Clinical Subtypes of Depression Are Associated with Specific Metabolic Parameters and Circadian Endocrine Profiles in Women: The Power Study

Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin.Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup.Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.ClinicalTrials.gov NCT00006180

Advanced RAI-refractory thyroid cancer: an update on treatment perspectives

During the last decades, the knowledge on follicular cell-derived thyroid cancer molecular biology has led to the evolution of a number of novel therapies for these tumors, mainly tyrosine kinase inhibitors. Lenvantinib, sorafenib and recently cabozantinib have been approved for differentiated thyroid cancer (DTC), while larotrectinib and entrectinib for neurotrophic-tropomyosin receptor kinase-fusion thyroid cancer. For radioiodine (RAI) refractory DTCs ongoing research aims to identify agents that may restore RAI-avidity via redifferentiation protocols (vemurafenib or dabrafenib and trametinib) or combination treatments. These treatments are based on the tumor molecular signature. The treatment with targeted therapies has changed the therapeutic strategies and the disease prognosis, however drug resistance remains the main reason for treatment failure. Thus, the understanding of both molecular pathways implicated in tumorigenesis, and tumoral escape mechanisms, are of paramount significance for the development of new therapies for DTC. The present review focuses on the molecular landscape of DTC, the approved targeted therapies as well as the mechanisms of drug resistance. Furthermore, it points to the ongoing research and the future perspectives for the development of more efficient drugs for DTC

Molecular markers for the classification of cytologically indeterminate thyroid nodules.

BACKGROUND: The diagnosis of indeterminate lesions of the thyroid is a challenge in cytopathology practice. Indeed, up to 30% of cases lack the morphological features needed to provide definitive classification. Molecular tests have been developed to assist in the diagnosis of these indeterminate cases. The first studies dealing with the preoperative molecular evaluation of FNA samples focused on the analysis of BRAFV600E or on the combined evaluation of two or three genetic alterations. The sensitivity of molecular testing was then improved through the introduction of gene panels, which became available for clinical use in the late 2000s. Two different categories of molecular tests have been developed, the 'rule-out' methods, which aim to reduce the avoidable treatment of benign nodules, and the 'rule-in' tests that have the purpose to optimize surgical management. The genetic evaluation of indeterminate thyroid nodules is predicted to improve patient care, particularly if molecular tests are used appropriately and with the awareness of their advantages and weaknesses. The main disadvantage of these tests is the cost, which makes them rarely used in Europe. To overcome this limitation, customized panels have been set up, which are able to detect the most frequent genetic alterations of thyroid cancer. CONCLUSIONS: In the present review, the most recent available versions of commercial molecular tests and of custom, non-commercial panels are described. Their characteristics and accuracy in the differential diagnosis of indeterminate nodules, namely Bethesda classes III (Atypical follicular lesion of undetermined significance, AUS/FLUS) and IV (Suspicious for follicular neoplasm, FN/SFN) are fully analyzed and discussed

Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ERα) gene in girls with precocious/early puberty

Purpose: Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty Methods: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene. Results: There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset <7 years, the association tended to become significant, p = 0.09. Girls with xxpp genotype were significantly taller, HSDS 1.63, p = 0.014. In controls, homozygosity for Xbal (xx) and PvuII (pp) was associated with significantly earlier menarche than in women with no polymorphism, p = 0.013 and p = 0.026, respectively, and xxpp genotype was associated with taller adult height, p = 0.017. Conclusion: XbaI and PvuII polymorphisms are not related to idiopathic precocious/early puberty. Early pubertal girls homozygous for both polymorphisms presented earlier onset of puberty, although statistically non-significant, and taller height than girls heterozygous or without these polymorphisms. Homozygosity for both polymorphisms is associated with earlier menarche and taller adult height. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Characteristics of the short children referred to an academic paediatric endocrine clinic in Greece

