LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal adrenal cortex and aldosterone producing adenoma.

Endocrine factors different from ACTH or angiotensin II can stimulate aldosterone secretion and have a role in the pathophysiology of hyperaldosteronism. Aldosterone may increase in luteotropic/progestogenic and in hypothyroid states; LH and, occasionally, TSH receptors have been detected in normal adrenal cortex and aldosterone-producing adenoma. The aim of the study was to compare adrenal contents of LH and TSH receptors between normal cortex and aldosterone-producing adenoma and to evaluate the ability of LH, its product progesterone, and TSH to stimulate aldosterone secretion in vitro from primary adrenocortical cells. Surgical aldosterone-producing adenoma fragments from 19 patients and adrenal cortex fragments from 10 kidney donors were used for Western blotting and cell cultures. LH (n=26), TSH (n=19) and progesterone (n=8) receptor proteins were investigated; LH receptor-mRNA was also tested in 8 samples. Aldosterone responses in vitro to LH, progesterone, and TSH stimulation were assayed. LH and TSH receptors were more expressed in adenoma than normal cortex (p<0.01, p<0.05, respectively); progesterone receptor was observed in 6/8 samples. Aldosterone increased after in vitro stimulation with LH (5/12 adenoma, 1/7 normal cells), progesterone (4/5 adenoma, 5/6 normal cells), and TSH (3/5 adenoma and 3/5 normal cells). LH and TSH receptors were more expressed in aldosterone producing adenoma than normal adrenal cortex. LH, progesterone, and TSH can stimulate aldosterone in vitro. Similar mechanisms could participate in vivo in the aldosterone increase in lutheotropic, progestogenic, or hypothyroid states and may exist in both normal adrenal cortex and adenoma in responsive individuals.

Cervical sympathetic chain schwannoma: a case report.

Nerve sheath tumours arising from the sympathetic chain are extremely rare and are a diagnostic challenge. We report the case of a 31- year-old man who presented with an asymptomatic right cervical swelling. He was evaluated with sonography, CT, MR and angiography. Surgical excision of the lesion was performed, and histological examination revealed a schwannoma. The differential diagnosis of such tumours and their management are discussed.

Genetic markers to discriminate benign and malignant thyroid nodules with undetermined cytology in an area of borderline iodine deficiency.

BACKGROUND: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. AIM: We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. SUBJECTS AND METHODS: The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. RESULTS: A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. CONCLUSIONS: The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.

Total parathyroidectomy without autotransplantation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease: clinical and laboratory long-term follow-up.

Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40 patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had four glands removed, while only three glands were found in the remaining two. Perioperative complications consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%). No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37 (86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of 1084+/-505 pg/ml to 120+/-381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients. tPTX should be considered a safe and successful procedure for the treatment of severe secondary hyperparathyroidism associated with chronic kidney disease.

Neck lesions mimicking thyroid pathology.

INTRODUCTION: Nodular lesions within the neck may origin from several structures. A misdiagnosed origin may expose the surgeon to inappropriate procedures. These lesions are paradoxically frequent in high specialised centre for endocrine surgery. PATIENTS AND METHODS: In the year 2006, three patients were first admitted to our department with a diagnosis of thyroid nodule (1) or lymphatic metastases of thyroid carcinoma (2). The first patient had ultrasound (US) and Tc-99-m scan orienting for thyroid nodule. The two other patients, presented with lateral neck lesion in ipsilateral sincronous and previous diagnosis of papillary thyroid carcinoma, respectively, with US and computed tomography scan confirmed lesion but with a FNA cytology negative for tumoural cells. RESULTS: All three patients underwent surgical exploration. In the first two cases, a whitish tender nodule (4 and 4.5cm), cleavable from surrounding structures, was removed with final histology of Schwannoma and Paraganglioma, respectively. Both patients experienced Bernard Horner Syndrome. In the last patients, a firm grey nodule of 5cm strictly adherent to muscular planes was removed with diagnosis of Castleman's Disease. CONCLUSIONS: Nodular neck lesions mimicking a thyroid pathology (thyroid nodules or metastatic lymph nodes) are rare but can represent a tough challenge for surgeons who might fall into incorrect surgical approaches, resulting in high morbidity. Pre-operative work-up would help the surgeon to obtain the correct diagnosis, thus, to follow the better surgical approach. Nevertheless, a careful approach would be used for that neurogenic tumour amenable of resection without jeopardising nervous structures.

