The association between thyroid disease and hearing loss: a meta-analysis.

BACKGROUND: It has been shown that there is a link between thyroid-related diseases and hearing loss. OBJECTIVES: The purpose of this study is to investigate the relationship between thyroid-related diseases and hearing loss by conducting a meta-analysis. MATERIAL AND METHODS: A thorough search was carried out in the following electronic databases: PubMed, Cochrane Library, Embase, Web of Science, Google Scholar, Semantic Scholar, and ResearchRabbit. The chi-square test and the I2 index examined the research's heterogeneity. A funnel plot and the Eger test were used to examine publication-biased effects. RESULTS: A total of 48,507 individuals (6482 hypothyroid patients, 4162 hearing loss patients, and 37863 controls) were included in this meta-analysis of 18 research. Individuals with hypothyroidism had a 1.69-fold increased risk of hearing loss compared to those without the condition (OR: 1.69; 95% CI: 1.11-2.57, p < 0.001). among hypothyroidism, the prevalence of hearing loss was 24% (EC: 0.24; 95% CI: 0.11-0.39, p = 0.00), while among hearing-impaired individuals, the prevalence of hypothyroidism was 7% (EC: 0.21; 95% CI: 0.07-0.40). CONCLUSION: This study demonstrated how thyroid dysfunction can raise the chance of hearing loss. To completely comprehend the underlying mechanisms and create efficient treatments for this illness, more study is required.

foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

BACKGROUND: FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. RESULTS: Mutant fish have increased expression of tshß in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). CONCLUSION: Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

Evaluation of thyroid profile among children aged 1-15 years with nephrotic syndrome: An observation study.

BACKGROUND: The interaction between the kidney and the thyroid is important for normal function of both organs. In nephrotic syndrome, proteinuria leads to loss of several proteins, which in turn causes hypothyroidism. AIM: To assess the thyroid function in children with nephrotic syndrome. METHODS: This cross-sectional study was conducted in a tertiary center, Bhopal, from February 2020 to January 2021. Consecutive children aged 1-15 years admitted with nephrotic syndrome (first-time diagnosed and all relapse cases) were included in the study. A thyroid profile was sent along with routine investigations, and thyroid hormone status was assessed in nephrotic syndrome children. RESULTS: Of the 70 patients, 39 (55.7%) showed abnormal thyroid profiles; 19 (27.1%) had overt hypothyroidism, and 20 (28.6%) had subclinical hypothyroidism. Overt hypothyroidism was seen in 16.1% of newly diagnosed cases, 40% of second relapses, and 2.7% of frequently relapsed cases (P < 0.001). The mean serum free T3 and free T4 levels in frequent relapses were 2.50 ± 0.39 ng/dL and 0.78 ± 0.12 ng/dL, respectively, which were significantly lower than in newly diagnosed cases (2.77 ± 0.37 ng/dL and 0.91 ± 0.19 ng/dL, respectively). The mean thyroid-stimulating hormone (TSH) level was significantly higher in frequent relapses 5.86 ± 1.56 µIU/mL) and second relapse (5.81 ± 1.78 µIU/mL) than in newly diagnosed cases (4.83 ± 0.76 µIU/mL) and first relapse cases (4.74 ± 1.17 µIU/mL), (P < 0.01). CONCLUSION: An abnormal thyroid profile was commonly observed in children with nephrotic syndrome, and overt hypothyroidism was more common in frequent relapse cases. Therefore, thyroid screening should be a part of the management of nephrotic syndrome so that hypothyroidism can be detected and managed at an early stage.

Diagnostic options, physiopathology, risk factors and genetic causes of permanent congenital hypothyroidism: A narrative review.

Background: In Permanent congenital hypothyroidism (PCH) is a lifelong condition characterized by a deficiency in thyroid hormone, leading to various neurodevelopmental complications. Early clinical signs are often nonspecific and easily overlooked, but newborn screening programs have improved early detection. Methods: This narrative review aims to provide insights comparatively transient and permanent PCH and also the diagnosis, risk factors, underlying pathophysiology, and genetic causes associated with PCH. Relevant studies were identified through a comprehensive search using the term 'Permanent congenital hypothyroidism' (Mesh) across scientific databases of electronic databases such as PubMed, Scopus, and Web of Science. Results: Prompt initiation of thyroid hormone replacement therapy, particularly within the initial two weeks postpartum, crucially enhances neurocognitive development outcomes. Multiple predictive approaches, encompassing screening TSH levels, maternal thyroid history, and levothyroxine dosage per kilogram assessment, aid in identifying PCH. Recent studies have demonstrated a mounting prevalence of PCH, contributing significantly to the overall rise in CH incidence. Genetic factors, primarily DUOX2 and DUOXA2 mutations, alongside environmental influences such as post-term birth, low birth weight, and macrosomia, may induce PCH. Nonetheless, reliable markers for early PCH prediction upon diagnosis remain elusive, leading to delayed recognition post-ceasing levothyroxine treatment around age 3. Conclusions: Recent studies have observed an increased incidence of PCH, contributing substantially to the overall rise in cases of congenital hypothyroidism. Understanding the diagnostic options and genetic etiologies associated with PCH is crucial for the early identification and appropriate management.

Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency.

In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3-6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

Brain Abnormalities in Young Single- and Double-Heterozygote Mice for Both Nkx2-1- and Pax8-Null Mutations.

In humans and mice, Nkx2-1 and Pax8 are crucial morphogenic transcription factors defining the early development of the thyroid and specific extrathyroidal tissues. By using 3-month-old single or double heterozygotes for Nkx2-1- and Pax8-null mutations (DHTP) mice, we studied brain abnormalities under different human-like dysthyroidisms, focusing on putative alterations of specific neurotransmitter systems, expression of markers of pre- and post-synaptic function and, given the physio-pathological role mitochondria have in controlling the bioenergetic status of neurons, of mitochondrial dynamics and oxidative balance. Compared to Wt controls, DHTP mice, bearing both systemic and brain hypothyroidism, showed altered expression of synaptic markers, generic and cholinergic (corroborated by immunohistochemistry in caudate, putamen, hippocampus, and basal forebrain) and glutamatergic ones, and reduced expression of key proteins of synaptic plasticity potency and several isoforms of glutamate receptors. The brain of DHTP mice was characterized by lower levels of H2O2 and imbalanced mitochondrial dynamics. Nkx2-1 + / - mice showed dopaminergic neuron-specific alterations, morphologically, more evident in the substantia nigra of DHTP mice. Nkx2-1 + / - mice also showed enhanced mitochondrial biogenesis and oxidative capacity likely as a global response of the brain to Nkx2-1 haploinsufficiency and/or to their elevated T3 circulating levels. Reduced transcription of both tyrosine hydroxylase and dopamine transporter was observed in Pax8 + / - euthyroid mice, suggesting a dopaminergic dysfunction, albeit likely at an early stage, but consistent with the deregulated glucose homeostasis observed in such animals. Overall, new information was obtained on the impact of haploinsufficiency of Pax8 and NKx2-1 on several brain neuroanatomical, molecular, and neurochemical aspects, thus opening the way for future targeting brain dysfunctions in the management of both overt and subclinical thyroid dysfunctions.

Pooled prevalence of hypothyroidism among Indian females with infertility: A systematic review & meta-analysis.

Background & objectives Studies suggest hypothyroidism is responsible for female infertility. This review aimed to determine the pooled prevalence of hypothyroidism in Indian infertile women so that hypothyroidism screening can be initiated, and policies are designed for prevalence reduction. Methods Electronic databases including PubMed, Google Scholar and Cochrane library were searched to obtain the relevant articles. Studies that reported the proportion of hypothyroidism in Indian infertile women were selected. Systematic procedures for study selection and data extraction were followed. Each study was evaluated for quality using the Joanna Briggs institute (JBI) critical appraisal checklist. To pool the effect sizes, a random effects model was utilized. Funnel plot and Egger's test were used to assess publication bias. To quantify heterogeneity among studies, I2 statistics were utilized. Subgroup and meta-regression analyses were used to further investigate the heterogeneity of pooled estimates. The sensitivity analysis done whereby each study was excluded in order to examine the influence of that study in the pooled estimate. A P-value of 0.05 or less was considered statistically significant. Results Out of 198 articles, a total of 20 studies involving 2396 cases met the inclusion criteria. The pooled prevalence of hypothyroidism in women with infertility was 28 per cent [95% confidence interval (CI): 20% to 36%] which was highest in Telangana at 62 per cent (n=1; 95% CI 48% to 74%) and lowest in Karnataka at 14 per cent (n=2; 95% CI: 10% to 18%). Interpretation & conclusions Infertile women have high proportion of hypothyroidism, suggesting that screening programmes during diagnostic workup for infertility may provide optimal care. The result of this meta-analysis will help design guidelines and earmark highest prevalence regions to initiate preventive and diagnostic measures for prevalence reduction in future.

A Study of Non-alcoholic Fatty Liver Disease in Patients With Hypothyroidism: A Cross-Sectional Study in a Tertiary Care Hospital.

Background Hypothyroidism occurs when the thyroid gland is underactive and fails to produce sufficient thyroid hormones. It can affect multiple organs including the heart, brain, liver, kidneys, and reproductive system, leading to symptoms such as fatigue, cognitive impairment, elevated cholesterol, fluid retention, fatty liver, and menstrual irregularities. Given the higher prevalence of fatty liver disease in patients with hypothyroidism, it is important to evaluate the need for routine screening for fatty liver in these patients. Materials and methods This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from October 2022 to June 2024. The study included 60 patients aged over 12 years who were known or recently diagnosed with hypothyroidism. Patients with type 2 diabetes mellitus, pregnant women, or those with chronic liver disease were excluded. Data collected included physical examination findings and laboratory test results. Fatty liver was diagnosed using magnetic resonance elastography. Statistical analysis was performed using IBM SPSS statistics for Windows, version 20 (IBM Corp., Armonk, New York). The statistical significance of parametric data was evaluated using the Chi-square test. A p-value less than 0.05 and a confidence interval of 95% were considered statistically significant. Result The study population had an average age of about 45 years, with most participants aged between 40 and 49 years. The majority of the participants were female, making up over 83% of the group, while males constituted about 17%. The most commonly reported symptom was weight gain, followed by constipation and fatigue. For individuals with fatty liver, the average thyroid-stimulating hormone (TSH) level was notably higher compared to those without fatty liver. Additionally, low-density lipoprotein (LDL) levels were higher in individuals with non-alcoholic fatty liver disease (NAFLD) compared to those without. Both TSH and LDL levels showed a statistically significant association with the occurrence of NAFLD. Conclusion Hypothyroidism was more prevalent in females and in the age group 40-49 years. There was a statistical significance between TSH and the occurrence of NAFLD. In this study, statistical significance was also found between LDL and the occurrence of NAFLD.

Roxadustat has risks of reversible central hypothyroidism in patients undergoing hemodialysis: a single-center retrospective cohort study.

Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60-4.51) mU/L before roxadustat treatment to 1.36 (0.72-2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78-4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97-1.24) ng/dL before roxadustat treatment to 0.92 (0.71-1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93-1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78-2.31) pg/mL before starting roxadustat, 1.97 (1.69-2.27) pg/mL during treatment, and 1.90 (1.63-2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.

Obesity and Hormonal Influences on Asthma: Mechanisms, Management Challenges, and Emerging Therapeutic Strategies.

Obesity and hormonal dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiological characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.

Comparative analysis of clinical profile, laboratory profile and outcome in COVID-19 patients with and without hypothyroidism.

Objectives: Previous studies suggest that patients' thyroid status might directly impact the course of Coronavirus disease 2019 (COVID-19). The objective of the study was to determine the clinical profile of COVID-19 patients with hypothyroidism and compare it with that of COVID-19 patients without hypothyroidism. Design: Retrospective observational study. Setting: The study was conducted in a tertiary healthcare centre in Tamil Nadu between May and June 2021. Participants: The study included 117 patients admitted with hypothyroidism and COVID-19 as well as 117 age and Gender matched COVID-19 patients without hypothyroidism. Main outcome measures: Data regarding the demography, comorbidities, presenting symptoms, method of diagnosis of COVID-19, computed tomography (CT) severity score, Interleukin 6 (IL-6), D-dimer, oxygen requirement, number of days in hospital and outcome were collected for both groups. Data analysis was conducted, and p<0.05 was considered statistically significant. Results: The study comprised 234 patients over two months, from May to June 2021. Distribution of presenting symptoms showed that the hypothyroidism group presented with a higher incidence of fever (66.67%), loose stool (18.80%) and myalgia (7.69%). Results show that RTPCR+, O2 Requirement, death, D-dimer, IL-6, number of days admitted as well as CT-severity did not show any statistically significant differences (p>0.05) between both groups. The outcomes also showed that both groups reported four mortalities. Conclusions: The results of the study help conclude that the hypothyroidism status of a COVID-19 patient is not associated with higher severity of clinical symptoms, deranged laboratory values as well as mortality. Funding: None declared.

Alport Syndrome With a Rare Collagen Type IV Alpha-4 (COL4A4) Gene Mutation: A Case Report.

Alport syndrome (AS) is a rare, progressive hereditary kidney disease characterized by sensorineural hearing loss and visual abnormalities. It is caused by a mutation in the collagen type IV alpha-4 (COL4A4) gene, which produces type IV collagen, and often manifests in individuals with hematuria, proteinuria, edema, and hypertension. Here, we present a case of AS in a 15-year-old boy with a COL4A4 gene mutation, with renal and extrarenal findings. The patient presented with subnephrotic proteinuria and microscopic hematuria, autoimmune hypothyroidism, and keratoconus. Light microscopy examination of renal biopsy revealed three globally sclerosed renal cortical parenchyma areas with periglomerular fibrosis, and electron microscopy showed variable thickness of glomerular basement membrane with festooned appearance, as well as splitting of lamina densa giving basket weave and criss-cross pattern.

Thyroid Dysfunction and Bipolar Disorder: A Literature Review Integrating Neurochemical, Endocrine, and Genetic Perspectives.

Thyroid disorders are common in medicine, while bipolar disorders (BDs), though less frequent, are significant due to global prevalence, the economic burden on healthcare systems and long-term health implications, and the effects of psychiatric illness on quality of life. Clinical research has suggested thyroid hormone imbalances can cause psychiatric symptoms similar to the clinical features observed in BDs. Despite increased attention in this area of study, much remains unknown regarding how thyroid issues contribute to the development of BDs. This review explores the complex link between thyroid disorders and BDs, focusing on neurochemical dynamics, changes in the hypothalamic-pituitary-thyroid (HPT) axis, and genetic factors. Furthermore, this literature review examines the importance of understanding these factors in linking both conditions and emphasizes the necessity for therapies targeting their shared underlying mechanisms.

The role of glycemic traits in the mediation of the causal effect of hypothyroidism on coronary heart disease.

Background: Hypothyroidism and coronary heart disease are both common diseases in life and both are increasing in prevalence. Many studies have found a strong association between the two. However, they have not been able to prove a causal relationship. Furthermore, numerous studies have demonstrated that glycemic traits play a role in both. Consequently, the objective of this study was to ascertain the causal estimation of the association between hypothyroidism and coronary heart disease and to quantify the potential mediating role of glycemic traits in this relationship. Methods: We used two-sample Mendelian randomisation (UVMR) to explore causality between hypothyroidism and coronary heart disease. Additionally, multivariate Mendelian randomisation (MVMR) was applied to quantify the potential mediation of glycemic traits in this relationship. A variety of Mendelian randomization methods were employed in this study, including the inverse variance weighting (IVW) method, weighted median method, and MR-Egger test. Heterogeneity and horizontal pleiotropy were evaluated through MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis to ensure the robustness of the study results. Results: The results of the MR analyses indicated that hypothyroidism was associated with an increased risk of coronary heart disease (IVW: OR=2.75, 95% CI: 1.53-4.94). In mediation analyses, the proportion of HbA1c-mediated effects of hypothyroidism on coronary heart disease was 7.3% (2.2%-12.5%). Conclusion: The results of our study indicate a causal relationship between hypothyroidism and coronary heart disease. Furthermore, HbA1c partially mediated the causal effect of hypothyroidism on coronary heart disease. Consequently, intervention in this factor may reduce the risk of coronary heart disease associated with hypothyroidism.

Comparison Between Ultrasonography and Radiography in the Detection of Epiphyseal Ossification Centers of the Knee in Infants With Permanent Congenital Hypothyroidism.

OBJECTIVE: To demonstrate the usefulness of ultrasonography in detecting knee ossification centers in infants with permanent congenital hypothyroidism (PCH). METHODS: From 2011 to 2021, all infants with PCH referred for thyroid ultrasound also underwent left knee ultrasound and radiography on the same day. Knee radiographs were compared with knee sonograms. Two pediatric radiologists reviewed the consensus knee radiographs and sonograms to identify femoral and tibial epiphyseal ossification centers (presence/absence). The concordance between ultrasonography and radiography was assessed. Another radiologist conducted a second late review to evaluate interobserver agreement. RESULTS: We identified 125 patients (65 girls, 60 boys) with a mean age of 24 days (5 days-5 months). On scintigraphy, the thyroid was in place in 66.4%, ectopic in 24%, and absent in 9.6% of patients. The femoral center was observed in 108 patients (86.4%) via sonography and 106 patients (84.8%) via radiography. The tibial center was observed in 84 patients (67.2%) via sonography and radiography. Both femoral and tibial centers were present on sonography and radiography in 84 patients (67.2%). A single nucleus was present in 24 patients (19.2%) on sonography and 22 patients (17.6%) on radiography; it corresponded to the femoral center in all patients. The concordance between ultrasonography and radiography was 99% and 100%, respectively, for the detection of the femoral and tibial centers. Interobserver agreement was substantial to almost perfect for both ultrasonography and radiography. CONCLUSION: Ultrasonography is as effective as radiography in detecting knee ossification centers in PCH. It can be performed at the same time as thyroid examination, in place of radiography.

Clinical hypothyroidism in a cat associated with sulfonamide administration for the management of intracranial nocardiosis.

A 2-year-old cat was referred for suspected generalised seizure activity and reclusive behaviour, with a history of non-resolving facial abscess. Magnetic resonance imaging (MRI) revealed a contrast enhancing lesion occupying the left calvarium and adjacent peripheral tissues. The intracranial lesion was causing significant mass effect, with oedema and transtentorial herniation. Nocardia nova was isolated from the lesion and identified by DNA sequencing. Treatment consisted of debridement via craniotomy and ventral bulla osteotomy, and combination antibiotic therapy with clarithromycin, amoxycillin and trimethoprim-sulfonamide (sulfadoxine parenterally, then sulfadiazine orally). After several weeks of antibiotic therapy, the cat developed weakness, bicavitary effusion, myxoedema, non-regenerative anaemia and azotaemia. Total thyroxine (TT4) was below the detectable limit and canine thyroid stimulating hormone (cTSH) assay was markedly elevated at 7.53 ng/mL (reference interval 0.15-0.3 ng/mL). Discontinuation of sulfonamides and administration of levothyroxine resulted in resolution of clinical signs. The cat was subsequently able to discontinue levothyroxine, with recovery of euthyroid state. To the authors' knowledge, this is the first report of clinical hypothyroidism in a cat treated with sulfonamide antibiotics and may influence antimicrobial selection and monitoring during therapy. This report also described the management of an atypical presentation of nocardiosis with intracranial extension.

STAT3 single-nucleotide variants in autoimmune thyroid disease in the Pakhtun population of Khyber Pakhtunkhwa, Pakistan.

The current study was conducted to assess the relationship between the STAT3 gene variants rs744166 and rs2293152 and autoimmune thyroid disorder in the Pakhtun population of the province, of Khyber Pakhtunkhwa, Pakistan. Blood was collected from 100 healthy individuals and 400 thyroid-disordered patients. Of these, one hundred were diagnosed with Hashimoto's thyroiditis (HT), while 32 were confirmed as Grave's disease (GD) patients. T3, T4, and TSH serum levels were checked to diagnose thyroid disorders. The blood was analyzed for anti-thyroid peroxidase antibodies (Anti-TPOAb) (AESKULISA- ATPO - elisa kit), (Germany), and thyroid stimulating hormone receptor antibodies (TSHRAb), TSHR Ab elisa kit (Diametra Italy), respectively. PCR was used to amplify the targeted STAT3 gene polymorphisms from rs744166 (301 bp) and rs2293152 (365 bp) sequences and then digested by specific restriction endonucleases (AluI) and AciI respectively. The disease displayed a female predominance. The genotype TC and CC of rs744166 showed a significant relationship with Grave's disease (p = 0.002, OR = 0.28, 95 % CI = 0.11-0.77) in patients. The C allele contributed significantly to the disease in GD patients. The SNP rs2293152 significantly differed between GD patients and control (p = 0.032, OR = 0.29, 95 % CI = 0.09-0.86). Similarly, the G and C alleles showed a significant (p = 0.02) difference between GD patients and the control. No significant association was found for both SNPs in Hashimoto's thyroiditis disease. It is concluded that the STAT3 gene (rs744166 and rs2293152) was found to have a potential role in autoimmunity in GD patients. Still, it needs further studies with larger sample sizes in the Pakhtun population to understand this relationship.

Pain as a presenting symptom of hypothyroidism.

Chronic back or limb pain is often debilitating and disabling resulting in loss of efficiency, depression, and low self-esteem. Diagnosis usually suggests arthritis or nerve root pathology and patients receive long-term oral analgesics and invasive procedures with little or no relief. Hypothyroidism may present as peripheral neuropathy which may be clinically indistinguishable from entrapment neuropathy as occurs with neural canal stenosis. Muscle cramps, aches, proximal symmetrical muscle weakness, stiffness, polymyositis, and exercise intolerance may be the only presenting symptom indicating hypothyroidism. We present five cases of acute on chronic pain that improved significantly on treatment with thyroxine. Neuromuscular pain may be the only presenting symptom of hypothyroidism. Thyroid profile (TSH, FT3, FT4) and anti-thyroid peroxidase (anti-TPO) antibodies should be screened before subjecting the patient to multiple analgesics and procedures.