High-dose intravenous methylprednisolone is effective in subacute thyroiditis unresponsive to oral steroids Simone Rodolfi, Guia Maria Vannucchi, Michela Perrino, Carla Colombo, Danila Covelli, et al. European Thyroid Journal, 2026 Objective Subacute thyroiditis (SAT) relapsing or refractory to standard of care oral prednisone (OP) therapy is rare, but affected patients experience significant discomfort due to prolonged and uncontrolled neck pain. Here, we report the efficacy of high-dose intravenous methylprednisolone (IVMP) therapy in the treatment of such cases. Methods In this pilot study, we included 14 patients diagnosed with SAT in the period 2014–2024, in a single center. Therapy consisted of 500 mg of IVMP, divided into two weekly infusions and titrated down based on clinical response. Thyroid function tests, thyroid ultrasound, and inflammatory markers were assessed at baseline and throughout the follow-up up to 3–6 months after IVMP discontinuation. Results At baseline, 4 and 10 patients had thyrotoxicosis or were euthyroid, respectively. The median (IQR) duration of treatment was 26 days (21–38). At the end of the treatment, we observed a complete clinical, ultrasonographic, and biochemical response in twelve patients (86%), whereas thirteen (93%) had immediate resolution of neck pain and thyrotoxicosis. Only one patient did not improve at the end of IVMP protocol, and she was the only one experiencing a delayed remission with persistent hypothyroidism. Mild grade 1 and 2 adverse events (hyperglycemia, arterial hypertension, and neutrophilia) occurred in 8 out of 14 patients. Conclusion IVMP therapy resulted in a rapid clinical and ultrasonographic improvement in most patients with relapsing SAT unresponsive to oral steroids. This response allowed for a shorter treatment duration, with good tolerability, minimal adverse events, and a low incidence of hypothyroidism during follow-up.
Lifestyle Interventions to Tackle Cardiovascular Risk in Thyroid Hormone Signaling Disorders Simone Rodolfi, Giuditta Rurale, Federica Marelli, Luca Persani, Irene Campi Nutrients, 2025 Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs—including resistance to thyroid hormone alpha (RTHα) and beta (RTHβ), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency—lead to complex, multisystemic clinical features. Although these conditions are rare, with RTHβ being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTHβ, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTHα, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research.
Case Report: Challenges of an extremely delayed diagnosis of classic congenital adrenal hyperplasia in a completely virilized 46,XX patient Alice Casiraghi, Irene Campi, Silvia Federici, Franco Cernigliaro, Soara Menabò, et al. Frontiers in Endocrinology, 2025 Classic Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency is typically diagnosed in early life. We report a 46,XX completely virilized 46,XX patient who was diagnosed with classic CAH at the age of 73 years. He was under follow-up for prostate hyperplasia and referred after the finding of giant bilateral adrenal myelolipomas. He presented with hormonal values initially interpreted as suggestive of hypogonadotropic hypogonadism, prompting further biochemical and genetic analysis. Next-generation sequencing identified heterozygous variants in X-linked genes, uncovering a 46,XX difference of sex development (DSD). Then, CYP21A2 molecular analysis revealed compound heterozygosity for two pathogenic variants (p.I173N, p.R357W), confirming simple virilizing CAH. The patient’s reticent attitude contributed to the diagnostic delay. However, this unique case reveals the challenges generated by the paraurethral glands hyperplasia - mimicking a prostate due to prolonged untreated hyperandrogenism - as well as the repeated failure to recognize Müllerian remnants on imaging and the critical issues related to diagnostic communication.