Unexpected histological findings of lesions diagnosed in the adrenal region in a series of 420 patients submitted to adrenal surgery. Review of our experience.

INTRODUCTION: The incidence of adrenal incidentalomas is reported to be up to 30% in the current literature; nevertheless, in some patients undergoing surgery, a final diagnosis of non-adrenal origin of the mass is performed. In this paper we present our experience of 13 patients with unexpected histological findings of lesions diagnosed in the adrenal region. PATIENTS AND METHODS: From June 1986 to December 2004, 420 patients underwent adrenalectomy in our Department. Since the introduction of videolaparoscopic technique in 1993, 228 adrenalectomies have been performed videolaparoscopically. Pre-operative diagnosis was: incidentaloma (34.0% of patients), Conn's adenoma (29.0%), Cushing's adenoma (13.9%), pheochromocytoma (8.8%), suspicious metastasis (7.3%), Cushing's disease (6.0%), other (1.0%). RESULTS: Final histology revealed an unexpected diagnosis of non-adrenal origin of the mass in 13 patients (3.1%). Histology demonstrated a benign neurogenic tumor in 10 patients. In the other 3 patients diagnosis was respectively of lymphnode, hemangioma and a gastric metastasis of melanoma. Five patients out of 7 had a successful laparoscopic resection of the lesion. Mean operative time in this group was higher compared to laparoscopic resection for adrenal lesion (95.3 min vs 73.2 min). CONCLUSION: A small percentage of our patients (3.1%) demonstrated unexpected findings of the lesion pre-operatively misinterpreted as an adrenal mass. Despite a complete pre-operative assessment, adrenal lesions might reveal a different origin, increasing the surgical challenge as well as the morbidity for the patient.

Proteomic analysis of human thyroid fine needle aspiration fluid.

The aim of this study was to determine the protein pattern of human thyroid fine needle aspiration fluid (FNA) using a proteomic approach. FNA proteins were separated using 2-dimensional gel electrophoresis (2DE), digested and then analyzed by peptide mass fingerprinting. For the first time, we provided an image of the protein components of the FNA, in which approximately 220 protein spots can be identified. The proteome analysis revealed a specific fingerprint of FNA with proteins appertaining to various functional systems. Our preliminary results of FNA protein pattern could be a starting point in studying the presence of potential markers implicated in thyroid diseases.

Vagal paragangliomas: two case reports.

Two uncommon cases of paragangliomas arising from the vagus nerve are described. The first patient underwent surgery for suspected carotid body tumour. In the second patient, computed tomography scan and digital angiography allowed a correct pre-operative diagnosis to be made. These cases confirm the prevalence of vagal paragangliomas in female sex and middle age, and the possibility of multiple similar tumours in the same patient. Histological benign features, absence of neurological symptoms, of local invasion or intracranial extension confirm the frequent benign behaviour of these neoplasms. Lack of catecholamine secretion confirms the low incidence of functioning tumours. Contrast computed tomography and digital angiography still remain the gold standard reliable instruments for diagnosis despite the success of magnetic resonance imaging, magnetic resonance angiography and octreotide scintigraphy to detect head and neck paragangliomas. A transcervical approach, without mandibulotomy, is suitable too for large tumours but complete removal, with sparing of involved segments of the vagus nerve, is rarely possible. Post-operative neurological morbidity is still an unsolved issue and, therefore, rehabilitation of deglutition and phonation is an integral part of management.

Role of frozen section associated with intraoperative cytology in comparison to FNA and FS alone in the management of thyroid nodules.

