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.

The influence of subclinical hyperthyroidism on blood pressure, heart rate variability, and prevalence of arrhythmias.

BACKGROUND: The impact of subclinical hyperthyroidism (sHT) on the cardiovascular system still needs to be elucidated. The aim of the study was to prospectively assess blood pressure (BP), variability in heart rate, and the prevalence of arrhythmias in patients with sHT, both before and after they are restored to the euthyroid state. METHODS: The study group consisted of 44 normotensive patients (37 women, 7 men), aged 22-65 years (mean±SD: 45.9±11.0) with sHT. Enrolled patients were drawn from 1080 patients referred to our department for treatment of hyperthyroidism. Study patients were treated with radioiodine treatment to restore the euthyroid state. Ambulatory BP monitoring and Holter electrocardiography were performed (i) when sHT was diagnosed and (ii) at least 6 months after they became euthyroid. RESULTS: sHT in comparison to the euthyroid state was associated with higher (109.3±7.1 vs. 107.1±7.7 mmHg) nocturnal systolic mean BP (p=0.035) and BP load (14.8 vs. 10.2%, p=0.033), mean diastolic BP (66.4±6.6 vs. 64.8±6.6 mmHg, p=0.047), and mean arterial pressure (80.8±43.1 vs. 79.3±43.6 mmHg, p=0.049). Moreover, significant changes in both the time and frequency domain measures of heart rate variability (HRV) were observed: decrease of the square root of the mean squared differences of successive NN intervals (rMSSD) (45.68±34.1 vs. 65.09±50.6 ms, p=0.03) and the low frequency power (LF) (5.71±0.99 vs. 6.0±1.01 ms(2), p=0.049) as well as increase of QT interval dispersion (58.25±28.5 vs. 46.90±12.1 ms, p=0.020). This was accompanied by a clinically insignificant increase in the frequency of ventricular extrasystoles (VES) (3.1±7.4 vs. 0.6±1.2 per hour, p=0.048) and increased mean heart rate (78.4±6.8 vs. 76.0±8.0 beats/min, p=0.004). Some of the parameters correlated positively with thyroid hormones: nocturnal diastolic BP with free triiodothyronine (FT(3)) (r=0.397, p=0.008), rMSSD with free thyroxine (FT(4)) (r=0.389, p=0.013), and QT interval dispersion with FT(4) (r=0.450, p=0.004). CONCLUSIONS: The study suggests that sHT in comparison to euthyroid status may be associated with a statistically significant but probably clinically insignificant increase of QT interval dispersion, prevalence of VES, elevated nocturnal arterial BP, and changes in HRV. These findings broaden our understanding of the cardiovascular effects of sHT.

[Thyroid ultrasound - a piece of cake?]. / Zrobic USG tarczycy kazdy moze, troche lepiej lub troche gorzej.

The introduction of sonographic imaging has revolutionized the diagnostics of thyroid pathologies. Nowadays, thyroid ultrasound examination has become an essential part of routine thyroid gland evaluation. Although one of the greatest advantages of this examination lies in its simplicity, it requires a solid theoretical background, as well as a lot of experience for the examiner to become fluent in adequate interpretation of its results. The aim of this summary is to present a review of the most important aspects of both the technique and interpretation of thyroid ultrasound pictures with regard to the most common difficulties a thyroid sonographer may come across in everyday practice.

The immunohistochemical demonstration of parafollicular cells and evaluation of calcium-phosphate balance in patients with thyroid hemiagenesis.

Thyroid hemiagenesis (TH) is characterized by the congenital absence of one thyroid lobe. The aim of this study was to evaluate the calcium-phosphate balance in TH. Twenty patients with TH and 20 controls with a bilobed thyroid were studied. Serum concentrations of total calcium, parathormon and calcitonin were measured. Additionally, the immunohistochemical expression of calcitonin, chromogranin A (chA), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP) was evaluated in surgical specimens from patients with TH and controls. There were no significant differences in biochemical parameters between TH and controls. Positive staining for calcitonin was demonstrated in 3/8 thyroid sections from three patients with TH, but only in 2/33 sections from four controls (p < 0.005). All sections from patients with TH positive for calcitonin also expressed chA, NSE and CGRP. Two sections from controls positive for calcitonin presented an additionally positive reaction for chA, and one of them also for NSE. None presented positive staining for CGRP. Of three TH sections, in one, hyperplasia of C cells of medium grade, and in another hyperplasia of C cells of high grade, could be detected. In the controls, hyperplasia of C cells of low and medium grade was observed. TH was associated with slightly enhanced C cells hyperplasia compared to controls, which might indicate compensatory proliferation. However, the calcium-phosphate balance does not seem to be significantly affected.

Diagnostic value of radionuclide scanning and ultrasonography in thyroid developmental anomaly imaging.

Thyroid is particularly prone to morphogenetic variability. Developmental failure of the thyroid gland is in 85% of cases the underlying cause of congenital hypothyroidism, diagnosed at birth with a frequency of 1:3000-1:4000 newborns. However, the incidence of less severe developmental variants of the thyroid is much higher. Determination of the aetiology of congenital hypothyroidism is crucial for predicting its severity and outcome as well as impacts dose of L-thyroxine during substitution. Thyroid imaging is necessary to establish diagnosis, and it involves mainly thyroid ultrasound examination and scintiscan. Awareness of both the advantages and limitations of sonographic and scintigraphic imaging are central to the successful interpretation of their results and reasonable recommendation of these procedures for patients with thyroid developmental anomalies of different age and clinical picture. Hence, the aim of this review is to provide the most important and up-to-date information on the place of radionuclide scanning and ultrasonography in visualization of different thyroid developmental abnormalities.

FOXE1 polyalanine tract length polymorphism in patients with thyroid hemiagenesis and subjects with normal thyroid.

BACKGROUND/AIMS: Recent studies have pointed to the correlation between FOXE1 polyalanine tract (FOXE1-polyAla) length polymorphism and genetic susceptibility to thyroid dysgenesis causing congenital hypothyroidism. The objective of this study was a first assessment of the role of FOXE1-polyAla expansion in the genetic background of thyroid hemiagenesis (TH). METHODS: The group studied consisted of 40 patients with TH, including 6 familial cases and a control group of 89 subjects with a normal thyroid. The polyAla tract and flanking sequence of FOXE1 was amplified using conventional PCR. Subsequently, capillary electrophoresis was performed to estimate the length of products. RESULTS: A short variant of FOXE1-polyAla, containing 12 alanines, was present in 5 control subjects (5.6%), but was not found in TH. The incidence of longer variants (≥16 codons) of FOXE1-polyAla was significantly higher in patients with the familial form of TH in comparison to those with sporadic TH (p = 0.003) and controls (p = 0.005). CONCLUSIONS: There is high polymorphic variability of FOXE1-polyAla in both groups. Shorter variants of FOXE1-polyAla are underrepresented in subjects with familial TH. Therefore, FOXE1-polyAla tract expansion may contribute to the molecular background of familial but not sporadic forms of TH. Further studies are still required to confirm such findings.

Prospective echocardiographic evaluation of patients with endogenous subclinical hyperthyroidism and after restoring euthyroidism.

