Hospital de Santa Maria

Destructive thyroiditis is among the most frequent endocrine adverse events of immune checkpoint inhibitors (ICIs). Most reports focus on thyroid dysfunction; less is known about how ICI-induced destructive thyroiditis may remodel thyroid architecture and alter pre-existing nodular disease. A 56-year-old woman with a previously documented high-risk thyroid nodule (13 mm, EU-TIRADS 5) was diagnosed with triple-negative breast cancer and started on neoadjuvant therapy including pembrolizumab. Several months into therapy, pre-operative routine testing revealed de novo asymptomatic overt primary hypothyroidism (TSH 123 mIU/L, fT4 0.14 ng/dL), leading to postponement of breast surgery. Levothyroxine was initiated (100 µg/day), normalizing fT4 within 2 weeks and allowing surgery to proceed, while TSH remained markedly elevated. Thyroid autoantibodies were negative; ICI-induced destructive thyroiditis was presumed. Follow-up ultrasound, performed for planned fine-needle aspiration of the EU-TIRADS 5 nodule, showed a markedly atrophic thyroid gland with no residual suspicious nodules, with the previously documented high-risk nodule no longer detectable. These changes were interpreted as sequelae of destructive thyroiditis. The patient remains asymptomatic on stable levothyroxine replacement, with controlled hypothyroidism, and no breast cancer recurrence at last follow-up. This case highlights that ICI-induced destructive thyroiditis can not only cause severe hypothyroidism but also dramatically remodel thyroid morphology, including regression of an EU-TIRADS 5 nodule. It also illustrates a real-world perioperative dilemma, namely, whether normal fT4, despite very high TSH, is sufficient to proceed with major surgery. Finally, it raises questions about optimal follow-up when a suspicious nodule vanishes following ICI-related thyroiditis.

Cyclical Cushing’s syndrome (CCS) is an uncommon form of endogenous hypercortisolism characterized by alternating periods of cortisol excess and remission. Its intermittent nature delays diagnosis and localization of the adrenocorticotropic hormone (ACTH) source and complicates therapeutic decision-making. We report a 46-year-old man with an incidentally detected anterior mediastinal mass, diagnosed as a well-differentiated neuroendocrine tumor (NET) with ectopic ACTH production. He presented with clinical and biochemical features of ACTH-dependent Cushing’s syndrome. Despite tumor resection and multiple subsequent therapies, including somatostatin analogues, chemotherapy (without concomitant glucocorticoids), and radiotherapy, the disease course was marked by recurrent peaks of hypercortisolism interspersed with partial remissions, consistent with CCS. Episodes were associated with hypertension, diabetes mellitus, hypokalemia, infections, and thromboembolism. Due to refractory disease, bilateral adrenalectomy was performed, achieving biochemical remission but requiring lifelong glucocorticoid replacement. CCS poses significant diagnostic and therapeutic challenges. Intermittent cortisol secretion may obscure diagnosis during remission phases and complicate assessment of treatment response. In NET-related CCS, tumor progression and therapeutic interventions may influence ACTH secretion, contributing to cyclical patterns. The “timing paradox”, whether to treat during peaks or remission, remains a key clinical dilemma. CCS requires prolonged biochemical surveillance, early recognition of cyclicity, and multidisciplinary management. The cumulative burden of recurrent hypercortisolism highlights the need for individualized strategies integrating endocrine and oncologic care. Bilateral adrenalectomy remains a life-saving option when sustained control is not achieved.

Metastatic urothelial carcinoma (mUC) is a lethal cancer with limited therapeutic options. Advances in genomic and transcriptomic research have deepened the understanding of mUC biology, leading to the identification of clinically relevant molecular alterations that represent potential actionable targets. This has broadened the treatment landscape of the disease to include novel agents, such as antibody-drug conjugates (e.g., enfortumab vedotin) and targeted therapies, including the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib. Genomic alterations in FGFR3 are well-established oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR-targeted therapies. The phase III THOR trial demonstrated the clinical benefit of erdafitinib in previously treated mUC patients harboring FGFR3 alterations and supported its subsequent approval by the European Medicines Agency. In this context, accurate molecular profiling is essential to guide patient selection for FGFR inhibitor therapy. Equally important is the standardization and timely implementation of FGFR3 testing in clinical practice to optimize treatment planning. This review addresses key considerations in FGFR3 testing in mUC and discusses how it can be routinely incorporated into clinical practice.

