甲状腺ホルモン不応症

Immune checkpoint inhibitors (ICIs) are increasingly used in oncology and commonly cause thyroid dysfunction. Most patients who develop hypothyroidism after ICI-induced thyroiditis respond to standard weight-based levothyroxine replacement. However, causes of treatment-refractory hypothyroidism are less well recognized in this context. We describe an 81-year-old woman with uterine cancer treated with lenvatinib and pembrolizumab who developed ICI-related thyroiditis with subsequent hypothyroidism. Despite progressive levothyroxine dose escalation to nearly twice the expected weight-based dose, thyroid-stimulating hormone (TSH) remained elevated after normalization of free thyroxine (FT4) and triiodothyronine (T3). Evaluation for malabsorption and nonadherence was unrevealing. Further investigation identified significant proteinuria associated with lenvatinib therapy. Given that thyroid hormone circulates primarily bound to plasma proteins, urinary loss of protein-bound thyroid hormone was suspected to contribute to the increased levothyroxine requirement. Following temporary discontinuation and subsequent dose reduction of lenvatinib, proteinuria improved and thyroid function tests (TFTs) normalized, allowing for a reduction in levothyroxine dose. This case highlights that excessive proteinuria can lead to urinary loss of protein-bound thyroid hormone, resulting in apparent levothyroxine resistance. Clinicians should consider renal losses along with gastrointestinal and medication-related causes when thyroid hormone requirements exceed expected dosing. This is particularly relevant in patients receiving combination cancer therapies that increasingly include ICIs.

BACKGROUND: Fluctuations in thyroid function among euthyroid individuals have been linked to cardiovascular disease (CVD). We investigated whether central thyroid hormone sensitivity correlates with CVD risk, CVD-related death, and overall mortality in subjects with normal thyroid function, particularly examining how age modifies these associations. METHODS: We analyzed data from 6,374 euthyroid adults enrolled in NHANES 2007-2012. Central thyroid hormone sensitivity was quantified using three indices: the thyroid feedback quantile-based index (TFQI), the thyrotropin-thyroxine resistance index (TT4RI) and the TSH index (TSHI). The Framingham Risk Score (FRS) estimated each participant's 10-year probability of developing CVD. CVD mortality and all-cause mortality were ascertained by linkage to the National Death Index through December 31, 2015. Associations were evaluated using logistic regression (10-year CVD risk) and Cox proportional hazards models (mortality), adjusted for sex and race, with analyses stratified by age (< 40 and ≥ 40 years). RESULTS: Of the 6,374 participants (mean age 48.24 ± 17.59 years; 52.0% male), 18.5% had a 10-year CVD risk > 10%; during follow-up. In sex- and race-adjusted models, all three indices were positively associated with an elevated 10-year CVD risk (> 10%): TFQI (OR 1.40, 95% CI 1.15-1.71), TSHI (OR 1.27, 95% CI 1.11-1.45), and TT4RI (OR 1.01, 95% CI 1.01-1.02). Each index was also significantly associated with higher CVD mortality and all-cause mortality, with TFQI showing the strongest associations (CVD mortality: HR 3.30, 95% CI 2.24-4.85; all-cause mortality: HR 2.19, 95% CI 1.83-2.62). These associations remained significant in participants aged ≥ 40 years (p < 0.001) but not in those aged < 40 years. CONCLUSION: Impaired central thyroid hormone sensitivity shows association with elevated CVD risk, CVD mortality, and all-cause mortality in euthyroid individuals aged 40 years and older.

Pseudohypoparathyroidism is a really rare inherited disorder characterized by either unresponsiveness or targeted organ resistance to the parathyroid hormone, classified either biochemically or by phenotype characteristics. Here, we report an atypical presentation of Albright hereditary osteodystrophy. An underweight 18-year-old male presented with painful subcutaneous nodules that progressively appeared over a period of 10 years and were confirmed by fine needle aspiration, and the pathology report indicated osteoma cutis.

Thyroid hormones may accelerate heart rate and enhance cardiac contractility, improving both systolic and diastolic functions of heart, while reducing systemic vascular resistance at rest. Thyroid dysfunction may be associated with an increased risk of cardiovascular disease (CVD). However, current findings are not entirely consistent, and variations in thyroid hormone sensitivity may serve as a key factor underlying the inconsistent associations between thyroid function and CVD. Hence, the present narrative review synthesizes the association between thyroid hormone sensitivity and common CVDs, such as hypertension, coronary heart disease (CHD), and stroke. The possible molecular mechanisms of thyroid hormone sensitivity-mediated cardiovascular pathology are also summarized. We found that most studies failed to establish a significant relationship between peripheral, central thyroid hormone sensitivity and hypertension. Further, current studies generally suggest a positive correlation between reduced peripheral thyroid hormone sensitivity and an increased risk of stroke. Similarly, most studies indicate that reduced thyroid hormone sensitivity is associated with an elevated risk of adverse clinical outcomes after CHD.

Although measurement of thyroid hormones (TH), TSH and thyroid autoantibodies is usually straightforward, erroneous results are occasionally generated, raising the possibility of incorrect or delayed diagnoses, unwarranted investigations and provision of inappropriate treatments. Assay interference can be due to acquired (e.g. antibodies), genetic (e.g. variant TH binding proteins) or pharmaceutical (e.g. displacing agents, biotin) in nature. In those with discordant thyroid function, assay interference must be excluded prior to the diagnosis of rare inherited (Resistance to Thyroid Hormone) or tumoral conditions (TSHoma). Liaison between the clinician and clinical biochemistry teams is essential when assay interference is being investigated; appropriate further biochemical testing depends on the clinical picture, initial biochemistry and local biochemical expertise. In a subset of cases, access to a regional centre where patients can be clinically assessed, in conjunction with performance of specialised clinical laboratory testing (biochemical, +/- genetic), may be required. When assay interference is identified, clear communication with the patient (ideally aided by reliable, accessible patient literature) and documentation to their physician is necessary. Professionals must stay updated on advances in testing and be alert for evolving assay interferences. An accompanying plain language summary is intended to provide an accessible overview of the key messages and recommendations contained in this guideline for non-specialist readers, including patients, carers, healthcare professionals outside the specialty, and the wider public.