Nodule size as predictive factor of efficacy of radiofrequency ablation in treating autonomously functioning thyroid nodules.

CONTEXT: No defined pre-treatment factors are able to predict the response to radiofrequency ablation (RFA) of an autonomously functioning thyroid nodule (AFTN). OBJECTIVE: Primary endpoint was to evaluate the success rate of RFA to restore euthyroidism in a cohort of adult patients with small solitary AFTN compared with medium-sized nodules. Secondary endpoints included nodule volume reduction and rate of conversion from hot nodules to cold using scintiscan. METHODS: This was a 24-month prospective monocentric open parallel-group trial. Twenty-nine patients with AFTN were divided into two groups based on thyroid volume: 15 patients with small nodules (<12 mL) in group A and 14 patients with medium nodules (>12 mL) in group B. All patients underwent a single session of RFA and were clinically, biochemically, and morphologically evaluated at baseline and at 1, 6, 12 and 24 months after treatment. RESULTS: After RFA, there was greater nodule volume reduction in group A compared with group B (p < 0.001 for each follow-up point). In group A, there was a greater increase in TSH levels than in group B at 6 (p = 0.01), 12 (p = 0.005), and 24 months (p < 0.001). At 24 months, the rate of responders was greater in group A than in group B (86 vs. 45%; p < 0.001). In group A, 86% of nodules converted from hot to cold compared with 18% in group B (p < 0.001). CONCLUSIONS: A single session of RFA was effective in restoring euthyroidism in patients with small AFTNs. Nodule volume seems to be a significant predictive factor of the efficacy of RFA in treating AFTN.

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis.

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism.

UNLABELLED: No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. METHODS: The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. RESULTS: After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study. CONCLUSION: The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium.

Osteoporosis: recent physiopatologic acquisitions and new therapeutic perspectives.

The World Health Organization (WHO) declared osteoporosis "social disease". The present revision of the literature will focus on the recent acquisitions in bone pathophysiology and the efforts in the formulation of new molecules able to change successfully the course of the disease. Osteocyte cell is now thought to be the main biomechanical transducer of bones, able to release sclerostin that produces inhibition on osteosynthesis and on the other hand to release substances like nitrid oxide and prostaglandins that provide a stimulus to osteosynthesis through direct or indirect activation of osteoblasts. In this work the authors analyze the most important clinical trials involving the use of new molecules, like denosumab, integrin avb3 inhibitor, cathepsin k inhibitors, able to interfere in the new osteometabolic pathways. Two trials, phase I and II, have been conducted using denosumab. The endpoint of the first phase was the evaluation of the markers of resorption and bone formation, while the second phase II trial focused on the use of this molecule in double-blind matching placebo and open alendronate with the evaluation of bone mass density (BMD) over one year in lumbar area. Another clinical trial in double-blind versus placebo was carried on and published on the use of a competitive integrin avb3 inhibitor in various dosages for the evaluation of bone mass modification in the lumbar and femoral area and of bone markers modification. Many studies focus on the use of cathepsin k inhibitors. Odanacatib has demonstrated to have worked on dose-dependent increase of densitometric value and to have reduced the bone turnover.

Evidence based medicine and effective interventions of pharmacological therapy for the prevention of osteoporotic fractures.

Osteoporosis and fractures associated with it constitute a real and serious socio-medical problem, which only recently has come to the forefront of social consciousness. The authors are carrying out a critical re-examination of the medical literature of osteoporosis pharmacological treatment. Particular attention has been paid to studies which show a clear reduction of the primary endpoint that, in the case of this pathology, consists of a reduction of the fracturing event. According to the examination of the clinical studies introduced, antiresorptive bone agents, such as alendronate and risenderonate, turn out to be molecules with higher levels of evidence implicated on the reduction of the main osteoporotic fractures, in particular the reduction of vertebral and femoral fractures. The 10 years long-term extension studies, in particular those that have seen the employment of alendronate, found a positive outcome regarding densitometry data and a favorable trend in antifracture effectiveness. Ibandronate is another amino-bisphosphonate which was recently validated as an effective drug for the treatment of osteoporosis with its documented ability to meaningfully reduce vertebral fractures. Also ranelate of strontium, a drug that seems to explain its own result in a different way from the other antiresorptive bone agents, constitutes another valid alternative in the treatment of this pathology. Both of these molecules however, need further studies in order to estimate their antifracture effectiveness in the long term, particularly those related to femoral fractures. Teriparatide and the entire molecule paratohormone are usually not prescribed for its high cost in treatment and because, typically, patients with high-risk level fractures that are already affected, produce more vertebral fractures from moderate to severe intensity.

