Results of Surgical Therapy in Patients with Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare form of malignancy, having an intermediate prognosis. Controversies exist regarding the best surgical approach. The aim of the study was to analyze the outcome in a group of patients with MTC, diagnosed and followed up in a single care center. We performed a retrospective analysis of all the patients diagnosed with MTC in the Department of Endocrinology from the County Emergency Hospital Timisoara between 1992 and 2012. The study group included 19 patients, 6 men (31.6 %), mean age 41.2 ± 12.5 years (20-72 years). The preoperative diagnosis was based on the protocol for nodular thyroid disease. Total or near-total thyroidectomy was performed in 10 out of 16 patients who could be operated. Postoperative follow-up included repeated measurements of serum calcitonin and imaging investigations. Nine out of the total of 19 (47.3 %) patients had hereditary forms of MTC. Most of the cases (84.2 %) were submitted to surgery. The median duration of follow-up was 84 months. The pTNM staging indicated that the majority of the patients with hereditary MTC were diagnosed in an earlier stage. Disease remission was achieved in 7 cases (43.8 %). Four patients, all with sporadic forms, died. Survival rates at 1, 5 and 10 years were significantly higher (p = 0.048) in patients with hereditary MTC. An early diagnosis of MTC allows a better surgical approach and an improved survival rate. We support the general recommendation that modified radical neck dissection is not necessary for all the patients with MTC.

Selenium status in patients with autoimmune and non-autoimmune thyroid diseases from four European countries.

CONTEXT: Selenium supplementation has been suggested for Hashimoto thyroiditis and Graves' ophthalmopathy. Objective, Design: Our aim is to measure selenium status (p-Se, p-SePP), urine iodine (UI) levels and urine iodine/creatinine ratio (UI/C) in different thyroid diseases (n = 416) from four European countries and to compare the results between patients with and without thyroid autoimmunity. RESULTS: p-Se and p-SePP showed positive correlation and did not correlate with UI/C. Also, these measurements were higher in patients from Italy in comparison with the other countries. Austria had the lowest UI/C ratios. Selenium deficiency exists in these four European countries. Selenium status was lower in patients with Hashimoto thyroiditis and Graves' disease in comparison with non-autoimmune thyroid disease patients and did not differ between autoimmune patients with or without thyroid peroxidase antibodies. The latter correlated positively with age. CONCLUSIONS: Our findings suggest that Se supplementation might have a beneficial effect in autoimmune thyroid patients.

Clinical, ultrasonographical and histopathological aspects in Hashimoto's thyroiditis associated with malignant and benign thyroid nodules.

INTRIDUCTION: The reported prevalence of chronic autoimmune thyroiditis associated with differentiated thyroid cancer (DTC) is heterogeneous.The aim of this study was to evaluate some epidemiological, clinical, sonographical and histological features of operated thyroidnodules with background diffuse autoimmune thyroiditis. MATERIAL AND METHODS: The study included 411 cases with Hashimoto's thyroiditis (HT), of which 118 presented thyroid nodular disease(TND). Thyroidectomy was performed in 76 cases. Of these patients, 24 presented histologically confirmed DTC and 52 benign lesions.DTC types were as follows: papillary thyroid cancer (PTC) (n = 6), follicular variant of PTC (FVPTC) (n = 6), papillary microcarcinomas(n = 8), follicular thyroid carcinoma (n = 1) and the mixed form (classic PTC and FVPTC) (n = 3). The benign nodules were dominatedby: follicular adenoma (48%), and colloid goitre (40.3%). RESULTS: The sonographic features with predictive risk for malignancy in cases with HT associated with TND were represented by: solidcomposition, hypoechogenicity and microcalcifications. The characters of margins, the nodular shape and the type of vascularity do notseem to be as useful for identification of malignant nodules in HT. Fine needle-aspiration biopsy (FNAB) showed in DTC cases differentcytological smears: malignant (ten), indeterminate (eight), benign (two), and non-diagnostic (four). In the group of benign nodules, theindeterminate smears represented also a significant percentage (n = 12). CONCLUSIONS: The incidence of TND associated with HT was 28.7%. Among 76 operated cases, 31.5% presented DTC. The accuracyof FNAB in the preoperative diagnosis showed higher sensitivity (90.0%) and specificity (61.5%) compared to sonographic criteria.

ARFI elastography for the evaluation of diffuse thyroid gland pathology: Preliminary results.

AIM: To assess whether acoustic radiation force impulse (ARFI) elastography can differentiate normal from pathological thyroid parenchyma. METHODS: We evaluated 136 subjects (mean age 45.8 ± 15.6 years, 106 women and 30 men): 44 (32.3%) without thyroid pathology, 48 (35.3%) with Basedow-Graves' disease (GD), 37 (27.2%) with chronic autoimmune thyroiditis (CAT; diagnosed by specific tests), 4 (2.9%) with diffuse thyroid goiter and 3 (2.2%) cases with thyroid pathology induced by amiodarone. In all patients, 10 elastographic measurements were made in the right thyroid lobe and 10 in the left thyroid lobe, using a 1-4.5 MHZ convex probe and a 4-9 MHz linear probe, respectively. Median values were calculated for thyroid stiffness and expressed in meters/second (m/s). RESULTS: Thyroid stiffness (TS) assessed by means of ARFI in healthy subjects (2 ± 0.40 m/s) was significantly lower than in GD (2.67 ± 0.53 m/s) (P < 0.0001) and CAT patients (2.43 ± 0.58 m/s) (P = 0.0002), but the differences were not significant between GD vs CAT patients (P = 0.053). The optimal cut-off value for the prediction of diffuse thyroid pathology was 2.36 m/s. For this cut-off value, TS had 62.5% sensitivity, 79.5% specificity, 87.6% predictive positive value, 55.5% negative predictive value and 72.7% accuracy for the presence of diffuse thyroid gland pathology (AUROC = 0.804). There were no significant differences between the TS values obtained with linear vs convex probes and when 5 vs 10 measurements were taken in each lobe (median values). CONCLUSION: ARFI seems to be a useful method for the assessment of diffuse thyroid gland pathology.

Amiodarone-induced thyroid dysfunction in an iodine-replete area: epidemiological and clinical data.

INTRODUCTION: The present study aims to evaluate the incidence, types, timing and risk factors in amiodarone (AMD)-induced thyroid dysfunction. MATERIAL AND METHODS: The study comprised 229 patients from an iodine-replete area (115 women, 114 men, mean age 63.8 ± 9.2 years), chronically treated with AMD. The cases were clinically investigated prior to, and during treatment, by thyroid 2D and color Doppler flow sonography, thyroid function tests (TSH, FT3, FT4), and antithyroid antibodies. RESULTS: Of 88 patients (38.4%) who developed thyroid dysfunction, 47 (20.5%) presented AMD-induced thyrotoxicosis (AIT) and 41 (17.9%) AMD-induced hypothyroidism (AIH). There is an evident prevalence of subclinical AIH (29 cases), compared to subclinical AIT (three cases). Regarding clinical forms, these prevailed in AIT (44 patients) (p 〈 0.001, Fisher's exact test). Thyrotoxic patients were classified in pathogenic types as follows: 11 cases as type 1, 15 cases as type 2, and 21 cases as mixed form. The most important risk factor for the development of thyroid dysfunction was represented by the underlying thyroid pathology. The patients with previous thyroid abnormalities (diffuse or nodular goitre and/or positive antithyroid antibodies) developed earlier thyroid dysfunction compared to those with an apparently normal thyroid gland. The thyroid dysfunction occurrence was heterogeneous (4-84 months). Thyrotoxicosis involved especially young ages, while AIH affected later years.The daily dose, the duration of the treatment and the cumulative dose of AMD do not represent risk factors in thyroid dysfunction development. The determination of serum AMD and desethylamiodarone concentrations does not offer benefits in the diagnosis and treatment of thyroid dysfunction. CONCLUSIONS: In the present study, the incidence of AIH was similar to that reported in iodine-replete areas. The incidence of AIT was higher that previously reported, a fact underlining the importance of the proper screening and monitoring of patients. Cases with previous thyroid morphologic and/or immunologic abnormalities require frequent monitoring.

Some clinical aspects in chronic autoimmune thyroiditis associated with thyroid differentiated cancer.

BACKGROUND: The coexistence of Hashimoto's thyroiditis (HT) with differentiated thyroid cancer (DTC) was reported with a heterogeneous incidence. The wide distribution of this association may be related to differences in the level of morphological examination, autoimmunity used criteria, patient selection, surgical indication, genetic background, geographical and environmental factors.Some consider the coexistence of these two entities a coincidental one, others suspecting a causative link between these conditions. METHODS: This retrospective paper included 216 patients with HT, issued from an iodine-replete area. 21 cases of nodular HT were investigated by means of: thyroid functional tests (TFT), immunological determinations, thyroid ultrasonography (US) and cytological analysis.ALL CASES WERE OPERATED BECAUSE OF DIFFERENT REASONS: compressive symptoms and signs, suspicious sonographic features and certain cytological smears (malignant, indeterminate and non-diagnostic). RESULTS: The morphologic investigation revealed 9 patients with DTC and 12 cases with benign thyroid disease (BTD).None of the US analyzed characteristics provided sufficient accuracy for the diagnosis of DTC in cases with HT. The preoperative cytological examination by means of fine-needle-aspiration biopsy (FNAB) showed a better sensitivity and specificity vs. US criteria. CONCLUSION: The coexistence of HT with DTC represents a clinical reality with yet unknown significance. The difficulty of diagnosis imposes the corroboration of different types of investigations. The best diagnostic accuracy seems to be offered by thyroid US and thyroid cytological investigation.