AIMS: The utilization of fine needle aspiration (FNA) biopsy is an accurate and cost-effective method in the diagnosis of thyroid diseases. However, the non-diagnostic cases and cases of suspicious carcinoma remain a dilemma, and in these cases thyroidectomy is usually recommended, even if only 15-20% of these patients really need a thyroidectomy. To avoid unnecessary surgical treatment, frozen section (FS) is usually performed. This method is well recognized, but is not useful for the diagnosis of follicular lesions. Therefore, many authors have tried to increase the specificity and sensibility of intraoperative examination, supporting it with an intraoperative cytological technique (IC). To clarify the role of intraoperative exam (FS and IC), also comparing to FNA, we have reviewed our own experiences. METHODS: In a period covering 6 years (2000-2005), FS was performed in 1,472 cases out of 11,420 total thyroidectomy operations. FS diagnosis and definitive diagnosis, were reviewed and confirmed, moreover, FNA diagnosis and definitive diagnosis were also considered and all intraoperatory cytological slides were reviewed. Diagnostic accuracy was assessed for FNA and FS with or without intraoperative cytology. We compared 1,472 FS diagnoses with their definitive histological diagnosis; 728 FNA out of 1,472 patients with definitive histological diagnosis, and 564 FS associated with IC out of 1,472 patients with definitive diagnosis. RESULTS: The diagnostic accuracy of these three methods were, respectively, 88.8%, 88.8% and 95.7%. CONCLUSION: We can assert that FS associated with IC remains the most accurate technique in the surgical management of thyroid nodules.

The electron energy dependence of the TL response for CVD diamonds.

The thermoluminescent (TL) response of CVD diamond is investigated after bombarding a sample with monoenergetic electrons (at 6 and 21 MeV). Irradiations are performed at room temperature with a medical linear electron accelerator PRIMUS (KD2-Siemens). The TL curve shows a peak at approximately 540 K. The area of this peak as a function of fluence exhibits saturation behaviour at high energies. Moreover, there is no significant difference between the TL response at 21 MeV electrons and that at 6 MeV. In order to explain these experimental results, calculations of the ionising dose have been performed with the code MCNPX (Monte Carlo N-Particle) for various incident energies from 0.1 MeV up to 100 MeV.

Influence of absorbed dose and deep traps on thermoluminescence response: a numerical simulation.

Numerical simulations based on standard rate equations are carried out to study the dependence of the thermoluminescence (TL) response on the absorbed dose. The model, which includes thermally stimulated exoelectronic emission (TSEE), uses three electron traps--two active and one thermally disconnected (TD)--and one deep hole trap acting as a recombination centre. After instantaneous creation of a given dose of electron-hole pairs, one first follows isothermal recombination and trap filling before simulating the TL readout. Influence of TD traps and specific effects due to trap saturation are illustrated. A systematic study of the TL response is performed in wide ranges of the determining parameters. The dose dependence is found to be quadratic, linear or intermediate according to their relative values. Results are explained in terms of recombination-trapping competition, trap occupancy and in relation with the presence of TSEE.

Radiation damage induced by krypton ions in sintered alpha-Al2O3.

Alpha-alumina is a useful thermoluminescence (TL) dosemeter. The knowledge of its behaviour under irradiation is thus of primary importance. The purpose of this paper is to characterise the radiation damage produced by swift krypton ions using various experimental methods, namely TL, optical absorption, fluorescence and electron paramagnetic resonance (EPR). After ion irradiation, the TL intensity is shown to decrease, whereas the optical absorption rises in the whole studied wavelength range. These two phenomena seem to be related to one another. Furthermore, optical absorption measurements highlight the appearance of new absorption bands probably owing to oxygen vacancies. Induced defects are also observed in the EPR spectra of irradiated pellets. They are likely related to electronic holes trapped on oxygen ions. The concentration of these defects increases with ion fluence and fluorescence measurements indicate that some pre-existing defects such as F2(2+) centres follow the same trend up to approximately 4.1 x 10(13) ions cm(-2).

Kerma rate effects on thermoluminescent response of CVD diamond.

The thermoluminescence (TL) response of chemical vapour deposition diamond is studied after X-irradiation (45 kV) at room temperature for various air kerma rates ranging from 0.7 to 100 Gy.min(-1). For a given air kerma, the TL signal as a function of air kerma rate exhibits large variations and is higher for low air kerma rates than for higher ones. In order to explain these results, the simplest energy-level scheme has been considered, that is, with only one electron trap and one recombination centre. Kinetic equations are numerically solved. Calculations are made for various electron-hole generation rates and show that the trap filling as a function of electron-hole generation rate follows, actually, the same evolution as the one of experimental TL response. The kerma rate effect on TL response is explained by the competitivity between the recombination and the trapping processes during irradiation.

