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The objectives of this study were: 1) to evaluate the role of color-Doppler ultrasonography (CDU) assessment of thyroid vascularity, measuring the peak systolic velocity (PSV) at the level of the inferior thyroid artery, and the intrathyroid vascularization in Graves' diseas; 2) to evaluate the role of contrast agent administration in predicting the relapse of hyperthyroidism or the biological activity of the disease after withdrawal of antithyroid drugs.The study included 74 Graves' patients (59 F/ 15 M; mean age 45 years; range 23-71). Graves' disease was diagnosed according to the usual clinical and laboratory criteria. On the basis of the clinical and biochemical findings we divided Graves' patients into 4 different groups. Treatment was continued for at least 12 months, CDU examination was carried out after discontinuing therapy. Eight patients showed a relapse of hyperthyroidism within 5 months after suspension of therapy. In all cases the evaluation of intraparenchymal vascularization and PSV at the level of the inferior thyroid artery in basal conditions was followed by administration of contrast agent (Levovist, 300 mg/ml), with slow infusion (2 ml/min) to avoid blooming artifact. Intraparenchymal vascularization was classified into 4 patterns according to Vitti et al.The value of the peak systolic velocity (PSV) at the level of the inferior thyroid artery was the best predictor of relapse. A value higher than 40 cm/sec was present in all the patients that showed relapse and only in two patients with stable remission. Administration of contrast agent is important to evaluate the biological activity of the disease. In the 5 patients exhibiting slightly increased vascularization after contrast agent administration we could assume the clinico-pathological recovery.CDU study of thyroid vascularization, based on the measurement of PSV at the level of the inferior thyroid artery and on the response to contrast agent administration is useful to distinguish three groups of patients: A) PSV40 cm/sec with pattern III for at least 10 minutes from the beginning of the contrast agent administration (High risk of relapse); B) PSV40 cm/sec with pattern II or III after contrast agent administration (Biological activity of the disease-Thyroiditis); C) PSV40 cm/sec with Pattern I after contrast agent administration (Poor biological activity of the disease-recovery).

Background Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. Methods Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. Results Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8–38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. Conclusions Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in thepost partumperiod, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine–vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month ofpost partumperiod respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational orpost partumautoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

The circadian rhythms of melatonin and cortisol were evaluated in seven outpatients with obsessive-compulsive disorder (OCD) before and after 8 weeks of fluoxetine treatment (20 mg/day in the first 2 weeks, and 40 mg/day afterwards), and in seven healthy subjects matched to patients on age, sex and season of testing. The results confirm our previous findings of a decreased 24-h production of melatonin (p < .05; two-way ANOVA with repeated measures) and of an increased circadian secretion of cortisol (p < .01) in OCD patients with respect to matched controls, and show, for the first time, that these hormonal alterations do not significantly change after 2 months of fluoxetine administration, in spite of a good clinical improvement. These data suggest that the normalization of the biochemical changes underlying the altered endocrine parameters in obsessive-compulsive patients is not necessary for effective therapy or clinical remission.

