Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study.

PURPOSE: Craniopharyngiomas (CPGs) are aggressive brain tumors responsible of severe morbidity in children. The best treatment strategies are under debate. Our study evaluates surgical, pituitary, and hypothalamic outcomes of a tailored staged-surgical approach compared to a single-stage radical approach in children with CPGs. METHODS: Multicenter retrospective study enrolling 96 children treated for CPGs in the period 2010-2022. The surgical management was selected after a multidisciplinary evaluation. Primary endpoint includes the inter-group comparison of preservation/improvement of hypothalamic-pituitary function, the extent of resection, and progression-free survival (PFS). Secondary endpoints include overall survival (OS), morbidity, and quality of life (QoL). RESULTS: Gross Total Resection (GTR) was reached in 46.1% of cases in the single-stage surgery group (82 patients, age at surgery 9 ± 4.7 years) and 33.3% after the last operation in the staged surgery group (14 patients age 7.64 ± 4.57 years at first surgery and 9.36 ± 4.7 years at the last surgery). The PFS was significantly higher in patients addressed to staged- compared to single-stage surgery (93.75% vs 70.7% at 5 years, respectively, p = 0.03). The recurrence rate was slightly higher in the single-stage surgery group. No significant differences emerged in the endocrinological, visual, hypothalamic outcome, OS, and QoL comparing the two groups. CONCLUSIONS: In pediatric CPGs' surgical radicality and timing of intervention should be tailored considering both anatomical extension and hypothalamic-pituitary function. In selected patients, a staged approach offers a safer and more effective disease control, preserving psychophysical development.

SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review.

PURPOSE: To perform a systematic review on published cases of subacute thyroiditis (SAT) secondary to SARS-CoV-2 vaccination, to highlight main features and increase the awareness of this condition. METHODS: Original reports of SAT developed after SARS-CoV-2 vaccination (mRNA, viral vector, or inactivated virus vaccines) were retrieved from a search of electronic databases. Individual patient data on demographics, medical history, type of vaccine, workup and therapies were collected. Wilcoxon rank-sum, Kruskal-Wallis and chi-squared tests were employed for comparisons. RESULTS: 30 articles including 48 reports were retrieved, 3 additional cases evaluated by the Authors were described and included for analysis. Of the 51 patients, 38 (74.5%) were women, median age was 39.5 years (IQR 34-47). Patients developed SAT after a median of 10 days (IQR 4-14) after the vaccine shot. Baseline thyroid exams revealed thyrotoxicosis in 88.2% of patients, decreasing at 31.6% at follow-up. Corticosteroids were used in 56.4% of treated patients. Patients undergoing non-mRNA vaccines were most frequently Asian (p = 0.019) and reported more frequently weight loss (p = 0.021). All patients with a previous diagnosis of thyroid disease belonged to the mRNA vaccine group. CONCLUSION: SARS-CoV-2 vaccine-associated SAT is a novel entity that should be acknowledged by physicians. Previous history of thyroid disease may predispose to develop SAT after mRNA vaccines, but further studies and larger cohorts are needed to verify this suggestion. SARS-CoV-2 vaccine-associated SAT is usually of mild/moderate severity and could be easily treated in most cases, thus it should not raise any concern regarding the need to be vaccinated.

SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?

INTRODUCTION: Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis. METHODS AND RESULTS: Specimen from fine-needle aspiration of a hypoechoic undefined area was analyzed for cytology and for SARS-CoV-2 detection. SARS-CoV-2 was retrieved by real-time polymerase chain reaction on the cytologic sample, which was then cultured on Vero E6 cells and demonstrated to be cytopathic. Whole-genome sequence was deposited. Histological exam diagnosed a rare case of primary thyroid sarcoma with diffuse and strong expression of mouse double minute 2 homolog (MDM2) oncoprotein. Ultrastructural examination confirmed, in several neoplastic cells, the presence of viral particles in cytoplasmic vacuoles. CONCLUSIONS: In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. Functional studies are needed to confirm this suggestive pathway.

Change in newly diagnosed Graves' disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression.