Indicators of mineralocorticoid excess in the evaluation of primary aldosteronism.

It is suggested to use the aldosterone-to-renin ratio (ARR) as a first test in the screening for primary aldosteronism (PA). However, many groups rather rely on the determination of urinary tetrahydroaldosterone secretion; others calculate a ratio of urinary aldosterone to plasma renin activity. The aim of the present study was to evaluate the usefulness of different parameters of aldosterone excess in the case finding of PA. The study included 28 patients with PA and 33 subjects with essential hypertension. Clinical data, which included the hormonal parameters, serum aldosterone, plasma renin concentration, urinary free aldosterone and metabolites and serum and urinary electrolyte levels were analyzed. These indices of aldosterone excess, the ARR, serum sodium to urinary sodium to (serum potassium)(2) to urinary potassium (SUSPPUP) ratio and combinations of these parameters were compared between the groups. Receiver-operating curve analysis revealed that the ARR multiplied by the SUSPPUP ratio (ARR x SUSPPUP) is the most reliable screening test, with a sensitivity of 92.3% and a specificity of 93.9% (cutoff point 199.2 (mmol l(-1))(-1)). The combination of ARR x SUSPPUP ratio with urinary free aldosterone divided by the plasma renin concentration rendered a specificity of 100%. Less useful was the correction of urinary free aldosterone and its metabolites for sodium excretion. Although the ARR and urinary free aldosterone divided by renin are good tests in the screening for PA, the combination of ARR with SUSPPUP ratio is a better indicator of an aldosterone excess and aldosterone action in patients with ongoing antihypertensive medication. Antihypertensive drugs only marginally interfere with the SUSPPUP ratio, but they may influence the ARR, whereby the effects in PA patients seem to be negligible.

Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation.

RET testing in multiple endocrine neoplasia type 2 for molecular diagnosis is the paradigm for the practice of clinical cancer genetics. However, precise data for distinct mutation-based risk profiles are not available. Here, we survey the clinical profile for one specific genotype as a model, TGC to TGG in codon 634 (C634W). By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism (HPT), as well as overall survival. Our series comprises 92 carriers from 20 unrelated families worldwide. Sixty-eight subjects had MTC diagnosed at age 3-72 years (mean 29). Lymph node metastases were observed in 16 subjects aged 20-72 and distant metastases in 4 subjects aged 28-69. Forty-one subjects had pheochromocytoma detected at age 18-67 (mean 36). Amongst the 28 subjects with MTC and pheochromocytoma, six developed pheochromocytoma before MTC. Six subjects had HPT diagnosed at age 26-52 (mean 39). Eighteen subjects died; of the 16 with known causes of death, 8 died of pheochromocytoma and 4 of MTC. Penetrance for MTC is 52% by age 30 and 83% by age 50, for pheochromocytoma penetrance is 20% by age 30 and 67% by age 50, and for HPT penetrance is 3% by age 30 and 21% by age 50. These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling.

Clinical and Immunological Aspects in Hashimoto's Thyroiditis.

We propose to establish the relationship between the clinical, functional and immunological parameters in a cohort of women with Hashimoto's thyroiditis. The study included 68 patients between 19 and 70 who were hospitalized for two years in the Endocrinology Clinic of the Hospital in Timisoara. The thyroidal dimensions and the aspects of the thyroidal stroma were shown by echography examinations. The functional parameters like the serum TSH and free T4 concentrations were determined by chemiluminescent methods. The immunological investigations (antithyroglobulin and antiperoxidase antibodies) were performed by the ELISA method. Comparisons were performed by the t test and the Pearson correlation analysis. The correlation between the aspects of thyroidal stroma and thyroid function revealed hypothyroidism in most cases with moderate (++) or severe (+++) echogenity. Another researched aspect was that of correlation of the serum levels of TSH with the thyroidal dimension. The following correlations were obtained: r= - 0.14 in patients with clinical hypothyroidism and r= - 0.3055 in those with subclinical hypothyroidism. The Pearson coefficients for the level of TSH in um and those of the antiperoxidase antibodies, according to clinical and functional categories, revealed the following results: r= - 0.1580 in patients with clinical hypothyroidism and r= - 0.1961 in those with subclinical hypothyroidism. Patients with clinical hypothroidism have significant higher serum level of TSH as compared with those of the patients with subclinical hypothyroidism (p=0.0001). We established a relation between the severe hypoechogenity and hypothyroidism status in patients with positive serum antibodies (r= 0.5695).