Flatter diurnal cortisol slopes contribute to stress-related dysregulation of central and peripheral circadian mechanisms with negative health outcomes.Due to hyperandrogenism, females may present with symptoms like hirsutism, oligomenorrhea, acne, infertility, and male-pattern baldness.Males are generally asymptomatic, but may present with acne, early balding, chronic prostatitis, chronic pelvic pain syndrome, and very rarely, testicular adrenal rest tumors.While symptoms are usually diagnosed after puberty, children may present with premature adrenarche.The degree of hormonal disorder in patients with LOCAH is relatively mild. However, alterations in the hypothalamic–pituitary–adrenal axis are present even in this mild form of the disease and might contribute to psychiatric vulnerability. Molecular genetics
LOCAH is most commonly attributed to mutations in the CYP21A2 gene, which encodes the 21-hydroxylase enzyme. Cases of LOCAH due to deficiencies in other enzymes that are known causes of CAH (3β-hydroxysteroid dehydrogenase, steroid 11β-hydroxylase, etc.) are rare and have no established prevalence estimates.Several severe mutations have been associated with LOCAH: the deletion of the CYP21A2 gene, small gene conversions, the p. I172N (rs6475, c.518T>A, CYP21A2*11) mutation, the c.293-13A/C>G (rs6467, CYP21A2*9) mutation, and the p.Gln318Stop (p.Q318X, rs7755898, c.952C>T, CYP21A2*17) mutation. Besides that, LOCAH due to 21-hydroxylase deficiency can be caused by duplications of CYP21A1P pseudogene and C4B gene. Due to the high degree of homology between the CYP21A2 gene and the CYP21A1P pseudogene, and the complexity of the locus, research on the sequencing level can be difficult.
Women taking gemcitabine should not become pregnant, and pregnant and breastfeeding women should not take it.As of 2014, drug interactions had not been studied. Adverse effects
Gemcitabine is a chemotherapy drug that works by killing any cells that are dividing. Cancer cells divide rapidly and so are targeted at higher rates by gemcitabine, but many essential cells also divide rapidly, including cells in skin, the scalp, the stomach lining, and bone marrow, resulting in adverse effects. : 265 The gemcitabine label carries warnings that it can suppress bone marrow function and cause loss of white blood cells, loss of platelets, and loss of red blood cells, and that it should be used carefully in people with liver, kidney, or cardiovascular disorders. People taking it should not take live vaccines. The warning label also states it may cause posterior reversible encephalopathy syndrome, that it may cause capillary leak syndrome, that it may cause severe lung conditions like pulmonary edema, pneumonia, and adult respiratory distress syndrome, and that it may harm sperm.More than 10% of users develop adverse effects, including difficulty breathing, low white and red blood cells counts, low platelet counts, vomiting and nausea, elevated transaminases, rashes and itchy skin, hair loss, blood and protein in urine, flu-like symptoms, and edema.Common adverse effects (occurring in 1–10% of users) include fever, loss of appetite, headache, difficulty sleeping, tiredness, cough, runny nose, diarrhea, mouth and lip sores, sweating, back pain, and muscle pain.Thrombotic thrombocytopenic purpura (TTP) is a rare but serious side effect that been associated with particular chemotherapy medications including gemcitabine.