OBJECTIVES: Clinical significance of, and the need for, treatment in subclinical hyperthyroidism (sHT) is still a matter of debate. The aim of the study was to assess the impact of sHT on echocardiographic parameters. DESIGN: Patients with endogenous sHT of nonautoimmune origin underwent full echocardiographic assessment at diagnosis and after restoring euthyroidism with radioiodine treatment. PATIENTS: Studied group consisted of 44 patients (37 women, 7 men), aged 22-65 years (mean 45·9±11·0). MEASUREMENTS: Full echocardiographic assessment included estimation of cardiac chamber diameters and volume as well as cardiac contractility, according to the guidelines of the American Society of Echocardiography. Left ventricular mass was calculated according to Penn's convention. For estimation of left ventricle diastolic function, the following echocardiographic parameters were obtained: maximal early filling wave velocity (E), maximal late filling wave velocity (A), E/A ratio, isovolumetric relaxation time and early filling wave deceleration time. RESULTS: In the studied group, phase of sHT was associated with increased volume of heart chambers, increased diameter of ascending aorta, increased left ventricle mass and disturbed left ventricle relaxation (P<0·05). The systolic function of the left ventricle was unaffected; however, the ejection time was shortened. The changes were reversible with restoring biochemical euthyroidism (P<0·05). Moreover, a significant correlation between some of the parameters and thyroid hormones concentration was demonstrated. CONCLUSIONS: sHT was associated with significant changes in echocardiographic parameters, which may contribute to increased cardiovascular risk in these patients. The alterations were reversible with restoring biochemical euthyroidism, what supports the necessity of treatment introduction in sHT.

Thyroid ultrasound - a piece of cake?

The introduction of sonographic imaging has revolutionized the diagnostics of thyroid pathologies. Nowadays, thyroid ultrasound examination has become an essential part of routine thyroid gland evaluation. Although one of the greatest advantages of this examination lies in its simplicity, it requires a solid theoretical background, as well as a lot of experience for the examiner to become fluent in adequate interpretation of its results. The aim of this summary is to present a review of the most important aspects of both the technique and interpretation of thyroid ultrasound pictures with regard to the most common difficulties a thyroid sonographer may come across in everyday practice.

Increased risk of thyroid pathology in patients with thyroid hemiagenesis: results of a large cohort case-control study.

OBJECTIVE: Thyroid hemiagenesis (THA) is an anomaly resulting from the developmental failure of one thyroid lobe. Etiopathogenesis, clinical significance, and management of patients in whom THA is diagnosed are still a matter of debate. The aim of the study is to provide the first systematic analysis of a large cohort of subjects with THA. DESIGN: Forty patients with THA are described in comparison to a control group of 80 subjects with fully developed thyroid gland. METHODS: Serum concentrations of thyrotropin (TSH), free thyroxine (FT(4)), free triiodothyronine (FT(3)), and thyroid autoantibodies were measured. In 37 patients, thyroid ultrasonography and Tc-99m thyroid scintiscan were performed, followed by fine-needle aspiration biopsy if indicated. The remaining archival three cases were diagnosed with the use of I-131 scintiscan under basal conditions and after TSH stimulation. RESULTS: Patients with THA, while usually clinically euthyroid, presented with significantly higher levels of TSH and FT(3) as well as with higher FT(3)/FT(4) concentration in comparison to the control group. Furthermore, a higher incidence of associated functional, morphological, and autoimmune thyroid disorders in patients with THA was observed when compared to subjects with bilobate thyroid (P<0.05). CONCLUSIONS: Our results revealed that individuals with THA are more likely to develop thyroid pathology. The observed high incidence of associated pathologies is presumably due to long-lasting TSH overstimulation. Therefore, THA diagnosis should be followed by systematic observation and adequate levothyroxine treatment in patients with elevated TSH level.

Congenital hypothyroidism simulating acromegaly - a diagnostic pitfall.

Since introduction of population-based neonatal screening for congenital hypothyroidism (CH), cases of long-term untreated inborn hypothyreosis have become very rare whereas its clinical symptoms are currently not well known. We report a patient with CH due to an ectopic thyroid. The presented case is exceptional due to both advanced age of diagnosis and unusual clinical presentation, as the anomaly was detected during evaluation of suspected acromegaly at the age of 62. This report indicates that there is still necessity of considering, in spite of its rarity, congenital form in differential diagnosis of hypothyroidism.

Radioiodine therapy in patients with amiodarone-induced thyrotoxicosis (AIT).

