Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made ...in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
Insulin resistance is a state in which higher than normal concentrations of insulin are required for normal response. The most common underlying cause is central obesity, although primary insulin ...resistance in normal-weight individuals is also possible. Excess abdominal adipose tissue has been shown to release increased amounts of free fatty acids which directly affect insulin signalling, diminish glucose uptake in muscle, drive exaggerated triglyceride synthesis and induce gluconeogenesis in the liver. Other factors presumed to play the role in insulin resistance are tumour necrosis factor α, adiponectin, leptin, IL-6 and some other adipokines. Hyperinsulinaemia which accompanies insulin resistance may be implicated in the development of many pathological states, such as hypertension and hyperandrogenaemia. Insulin resistance underlies metabolic syndrome and is further associated with polycystic ovary syndrome and lipodystrophies. When β-cells fail to secrete the excess insulin needed, diabetes mellitus type 2 emerges, which is, besides coronary heart disease, the main complication of insulin resistance and associated diseases.
Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic ...disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk, which worsens with severity of androgen excess. Due to methodological difficulties, longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.
The COVID-19 pandemic has strongly affected global healthcare systems. Prior epidemiological studies on different infectious diseases have shown a strong correlation between serum vitamin D levels ...and the incidence of certain infectious diseases. Vitamin D has an important immunomodulatory effect on innate immunity and exhibits several other mechanisms in the pathogenesis of the cytokine storm, which is one of the main contributing factors to fatality in COVID-19 patients.
A keyword search was conducted in the PubMed and Google Scholar research databases. The abstracts and/or full texts of selected papers were further evaluated. Articles that fulfilled the inclusion criteria were included in the systematic review.
The 28 studies summarized in this review provide observational findings that vitamin D levels are related to the incidence, severity, and mortality rate of COVID-19 infection. The literature does not suggest that COVID-19 could be eliminated with supplementation of vitamin D, but there are implications that vitamin D deficiency might increase the risk for COVID-19 infection and severity of the disease progression.
Current literature and several guidelines support the supplementation of vitamin D as a reasonable strategy for correcting and preventing vitamin D deficiency. The recommended dose for maintaining normal 25(OH)D levels by consensus is 1000 to 2000 IU vitamin D daily for at-risk teens and adults.
Vitamin D supplementation might play an important role in protecting from acute respiratory infections like the SARS CoV2, and in high-risk individuals with COVID 19 from progressing to critical clinical condition and reducing mortality.
ObjectiveThe European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS).Design and methodsBaseline data on 481 CS ...patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%).ResultsProportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups.ConclusionsThe ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.
Adrenal failure and antiphospholipid syndrome Mlekuš Kozamernik, Katarina; Jensterle, Mojca; Ambrožič, Aleš ...
Journal of international medical research,
07/2020, Letnik:
48, Številka:
7
Journal Article
Recenzirano
Odprti dostop
We herein report two cases of primary adrenal insufficiency (AI) associated with antiphospholipid syndrome (APS). In both patients, the main finding that led to the diagnosis was hyponatraemia. The ...major difference between the two cases was the time at which AI evolved during the course of APS. In the first patient, AI developed acutely along with other presenting features of APS. In the second patient, the AI was unmasked during a stressful situation induced by severe inflammation that occurred 7 years after the first APS manifestation and had probably evolved slowly during the previous few years. These cases emphasise the importance of considering AI in patients with either suspected or newly diagnosed APS as well as in patients who have long been known to have APS. The symptoms and signs alerting the clinician to possible AI are general abdominal complaints, fever, hypotension, and hyponatraemia. Conversely, patients with primary AI should be questioned about the signs and symptoms of APS.
