Thyroid Hormone Supplementation Research Articles

Abstract PS14-01: Immune related adverse events in patients ≥65 years vs. <65 years with breast cancer treated with immunotherapy

Abstract Background: Pembrolizumab is approved for early/advanced triple negative breast cancer (TNBC), and atezolizumab was previously approved for advanced TNBC. Toxicity of immunotherapy (IO) and immune related adverse events (irAEs) in patients ≥65 years with TNBC is not described in detail in results from registration trials (KEYNOTE 522, KEYNOTE 355, and IMPassion130), where patients ≥65 years were a minority. Understanding real-world IO toxicity and irAEs in patients with breast cancer ≥65 years may inform clinical decision making. Methods: We studied IO toxicity and irAEs in patients with breast cancer ≥65 years vs. < 65 years (at IO start) who received IO at an academic institution. A retrospective review was conducted to identify IO toxicity and irAEs (classified by CTCAE v 5.0). Cohorts were compared with Pearson's chi-squared test (categorical variables) and Wilcoxon rank-sum test (continuous variables). Results: Cohorts had 25 patients ≥65 years (median age 73 years, interquartile range (IQR) 69-74 years) and 104 patients < 65 years (median age 48 years, IQR 39-56 years). Stage I-III/IV breast cancer distribution was 36%/64% for ≥65 years and 68%/32% for < 65 years. Baseline ECOG performance status was mainly 0-1 in both cohorts. IO was mainly pembrolizumab (≥65 years: 96%; < 65 years: 83% for first IO regimen) vs. atezolizumab. Table 1 depicts characteristics of IO toxicity. IO duration was longer in patients < 65 years. While rates of IO interruption for toxicity and discontinuation for toxicity were numerically higher in patients ≥65 years, these findings did not reach statisticial significance, possibly due to the sample size. Similar overall rates of irAEs were seen (≥65 years: 72%; < 65 years: 65%, p=0.47) but there were differences in the types of irAEs. Patients < 65 years had more transaminitis (≥65 years: 12%; < 65 years: 33%, p=0.04), and grade 2-3 hypothyroidism (among patients developing hypothyroidism, ≥65 years: grade 1- 75%, grade 2- 25%, grade 3- 0%; < 65 years: grade 1- 11%, grade 2- 79%, grade 3- 11%, p=0.017). Conversely, patients ≥65 years had higher rates of irAE nephritis (≥65 years: 12%; < 65 years: 1%, p=0.004); notably, none of the patients had baseline chronic kidney disease. Rates of full resolution of irAEs were similar between cohorts (≥65 years: 67%; < 65 years: 57%, p=0.47), but patients ≥65 years had more steroid use for management of first irAE while patients < 65 years required more thyroid hormone supplementation (first irAE management distribution, ≥65 years: steroids- 71%, thyroid hormone- 7%, supportive care- 21%; < 65 years: steroids- 31%, thyroid hormone- 25%, supportive care- 44%, p=0.025). Late onset irAEs and deaths from irAEs were rare in both cohorts, with 1 irAE related death in the cohort ≥65 years. Conclusions: In this real-world cohort, similar overall rates of irAEs were observed in patients ≥65 years and < 65 years. However, patients ≥65 years had higher rates of irAE nephritis and steroid use for irAEs, while patients < 65 years had more transaminitis and higher grade hypothyroidism, requiring more thyroid hormone supplementation. Given these age specific differences, validation in a larger cohort is merited. Table 1. Characteristics of IO toxicity. Citation Format: Neelima Vidula, Jennifer Hutchinson, Abigail McLaren, Lianne Ryan, Andrzej Niemierko, Aditya Bardia. Immune related adverse events in patients ≥65 years vs. <65 years with breast cancer treated with immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-01.

Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Schmidt's Syndrome: An Uncommon Cause of Spontaneous Hypoglycemia

AbstractSchmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.

