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  • Author: Silvia Martina Ferrari x
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Alessandro Antonelli, Clodoveo Ferri, Poupak Fallahi, Massimiliano Cazzato, Silvia Martina Ferrari, Marco Sebastiani and Ele Ferrannini

Objective: Several studies have reported the association of systemic sclerosis (SSc) with thyroid autoimmune disorders, but most of them have neither an appropriate control group nor include a complete thyroid work-up.

Design: The aim of our study was to evaluate the prevalence of thyroid disorders in a large number of patients with SSc using a complete clinical evaluation.

Methods: Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid-peroxidase (AbTPO) autoantibodies, thyroid ultrasonography and blood flow and fine needle aspiration were performed in 202 SSc patients versus 404 gender- and age-matched controls from the general population, with similar iodine intake, to evaluate the prevalence of clinical and subclinical thyroid disorders.

Results: Odds ratio (OR) for female SSc versus controls was: for subclinical hypothyroidism, 3.2 (95% CI) = 1.8–5.7); for clinical hypothyroidism, 14.5 (95% CI = 2.3–90.9); for AbTPO positivity, 2.7 (95% CI = 1.8–4.1); for hypoechoic pattern, 3.2 (95% CI = 2.2–4.7); for thyroid autoimmunity, 3.7 (95% CI = 2.6–5.4); for thyroid volume <6 ml, 1.8 (95% CI = 1.2–2.7). OR for thyroid autoimmunity in male SSc versus controls was 10.8 (95% CI = 2.2–52.4). Mean values of TSH in female SSc, and of AbTPO in female and male SSc were higher (P <0.01) than in controls. We observed three cases of Graves’ disease in female SSc versus zero in controls (P = 0.0140), and two cases of papillary thyroid cancer in SSc patients.

Conclusions: Thyroid function, AbTPO and ultrasonography should be tested as part of the clinical profile in SSc patients. Females, subjects with positive AbTPO and hypoechoic and small thyroid should have thyroid function follow-up and appropriate treatment in due course.

Free access

Alessandro Antonelli, Mario Rotondi, Poupak Fallahi, Paola Romagnani, Silvia Martina Ferrari, Aldo Paolicchi, Ele Ferrannini and Mario Serio

Objective: To measure serum levels of CXCL10 and CCL2 prototype chemokines of the two major subclass (CXC and CC) in patients with newly diagnosed chronic autoimmune thyroiditis (AT), and relate the findings to the clinical phenotype.

Design and methods: Serum CXCL10 and CCL2 were assayed in 70 consecutive patients with newly diagnosed chronic AT, in sex- and age-matched healthy volunteers (n = 37) and in 20 patients with non-toxic multinodular goiter, extracted from a random sample of the general population from the same geographic area.

Results: CXCL10 serum levels were significantly higher in patients with thyroiditis than in controls or multinodular goiter patients, while comparable CCL2 levels were found between groups. CXCL10 levels were significantly increased in hypothyroid patients and in those with an hypoechoic pattern (P = 0.0004 and P = 0.0001, respectively) while serum CCL2 levels were significantly increased in patients older than 50 years and in those with hypothyroidism (P = 0.0001 and P = 0.03, respectively). No correlation between CXCL10 and CCL2 serum levels could be demonstrated. CXCL10 and CCL2 were studied separately in relation to clinical features of AT patients. Two separate multiple linear regression models for CXCL10 and CCL2 were performed, including age, thyroid volume, thyroid stimulating hormone (TSH), FT4, anti-thyroid peroxidase (AbTPO), hypoechoic pattern, and the presence of hypervascularity, demonstrating that ln of serum CXCL10 levels was associated with TSH independently of other possible confounders levels [regression coefficient (R.C.) 0.143 confidence interval (C.I.) (0.042–0.245); P = 0.0059], while serum CCL2 were significantly associated only with age [R.C. 5.412 C.I. (3.838–6.986); P < 0.0001].

Conclusion: Our results, obtained in a large cohort of newly diagnosed AT patients demonstrate increased CXCL10 especially in hypothyroid patients with a more aggressive disorder, and normal CCL2 serum levels in AT.

Free access

Alessandro Antonelli, Poupak Fallahi, Mario Rotondi, Silvia Martina Ferrari, Paola Romagnani, Mariano Grosso, Ele Ferrannini and Mario Serio

Objective: Serum CXCL10 (an interferon-γ-inducible chemokine) levels (sCXCL10) are increased in several autoimmune conditions, including Graves’ disease (GD) and autoimmune thyroiditis (AT). Longitudinal assessment of sCXCL10 in autoimmune hypo- or hyperthyroidism has not yet been performed.

Design and methods: We longitudinally assayed sCXCL10 in the following groups:

  1. thirty-three GD and 11 toxic nodular goiter (TNG) patients when hyperthyroid (Hyper) and when reaching euthyroidism (Eu) with methimazole therapy (MMI)

  2. sixty-six AT (33 hypothyroid (Hypo) and 33 Eu) patients, basally and after reaching EU (for Hypo) with levothyroxine (L-T4) therapy

  3. twenty-two patients with thyroid cancer (CA) under L-T4-suppressive treatment, of whom 11 were re-evaluated after L-T4 withdrawal for diagnostic WBS, and 11 after recombinant TSH (rhTSH) administration

  4. thirty-three healthy controls.

Results: At initial evaluation, Hyper GD and AT (Hypo significantly higher than Eu) showed significantly higher mean sCXCL10 than all other groups. MMI treatment led to a significant decrease in sCXCL10 only in GD (not in TNG), while restoration of Eu, in Hypo AT, by L-T4 was not accompanied by significant sCXCL10 change. CA showed sCXCL10 comparable to controls, and both Hypo after L-T4 withdrawal and rhTSH injection had no effect on sCXCL10.

Conclusions: Treatment of Hyper leads to a significant decrease in sCXCL10 only in GD, and this probably depends upon the MMI immunomodulatory effect. L-T4 correction of Hypo is not accompanied by significant modification of sCXCL10 in AT. Increased sCXCL10 is not associated with Hyper or Hypo per se, but is specifically sustained by the autoimmune inflammatory event occurring in both GD and AT.

Free access

Alessandro Antonelli, Silvia Martina Ferrari, Poupak Fallahi, Piero Berti, Gabriele Materazzi, Ivo Marchetti, Clara Ugolini, Fulvio Basolo, Paolo Miccoli and Ele Ferrannini

Objective

Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now ‘primary ATC cell cultures’ (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures.

Design

To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD).

Methods and results

FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P<0.0001) FNA-ANA proliferation, such as TZD (P<0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The V600E BRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without V600E BRAF mutation.

Conclusions

Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro.