically significant changes during post-operative follow-up (P = 0.848). The TGAB level decreased at 6th month (P < 0.001), but increased at 1 year after ICM exposure (P = 0.002). Patients with T3 reduction are at risk of transient subclinical TD and hypothyroidism after a single large dose of ICM. Follow-up of this population at 9-12 months after ICM exposure is warranted.

Sex-specific effect of urinary metabolites of polycyclic aromatic hydrocarbons on thyroid profiles: results from NHANES 2011-2012.

The current study aims to evaluate the associations between 10 urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid profiles. The levels of 10 PAH metabolites and thyroid profiles were obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2012. Spearman analysis was utilized to evaluate the correlation coefficients among these 10 PAH metabolites. Multivariate linear and logistic regression models assessed the relationship between urinary PAH metabolite levels, thyroid hormones, and thyroid autoantibodies after adjusting potential confounders. Stratified analysis by gender was performed to evaluate sex-specific effect of urinary metabolites of PAH on thyroid profiles. One thousand six hundred forty-five eligible adult participants with complete research data were enrolled. Of note, the concentrations of the majority of urinary PAH metabolites were remarkedly higher in females compared with males. 2-hydroxyfluorene (2-FLU) was associated with higher total triiodothyronine (T3) levels in whole population (β = 2.113, 95% CI 0.339-3.888). In males, positive associations were observed in 1-hydroxynaphthalene (1-NAP) and free thyroxine (T4) (β = 0.0002, 95% CI 0.0000-0.0004). 2-FLU was also found positively associated with total T3 (β = 2.528, 95% CI 0.115-4.940) in male subjects. While in female participants, 2-hydroxynaphthalene (2-NAP) was associated with free T3 (β = 0.002, 95% CI 0.000-0.005). 2-FLU was associated with total T3 (β = 2.683, 95% CI 0.038-5.328), free T3 (β = 0.050, 95% CI 0.012-0.087), and total T4 (β = 0.195, 95% CI 0.008-0.382). 2-Hydroxyphenanthrene (2-OHP), 1-hydroxypyrene (1-HP), and 9-hydroxyfluorene (9-FLU) were all positively related to total T3 levels, and the corresponding coefficients were 16.504, 6.587, and 3.010. 9-FLU was also associated with free T3 (β = 0.049, 95% CI 0.008-0.090). No statistical significances were found between PAH metabolite levels and increased prevalence of increased thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) when PAH metabolites were treated as continuous variables. Meanwhile, in the quartile analyses, increased prevalence of elevated TgAb was observed in participants with quartile 2 2-NAP compared with lowest quartile (OR = 1.753, 95% CI 1.021-3.008). Male subgroup analyses indicated that increased prevalence of elevated TgAb was observed in higher quartile of 1-NAP, 2-NAP, and 3-hydroxyfluorene (3-FLU). Increased prevalence of elevated TPOAb was associated with higher 2-NAP quartile. However, in subgroup analysis of females, no statistical significances were found between PAH quartiles and increased TgAb/TPOAb. Significant correlations were found among these 10 PAH metabolites. In conclusion, the cross-sectional study indicated that exposure to PAH might disturb the concentrations of thyroid hormones and thyroid autoantibodies. It is noteworthy that significant differences existed in males and females. Further prospective research is warranted to explore the causal relationship and underlying mechanism of PAH exposure on thyroid dysfunction.

PSAT378 Hashimoto's Thyroiditis and Differentiated Thyroid Cancer Aggressiveness

Abstract Background Hashimoto's thyroiditis (HT) is associated with a 1.5-fold increased risk of differentiated thyroid cancer (DTC). It is postulated that the inflammatory milieu in HT may damage thyrocytes, increasing the risk of cancer. However, it is not precisely known how the presence of thyroiditis affects aggressiveness of DTC and if a causal relationship exists. It has been suggested HT may correlate with a less aggressive phenotype with smaller tumor size, lower rate of aggressive variants, less frequent radioactive-iodine administration, and higher rates of clinical remission. The aim of this study was to investigate the pathological features of DTC in patients with HT and whether length of time with HT affects tumor aggression. Method Charts of 367 consecutive patients with DTC undergoing thyroidectomy were reviewed. Clinical and pathological factors were analyzed. A composite score of tumor aggressiveness was calculated using the presence of multifocality, angioinvasion, lymphatic invasion, extrathyroidal extension, central and lateral lymph node (LLN) involvement. This score and tumor size were compared in patients with clinical (elevated thyroid peroxidase or anti-thyroglobulin antibodies) or pathological (presence of inflammation on pathology) HT. Time to surgery from diagnosis of HT was also evaluated. Results In 367 patients with DTC (343 papillary, 29 follicular, 5 both), mean size of the largest tumor was 1.5±1.7cm, mean composite score was 1.3±1.6cm. Seventy-three (19.9%) and 156 (42.5%) patients had clinical or pathological HT, respectively; 92 (25.1%) had preoperative hypothyroidism. Patients with clinical HT alone, or in addition to pathological HT, had a reduced risk of LLN disease (Odds Ratio: 0.21 p&amp;lt;0.005, and OR: 0.43 p=0.01, respectively); those with pathological HT alone had a trend towards lower risk (p=0.06). Neither the overall score for tumor aggressiveness nor tumor size correlated with clinical or pathological HT. Length of time from diagnosis of clinical HT to surgery was not associated with tumor size, aggressiveness or presence of inflammation on pathology. Conclusion Clinical HT is associated with reduced risk for LLN metastasis, supporting the suggestion that presence of HT confers a better prognosis in DTC. Length of time with HT does not alter the risk for aggressive features of DTC indicating lack of an escalating causal relationship. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Hypothyroidism and Depression: A Narrative Review.

There has been an established relationship between hypothyroidism and depression. Studies have demonstrated that somatostatin and serotonin influence the hypothalamus-pituitary-thyroid axis, which links hypothyroidism to depression. Multiple studies concluded that undiagnosed, untreated, undertreated patients with hypothyroidism are at increased risk of developing depression. Autoimmune thyroiditis is also associated with an increased risk of depression. Elevated thyroid-stimulating hormone (TSH), antithyroglobulin (TgAb), and thyroid peroxidase antibodies (TPOAb) levels have all been linked to depression and an increased risk of suicide. Moreover, hypothyroidism is known to be one of the leading causes of treatment-resistant depression. Treating underlying hypothyroidism with thyroid replacement therapy could significantly improve mood disorders such as depression. Levothyroxine therapy is also used as adjunctive therapy to antidepressants in the management of depression, and it is known to improve the symptoms of depression rapidly when compared to antidepressants alone. This review strengthens the link between hypothyroidism and depression, and it also demonstrates how treating the underlying hypothyroidism in people who have been diagnosed with depression will be very beneficial.

Correlations of thyroid autoantibodies with allergic diseases: A case-control study of 434 Chinese patients.

There is growing interest in the relationship between allergies and autoimmune diseases, although previous studies have yielded inconsistent results.The thyroglobulin (Tg)/thyroid peroxidase antibody (TPOAb) group consisted of 217 patients with positive thyroglobulin antibody (TgAb) and/or TPOAb test results. Another set of 217 age- and sex-matched individuals with both TgAb- and TPOAb-negative results were selected as control group. History of allergic rhinitis (AR), chronic spontaneous urticaria (CSU), and/or atopic dermatitis (AD) was elicited before autoantibody detection. The association of thyroid autoantibodies with allergic diseases was assessed using univariate and multivariate logistic regression analysis, and the results were reported as odds ratios (ORs).TgAb positivity (OR, 2.333) was identified as a risk factor for AR, AD, or CSU in Chinese patients, suggesting the involvement of thyroid autoantibodies in the pathogenesis of atopic reactions. Multivariate regression analysis also confirmed that the presence of TgAb (P = .004), rather than TPOAb (P = .468), had a significant impact on the occurrence of allergic disease.Physicians should carefully monitor atopic symptoms in individuals with elevated TgAb or TPOAb levels to reduce the risk of allergic diseases, such as AR, AD, and CSU.

Association between thyroid function and comorbid anxiety in first-episode and drug naïve patients with major depressive disorder.