Aim: To describe the characteristics of short children in relation to gender and the various diagnoses. Methods: All new patients of Greek origin that were referred to our institution in the years 2007 and 2008 for evaluation of short stature were included in the study. Children were categorized according to the severity of their short stature in those with height standard deviation score (HSDS) >-3 and HSDS >-3. Results: Two hundred ninety-five children (162 boys and 133 girls, ratio 1.2) were referred. HSDS of boys was -2.3 (0.6) and of girls -2.1 (0.5), P= 0.004. Girls had shorter parents, and the predicted adult HSDS was also shorter for girls -1.7 (0.8) than for boys -1.35 (0.76), P= 0.003. Seventy per cent of the children of both sexes had familial short stature (FSS), constitutional delay of growth or a combination of the two conditions. About 10% presented the auxological and biochemical criteria for growth hormone deficiency (GHD). In addition, 11.8% had a HSDS a;circ-3, the most common diagnosis being GHD (36.1%); the less severely short children most commonly presented FSS (41.2%). Conclusions: There is no gender bias in referrals for short stature in Greece. About 70% of children of both sexes presented FSS or constitutional delay of growth or a combination of the two conditions, whereas GHD was diagnosed in about 10% of the children. Normal variants of growth were present in about 80% of children with HSDS >-3, but in only 40% when HSDS was >-3. © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

Early Adiposity Rebound and Premature Adrenarche

Objectives To examine differences in the growth pattern and the age at adiposity rebound (AR) between children with premature adrenarche (PA) and their healthy peers (controls). Study design In this cross-sectional study of 82 prepubertal children with PA and 63 controls, the main outcome measures were height and body mass index SDS progression, from birth to presentation at the clinic, baseline biochemical and hormonal evaluation, bone age determination, and age at AR. Results Children with PA were significantly taller and more adipose than controls from the first years of life. 33% of children with PA presented the growth pattern of constitutional advancement of growth (ie, early growth acceleration) vs 19% of controls (P = .045). Children with PA had an earlier AR compared with controls; mean age at AR in girls with PA was 3.73 (1.03) years vs 4.93 (1.36) years for control girls (P = .001) and in boys with PA was 3.45 (0.73) vs 5.10 (1.50) years in control boys (P = .048). Both obese and nonobese girls with PA were taller and had earlier age at AR compared with nonobese controls. Conclusions Early AR and constitutional advancement of growth may be triggering factors for adrenal androgen production and PA. © 2017 Elsevier Inc

VPA-induced recurrent pancreatitis in a cystic fibrosis carrier

A 4.5 years old male with myoclonic epilepsy on Valproic acid (VPA) monotherapy, developed an acute pancreatitis. The discontinuation of VPA and substitution with Levetiracetam was followed by clinical improvement but a relapse of the pancreatitis was noted one month later. The investigation excluded a structural abnormality but revealed a heterozygous CTFR mutation. The contribution of the CTFR mutation on this VPA-induced recurrent pancreatitis cannot be ignored. © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas

ObjectiveThe treatment of subclinical hypercortisolism in patients with bilateral adrenal incidentalomas (AI) is debatable. We aimed to compare the biochemical and clinical outcome of unilateral adrenalectomy vs a conservative approach in these patients.DesignRetrospective study.MethodsThe study included 33 patients with bilateral AI; 14 patients underwent unilateral adrenalectomy of the largest lesion (surgical group), whereas 19 patients were followed up (follow-up group). At baseline and at each follow-up visit, we measured 0800 h plasma ACTH, midnight serum cortisol (MSF), 24-h urinary-free cortisol (UFC) and serum cortisol following a standard 2-day low-dose-dexamethasone-suppression test (LDDST). We evaluated the following comorbidities: arterial hypertension, impaired glucose tolerance or diabetes mellitus, dyslipidemia and osteoporosis.ResultsBaseline demographic, clinical characteristics and the duration of follow-up (53.9±21.3 vs 51.8±20.1 months, for the surgical vs the follow-up group) were similar between groups. At the last follow-up visit the surgical group had a significant reduction in post-LDDST cortisol (2.4±1.6 vs 6.7±3.9 μg/dl,P=0.002), MSF (4.3±2 vs 8.8±4.6 μg/dl,P=0.006) and 24-h UFC (50.1±21.1 vs 117.9±42.4 μg/24 h,P=0.0007) and a significant rise in mean±s.d.morning plasma ACTH levels (22.2±9.6 vs 6.9±4.8 pg/ml,P=0.002). Improvement in co-morbidities was seen only in the surgical group, whereas no changes were noted in the follow-up group.ConclusionsOur early results show that removal of the largest lesion offers significant improvement both to cortisol excess and its metabolic consequences, without the debilitating effects of bilateral adrenalectomy. A larger number of patients, as well as a longer follow-up, are required before drawing solid conclusions.</jats:sec