Summary objective The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves’ patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves’ patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease. patients We evaluated sera of Graves’ patients previously tested for G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19 Graves’ patients without ophthalmopathy previously tested for anti-GS2 (G2sAb) and antiflavoprotein antibodies (FpAb; group 3). During the 18-month follow-up, four of them did not develop ophthalmopathy (group 3a), and 15 did: seven developed eye disease (group 3b) with clinical EM involvement. In particular, moderate disease and clinical activity score (CAS) ≥ 4 in four of them, severe ophthalmopathy and CAS ≤ 1 in three were observed. The remaining eight patients showed moderate ophthalmopathy and CAS ≥ 4 without EM involvement (group 3c). measurements EMAb were evaluated in all samples by indirect immunofluorescence method. results EMAb were detected in 13 out of 18 patients (72·2%) in group 1 (titre 1/32–1/128) and in five out of 14 patients (35·7%) in group 2 (titre 1/2–1/8). As regards to group 3, at the start of the study EMAb were detected in 13 out of 19 patients (72%) at titres 1/2–1/8; during the follow-up they became or persisted negative in all patients in group 3a, while they increased at titres ranging from 1/64 to 1/128 in all patients in group 3b before the onset of ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8–1/16) of EMAb before the onset of eye disease, while four patients were negative during the entire follow-up. conclusions Our results indicate that EMAb are a good marker of ophthalmopathy with EM involvement and their titre is higher in patients with active than in those with inactive disease. Thus, even if our results must be confirmed on a larger cohort of patients, the increase of EMAb in patients with Graves’ disease could be considered as a risk factor for the development of ophthalmopathy with subclinical/clinical EM impairment. In this connection we propose the evaluation of EMAb, in Graves’ patients with subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the EM inflammatory process.

It is commonly recognized that a few patients with Graves’ disease (GD) develop an overt ophthalmopathy, although most of them show subclinical extraocular muscle enlargement by appropriate imaging techniques. At present, it is not possible to identify the subgroup of GD patients with subclinical retroorbital connective involvement. Recently, it has been shown that increase of soluble intercellular adhesion molecule-1 (sICAM-1) serum levels is correlated to clinical activity score in active Graves’ ophthalmopathy (GO) patients with or without hyperthyroidism, suggesting that sICAM-1 serum values could reflect the degree of ocular inflammatory activity. The aim of this longitudinal study was to evaluate sICAM-1 serum levels in GD patients without clinical ophthalmopathy and to assess their possible relationship with occurrence of GO. We measured sICAM-1 serum levels in 103 initially hyperthyroid GD patients without clinical ophthalmopathy and in 100 healthy subjects. All patients were treated with methimazole for 2 yr. Sera were collected from all patients before treatment and then monthly for the first 6 months of therapy, every 2 months in the following 6 months, and finally at the end of the follow-up study. Patients developing GO were excluded from the follow-up at the onset of ophthalmopathy. During the follow-up 17 GD patients (16.5%, group 1) developed overt eye involvement (14 as active inflammatory ophthalmopathy and 3 as ophthalmopathy without clinical retroorbital connective inflammation) and 86 (83.5%, group 2) did not. At start of the study, the mean of sICAM-1 serum concentrations did not differ significantly between the 2 groups, but it was significantly higher than in controls in both groups. No significant correlation between serum sICAM-1 concentrations and free thyroid hormone levels was found in the 2 groups of patients. During the follow-up study, a further increase of sICAM-1 serum levels was observed in 12 of the 14 patients (85.7%) of group 1 who developed active inflammatory ophthalmopathy not only at the onset but also before clinical GO appearance. On the contrary, the 3 patients of group 1 that developed ophthalmopathy without clinical retroorbital inflammation did not show any further increase of sICAM-1 levels at every time of follow-up in comparison with the starting values, even if their sICAM-1 levels were always higher than in normal controls. Finally, group 2 patients showed significantly decreased sICAM-1 levels throughout the follow-up period when compared with the starting values, although they were still significantly higher than in controls. These results indicate that a further increase of sICAM-1 serum levels before the onset of clinical ophthalmopathy may be a marker of subclinical retroorbital connective inflammation in GD patients. Therefore, our study suggests that serial determinations of sICAM-1 serum levels could help to identify and trace at the right time those GD patients prone to developing active inflammatory ophthalmopathy.

Zinc has important effects on metabolism, and on the thermoregulation of obese individuals. The aim of our investigation was to evaluate the serum zinc levels in obese patients before and after severe hypocaloric diets and to evaluate its correlation with the body mass index (BMI). Patients followed a severe hypocaloric diet (737 Kcal) for 60 days. Serum Zn levels and BMI were evaluated. Zn levels in obese patients were significantly (p0.01) lower than in controls, whereas the BMI values were significantly greater. At the end a severe hypocaloric diet, serum Zn and BMI levels returned to normal values. Our data show a possible relationship of the serum Zn levels with the anabolic and catabolic mechanisms in obesity, although the exact metabolic role of this bio-element remains unclear.

A 36-year-old woman with central diabetes insipidus (DI), diagnosed when she was 7, was referred to our Endocrine Unit in January 1993 for further hormonal investigations. Clinical and laboratory findings confirmed the diagnosis of central DI. Cranial computed tomography and magnetic resonance imaging showed only an empty sella. Moreover, we noted impaired glucose tolerance and unusual findings of subclinical adrenocortical failure, i.e. high plasma renin activity with normal aldosterone levels, high ACTH despite normal basal and ACTH-stimulated cortisol levels. Immunological study of the patient's serum showed the presence of arginine vasopressin (AVP)-secreting cell antibodies (Abs), steroid-producing cell Abs, adrenal and islet cell Abs. The following aspects of our case are stressed and discussed: (1) the presence of AVP-secreting cell Abs 29 years after the diagnosis of DI; (2) the association between DI, empty sella and subclinical autoimmune adrenocortical failure with unusual hormonal findings, and (3) impaired glucose tolerance with islet cell antibody positivity.

Summary OBJECTIVE Cytoplasmic autoantibodies to vasopressin cells (AVP) have been detected in patients with idiopathic central diabetes insipidus and only in one patient with endocrine autoimmune diseases without clinical diabetes insipidus. The aim of this study was to look for AVP cell antibodies (AVP-cell-Ab) in human sera of a large population of autoimmune endocrine disease patients without diabetes insipidus and to test whether an occurrence of these antibodies in some patients can be associated with partial impairment of posterior pituitary function. MEASUREMENT Sera from 410 patients (310 females, 100 males, age range 10–46 years) with autoimmune endocrine disorders (260 with thyroid autoimmune disease, and 150 with insulin dependent diabetes mellitus) without clinical diabetes insipidus, and from 100 normal subjects, were investigated for hypothalamic autoantibodies by an indirect immunofluorescence method. Positive sera were subsequently tested with specific rabbit anti AVP serum. RESULTS None of controls, but five out of 410 patients (1–2%) were AVP-cell-Ab positive. All positive and nine negative from the 410 screened patients were tested for posterior pituitary function. Two out of five AVP-cell-Ab positive patients showed partial diabetes Insipidus. CONCLUSION AVP cell antibodies can be shown in some patients with endocrine autoimmune disease without diabetes insipidus and can sometimes be associated with findings of partial posterior pituitary dysfunction. This suggests that clinical diabetes insipidus could be preceded by a long subclinical period characterized only by the occurrence of AVP-cell-Ab in the sera associated or followed by alterations in functional tests. Longitudinal studies are needed to confirm this hypothesis.

BackgroundAlthough several studies have directly explored serotonin (5-HT) transmission in patients with obsessive compulsive disorder (OCD), their results have been inconsistent and their clinical relevance is doubtfulMethodAccording to a double-blind placebo-controlled design, plasma prolactin (PRL) response to a specific serotonergic probe, d-fenfluramine, was measured in 20 drug-free obsessive compulsive patients and in 20 matched healthy controls. After the neuroendocrine test, 5 patients completed a lO-week treatment with fluvoxamine. Psychopathological assessment was performed before and after therapy.ResultsPRL response in OCD patients was blunted under the drug-free condition; correlated inversely with pretreatment ratings of obsessive-compulsive and depressive symptomatology; and correlated inversely with the improvement in obsessive-compulsivescore observed after fluvoxamine treatment.ConclusionsThese results support the idea of a dysfunction of 5-HT transmission in OCD, and suggest that the greater this impairment, the better the response to drugs which selectively block the reuptake of 5-HT.