Slovenska medicinska akademija (SMA), katere poslanstvo je tudi spodbujanje znanstveno-raziskovalnega dela, je organizirala okroglo mizo o pomenu in stranpoteh znanstveno-raziskovalnega dela v ...medicini. Sodelujoči so poudarili, da je znanost vodilna sila razvoja na vseh področjih življenja, vključno z medicino. Znanstveno-raziskovalno delo neposredno koristi medicinski praksi in omogoča bolj kakovostno obravnavo bolnikov. Medicinska znanost je v primerjavi z drugimi vedami v posebnem položaju, saj je večina raziskav povezana s poseganjem v telesno integriteto človeka. Zato mora biti pod drobnogledom nadzornih struktur, ki skrbijo za varnost in etičnost ravnanja na tem področju. Potrebno je pred samim začetkom etično oceniti vsako medicinsko raziskavo, kar opravlja Komisija za medicinsko etiko RS. Znanstvena dejavnost v medicini je glede financiranja v neenakopravnem položaju z raziskovalnim delom na številnih drugih področjih, saj so klinični zdravniki in zdravniki na obeh medicinskih fakultetah lahko raziskovalci le manjši del svojega delovnega časa. Celo na terciarnih ustanovah so raziskovalci entuziasti, ki opravljajo raziskovalno delo v svojem prostem času. Žal je tudi medicinska znanost neredko izpostavljena dejavnikom, ki ogrožajo njeno nevtralnost in objektivnost, ker je v ospredju tekmovalnost in interes institucij, od katerih je raziskovalno delo finančno odvisno. Prihaja do improvizacij in hitenja z objavami delnih rezultatov še pred zaključkom kompleksnih raziskav. V akademski sferi so vedno večji pritiski, saj so objave, čeprav tudi za lase privlečenih rezultatov, pogoj za napredovanje. Raziskovalec je neredko odvisen od financiranja raziskav od sponzorjev (zlasti farmacevtske industrije), ne pa od neodvisnih finančnih virov, kar lahko vpliva na verodostojnost rezultatov. V zadnjih letih se klasičnim raziskavam pridružujejo raziskave, ki uporabljajo umetno inteligenco. Analiza rezultatov, ki jo opravi umetna inteligenca, je neprimerno hitrejša in natančnejša, a ne vedno pravilnejša. Tudi uporabo umetne inteligence spremljajo pasti. Ni namreč vedno jasno, ali je besedilo napisal človek ali umetna inteligenca, kar odmika odgovornost za objavljene rezultate. Poleg tega se na internetnih zapisih pojavljajo tudi izmišljotine, ki postavljajo pod vprašaj verodostojnost poročanja o ugotovitvah raziskav. Znanost je gonilo razvoja medicine, mora pa biti vrednotenjsko nevtralna in temeljiti na preverjenih dejstvih.
Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone.
F-fluorocholine (FCH), PET marker of ...cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism.
43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUV
), retention index and lesion contrast for parathyroid and thyroid tissue were calculated.
Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUV
in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05).
According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH.
ObjectiveAccumulating evidence connects polycystic ovary syndrome (PCOS) with increased risk of cardiovascular disease. Endothelial dysfunction is present in PCOS and represents an early, reversible ...marker of cardiovascular damage. As androgens and renin–angiotensin–aldosterone system are implicated in the atherogenesis process of PCOS, we tested the hypothesis that treatment with spironolactone, an androgen and mineralocorticoid receptor blocking drug, might reverse endothelial dysfunction in PCOS.PatientsA total of 30 non-obese PCOS patients, compared with 20 body mass index matched control subjects, were evaluated. PCOS patients were given spironolactone 100 mg daily in 21-day long intervals followed by a 7-day pause, for 6 months.MeasurementsFlow-mediated dilatation (FMD), glyceryl trinitrate-induced dilatation, free testosterone, androstenedione, DHEA-sulfate, total, low-density lipoprotein (LDL)-, high-density lipoprotein-cholesterol, and triglycerides were determined at baseline and after 6 months.ResultsResults are expressed as median (25–75th percentile). At baseline, FMD was significantly lower in PCOS patients than in controls: 6.0 (0.0–11.7) vs 10.2 (6.8–15.9) %, P=0.018. This difference disappeared after 6 months of spironolactone treatment, as FMD in PCOS patients significantly increased to 8.3 (5.7–10.3) %, P=0.034, and was no longer different from controls. In PCOS patients, serum androgen levels did not change during treatment, while total and LDL-cholesterol decreased significantly from 4.8 (4.1–5.1) mmol/l to 4.4 (3.9–4.8) mmol/l and from 2.5 (2.1–3.1) to 2.2. (2.1–2.5) mmol/l, P<0.05 and P<0.05 respectively.ConclusionTreatment with spironolactone normalized endothelial function and improved cholesterol levels in non-obese PCOS patients.
LHX4 is a LIM homeodomain transcription factor involved in the early steps of pituitary ontogenesis. To date, 8 heterozygous LHX4 mutations have been reported as responsible of combined pituitary ...hormone deficiency (CPHD) in Humans. We identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R. Our objective was to determine the role of LHX4 variants in patients' phenotypes. Heterologous HEK293T cells were transfected with plasmids encoding for wild-type or mutant LHX4. Protein expression was analysed by Western Blot, and DNA binding by electro-mobility shift assay experiments. Target promoters of LHX4 were cotransfected with wild type or mutant LHX4 to test the transactivating abilities of each variant. Our results show that the W204X mutation was associated with early GH and TSH deficiencies and later onset ACTH deficiency. It led to a truncated protein unable to bind to alpha-Gsu promoter binding consensus sequence. W204X was not able to activate target promoters in vitro. Cotransfection experiments did not favour a dominant negative effect. In contrast, all other mutants were able to bind the promoters and led to an activation similar as that observed with wild type LHX4, suggesting that they were likely polymorphisms. To conclude, our study underlines the need for functional in vitro studies to ascertain the role of rare allelic variants of LHX4 in disease phenotypes. It supports the causative role of the W204X mutation in CPHD and adds up childhood onset ACTH deficiency to the clinical spectrum of the various phenotypes related to LHX4 mutations.
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