Existing studies have shown that thyroid dysfunction is associated with depression. However, its role in major depressive disorder (MDD) with comorbid anxiety remains unclear. The main purpose of this study was to compare thyroid function in a large sample of first episode drug naïve (FEDN) MDD patients with and without anxiety. This cross-sectional study examined 1718 outpatients who were drug-naïve and diagnosed as MDD at first episode. Socio-demographic and clinical data, as well as thyroid function-related parameters, including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin (TGAb), were evaluated. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were used to evaluate depressive, anxiety and psychotic symptoms, respectively. Compared to MDD patients without anxiety, MDD patients with anxiety were more likely to have more suicide attempts and psychotic symptoms, as well as higher serum levels of TSH, TPOAb and TGAb (all p < 0.001). Among patients with abnormally elevated serum TSH, TPOAb, and TGAb, 83.5% (872/1044), 89.3% (391/438) and 89.6% (266/297) had comorbid anxiety disorders, respectively. The odds ratio between patients with comorbid and without comorbid anxiety was 1.657 (95% CI 1.304-2.105) for elevated TSH levels, 1.943 (95% CI 1.444-2.613) for elevated TGAb levels, and 2.448 (95% CI 1.760-3.403) for elevated TPOAb levels. Furthermore, multivariable linear analysis showed that elevated TSH and TGAb were significant predictors of anxiety in MDD patients. Our results suggest that comorbid anxiety in FEDN MDD patients is positively associated with elevated TSH and TGAb levels, which may be promising biomarkers of comorbid anxiety in MDD patients. Clinical treatment of impaired thyroid function may be useful for comorbid anxiety in MDD patients.

Abstract #1176275: A Rare Case of Hashimoto Encephalopathy

Hashimoto’s encephalopathy (HE) is a rare disorder characterized by an autoimmune encephalopathy associated with elevated Thyroid Peroxidase (TPO) antibodies. Clinical features include neurocognitive dysfunction, psychiatric manifestations (paranoia, hallucinations, depression), sleep disturbance, seizures, and transient neurological deficits. The heterogeneity of it’s symptoms, and the broad differential of neuropsychiatric conditions make it a challenging diagnosis. Diagnosis is made in patients with an appropriate clinical picture, elevated TPO antibodies and response to treatment.

Value of Thyroid Peroxidase Antibodies in Neuroimmune Diseases: Analysis of Interference During Treatment with Intravenous Immunoglobulins.

The absence of specific markers can make the diagnosis of neuroimmune disorders difficult, making other biomarkers such as thyroid peroxidase antibodies (TPO-Abs) more relevant. Laboratory tests are susceptible to interference, especially those tests performed using immunoassay techniques. The effect of treatment with human intravenous immunoglobulin (IVIG) on the results of TPO-Abs assays has not been previously characterized. We analyzed TPO-Abs levels in 170 children monitored in the neuroimmune disease department of a tertiary hospital. We analyzed the characteristics of patients with increased TPO-Abs values and compared their progress with and without treatment. We found that 97% of patients with elevated TPO-Abs had received IVIG. After withdrawal from IVIG, a mean TPO-Abs decrease of 62.5% at 1 month was observed. The IVIG drug preparation was found to contain 1176 U/mL of TPO-Abs. An interferogram confirmed interference. It is advisable to measure levels of TPO-Abs before starting immunotherapy and remain vigilant regarding possible interference in the event of unsubstantiated elevations of this analyte.

Association Between Elevated Thyroid Peroxidase Antibody and Abdominal Fat Distribution in Patients with Type 2 Diabetes Mellitus.

ObjectiveObesity and autoimmune thyroid disease (AITD) are both common disorders in the general population, which are major drivers for adverse medical conditions. While an interaction between thyroid function and visceral obesity is thought to exist, but very few studies have examined the relationship between AITD and visceral obesity, especially in the patients with type 2 diabetes mellitus (T2DM). In the present study, we investigated the association between elevated thyroid peroxidase antibody (TPOAb) titer and visceral fat area in T2DM patients.MethodsA total of 390 T2DM patients who met the criteria for admission and joined the National Metabolic Management Center (MMC) in the Zhejiang Provincial People’s Hospital from April 2020 to December 2020 were enrolled in this study. The participants were divided into two groups based on visceral obesity. Thyroid function, thyroid associated antibody and other metabolic indicators were measured by blood tests. The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured by bioelectrical impedance analysis.ResultsThere were 185 participants (47.4%) had visceral obesity. The positive rate of TPOAb was significantly higher in T2DM patients with visceral obesity (12.97% vs 5.37%, p < 0.01). Free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) were both significantly higher in T2DM patients with visceral obesity (p < 0.05). The increased TPOAb titer was significantly positively correlated with visceral fat area (r = 0.175, p < 0.01). Binary logistic analysis showed that the positive rate of TPOAb was associated with an increased risk of visceral obesity [(OR) 4.258, 95% confidence interval (CI) 1.594, 11.375, p = 0.004].ConclusionTPOAb-positive is more common in T2DM patients with visceral obesity, which has some effects on visceral obesity independent of thyroid function. This suggests that elevated TPOAb titer is a predictor of visceral obesity in T2DM patients.

