Patients with chronic hepatitis type C and interferon-alpha-induced hyperthyroidism in two-years clinical follow-up.

OBJECTIVES: Interferon-α (IFN-α) is a gold standard in the therapy of viral chronic hepatitis type C (CHC). However, such treatment might lead to thyroid dysfunction. Patients usually present hypothyroidism, but rarely also hyperthyroidism may develop. The aim of the study is to present two-year clinical follow-up of patients with CHC and IFN-α-induced hyperthyroidism (IIH), with special regard to the methods and efficacy of the therapy. METHODS: A group of 106 patients with CHC and IIH were analyzed. Subjects were divided into two groups according to etiology: group 1, with Graves' disease (GD) and group 2, with Hashitoxicosis (HT). The diagnosis of GD and HT was based on: clinical signs of hyperthyroidism, hormonal profile (TSH, fT4, fT3), level of thyroid autoantibodies (Tg-Abs, TPO-Abs, TSHRAbs). Treatment of hyperthyroidism was monitored by repeated clinical assessment and laboratory tests. RESULST: 28 patients (26 with GD of which 5 exhibited mild orbitopathy and 2 with HT) were treated with radioiodine [the average dose of was 17 mCi [668 MBq]. In adition 78 out of 80 patients with HT mostly ß-blocker therapy was successful (transient hyperthyroidism). At the end of the observation period, in group 1 remission was achieved in 17 (65.4%) cases, 6 (23.1%) patients showed hypothyroidism and 3 (11.5%) presented recurrence of hyperthyroidism. CONCLUSIONS: Most patients with IIH present Hashitoxicosis, while a minority of them develop Graves' disease. In a majority of patients with HT spontaneous remission of disease occurs. In patients with long-term hyperthyroidism, radioiodine therapy is an effective and well-tolerated.

The influence of radioiodine therapy on ocular changes and their relation to urine cotinine level in patients with Graves' Ophthalmopathy.

OBJECTIVES: Radioiodine therapy (RIT) is frequently used as the definitive treatment in patients with Graves' hyperthyroidism when remission is not achieved with anti-thyroid drugs (ATDs). In this observational study, we intended to examine whether the use of high doses of radioiodine (RAI) [22 mCi (814 MBq)] with prophylaxis of oral glucocorticoids (oGCS) does not exacerbate Graves ophthalmopathy (GO) in smokers and non-smokers, especially regards to the urine level cotinine and ocular changes before and after RIT. PATIENTS AND METHODS: The studied group consisted of 26 smokers, aged 28-61 years and 25 non-smoker patients, aged 21-54 years, respectively. The patients were enrolled to RAI after one-year of ineffective ATDs treatment. Criterion for inclusion in the study were patients with mild GO with hyperthyroidism at diagnosis based on the severity (NOSPECTS) and activity (CAS) scale. All the patients were subjected to RIT with oGCS prophylaxis and evaluated prospectively during a one-year follow-up. The ophthalmological examination was performed at various stages of RIT: initial pre-radioiodine administration, at the time of treatment 6, and 12 months after RAI. The present study is unique, because the urine cotinine measurement was employed to detect nicotine exposure, also in regard to smoking intensity. RESULTS: In smokers, the values of serum TPO-Abs were statistically significant in the second and six month (p<0.05) and in the second and after one year (p<0.005). The TSHR-Abs concentration was significantly higher in smokers (p<0.05), rising from 22.9±1.2 IU/L before therapy to 29.6±5.3 IU/L - 2 months, 32.6±8.6 IU/L - 6 months, and slightly decreased 28.9±10.6 IU/L - 12 months. These observed changes were statistically different between groups at baseline (p<0.05) and after one-year of follow-up (p<0.005). Mean urine cotinine were considerably higher in smokers comparing to non smokers in each point of observation [903.4±770.0 and 5.2±1.7 ng/mL at baseline (p<0.001), 412.8±277.3 and 3.0±0.6 ng/mL after 2 months (p<0.001), 452.0±245 and 6.6±3.6 after 6 months (p<0.001), 379.4±236.8 and 1.0±1.2 after one year (p<0.001)]. The CAS values in the smoking group before RIT increased statistically from 2.8±0.2 points at baseline to 4.3±0.3 after 6 months, and 4.0±0.5 (12 months), while in the non-smoking patients it was 1.4±0.2, 2.8±0.3 and 2.2±0.2, respectively. The level of urine cotinine correlated positively with CAS and TSHR-Ab in the smoking group (r=0.41; p<0.05) at baseline and during follow-up (2 months: r=0.46; p<0.001, 6 months: r=0.47, p<0.005; 12 months: r=0.46; p<0.005). In the NOSPECS classification, the symptoms changed from mild to moderate, mostly in smoking patients. CONCLUSIONS: 1) ablative RIT dose with prophylactic oral prednisone is a safe treatment in both smokers and non-smokers with mild GO; 2) The post hoc analysis showed that urinary level of cotinine can be very helpful in the assessment of exacerbation of ophthalmological clinical symptoms before and after RIT particularly in smokers.

