Incidence and prevalence of hypothyroidism in patients affected by chronic heart failure: role of amiodarone.

BACKGROUND: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodine-containing antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. AIM OF THE STUDY: To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. RESULTS: Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17%and, as expected, it was significantly higher in females than males (33% vs 13%; p < 0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. CONCLUSIONS: Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

The role of long-acting parenteral testosterone undecanoate compound in the induction of secondary sexual characteristics in males with hypogonadotropic hypogonadism.

INTRODUCTION: Androgens are able to induce the development of secondary sexual characteristics in male patients suffering from hypogonadism. So far, the most common method of administering testosterone to induce puberty in these patients has been via the injection of testosterone ester formulations. Moreover, some evidence has showed that the length of polymorphism Cytosine-Adenine-Guanine (CAG) trinucleotide repeats present in androgen receptor (AR) gene might co-regulate the effectiveness of testosterone therapy. AIM: The aim of this study is to evaluate the effectiveness of a long-acting injectable testosterone undecanoate (TU) formulation for the induction of secondary sexual characteristics in young males with hypogonadotropic hypogonadism (HH). MAIN OUTCOME MEASURES: We studied the different stages of puberty development that occur progressively according to the continuous increase in serum testosterone levels and, secondly, whether these changes might be modulated by the length of CAG repeats. METHODS: Nine male subjects over the age of 17 that had not undergone pubertal development because of HH were enrolled in this study and compared with 15 control males. Of these patients, 6/9 suffered from idiopathic HH and 3/9 experienced hypogonadism related to ß-thalassemia (BT). All patients underwent a clinical examination and a determination of follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin (SHBG), and total testosterone (T) serum levels; the free fraction (FT) and biologically active fraction of testosterone were also determined. The number of CAG triplets present in the AR gene was obtained for each patient. For treatment, HH patients received an oral TU (Andriol, 120 mg/day) for 3 months, followed by intramuscular injection of parenteral TU (Nebid, 1,000 mg) every 14 weeks for 1 year, then every 12 weeks for a second year. Serum T and SHBG levels were assayed 3 months after the start of oral TU treatment and also in the 10th week following the start of the second round of intramuscular TU injections (e.g., the eighth month). Levels were also determined 12, 18, and 24 months after the start of the parenteral TU treatments. RESULTS: Serum levels of T, SHBG, FT, and BT increased in all of the patients receiving oral TU and parental TU treatments, and this was accompanied by a development of secondary sexual characteristics. For treated patients with >24 CAG triples vs. the HH subjects with ≤24 CAG triplets, a slight delay in the appearance of the most advanced phases of puberty and a slightly reduced final penis length were observed, suggesting that AR CAG polymorphism might co-regulate the effectiveness of T treatment. CONCLUSIONS: Long-acting parental TU was able to induce the puberty in our group of HH patients, even though additional studies are needed to elucidate the possible role of CAG repeats' length for the development of secondary sexual characteristics in young men with HH.

Papillary thyroid carcinoma in Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare dominantly inherited disease characterized by the association of gastrointestinal hamartomatous polyposis, mucocutaneous hyperpigmentation, and increased risk of cancer at different target organs. Its occurrence with differentiated thyroid cancer, particularly papillary thyroid carcinoma (PTC), even if rare, has been described. SUMMARY: We here present a case of PTC observed in a PJS patient and a review of the literature aiming at discussing the utility of thyroid surveillance in the management of these patients. A 22-year-old woman presenting with hyperpigmented lesions of the lips and hamartomatous polyps in the stomach, duodenum, jejunum, and ileum, leading to the suspicion of PJS, was submitted to genetic analysis. Mutation scanning of the Liver Kinase B1 (LKB1) gene identified the presence of the truncating mutation E265X, thus confirming the clinical diagnosis. Beside the endoscopic, radiologic, and echographic evaluations required by the standard surveillance guidelines, the patient had a neck ultrasound (US), which showed a 5×4×6 mm hypoechoic nodule in the right thyroid lobe. The nodule contained microcalcifications and a perinodular vascular pattern. The cytological preparations derived from US-guided fine-needle aspiration biopsy of the nodule demonstrated the presence of PTC. The patient underwent a video-assisted total thyroidectomy and the histological examination revealed a follicular variant of papillary microcarcinoma. Radioactive iodine therapy was not performed because of the small size of the lesion. The patient was started on levothyroxine therapy to keep the serum thyrotropin levels suppressed. Both the sequencing and the multiplex ligation-dependent probe amplification analysis could not identify any LKB1 mutation in the tumor specimen, and the methylation-specific polymerase chain reaction assay excluded hypermethylation of the LKB1 promoter as the mechanism of inactivation for the remaining normal allele in the tumor. CONCLUSIONS: Although other mechanisms of LKB1 silencing may be responsible for its inactivation in the thyroid cancer, we cannot rule out that the occurrence of thyroid carcinoma could be a coincidental finding in this patient. However, the case here presented suggests that US of the thyroid could possibly become an integral part of the evaluation and the follow-up program adopted for PJS patients.

Role of iodine, selenium and other micronutrients in thyroid function and disorders.

Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. Nowadays about 800 million people are affected by iodine deficiency disorders that include goiter, hypothyroidism, mental retardation, and a wide spectrum of other growth and developmental abnormalities. Iodine supplementation, under form of iodized salt and iodized vegetable oil, produced dramatic improvements in many areas, even though iodine deficiency is still a problem not only for developing countries. In fact, certain subpopulations like vegetarians may not reach an adequate iodine intake even in countries considered iodine-sufficient. A reduction in dietary iodine content could also be related to increased adherence to dietary recommendations to reduce salt intake for preventing hypertension. Furthermore, iodine intakes are declining in many countries where, after endemic goiter eradication, the lack of monitoring of iodine nutrition can lead to a reappearance of goiter and other iodine deficiency disorders. Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormones, making selenium an essential micronutrient for normal development, growth, and metabolism. Furthermore, selenium is found as selenocysteine in the catalytic center of enzymes protecting the thyroid from free radicals damage. In this way, selenium deficiency can exacerbate the effects of iodine deficiency and the same is true for vitamin A or iron deficiency. Substances introduced with food, such as thiocyanate and isoflavones or certain herbal preparations, can interfere with micronutrients and influence thyroid function. Aim of this paper is to review the role of micronutrients in thyroid function and diseases.

Microcalcifications and psammoma bodies in thyroid tumors.

Microcalcifications are a highly specific sign of malignancy being frequently detected in papillary or medullary cancers, while only 5% of nodular goiters and 3-4% of adenomas show this feature on thyroid sonogram. They correspond to clusters of psammoma bodies at cytological or histological examination. The microphotographs of cytological smears show psammoma bodies as 50 to 70 < m round-shaped calcific concretions with a glassy appearance, concentrically laminated.

Association of a wide invasive malignant thymoma with myastenia gravis and primary hyperparathyroidism due to parathyroid adenoma: case report and review of the literature.

There are few cases described in the world literature reporting an association of thymoma (with myasthenia gravis or not) with hyperparathyroidism. In these cases the hyperparathyroidism was due to the presence of an adenoma or hyperplasic parathyroid tissue either in the cervical region or in an ectopic intrathymic location.(12345) In other cases the syndrome of hypercalcemia was due to the secretion of parathyroid-related protein (PTHRP) (6) or parathyroid hormone (PTH) (7) by the thymoma itself. We report the first case, at the best of our knowledge, of a wide invasive malignant thymoma (type B3), associated with myasthenia gravis and hyperparathyroidism caused by parathyroid adenoma.

Role of antioxidants, essential fatty acids, carnitine, vitamins, phytochemicals and trace elements in the treatment of diabetes mellitus and its chronic complications.

Nowadays, the treatment of diabetes mellitus is based on the variable use and combination of diet, antidiabetic oral agents (metformin, sulphanylureas, glynides, acarbose and thiazolidinediones) and insulin or its analogs, depending on the type of diabetes and the needs of the patient. The prevention and treatment of chronic micro- and macrovascular complications, on the other hand, is based on the achievement and maintenance of an optimal glycaemic control and requires the combined use of adjunctive therapy such as antihypertensive drugs and cholesterol-lowering medications. Furthermore, several herbal preparations and dietary supplements, such as antioxidants, essential fatty acids, lipid metabolism activators, vitamins and trace elements, are advertised and prescribed to patients as a useful adjuvant to a diabetic diet and conventional medications in order to improve glycaemic control and reduce the impact of chronic complications. In this regard, we have attempted to review the current concepts dealing with the usefulness of these complementary therapies in treating diabetic patients.

Prospective study of post-partum thyroid immune dysfunctions in type 1 diabetic women and in a healthy control group living in a mild iodine deficient area.

Second to diabetes mellitus, thyroid diseases are the most common endocrinopathies seen in pregnancy. The incidence of post-partum thyroid dysfunction (PPTD) in women with type 1 diabetes mellitus is three-fold increased. We determined the incidence of thyroid abnormalities in a well-defined group of young subjects with type 1 diabetes and in an age-matched healthy controls during and six months after pregnancy in an area of mild iodine deficiency. Twenty-five out of twenty-eight pregnant women completed the study. Fifteen were affected by type 1 diabetes and ten were controls. Our protocol of study consisted of four evaluations of each subject: in the first, in the second trimester, at delivery and six months after. At each control the patients were submitted to physical examination, thyroid ultrasonography, and determination of fT3, fT4, TSH, Antithyroglobulin antibodies (TgAbs), Antithyroperoxidase antibodies (TPOAbs). The variation of thyroid volume is statistically significant in both the diabetics and in the controls during the different times of observations. Four out of the fifteen diabetic pregnant patients (27%) developed a thyroid disease: two cases of post-partum thyroiditis (PPT) and two cases of euthyroid benign nodular goiter, as confirmed by cytological examination. Two out ten controls (20%) developed positive antibodies (TPO Abs and TgAbs) since the first observation and showed an autoimmune thyroiditis six months after delivery. Both of them showed a familial history of thyroid disease. Our study suggests that in an area of mild iodine deficiency the incidence of thyroid autoimmunity in pregnant women is similar, whether diabetic or not; moreover, thyroid volume is increasing in the diabetics as much as in the non diabetics during pregnancy.