S1639 Type I Autoimmune Pancreatitis—A Rare Cause of Acute Pancreatitis

Introduction: IgG4-related disease (IgG4-RD) is a clinical entity characterized by multi-organ lymphoplasmacytic infiltration with IgG4 positive plasma cells that results in fibrosis. Type I autoimmune pancreatitis (AIP), one of the manifestations of IgG4-RD, is a rare cause of acute pancreatitis and it has different prognostic and therapeutic implications from other etiologies of pancreatitis. Case Description/Methods: A 27-year-old morbidly obese male presented with nausea, bilious emesis, epigastric pain and non-bloody diarrhea for 4 weeks. Exam revealed papules throughout the body, lower extremity edema and brown stool on rectal exam. Patient had severe anemia (Hg 4.6 g/dL), hyperkalemia (6.6 mmol/L), uremia (BUN 247 mg/dL), elevated creatinine (33.04 mg/dL) and lipase (1,164 U/L) levels. He also had elevated TSH (7.37 uIU/mL), decreased free T4 (0.61 ng/dL) and mildly elevated thyroid peroxidase antibody level (43.6 IU/mL). Alkaline phosphatase, total bilirubin and transaminases were normal.US and CT abdomen showed cholelithiasis without intra/extra hepatic ductal dilation and acute pancreatitis, respectively. In the absence of biliary tract obstruction, alcohol use and with normal triglyceride levels, AIP was suspected. IgG level was elevated (2305 mg/dL) with elevated IgG4 subclass (229 mg/dL) supporting the diagnosis of type 1 AIP. Diagnosis was confirmed with kidney biopsy showing diffuse TIN with lymphoplasmacytic cells positive for IgG4; other autoimmune work up including C3, C4, ANA, ds-DNA, ANCAs was negative. The patient improved with Methylprednisolone and Rituximab therapy. He was referred for kidney transplant and continues to require hemodialysis. Discussion: IgG4-RD is an autoimmune disease with multi-organ involvement and eventual fibrosis.Type I AIP can be diagnosed based on the presence of HISORt criteria; these include histologic, imaging, serologic, other organ involvement and response to glucocorticoid therapy. In our patient, elevated IgG4 level, renal biopsy and response to steroids confirmed the etiology of Type I AIP. Organs affected included kidneys (TIN), thyroid gland (Hashimoto’s thyroiditis), pancreas (AIP type I), lymphatics and skin. This case not only serves an important purpose of demonstrating the heterogeneity of IgG4-RD, but also, stresses the importance of appropriate diagnosis because AIP often can be confused with pancreatic malignancy, which, if incorrectly diagnosed, would alter the management significantly.Figure 1.: Markedly Increased Interstitial Plasma Cells Seen on H&E stain (400x) on Renal Biopsy.Figure 2.: Immunohistochemistry Stain of Renal Biopsy Staining Positive for IgG 4.

Comparison of diagnostic performance of thyroid autoantibodies and high-resolution ultrasound in euthyroid Hashimoto's thyroiditis

Objective: To compare the diagnostic performance of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and high-resolution ultrasound (HRUS) in euthyroid Hashimoto's thyroiditis (HT). Methods: From January 2016 to January 2019, patients with complete data of preoperative thyroid function, TPOAb, TgAb and HRUS who had undergone thyroid surgery treatment at the First Affiliated Hospital with Nanjing Medical University were reviewed. The diagnostic value of different diagnostic methods was compared using histopathology (HP) examination result as the gold standard. Results: The data of 792 patients (217 males and 575 females) was retrospectively collected. The M(Q1,Q3)of patients' age was 41(32,52)years and the range was 16-75 years. With HP as the diagnostic gold standard, TPOAb exhibited similar sensitivity (59.3% vs 61.2%, P=0.752), accuracy (85.0% vs 83.6%, P=0.379), area under the receiver operating characteristic curve (AUC) (0.767 vs 0.764, P=0.886) and higher specificity (94.2% vs 91.6%, P=0.033) when compared with TgAb in diagnosing euthyroid HT. They both exhibited a higher sensitivity (59.3% vs 44.5%, P = 0.002; 61.2% vs 44.5%, P<0.001), accuracy (85.0% vs 79.7%, P = 0.001; 83.6% vs 79.7%, P = 0.013) and AUC (0.767 vs 0.684, P<0.001; 0.764 vs 0.684, P<0.001) than HRUS. Compared with each method alone, the sensitivity and AUC of TPOAb combined with TgAb or HRUS were improved. The combination of three methods showed the greatest sensitivity. Concordance analysis demonstrated that TPOAb and HP had a moderate agreement (Kappa=0.580, 95%CI:0.513-0.647,P<0.001). Conclusions: The combination of thyroid antibodies, TPOAb and TgAb, can improve sensitivity, accuracy and AUC of diagnosis in euthyroid Hashimoto's thyroiditis. The two antibodies combined with HRUS exhibited the highest diagnostic performance. Elevated TPOAb showed moderate diagnostic consistency with histopathologic evidence of HT.

