Radioactive iodine therapy requires individualized decisions regarding patient selection, administered activity planning, imaging assessment, and follow-up. This systematic review summarizes current applications of artificial intelligence (AI) in the [131]I treatment pathway and evaluates barriers limiting clinical implementation. Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Wiley databases were searched for original studies involving human patients treated with [131]I for differentiated thyroid cancer or benign thyroid disease, where AI, deep learning (DL), or machine learning (ML) methods were utilized. Evidence was synthesized, and study quality was assessed using the NIH/NHLBI Study Quality Assessment Tool. Among 775 identified records, 24 studies met inclusion criteria. AI applications included pretreatment decision support, detection and characterization of iodine-avid disease, dosimetry and activity optimization, radiation-safety assessment, treatment response prediction, levothyroxine dose estimation, and recurrence-risk stratification. The available evidence was dominated by retrospective, single-center studies, primarily focused on differentiated thyroid cancer, with limited external validation. AI has the potential to improve standardization and personalization of [131]I therapy, but heterogeneous methodologies and insufficient evidence of clinical utility currently restrict routine adoption. Prospective multicenter studies with harmonized endpoints and robust validation are required to facilitate clinical translation.

During puberty, free thyroxine (fT4) concentrations transiently decrease with a nadir around Tanner stage 3. Due to the interindividual variation in timing of pubertal onset, this transient fT4 dip occurs at different ages and becomes less apparent within an age-specific reference interval (RI). This may result in fT4 concentrations temporarily falling below the lower limit of the RI when age-specific instead of Tanner stage-specific RIs are used. As thyroid stimulating hormone (TSH) levels usually remain within the age-specific RI, the resulting biochemical profile resembles central hypothyroidism and frequently triggers extensive, but often unnecessary diagnostic work-ups. We present two cases of asymptomatic adolescents with low fT4 concentrations in combination with a normal TSH, in whom central hypothyroidism was initially suspected but subsequently excluded. In all cases, fT4 concentrations normalized later in puberty without intervention. This phenomenon likely reflects increased peripheral conversion of T4 to triiodothyronine (T3) under the influence of growth hormone and sex steroids. Awareness of this physiological phenomenon is essential to avoid misdiagnosis, overtreatment, and undue psychological stress. Our findings highlight the need for Tanner stage-specific fT4 RIs to guide thyroid function interpretation in adolescents.

Roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, is effective for treating renal anemia, with efficacy noninferior to erythropoiesis-stimulating agents. However, data on its adverse effects remain scarce. In medical practice, roxadustat administration reportedly leads to central hypothyroidism; however, the frequency of its occurrence remains unclear. We investigated thyroid function in patients undergoing dialysis who received roxadustat at Saiseikai Yokohamashi Tobu Hospital, with particular focus on the timing of the decrease in serum thyroid-stimulating hormone (TSH) levels after roxadustat initiation and the subsequent course of thyroid function. HIF-PH inhibitors were administered to 43 chronic kidney disease patients including dialysis. After 2 weeks of roxadustat administration, we extracted the data of 16 hemodialysis patients who exhibited absence of residual urine and were able to undergo blood tests. All patients revealed decreased serum TSH levels. In contrast, changes in serum free triiodothyronine and free thyroxine levels were minor. None of the patients reported fatigue, bradycardia, or constipation, which are common symptoms of hypothyroidism. Our findings revealed that roxadustat may cause TSH reduction after 2 weeks of administration, though some patients showed subclinical hypothyroidism with high TSH levels. In a few cases, TSH levels decreased to one-tenth of the normal values. Despite these rapid changes, none of the patients exhibited clinical symptoms. Hence, regular thyroid hormone level monitoring is necessary with roxadustat administration, regardless of patients' history of thyroid function.

Cancer-associated fibroblasts (CAF) are major regulators of the tumor microenvironment (TME), yet the pathways governing CAF function remain incompletely understood. Type 2 deiodinase (DIO2, D2), which converts thyroxine (T4) to the active thyroid hormone triiodothyronine (T3), has not been systematically investigated in CAF across different solid tumors.

Clinical (CH) and subclinical (SCH) hypothyroidism reduces the metabolic rate and alter body composition. The current treatment with levothyroxine (LT4) restores the thyroid axis hormonal levels; however, its efficacy in reversing the anthropometric alterations remains unclear. This review was prospectively registered on PROSPERO (CRD42024589156), followed PRISMA guidelines, and aimed to include studies involving CH and/or SCH treated with LT4 monotherapy until achieving physiological hormonal levels. Eligible studies reported pre- and post-LT4 treatment data of BMI, BW, fat mass (FM), and lean mass/fat-free mass (LM/FFM). Each variable was analyzed according to treatment duration, sex distribution, initial and final TSH levels. 35 studies were included, comprising 1,116 individuals with hypothyroidism (672 CH; 444 SCH). In CH, LT4 led to negligible changes in BMI in the general analysis (Standardized mean difference [SMD] -0.18; 95% confidence interval [CI] -0.26, -0.10; mean difference [MD] -0.68 kg/m[2]), while moderate BMI reductions were observed after 12 months of treatment (SMD - 0.56; CI -0.87, -0.24; MD -2.29 kg/m[2]). LT4 reduced BW in CH (SMD - 0.24; CI -0.34, -0.15; MD -2.15 kg), primarily in the first 3 months of treatment; it did not change FM and led to a small reduction in LM/FFM (SMD - 0.21; CI -0.37, -0.05). However, LT4 showed no significant effects on BMI, BW, FM, or LM/FFM in SCH, regardless of the analysis. Despite restoring thyroid hormonal homeostasis, LT4 showed limited efficacy in reversing the anthropometric alterations associated with CH and mainly SCH, suggesting that therapies beyond hormonal normalization may be required. Moreover, our data reinforces that LT4 monotherapy must not be prescribed for weight loss.

Background Albuminuria is an important marker of diabetic kidney disease (DKD) and is associated with adverse renal and cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM). Although sustained hyperglycemia is a recognized contributor to DKD, glycated hemoglobin (HbA1c) does not fully capture short-term glycemic variability. Emerging evidence suggests that hypomagnesemia and altered thyroid function may be associated with albuminuria, but their combined relationships with albuminuria and the possible statistical mediating role of thyroid hormones remain unclear. This study was conducted to identify the associations of albuminuria with glycemic variability, serum magnesium, and thyroid function in T2DM patients. Materials and methods A cross-sectional study included 330 adults aged 30-84 years with T2DM of more than five years' duration. Continuous glucose monitoring (CGM)-derived measures, including mean glucose, glucose standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), were assessed alongside HbA1c, serum magnesium, free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and urinary albumin-to-creatinine ratio (UACR). Associations with albuminuria were examined using univariable and multivariable logistic regression, with additional correlation and exploratory regression-based mediation analysis. Ethical approval and written informed consent were obtained. Results Among 330 participants, 208 (63%) had normal UACR, 98 (29.7%) had microalbuminuria, and 24 (7.3%) had macroalbuminuria. Hypomagnesemia was associated with more than twofold higher odds of albuminuria in univariable analysis (odds ratio (OR)=2.26; 95% confidence interval (CI): 1.38-3.70; p=0.001). In Model IV, which was adjusted for demographic variables, higher HbA1c (OR=1.66; 95% CI: 1.34-2.05; p<0.001), SD (OR=1.63; 95% CI: 1.18-2.26; p=0.003), CV (OR=1.06; 95% CI: 1.01-1.10; p=0.016), and MAGE (OR=1.25; 95% CI: 1.07-1.45; p=0.005) were independently associated with higher odds of albuminuria. In contrast, higher FT3 was inversely associated with albuminuria (OR=0.46; 95% CI: 0.28-0.74; p=0.001). TIR, FT4, and TSH were not significantly associated with albuminuria in univariable analysis. HbA1c was negatively correlated with FT3 (ρ=-0.133; p=0.016). Similarly, SD was negatively correlated with FT3 (ρ=-0.227; p<0.001). Exploratory mediation analysis indicated that FT3 statistically accounted for 6.9% of the association between HbA1c and albuminuria and 21.4% of the association between glucose SD and albuminuria. Conclusion Greater glycemic variability and lower FT3 levels were independently associated with albuminuria in patients with T2DM, while hypomagnesemia was associated with albuminuria in univariable analysis. Exploratory mediation analysis suggested that FT3 statistically accounted for a modest proportion of the associations of HbA1c and glucose SD with albuminuria. These findings indicate that CGM-derived variability measures, alongside magnesium status and thyroid function, may provide complementary information in the assessment of DKD. Prospective multicenter studies are required to clarify the temporal relationships and clinical significance of these findings.

Nonthyroidal illness syndrome is a common condition among intensive care unit patients. Previous studies showed conflicting findings regarding association with poor clinical outcomes. Studies examining whether levothyroxine administration improves clinical outcomes in critical patients with nonthyroidal illness syndrome and low free thyroxine levels are lacking. We aimed to examine whether levothyroxine administration in intensive care unit patients with the nonthyroidal illness syndrome and low thyroxine levels (< 0.8 ng/dL) resulted in differences in 28-day mortality and in-hospital morbidity. A retrospective study using electronic data retrieval for patients admitted to a general intensive care unit who presented with low free thyroxine levels and nonthyroidal illness syndrome. This study included 123 patients. A total of 53 patients received levothyroxine. No significant differences were found between groups regarding demographics, comorbidities or reasons for intensive care unit admission. Hospital length of stay was significantly longer in the treatment group (39±24 d) compared to that in the non-treatment group (30±19 d; p<0.05). The duration of mechanical ventilation was significantly longer in the treatment group (21±21 d) vs. non-treatment group (14±14 d; p<0.05). Intensive care unit length of stay showed a trend toward being longer in the treatment group (22±20 d) compared to that in the non-treatment group (16±13 d; p=0.058). Higher free thyroxine levels were associated with better clinical outcomes, including the reduced need for vasopressors and dialysis, and lower 28-day mortality. Low free thyroxine levels in intensive care unit patients with nonthyroidal illness syndrome are associated with higher morbidity. Levothyroxine administration did not improve clinical outcomes in this population.

A previously healthy 24-year-old woman presented with jaundice, diarrhea, tachycardia, fever, and altered mental status. Laboratory evaluation revealed severe hyperbilirubinemia, mixed hepatocellular-cholestatic injury, international normalized ratio 4.99, hypofibrinogenemia, and encephalopathy, fulfilling criteria for acute liver failure (ALF). Thyroid studies demonstrated suppressed thyroid-stimulating hormone, elevated free thyroxine and triiodothyronine, and strongly positive anti-thyroid peroxidase and anti-thyroid‑stimulating hormone receptor antibodies, confirming thyroid storm. Profound hypergammaglobulinemia (immunoglobulin G 9,079 mg/dL), anti-smooth muscle antibody positivity (1:40), and antinuclear antibody positivity (1:80) suggested autoimmune hepatitis (AIH) overlap. Immunoglobulin M levels were not available. AIH frequently coexists with other autoimmune disorders, occurring in up to 20%-30% of cases, and may exacerbate liver injury during endocrine crises. Despite corticosteroids, iodine therapy, and supportive care, the patient deteriorated and died. This case highlights the rare intersection between thyroid storm, ALF, and AIH overlap, emphasizing the importance of early recognition of autoimmune markers in endocrine emergencies.

Ascites is a rare presentation of hypothyroidism and can be easily mistaken for malignancy when it occurs alongside pleural effusion and radiological lymphadenopathy. We report the case of a 63-year-old man who presented with progressive generalized anasarca, abdominal distension, and worsening breathlessness. Diagnostic paracentesis revealed exudative ascites with a low serum-ascites albumin gradient (SAAG) and markedly elevated protein content, and thyroid function testing showed profound, previously undiagnosed primary hypothyroidism (thyroid-stimulating hormone (TSH) 221.2 µIU/mL). On a subsequent admission, contrast-enhanced CT additionally revealed bilateral pleural effusion with mediastinal lymphadenopathy and omental fat stranding, raising concern for an underlying malignant or granulomatous process. Repeat ascitic fluid analysis, cytology, tumor markers, and cartridge-based nucleic acid amplification test (CBNAAT) were unremarkable, and an omental biopsy was performed and was not suggestive of inflammatory pathology; in view of this reassuring result, together with the patient's frailty and early clinical improvement, the higher-risk procedure, mediastinal lymph node biopsy, was deferred by multidisciplinary consensus in favor of a trial of thyroid hormone replacement. This strategy proved correct: with initiation and titration of levothyroxine, the patient's ascites, pleural effusion, and edema resolved completely on serial follow-up, obviating the need for mediastinal lymph node sampling. This case illustrates that myxedema ascites can radiologically mimic malignancy and that thyroid function testing, together with judicious, risk-stratified tissue sampling and, where clinically appropriate, a closely monitored trial of thyroid hormone replacement, can help a frail older adult avoid an unnecessary high-risk biopsy.