Diagnosis of dysferlinopathy masked by a superimposed hypothyroid myopathy.

We report a woman in her 30s with dysferlinopathy whose diagnosis was masked by superimposed hypothyroidism. Laboratory studies revealed Hashimoto's thyroiditis and markedly raised serum creatine kinase (CK of 6255 U/L; reference range 0-170 U/L). Electromyography, nerve conduction studies and MRI of the hip and thigh were consistent with a diagnosis of hypothyroid myopathy, but thyroxine failed to resolve her clinical presentation or normalise the CK level. Immunohistochemical (IHC) staining of right vastus lateralis muscle biopsy revealed the selective absence of dysferlin leading to a diagnosis of limb-girdle muscular dystrophy type IIB. Dysferlinopathy is a challenging diagnosis due to a varied clinical picture and low incidence. Misdiagnosis is common even in uncomplicated presentations, and this case outlines the need for routine inclusion of IHC and a low threshold for genetic testing, in the workup of complex myopathy.

Thyroid Disorders.

This article includes a review of information primary care physicians need to know direct their evaluation and treatment of thyroid disorders that include sick euthyroid, hyperthyroidism, hypothyroidism, and subclinical thyroid disorders.

The interference of anti-TSH autoantibody on clinical TSH detection.

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment.

Comparison of Insulin Sensitivity in Subclinical and Overt Hypothyroidism.

OBJECTIVE: To assess the association of thyroid hormone levels with insulin sensitivity in patients with subclinical (SCH) and overt hypothyroidism (OH). MATERIALS AND METHODS: The present cross-sectional case-control study observed the association of thyroid hormone levels with insulin sensitivity in patients with SCH and OH as compared to their age-matched controls with euthyroidism (ET). Thyroid profile status, fasting blood sugar and triglyceride level, and basic anthropometric measurements were noted. Fasting insulin level (FIL) was analyzed using serum. Body mass index (BMI) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Insulin levels were found to be significantly increased (p = 0.038) in patients with SCH as well as those with OH when compared with compared with age-matched ET controls. insulin sensitivity index (ISI) was comparable among the subjects of the three groups. CONCLUSION: Subclinical hypothyroidism (SCH) and OH had high insulin levels but without statistically significant association between thyroid-stimulating hormone (TSH) levels and QUICKI.

Assessing the relationship between psoriasis and thyroid dysfunction through two sample MR analysis.

BACKGROUND: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. OBJECTIVES: This study employs Mendelian randomization methods to assess the potential relationship. METHODS: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. RESULTS: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However,  vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95% confidence interval (CI) = 1.00-1.00, P = 2.53E-03), and Graves' disease (IVW OR = 0.86, 95% CI = 0.72-1.01, P = 4.75E-02).In a subsequent analysis, we observed that hypothyroidism with mucinous edema showed no correlation with Graves' disease in the opposite(P = 9.33E-01). CONCLUSION: This MR analysis suggests no association between psoriasis and thyroid dysfunction, but highlights associations of vulgar/guttate psoriasis with hypothyroidism/myxedema and Graves' disease. In clinical practice, diagnosing guttate psoriasis requires vigilance for associated risks from hypothyroidism and Graves' disease. For patients with both vulgar psoriasis and hypothyroidism, careful monitoring for mucinous edema is crucial, as it may signal a hypothyroid crisis.

Immune Checkpoint Inhibitors-Induced Endocrinopathies: Assessment, Management and Monitoring in a Comprehensive Cancer Centre.