Synchrotron-based XRD from rat bone of different age groups.

Synchrotron-based XRD spectra from rat bone of different age groups (w, 56 w and 78w), lumber vertebra at early stages of bone formation, Calcium hydroxyapatite (HAp) [Ca10(PO4)6(OH)2] bone fill with varying composition (60% and 70%) and bone cream (35-48%), has been acquired with 15keV synchrotron X-rays. Experiments were performed at Desy, Hamburg, Germany, utilizing the Resonant and Diffraction beamline (P9), with 15keV X-rays (λ=0.82666 A0). Diffraction data were quantitatively analyzed using the Rietveld refinement approach, which allowed us to characterize the structure of these samples in their early stages. Hydroxyapatite, received considerable attention in medical and materials sciences, since these materials are the hard tissues, such as bone and teeth. Higher bioactivity of these samples gained reasonable interest for biological application and for bone tissue repair in oral surgery and orthopedics. The results obtained from these samples, such as phase data, crystalline size of the phases, as well as the degree of crystallinity, confirm the apatite family crystallizing in a hexagonal system, space group P63/m with the lattice parameters of a=9.4328Å and c=6.8842Å (JCPDS card #09-0432). Synchrotron-based XRD patterns are relatively sharp and well resolved and can be attributed to the hexagonal crystal form of hydroxyapatite. All the samples were examined with scanning electron microscope at an accelerating voltage of 15kV. The presence of large globules of different sizes is observed, in small age groups of the rat bone (8w) and lumber vertebra (LV), as distinguished from, large age groups (56 and 78w) in all samples with different magnification, reflects an amorphous phase without significant traces of crystalline phases. Scanning electron microscopy (SEM) was used to characterize the morphology and crystalline properties of Hap, for all the samples, from 2 to 100µm resolution.

Effectiveness and safety of calcium and vitamin D treatment for postmenopausal osteoporosis.

Imbalance of bone resorption and bone formation is responsible for osteoporosis that is characterized by decreased bone mass and mineral density. The aim of this study was to evaluate the available data that could clarify the effectiveness and safety of supplementations with calcium and vitamin D, alone or in combination, to slow down bone loss in postmenopausal and elderly women. Using search key words, we performed a research both in the PubMed and Cochrane Library in order to find all meta-analysis, prospective and randomized clinical studies published from 2000 to 2014 that had investigated the effectiveness of calcium and vitamin D in the treatment of osteoporosis. At the moment it is not possible either to provide reassurance that calcium supplements given with vitamin D do not cause adverse cardiovascular events or to link them with certainty to increased cardiovascular risk. According to the data now available, vitamin D, at dosage of at least 800 IU/day, alone or in combination with antiresorptive drugs, should be administered in osteoporotic and osteopenic patients for a primary and secondary prevention. Further studies are needed and the debate remains ongoing. However, every administration needs the calculation of the absolute fracture risk of the patient. Especially considering the high cost of osteoporosis prevention, more studies are mandatory to clarify indications and contraindications.

Labelling of blood platelets with stable tracers.

Half-time values of platelets labelled with stable rubidium are compared to those of platelets labelled with Cr51. Platelets labelled with stable rubidium are assayed by a very simple version of the X-Ray fluorescence equipment. The mean quantity of rubidium incorporated by the cells is of about some microgram Rb per ml blood. The in vitro half-time of human Rb labelled platelets stored at 22 degrees C is 41.2 +/- 3h compared with the value 44.8 +/- 3h for platelets labelled with Cr51, as deduced by six experiments. The in vivo half-time of rabbit platelets labelled with stable rubidium is 22 +/- 3h compared with the value 18 +/- 3h of platelets labelled with Cr51; ten experiments were carried out.

