The role of Graves' disease in the development of thyroid nodules and thyroid cancer.

Aim: The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves' disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules and cancer in patients with Graves' disease. Methods: Retrospective observational study of adult subjects with Graves' disease (positive autoantibodies thyrotropin receptor antibodies (TRAbs)) between 2017 and 2021 at our center was done. We evaluated the prevalence of thyroid nodules and cancer in this population and characterized the predictive factors for thyroid malignancy using linear and logistic regression models. Results: We evaluated a total of 539 patients with Graves' disease during a median follow-up of 3.3 years (25th-75th percentiles 1.5-5.2 years). Fifty-three percent had thyroid nodules and 18 (3.3%) were diagnosed with thyroid cancer (12 papillary microcarcinomas). All tumors were classified using TNM classification as T1, and only one had lymph node metastasis; there were no recordings of distant metastasis. Sex, age, body mass index, smoking, TSH, and TRAbs levels were not significantly different between patients with and without thyroid cancer. Patients with multiple nodules on ultrasound (OR 1.61, 95%CI 1.04-2.49) and with larger nodules (OR 2.96, 95%CI 1.08-8.14, for 10 mm increase in size) had a greater risk of thyroid cancer diagnosis. Conclusion: Patients with Graves' disease had a high prevalence of thyroid nodules and their nodules had a significant risk of thyroid cancer. The risk was higher in those with multiple and larger nodules. Most had low-grade papillary thyroid cancer. More studies are needed to clarify the clinical relevance of these findings.

Ectopic Cushing's Syndrome Unveiling a Metastatic Parotid Carcinoma.

INTRODUCTION: Adrenocorticotropic hormone (ACTH) ectopic production is a rare cause of Cushing syndrome (CS). The most commonly associated tumours are small-cell lung carcinoma along with bronchial and thymic carcinoids. To date, only 5 cases have been published in the literature featuring ectopic ACTH secretion from metastatic acinic cell carcinoma (ACC) of the parotid gland. We hereby describe a very uncommon case of ectopic CS (ECS) unveiling a metastatic parotid ACC. CASE PRESENTATION: A 46-year-old man with hypertension and dyslipidemia diagnosed 4-months before, as well as new-onset diabetes mellitus unveiled 1-month earlier, was referred to emergency department for hypokalemia. Hormonal study and dynamic biochemical tests performed indicated ECS. Imaging and cytological findings pointed toward a likely primary right parotid malignancy with liver metastases. Somatostatin receptor scintigraphy has shown an increased uptake in the parotid gland and mild expression in liver metastasis. The patient underwent right parotidectomy, and histopathologic examination confirmed ACC. Meanwhile, hypercortisolism was managed with metyrapone, ketoconazole, and lanreotide. Despite chemotherapy onset, a rapid disease progression and clinical course deterioration was observed. CONCLUSION: The present report highlights a rare ECS, exposing a metastatic parotid ACC, with an aggressive and challenging clinical course, representing the first case whose diagnosis of ECS came prior to ACC.

Pituitary incidentalomas: analysis of a neuroradiological cohort.

PURPOSE: Most pituitary lesions are detected during the investigation of symptoms associated with hormonal dysfunction and vision abnormalities. When the lesion is identified in an image performed for reasons not related to the tumor, the term incidentaloma applies. Our aim was to describe the diagnosis behind pituitary incidentalomas, patient characteristics and their follow up. METHODS: We searched for the terms "pituitary", "hypophysis" and "incidentaloma" in the requisitions and reports of all CTs and MRIs performed between 1st September 2008 and 30th October 2013. We retrieved demographic data as well as information regarding presentation and follow-up. RESULTS: We detected 71 pituitary incidentalomas, 3 in children/adolescents. In adult patients, mean age was 51.6 ± 18.46 years and 42 were female (61.8 %). The most frequent reason for imaging was headache (33.8 %). The image that first detected the incidentaloma was CT scan in 63.2 and 17.6 % patients presented symptoms that could have led to earlier diagnosis. Pituitary adenoma is the most prevalent lesion (n 48; 70.6 %), followed by Rathke's cleft cyst (n 9; 13.2 %). Hormonal evaluation revealed hypopituitarism in 14 patients and hypersecretion in 6: 5 prolactinomas and 1 somatotroph adenoma. Twenty-one (28.8 %) patients underwent surgery and there was no malignancy. CONCLUSIONS: In concordance with available literature, adenomas are the most frequent incidentally found pituitary lesions. Hormonal dysfunction is quite prevalent, including symptomatic presentations, which suggests that there seems to be a low sensitivity for the diagnosis of pituitary disease.

Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune thyroid disease.

BACKGROUND: Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD. METHODS: Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays. RESULTS: A significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37-2.43, p-value = 4.4×10(-5)) and log-additive (OR = 1.64, CI = 1.28-2.10, p-value = 8.2×10(-5)) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06-1.54, p-value = 8.9×10(-3)). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19-2.87, p-value = 7.0×10(-3)) and log-additive (OR = 1.69, CI = 1.17-2.44, p-value = 6.6×10(-3)) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59). CONCLUSIONS: This study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD.

[Thyroid associated orbitopathy]. / Abordagem da orbitopatia associada à tiróide.

Thyroid associated orbitopathy is a clinical entity with pathogenic mechanisms not fully understood, and appears in about 90% of cases in association with hyperthyroidism of Graves' disease. Its approach involves the recognition of typical features and the exclusion of other diseases in the less common presentations. The treatment is conditioned by the determination of the activity and severity of the disease. The restoration of the euthyroid state and avoiding of hypothyroidism are essential in mitigating the progression of orbitopathy. Glucocorticoid intravenous therapy is the treatment of choice in the active phase and surgical treatment in the inactive phase. Radiotherapy and cyclosporine in combination with corticosteroids are alternatives when monotherapy is insufficient in the active phase. Treatment should be instituted in specialized centers, with ophthalmologists and endocrinologists acting in synergy to avoid consequences of delays in intervention and in optimizing therapy.

Morbid obesity and inflammation: a prospective study after adjustable gastric banding surgery.

BACKGROUND: Inflammatory status underlying obesity seems to be implicated in several aspects of metabolic syndrome. OBJECTIVE: This study aimed to investigate the association between weight loss achieved by laparoscopic gastric banding (LAGB) surgery, chronic inflammatory markers, and nutritional state. METHODS: Thirty-two morbid obese females were enrolled in the study and evaluated at baseline, 1 and 18 months after LAGB surgery. Serum immunoglobulin G (IgG), IgA, IgM, C-reactive protein (CRP), haptoglobin, alpha-1 antitrypsin, total proteins, albumin, prealbumin, transferrin, ferritin, and transferrin soluble receptor were evaluated. In addition, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting glucose were also evaluated. RESULTS: In average, patients presented 18.7% and 63.2% excess body weight loss 1 and 18 months after LAGB, respectively (p < 0.01). CRP and total cholesterol mean levels were elevated (1.03 +/- 1.11 mg dL(-1) and 2.02 +/- 0.41 g L(-1)) at the presurgery study. CRP mean levels were significantly reduced when compared to reference range (p < 0.01) 18 months after the LAGB surgery. Prealbumin as well as serum total protein mean levels decreased 1 month after surgery (p < 0.01) and values returned to normal at 18 months after surgery. Albumin mean levels showed an increase during the postsurgery evaluations. Serum IgA and IgM concentrations were significantly increased at 1 month after surgery compared to baseline (p < 0.01, both cases). CONCLUSIONS: Our results indicate that amelioration of inflammatory markers after LAGB does not seem to negatively impact nutritional status following weight reduction surgery. However, careful attention should be driven to serum IgA. Adequacy of nutritional intake and complete serial laboratory measurements should be always included in the required life-long follow-up of patients surgically treated for morbid obesity.