OBJECTIVES: To determine the incidence, presentation, frequency and management of immune checkpoint inhibitors (ICI)-related endocrinopathies in a comprehensive cancer centre in Oman, particularly with programme death 1/programme death-ligand 1 (PD-1/PD-L1) inhibitors. BACKGROUND: A high number of patients treated with PD-1/PD-L1 inhibitors for the management of solid tumours developed endocrinopathies. METHODS: This is a retrospective study of patients admitted to Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) from August 2021 to December 2022. All adults diagnosed with solid cancers and have received at least one dose of ICIs were included. Patients with incomplete data were excluded from the analysis. Data regarding the ICI-induced endocrinopathy were collected. RESULTS: A total of 139 patients were included in the study of which 58% were females. The median age of the cohort was 56 years. The incidence of endocrine-related adverse events was 28%. The mean time for the development of endocrine adverse events after treatment initiation was 4.1 ± 2.8 months. Of the patients who developed toxicity, 90% had hypothyroidism. Ten patients developed hyperthyroidism, two patients were diagnosed with secondary adrenal insufficiency/hypophysitis and one patient developed Type 1 diabetes mellitus (DM). Using univariable logistic regression weight and body mass index (BMI) significantly impacted the development of endocrine immune-related adverse events (irAEs). CONCLUSIONS: This is the first study from the Sultanate of Oman to assess PD-1/PDL-1 ICI-induced endocrinopathies. The most common endocrine adverse event is thyroid dysfunction, mainly hypothyroidism followed by hyperthyroidism. Hypophysitis, primary adrenal insufficiency and CIADM occur less frequently, but have a more significant effect on the patient's health. The treating physician should be aware of ICI-induced endocrinopathies, screening and treatment. Furthermore, our study showed that patients with a higher BMI have a greater risk of developing irAES. Further studies are needed to establish the predictors of endocrine irAEs.

Current utility of first-line FT4 and TSH in screening for central hypothyroidism.

BACKGROUND: Thyroid testing strategies vary across laboratories. First-line combined thyroid stimulating hormone (TSH) and freeT4 (FT4) have historically been preferred by many laboratories as this detects individuals with undiagnosed central hypothyroidism who can be missed with a first-line TSH-only strategy. However, an up-to-date evaluation of the utility of this approach is lacking. OBJECTIVES: We investigated the clinical utility of first-line TSH and FT4 in the detection of central hypothyroidism in current day practice. DESIGN, PATIENTS, AND MEASUREMENTS: The All-Wales laboratory information system was queried to identify thyroid function tests in patients aged ≥16 years with decreased FT4 and inappropriate TSH (low-FT4). The 1-year incidence of low-FT4 was determined using mid-year population data. Clinical information of patients with low-FT4 was reviewed to determine causes of low-FT4 and the incidence of central hypothyroidism. RESULTS: The incidence of low-FT4 varied according to FT4 assay method (range: 98-301 cases/100,000 population/year). Fifteen new cases of central hypothyroidism were detected in two health boards, equivalent to 2 cases/100,000 population/year. Positive predictive value of low-FT4 for central hypothyroidism was 2%-4%. In a cross-section of primary care patients, low-FT4 was detected in 0.5% of all thyroid tests with assay-related differences in detection rates. CONCLUSIONS: Although low-FT4 is a common laboratory finding, the incidence of central hypothyroidism remains rare. With the currently increased rates of thyroid testing and increased use of medications that decrease FT4, low-FT4 has a much lower predictive value for central hypothyroidism than previously reported. Thyroid screening strategies will need to balance the yield from first line TSH and FT4 testing with the cost of investigating individuals with non-pathological laboratory abnormalities.

Hypothyroidism's effect on stroke limited to specific subtypes: A Mendelian randomization study.

BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes. RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant. CONCLUSION: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.

Diagnoses of obstetric and postpartum thyroid disease: a Danish validation study.

Different diagnoses of thyroid disease are available in the 10th International Classification of Diseases (ICD-10), but the validity of diagnoses related to obstetric and postpartum thyroid disease is unknown. This was a retrospective cohort study of all patients in the North Denmark Region with a diagnosis of postpartum thyroiditis (PPT) (ICD-10: O905) from 2016 to 2019 or obstetric thyroid disease in 2019 (ICD-10: O992B (hypothyroidism) or O992C (hyperthyroidism)) registered in the Danish National Hospital Register. Information from nationwide registers and medical records were used to assess the validity. Among patients with an O905-diagnosis (n = 40), abnormal thyroid function test results were seen in all cases. A total of eight patients (20.0%) were positive for thyrotropin receptor antibodies postpartum, however, in low titers, and PPT was verified in 39 of 40 cases (97.5%). Altogether 45 of 50 patients with an O992B-diagnosis (90.0%) correctly had hypothyroidism, whereas hyperthyroidism was found in 25 of 39 patients with an O992C-diagnosis (64.1%). This is the first study to validate ICD-10 diagnoses of obstetric and postpartum thyroid disease. A high validity was seen for PPT (O905) and obstetric hypothyroidism (O992B), whereas for obstetric hyperthyroidism (O992C), the diagnosis could not be verified in one third of the cases.

