Iodine, thyroid autoimmunity and cancer

This review focuses on two different topics: (a) iodine and autoimmune thyroid disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake modifies the expression of thyroid diseases and has been associated with induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated Tg, as suggested in animal models. We have shown that the unmasking of a cryptic epitope on Tg contributes to iodine-induced thyroid autoimmunity in humans. The relationship between AITD and PTC has been suggested in many studies. The presence of two different mechanisms has been hypothesized, one typical of AITD and the other of an immune reaction to PTC. We have shown that in AITD, the pattern of Tg recognition by anti-Tg antibodies (TgAb) is 'restricted' to the immunodominant regions of Tg, while in patients with non-AITD, such as nodular goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid function may also affect the frequency of PTC, the risk of cancer increasing with serum TSH levels. We have shown that this mechanism, rather than thyroiditis per se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as a consequence of the autoimmune process leading to a progressive increase of serum TSH in these patients

Efficacia e sicurezza dell'analogo della triiodotiroinina (Triac) nei bambini e negli adulti con deficit di MCT8: un trial internazionale, a singolo braccio, open label di fase 2

n/

Analisi della funzione tiroidea in 50 pazienti con COVID-19: uno studio retrospettivo

n/

A patient with MEN1 and end‑stage chronic kidney disease due to Alport syndrome: Decision making on the eligibility of transplantation

Absence of neoplastic disease in the organ‑recipient is required in order to allow organ transplantation. Due to its rarity, no data regarding management of patients with Multiple endocrine neoplasia type 1 (MEN1) and end‑stage renal failure candidates for kidney transplantation are available. A 36 year‑old man was referred to the present hospital with MEN1, with a neuroendocrine pancreatic tumor and primary hyperparathyroidism and associated Alport syndrome with end stage renal failure. The present study aimed to establish the eligibility of the patient for a kidney transplantation. The neuroendocrine tumor had been treated with duodenopancreatectomy two years earlier and hyperparathyroidism by parathyroidectomy. The review of the literature did not provide data regarding the eligibility for kidney transplantation of patients harboring a neuroendocrine pancreatic tumor in the context of MEN1. Due to the end‑stage renal failure, neuroendocrine markers were unreliable and the investigation therefore relied on imaging studies, which were unremarkable. Young age, low‑grade tumor, low expression of Ki67, absence of metastatic lymph nodes, onset in the setting of a MEN1 were all positive prognostic factors of the neuroendocrine tumor. Normal serum calcium ruled out persistent primary hyperparathyroidism. Overall, hemodyalisis is known to significantly reduce life expectancy. Benefits of kidney transplantation overcome the risk of neuroendocrine tumor recurrence in a young patient bearing MEN1

Il gozzo multinodulare

SommarioSi definisce gozzo l'incremento diffuso o nodulare della ghiandola tiroidea. Il suo sviluppo è legato a fattori genetici e ambientali, di cui il più importante è rappresentato dalla carenza iodica. L'inquadramento clinico prevede un'attenta valutazione dei sintomi, dei segni, dei risultati degli esami ormonali, delle caratteristiche ecografiche e citologiche. Il trattamento deve essere poi individualizzato tenendo conto della disponibilità di molteplici opzioni terapeutiche

