Low TSH Research Articles

Advanced glycation end products and their soluble receptor (sRAGE) in patients with Hashimoto's thyroiditis on levothyroxine substitution.

Advanced glycation end products (AGEs) are heterogenous group of irreversible chemical moieties originated from non-enzymatic glycation and oxidation of proteins, nucleic acids, and lipids. The engagement of AGEs with their chief cellular receptor (RAGE) activates a myriad of signaling pathways contributing to the progression of chronic diseases like autoimmune thyroiditis, type 2 diabetes mellitus and its complications. Soluble RAGE (sRAGE) prevents AGE-RAGE interaction in a competitive manner. We investigated the association between serum AGE, sRAGE and thyroid function in 73 Hashimoto thyroiditis patients (HT) on levothyroxine substitution, and in 83 age, BMI and gender-matched healthy controls. The serum AGEs levels were determined by autofluorescence on a multi-mode microplate reader, and the serum sRAGE levels by ELISA method. Mean AGE level was lower (10.71 vs 11.45 AU/µg protein; p=0.046), while mean sRAGE level was higher (923 vs 755 pg/mL; p<0.0005) in the serum of HT patients than the controls. AGE correlated with age, while sRAGE correlated negatively with BMI in both groups. We found negative correlation between AGE and fT3 levels (r=-0.32; p=0.006) and sRAGE and TSH levels (r=-0.27; p=0.022) in HT patients, while we failed to find association between AGE, sRAGE and parameters of thyroid function in the control group. Median AGE/sRAGE ratio was lower in HT patients than in controls (2.4, IQR 1.9 - 3.1 vs 3.3, IQR 2.3 - 4.1 AU/pg; p < 0.001). In HT patients, the AGE/sRAGE ratio correlated positively with BMI and correlated negatively with fT3. According to our results in HT patients lower TSH and higher fT3 levels within the reference range is accompanied by a favorable AGE/RAGE balance. Further investigations are needed to confirm these results.

Challenging Thyroid Cases in Clinical Practice

Thyroid disorders are prevalent, and their manifestations are divergent and sometimes it is very challenging to diagnose and deal with some Thyroid cases in clinical practice. Here seven different challenging cases will be discussed that will help clinicians to diagnose and treat such cases in dayto- day clinical practice. First case enlightened us that Thyroid function should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction, since there are many other factors in acutely or chronically ill euthyroid patients that influence thyroid function tests. The second case taught us that there is assay interference with Biotin ingestion and patients taking Biotin should hold the supplement for two days prior to assessing thyroid function. Subacute thyroiditis is a self-limiting inflammatory condition of the thyroid gland and COVID-19 virus infection may be associated with subacute thyroiditis as a complication that may occur in patients without any previous thyroid disorder that is revealed in third case. In Secondary hypothyroidism/Hypopituitarism, TSH may be low, normal, or even slightly elevated due to inactive TSH isoform in blood. The fourth case shows us that only TSH testing in clinical practice leads to missing Secondary hypothyroidism/Hypopituitarism. Learning from fifth case is that during monitoring of thyrotoxic patients taking ATDs, serum TSH may remain suppressed for several months after starting therapy and it is therefore not a good parameter for monitoring therapy early during treatment, rather we should rely on FT4 and FT3. The sixth case enlightened us that in case of low TSH in early pregnancy, Gestational transient Thyrotoxicosis should be excluded which is commonly associated with hyperemesis gravidarum with no prior history of thyroid disease, no stigmata of Graves’ disease (Goiter, ophthalmopathy) and a self-limited mild disorder. In poorly compliant patients, there may be a combination of high FT4 and high TSH that is revealed in the seventh case. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 189

A Case Report of COVID-19 and Subacute Thyroiditis in Fars, Iran

Background &amp; Objective: COVID-19 can affect thyroid gland and causes subacute thyroiditis.&#x0D; Case Presentation: We introduced a 60-year-old woman with an initial symptom of anterior cervical pain without any other constitutional symptoms. Nasopharyngeal and oropharyngeal swabs were detected positive for COVID-19 using RT-PCR assay. According to ultrasonographic, laboratory (lowered TSH, elevated CRP and ESR), and physical findings, subacute thyroiditis was found following the SARS-CoV-2 infection.&#x0D; Conclusion: As subacute thyroiditis associated with SARS-Cov-2 may be represented without any fever, ruling out this infection in these patients is considerable.