Recommendations for managing patients with hypothyroidism.

ABSTRACT: The American Thyroid Association recommends levothyroxine monotherapy for treating hypothyroidism, a condition that affects 4.6% of the US population. However, up to 15% of these patients experience residual symptoms despite normalized thyroid-stimulating hormone levels, and may benefit from an endocrinology referral. Additional high-quality studies are needed to further evaluate patient preferences, as well as to investigate long-term outcomes of combination therapy and continue exploring therapeutic options for hypothyroidism management among specific patient subgroups.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Impact of subclinical hypothyroidism on outcomes after coronary artery bypass grafting: a systematic review and meta-analysis.

INTRODUCTION: Coronary artery bypass grafting (CABG) is a surgical procedure that restores blood flow to heart muscle by bypassing the blocked or narrowed coronary arteries. On the other hand, subclinical hypothyroidism (SCH) is characterized by an elevated serum concentration of thyroid stimulating hormone with normal levels of serum free thyroxine. With limited research into the impact of SCH on postoperative CABG outcomes, this systematic review and meta-analysis was performed. EVIDENCE ACQUISITION: An electronic search of PubMed, Cochrane Library, and Scopus was performed from inception to April 2023. After the inclusion of five studies, a total of 2,786 patients were pooled in this quantitative synthesis. EVIDENCE SYNTHESIS: It was observed that SCH significantly increased cardiovascular mortality (OR: 2.80; 95% CI: 1.37, 5.72; P=0.005), and all-cause mortality (OR: 2.62; 95% CI: 1.80, 3.80; P<0.00001). However, no significant differences were observed for secondary outcomes, including major adverse cardiac events, incidence of postoperative stroke, and incidence of postoperative myocardial infarction. CONCLUSIONS: To the best of our knowledge, this is the first meta-analysis conducted that evaluates the impact of SCH on outcomes after CABG. The preoperative assessment of thyroid function may be considered prior to cardiovascular procedures, particularly within CABG. However, future comprehensive studies, with individual participant-level data, are necessary in order to arrive at a valid conclusion and recommendation.

Aversion of surgical exploration in patients with complex ovarian cysts secondary to overt hypothyroidism: A series of three cases.

Long-standing, overt hypothyroidism-induced bilateral multiloculated ovarian cysts represent an infrequent occurrence. Our first case, presented with bilateral complex ovarian masses, exhibited overt hypothyroidism symptoms, including lethargy, weight gain and subfertility, prompting consideration for surgical intervention. Similarly, in the second case, a girl aged 11 years with stunting, delayed bone age and academic challenges was referred for surgical exploration due to bilateral complex ovarian masses. Both cases revealed elevated thyroid-stimulating hormone levels during preoperative workup. Commencing levothyroxine replacement therapy resulted in complete regression of ovarian cysts and substantial symptom improvement within an 8-week timeframe. The third case, a previously diagnosed patient with Hashimoto's thyroiditis, benefited from the lessons gleaned in managing the initial cases, responding well to levothyroxine therapy, thereby averting the necessity for surgery in all three instances. These cases underscore the significance of considering thyroid function in the evaluation of ovarian masses and highlight the efficacy of levothyroxine replacement therapy in resolving both hypothyroidism and associated ovarian cysts, thereby obviating the need for surgical intervention.

The link between underactive thyroid and leg oedema.

There is an established link between hypothyroidism and leg oedema. This article presents a case study of a female known to have an underactive thyroid gland who developed symptoms and was referred to a local Lindsay Leg Club.