A rare case of Interferon-alpha-Induced Hyperthyroidism in patients with a chronic hepatitis C with granulocytopenia and transaminasemia treated successfully with radioiodine.

BACKGROUND: Conventional management of Interferon-α-Induced Hyperthyroidism (IIH) with radioactive iodine (RAI) may be used when treatment with beta blockers or antithyroid drugs (ATD), proves ineffective or is contraindicated. CASE PRESENTATION: We present a 38-year-old woman who has been treated with combined pegylated interferon alpha (INF-α) and Ribavirin for chronic hepatitis C. Destructive thyrotoxicosis appeared after four months of continuous IFN-α therapy and a beta blocker was prescribed. Initially, the patient presented normal TSH 2.4 µIU/mL, however during therapy with INF-α, TSH diminished to 0.05 and thyroid hormones were elevated: fT4 23.1 pmol/L, fT3 7.2 pmol/L. Ultrasound examination showed completely irregular and greatly decreased echogenicity of the thyroid gland. The radioiodine uptake (RAIU) was deeply decreased to 2 and 3% at 5 h and 24 h, respectively. The thyroid scintiscan showed lack of isotope accumulation. Hypothyroidism developed and L-thyroxine was prescribed. The following year, hyperthyroidism reoccurred with TSH 0.08 µIU/mL, fT4 26.4 pmol/L, fT3 8.2 pmol/L, positive TSHR-Abs 6.2 (normal <2 IU/L) and mild Graves' Ophthalmopathy (GO). RAIU values were 23% at 5 h and 46% at 24 h. Thyroid scintiscan showed diffuse goiter. At this point beta blocker was introduced and ATD was started. After three months of therapy an increased level of aminotransferases and granulocytopaenia were observed. Hence, the patient received RAI and glucocorticosteroid, while INF-α therapy was continued. After approximately 4 months, hypothyroidism reappeared with insignificantly raised TSH level. One year later the patient was euthyroid and required no further treatment. CONCLUSIONS: Our report suggests that: 1. Radioiodine therapy might be an effective and safe method of treatment in cases of IIH with mild GO. 2. IFN-α therapy need not be discontinued in patients with IIH.

Smoking and thyroid diseases--what is new?

Cigarette smoking has multiple effects on the thyroid gland, which is associated with important clinical implications such as increased risk and severity of autoimmune thyroid disorders, especially Graves' ophthalmopathy. The influence of cigarette smoking is mainly associated with the pharmacological action of nicotine and also with toxins such as thiocyanate. The present review of relevant literature concentrates on the effect of smoking on the Graves' ophthalmopathy and other autoimmune thyroid disorders (such as Hashimoto's disease). The effect of passive smoking on children and the influence of smoking on the fetus is also shown. In contrast, the protective influence of cigarette smoke on thyroid cancer is also widely observed.