Reversible increase of intraocular pressure in subclinical hypothyroid patients.

OBJECTIVE: The aim of the study was to analyse the relationship between the ocular parameters, namely intraocular pressure (IOP), and the early forms of subclinical hypothyroidism. DESIGN: Fifty-three subjects (9 male and 44 female) aged from 18 to 45 years (mean 32 +/- 7 years) were selected for this study. Twenty-nine met the criteria of subclinical hypothyroidism and 24 euthyroid subjects, age- and sex-matched, were used as controls. METHODS: All individuals underwent a complete ocular examination, including visual field examination and serial measurement of IOP by means of a Goldmann tonometer. A tonographic examination was also performed. RESULTS: The hypothyroid patients showed a substantially higher pressure in both eyes compared with control subjects (right eye = 17.52 +/- 4.74 vs 13.42 +/- 1.95 mmHg, P < 0.0001; left eye = 17.55 +/- 3.99 vs 13.71 +/- 1.55 mmHg, P < 0.0001). Indeed, the tonometric pressure exceeded 18 mmHg in 11 out of the 29 (38%) patients in the right eye and in 8 out of 29 (27%) patients in the left eye. The outflow index was normal in all subjects except in two hypothyroid patients. After two months of L-thyroxine (L-T4) replacement therapy, only one patient continued to show tonometric values above 18 mmHg and the hypothyroid patients showed a significant reduction in mean IOP in both eyes compared with pre-treatment values (right eye = 14.96 +/- 1.32 mmHg, P < 0.0097; left eye = 15.03 +/- 1.38 mmHg, P < 0.0018). Treatment did not lead to any change in the outflow indices; however, the C value (outflow coefficient at the sclerocorneal corner) returned to normal in the two patients with increased pre-treatment tonographic values. CONCLUSIONS: These findings indicate that the intraocular pressure is increased even in subclinical hypothyroid patients and that, at this early stage, the impairment is fully reversible with L-T4 therapy.

Increased plasma levels of endothelin-1 in patients with hyperthyroidism.

Plasma concentrations of endothelin-1 (ET-1) were measured in 25 hyperthyroid subjects, 15 hypothyroid subjects, and 21 age-matched normal controls. In hyperthyroid patients, plasma concentrations of ET-1 were significantly higher than in the control group (P < .0001) and in hypothyroid patients (P < .0001). In contrast, no differences were found between hypothyroid patients and controls. Plasma levels of ET-1 were similarly elevated as in patients with Graves' disease and those with toxic adenoma. No correlations were found between plasma ET-1 levels, thyroid hormones, and thyrotropin (TSH) in hyperthyroid, hypothyroid, and euthyroid groups. The results of our study clearly indicate that in hyperthyroidism, circulating levels of ET-1 are strongly increased, although the pathogenesis of the increase is unclear.

Determination of red cell survival in rabbits by fluorescent excitation analysis of stable rubidium.

Nonradioactive rubidium was used to label red cell in rabbits and its concentration was determined by employing a simple version of radioisotope-induced x-ray fluorescence analysis. About 10 ml of red cells were labeled in vitro with 0.5-1 mg of RbCl and subsequently reinjected, resulting in a Rb concentration of about 50 ppm by the red cells. Four milliliters of blood were collected about every week, the concentrated erythrocytes deposited on filter paper disks, and the Rb content analyzed. Except for the first four to seven days, a function of the type N = Noe-kt fitted very well the experimental Rb disappearance curve data. The mean half-time value deduced from the experimental data was 310 +/- 15 days, which should be compared with the values of T1/2 = 260 +/- 20 h and T1/2 = 206 +/- 30 h obtained, respectively, by these authors and by Price et al., employing radioactive 51Cr-labeled red cells. The possibility of labeling human red cells with stable Rb is discussed.

Use of differential tomography in the study of natural processes.

A few natural processes are studied using the method of differential computer-assisted tomography (DICAT). The detection of an element in any sample either naturally present or given as tracer can be located in a selective manner, which may be used for important medical and nonmedical applications.