Increased cardiovascular morbidity and reduced life expectancy in a large Italian cohort of patients with resistance to thyroid hormone β (RTHβ) Irene Campi, Simona Censi, Flavia Prodam, Luisa Petrone, Giulia Brigante, et al. European Journal of Endocrinology, 2024 Objective Decreased survival and higher cardiovascular morbidity have been recently reported in a UK cohort of 61 RTHβ patients, but there is no evidence from other countries. Design Retrospective cohort study from an historical group of 284 Italian RTHβ patients, diagnosed between 1984 and 2023. Methods We collected data on diagnosis of 284 cases and longitudinal data of 249 RTHβ who carried heterozygous pathogenic variants in the THRB gene. We studied how thyroid function and recognized risk factors for cardiovascular disease, such as hypertension and diabetes, affected overall mortality and major cardiovascular events. Results The cumulative prevalence of sinus/supraventricular tachycardia and atrial fibrillation was 40% and 18%, respectively. FT4 values 57% higher than the upper limit of normal were associated with premature cardiovascular manifestations. Major cardiovascular events (MACEs) occurred in RTHβ patients at a median age (IQR) of 59.4 years (50.4-66.4) and early mortality resulted in a mean of 11 years of life lost. While at univariable analysis hypertension, dyslipidemia, high fasting glucose/diabetes were also associated with MACEs, at multivariable analysis only age at diagnosis, increased fT4 levels, and male gender remained significantly associated with MACEs and age at diagnosis and higher fT4 levels with mortality. Previous thyroidectomy or radioiodine therapy had no statistically significant effect in the prevention of major cardiovascular events or all-cause mortality. Conclusions These data should raise the general awareness on the cardiovascular risk and prompt a proactive cardiovascular monitoring in RTHβ, especially in men and those with fT4 levels above 30 pmol/L.
Challenging diagnosis of resistance to thyroid hormone in a patient with COVID-19, pituitary microadenoma and unusual response to octreotide long-acting release test Cristian Petolicchio, Sara Brasili, Stefano Gay, Francesco Cocchiara, Irene Campi, et al. Endocrinology Diabetes and Metabolism Case Reports, 2024 Summary The resistance to thyroid hormone syndrome (RTHβ) occurs uncommonly and requires a high level of clinical suspicion and specific investigations to reach a precise diagnosis and to avoid unnecessary and potentially harmful therapies. We report a case of a young male patient referred to our unit for SARS-CoV-2 infection and atrial fibrillation with elevated thyroid hormones and non-suppressed thyroid-stimulating hormone (TSH), for which antithyroid therapy was prescribed. A mood disorder was reported in the medical history. The family history was unknown as the patient was adopted. Thyroid-specific antibodies were undetectable, and thyroid ultrasound revealed a normal thyroid gland without nodules. After the resolution of SARS-CoV-2 infection, the diagnostic workup continued, and the pituitary MRI revealed a small area ascribable to a microadenoma. Due to atrial fibrillation, the execution of the T3 test was contraindicated. The octreotide long-acting release (LAR) test showed an initial reduction of free thyroid hormones levels at first administration, which was consistent with the presence of a TSH-secreting pituitary tumour, although an escape from the response was observed after the following two injections of octreotide LAR. Indeed, the genetic investigation revealed a variant in heterozygosity of the THRβ gene (Pro453Ser), thus leading to an RTHβ diagnosis, and, therefore, medical treatment with triiodothyroacetic acid was initiated. After 2 years from the SARS-CoV-2 infection, the patient continues the follow-up at our outpatient clinic, and no other medical interventions are needed. Learning points RTHβ is a rare genetic syndrome characterised by discrepant thyroid function tests and by a dissociation between the observed hormone levels and the expected patient signs and symptoms. Features of thyroid hormone deficiency in TR-ß dependent tissues (pituitary gland, hypothalamus, liver and neurosensitive epithelia), as well as thyroid hormone excess in TR-α-dependent tissues (heart, bone, skeletal muscle and brain), may coexist in the same individual. Clinical pictures can be different even when the same variant occurs, suggesting that other genetic and/or epigenetic factors may play a role in determining the patient’s phenotype. Differentiating RTHβ from a TSH-secreting pituitary tumour is very difficult, especially when a concomitant pituitary adenoma is detected during diagnostic workup. The injection of long-acting somatostatin analogues can help differentiate the two conditions, but it is important to detect any interference in the dosage of thyroid hormones to avoid an incorrect diagnosis. Genetic testing is fundamental to prevent unnecessary and potentially harmful therapies. Medical treatment with triiodothyroacetic acid was demonstrated to be effective in reducing thyroid hormone excess and controlling symptoms.
Hormones and Autoimmunity Roberta Gualtierotti, Carolina Artusi, Guia Maria Vannucchi, Irene Campi, Luca Persani, et al. Mosaic of Autoimmunity the Novel Factors of Autoimmune Diseases, 2019
TSH-secreting adenomas Paolo Beck-Peccoz, Luca Persani, Deborah Mannavola, Irene Campi Best Practice and Research Clinical Endocrinology and Metabolism, 2009