Subclinical Hypothyroidism as a Possible Cause of Herpes Zoster Reactivation

Background: Hypothyroidism was considered as a predisposing factor for herpes zoster (HZ) infection. Thus, Thyroxine deficiency may be a risk factor for varicella zoster virus reactivation. The aim of this study was to test if thyroid hormone supplementation will ameliorate the clinical course of HZ infection.
 Methodology: This was a prospective cohort conducted on 60 herpes zoster infected patients, who had a subclinical hypothyroidism. Serum TSH and FT4 measurements were made by using electrochemiluminescence immunoassay. All patients were divided into two groups. Group A included 30 patients who were treated with Eltroxin 25 µg daily for 3 months. Group B included 30 patients who took placebo. All were submitted to cutaneous examination (e.g., rash and new lesions). Any complications were documented. Pain was assessed before and after treatment, and any pain-controlling medications were registered. The primary endpoints were time to achieve complete pain cessation, time to cessation of the formation of the new lesions, and time to > 50% crusting/healed lesions. Secondary outcome included time to 100% crusting/healed lesions, time to complete absence of moderate to excruciating pain, time to first pain-free period, and time to absence of abnormal sensations.
 Results: Both groups were comparable regarding patient age, gender, chronic medical diseases, and characteristics of herpes zoster rash. Ophthalmic zoster was reported in 6.7% and 10% of groups A and B respectively. However, group A (Eltroxin supported) had much better and rapid and rash healing of pain than group B. Finally, zoster-related complications were significantly lower in group A than group B.
 Conclusions: Subclinical hypothyroidism is associated with HZ reactivation process, so hypothyroid medical treatments are effective in this case.

Research progress of plant-derived natural products in thyroid carcinoma.

Thyroid carcinoma (TC) is a prevalent malignancy of the endocrine system, with a notable rise in its detection rate in recent decades. The primary therapeutic approaches for TC now encompass thyroidectomy and radioactive iodine therapy, yielding favorable prognoses for the majority of patients. TC survivors may necessitate ongoing surveillance, remedial treatment, and thyroid hormone supplementation, while also enduring the adverse consequences of thyroid hormone fluctuations, surgical complications, or side effects linked to radioactive iodine administration, and encountering enduring physical, psychosocial, and economic hardships. In vitro and in vivo studies of natural products against TC are demonstrating the potential of these natural products as alternatives to the treatment of thyroid cancer. This therapy may offer greater convenience, affordability, and acceptability than traditional therapies. In the early screening of natural products, we mainly use a combination of database prediction and literature search. The pharmacological effects on TC of selected natural products (quercetin, genistein, apigenin, luteolin, chrysin, myricetin, resveratrol, curcumin and nobiletin), which hold promise for therapeutic applications in TC, are reviewed in detail in this article through most of the cell-level evidence, animal-level evidence, and a small amount of human-level evidence. In addition, this article explores possible issues, such as bioavailability, drug safety.

Association of thyroid dysfunction in individuals ≥ 65 years of age with subclinical cardiac abnormalities.

The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined. To evaluate the impact of thyroid dysfunction on structure and function of the left-heart chambers and blood markers of cardiac disease. Cross-sectional analysis. The Cardiovascular Health Study, a community-based cohort of older individuals recruited from four urban areas in the United States. Of 3163 participants studied, 2477 were euthyroid, 465 had subclinical hypothyroidism (SCH), 47 overt hypothyroidism (OH), 45 endogenous (endo) subclinical hyperthyroidism (endo-SCT), and 129 had exogenous (exo) SCT due to thyroid hormone supplementation. Clinical evaluation, blood sampling and biomarker measurement, 2-dimensional and speckle-tracking echocardiography. Left heart myocardial deformation, circulating biomarkers of diastolic overload (NT-proBNP), fibrosis (sST2, gal-3), and cardiomyocyte injury (hs-cTnT). SCH was associated with higher NT-proBNP (beta = 0.17, p = 0.004), whereas OH was associated with higher hs-cTnT (beta = 0.29, p = 0.005). There were also suggestive associations of SCH with higher sST2, as well as endo-SCT with higher gal-3 and lower (worse) left atrial reservoir strain. Left ventricular longitudinal strain and end-diastolic strain rate did not differ significantly from euthyroid participants in SCH, OH, or exo-SCT. In this free-living elderly cohort, subclinical and overt hypothyroidism were associated with abnormalities of blood biomarkers consistent with diastolic overload and myocardial necrosis respectively, whereas subclinical hyperthyroidism tended to be associated with myocardial fibrosis and decreased left atrial strain. Our findings could represent stage B heart failure and illuminate distinct aspects of the pathobiology of heart disease related to thyroid gland dysfunction with potential clinical implications.

