Research Article: Nocturnal sleep duration, clinical activity score, and thyroid functional remission after radioactive iodine therapy in Graves’ disease with thyroid-associated ophthalmopathy
Abstract:
To examine whether pretreatment nocturnal sleep duration and Clinical Activity Score (CAS) are associated with thyroid functional remission after radioactive iodine (¹³¹I) therapy in Graves’ disease (GD) with concomitant thyroid-associated ophthalmopathy (TAO). The primary endpoint was thyroid functional remission, not ocular cure.
We retrospectively reviewed 153 patients at a single center (53 in remission; 100 not in remission), followed for at least 12 months after ¹³¹I therapy. Sleep duration and CAS were pretreatment baseline measures; 20 patients received prednisone before ¹³¹I therapy (discontinued ? 3 days prior) and 133 received none; no thyroid-directed or immunosuppressive treatment was given during follow-up. Remission was coded using the response categories of the 2021 Chinese Society of Nuclear Medicine ¹³¹I treatment guideline (euthyroidism or hypothyroidism vs. partial or ineffective response). Missing continuous values were multiply imputed (20 chains). Analyses included false discovery rate (FDR)–controlled univariate screening, cross-validated least absolute shrinkage and selection operator (LASSO) selection, post-selection logistic regression, Firth sensitivity analysis, interaction tests, and mutually adjusted restricted cubic splines (RCS).
No patient sleeping less than 6h achieved remission [0/31; 95% confidence interval (CI) 0%–9.2%]. After FDR adjustment, GD duration, TAO duration, sleep duration, and CAS remained associated with remission. LASSO (one-standard-error rule, C = 0.142) retained GD duration, sleep duration, and CAS. In the post-selection model, the odds ratio (OR) per month of GD duration was 0.991 (95% CI 0.979–1.003; P = 0.152); per additional sleep hour, 6.13 (95% CI 3.16–11.91; P < 0.001; Firth OR 5.64, 95% CI 2.99–10.63); and per CAS point, 0.64 (95% CI 0.48–0.86; P = 0.003). The CAS × sleep interaction was not significant (Wald P = 0.096; likelihood-ratio P = 0.086). Mutually adjusted RCS supported non-linearity for CAS ( P < 0.001) but not for sleep ( P = 0.585).
Longer pretreatment nocturnal sleep and lower CAS were associated with thyroid functional remission after ¹³¹I therapy in this single-center cohort, with consistent directions across sensitivity models. These retrospective, post-selection associations require prospective validation; the absence of remission below 6h and the fitted threshold effects are exploratory post hoc observations, not validated thresholds.
Introduction:
Thyroid-associated ophthalmopathy (TAO) is the most common extrathyroidal manifestation of Graves’ disease (GD), affecting 25%–50% of patients ( 1 , 2 ). Orbital fibroblasts co-express thyrotropin (TSH) receptor and insulin-like growth factor-1 receptor, which drives orbital inflammation, hyaluronic acid deposition, and adipogenesis ( 2 , 3 ). Clinical features range from eyelid retraction and proptosis to diplopia and dysthyroid optic neuropathy. About 3%–5% of patients progress to sight-threatening disease ( 1 ,…
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