PURPOSE: According to a few recent studies, the clinical phenotype of Graves' disease (GD) at onset is becoming milder in recent years, in terms of prevalence and severity of hyperthyroidism, goiter and overt eye disease. The aim of this study was to assess the change in GD phenotype across the late twentieth and the early twenty-first centuries. MATERIALS AND METHODS: We carried out a systematic search of studies published between 1/1/1980 and 12/31/2017 describing naïve GD patients at diagnosis. We collected epidemiological, clinical, biochemical and serological data reported in the selected studies, and (1) conducted a single-arm meta-analysis to compare clinical and biochemical characteristics of naïve GD patients before and after year 2000 and (2) performed a meta-regression to identify the trend of the observed clinical presentations. RESULTS: Eighty selected articles were related to the period before the year 2000, 30 to the years 2000-2017. According to demographics, the two defined populations were homogeneous at meta-analysis: overall estimated female prevalence was 81% [95% CI 79-82], mean estimated age of the entire population was 39.8 years [95% CI 38.4-41.1], with no significant differences between pre- and post-2000 groups (p > 0.05). The overall estimated prevalence of smokers was 40% [95% CI 33-46], with no significant difference between the two groups (p > 0.05). Mean estimated free thyroxine (FT4) and free triiodothyronine (FT3) levels at diagnosis were higher in the pre-2000 group: 4.7 ng/dl [95% CI 4.5-4.9] for FT4 and 14.2 pg/ml [95% CI 13.3-15.1] for FT3, as compared to the post-2000 group: 3.9 ng/dl [95% CI 3.6-4.2] for FT4 and 12.1 pg/ml [95% CI 11.0-13.3] for FT3 (all p < 0.01). Goiter estimated prevalence was higher in the pre-2000 group, 87% [95% CI 84-90], than in the post-2000 group, 56% [95% CI 45-67]. Estimated prevalence for Graves' Orbitopathy (GO) was 34% [95% CI 27-41] in the pre-2000 group and 25% [95% CI 19-30] in the post-2000 group (p = 0.03). Accordingly, meta-regression adjusted for covariates showed an average annual reduction of FT4 (- 0.040 ± 0.008 ng/dl, p < 0.0001), FT3 (- 0.316 ± 0.019 pg/ml, p < 0.0001), goiter prevalence (- 0.023 ± 0.008%, p = 0.006), and goiter size (- 0.560 ± 0.031 ml, p < 0.0001). CONCLUSIONS: Our meta-analysis and meta-regression confirmed that GD phenotype at diagnosis is nowadays milder than in the past; we hypothesize that conceivable factors involved in this change are iodoprophylaxis, worldwide decrease in smoking habits, larger use of contraceptive pill and micronutrient supplementation, as well as earlier diagnosis and management.

Thyroid surgery during coronavirus-19 pandemic phases I, II and III: lessons learned in China, South Korea, Iran and Italy.

OBJECTIVE: We compared demographic and clinic-pathological variables related to the number of surgeries for thyroid conditions or for cancer, morbidity, and fine needle aspiration (FNA) practices among Covid19 pandemic phases I, II, III and the same seasonal periods in 2019. METHODS: The prospective database of the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China was used for this study. Covid19 emergency levels were stratified according to the World Health Organization: phase I (January 25-February 25, 2020), phase II (February 26-March 19), phase III (March 20-April 20). RESULTS: There were fewer outpatient FNAs and surgeries in 2020 than in 2019. There were no thyroid surgeries during phase I. There were also fewer surgeries for cancer with a significant reduction of advanced stage cancer treatments, mainly stage T1b N1a in phase II and T3bN1b in phase III. Operative times and postoperative stays were significantly shorter during the pandemic compared to our institutional baseline. In phase III, vocal cord paralysis (VCP) increased to 4.3% of our baseline numbers (P = 0.001). There were no cases of Covid19-related complications during the perioperative period. No patients required re-admission to the hospital. CONCLUSION: The Covid19 outbreak reduced thyroid surgery patient volumes. The decrease of Covid19 emergency plans contributed to unexpected outcomes (reduction of early stage cancer treatment, decreased operative times and hospital stays, increased VCP rate).