A Rare Clinical Scenario of Hypothyroid-induced Rhabdomyolysis

Abstract Muscle involvement is common in hypothyroidism and is seen in nearly 80% of the cases. However, rhabdomyolysis is a rare manifestation and is usually triggered by precipitating factors such as exercise, statins, and toxins. We describe the case of a 58-year-old woman with de novo hypothyroidism presenting with severe rhabdomyolysis requiring hemodialysis. A 58-year-old diabetic and hypertensive female was presented at our tertiary care center with symptoms of generalized weakness, difficulty in walking, and decreased urine output. Her blood investigations showed elevated creatine phosphokinase (CPK), renal parameters, and thyroid-stimulating hormone (TSH) levels suggestive of autoimmune thyroiditis with rhabdomyolysis. She was treated with thyroid hormone supplementation and hemodialysis. The patient recovered gradually with normalization of renal parameters. Although muscle involvement is common in hypothyroidism, rhabdomyolysis is a rare manifestation. Diagnosis is established by demonstrating elevated CPK and TSH levels. Management consists of hydration and thyroid hormone supplementation. Hemodialysis is required in severe cases with established acute kidney injury.

A national study of postoperative thyroid hormone supplementation rates after thyroid lobectomy

BackgroundThe American Thyroid Association updated guidelines in 2015 to allow lobectomy for low-risk thyroid cancers. The objectives of this study were (1) to determine thyroid hormone supplementation rates after lobectomy and (2) to evaluate the effect of the American Thyroid Association guideline change on lobectomy and hormone supplementation rates among thyroid cancer patients. MethodsThe Merative MarketScan Databases was used to identify adult (≥age 18) patients who underwent thyroidectomy for benign nodules or thyroid cancer. The association between indication for surgery and postoperative thyroid hormone supplementation was examined using χ2 analyses and multivariable logistic regression models. Among patients with thyroid cancer, lobectomy and hormone supplementation rates were compared in the periods before (2008–2015) and after the guideline change (2016–2019). ResultsOf the 81,926 patients identified, 33,756 (41.2%) underwent thyroid lobectomy, 45,104 (55.1%) underwent total thyroidectomy, and 3,066 (3.7%) underwent completion thyroidectomy. Patients who underwent lobectomy for malignancy were significantly more likely to require hormone supplementation (59.3% vs 39.4% [P < .001], adjusted odds ratio 2.34 [95% confidence interval 2.20–2.48]) compared to those with benign disease. Compared to the 2008 to 2015 period, the proportion of patients who underwent lobectomy for thyroid cancer was higher in the 2016 to 2019 period (34.3% vs 30.3%, P < .001), with fewer patients requiring completion thyroidectomy (25.6% vs 29.8%, P < .001) and thyroid hormone supplementation (56.9% vs 60.1%, P = .04). ConclusionThe postoperative thyroid hormone supplementation rate was significantly higher in patients who had thyroid cancers compared to benign diseases. After the American Thyroid Association guidelines changed, lobectomy rates increased significantly without a concomitant increase in the completion of thyroidectomy.

Adequacy of thyroid hormone replacement for people with hypothyroidism in real-world settings: A systematic review and meta-analysis of observational studies.

Thyroid hormone under-replacement and over-replacement are associated with adverse health outcomes. This systematic review aimed to evaluate the extent of thyroid hormone replacement adequacy for patients with known hypothyroidism in real-word settings, excluding those receiving thyroid hormone suppressive therapy as thyroid cancer treatment. Four electronic databases (Embase [Ovid], Medline [Ovid], PubMed and SCOPUS) were searched for published and unpublished observational studies until 12 December 2022. The results of the studies were meta-analysed to calculate pooled prevalence estimates for thyroid hormone supplementation adequacy, over-replacement and under-replacement. Quality assessment of studies was performed using the Joanna-Briggs appraisal tool for prevalence studies. Seven studies with a total of 4230 patients were eligible for quantitative synthesis. The pooled prevalence estimates of adequate thyroid replacement, over-replacement and under-replacement were 0.55 (95% confidence interval [CI]: 0.49-0.60, p = .001), 0.20 (95% CI: 0.14-0.27, p = .001) and 0.24 (95% CI: 0.13-0.36, p = .001), respectively. Four studies subclassified hypothyroidism and hyperthyroidism into overt and subclinical. The pooled prevalence of overt and subclinical hyperthyroidism was 0.04 (95% CI: 0.00-0.11, p = .01) and 0.17 (95% CI: 0.09-0.27 p = .001), respectively. For overt and subclinical hypothyroidism, the pooled prevalence was 0.02 (95% CI: 0.01-0.03, p = .001) and 0.20 (95% CI: 0.12-0.29, p = .001), respectively. On average, approximately half of patients with hypothyroidism are only treated to target euthyroidism. In real-world practice, a significant number of patients are over-treated or under-treated, leading to adverse healthcare outcomes. It is imperative that more effective thyroid monitoring strategies be implemented, with an emphasis on primary care thyroid function monitoring, to minimise inappropriate thyroid replacement treatments and optimise healthcare outcomes at a population level.