PURPOSE:The Iberian Registry of Ocular Syphilis aims to describe the epidemiology, clinical manifestations and treatment outcomes of ocular syphilis in Spain and Portugal. This re-emerging condition, associated with rising global syphilis rates and HIV coinfection, presents with diverse ocular and systemic features. The study seeks to fill knowledge gaps regarding incidence, presentation and therapeutic response. METHODS:This multicentre, observational cohort study includes patients aged ≥18 years with newly diagnosed ocular syphilis confirmed by treponemal and nontreponemal serological tests. Conducted across 23 centres, data collection followed routine clinical practice and included demographics, ocular/systemic findings, treatment regimens and outcomes at 3-6 months post-treatment. RESULTS:In the first year, 41 patients met the inclusion criteria, of whom 39 consented to participate in the registry, with an incidence of 0.57 cases per 100 000 persons/year. Most were male (94.9%), especially men who have sex with men (66.7%) and HIV coinfection (20.5%). Bilateral ocular involvement was observed in 64.1% of patients, with anterior segment inflammation in 64.1%, vitritis in 53.8%, retinal or choroidal involvement in 69.2% and optic nerve involvement in 59.0%. Systemic syphilis stage included primary (7.7%), secondary (25.6%) and tertiary or quaternary (15.4%). Treatment was initiated after a mean of 6.2±9.3 weeks after the onset of symptoms, and 2.6±6.0 weeks after the initial presentation at the hospital. Intravenous penicillin G was used in 65.8%, and 61.3% achieved a four-fold titre reduction in the reaginic test at the final visit (3 to 6 months after antibiotic therapy). Final visual acuity improved to 0.17 LogMAR (p<0.001), with 56% of eyes gaining ≥0.1 LogMAR. CONCLUSIONS:Ocular syphilis in the Iberian Peninsula shows a wide clinical spectrum and frequent posterior segment involvement. Most patients achieved favourable serological and visual outcomes. These findings support the effectiveness of standard therapies and highlight the need for early diagnosis, especially in high-risk populations.

Introduction: Joubert syndrome (JS) is a rare genetic disorder char­acterized by a distinctive midbrain-hindbrain malformation identifiable through brain imaging. Clinically, JS manifests as hypotonia, irregular respiratory patterns, oculomotor apraxia, ataxia, and developmental delay, and it is often accompanied by multi-organ involvement. Although no definitive treatment exists, early diagnosis is crucial for timely intervention and improved outcomes. This case report describes a neonatal presentation of JS, emphasizing the importance of early recognition and radiological data. Case report: We present the case of a female neonate born at 39 weeks and 3 days, initially diagnosed with transient respiratory distress. The infant subsequently exhibited recurrent episodes of desaturation, abnormal eye movements, and hypotonia. Magnetic resonance imaging (MRI) revealed posterior fossa malformations consistent with JS, in­cluding vermian dysplasia, the characteristic “molar tooth sign” of the mesencephalon, and a “bat-wing” morphology of the fourth ventricle. Genetic testing confirmed JS. Further evaluations showed no evidence of systemic involvement. Discussion: JS remains a diagnostic challenge due to its broad phenotypic spectrum. Early symptoms, such as respiratory distress and oculomotor abnormalities, can be subtle or mistaken for other neonatal conditions. MRI findings play a critical role in confirming the diagnosis, while genetic testing provides valuable information for family counseling. Comprehensive and multidisciplin­ary management, including neurological, oph­thalmological, and developmental monitoring, is key for improving patient outcomes. This case highlights the importance of early diagnosis and multidisciplinary care in rare genetic disorders such as JS.