Skeletal health in patients with differentiated thyroid carcinoma.

Osteoporosis and fractures are important comorbidities in patients with differentiated thyroid cancer (DTC), with potential negative impact on quality of life and survival. The main determinant of skeletal fragility in DTC is the thyrotropin (TSH)-suppressive therapy, which is commonly recommended to prevent disease's recurrence, especially in patients with structural incomplete response after thyroid surgery and radio-iodine therapy. TSH-suppressive therapy can stimulate bone resorption with consequent bone loss, deterioration of bone microstructure and high risk of fragility fractures. The skeletal effects of TSH-suppressive therapy may be amplified when thyroid cancer cells localize to the skeleton inducing alterations in bone remodelling, impairment of bone structure and further increase in risk of fractures. The management of skeletal fragility in DTC may be challenging, since prediction of fractures is a matter of uncertainty and data on effectiveness and safety of bone-active agents in this clinical setting are still scanty. This review deals with pathophysiological, clinical and therapeutic aspects of skeletal fragility of patients with DTC.

The interplay between thyroid and liver: implications for clinical practice.

A complex relationship exists between thyroid and liver in health and disease. Liver plays an essential physiological role in thyroid hormone activation and inactivation, transport, and metabolism. Conversely, thyroid hormones affect activities of hepatocytes and hepatic metabolism. Serum liver enzyme abnormalities observed in hypothyroidism may be related to impaired lipid metabolism, hepatic steatosis or hypothyroidism-induced myopathy. Severe hypothyroidism may have biochemical and clinical features, such as hyperammonemia and ascites, mimicking those of liver failure. Liver function tests are frequently abnormal also in hyperthyroidism, due to oxidative stress, cholestasis, or enhanced osteoblastic activity. Antithyroid drug-associated hepatotoxicity is a rare event, likely related mainly to an idiosyncratic mechanism, ranging from a mild hepatocellular damage to liver failure. Propylthiouracil-induced liver damage is usually more severe than that caused by methimazole. On the other hand, thyroid abnormalities can be found in liver diseases, such as chronic hepatitis C, liver cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma. In particular, autoimmune thyroid diseases are frequently found in patients with hepatitis C virus infection. These patients, especially if thyroid autoimmunity preexists, are at risk of hypothyroidism or, less frequently, thyrotoxicosis, during and after treatment with interpheron-alpha alone or in combination with ribavirin, commonly used before the introduction of new antiviral drugs. The present review summarizes both liver abnormalities related to thyroid disorders and their treatment, and thyroid abnormalities related to liver diseases and their treatment.

Features and outcome of differentiated thyroid carcinoma associated with Graves' disease: results of a large, retrospective, multicenter study.

BACKGROUND: Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves' disease (GD) is more aggressive and bound to a less favorable outcome is controversial. OBJECTIVE: Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD-). PATIENTS: Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD-. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. RESULTS: Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD- patients were free of disease. Patients with persistent or recurrent disease (PRD) had "biochemical disease" in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves' orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism. CONCLUSIONS: GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD.

Immunomodulatory effect of vitamin D and its potential role in the prevention and treatment of thyroid autoimmunity: a narrative review.

The main role of vitamin D is to control mineral homeostasis. However, recent studies suggested the existence of a number of extraskeletal effects. Among the latter, preclinical studies provided consistent data on the involvement of vitamin D in innate and adaptive immunity and autoimmunity. Molecular biology studies showed that both vitamin D receptor and vitamin D enzymatic complexes are expressed in a large number of cells and tissues unrelated to mineral homeostasis. In contrast, only a few randomized clinical trials in humans investigated the possible role of vitamin D in the prevention or treatment of immunological disorders. In this regard, low serum vitamin D levels have been reported in observational trials in human autoimmune disorders. The aim of the present paper was to review the potential implications of vitamin D in immune modulation, with special focus on thyroid autoimmune disorders.