Hashimoto’s thyroidits and other causes of hypothyrodisim – systematic review

Introduction and objective: The aim of the study is to summarize the knowledge about hypothyroidism, with particular emphasis on Hashimoto's disease, as its most common cause.&#x0D; Review metods: Literature review of PubMed database using key words contained in ‘Medical Subject Headings’ MeSH.  State of Knowledge: Hashimoto's disease is the most common form of thyroiditis, as well as main cause of hypothyroidism. It is an autoimmune disease that leads to gradual fibrosis and atrophy of the thyroid gland. It occurs several times more frequently in women than in men. Treatment mainly involves supplementation of thyroid hormones due to the progressive hypothyroidism. Levothyroxine (L-T4) therapy has a long history of clinical use, a defined pharmacological profile, and is considered as safe treatment of hypothyroidism of the thyroid gland. There are also other, less common causes of hypothyroidism, such as postoperative hypothyroidism, de Quervain's disease, post-radioactive iodine treatment status, drug-induced and central hypothyroidism, which are equally important and should not be forgotten during the diagnostic process.&#x0D; Summary: Hypothyroidism can be caused by various factors, the main being Hashimoto’s thyroiditis. Regardless of the etiology, treatment in most cases involves levothyroxine (LT-4) supplementation, which leads to euthyroidism and resolution of symptoms. Surgery may need to be performed in pateitns who meet the surgical criteria and show unresponsiveness to conservative treatment.

SAT503 Acute Psychosis and Paranoia as an Initial Manifestation of Myxedema Madness

Abstract Disclosure: S. Atam: None. M. Ahmad: None. G.A. McGrath: None. Introduction: Hypothyroidism is a common disease affecting approximately 1 in 300 Americans, with autoimmunity being the most common cause in the United States. Hypothyroidism is known to present with numerous psychiatric manifestations, including depression, cognitive deficits, and rarely psychosis. We present a case of profound hypothyroidism found in a patient who presented with visual hallucinations and paranoia. Case description: The patient was a 64-year-old man with past medical history of follicular Non-Hodgkin's Lymphoma, Type 2 diabetes, hypertension, and sinus bradycardia who presented to the emergency department with three-week history of increasing agitation, insomnia and cold intolerance. He had auditory and visual hallucinations with paranoid ideations, which started a few days prior. His initial vitals were temperature: 98.2°, heart rate: 81 beats per minute, respiratory rate: 20 breaths per minute, and blood pressure: 135/88 mmHg. The patient’s initial lab work was significant for: sodium: 143 mmol/L, potassium: 3.6 mmol/L, creatinine: 1.55 mg/dL (baseline of 1.2 mg/dL), AST: 240 IU/L, ALT: 252 IU/L, INR: 1.1, ammonia: 20 mcmol/L, TSH: 51.7 uIu/ml, free t4: &amp;lt;0.1 ng/dL, free t3: &amp;lt;0.4 ng/dL, and urine drug screen positive for cannabinoids. MRI imaging of the patient’s brain was negative for any acute intracranial process. Although the absence of hypothermia made myxedema coma unlikely, both the acuity and the severity of his psychiatric symptoms in the context of profound hypothyroidism, with no other identifiable cause, collectively suggested “myxedema madness”. The patient was started on intravenous levothyroxine therapy along with quetiapine and haloperidol for agitation. Further lab work demonstrated an anti-tpo antibody of 9.0 IU/mL (&amp;lt; 9) along with a benign lumbar puncture (glucose: 89 mg/dL, protein: 54 mg/dL, WBC: 9/uL, RBC: 1/uL). A review of his recent medical history revealed that last summer, as part of a chemotherapy regimen for relapsed lymphoma, he had been started on Lenalidomide, which is reported to cause primary hypothyroidism in 7% of patients. His overall neurologic function improved over a two-week course, and he was subsequently discharged. Discussion: Hypothyroidism can present with a spectrum of different psychiatric manifestations. However, cases of hypothyroidism-induced psychosis are infrequent. It is reported that only 5-15% of myxedematous patients develop some form of psychosis. Treatment of this altered mental state is centered on thyroid hormone supplementation along with the administration of antipsychotic medications. Improvement in psychotic symptoms is typically seen within weeks to months after initiation of treatment. Through this case, we hope to highlight this rare presentation of hypothyroidism and current proposed treatment strategies. Presentation Date: Saturday, June 17, 2023