26966 Tofacitinib treats unresponsive vitiligo and elevated thyroid peroxidase antibodies

A 56-year-old female presented with expanding vitiligo to 35% total body surface area (TBSA) despite treatment with alpha lipoic acid, vitamin C, vitamin E, polypodium leucotomus, topical pimecrolimus, narrowband ultraviolet B, and excimer laser for 2 months. Past medical history was pertinent for Hashimoto thyroiditis treated with levothyroxine with normal levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4), psoriatic arthritis, alopecia, and localized psoriasis on the elbows. Notably, lab tests confirmed normal levels of serum TSH and FT4 but elevated thyroid peroxidase antibodies (TPO) of 795 and elevated thyroglobulin antibodies (TG) of 3. Her endocrinologist denied necessity of treating patients for elevated TPO but stated that patients were only treated with increased dosages of levothyroxine. Because of reported case reports of success in treating vitiligo and FDA-approval for psoriatic arthritis, tofacitinib 5 mg (Tofa) twice daily (BID) was added to the treatment regimen. Serum levels of TPO and TG normalized within 1 month, with simultaneous improvement in vitiligo. Because of gastrointestinal side effects after BID dosing for 5 months, Tofa was decreased to once daily, with continued vitiligo repigmentation. By then, vitiligo had decreased to 12% TBSA, with accompanying improvement in alopecia, psoriatic arthritis, and psoriasis. This case suggests that unstable vitiligo may be associated with elevated TPO and TG, because of a disregard of endocrinologists to treat elevated antibodies, and should be tested in patients with unresponsive vitiligo. Tofacitinib may ameliorate vitiligo not only as a Janus kinase inhibitor but also through an effect on TPO and TG.

28131 Hashimoto thyroiditis associated with unilateral Graves ophthalmopathy

Thyroid-associated orbitopathy (TAO) is caused by T-cell activation of retro-ocular fibroblasts and autoantibodies against thyroid-stimulating hormone receptor (TSHR) leading to accumulation of glycosaminoglycans and inflammation. The condition can present with soft tissue inflammation, proptosis, restrictive myopathy, and optic neuropathy. Although typically associated with Graves disease, TAO is occasionally seen in Hashimoto thyroiditis. We report a case of TAO presenting with unilateral periorbital edema in a patient with Hashimoto disease. A 63-year-old female with hypothyroidism was referred to our dermatology clinic by the ophthalmology service with a 2-year history of persistent and progressive right-sided nontraumatic periorbital swelling, associated with blurry vision, pain upon eye movement, and facial paresthesia. The patient was treated with high-dose systemic corticosteroids and radiotherapy for suspected Graves ophthalmopathy with partial response. Physical examination was remarkable for right-sided erythema and edema of the upper and lower eyelids. Skin biopsy revealed a superficial and deep lymphocytic infiltration with mucin. An orbital CT scan revealed right-sided hypertrophy of the medial rectus muscle and proptosis. Laboratory findings demonstrated elevated thyroglobulin, thyroid peroxidase, and TSHR antibodies. TSH and free T4 levels were normal. Clinicopathologic correlation supported a diagnosis of TAO in the setting of Hashimoto disease. TAO affects 2-5% of patients with Hashimoto thyroiditis. As seen in our patient, asymmetrical ophthalmopathy may be present, and in fact, these symptoms may precede endocrine manifestations. Prompt recognition and management of this condition may spare permanent neurological damage, including vision loss.