Optical bleaching, TSL and OSL features of CVD diamond.

Luminescence and optical features of chemical vapour deposition (CVD) diamond have been studied in view of the potential application of this material in ionising radiation dosimetry field. For this purpose, thermally stimulated luminescence (TSL) and optically stimulated luminescence (OSL) techniques have been used. A large amount of work has emphasised the excellent dosimetric properties of CVD diamond. Nevertheless, TSL measurements showed that after irradiation, this material is extremely sensitive to ambient light and the stored dose information is drastically affected by optical bleaching. From OSL analysis, it follows that both types of processes (TSL and OSL) were characterised by the same excitation and emission spectra and that optical bleaching originated from a broad stimulation band lying from visible to near infrared with a continuous character.

Thermoluminescence properties of CVD diamond for clinical dosimetry use.

The application of diamond to dosimetry is desirable because of its tissue equivalence, chemical inertness and small size, but this has not been commercially viable owing to the non-reproducible response of natural diamond. The chemical vapour deposition (CVD) of diamond permits controlled, reproducible and large-scale production of this material at potentially low cost. An investigation of some clinically relevant features like the depth-dose distribution as well as the absorbed dose profile, obtained using thermoluminescence (TL), is reported for several CVD diamond films. The TL characterisation presented here shows that CVD diamond films should be excellent TL-mode detectors in instances of radiotherapy and in vivo radiation dosimetry.

Neutron absorbed dose determination by calculations of recoil energy.

The aim of this work is to calculate the absorbed dose to matter due to neutrons in the 5-150 MeV energy range. Materials involved in the calculations are Al2O3, CaSO4 and CaS, which may be used as dosemeters and have already been studied for their luminescent properties. The absorbed dose is assumed to be mainly due to the energy deposited by the recoils. Elastic reactions are treated with the ECIS code while for the non-elastic ones, a Monte Carlo code has been developed and allowed to follow the nucleus decay and to determine its characteristics (nature and energy). Finally, the calculations show that the absorbed dose is mainly due to non-elastic process and that above 20 MeV this dose decreases slightly with the neutron energy.

Peripheral type benzodiazepine receptor in human parathyroid glands: up-regulation in adenoma.

In this study we report the presence of peripheral benzodiazepine receptors (PBRs) in human parathyroid glands and describe the effect of their benzodiazepine type ligands on parathyroid cell function. PBR binding features in normal parathyroid tissue were characterized and compared to parathyroid adenoma, using a specific and selective ligand for PBR, [3H] 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline-carboxamide ([3H]PK11195). Affinity and density of [3H]PK11195 binding sites in homogenate membrane preparations from adenomatous and normal tissues were determined. Parathyroid adenoma showed a statistically significant 2.2 fold increase of [3H]PK11195 binding sites, while the affinity remained unchanged. Our results represent the first evidence of PBRs in parathyroid glands and suggest for them a role in influencing PTH release. A clear trend of PBR up-regulation in parathyroid adenoma was also found.

Angiogenesis in human normal and pathologic adrenal cortex.

The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 +/- 27.8) than in N (336.6 +/- 14.5), APA (322.8 +/- 19.1), CPA (288.5 +/- 14.3), and NFA (274.2 +/- 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 +/- 2.1) than in APA (56.5 +/- 7.5), CPA (38.5 +/- 7.0), N (33.1 +/- 6.1), and NFA (0.76 +/- 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found. In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.

Influence of thermal quenching on the thermostimulated processes in alpha-Al2O3. Role of F and F+ centres.

Anion deficient alpha-Al2O3 is highly sensitive to ionising radiations and is widely used as a thermoluminescence and optically stimulated luminescence dosemeter in environmental monitoring. Two types of alpha alumina were studied and it was observed that both were affected by thermal quenching of luminescence. This effect, which manifests itself by the decay of the TL response when the heating rate increases, can be described by the Mott-Seitz theory. It was observed that thermostimulated exoemission response increased when the heating rate increased, whereas thermostimulated conductivity remained constant. However, none of the available theories could explain the dependence of the F- centre emission on the heating rate. A model is proposed to describe simultaneously the various thermally stimulated processes.