Can dysglycemia in OGTT be predicted by baseline parameters in patients with PCOS?

BackgroundPolycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the studyTo determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methodsThe oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. ResultsDysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. ConclusionsOne-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported

Links between aldosterone excess and metabolic complications: A comprehensive review

Shortly after the first description of primary aldosteronism (PA) appeared in the 1950s by Jerome Conn, an association of the condition with diabetes mellitus was documented. However, a clear pathophysiological interrelationship linking the two entities has yet to be established. Nevertheless, so far, many mechanisms contributing to insulin resistance and dysregulation of glucose uptake have been described. At the same time, many observational studies have reported an increased prevalence of the metabolic syndrome (MetS) among patients with PA. Regarding the relationship between aldosterone levels and obesity, a vicious cycle of adipokine-induced aldosterone production and aldosterone adipogenic action may be further contributing to MetS manifestations in PA patients. However, whether aldosterone excess affects lipid metabolism is still under investigation. Also, recent findings of the coexistence of glucocorticoid excess in many cases of PA highlight the need for further studies to examine the presumed link between high aldosterone levels and various metabolic parameters. In the present review, our focus is to comprehensively present the spectrum of available research findings concerning the possible associations between aldosterone excess and metabolic alterations, including impaired glucose metabolism, insulin resistance and, consequently, diabetes, altered lipid metabolism and the development of fatty liver. In addition, the complex relationship between obesity and aldosterone is discussed in detail

Breast capillary hemangioma at the tail of Spencer: A rare entity

A palpable breast lump is a frequent clinical finding and preoperative evaluation varies depending on its localization and characteristics. Vascular tumors are rarely diagnosed especially regarding the tail of Spencer region. In general, they appear oval-shaped with wellcircumscribed margins, but their echostructure varies, and it might be quite difficult for the breast specialist to differentiate it from complex cysts, fibroadenomas or some carcinomas. The authors describe a rare location of breast hemangioma with mammographic characteristics that were suspicious for malignancy. There were no identifiable risk factors, no familial history of breast lumps, and patient did not mention the intake of hormonal therapy. The lump was evaluated by mammography and breast ultrasonography, whereas due to the high vascularity of the nodule, the decision not to perform fine-needle aspiration (FNA) was made and an excisional biopsy was performed. The histological result was "breast capillary hemangioma"

Levothyroxine Replacement Therapy and Overuse: A Timely Diagnostic Approach

Levothyroxine (LT4) is one of the most prescribed drugs worldwide. Once started, approximately 90% of patients continue treatment long term. However, accumulating evidence suggests that many patients, for whom the indication for its administration is not adequately established and the diagnosis is not well documented, are overusing it. This study aimed to evaluate the necessity for and determine potential prognostic factors of long-term LT4 supplementation. Methods: A prospective clinical cohort follow-up study was carried out. In 291 subjects (84% females) aged 48 ± 16 years on LT4 replacement therapy without a solid diagnosis of hypothyroidism being provided, the treatment was paused. At the beginning and after six to eight weeks of treatment discontinuation, thyrotropin (TSH) and free thyroxine levels were assessed, and thyroid ultrasound was performed. A TSH value of ≥4.5 IU/mL was considered as underlying hypothyroidism. Results: Among the 291 individuals, 114 became hypothyroid (group A), while 177 subjects remained euthyroid off LT4 (group B; 39.2% vs. 60.8%, p < 0.001). The groups were comparable regarding sex, family history, age, body mass index, duration of treatment, basal TSH and free thyroxine values, thyroid volume, and presence of thyroid autoantibodies. However, diffuse inhomogeneous echogenicity on ultrasound examination was significantly higher (p < 0.001) in group A. Conclusions: These findings suggest considerable overuse of thyroxine therapy. The results underline the initial need to establish the diagnosis firmly before treatment initiation and to undertake periodic evaluation of all patients on chronic LT4 treatment as to the necessity for treatment continuation. In all patients on long-term LT4 therapy in whom the diagnosis has not been definitively established, it appears rational to introduce a six- to eight-week period of LT4 replacement therapy discontinuation, preceded and followed by TSH tests, as the first-line approach - a procedure that could be implemented as part of a common strategy among the scientific community to decrease current LT4 overuse. © Copyright 2018, Mary Ann Liebert, Inc

A comprehensive investigation of steroidogenic signaling in classical and new experimental cell models of adrenocortical carcinoma.

Adrenocortical carcinoma is a heterogeneous and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. In this study, we have assessed for the preclinical gold standard NCI-H295 in direct comparison with the more recently established MUC-1 and a here newly reported ACC cell line (TVBF-7) the mutational status of important driver genes (TP53, MEN1, PRKAR1A, CTNNB1, APC, ZNRF-3, IGF-2, EGFR, RB1, BRCA1, BRCA2, RET, GNAS and PTEN), Wnt-signaling specificities (CTNNB1 mutation vs. APC mutation vs. wildtype), steroidogenic-(CYP11A1, CYP17A1, HSD3B2, HSD17B4, CYP21A2, CYP11B1, CYP11B2, MC2R, AT1R) and nuclear-receptor-signaling (AR, ER, GCR), varying electrophysiological potentials as well as highly individual hormone secretion profiles (Cortisol, Aldosterone, DHEA, DHEAS, Testosterone, 17-OH Progesterone, among others) which were investigated under basal and stimulated conditions (ACTH, AngII, FSK). Our findings reveal important genetic and pathophysiological characteristics for these three cell lines and reveal the importance of such cell-line panels reflecting differential endocrine functionalities to thereby better reflect clinically well-known ACC patient heterogeneities in preclinical studies

Correction to: A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma (Cells, (2022), 11, 9, (1439), 10.3390/cells11091439)

The authors made the following changes to their paper [1]. The authors noticed a mistake on the SF-1 results for the cell line NCI-H295 in Figure 6. A mistake happened during data transfer for graph preparation. The authors are very sorry about this error. They have now repeated the specific experiment for a total of five times; it was performed by two independent persons and with two different primer pairs (only the original primer pair is included here, but two different primer pairs were used to ensure that the effect between different SF-1 primers is consistent). Figure 6I (marked in red) was corrected from to A correction has been made to Section 3.7: The sentence “In contrast, HSD17B4 remained unchanged and the AR, ER1 and SF-1 were conversely down-regulated for NCI-H295R.For TVBF-7, again, all levels remained unchanged” was modified to “In contrast, HSD17B4 remained unchanged, SF-1 was upregulated and AR and ER1 were conversely down-regulated for NCI-H295R. For TVBF-7, again, all levels remained unchanged”. A correction has been made to Section 4, paragraphs 4 and 5: The sentence “Of note, SF-1 is a key regulator of human sex determination [39] and was upon FSK stimulation strikingly different regulated in NCI-H295R (down), MUC-1 (up) and TVBF-7 (unchanged)” was corrected to “Of note, SF-1 is a key regulator of human sex determination [39] and its activation might lead to different downstream effects in tissues of male and female origin”. The sentence “Of note, the AR was again markedly different regulated following the same patterns as observed for SF-1 in NCI-H295R (down), MUC-1 (up) and TVBF-7 (unchanged)” was corrected to “Of note, the AR was markedly differently regulated in NCI-H295R (down), MUC-1 (up) and TVBF-7 (unchanged)”. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated

Current management and outcome of pregnancies in women with adrenal insufficiency: experience from a multicenter survey

Context: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective: Multicenter survey on current clinical approaches in managing AI during pregnancy. Design: Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and Patients: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes