Does Radioactive Iodine Treatment Damage the Lacrimal System?

PURPOSE: In this prospective study, we aimed to make a quantitative assessment of the lacrimal glands before and after radioactive iodine (RAI) treatment in patients with hyperthyroidism and thyroid cancer. METHODS: The study included 80 eyes of 40 patients. There were 25 patients in group 1 (hyperthyroid group) and 15 patients in group 2 (thyroid cancer group). Group 1 has received low dose ( 131 I) and group 2 high dose ( 131 I). Before, and at the first and sixth month after RAI treatment, all patients underwent ophthalmological examinations, Schirmer tests, TBUT tests, tear osmolarity (TO), and ocular surface examinations. RESULTS: The age and sex characteristics of both groups were similar. Although no significant change was observed in tear film tests before and after treatment in group 1, a significant decrease in Schirmer and TBUT values and a significant increase in TO were observed in group 2 in the first month after treatment. These values returned to normal in the sixth month. Although no Schirmer test was observed lower than 10 mm in any patient before RAI treatment, the Schirmer test was measured 5 to 10 mm in 4 (10%) patients in group 2 in the first month after treatment. Again, in these patients, TBUT was below 10 seconds and TO was greater than 308 mOsm/L. CONCLUSIONS: In this study, although no change was observed in tear function tests in patients receiving low doses of RAI, a decrease in tear secretion and an increase in TO were detected in patients receiving high doses in the early period.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats.

BACKGROUND: Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation. METHODS: Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-ß1) were determined. RESULTS: MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes' activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-ß1/Smad pathway. CONCLUSION: Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function.

Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.

Autoimmune Thyroid Diseases.

Autoimmune thyroid diseases (AITDs) include a wide spectrum of thyroid diseases affecting more commonly women than men. The most frequent forms are Graves' Disease (GD) and Hashimoto's thyroiditis / Autoimmune Thyroiditis (AIT), but there are also other immunogenic destructive forms of thyroiditis, that is, silent and postpartum thyroiditis. In the last decade, AITDs and other inflammatory thyroid diseases related to anti-tumor molecular drugs are more frequently seen due to the widespread use of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs). Autoimmune thyroiditis related to SARS-CoV-2 infection has been a novel entity in recent years. Graves' Disease and AIT may shift from hyperthyroidism to hypothyroidism, which may complicate the differential diagnosis and further treatment strategy. Moreover, all AITDs may manifest with thyrotoxicosis (a clinical condition marked with high serum levels of thyroid hormones) which has to be distinguished from hyperthyroidism (increased thyroid hormone production and secretion as a result of hyperfunctioning thyroid gland) due to different therapeutic approaches. Nuclear medicine techniques, such as radioiodine uptake (RAIU) and thyroid scintigraphy, using 99mTc- pertechnetate (Na[99mTc]TcO4) or 123-Iodine (Na[123I]I), have a crucial role in the differential diagnosis. Measurement of thyroid antibodies, e.g. thyroid peroxidase antibodies (TPO) and thyrotropin receptor antibodies (TRAb), as well as thyroid ultrasound, are complementary methods in the evaluation of thyroid disorders.

Thyrotoxic periodic paralysis presenting with quadriparesis and hyperreflexia.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that manifests as painless flaccid paralysis. An East Asian man in his late 20s presented to the emergency department with an acute onset of quadriparesis associated with hypertonia and hyperreflexia. His initial symptoms and signs suggested involvement of the brain and spinal cord; however, MRI of the neuroaxis was normal. His serum potassium concentration was low, and thyroid test results were consistent with hyperthyroidism. The patient was diagnosed with TPP associated with Graves' disease and was treated with potassium supplementation, propranolol and methimazole. Motor strength improved to his baseline level of power; bulk was normal, and tone was increased. Although flaccid paralysis is a typical presentation of TPP, brisk reflexes and muscle spasticity cannot rule out this condition. This case highlights the importance of considering TPP as a possible diagnosis in patients presenting with acute quadriparesis.

Effectiveness and potential mechanism of Jiawei-Xiaoyao-San for hyperthyroidism: a systematic review.

Objectives: To evaluate the effectiveness and potential mechanism of traditional Chinese medicine Jiawei-Xiaoyao-San (JWXYS) as an adjunct or mono- therapy for antithyroid drugs (ATDs) in the treatment of hyperthyroidism. Methods: Eight databases and three trial registries were searched from inception until May 2023. Randomized controlled trials (RCTs) were included and meta-analysis was conducted using RevMan 5.4 and Stata 14.0. The Cochrane risk of bias (ROB) tool 1.0 and GRADE tool was used for quality appraisal. The findings from case reports using mono-JWXYS and pharmacological studies were summarized in tables. Results: Thirteen RCTs with 979 participants were included. The majority of the included studies were assessed as high risk of bias in one ROB domain. Compared with ATDs, JWXYS plus ATDs resulted in lower free triiodothyronine (FT3) (MD = -1.31 pmol/L, 95% CI [-1.85, -0.76]; low-certainty), lower free thyroxine (MD = -3.24 pmol/L, 95% CI [-5.06, -1.42]; low-certainty), higher thyroid stimulating hormone (MD = 0.42 mIU/L, 95% CI [0.26, 0.59]; low-certainty), higher effectiveness rate of traditional Chinese medicine syndrome (RR = 1.28, 95% CI [1.08, 1.52]; low-certainty), lower goiter score (MD = -0.66, 95% CI [-1.04, -0.29]; very low-certainty), lower thyrotrophin receptor antibody (SMD = -0.44, 95% CI [-0.73, -0.16]; low-certainty) and fewer adverse events (AEs) (RR = 0.34, 95% CI [0.18, 0.67]; moderate-certainty). Compared with regular dosage of ATDs, JWXYS plus half-dose ATDs resulted in fewer AEs (RR = 0.24, 95% CI [0.10, 0.59]; low-certainty). Compared with ATDs in 1 trial, JWXYS resulted in higher FT3, lower goiter score and fewer AEs. Three case reports showed that the reasons patients sought TCM-only treatment include severe AEs and multiple relapses. Three pharmacological studies demonstrated that JWXYS restored Th17/Treg balance, lowered deiodinases activity, regulated thyroid cell proliferation and apoptosis, and alleviated liver oxidative stress in mouse or rat models. Conclusion: JWXYS may enhance the effectiveness of ATDs for hyperthyroidism, particularly in relieving symptoms and reducing AEs. Mono-JWXYS is not recommended except in patients intolerant to ATDs. The findings should be interpreted with caution due to overall high risk of bias. Further pharmacological studies with more reliable models are needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023394923.

Manejo del paciente con Hipertiroidismo en consulta externa de la Unidad Técnica de Endocrinología del Hospital Carlos Andrade Marín / Management of the patient with hyperthyroidism in the outpatient clinic of the Technical Unit of Endocrinology of the Endocrinology Technical Unit of the Carlos Andrade Marín Hospital

El hipertiroidismo es un trastorno caracterizado por el exceso de hormonas tiroideas. El déficit de yodo es un factor clave en dicha patología y en lugares con suficiencia del mismo se asocian a au-toinmunidad tiroidea. La prevalencia de hipertiroidismo mani-fiesto varía del 0,2% al 1,3% en áreas con suficiencia de yodo, sin embargo, esto puede variar en cada país por diferencias en umbrales de diagnóstico, sensibilidad de ensayo y población se-leccionada. Un reporte de The Third National Health and Nutri-tion Examination Survey (NHANES III) mostró que el hiperti-roidismo manifiesto se presenta en 0,7% de la población general e hipertiroidismo subclínico en el 1,7%1,2.En incidencia, la patología se asocia con la suplementación de yodo, con la mayor frecuencia en áreas de deficiencias, por au-mento de nódulos tiroideos en la población anciana, teniendo a regiones de áreas montañosas como América del Sur, África Central y suroeste de Asia dentro de este grupo. Un meta aná-lisis de estudios europeos mostró una incidencia general de 50 casos por 100000 personas/años1. En Ecuador, según los datos del Instituto Nacional de Estadísticas y Censos (INEC) del 2017, se reportaron 157 casos de hipertiroidismo, de los cuales la En-fermedad de Graves (EG) fue la causa más común, seguida por el bocio multinodular tóxico (BMNT) y finalmente el adenoma tóxico (AT) con una incidencia de 61 %, 24 % y 14 % respecti-vamente3.Los pacientes con esta patología tienen aumento de riesgo com-plicaciones cardiovasculares y mortalidad por todas las causas, siendo falla cardíaca uno de sus principales desenlaces, así el diagnóstico precoz evita estos eventos, principalmente en pobla-ción de edad avanzada.El presente protocolo se ha realizado para un correcto trata-miento de esta patología en el Hospital de Especialidades Carlos Andrade Marín (HECAM).