The Etiology of Abnormal TSH in Veterans Cared by a VA Medical Center – One High Serum Thyrotropin is Associated with Higher 5-Years Mortality

Objective: By analyzing the etiology of abnormal TSH in randomly selected veteran patients, we set our heart on improving future clinical care/management of the clinical/subclinical hyper- and hypothyroidism in the aging veteran population. Methods: A total of 1100 patients’ charts in alphabetical order were selected. Excluded cases of insufficient information, 897 patients’ charts were reviewed and analyzed for causes of abnormal TSH. Among them, 602 for the cause of low TSH (below 0.55 uU/mL) and 295 for high TSH (above 4.78 uU/mL) were reviewed retrospectively. Findings: Among the 1100 patients selected, 680 (61.8%) were 60 y or older (female=44, 6.8%); 420 were under 60 y (female=80, 19.0%); significantly more female patients were found in the younger age group (P&lt;0.001). After excluding patients with insufficient data, the most common cause of suppressed TSH is iodine-induced, CT iodinated contrast and betadine use caused 35.0% in the older group (n=126) compared to 23.6% in the younger group(n=57) (P = 0.027). The significant difference is that older veterans received more contrast CTs (P &lt; 0.05 compared to the younger group). In both age groups with concurrent FT4 study, we found four high FT4 among 90 studies, 4.4% overt hyperthyroidism. The second most common cause of suppressed TSH is due to thyroid hormone (TH) replacement in the older group (119 patients, 33.1%) with age &gt; 60y, significantly more frequent compared to the younger group, P&lt;0.001. There is significantly more overt hyperthyroidism, 27.8/%, than the iodine-load induced suppression of TSH, P&lt;0.001, due to 17 patients on TSH suppression therapy after total thyroidectomy for thyroid cancer. Among the 295 patients with elevated TSH, the most common cause of high TSH was due to hypothyroidism on T4 replacement: a total of 128 (59.3%) in the older group (N=216) is, similar to 47 (59.5%) in the younger group (N=79). In both age groups, there were 139 patients with concomitant FT4 measurement; 17 overt hypothyroidism were found, 12.2%. No significant difference is seen in the two age groups. The next most common causes of elevated TSH are CT contrast infusion, 23 (10.6%) in the older group and 7 (8.9%) in the younger group. We find high TSH is associated with a higher death rate of 101/238 (42.4%) in a 5-year follow-up (from 2016 to 2021), as compared to low TSH of 68/238 (28.6%), in the older age group, p&lt;0.03； both were significantly higher than the age- and sex-matched general US population, 19.7%, P&lt;0.01. Conclusion: Even though most, ~ 90%, were subclinical, the suppressed and elevated TSH are associated with severe consequences in CV/CNS and immune-suppression complications in aging veterans. Therefore, cautious use (and more frequent check of TSH) of TH replacement and CT contrast in aging veterans is recommended. The alarming increase in the 5-year death rate in older patients with elevated TSH deserves further study.

Abstract #1412763: Hustle for The Muscle: A Rare Case of Non-traumatic Rhabdomyolysis Secondary to Thyrotoxicosis

Rhabdomyolysis (RM) is a rare potentially life-threatening condition characterized by breakdown of striated muscle which can lead to progressive acute kidney injury. Common etiologies include trauma, infection, drugs, or surgery. Rarely, endocrinopathies including thyrotoxicosis have been associated with RM. Here, we present a case of non-traumatic and non-exertional RM secondary to thyrotoxicosis. A 50-year-old man recently diagnosed with Graves’ disease a month ago presented to the hospital with fever for 3 days. A week prior to presentation, thyroid function tests (TFT) showed normalizing FT4 (1.13ng/dL) and T3 (112ng/dL) levels with low TSH (<0.005ulU/m) which prompted his endocrinologist to decrease the methimazole dose from 20mg thrice daily to 10mg once daily. His fever was associated with nausea, vomiting, chills, and non-bloody diarrhea. On admission, the following vital signs were obtained: temperature 101.6F, blood pressure 140/85 mmHg, pulse rate 108 bpm, respiratory rate 16 bpm, and oxygen saturation 99% on room air. He was found to be alert, conscious, and coherent. Physical examination was notable for exophthalmos, absence of jugular vein distention, diffusely enlarged non-tender thyroid, clear breath sounds, no jaundice, and no peripheral edema. His calculated Burch-Wartofsky score was 40. Laboratory evaluation showed leukocytosis, elevated FT4 (4.01ng/dL), elevated FT3 (5.87pg/mL), and low TSH (<0.015uIU/mL) levels. He was also found to have acute kidney injury with creatinine of 1.33 mg/dL associated with hemoglobinuria. Further testing revealed a significantly elevated creatinine kinase (CK) at 98,760 U/L. On imaging, chest x-ray and CT scan were consistent with left lower lobe pneumonia. During the hospital stay, the patient was treated with methimazole 20mg daily together with antibiotics, aggressive hydration, and propranolol. His kidney function initially rapidly worsened but eventually improved as the CK levels normalized. FT4 levels were monitored and it gradually trended back to normal after 5 days. He was discharged stable and advised to follow up with his endocrinologist after a week. This is a case of a thyrotoxicosis complicated by rapidly worsening renal function. With a markedly elevated CK level accompanied by hemoglobinuria, absence of trauma or physical exertion, patient developed a concomitant non-traumatic RM. Non-traumatic RM is a rare complication of thyrotoxicosis and/or hyperthyroidism. Due to increased metabolic rate and energy consumption, rapid depletion of myocyte energy storage and substrates escalates, ultimately leading to necrosis. Based on literatures, only four cases were reported regarding the similar condition. In these cases, CK levels reported was less than 10 times the normal range. Our patient is unique that without history of trauma or exertion, a non-traumatic, non-drug-induced rhabdomyolysis transpired in the setting of acute thyrotoxicosis, with CK levels almost 580 times the upper normal limit. Management wise, aggressive hydration remains the treatment of choice to provide adequate renal perfusion and prevent renal damage.