FRI479 Resistance To Thyroid Hormone Due To Thyroid Hormone Receptor Alpha (THRA) Gene Mutation

Abstract Disclosure: J.O. Abdelkarim: None. S. Parveen: None. M.G. Jakoby: None. J. Fleischer: None. Introduction: Resistance to thyroid hormone (RTH) is a heritable disorder characterized by diminished response to triiodothyronine (T3). Most cases of RTH are due to mutations in the thyroid hormone receptor beta (THRB) gene (“RTH-beta”). Mutations in thyroid hormone receptor alpha (THRA) gene appear to be a rare cause of RTH (“RTH-alpha”), with the first case reported in 2012. We present a case of RTH-alpha in a patient confirmed to have a pathogenic THRA mutation. Clinical Case: A 38-year-old Caucasian male was referred to genetic clinic due to mild developmental delay, dyscalculia and mild autism spectrum disorder. He was born at term by uncomplicated spontaneous vaginal delivery. Parents first noticed developmental delays at age 5 y, though no evaluation occurred during childhood. As an adult, the patient completed seminary studies and was employed as a Catholic priest. An intellectual disability gene panel revealed a pathogenic variant of the THRA gene (c.1151G&amp;gt;A p.R384H). Both parents tested negative for the mutation. Examination was notable for obesity (183 cm, 186 kg, BMI 55.5), macrocephaly, hypertelorism, pectus excavatum and small hands with short digits. No thyroid anatomic thyroid abnormalities were appreciated on neck examination or ultrasonography. TSH was 1.860 mIU/L (0.358-3.740), free T4 0.71 ng/dL (0.76-1.46), and free T3 3.2 pg/mL (2.2-4.0). The patient had no symptoms of hypothyroidism, and supplemental thyroid hormone was deferred. Discussion: There are 29 reported THRA gene mutations and 32 cases of RTH-alpha reported in the peer reviewed literature. Common clinical features include mild-to-moderate intellectual impairment, low basal metabolic rate (BMR), mild skeletal dysplasia, normocytic anemia, bradycardia, consistent with high expression of THRA in brain, heart, gastrointestinal tract, skeletal muscle, and bone. TSH is normal to slightly increased, free T4 is low to low normal, and free T3 is normal to modestly elevated. This is the third reported case of the c.1151G&amp;gt;A missense mutation resulting in an arginine to histidine substitution at codon 384. Thyroid function tests conform to the pattern described for other cases of RTH-alpha. Like the other two patients with the R384H mutation, developmental delays occurred, though intellectual manifestations mitigated with time and the patient completed seminary studies without difficulty. Mitigation of phenotype with age has been reported in RTH-alpha mice with the R384C missense mutation. Short stature did not occur in this patient or the other R384H cases. Unlike other patients, this patient did not experience anemia or constipation. Macrocephaly is a common feature of the three R384H cases, but the patient’s other skeletal manifestations (e.g. pectus excavatum) were not reported. This case demonstrates the difficulty of recognizing THR-alpha and extends our understanding of the R384H phenotype. Presentation: Friday, June 16, 2023

FRI507 Thyrotoxic Periodic Paralysis: A Rare Occurrence Of Exogenous Thyroid Replacement