Trace element analysis in biological samples by using XRF spectrometry with secondary radiation.

An x-ray fluorescence method for in vitro analysis of trace elements in biological samples is presented. The method is characterised by the use of an x-ray tube with secondary targets as a monoenergetic radiation source, and by 'infinitely thin' specimens. In the experimental work, different aspects have been examined in order to optimise the sensitivity of the method. It is shown that it is extremely important to use collimators of high purity materials and very pure and thin sample supports. Regarding the geometry, it is pointed out that a collimator between specimen and detector reduces the counting rate caused by scattering in air and other materials. Scattering in the biological matrix is reduced by preconcentration of biological liquids or tissues. The method has been applied to the analysis of blood serum samples. Typical sensitivities for Fe and Rb are 1.6 ng cm-2 and 1.5 ng cm-2 respectively, in a counting time of 10(3) s.

[Tolosa Hunt syndrome and autoimmune polyglandular syndrome. A rare case report]. / Sindrome di Tolosa Hunt e sindrome polighiandolare autoimmune. Un raro caso clinico.

The authors refer to a case report in which two rare clinical syndromes, the Tolosa Hunt Syndrome (THS) and the polyglandular auto-immune syndrome (PGA) co-exist in the same patient and make a detailed analysis of the literature regarding this kind of diseases. The THS is a rare clinical condition characterized by a painful ophthalmoplegia due to an involvement of the cranial nerves and of the sympathetic nerve-fibres going through the cavernous sinus and the superior orbit cavity. Nowadays the diagnosis of TSH is made by high resolution computerized tomography aimed at the cavernous sinus and the upper orbital cavity. This method allows to notice if at the basis of this syndrome there are vascular, neoplastic or inflammatory diseases or if, as in e case here presented, by exclusion, we must think of an inflammatory process with unknown pathogenesis. In this case report the patient under observation process to be affected by THS and also by auto-immune polyglandular syndrome type III, as she was affected by diabetes type I, Basedow disease and alopecia. The authors believe that an auto-immune mechanism can be at basis of the THS, and this fact has already been pointed out in the literature in two previous works. An important feature of this case report has been the definitive improvement of the symptoms by an antithyroid effect and, also, by an immune suppressor activity. The Authors hope that there will be reported a greater number of cases pointing to the coexistence of the THS with autoimmune diseases.

Plasmatic endothelin-1 levels in hyperthyroid patients before and after antithyroid therapy.

BACKGROUND: The Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial cells in many vascular diseases probably as a response to vessel damage. In hyperthyroidism as in other endocrinological diseases elevated ET-1 plasma levels have been found. METHODS: The effect of antithyroid therapy on ET-1 plasmatic levels was evaluated by measuring ET-1 plasma levels before and 2 and 6 months after treatment with methimazole in 14 patients affected by hyperthyroidism. RESULTS: The hyperthyroid patients had significantly higher ET-1 levels than the controls (18.85 +/- 5.7 vs 10.9 +/- 2.1 pg/ml), while after treatment no difference was found. The ET-1 plasma levels of hyperthyroid patients correlated closely with the raised thyroid metabolic activity independently of its cause. It is possible that the increased ET-1 levels in hyperthyroid patients are the expression of blood vessel damage caused by high thyroid hormone levels. CONCLUSIONS: Moreover the results of this study could suggest that, in future, ET-1 plasmatic levels might be considered as a functional thyroid index in hyperthyroid diseases.

[Hypernatremia. Etiopathogenetic classification and description of a rare clinical case]. / Le ipernatremie. Inquadramento etiopatogenetico e descrizione di un raro caso clinico.

On the basis of a rare case of hypernatremia, the essential lines which allow a correct diagnostic and therapeutic approach to hypernatremia are underlined. Hypernatremia is classified according to the patient's state of hydratation and on the content of sodium as: hypovoloemic, euvolemic and hypervolemic. Even the concentrations of sodium in urine are often of great importance for a correct diagnosis. The patient studied suffered from hypernatremia, which is based on genetical factors. The state of dehydration, together with hypovolemia and acute tubular necrosis secondary to rhabdomyolisis, were the causes of hypernatremia. The above mentioned causes were resolved but an enterocutaneous fistula showed to be the cause, quite rare, of hypernatremia. It is suggested that this rare cause should always be mentioned when diagnosing hypernatremia; which it is important since this cause could be solved with an operation. All this was useless in our case since the patient had a drastic deterioration of his general clinical conditions.