Abstract #1402123: A Rare Case of Hypophysitis with Isolated ACTH Deficiency and Thyroiditis Complicating Treatment with Pembrolizumab

Immune checkpoint inhibitors (CPIs) have been shown to be beneficial in the treatment of cancers by enhancing antitumor immunity. CPIs block intrinsic down regulators of immunity, such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand programmed cell death ligand 1 (PD-L1). While useful for targeting malignant tissue, CPIs can have destructive effects on normal tissues, including endocrine organs. Hypophysitis is more common in those receiving anti-CTLA-4 therapy (up to 10% of patients) than those receiving anti-PD1-therapy (<1% of patients) whereas the opposite stands true for thyroiditis. We present a rare case of a woman with breast cancer treated with the anti-PD-1 therapy pembrolizumab who developed isolated ACTH deficiency from hypophysitis along with thyroiditis. A 39-year-old female with breast cancer treated with pembrolizumab presented with several weeks of fatigue and confusion. On exam, she was well-appearing and normotensive. Cortisol and TSH were found to be low at <0.1ug/dL and <0.01uIU/mol, respectively, raising concern for central adrenal insufficiency and hypothyroidism. Free T4 and free T3 were high indicating the low TSH was from primary thyroid rather than pituitary dysfunction. Cosyntropin stimulation test showed an insufficient rise in cortisol to 1.7ug/dL, which, along with an inappropriately normal ACTH of 9.9pg/mL, confirmed the diagnosis of central adrenal insufficiency. Sellar MRI revealed no abnormalities. Adrenal insufficiency was treated with hydrocortisone. Hyperthyroidism quickly transitioned to hypothyroidism, supporting a diagnosis of thyroiditis, which was treated with levothyroxine. Pembrolizumab was stopped and later resumed once clinical symptoms were stabilized while on the hormonal therapy. CPIs have been associated with a variety of immune mediated adverse endocrine events, including hypophysitis, primary thyroid dysfunction, autoimmune diabetes, and adrenalitis. Although thyroiditis is the most commonly reported adverse endocrine event associated with anti-PD-1 therapy, other adverse events can occur, including hypophysitis rarely. While the diagnosis of hypophysitis can be supported by sellar changes on MRI, it is important for clinicians to be aware that hypophysitis in those on anti-PD1 therapy may lack classic MRI changes. As the endocrine dysfunction can be life-threatening and symptoms often overlap with those of malignancy and related treatments, a high index of suspicion is necessary to ensure prompt diagnosis and treatment. In addition, screening for endocrine dysfunction is recommended in all patients receiving CPIs.

Abstract #1406850: Prevalence of Primary and Sub-clinical Hypothyroidism and Impact of Metformin on Thyroid Hormones in Patients with Type 2 Diabetes Mellitus in a Tertiary Care Hospital in Kashmir