Abstract Disclosure: J. Case: None. D. Suravajjala: None. V. Eranki: None. Thyrotoxic periodic paralysis (TPP) occurs suddenly through excess thyroxine in tandem with insulin spurring an intracellular shift of potassium via increased activity of Na+/K+ ATPase pump leading to depletion of extracellular potassium with subsequent destabilization of cellular membranes and ensuing paralysis presenting with proximal muscle weakness of the legs. Common triggers involve vigorous exercise, infection, carbohydrate-rich meals, thyroiditis and graves' disease. Patients may be treated with IV potassium, non-selective beta blockers and treating the underlying cause. Exogenous thyroid hormone replacement causing iatrogenic hyperthyroidism as a cause of TPP is very rare. We present one such case below. A 61-year-old male with a history of primary hypothyroidism on thyroid replacement, atrial fibrillation, diabetes mellitus and hypertension, was admitted in September 2019 for lower extremity weakness at which time he was found with hypokalemia; he symptomatically improved following potassium replacement. He had a similar hospitalization in October, 2022 at which time he was found to have weakness alongside hypokalemia and hypomagnesemia, both of which were replaced with symptomatic improvement. He presented as an outpatient for follow up with likely etiology being TPP. Upon further review he had been taking both LT4 (Synthroid) 75mcg daily and T4/T3(Armour) 60mg daily; of note his TSH had been suppressed since 2019, three years prior to presentation. He was unsure why he had been on combination therapy. At our initial visit his labs were: TSH &amp;lt;0.005mIU/mL, free T4 1.38 ng/dL and T3 199 ng/dL. He was advised to stop all thyroid hormone replacement and experienced symptomatic improvement with normalization of potassium and magnesium. Repeat TFTs are pending for appropriate replacement dosing. Recognition of TPP and distinguishing from other etiologies of lower extremity weakness as well as other forms of periodic paralysis would aid in early resolution of an easily treatable, yet severe, condition given the implications of prolonged hypokalemia; earlier recognition of TPP in this patient as a sign of thyrotoxicosis may have prevented later hospitalizations and reduced risk of development of atrial fibrillation. This case also demonstrates the need for adequate monitoring and dosing of thyroid hormone supplement as well as potential complexities and risks of combination therapy in preventing an exogenously induced thyrotoxic state. Presentation: Friday, June 16, 2023

Effect of thyroid hormone replacement treatment on cardiac diastolic function in adult patients with subclinical hypothyroidism: a meta-analysis.

Although subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography. This meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle-Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Seventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e' wave (E/e') had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine. In adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083). https://inplasy.com/inplasy-2023-2-0083.

Full Recovery of Sensorineural Hearing Loss in a Patient with Congenital Hypothyroidism.

Congenital hypothyroidism (CH) is one of the most preventable causes of intellectual disability in the world. Screening programs have led to earlier detection of CH, and children with adequate thyroid supplementation can have minor long-term differences in overall neuropsychological testing compared to baseline. However up to one- fourth of children born with CH suffer from hearing loss even with early and adequate thyroid hormone supplementation. We report a rare case of a patient with hearing loss attributed to congenital hypothyroidism who had complete recovery of hearing after early thyroid hormone replacement.

Severe hypothyroidism as the cause of rhabdomyolysis and acute kidney injury – a case report

Hypothyroidism is a set of clinical symptoms associated with a deficiency of thyroid hormones. Musculoskeletal symptoms, i.e. stiffness, pain or muscle fatigue, are among the many manifestations of the disorder. Rhabdomyolysis, a syndrome accompanying muscle tissue damage, which leads to acute kidney injury, may be a complication of hypothyroidism. In this paper, we present a case of a 35-year-old patient with hypothyroidism due to Hashimoto’s disease, with a 4-year history of diagnosis for periodic pain and muscle weakness in the lower extremities. The patient presented to the hospital due to the recurring symptoms. One month before admission, she had discontinued thyroid hormone supplementation. Laboratory tests showed unquantifiable low levels of free thyroid hormones, elevated creatine kinase levels, and elevated kidney function parameters. Non-compliance can lead to potentially life-threatening complications in hypothyroid patients. Prompt diagnosis and implementation of treatment can lead to symptom resolution.

Diagnosis and management of thyroid disorders and thyroid hormone supplementation in adult horses and foals.