Unraveling the Role of Hypothyroidism in Non-alcoholic Fatty Liver Disease Pathogenesis: Correlations, Conflicts, and the Current Stand.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver diseases globally. Because thyroid hormones play a crucial role in lipid metabolism, thyroid dysfunction has been implicated in NAFLD pathogenesis in the past decade, with hypothyroidism-induced NAFLD being regarded as a distinct disease entity. However, there has been no common consensus yet, and several studies have found contradictory results. Hence, we conducted this systematic review to represent the current view on the role of hypothyroidism (HT) and individual thyroid function parameters such as thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in NAFLD pathogenesis. We searched PubMed, PubMed Central, and Semantic Scholar databases from inception until January 2021 to identify relevant observational (case-control, cross-sectional, and longitudinal) studies. A total of 699 articles were recognized through our database search. After applying the eligibility criteria and performing quality assessment, 10 studies involving 42,227 participants were included in the final systematic review. Each of these studies assessed different thyroid function parameters, and NAFLD was found to be associated with HT in two studies, elevated TSH in three studies, suppressed T4 in three studies, elevated T3 in one study, and elevated TPOAb in one study. There was also a wide heterogeneity in HT definition, study population characteristics, and study design among these studies, making a direct comparison difficult. Because the recognition of HT-induced NAFLD has possible diagnostic, therapeutic, and prognostic implications, we recommend that comprehensive, long-term prospective studies be carried out to determine if HT or thyroid function parameters are causally associated with NAFLD.

Case Report: Primary Hypothyroidism Caused by Autoimmune Thyroiditis in Infancy Requires Early Intervention

Abstract Background: Primary hypothyroidism due to autoimmune thyroiditis is extremely rare in infants, especially under the age of 3 years. For infants, hypothyroidism is most commonly congenital, originating from thyroid dysgenesis with an absent, ectopic, or hypoplastic thyroid gland (1 in 4,000 live births). If left untreated, it can lead to permanent neurodevelopmental deficits. In this report, we describe a male infant who was diagnosed with Hashimoto thyroiditis at 18 months of life, providing a learning example to aid in recognition of this rare disease and enable timely intervention. Clinical Case:Patient was a 2,765 gram, appropriate for gestational age, male born at term with hypospadias of the penis (surgical correction at 11 months). Patient passed meconium in the first 24 hours of life. During the first few months of life, patient developed constipation. Patient had amblyopia necessitating eye patching and began to wear eye glasses at 18 months of life. Patient’s linear and weight growth were within normal limits. Patient had normal motor development, however had language development delay. No known family history of thyroid disease. Screening labs performed at 17-months of age showed abnormal thyroid function: elevated TSH at 14.86 µIU/mL (ref: 0.45 - 4.50 µIU/mL) and normal free T4 level at 1.24 ng/dL (ref: 0.85-1.75 ng/dL). Repeat testing at 18 months of age continued to show elevated TSH at 6.18 µIU/mL (ref: 0.64 - 4.00 µIU/mL), normal free T4 at 1.07 ng/dL (ref: 0.88 - 2.03 ng/dL), and elevated thyroid peroxidase (TPO) antibodies at 163 IU/ml (ref: &amp;lt;35 IU/ml). At 21 months of age, patient was initiated on L-thyroxine therapy for elevation of TSH (9.570 µIU/mL; ref: 0.64 - 4.00 µIU/mL) and free T4 was normal (1.03ng/dL; ref: 0.88 - 2.03 ng/dL). Notably, the newborn screen for hypothyroidism was within normal limits, suggesting chronic autoimmune thyroiditis instead of congenital thyroid dysgenesis. Conclusions: This case report provides insights into autoimmune thyroiditis in infancy, which, although especially rare under age 3 years, should be considered in infants who present with autoimmunity or abnormal thyroid testing. In the neonatal period, infants’ immune systems are learning to discriminate requirements for self-tolerance versus protection against pathogens and may be more prone to infections. Although autoimmunity in this stage of development is uncommon, there can be breakthroughs in tolerance, as seen in this case. In addition to this patient, two other infants were seen with elevated TPO antibodies, diagnosed at 17 and 31 months old, with similar clinical trends. There remains a need for additional studies providing further insights into autoimmunity in infancy. Importantly, this case illustrates that, when infants have abnormal thyroid levels (with or without other autoimmune conditions), consideration should be made for anti-thyroid antibody testing.

Palpitations and Fatigue Post COVID: A Harbinger of Silent Thyroiditis!

Background: Subacute thyroiditis is a self-limiting condition brought about by an inflammatory reaction often linked to a recent viral infection. SARS-COV2 (COVID-19), an RNA coronavirus that started a global pandemic in December 2019 has been linked mostly to severe acute respiratory distress syndrome. However, there have been increasing reports of its effect on other organ systems. We present a case of a 32-year-old female recovering from COVID-19, only to develop silent thyroiditis afterwards. Clinical Case: A 32-year-old female with anxiety disorder but otherwise in excellent health was diagnosed with COVID-19 via nasal swab RT-PCR after experiencing low grade fever and cough. She quarantined at home and was on her way to recovery when, a few weeks later, she began to experience increasing bouts of chest pain with no relation to activity, intermittent headaches and lower extremity edema. This prompted her to visit the emergency department. Work-up done at that time was unremarkable and her symptoms were attributed mostly to anxiety. She was advised to follow-up as an outpatient with a cardiologist. One month later, due to the persistence of her fatigue, low exercise tolerance and tremors, she decided to seek consult with a cardiologist. An electrocardiogram done during that visit showed normal sinus rhythm with poor-R wave progression and early repolarization changes. Both the echocardiogram and 24-hour Holter monitoring, which were subsequently done, were unremarkable. Blood work-up, however, revealed a significantly low thyroid stimulating hormone (TSH) level of 0.17 mU/L, for which she was referred to an endocrinologist. A month later, she sought consult with an endocrinologist. Thyroid gland was non-tender on palpation. Repeat blood work-up showed an elevated TSH level (23.50 mU/L) with a low Free T4 (0.42 ng/dL) and an elevated thyroid peroxidase antibody (TPO-Ab) level (900 mU/mL), indicative of subacute thyroiditis, but without associated neck pain. Thyroid sonography done showed diffusely heterogeneous thyroid lobes with no evidence of a dominant mass or nodule. A decision was made to start her on low dose levothyroxine. Two months into treatment, she underwent repeat thyroid hormone levels. Normal TSH and normal free T4 were observed. However, TPO-Ab was still elevated. It was decided to continue her therapy for one more month before gradually tapering her levothyroxine dose. She was told to follow-up in a month for further monitoring. Conclusion: Subacute thyroiditis associated with COVID-19 infection has become a more common occurrence as more cases of COVID-19 are noted worldwide. Our patient followed the usual course of subacute thyroiditis, initially presenting with a thyrotoxicosis phase which typically lasts 4-10 weeks, then subsequently developing hypothyroidism, inadvertently needing thyroid hormone replacement. What made this case more intriguing was that she did not have severe anterior neck pain, the classic clinical presentation of subacute thyroiditis. While there is a very strong association between COVID-19 and respiratory failure, there is paucity of evidence linking COVID-19 to dysfunction of other body systems. This case of thyroiditis presenting post COVID-19 illness, buttresses the versatility of COVID-19. Physicians should keep this in mind when evaluating a COVID-19 survivor who continue to present with persistent tachycardia or palpitations with or without anterior neck pain even after a month or two from infection. Routine follow-up TSH assay on COVID-19 survivors may be a valuable consideration.

Coexistence of Thyroid Hormone Resistance and Autoimmune Thyroid Disease: Not a Mere Coincidence

Introduction: The coexistence of thyroid hormone resistance and autoimmune thyroiditis was initially thought to be a chance event. In a large cohort study, Barcoff et al. demonstrated an increased likelihood of thyroid autoantibodies in patients with thyroid hormone resistance (RTH). We report a unique case to epitomize the coexistence of these two conditions and discuss the postulated mechanisms.Clinical Case: A 22-year-old woman with a history of Hashimoto’s thyroiditis, attention deficit hyperactivity disorder, and migraine presented to the endocrinology clinic with symptoms of weight loss, fatigue, decreased appetite, and heat intolerance for 4 months. She was diagnosed with Hashimoto’s thyroiditis at age 12 with elevated TSH only and had been on levothyroxine 25 mcg since diagnosis. Physical exam demonstrated a body mass index of 34.14 kg/m2, blood pressure of 138/91 mmHg, pulse of 77 bpm, and an enlarged palpable thyroid gland. Laboratory investigations revealed elevated thyroid peroxidase (TPO) antibody at 234 IU/mL (<9) and thyroglobulin Antibody at 3 IU/mL (<1) with elevated free T4 of 3.76 ng/dL (0.61-1.36), elevated total T4 of 21.58 mcg/dL (6.09-12.23), increased T3 uptake of 51.2% uptake (32-48.4), and upper normal TSH of 3.99 uIU/mL (0.44-5.33). Elevated free T4 was confirmed by the equilibrium dialysis method at 6.2 ng/dL (0.9-2.2) with upper normal TSH at 3.77 uIU/mL. Thyroid ultrasound demonstrated thyromegaly and hypervascularity of the gland. TSH secreting pituitary adenoma was ruled out with a normal alpha subunit of 0.2 ng/ml (0.1-0.6) and molar ratio of the alpha subunit to TSH ratio <1 along with a normal pituitary MRI. She was not taking other medications or supplements. She was diagnosed with thyroid hormone resistance and is undergoing genetic testing to differentiate the THRB genetic mutations from Non-TR-RTH. Her symptoms improved after discontinuing her levothyroxine.Clinical Lesson: Our case highlights the importance of evaluating thyroid disorders properly before starting treatment and illustrates the coexistence of autoimmune thyroiditis with thyroid hormone resistance. Barcoff et al. demonstrated that there was an increased likelihood of thyroid autoantibodies with odds ratio = 2.36 (p = 0.002) in a large patient cohort with RTH, compared to their unaffected first-degree relatives. However, since there was no correlation in increased antibody with increased age and the duration of the disease, the proposed hypothesis did not substantiate chronic TSH stimulation inducing autoimmune response. The proposed mechanism is that the elevated TSH in RTH stimulates the immune system at the TRα level which was demonstrated in murine models with increased activation of thymic function in correlation with TSH level. More research is needed to understand the underlying mechanism of their coexistence.

A Rare Case of Massive Pericardial Effusion as the First Presentation of Hashimoto’s Hypothyroidism With Complete Resolution With Levothyroxine Treatment - A Case Report

Introduction: Hypothyroidism is a common endocrine disorder with multi-system involvement, with prevalence rate of 4.6% among the U.S. population. Clinical manifestations of hypothyroidism can vary widely from subclinical condition to multi-organ failure. One of the rare but serious complications of hypothyroidism is pericardial effusion (PE). To our knowledge, there are few case reports of PE secondary to hypothyroidism. We report a case of massive PE without tamponade secondary to hypothyroidism. Case Presentation: 52 year old obese male presented to the hospital with worsening dyspnea, dry cough, chest discomfort and lower extremity edema for 2 months. He was in mild respiratory distress, and afebrile. He had myxedematous facies, with dry skin. Thyroid gland was palpable. He was noted to have distant heart sounds and bradycardia with lower extremity edema and delayed deep tendon reflexes. Chest X-ray showed marked cardiomegaly suggestive of pericardial effusion. Laboratory testing was noted for elevated thyroid stimulating Hormone 55.9 mU/L, Low T4F <0.07 mU/L, low T3F 1.0 mU/L, and elevated Thyroid peroxidase antibodies of 520 IU/ml. Troponin-I, BNP, and D-Dimer were normal. Echocardiography showed left ventricular ejection fraction of 50%, and a large, free-flowing pericardial effusion >2 cm with focal strands. Patient was given intravenous Levothyroxine 100 mcg once, then was started on oral Levothyroxine 75 mcg daily. No pericardiocentesis was done. Patient was discharged and followed up after 6 month of treatment with resolution of his symptoms, facies, and pericardial effusion. Discussion: Hypothyroidism is predominant worldwide with reported prevalence rates of 5–10% in women and 1–3% in men. Common symptoms include: fatigue, cold intolerance, and constipation. Cardiovascular involvement is less common. Small PE has been reported in 10-30% of cases. Severe PE -with or without tamponade- is a very rare complication and is only linked to severe degrees of myxedema. A recent study evaluating 70 newly diagnosed adult hypothyroid patients showed mild PE prevalence of 17%, with moderate PE seen in only 1 patient (0.01%). Severe PE or tamponade was not observed in this cohort. The development of PE secondary to hypothyroidism is not well understood. Increased systemic capillary permeability and decreased lymphatic drainage of albumin which leads to increased pericardial colloid pressure are proposed mechanisms for hypothyroid PE. Most of hypothyroidism clinical symptoms can be reversed with thyroid hormone replacement within 1-15 months. Pericardiocentesis is reserved for symptomatic patients despite treatment, patients with tamponade or with persistent PE for more than 3 months. Our case sheds light on a rare, yet, serious complication of hypothyroidism, most likely explained by low socio-economic status. Hence the importance of patient education and proper follow up.