Background: In the current conventional recombinant human thyrotropin (rhTSH) protocol, radioiodine therapy (RAIT) is given at 24 h post-second injection and diagnostic 131I whole-body scan (Dx-WBS) at 72 h; hence, Dx-WBS cannot precede RAIT within the same two-injection cycle. This study aimed to evaluate whether Dx-WBS could be performed within 24 hours after the second injection of a novel rhTSH, thereby enabling timely pre-RAIT evaluation without altering the established rhTSH-based RAIT schedule. Methods: This single-center, prospective trial enrolled patients with differentiated thyroid carcinoma (DTC) who had undergone total thyroidectomy. All patients received rhTSH (0.9 mg daily) on 2 consecutive days. On the same day, about 6 hours after the second rhTSH injection, a low-dose diagnostic activity of I-131 was given, followed by Dx-WBS at approximately 12, 18, and 24 hours post-administration. RAIT was administered on the same day following the 24-hour Dx-WBS, and post-treatment whole-body scan (Rx-WBS) served as the reference standard for assessing concordance with Dx-WBS. Thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) levels were measured at baseline and at 6, 24, and 72 hours following the second rhTSH injection. In TgAb-negative patients, sTg values were stratified into three categories (<1, 1-10, and >= 10 ng/mL), and concordance of 6h-and 24h-sTg with 72h-sTg was assessed based on identical categorization. Results: A total of 110 patients were eventually enrolled, concordance rates of 12h-, 18h-, and 24h-Dx-WBS with Rx-WBS were 82.7% [CI: 74.3-89.3%], 91.8% [CI: 85.0-96.2%], and 92.7% [CI: 86.2-96.8%], respectively. Concordance at both 18 and 24 hours was significantly higher than that at 12 hours (p < 0.05). The concordance rate of 24-hour sTg with 72-hour sTg was significantly higher than that of 6-hour sTg (89.3%, [CI: 80.1-95.3%] vs. 72.0%, [CI: 60.4-81.8%], p < 0.05). Conclusions: The rhTSH-aided Dx-WBS and sTg, performed within 24 hours post-second rhTSH injection, are reliable and efficient in enabling pre-RAIT disease evaluation and subsequent RAIT within the same two-injection cycle, providing a cost-effective strategy.
Background Fat embolism syndrome (FES) is a rare but potentially life-threatening complication classically associated with long-bone fractures and orthopedic procedures. Patients with Duchenne muscular dystrophy (DMD) are at increased risk because of severe osteoporosis, chronic corticosteroid therapy, loss of ambulation, and fatty bone marrow replacement. However, FES remains underrecognized in this population, particularly when triggered by minor trauma without radiographic evidence of fracture. Case Presentation We report the case of a 12-year-old boy with DMD receiving long-term corticosteroid therapy who developed severe FES following a low energy fall. Twenty-four hours after the trauma, he presented with respiratory failure, encephalopathy, petechial rash, thrombocytopenia, and markedly elevated D-dimer levels. Initial computed tomography studies were unremarkable. Brain magnetic resonance imaging demonstrated multiple acute ischemic lesions involving the bilateral centrum semiovale, watershed territories, basal ganglia, thalami, and cerebellum, consistent with the characteristic “starfield” pattern of cerebral fat embolism. The patient also developed acute pulmonary hypertension and right ventricular dysfunction requiring vasoactive support. Intensive supportive treatment, including non-invasive ventilation and hemodynamic support, resulted in progressive clinical improvement with complete neurological recovery. Conclusion This case highlights the extreme susceptibility of patients with DMD to develop severe FES after seemingly trivial trauma, even in the absence of radiographically evident fractures. Early recognition of the characteristic clinical syndrome and prompt neuroimaging are essential for timely diagnosis and appropriate supportive management. Clinicians caring for patients with DMD should maintain a high index of suspicion for FES when respiratory or neurological deterioration occurs after minor injury.
Background: Resistance to thyroid hormone alpha (RTH alpha) is a rare disorder caused by pathogenic THRA variants. We investigated the molecular basis of RTH alpha in a child with developmental delay, dysmorphic features, and a suggestive biochemical profile.Methods: Whole-exome sequencing identified a de novo THRA variant. Cell-based transcriptional assays assessed thyroid hormone responsiveness, coactivator dependence, and dominant-negative activity.Results: A novel heterozygous frameshift variant, c.1125_1132dup (p.Gly378Alafs*2), truncating the ligand-binding domain, was identified. The mutant receptor showed markedly impaired responses to triiodothyronine (T3) and TRIAC. CBP/p300 and PGC1 alpha failed to activate the variant, supporting loss of function. Co-expression studies demonstrated strong inhibition of wild-type THRA activity that was not rescued by high T3 concentrations, indicating a potent dominant-negative effect. Disruption of DNA binding abolished this interference, showing that DNA occupancy is required.Conclusions: These findings expand the spectrum of pathogenic THRA variants and provide new insight into transcriptional repression in RTH alpha.
Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risk Reporting the phenotypic spectrum of ATM variants is essential to refine genotype-phenotype correlations. We report a 6-year-old boy presenting with progressive gait ataxia, recurrent respiratory infections, chronic otorrhea, and conjunctival telangiectasias. Laboratory studies revealed immunodeficiency with reduced IgG and IgA, and elevated IgM. Brain MRI showed mild cerebellar atrophy, while chest X-ray revealed bilateral interstitial infiltrates. Whole-exome sequencing identified a homozygous missense variant in ATM (c.4940 T > G; p.Leu1647Arg), currently classified as a variant of uncertain significance (VUS); this represents only the second reported family with this variant.The patient improved with intravenous antibiotics and IVIG. Family genetic testing was recommended given parental consanguinity and an affected sibling. This case illustrates the classical phenotype of A-T with immunodeficiency and neurological dysfunction. Such cases reinforce genotype-phenotype correlations and may guide diagnosis and counseling. Although the variant's pathogenicity remains to be functionally validated, its clinical correlation supports disease relevance. Careful clinical and familial correlation of ATM variants is crucial for advancing diagnostic precision, genetic counseling, and future therapeutic strategies in A-T.
Background: Treatment in phenylketonuria (PKU) is aimed at lowering blood phenylalanine (Phe) levels, however the target blood Phe levels in adults with PKU are a matter of ongoing debate. Objective: To describe the experience of adults with PKU regarding mood and self-reported functioning during a period with higher and/or lower blood Phe levels than they were used to during an interventional trial with Sepiapterin. Methods: Eight adults with PKU were included in an open label interventional trial with Sepiapterin (Sephience (R), Phase 3 APHENITY Extension Study NCT05166161). Per protocol, participants who were receiving Sapropterin (N = 4) had a washout week before starting with Sepiapterin. The experience of the participants concerning their functioning and feelings were described during the first weeks of the trial when their blood Phe levels changed to higher than usual (in N = 4 during a Sapropterin washout week) and to lower than usual (N = 8) during treatment with Sepiapterin. Results: Participants reported worse functioning when their blood Phe levels were higher than usual and improved functioning when their blood Phe levels were lower than usual. Conclusions: Adults with PKU may experience worsened self-reported functioning at higher blood Phe levels and improved functioning when Phe is lower than their usual blood Phe levels. Therapies that reduce blood Phe levels without the need of a strict diet offer the possibility to objectively study the impact of lower blood Phe levels in adults with PKU and may eventually facilitate individualized target blood Phe levels.