Equine thyroid disorders pose a diagnostic challenge in clinical practice because of the effects of nonthyroidal factors on the hypothalamic-pituitary-thyroid axis, and the horse's ability to tolerate wide fluctuations in thyroid hormone concentrations and survive without a thyroid gland. While benign thyroid tumours are common in older horses, other disorders like primary hypothyroidism or hyperthyroidism in adult horses and congenital hypothyroidism in foals are rare. There is a common misunderstanding regarding hypothyroidism in adult horses, especially when associated with the clinical profile of obesity, lethargy, and poor performance observed in dogs and humans. Low blood thyroid hormone concentrations are often detected in horses as a secondary response to metabolic and disease states, including with the nonthyroidal illness syndrome; however, it is important to note that low thyroid hormone concentrations in these cases do not necessarily indicate hypothyroidism. Assessing equine thyroid function involves measuring thyroid hormone concentrations, including total and free fractions of thyroxine (T4) and triiodothyronine (T3); however, interpreting these results can be challenging due to the pulsatile secretion of thyroid hormones and the many factors that can affect their concentrations. Dynamic testing, such as the thyrotropin-releasing hormone stimulation test, can help assess the thyroid gland response to stimulation. Although true hypothyroidism is extremely rare, thyroid hormone supplementation is commonly used in equine practice to help manage obesity and poor performance. This review focuses on thyroid gland pathophysiology in adult horses and foals, interpretation of blood thyroid hormone concentrations, and evaluation of horses with thyroid disorders. It also discusses the use of T4 supplementation in equine practice.

The Role of Recipient Thyroid Hormone Supplementation in Primary Graft Dysfunction After Heart Transplantation: A Propensity-Adjusted Analysis

To investigate whether recipient administration of thyroid hormone (liothyronine [T3]) is associated with reduced rates of primary graft dysfunction (PGD) after orthotopic heart transplantation. Retrospective cohort study. Single-center, university hospital. Adult patients undergoing orthotopic heart transplantation. A total of 609 adult heart transplant recipients were divided into 2 cohorts: patients who did not receive T3 (no T3 group, from 2009 to 2014), and patients who received T3 (T3 group, from 2015 to 2019). Propensity-adjusted logistic regression was performed to assess the association between T3 supplementation and PGD. After applying exclusion criteria and propensity-score analysis, the final cohort included 461 patients. The incidence of PGD was not significantly different between the groups (33.9% no T3 group v 40.8% T3 group; p=0.32). Mortality at 30 days (3% no T3 group v 2% T3 group; p=0.53) and 1 year (10% no T3 group v 12% T3 group; p=0.26) were also not significantly different. When assessing the severity of PGD, there were no differences in the groups' rates of moderate PGD (not requiring mechanical circulatory support other than an intra-aortic balloon pump) or severe PGD (requiring mechanical circulatory support other than an intra-aortic balloon pump). However, segmented time regression analysis revealed that patients in the T3 group were less likely to develop severe PGD. These findings indicated that recipient single-dose thyroid hormone administration may not protect against the development of PGD, but may attenuate the severity of PGD.

Effect of thyroid hormones administration on urinary endogenous steroid profile of the athlete biological passport.

This work focused on the possible alterations of the markers of the steroidal module of the athlete biological passport, considering samples of athletes declaring and not-declaring the supplementation of thyroid hormones (TH) in the Doping Control Form (DCF). Concentrations of 5α-androstane-3α,17β-diol (5α-Adiol), 5β-androstane-3α,17β-diol (5β-Adiol), testosterone (T), androsterone (A), etiocholanolone (Etio), epitestosterone (E), pregnanediol (PD), dehydroepiandrosterone (DHEA), and 11β-hydroxy-androsterone (OHA) were calculated using internal standards and external calibration by gas chromatography-tandem mass spectrometry. Also, ratios between the above biomarkers were also estimated. The data set was composed of samples from females and males declaring and not-declaring TH supplementation in the DCF. To corroborate these observations, a controlled urinary excretion study was carried out with multiple doses of sodium liothyronine (T3). Female data showed significant differences for the concentrations of 5α-Adiol, A, DHEA, E, OHA, and T and the ratio A/Etio between FD and FND groups, whereas the male groups only showed significant differences in OHA concentration. In both cases, males and females declaring the consumption of levothyroxine showed narrower data distribution and diminished percentiles from 17% to 67% with respect to the not-declaring corresponding groups (p< 0.05). Concentrations of 5α-metabolites showed a higher depression for the FND, and both FD and MD groups showed a peculiar behavior for the PD concentrations. The controlled study agreed with the observations, mainly for the female group with significant differences for concentrations of E, Etio, 5α-Adiol, and 5β-Adiol after TH administration. The interpretation of the steroid markers of the ABP should consider TH administrations.

Post-thyroidectomy hypothyroidism and thyroid hormone supplementation: a narrative review of the history, treatment, and patient experience

Post-thyroidectomy hypothyroidism and thyroid hormone supplementation: a narrative review of the history, treatment, and patient experience