Thyroid function and structure are affected in childhood obesity.

OBJECTIVE: Alterations in thyroid function are reported in obesity, although no relevant data exist on the thyroid structure of these patients and the frequency of autoimmunity. The aim of our study was to evaluate the involvement of the thyroid gland in a large group of obese children. DESIGN: This was a cross-sectional study. METHODS: The study was conducted between March 2004 and December 2007 in 186 overweight and obese children. In all subjects, serum free T(3), free T(4), TSH, antithyroid antibodies, and a thyroid ultrasound were assessed. A total ot 40 healthy children matched for age and of normal weight for height served as controls. RESULTS: A total of 23 children (12.4%) showed antithyroid antibodies and an ultrasound pattern suggestive of Hashimoto's thyroiditis (group A). Of them, 20 (10.8%) showed antithyroid antibodies and normal ultrasound (group B). A total of 70 subjects (37.6%) showed absent antithyroid antibodies and an ultrasound pattern suggestive of Hashimoto's thyroiditis (group C), and 73 children (39.2%) showed no thyroid antibodies with normal ultrasound (group D). TSH was higher in groups A and C compared with groups B and C, and controls (P < 0.05). Mean free T(4) was lower in group B (P < 0.05) than in controls, whereas free T(3) was higher in group C than in controls (P < 0.05). TSH and body mass index sd scores were significantly correlated in group C (P < 0.001), and TSH was also significantly associated with the degree of thyroid structure alterations (P < 0.05). CONCLUSION: Obese children frequently show alterations of thyroid structure and function that are not completely explained by the presence of an autoimmune involvement.

Paraneoplastic stiff-person syndrome, heterotopic soft tissue ossification and gonarthritis in a HLA B27-positive woman preceding the diagnosis of Hodgkin's lymphoma.

Paraneoplastic neurologic syndromes associated with Hodgkin's lymphoma include the stiff-person syndrome. A case of stiff-person syndrome is reported who first presented with muscular hyperactivity and acute respiratory failure followed by heterotopic soft tissue ossification and acute seronegative gonarthitis. Initial improvement of a tetanus-like clinical picture was achieved with benzodiazepam given by continuous infusion for analgo-sedation to mechanically ventilate the patient followed by baclofen after successful weaning. The patient was HLA B27 positive and on conventional testing no autoantibodies were detected including anti-glutamic acid decarboxylase antibodies (anti-GAD). Months later in the absence of signs of stiff-person syndrome, mediastinal lymphadenopathy and pleural effusions developed which were diagnosed as classical Hodgkin's lymphoma that was successfully treated with polychemotherapy. No relapse of paraneoplastic neurologic syndromes was seen after two years of lymphoma remission. The case illustrates that stiff-person syndrome may precede the clinical appearance of symptomatic Hodgkin's lymphoma.

Germline prokineticin receptor 2 (PROKR2) variants associated with central hypogonadism cause differental modulation of distinct intracellular pathways.

INTRODUCTION: Defects of prokineticin pathway affect the neuroendocrine control of reproduction, but their role in the pathogenesis of central hypogonadism remains undefined, and the functional impact of the missense PROKR2 variants has been incompletely characterized. MATERIAL AND METHODS: In a series of 246 idiopathic central hypogonadism patients, we found three novel (p.V158I, p.V334M, and p.N15TfsX30) and six already known (p.L173R, p.T260M, p.R268C, p.V274D, p.V331M, and p.H20MfsX23) germline variants in the PROKR2 gene. We evaluated the effects of seven missense alterations on two different prokineticin receptor 2 (PROKR2)-dependent pathways: inositol phosphate-Ca(2+) (Gq coupling) and cAMP (Gs coupling). RESULTS: PROKR2 variants were found in 16 patients (6.5%). Expression levels of variants p.V158I and p.V331M were moderately reduced, whereas they were markedly impaired in the remaining cases, except p.V334M, which was significantly overexpressed. The variants p.T260M, p.R268C, and p.V331M showed no remarkable changes in cAMP response (EC50) whereas the IP signaling appeared more profoundly affected. In contrast, cAMP accumulation cannot be stimulated through the p.L173R and p.V274D, but IP EC50 was similar to wt inp.L173R and increased by 10-fold in p.V274D. The variant p.V334M led to a 3-fold increase of EC50 for both cAMP and IP. CONCLUSION: Our study shows that single PROKR2 missense allelic variants can either affect both signaling pathways differently or selectively. Thus, the integrity of both PROKR2-dependent cAMP and IP signals should be evaluated for a complete functional testing of novel identified allelic variants.

Screening of Cushing's syndrome in outpatients with type 2 diabetes: results of a prospective multicentric study in Italy.

CONTEXT: Cushing's syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushing's syndrome in patients with type 2 diabetes. OBJECTIVE: Our aim was to evaluate the prevalence of unsuspected Cushing's syndrome among outpatients with type 2 diabetes. DESIGN AND SETTING: This was a cross-sectional prospective study in 24 diabetes clinics across Italy. PATIENTS: Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test. RESULTS: Forty patients failed to suppress serum cortisol less than 5.0 µg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 µg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushing's syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents. CONCLUSIONS: The present data do not support widespread screening of patients with type 2 diabetes for Cushing's syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.

Fatal cardiac arrest in an adult patient with euthyroid anti-SSA/Ro-positive connective tissue disease: a case report.

BACKGROUND: Until recently, anti-SSA/Ro antibodies were not considered pathogenic for severe heart disease in adults. Prolongation of the mean QTc interval in electrocardiograms of adult patients with anti-SSA/Ro-positive connective tissue disease has been reported and could contribute to complex arrhythmias in such patients. Furthermore, complete heart block may also be related to these autoantibodies. CASE PRESENTATION: We describe the occurrence of fatal complete heart block in a euthyroid adult patient with undifferentiated connective tissue disease and polyglandular autoimmune syndrome type 2 associated with cardiovascular autonomic dysfunction who had normal QTc interval. The patient's serum contained anti-SSA/Ro. CONCLUSION: This case might indicate that, although the adult heart conduction system may be relatively resistant to the development of anti-Ro-associated complete heart block, cardiac arrest may develop and even be fatal.

Clinical and diagnostic aspects of cystic insulinoma.

Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma have been reported to date. Diagnosis of insulinoma could be difficult if the functional activity is incomplete, possibly leading to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by histological examination after surgery, characterized by a high intracystic insulin concentration despite normal blood basal levels of the hormone. New diagnostic findings from dynamic tests and cystic fluid examination have been carefully focused on.