INTRODUCTION: Amiodarone (AM) is frequently used in the therapy of patients with cardiac disorders. However, due to high iodine content, it has side effects on thyroid function. The use of radioiodine therapy (RIT) in amiodarone-induced thyrotoxicosis (AIT) with low radioactive iodine uptake (RAIU) is still controversial. In these patients therapeutic choices for refractory disease include surgery, antithyroid drugs, or glu ocorticosteriods. AIM: The aim of the study was to evaluate the efficacy of RIT in patients presenting AIT and low RAIU in two-year follow-up. PATIENTS AND METHODS: 40 patients (25 men and 15 women) aged from 63 to 83 years (x +/- SD: 66.2 +/- 5.0 years; median: 65 years) treated with RIT were included into the study. In these patients AM therapy was essential for the underlying heart disorder, while surgery, antithyroid drugs or glucocorticosteroids, were contraindicated. Forty seven patients with toxic multinodular goiter (TMNG) (39 women and 8 men), matched for age (67 +/- 12 yr; range 54-89 yr), were enrolled into the study as a comparative group. The diagnostic procedures included baseline thyroid function tests (thyrothropin - TSH, free triiodothyronine - fT3 and free thyroxine - fT4 levels), thyroid autoantibodies measurement (antithyroglobulin autoantibodies - TgAb, antithyroid peroxidase autoantibodies - TPOAb, anti-TSH receptor autoantibodies - TRAb), thyroid ultrasonography, thyroid scintiscan and RAIU assessment. RESULTS: Serum values of TSH, TgAb, TPOAb and TRAb were undetectable in both groups. In patients with AIT fT4 level was 18.7 to 38.7 pmol/l (mean: 27.1 +/- 5.8) and fT3 concentration was 3.9 to 5.6 pmo/l (mean: 5.7 +/- 1.4), while in TMNG patients level of fT4 was 31.5 to 22.2 pmol/l (mean: 25,3 +/- 5,8) and fT3 concentration was 3.8 to 4,2 pmo/l (mean: 4,2 +/- 0,2). Mean RAIU values after 5h and 24h in AIT patients were 2.3 +/- 0.5 and 3.1 +/- 0.9%, while in TMNG patients were 18,0 +/- 3,8 and 35,7 +/- 9,1%, respectively. A significant difference (p<0.001) between 5h and 24h RAIU in AIT compared to TMNG was noted. In all patients with AIT, a dose of 800 MBq of 131I was administered. During two-year-observation recurrence of hyperthyroidism was observed in two patients (5%) with TMNG. These patients received a second radioiodine dose 16.2 +/- 15 months later (the mean re-treatment dose was 735.93 +/- 196.1 MBq). In comparison, none of the patients with AIT required a second 131I dose and only one patient (2.5%) 6 months after ablative 131I dose needed anti-thyroid medication. Transient hypothyroidism was observed in only two patients (5%) with AIH, though was not observed in TMNG. During follow-up time, no sudden deaths in AIT patients were observed; one patient was diagnosed with prostate cancer, and in one patient acute toxic hepatitis after AM occurred. CONCLUSION: RIT may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.

Graves' hyperthyroidism following primary hypothyroidism due to Hashimoto's thyroiditis in a case of thyroid hemiagenesis: case report.

Thyroid hemiagenesis (TH) is a rare inborn anomaly, resulting from failure of one thyroid lobe development. It is usually detected incidentally during investigation of concomitant thyroid disorders. The reported patient first presented hypothyroidism at the age of 49, when Hashimoto's thyroiditis (HT) and left thyroid lobe agenesis was diagnosed. L-thyroxine (LT4) replacement therapy restored hormonal balance. Two years later, the patient developed features of Graves' hyperthyroidism. The antithyroid pharmacotherapy by thiamazole was used. However, due to severe side-effects it was discontinued, and radioiodine treatment was applied. Four months after 131I administration, symptoms of hypothyroidism appeared, so thyroid hormone substitution was reintroduced. The patient, whose observation period has now reached 5 years, under LT4 replacement therapy, remains both clinically and biochemically euthyroid. The described case displays a very rare coincidence of hypothyroidism due to HT converted into Graves' hyperthyroidism, accompanying TH. Each of these three entities, may influence the thyroid function in a different way, hence, systematic follow-up and individual therapeutic management is required.