Hyperthyroidism is a disorder characterized by an excess of thyroid hormones. Iodine deficiency is a key factor in this pa-thology and in places with iodine deficiency it is associated with thyroid autoimmunity. The prevalence of overt hyperthyroidism varies from 0,2% to 1,3% in iodine-sufficient areas; however, this may vary from country to country due to differences in diag-nostic thresholds, assay sensitivity, and selected population. A report from The Third National Health and Nutrition Examina-tion Survey (NHANES III) showed that overt hyperthyroidism occurs in 0,7% of the general population and subclinical hyper-thyroidism in 1,7%1,2.In incidence, the pathology is associated with iodine supplemen-tation, with the highest frequency in areas of deficiencies, due to increased thyroid nodules in the elderly population, having regions of mountainous areas such as South America, Central Africa and Southwest Asia within this group. A meta-analysis of European studies showed an overall incidence of 50 cases per 100000 person/years1. In Ecuador, according to data from the National Institute of Statistics and Census (INEC) in 2017, 157 cases of hyperthyroidism were reported, of which, Graves' di-sease (GD) was the most common cause, followed by toxic mul-tinodular goiter (BMNT) and finally toxic adenoma (TA) with an incidence of 61 %, 24 % and 14 % respectively3.Patients with this pathology have an increased risk of cardiovas-cular complications and all-cause mortality, with heart failure being one of the main outcomes, so early diagnosis avoids these events, mainly in the elderly population.The present protocol has been carried out for the correct treat-ment of this pathology at the Carlos Andrade Marín Specialties Hospital (HECAM).

Radix Scrophulariae Extracts Exert Effect on Hyperthyroidism via MST1/Hippo Signaling Pathway.

OBJECTIVE: To explore the mechanism of Radix Scrophulariae (RS) extracts in the treatment of hyperthyroidism rats by regulating proliferation, apoptosis, and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1 (MST1)/Hippo pathway. METHODS: Twenty-four rats were randomly divided into 4 groups according to a random number table: control, model group, RS, and RS+Hippo inhibitor (XMU-MP-1) groups (n=6 per group). Rats were gavaged with levothyroxine sodium tablet suspension (LST, 8 µ g/kg) for 21 days except for the control group. Afterwards, rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg, and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1. After 15 days of administration, thyroid gland was taken for gross observation, and histopathological changes were observed by hematoxylin-eosin staining. The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy. The expression of thyrotropin receptor (TSH-R) was observed by immunohistochemistry. Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues. Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1, p-large tumor suppressor gene 1 (LATS1), p-Yes1 associated transcriptional regulator (YAP), proliferating cell nuclear antigen (PCNA), G1/S-specific cyclin-D1 (Cyclin D1), B-cell lymphoma-2 (Bcl-2), Caspase-3, microtubule-associated proeins light chain 3 II/I (LC3-II/I), and recombinant human autophagy related 5 (ATG5). Thyroxine (T4) level was detected by enzyme-linked immunosorbent assay. RESULTS: The thyroid volume of rats in the model group was significantly increased compared to the normal control group (P<0.01), and pathological changes such as uneven size of follicular epithelial cells, disorderly arrangement, and irregular morphology occurred. The secretion of small vesicles by Golgi apparatus was reduced, and the expressions of receptor protein TSH-R and T4 were significantly increased (P<0.01), while the expressions of MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 were significantly decreased (P<0.01). The expressions of Bcl-2, PCNA, and cyclin D1 were significantly increased (P<0.01). Compared with the model group, RS extracts reduced the volume of thyroid gland, improved pathological condition of the thyroid gland, promoted secretion of the secretory vesicles with double-layer membrane structure in thyroid Golgi, significantly inhibited the expression of TSH-R and T4 levels (P<0.01), upregulated MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 expressions (P<0.01), and downregulated Bcl-2, PCNA, and Cyclin D1 expressions (P<0.01). XMU-MP-1 inhibited the intervention effects of RS extracts (P<0.01). CONCLUSION: RS extracts could inhibit proliferation and promote apoptosis and autophagy in thyroid tissues through MST1/Hippo pathway for treating hyperthyroidism.

What are the risks associated with lipiodol hysterosalpingography? A literature review.

INTRODUCTION: Hysterosalpingography is widely used as a first-line investigation for infertility, and may also be therapeutic, increasing pregnancy rates. Aqueous and oil-based contrast agents can be used. Some studies suggest Lipiodol hysterosalpingography has a greater therapeutic effect on fertility than aqueous contrast, though this is contentious. There are additionally safety concerns surrounding Lipiodol hysterosalpingography. This review summarises the adverse effects associated with Lipiodol hysterosalpingography, particularly on thyroid function. KEY FINDINGS: 331 articles were identified. Of these, 46 met inclusion criteria. 3 further articles were identified from reference lists. Complications typically cited in the literature include pain, intravasation, life-threatening oil embolism, and lipogranuloma formation. Emerging evidence suggests that Lipiodol hysterosalpingography may also impact maternal and neonatal thyroid function. Women may develop hypo- or hyperthyroidism. Thyroid dysfunction is clinically significant as even subclinical hypothyroidism reduces fertility, increases the risk of pregnancy complications including miscarriage, pre-eclampsia and perinatal mortality, and adversely impacts foetal neurodevelopment. One study suggested a possible link with neonatal congenital hypothyroidism. CONCLUSION: There is emerging evidence to suggest that Lipiodol hysterosalpingography can cause hypo- or hyperthyroidism, in addition to known adverse effects of pain, intravasation, oil embolism, and lipogranuloma formation. IMPLICATIONS FOR PRACTICE: Given the significance of these risks, and contention surrounding whether Lipiodol truly increases pregnancy rates compared to aqueous mediums, careful consideration is required in the selection of contrast agent. In particular, Lipiodol hysterosalpingography may not be suitable for women with pre-existing thyroid dysfunction.

Povidone-iodine-induced transient triiodothyronine thyrotoxicosis in a Japanese patient with prolonged habitual gargling: A case report and literature review.

RATIONALE: Iodine-induced hyperthyroidism and triiodothyronine (T3) thyrotoxicosis in patients who routinely gargle with povidone-iodine (PVP-I) gargling solution are rare in Japan. PATIENT CONCERNS: A 50-year-old man presented to our hospital for a close examination of an enlarged thyroid, which was noted during a complete health checkup. The thyroid was slightly enlarged with no palpable nodules. He had an increased appetite but no weight gain. He had been routinely gargling with PVP-I gargling solution 4 times daily for >10 years. He had no history of thyroid disease. DIAGNOSES: Test results revealed suppressed thyroid-stimulating hormone, normal free thyroxine, and increased free triiodothyronine levels, leading to the diagnosis of T3 thyrotoxicosis. INTERVENTIONS: The patient agreed to stop gargling with PVP-I gargle solution. OUTCOMES: The free triiodothyronine and thyroid-stimulating hormone levels returned to normal at 18 and 21 weeks, respectively, after discontinuation of PVP-I gargling. After an improvement in thyroid function, he gained 5 kg in 1 year. LESSONS: To our knowledge, this is the first case report that describes PVP-I gargle-induced T3 thyrotoxicosis in a healthy individual without thyroid disease. In Japan, which is an iodine-sufficient country, considering the possibility of high-dose iodine intake-induced thyrotoxicosis due to long-term PVP-I gargling or other causes is necessary, even in individuals with no history of thyroid disease.

Urine concentrating ability in cats with hyperthyroidism: Influence of radioiodine treatment, masked azotemia, and iatrogenic hypothyroidism.

BACKGROUND: Hyperthyroid cats often have urine specific gravity (USG) values <1.035. It remains unclear how USG changes after treatment, if USG can be used to predict azotemia after treatment, or how iatrogenic hypothyroidism influences USG values. OBJECTIVES: To determine the proportion of hyperthyroid cats with USG <1.035 vs ≥1.035; if USG changes after treatment; and whether USG <1.035 correlated with unmasking of azotemia or hypothyroidism. ANIMALS: Six hundred fifty-five hyperthyroid cats treated with radioiodine; 190 clinically normal cats. METHODS: Prospective, before-and-after study. Hyperthyroid cats had serum thyroxine, thyroid-stimulating hormone, and creatinine concentrations, and USG measured before and 6 months after successful treatment with radioiodine. RESULTS: Of untreated hyperthyroid cats, USG was ≥1.035 in 346 (52.8%) and <1.035 in 309 (47.2%). After treatment, 279/346 (80.6%) maintained USG ≥1.035, whereas 67/346 (19.4%) became <1.035; 272/309 (88%) maintained USG <1.035, whereas 37/309 (12%) became ≥1.035. Only 22/346 (6.4%) with USG ≥1.035 developed azotemia after treatment, compared with 136/309 (44%) with <1.035 (P < .001). Of cats remaining nonazotemic, 38% had USG <1.035, compared with 20% of normal cats (P < .001). The 137 cats with iatrogenic hypothyroidism had lower USG after treatment than did 508 euthyroid cats (1.024 vs 1.035), but USGs did not change after levothyroxine supplementation. USG <1.035 had high sensitivity (86.1%) but moderate specificity (65.2%) in predicting azotemia after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperthyroidism appears not to affect USG in cats. However, cats with evidence of sub-optimal concentrating ability before radioiodine treatment (USG < 1.035) are more likely to develop azotemia and unmask previously occult chronic kidney disease. Iatrogenic hypothyroidism itself did not appear to affect USG values.

Biotin induced biochemical hyperthyroidism: a case report and review of the literature.

BACKGROUND: Biotin is a commonly used supplement for hair, nail, and skin. Recent literature suggests that high-dose biotin therapy for neurological diseases like Multiple sclerosis can interfere with lab results that use biotin/streptavidin immunoassay, called biotin interference. Biotin interference can affect thyroid lab results, giving biochemical hyperthyroidism. CASE PRESENTATION: Our patient, a 64-year-old white man with a known history of multiple sclerosis, presented with elevated free T3, free T4, and low TSH that resembled hyperthyroidism. He had no symptoms of hyperthyroidism except some fatigue and tachycardia on the first encounter. He was started on anti-thyroid medications. He was then re-evaluated since his lab results remained the same after two months of anti-thyroid medications. It was found that he was on biotin, 10000mcg/day, for his multiple sclerosis. Biotin was discontinued, and five days later his lab results returned to normal values. CONCLUSION: The lack of knowledge of biotin use by patients can lead to misdiagnosis of patients' thyroid lab results and improper management. Awareness about biotin interference and abnormal thyroid lab values should be a priority among clinicians and the public. If the biotin is discontinued on time, such misdiagnosis can be avoided.

Immunomodulatory role of vitamin D and selenium supplementation in newly diagnosed Graves' disease patients during methimazole treatment.

Introduction: Methimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group. Methods: In the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment. Results: At baseline, circulating total CD3-CD56+NK cells and CD56bright NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56bright NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56dim NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p<0.001). Following 6 months of treatment, NK cells decreased in both the intervention and MMI-alone groups, but significantly more in the intervention group (total NK: -10.3%, CI 95% -15.8; -4.8% vs -3.6%, CI 95% -9; 1.8%, p=0.09 and CD56bright NK cells: -6.5%, CI 95% -10.1; -3 vs -0.9%, CI 95% -4.4; 2%, p=0.03). Compared to baseline, CD69+ NK cells significantly decreased, while degranulation ability slightly improved, although no differences emerged between the two treatment groups. Compared to baseline, Treg cell frequency increased exclusively in the intervention group (+1.1%, CI 95% 0.4; 1.7%). Discussion: This pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study.

Postoperative Hypocalcemia in Hyperthyroid Patients: The Parathyroids Aren't Always to Blame.

INTRODUCTION: Hypocalcemia is commonly reported after thyroidectomy and has multiple possible etiologies including: parathyroid devascularization, reactive hypoparathyroidism from relative hypercalcemia in thyrotoxicosis, and abrupt reversal of thyrotoxic osteodystrophy. In patients that are actively hyperthyroid and undergoing thyroidectomy, it is not known how many experience hypocalcemia from nonhypoparathyroidism etiologies. Therefore, our aim was to examine the relationship among thyrotoxicosis, hypocalcemia, and hypoparathyroidism. METHODS: A retrospective review was performed of prospectively-collected data from all patients undergoing thyroidectomy for hyperthyroidism by 4 surgeons from 2016 to 2020. All patients carried a diagnosis of Graves' disease or toxic multinodular goiter. Patient demographics, preoperative medications, laboratory reports, and postoperative medications were reviewed. Hypocalcemia within the first month of surgery despite a normal parathyroid hormone (PTH) level was the primary outcome of interest and was compared between patients with and without thyrotoxicosis. Secondary outcomes were duration of postoperative calcium use and the relationship between preoperative calcium supplementation and postoperative calcium supplementation. Descriptive statistics, Wilcoxon rank-sum, and chi-square tests were used for bivariate analysis, as appropriate. RESULTS: A total of 191 patients were identified, with mean age of 40.5 y (range 6-86). Most patients were female (80%) and had Graves' disease (80%). At the time of surgery, 116 (61%) had uncontrolled hyperthyroidism (thyrotoxic group, Free Thyroxine >1.64 ng/dL or Free Triiodothyronine > 4.4 ng/dL), with the remaining 75 (39%) considered euthyroid. Postoperative hypocalcemia (calcium < 8.4 mg/dL) developed in 27 (14%), while hypoparathyroidism (PTH < 12 pg/mL) was observed in 39 (26%). Thyrotoxic patients comprised a majority of those with hypocalcemia (n = 22, 81%, P = 0.01) and hypoparathyroidism immediately following surgery (n = 14, 77%, P = 0.04). However, a majority of initially hypocalcemic, thyrotoxic patients had normal PTH values within the first month after surgery (n = 17, 85%), pointing to a potential nonparathyroid etiology. On bivariate analysis, no significant relationship was found for thyrotoxic patients with initial postoperative hypocalcemia (18%) and hypoparathyroidism <1-month after surgery (29%, P = 0.29) or between 1 and 6 mo after surgery (2%, P = 0.24). Of the 19 patients in the nonhypoparathyroidism group, 17 (89%) were off all calcium supplements by 6 mo postop. CONCLUSIONS: In patients with hyperthyroidism, those in active thyrotoxicosis at time of surgery have a higher rate of postoperative hypocalcemia compared to euthyroid patients. When hypocalcemia lasts >1 mo postoperatively, data from this study suggest that hypoparathyroidism may not be the primary etiology in many of these patients, who typically require calcium supplementation no more than 6 mo postoperatively.

Significant Interference of Biotin in Thyroid Function Tests Using Beckman Analyzer: How to Identify such Interferences?

OBJECTIVE: Biotin in elevated concentration interferes with biotin-based immunoassays. We studied biotin interferences in TSH, FT4, FT3, total T4, total T3 and thyroglobulin assays both in vitro and in vivo using Beckman DXI800 analyzer. METHODS: Two serum pools were prepared from left-over specimens. Then aliquots of each pool (and serum control) were supplemented with various amounts of biotin followed by measuring thyroid function tests again. Three volunteers each took 10 mg biotin supplement. We compared thyroid function tests before and 2 h after taking biotin. RESULTS: We observed significant biotin interferences in biotin-based assays (positive interference with FT4, FT3, and total T3 assay but negative interference with thyroglobulin) both in vitro and in vivo but non-biotin-based assays (TSH and total T4) were not affected. CONCLUSIONS: Elevated FT3 and FT4 in the presence of normal TSH is inconsistent with hyperthyroidism and should be followed up with total T3 and T4 test. Significant discrepancy between total T3 (falsely elevated value due to biotin) and total T4 (not affected as the assay is not biotin based) maybe an indication of biotin interference.

Factitious thyrotoxicosis and thyroid hormone misuse or abuse.

Factitious thyrotoxicosis (FTT) is a common form of thyroid hormone (TH) abuse involving voluntary but concealed intake of an excessive amount of TH. In most cases, FTT seeks to improve body composition with a decrease in body fat and weight while maintaining apparent fitness. It is frequent in Munchausen syndrome, to attract attention for care. It can involve excessive intake either of thyroxine (T4) or of thyroid extracts or liothyronine (T3). In addition, several dietary supplements available on-line were shown to contain clinically relevant amounts of T4 and T3. TH abuse also occurs in elite athletes and bodybuilders, to reach the appropriate weight and prioritize fat loss. Diagnosis should be suspected whenever the typical features of hyperthyroidism or endogenous thyrotoxicosis are not present, as prolonged overlooked TH abuse can lead to severe consequences, including life-threatening events.

Effect of a polyherbal formulation on L-thyroxine induced hyperthyroidism in a rat model: In vitro and in vivo analysis and identification of bioactive phytochemicals.

An excess of thyroid hormones in the blood characterizes hyperthyroidism. Long-term use of prescription medications to treat hyperthyroidism has substantial adverse effects and when discontinued, the symptoms frequently recur. Several plant species have been utilized to cure hyperthyroidism. In the present work, we investigated the impact of polyherbal extract (POH) of four medicinal plants to treat hyperthyroidism. Biochemical analysis revealed the presence of a high concentration of phytochemicals in the POHs. The in vitro antioxidant study revealed their antioxidant and free radical scavenging capacity. The gas chromatography coupled mass spectrometry analysis of the POHs showed the presence of 13 bioactive phytochemical compounds. The effect of various concentrations of POHs on L-thyroxine-induced hyperthyroidism in Wistar albino rats was evaluated for 18 days. The TSH, T3 and T4 levels increased significantly and reduced the increase of liver enzymes caused by hyperthyroidism in POH-treated rats. The data showed that POH therapy could restore thyroid function to normal. The injection of POH increased the size comprising vacuolated cells, columnar follicular cells and highly coloured nuclei with increasing POH content and the number of normal thyroid follicles rose. The findings indicate that polyherbal formulations of these medicinal plants include credible antithyroid compounds that may offer a protective and an effective alternative treatment to synthetic thyroid medications.

Thyrotoxic periodic paralysis associated with lactic metabolic acidosis: Case report of an African man and review of literature.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare and most often acquired subtype of hypokalemic periodic paralysis. The association of varying degrees of muscle weakness, hyperthyroidism and hypokalemia characterizes it. The treatment requires potassium supplementation, control of hyperthyroidism and prevention measures. It is a frequent disease in Asian men, but much rare in Caucasian or African populations. This is the first report of TPP associated with lactic metabolic acidosis in an African man. CASE PRESENTATION: A 23 year-old African man, native from Morocco, with recurrent episodes of tetraparesis for eleven months, and abdominal pain, was referred for evaluation. Biochemical investigations showed severe hypokalemia associated with hyperthyroidism and lactic metabolic acidosis. His EKG showed signs of hypokalemia such as sinus tachycardia and U waves. After potassium supplementation, neurological recuperation was quick and complete. Thyroid ultrasound identified a hypoechogenic and hypervascularized goiter, associated with high levels of thyroid antibodies, in favor of Grave's disease. With antithyroid drugs and life-style changes, the patient did not have any other attack. REVIEW OF LITERATURE: In addition to the case report, this article presents an extended review of literature, from the first large study reporting the diagnosis and incidence of TPP in 1957 to nowadays. Are reported here the latest information concerning epidemiology, clinical manifestations, complementary examinations, management and genetic finding. The lactic acidosis observed initially is exceptional, never described in TPP. TPP is a diagnostic and therapeutic emergency, requiring careful potassium supplementation, in order to avoid the risk of the onset of rebound hyperkalemia, to be maintained until the etiological treatment is effective. Paraclinical assessment with emergency EKG and electromyogram are essential to assess the impact. DISCUSSION: It is essential in the face of any hypokalaemic periodic paralysis, including in non-Asian subjects, to search hyperthyroidism. CONCLUSIONS: This report demonstrates the importance of thyroid testing in case of acute muscle weakness, even in non-Asian patients in order to diagnose TPP. This is a rare but possible etiology, to be distinguished from the familial form of hypokalemic periodic paralysis. It also questions on the impact of TPP on energetic metabolism, in particular on lactic metabolism.

Graves' Disease in Children Presenting With Fragility Fracture: A Case Report.

Background: Adults with hyperthyroidism have been found to have decreased bone mineral density (BMD) and higher fracture risk. The most typical cause of hyperthyroidism is Graves' disease. However, there are limited studies on how hyperthyroidism affects bone metabolism and fractures in children. We describe a unique instance of a patient who initially displayed a fragility fracture and was ultimately identified with Graves' disease after biochemical evaluations. Case Summary: A 2-year-8-month-old female presented with fragility fractures three times in only 7 months. A series of examinations were performed to evaluate any possible malformations or abnormalities of bone metabolism. Graves' disease was found, and drug therapies were employed (methimazole, propranolol, calcium carbonate, vitamin D). Since children with Graves' disease and fragility fractures have been uncommonly described in the past, a stringent and thorough long-term follow-up was initiated. Conclusions: Children with undiagnosed Graves' disease had a higher risk of fractures and osteoporosis. This case suggests that BMD measurement may be necessary for the initial evaluation of Graves' disease in children.