Thyroid autoimmunity, thyroglobulin autoantibodies and thyroid cancer prognosis

Relevance of thyroid autoimmunity to prognosis of papillary thyroid carcinoma is still unsettled. We decided to investigate the impact of thyroid autoimmunity on prognosis of papillary thyroid carcinoma and the handling of TgAbs. We evaluated the clinical course of a large group of patients according to the presence (PTC-LT) or absence (PTC) of lymphocytic thyroiditis at histology. We studied 194 consecutive patients with a diagnosis of PTC and treated with total thyroidectomy plus ¹³¹I ablation between 2007 and 2009. Median follow-up (with 25th-75th percentiles) was 84·0 (56·4-118·0) months. The remission criteria were: basal Tg <0·2 ng/mL (or stimulated Tg <1), TgAbs <8 IU/mL (otherwise "decreasing TgAb trend", a decline of ≥20% in sequential TgAb measurements) and unremarkable imaging. PTC-LT and PTC patients had comparable treatment.TgAbs were detectable in 72·5% of PTC-LT and 16·5% of PTC patients. Time to remission was longer in the detectable than in the undetectable TgAb cohort (28·5 vs· 7·5 months [median]; HR 0·54, CI 0·35-0·83, p=0·005). When comparing PTC-LT to PTC patients the difference was maintained in the detectable TgAb (29·3 vs 13·0 months; HR 0·38, CI 0·18-0·80; p=0·01), but not in the undetectable TgAb cohort (7·7 vs 7·3 months; HR 0·90, CI 0·55-1·47; p=0·68). Using the decreasing TgAb trend, the influence of detectable TgAbs on time to remission was abolished. Thyroid autoimmunity does not influence the prognosis of papillary thyroid carcinoma. A decreasing TgAb trend seems an appropriate criterion to establish the remission of papillary thyroid carcinoma

Chronic polyarthritis associated to Cercopithifilaria bainae infection in a dog.

Despite the widespread distribution of Cercopithifilaria bainae among canine and tick populations worldwide, this filarioid is currently considered of 'minor importance' in veterinary medicine, particularly when compared to related filarioids, such as Dirofilaria immitis and Dirofilaria repens. To date, only a single case of dermatological alterations possibly associated to infection by C. bainae had been reported in a dog. In the present study, we describe the first case of systemic alterations associated to C. bainae infection in a dog suffering from diffused chronic polyarthritis. The animal had a previous history of reluctance to move and stiff gait and displayed multiple joint pain during manipulation of limbs. No biochemical, haematological and X-ray alterations were detected; microfilariae were observed in the synovial fluids collected from the joints. In spite of the morphological and molecular identification of these microfilariae as C. bainae, the dog did not respond to multiple microfilaricidal treatments with milbemicyn oxyme. The potential role of C. bainae in the pathogenesis of this clinical condition is discussed. Given the potential pathogenicity of this parasite, improved knowledge of this little known tick-borne nematode is warranted in order to assist the development of novel and effective treatment strategies.This is the author accepted manuscript. The final version can be found on the publisher's website at: http://www.sciencedirect.com/science/article/pii/S0304401714003744# © 2014 Published by Elsevier B.V

Low elasticity of thyroid nodules at ultrasound elastography is correlated with malignancy, degree of fibrosis and high expression of galectin-3 and fibronectin-1

ackground: Thyroid ultrasound (US) elastography provides an estimation of tissue stiffness and is helpful to differentiate malignant from benign lesions. Tissue proprieties and molecules causing stiffness are not established. The aim of the study was to correlate US elastography findings with tissue properties in thyroid nodules. Methods: A total of 115 thyroid nodules from 112 patients who underwent surgery for the presence of Thy 3 (indeterminate) cytology (n = 67), Thy 4-5 (suspicious - indicative of carcinoma) cytology (n = 47), or large goiter in the presence of Thy 2 cytology (n = 1) and suspicious US features were examined by US elastography. Tissues obtained after surgery were characterized for cell number, microvessel density, fibrosis, and expression of galectin-3 (Gal-3) and fibronectin-1 (FN-1). Results: Low elasticity on qualitative US elastography (LoEl) was found in 66 nodules (one benign and 65 carcinomas); high elasticity (HiEl) was found in 49 nodules (46 benign and three carcinomas; p < 0.0001). Quantitative analysis, performed in 24 nodules and expressed as elastic ratio between the strain of the nodule and that of the surrounding thyroid parenchyma, showed a mean of 1.90 (interquartile range [IQR] 1.18-2.77) in 14 nodules with LoEl, and a mean of 1.01 (IQR 0.91-1.10) in 10 nodules with HiEl (p = 0.002). Stiffness did not correlate with cell number and was inversely correlated with microvessel density. Fibrosis was higher in nodules with LoEl than in those with HiEl (p = 0.009) and in carcinomas than in benign nodules (p = 0.02). Fibrosis was higher in nodules with high expression of Gal-3 (p < 0.001) and FN-1 (p = 0.004). Fibrosis and expression of Gal-3 and FN-1 were higher in the classic compared with the follicular variant of papillary thyroid carcinoma and lower in follicular adenomas. Conclusions: Low elasticity at US elastography is highly correlated with malignancy. Nodule stiffness is correlated with fibrosis and expression of Gal-3 and FN-1. These features are more evident in the classic than in the follicular variant of papillary thyroid carcinoma

Effect of thyroglobulin autoantibodies on the metabolic clearance of serum thyroglobulin

Background: In order to establish whether thyroglobulin autoantibodies (TgAb) influence the metabolic clearance of thyroglobulin (Tg) in humans, serum Tg and TgAb were correlated shortly after radioiodine (131I) treatment. Methods: Samples were collected from 30 consecutive patients undergoing 131I activity for Graves' hyperthyroidism at the time of treatment and every 15 days thereafter, up to 90 days. Tg and TgAb were measured by immunometric assays (functional sensitivities: 0.1 ng/mL and 8 IU/mL). Results: Tg was detectable in all patients at day 0. Tg concentrations rose from a mean of 33.2 ng/mL [confidence interval (CI) 17.8–61.0 ng/mL] at day 0 to a mean of 214.6 ng/mL [CI 116.9–393.4 ng/mL] at day 30 and then steadily decreased, reaching the lowest concentration at day 90 (M = 10.9 ng/mL [CI 5.5–20.9 ng/mL]). Compared to their levels at day 0 (M = 23.6 IU/mL [CI 10.5–52.9 IU/mL]), TgAb remained stable through day 15 and then gradually increased up to a mean of 116.6 IU/mL [CI 51.9–262.2 IU/mL] at day 90. Patients were then split into two groups according to their TgAb status at day 0: undetectable (<8 IU/mL; 9 patients) or detectable (≥8 IU/mL; 21 patients) TgAb. Compared to the other cohort, patients with detectable TgAb showed significantly lower Tg concentrations at day 0 (M = 20.3 ng/mL [CI 10.1–40.2 ng/mL] vs. M = 101.8 ng/mL [CI 36.6–279.8 ng/mL]), similar at day 15, lower levels at day 30 (M = 146.5 ng/mL [CI 74.3–287.8 ng/mL] vs. M = 514.8 ng/mL [CI 187.8–1407.9 ng/mL]), at day 45 (M = 87.5 ng/mL [CI 43.1–176.6 ng/mL] vs. M = 337.9 ng/mL [CI 120.1–947.0 ng/mL]), at day 60 (M = 61.6 ng/mL [CI 31.0–121.4 ng/mL] vs. M = 255.8 ng/mL [CI 79.0–823.8 ng/mL]), and at day 75 (M = 24.5 ng/mL [CI 11.9–49.2 ng/mL] vs. M = 249.5 ng/mL [CI 63.5–971.1 ng/mL]), and similar levels at day 90. Patients with detectable TgAb showed a lower (M = 182.5 ng/mL [CI 92.0–361.0 ng/mL] vs. M = 514.8 ng/mL [CI 187.8–1407.9 ng/mL]) and an earlier (day 15 vs. day 30) peak of Tg. The mean Tg concentration was lower in patients with detectable TgAb than in those with undetectable TgAb (area under the curve: 17,340 ± 16,481 ng/mL vs. 36,883 ± 44,625 ng/mL; p = 0.02). Conclusions: TgAb influence the changes in Tg concentrations observed immediately after 131I treatment, inducing lower levels and an earlier peak of Tg. These observations indicate that TgAb significantly influence the metabolic clearance of Tg, supporting the concept that their interference in the measurement of Tg is mainly due to an in vivo effect