甲状腺ホルモン不応症

Objective: To analyze the clinical, radiographic, and genetic characteristics of children with acrodysostosis (ACRDYS). Methods: This case series study enrolled 6 children with ACRDYS from Capital Center for Children's Hospital of Capital Institute of Pediatrics, Beijing Children's Hospital Affiliated of Capital Medical University, and the Second Affiliated Hospital of Guangxi Medical University. Diagnosis was confirmed by whole-exome sequencing between July 2023 and April 2026. Clinical data, laboratory findings, radiographic features, treatment details, and genetic test results were reviewed. Results: Among the 6 ACRDYS children, 5 had PRKAR1A gene variation (ACRDYS1) and 1 had PDE4D gene variation (ACRDYS2). There were 3 boys and 3 girls. The age at diagnosis was 6.3 (5.3,9.1) years. Four children presented with short stature and 2 with short hands and feet. One child was born preterm, 1 was small for gestational age, and 1 had a positive family history. All 6 children had brachydactyly and characteristic facial features, including depressed nasal bridge, upturned nasal tip, long philtrum, and micrognathia. Two children were obese. The 4 children with ACRDYS1 had parathyroid hormone resistance and 3 had thyroid-stimulating hormone (TSH) resistance (1 child was not tested for TSH). The child with ACRDYS2 had mild intellectual developmental delay and no hormone resistance. Hand radiographs showed shortened metacarpals and phalanges with cone-shaped epiphyses in all patients. Bone age was advanced in 3 children and delayed in 1. Genetic testing showed PRKAR1A variants in 5 children and a PDE4D variant in 1 child. The PRKAR1A nonsense variant p.Arg368* was the most common, detected in 3 of the 5 children. One PDE4D variant was previously unreported. Conclusions: Children with ACRDYS typically present with brachydactyly or brachytelephalangy, midfacial hypoplasia, and hand radiographic abnormalities. ACRDYS1 is often accompanied by mild hormone resistance, while ACRDYS2 features neurodevelopmental delay without obvious endocrine abnormalities.

CONTEXT: Postsurgical radioactive iodine (RAI) therapy is indicated for adults with differentiated thyroid cancer (DTC) who are at an intermediate-to-high risk of recurrence. Thyrotropin (TSH) stimulation to facilitate RAI uptake can be achieved by injection of recombinant human TSH (rhTSH) or thyroid hormone withdrawal (THW). OBJECTIVE: This study aimed to compare the effects of rhTSH administration and THW programs on insulin resistance. METHODS: This prospective observational study included 47 patients who received rhTSH injections and 29 patients who underwent THW. All participants underwent a baseline assessment 4 weeks before RAI administration and a follow-up assessment on the day of RAI administration. Blood samples were collected for laboratory analysis, and insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Homeostasis model assessment of insulin resistance significantly decreased after rhTSH administration (from 1.5 [0.8, 1.7] to 1.1 [0.7, 1.4], P = .004) and after THW (from 1.4 [0.9, 1.7] to 0.7 [0.5, 1.0], P < .001). These changes in HOMA-IR were not significantly different between the rhTSH and THW groups (-0.3 [-0.8, 0.2] vs -0.5 [-1.1, -0.2], P = .120). Logistic regression analysis identified a greater reduction in triglyceride levels (a decrease of ≥0.028 mmol/L) as an independent factor for HOMA-IR reduction (the decrease ≥0.4) in the rhTSH group (odds ratio = 6.064, 95% confidence interval: 1.428-25.757, P = .015). CONCLUSION: The rhTSH administration program attenuates insulin resistance in patients with DTC. The magnitude of HOMA-IR reduction in the rhTSH administration program is not significantly different from that in the THW program.

PURPOSE OF REVIEW: This review evaluates the epidemiological, molecular, pathophysiological, and clinical relationships between hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD), with emphasis on hepatic lipid metabolism, mitochondrial function, insulin resistance, thyroid hormone signaling, and therapeutic implications. RECENT FINDINGS: Recent observational studies and meta-analyses indicate a correlation between hypothyroidism, especially overt hypothyroidism, and a heightened risk of hepatic steatosis and fibrosis. Research indicates that thyroid-stimulating hormone might exert direct effects on the liver through signalling via thyroid-stimulating hormone receptors. Moreover, current research suggests that levothyroxine could enhance hepatic enzymes and steatosis in certain patients, whereas thyroid hormone receptor-β agonists have surfaced as potential liver-specific treatments for MASLD. The existing research indicates that thyroid dysfunction is a significant risk factor in MASLD. Regular evaluation of thyroid function might be suitable for certain patients with MASLD, and meticulous minimisation of metabolic risk is crucial. Nonetheless, the causal relationship is not fully determined, and additional longitudinal and mechanistic research is required to elucidate which patients would derive the greatest advantage from thyroid-targeted treatments.

BACKGROUND: Thyroid hormone regulates cardiac and vascular function, and overt hypothyroidism predisposes to impaired ventricular relaxation, raised systemic vascular resistance, and heart failure with preserved ejection fraction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive marker of myocardial wall stress and is itself under thyroid-hormone control, while cyclic-nucleotide phosphodiesterases (PDEs) shape the intracellular signalling that underlies myocardial contractility. The two have rarely been measured together in adults with overt hypothyroidism and seldom in India. We compared serum NT-proBNP and phosphodiesterase 4D (PDE4D), a cAMP-specific isoform, between adults with overt hypothyroidism and euthyroid controls. MATERIALS AND METHODS: This hospital-based case-control study at a tertiary-care teaching hospital in north India was conducted with institutional ethics committee approval and written informed consent. We enrolled 80 adults (older than 20 years) in equal, age- and sex-matched overt hypothyroid and euthyroid groups (40 each). Blinded personnel measured serum triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and NT-proBNP by chemiluminescent immunoassay and serum PDE4D by a sandwich enzyme-linked immunosorbent assay. Groups were compared with the independent-samples t-test or Mann-Whitney U test and the chi-square or Fisher's exact test, alongside univariable logistic regression and effect-size analysis (point-biserial r, Cramer's V); p < 0.05 was taken as significant. RESULTS: The groups matched closely for age (p = 0.617) and sex (72.5% female in each). Serum NT-proBNP ran about fourfold higher in the hypothyroid group (927.10 ± 487.47 vs 233.32 ± 126.12 pg/mL; p < 0.001; r = 0.70), while serum PDE4D ran about twofold lower (19.0 ± 5.9 vs 38.7 ± 9.7 ng/mL; p < 0.001; r = 0.78); PDE4D gave the highest Nagelkerke R² of any variable studied (0.884). The two markers thus moved in opposite directions. The hypothyroid group also carried higher BMI and blood pressure and more hypertension (35% vs 10%) and peripheral oedema (45% vs 20%). CONCLUSIONS: In adults with long-standing overt hypothyroidism, serum NT-proBNP was markedly higher and serum PDE4D markedly lower than in euthyroid controls, a reciprocal pattern set against raised blood pressure, BMI, and hypertension. Cardiovascular surveillance in overt hypothyroidism may therefore be worthwhile, and serum PDE4D emerges as a promising, hypothesis-generating candidate marker that still needs prospective, multivariable-adjusted validation.

Diabetes mellitus (DM) and hypothyroidism (HypoT) are common endocrine-metabolic disorders that frequently coexist, forming a biologically complex comorbidity rather than a simple clinical overlap. Increasing evidence suggests that DM-HypoT comorbidity arises from reciprocal disturbances in insulin action, thyroid hormone signaling, immune-inflammatory regulation, and cellular energy sensing. Thyroid hormone deficiency may impair glucose utilization, promote insulin resistance, and aggravate metabolic stress, whereas diabetes-associated hyperinsulinemia, oxidative stress, and chronic inflammation may disrupt hypothalamic-pituitary-thyroid axis activity, thyroid hormone synthesis, and peripheral hormone activation. Subclinical hypothyroidism may represent an early biochemical phenotype within this interaction and often intersects with obesity and metabolic syndrome. Additional biological nodes, including gut dysbiosis, micronutrient imbalance, AGE-RAGE signaling, and tissue-specific mitochondrial dysfunction, may further amplify endocrine-metabolic dysregulation. However, causal hierarchy, tissue specificity, phenotype heterogeneity, and responsive patient subgroups remain incompletely defined. This review synthesizes current epidemiological and mechanistic evidence and proposes an integrated pancreatic islet-immune-gut-thyroid axis framework to support mechanism-informed risk stratification, biomarker development, and translational intervention strategies for DM-HypoT comorbidity.