Biomedical applications of photon-induced X-ray fluorescence.

An X-ray fluorescence method for in vitro analysis of trace elements is presented. The method is characterized by the use of an X-ray tube with secondary targets as a quasimonoenergetic radiation source, and by "infinitely thin" specimens.Different aspects have been examined in order to optimize the sensitivity of the method. It is extremely important to use secondary targets as pure as possible and collimators internally covered by the same element as the secondary target. It is also important to reduce the contribution at the XRF spectrum of photons scattered by the sample, by the sample support, and by the air.Preconcentration techniques can conveniently also be used to this purpose. In this work, biological samples are preconcentrated by reducing them to ash.Typical sensitivities obtained are in the order of 1-5 ng/cm(2) in a counting time of 10(3) s for elements with atomic number ranging from 24 (chromium) to 40 (zirconium).

[Thyroid cancer and Hashimoto's thyroiditis]. / Cancro della tiroide e tiroidite di Hashimoto.

In a 45 years old women affected by Hashimoto's thyroiditis appeared a thyroid nodule that at the cytologic and than at the histologic examination proved to be a papillar carcinoma. Concerning this problem the authors make a thorough analysis of the literature. Regarding the possible associations between these two diseases, they observe how there is an extreme discordance of opinions on considering statistically significant the relationship between thyroid cancer and Hashimoto's thyroiditis. They make the hypothesis that the association of these two diseases is not casual: several etiological factors could be considered, but the chronic stimulus of TSH on the thyroid tissue affected by the autoimmune disease and progressively hypofunctioning, could be the main factor responsible for the development of the neoplasia. Then they give some advice to recognise patients at high risk for thyroid carcinoma. The patients at higher risk for thyroid cancer are those that present a single or prevalent nodule; the growth of a nodule on suppressive treatment with levothyroxine is also a negative prognostic index. Patients with an enlarged gland without nodules or with nodular goiter without a prevalent nodule are at low risk for cancer.

[Pre-surgical medical therapy of hyperthyroidism]. / Trattamento medico pre-chirurgico dell'ipertiroidismo.

The Authors analyze the use and the efficacy of antithyroidal drugs administered to the patients affected by hyperthyroidism, that must undergo thyroidectomy. The aim is that the patients arrive to the operation in euthyroidism: this is very important to avoid the complications that can occur during or just after the thyroidectomy. They believe that till today the most effective treatment of hyperthyroidism before thyroidectomy is based on the use of thyonamide and iodine. In case of intolerance to these drugs or if it is necessary an emergency thyroidectomy or in case of a low compliance of the patient, there is the possibility to use different therapeutic approaches with beta-blockers or betametasone plus iopanoic acid and propranolol administered together for a few days. As concerning the possible complications that can occur during or after the thyroidectomy, the Authors analyze in particular the thyrotoxicosis and the "hungry bone" syndrome.

[Hashimoto's thyroiditis. A rare case of familial hereditary transmission]. / Tiroidite di Hashimoto. Un raro caso di trasmissione eredofamiliare.

Authors describe an uncommon case of inheritance of Hashimoto's thyroiditis that affected all the members of a family throughout three generations. Authors analyze recent advances about etiopathogenesis of this disease. In a recent paper was demonstrated that antithyroid peroxidase antibodies (anti-TPO) that have a cytotoxic activity are inherited in a dominant autosomic pattern. However only some epitopes of the antigen thyroid peroxidase predispose to the development of this disease. The peculiarity of this paper is that all the members of this family not only have elevated levels of anti-TPO, but are also all affected by disease. The study on the histocompatibility of antigens did not demonstrate significant date. Authors assert that in the pathogenesis of this disease, genetic factors have a relevant role, also if they are not well known yet. The involvement of environmental factors in this case seems to be unlikely: in fact not all the members of this family were born and lived in the same geographic area.