Diabetes mellitus and hypothyroidism are the commonest endocrine disorders worldwide and tend to coexist and mutually influence each other. We aim to determine the prevalence of overt (OH) and subclinical hypothyroidism (SCH) and impact of metformin on thyroid hormones in patients with type 2 diabetes mellitus (T2DM). In this cross-sectional observational study, 257 adult patients of T2DM enrolled were evaluated for thyroid dysfunctions by testing thyroid profile. The levels of fT3, fT4, serum TSH, and anti-TPO antibody were estimated by chemiluminescent micro-particle immunoassay (CMIA). The correlation analysis of prevalence of thyroid disorder with age distribution, gender distribution, BMI, duration of diabetes and glycated hemoglobin (HbA1C) was done. The mean age in our study was 56.3±7.82 (28-74) years with female to male ratio of 1.62:1(159 females vs. 98 Males). The mean (± SD) duration of diabetes HbA1c of the study cohort was 6.7±2.19years and 8.1±2.53% respectively. The prevalence of OH and SCH was 7.4% (Female vs. Male; 10.7% vs. 2%; p=0.013) and 12.1 % (Female vs. Male; 15.7% vs. 6.1%; p=0.021) respectively. The prevalence of anti-TPO positivity was 94.7%, 51.6%and 10.6% in OH, SCH and euthyroid patients respectively. The prevalence of hypothyroidism and subclinical hypothyroidism was higher in patients of female gender, age >60 years, long duration and uncontrolled diabetes. Among 257 patients, 63% (n=163) patients were on metformin. The mean TSH of patients who were on metformin was significantly lower (1.34±0.95 vs. 3.19±1.41; p < 0.001). However, the mean free T4 and free T3 levels were not significantly different between the two groups. There is high prevalence of hypothyroidism especially subclinical hypothyroidism in diabetic patients. Patients on metformin therapy had significantly lower TSH levels. Screening for thyroid dysfunction among patients with diabetes mellitus should be routinely considered for early diagnosis and effective management.

Abstract #1404976: Severe Gestational Thyrotoxicosis Complicated by Thyroid Storm in a Primigravid Patient with Hyperemesis Gravidarum in a Multiple Pregnancy

Gestational transient thyrotoxicosis (GTT) is seen in 3% of pregnancies and occurs in 30-60% of patients with hyperemesis gravidarum (HG). The incidence of thyroid storm in this setting has not yet been reported. The severity of GTT and HG is positively related to serum hCG levels. Treatment in GTT with antithyroid drugs is not routinely indicated since GTT usually is described as a disorder of spontaneous resolution without unfavorable maternal and fetal outcomes. We describe a case of severe GTT complicated by thyroid storm in a primigravid 20-year-old patient with twin gestation and HG. A 20-year-old female primigravida with twin gestation and HG presented with nausea, vomiting, altered sensorium, and weakness for four days at 14 weeks’ gestation. At 9 weeks’ gestation during inpatient management for HG, TSH < 0.01 was found. Outpatient FT4 3.1 was obtained. On current presentation, tachycardia HR 169 bpm, mild abdominal tenderness, disorientation, a repeated TSH < 0.01 resulting in Burch-Wartofsky point scale of 45 warranted MICU admission for thyroid storm management. FT4 3.3, T3 239, and hCG level 99,080 were found. Transvaginal US and positive MSSA blood cultures confirmed spontaneous septic abortion. Antibiotics were given, and dilation and evacuation were performed. FT4 and T3 improved to 2.1 and 114, respectively. TSH receptor antibody (TRAb) was found negative and thyroid US did not reveal hypervascularity or nodules. Post admission TSH 0.544 and FT4 1.02 were found. The association between HG and thyrotoxicosis was made in 1980 by Valentine et al. Estrogen and hCG levels are significantly higher in women with HG, leading to increased thyroid hormone secretion and lower TSH levels. GTT resulting from inappropriate hCG secretion is a common form of hyperthyroidism in HG. GTT usually is described as an entity with spontaneous resolution as thyroid hormones normalize by the second trimester. Treatment for GTT with antithyroid drugs is not routinely indicated and they are reserved for a minority of patients with extremely severe GTT. Fasting, hydration, and evaluation of thyroid function are recommended as the most appropriate management for GTT in HG. Genetic mutations changing lysine into an asparagine leading to an increased sensitivity of TSH receptor to hCG ultimately causing severe and prolonged GTT have been found. TRAb is recommended as a more sensitive and specific diagnostic tool to differentiate GTT and Graves’ disease. However, physiological immunosuppression tends to suppress the TRAb levels during pregnancy. Comparative follow-up studies are required to establish a final diagnosis.

A Curious Case of Cocaine-Induced Hypokalemic Periodic Paralysis Mimicking Guillain-Barre Syndrome (P10-5.003)

<h3>Objective:</h3> To describe a rare cause of progressive ascending paralysis resembling Guillain-Barre Syndrome (GBS). <h3>Background:</h3> Cocaine inhibits the reuptake of monoamines at the synaptic cleft to prolong sympathetic output. This adrenergic hyperresponsiveness mimics thyrotoxicosis as it replicates sodium/potassium ATPase hyperactivity, causing a cellular influx of potassium (hypokalemia), hyperpolarization, and sodium channel inactivation that presents as sudden, painless muscle weakness and paralysis. <h3>Design/Methods:</h3> Consent obtained from patient. <h3>Results:</h3> A 30-year-old female with no past medical history was evaluated in the ED for acute lower extremity weakness that ascended to the upper extremities within &lt; 12 hours. Labs were significant for hypokalemia at 1.6, elevated inflammatory markers, elevated Free T4 at 2.58, and low TSH at &lt; 0.015. Urine drug screen was positive for cannabis and cocaine. Serum toxicology was negative. MRI of the T-spine and L-spine were unremarkable. Lumbar puncture was unremarkable. Cranial nerves were intact. Strength was 1/5 throughout, including at the neck. Flaccid tone. Lower extremity reflexes were 2+. Negative Babinski. Positive Hoffman bilaterally. Preserved sensation. The patient was admitted to the ICU, intubated for impending respiratory distress, and treated with IVIg. MRI of the C-spine was unremarkable. Further labs demonstrated elevated Free T3 at 7.13 and positive anti-TPO antibodies, significant for Grave’s disease. Urine labs were substantial for distal RTA. Anti-SSA and SSB antibodies were positive, indicating likely Sjogren’s syndrome (SS). Ganglioside panel was negative. Potassium was aggressively repleted. By day 1, the patient was moving all four extremities, and IVIg was discontinued. By day 2, she was successfully extubated. She was ambulating without difficulty on discharge. <h3>Conclusions:</h3> Secondary hypokalemic periodic paralysis may mimic Guillain Barre syndrome (GBS), a life-threatening demyelinating neuropathy that presents as rapidly progressive, symmetric, ascending paralysis or paresthesia with loss of reflexes. In our case, cocaine was the most plausible trigger for hypokalemia. <b>Disclosure:</b> Dr. Baumann has nothing to disclose. Dr. Rizvi has nothing to disclose. Ms. Alayon has nothing to disclose. Mr. Kendall has nothing to disclose. Dr. Shaffer has nothing to disclose. Dr. Mouhanna has nothing to disclose. Dr. Kenniff has nothing to disclose.

Biochemical Assessments of Thyroid Profile and Renal Function Test in Chronic Kidney Disease

Introduction: CKD is a clinical syndrome which occurs due to irreversible loss of renal function leading to metabolic, endocrine, excretory and synthetic function resulting in accumulation of non – protein nitrogenous substances which leads to metabolic derangements and ends up with distinct clinical manifestations. Aim: To study thyroid function abnormalities in patients with chronic kidney disease. To correlate the thyroid function abnormalities with severity of renal failure. To differentiate primary hypothyroidism from thyroid dysfunction due to chronic kidney disease. Methodology: After selection of patients, fulfilling the above criteria, about 5 ml of blood sample is collected in non-heparinised serum bottle and sent for thyroid profile test. Components of thyroid profile included in our study and Quantitative determination of T3, T4 and TSH is done by Enzyme Linked Immunosorbent Assay. Result: In our study out of 50 patients, 33 patients had low serum T3 levels . 4 patients among low serum T3 value, they also had low T4 and high TSH suggesting primary hypothyroidism. So excluding 4 patients of hypothyroidism 29 patients had low T3 syndrome in our study. Low T4 levels in our study, out of which 4 patients had low T3 and high TSH suggesting primary hypothyroidism. Conclusion: In my study population, 50 CKD patients who were on conservative management were studied. Among them 66% of the patients had low T3 values. The change in the serum levels of T3 and T4 in patients with CKD can be considered as being protective, promoting conservation of protein. There is increase in incidence of hypothyroidism in patients with chronic kidney disease.

Thyroid evaluation in suspicious hypothyroid adult dogs before and after treatment.

The purpose of this study was to measure circulating TSH, T4 and fT4 concentrations in dogs submitted to a clinical visit for general symptoms (weight gain, polyuria and polydipsia, changes in hair coat). Twenty-eight dogs, 14 cross-breed and 14 purebreds (Golden Retriever, Labrador, Doberman), of both sexes (14 males and 14 females), aged 8 to 14 years, were assessed. No significant differences of circulating TSH, T4 , fT4 concentrations between the baseline and after therapeutic treatment nor between intact and neutered females were observed. Compared to baseline values, intact males showed higher TSH concentrations (p⟨0.01), and castrated males lower TSH concentrations (p⟨0.01) after therapeutic treatment. Compared to intact males, castrated males showed baseline TSH concentrations higher (p⟨0.01), but lower (p⟨0.01) after therapeutic treatment. No significant differences of T4 and fT4 concentrations between baseline conditions and after therapeutic treatment, nor between intact and castrated males, were observed. The experimental sample considered in this study falls within that casuistry involving elevated TSH concentrations but low serum T4 and fT4 concentrations or close to the minimum physiological cut-off, in which the common clinical signs suggestive of hypothyroidism was, essentially, overweight and neglected appearance of the hair.

