Genetska etiologija prijevremene insuficijencije jajnika

Primary premature ovarian insufficiency (PPOI) is characterized by hypergonadotropic amenorrhea and hypoestrogenism in women under 40 years of age. PPOI incidence is 1:10,000 in women aged 18-25, 1:1000 in women aged 25-30 and 1:100 in women aged 35-40. In 10%-28% of cases, PPOI causes primary and in 4%-18% secondary amenorrhea. The process is a consequence of accelerated oocyte atresia, diminished number of germinated cells, and central nervous system aging. Specific genes are responsible for the control of oocyte number undergoing the ovulation process and the time to cessation of the reproductive function. A positive family history of PPOI is found in 15% of women with PPOI, indicating the existing genetic etiology. Primary POI comprises genetic aberrations linked to chromosome X (monosomy, trisomy, translocation, deletion) or to autosomal chromosome. Secondary POI implies surgical removal of ovaries, chemotherapy and radiotherapy, and infections. Diagnostic criteria include follicle stimulating hormone level >40 IU/L and estradiol level <50 pmol/L.Primarna prijevremena insufi cijencija jajnika (PPIJ) je sindrom koji je obilježen hipergonadotropnom amenorejom i hipoestrogenizmom. Incidencija PPIJ je 1:10.000 kod žena starosti 18-25 godina, 1:1000 kod žena starosti 25-30 godina i 1:100 kod žena starosti 35-40 godina. U 10%-28% slučajeva PPIJ je uzrok primarnih, a u 4%-18% sekundarnih amenoreja. Bolest nastaje kao posljedica ubrzanog procesa atrezije oocita, smanjenja broja germinativnih stanica i starenja središnjeg živčanog sustava. Specifi čni geni su odgovorni za kontrolu broja oocita koji prolaze proces ovulacije i vrijeme prekida repro- duktivne funkcije. Pozitivna obiteljska anamneza PPIJ nađena je u oko 15% žena s PPIJ, što ukazuje na postojanje određene genetske etiologije. Primarna insufi cijencija jajnika (PIJ) dijeli se na primarnu i sekundarnu. U primarnu PIJ spadaju genetske aberacije vezane za kromosom X (monosomije, trisomije, translokacije, delecije) ili one vezane za autosomne kromosome. U sekundarnu PIJ spadaju kirurško odstranjenje jajnika, liječenje kemoterapijom i radioterapijom te infekcije. Simptomi su razdražljivost, nemir, gubitak libida, depresija, nesanica, dekoncentracija, napadaji vrućine, povišenje tjelesne težine, suhoća vagine i drugih sluznica. Kriteriji za dijagnozu su folikulostimulirajući hormon viši od 40 IJ/L i estradiol (E2) niži od 50 pmol/L kod žena mlađih od 40 godina

Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

BACKGROUND Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined. OBJECTIVE To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS. DESIGN Cross-sectional study. SETTING 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016). PARTICIPANTS 1305 prospectively recruited persons with benign adrenal tumors. MEASUREMENTS Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: 138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry. RESULTS Of the 1305 participants, 49.7% had NFAT ( = 649; 64.1% women), 34.6% had MACS-1 ( = 451; 67.2% women), 10.7% had MACS-2 ( = 140; 73.6% women), and 5.0% had CS ( = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased. LIMITATIONS Cross-sectional design; possible selection bias. CONCLUSION A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes. PRIMARY FUNDING SOURCE Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research