Abstract P245: Early Pregnancy Exposure to Per- And Polyfluoroalkyl Substances and Thyroid Function Throughout Gestation: A Longitudinal Study

Introduction: Thyroid function during pregnancy is pivotal for both maternal and fetal health. Data on environmental determinants of thyroid function in pregnancy are yet limited. We prospectively investigated associations of early pregnancy per- and polyfluoroalkyl substances (PFAS), known environmental endocrine disruptors, with thyroid function longitudinally measured throughout pregnancy. Hypothesis: Early pregnancy PFAS exposure adversely affects thyroid function. Methods: Within the NICHD Fetal Growth Studies-Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks (gw) 10-14 and measured concentrations of 9 PFAS (NMeFOSAA, PFDA, PFDoDA, PFDS, PFHpA, PFHxS, PFNA, PFOA, PFOS, PFOSA, PFUnDA) in plasma samples collected at enrollment. In a subsample of 321 pregnant women, we determined thyroid markers (fT3, fT4, TSH) at gw 10-14, 15-26, 23-31, 33-39. Associations were assessed with multivariable regressions per standard deviation increase in ln-transformed PFAS (ng/ml), adjusting for age, body mass index, diet, lifestyle and socio-economic factors, and plasma lipids. Results: Plasma PFAS in early pregnancy were associated with markers of thyroid function throughout pregnancy. The associations varied by gestational age. Higher levels of several PFAS were associated with lower TSH and higher fT3 and fT4 levels at gw 10-14. Adjusted beta coefficients [95%CI] with TSH (mIU/L) were: -1.13 [-2.30, 0.05] for PFOS, -3.15 [-4.45, -1.86] for PFDA, -1.75 [-2.95, -0.55] for NMeFOSAA, -1.68 [-3.00, -0.37] for PFNA, -1.29 [-2.62, 0.03] for PFDoDA, -2.07 [-3.30, -0.83] for PFOA, but 1.11 [0.12, 2.09] for PFHxS. Most of these associations were attenuated to non-significant or changed the direction of the association in later pregnancy (for instance, PFOS-TSH association at gw 10-14: -1.13 [-2.30, 0.05], gw 15-26: 0.98 [0.18, 1.78], gw 23-31: 1.31 [0.50, 2.13], PFDA-TSH association at gw 10-14: -3.15 [-4.45, -1.86], at gw 23-31: 1.13 [0.16, 2.11]). Consistent and positive associations across pregnancy were observed for PFOA-fT3 (at gw 10-14: 0.48 [0.05, 0.91], gw 15-26: 0.41 [0.04, 0.78], gw 23-31: 0.42 [0.02, 0.80] pmol/L) and PFHxS-fT4 (at gw 10-14: 0.12 [0.02, 0.21], gw 15-26: 0.67 [0.54, 0.81], gw 23-31: 0.22 [0.12, 0.33], gw 33-39: 0.14 [0.02, 0.26] ng/dL). Conclusions: Plasma levels of selected PFAS congeners in early pregnancy are significantly associated with thyroid markers in pregnancy. The associations varied by gestational timing. These findings indicate a potential environmental impact on thyroid function. In perspective, multiple assessments of PFAS and thyroid markers throughout pregnancy might be necessary and relevant for conducting gestational age-specific interventional trials.

Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA

A 32-year-old woman presented to the outpatient clinic with persistent fever, anterior neck pain, and palpitations over the past week which developed 2 days after she had received the first dose of the Pfizer/BioNTech SARS-CoV-2 mRNA vaccine. On examination, the patient’s heart rate was 140 beats per minute and the thyroid gland was tender on palpation. Laboratory studies showed a low serum TSH level with elevated free thyroxine. Thyroid ultrasound revealed low-echoic lesions compatible with the site of tenderness. The patient was diagnosed with subacute thyroiditis and treatment was initiated with acetaminophen and propranolol, which resulted in symptom resolution within 2 weeks. Clinicians should be aware that subacute thyroiditis may occur within a few days following COVID-19 vaccination, especially in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations, because differentiating them from early non-specific adverse reactions can be challenging.

Long-term outcome of thyroid abnormalities in patients with severe Covid-19.

We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated with non-thyroidal illness syndrome), in patients with severe acute respiratory syndrome coronavirus 2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time. One hundred eighty-three consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan. At baseline, after excluding from TSH analysis, 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, and 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal hypoechogenicity in 28% of patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal hypoechogenicity was associated with baseline low TSH (P = 0.034), high free-thyroxine (FT4) (P = 0.018) and high interleukin-6 (IL6) (P = 0.016). Focal hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months, thyroid 99mTc/123I uptake partially recovered from baseline (+28%) but was still reduced in 67% patients. Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal hypoechogenicity, associated with baseline high FT4, IL6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after 1 year although decreasing in size. Long-term consequences seem unlikely.

Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA.

Cases of subacute thyroiditis after vaccination, including against COVID-19, have been increasingly reported.Subacute thyroiditis should be considered in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations after COVID-19 vaccination because these can be diagnostic clues.It is important to note that this condition can occur as early as a few days after vaccination, in order to avoid diagnostic pitfalls.

Impact of Age and Clinico-Biochemical Parameters on Clinical Severity of SARS-CoV-2 Infection

Introduction: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and policy makers prioritize treatment and to decrease the burden on health systems caused by COVID-19, clinical severity along with various clinico-biochemical parameters was evaluated by designing a cross-sectional study comprising 236 SARS-CoV-2-infected individuals from Kashmir Valley, India. Methods: Briefly, real-time polymerase chain reaction (RT-PCR) was used for the confirmation of SARS-CoV-2 infection. The principles of spectrophotometry and chemiluminescent microparticle immunoassay (CMIA) were employed to estimate the levels of glucose, TSH, and 25-hydroxy vitamin D levels in serum of infected patients. Results: A total of 236 patients infected with SARS-CoV-2 were taken for this cross-sectional study. Patients with COVID-19 had a male predominance (72.9 vs. 27.1%) and a higher prevalence of 25-hydroxy vitamin D deficiency (72.0 vs. 28.0%) with a mean 25-hydroxy vitamin D levels of 24.0 ± 13.9 in ng/mL. We observed a varied clinical spectrum of SARS-CoV-2 infection with 36.4%, 23.7%, and 29.7% patients having mild, moderate, and severe disease, respectively. We observed that severity of SARS-CoV-2 infection was significantly associated with older age group, hypertension, low TSH levels, and 25-hydroxy vitamin D deficiency. Conclusion: We conclude that not only old age but also hypertension and low levels of TSH and 25-hydroxy vitamin D levels could significantly lead to clinical severity of SARS-CoV-2 infection.

Time to Hypothyroidism Following Hemithyroidectomy.

Background The time to hypothyroidism post hemithyroidectomy is variable.There are multiple risk factors for developing hypothyroidism. The aim of this study was to identify the time of hypothyroidism and other predictors of hypothyroidism in euthyroid patients following hemithyroidectomy. Methods This was a retrospective study. Of 170 euthyroid patients who underwent hemithyroidectomy for benign disease between 2006 - 2014, age, gender, pre-operative thyroid function tests, body mass index (BMI), and other co-morbidities were examined to determine predictors of early (<3 months) or late (>3 months)hypothyroidism.A high normal preoperative thyroid stimulating hormone (HN-TSH) was defined as ≥2.01 uIU/ml, and a low normal TSH (LN-TSH) was defined as <2.01 uIU/ml. Results A total of 63 of the 170 patients (37%) became hypothyroid.At 3 months, 21.5% of patients were hypothyroid. At 6 months after operation, an additional 5% had become hypothyroid, and after 1 year, 8% more were hypothyroid. The only independent predictor of hypothyroidism was preoperative HN-TSH (≥2.01) (p<0.001) on multivariate analysis. Conclusion In addition to known predictors of hypothyroidism following hemithyroidectomy for benign disease, such as the size of the thyroid remnant, a history of neck irradiation, and coexisting thyroid autoimmune disease, a BMI ≥35 kg/m2, age ≥45, and preoperative HN-TSH are risk factors for postoperative hypothyroidism within 3 months of operation. Such patients should be closely monitored.

Relationship between thyroid hormone and sex hormone levels and non-suicidal self-injury in male adolescents with depression.

Non-suicidal self-injury (NSSI) is the intentional and repeated direct injury to one's bodily tissues or organs without the intent to die, which is not socially sanctioned and does not result in death. This study will be the first to explore the relationship between NSSI behavior and thyroid hormone and sex hormone levels in male adolescents with depression. Among the inpatients in the children's ward of Shandong Mental Health Center, eighty male patients with first-episode depressive disorder were randomly selected. Forty male adolescent depressed patients with NSSI behaviors were set as the NSSI group, and forty male adolescent depressed patients without NSSI behaviors were set as the No-NSSI group. Their thyroid hormones (free triiodothyronine, free thyroxine, and thyroid stimulating hormone) and sex hormones (estradiol, progesterone, and testosterone) were measured, and the severity of self-injury in the NSSI group was assessed using the Adolescent Self-Injury Questionnaire. The NSSI group was tested again after 6 weeks of sertraline treatment for biological indicators and assessed by the Self-Injury Questionnaire to compare the hormonal differences between the NSSI group and the No-NSSI group and compare the differences of each index before and after treatment in the NSSI group. T3/T4 (p = 0.001) and FT3 (p = 0.023), TSH levels (p < 0.001) were lower in the NSSI group than in the No-NSSI group before treatment, and FT4 (p = 0.036) and T (p < 0.001) levels were higher than in the No-NSSI group. T3/T4 levels were higher in the NSSI group after treatment (p < 0.001). FT4 (p < 0.001) and T (p = 0.001) levels and self-injury questionnaire scores (p < 0.001) decreased after treatment in the NSSI group. In the NSSI group at baseline, FT4 levels were negatively correlated with self-injury questionnaire scores (r = -0.459, p = 0.003) and testosterone levels were positively correlated with self-injury questionnaire scores (r = 0.383, p = 0.015), and in the NSSI group after treatment, FT4 difference was negatively correlated with self-injury questionnaire score reduction rate (r = -0.037, p = 0.019), and testosterone difference was positively correlated with self-injury questionnaire score reduction rate (r = 0.424, p = 0.006). Logistic regression analysis showed that low TSH and high testosterone levels were independent risk factors for the development of non-suicidal self-harming behaviors in male adolescent depressed patients. Changes in thyroid hormone and sex hormone levels may be associated with non-suicidal self-injurious behavior in male adolescent depressed patients.

Anti-thyroid antibodies in the relation to TSH levels and family history of thyroid diseases in young Caucasian women.

In young women, hypothyroidism is associated with impaired fertility, increased risk of pregnancy loss, premature delivery, and impaired infant neurodevelopment, justifying the need to recognize the risk of hypothyroidism in women of reproductive age. Thus, this study aimed at assessing the frequency of occurrence of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb) in young Caucasian women in connection with various confounders. The cross-sectional study involved 366 women aged 18-40 years without a diagnosis of thyroid disease. The personal and family medical history was collected, body mass and height were measured and an ultrasound examination of the thyroid gland was performed. Thyrotropin (TSH), free thyroxine, and free triiodothyronine levels, as well as TPOAb and TGAb titers, were determined by ECLIA. Two cases of hyperthyroidism (0.5%) and 6 cases (1.6%) of subclinical hypothyroidism were detected. TPOAb was detected in 21 (5.7%) and TGAb in 31 (8.6%) and any of the antibodies in 42 (11.6%) women. Antibodies were more frequent in the subgroup with TSH levels ≥ 2.5 mIU/L than in the subgroup with lower TSH levels (15.5% vs 6.9%, respectively, p<0.05). Any anti-thyroid antibodies were also detected more frequently in the subgroup with TSH levels ≥ 2.5 mIU/L (18.3% vs 10.0%, respectively, p<0.05). Women with the presence of TGAb or seropositive for either TGAb or TPOAb or TPOAb and TGAb antibodies were more likely to have higher TSH levels (OR = 2.48 and OR = 2.02; respectively, p < 0.05 for both). A family history of any thyroid diseases increased the risk of any anti-thyroid antibodies positivity (OR = 1.94; p < 0.05). The results of our study suggest that TSH ≥ 2.5 mIU/L and a family history of any thyroid diseases justify screening for anti-thyroid antibodies in women of reproductive age, although the occurrence of these antibodies in the majority of cases is not related to thyroid dysfunction.

Anomalies cardiaques associées à l'hyperthyroïdie : étude clinique, structurelle et rythmique

IntroductionThe prevalence and nature of cardiac complications associated with hyperthyroidism vary considerably in the literature depending on the population studied and the means of investigation used to detect them. The aim of this study was to determine the structural, functional, and rhythmic cardiac abnormalities associated with hyperthyroidism and to identify their risk factors. MethodsIt is a cross-sectional study conducted in thirty adult patients with overt or subclinical hyperthyroidism. Each patient underwent a clinical cardiovascular examination, a cardiac Doppler ultrasound, a pulmonary ultrasound and a 24-hours rhythm holter. The diagnosis of cardiothyreosis (thyrotoxic heart disease) was retained if an arrhythmia, heart failure (HF) and/or pulmonary arterial hypertension (PAH) were noted following the investigations carried out. ResultsThe mean age of the patients was 44.8 ± 14.4 years. The sex ratio (M/F) was 0.3. Five patients (17%) had subclinical hyperthyroidism and 25 (83%) had overt hyperthyroidism. Thirteen patients (43%) had cardiothyreosis. It consisted of a rhythm disorder in three patients (10%), PAH in twelve patients (40%) and HF in eight patients (27%). An age over 50 years and toxic nodular etiology were associated with atrial fibrillation (AF), p = 0.041 and p = 0.004 respectively. Tachycardia and a higher number of atrial extrasystoles were associated with HF, p = 0.039 and p = 0.007 respectively. A lower TSH, tachycardia and a higher number of atrial extrasystoles were associated with the presence of PAH, p = 0.004, p = 0.011 and p = 0.007 respectively. ConclusionCardiac complications should be sought in all patients with hyperthyroidism, especially in elderly and tachycardic patients. Specialized investigations such as echocardiography or 24 hours rhythmic holter should be requested in these cases.