Congenital Adrenal Hyperplasia Cah

This study will evaluate and gather information in patients with genetic causes of too much androgen (male-like hormone) in order to better understand the effects of too much androgen and describe problems associated with it. Too much androgen in childhood, if untreated, results in rapid growth and early puberty with early cessation of growth and short stature in adulthood. Too much androgen in adulthood may result in infertility, and women may have excess facial hair, acne and a more male-like appearance. Excess androgen may also affect mood and behavior and possibly the secretion of other hormones, such as insulin. Two genetic diseases that result in early childhood androgen excess are congenital adrenal hyperplasia (CAH) and familial male-limited precocious puberty (FMPP). Patients with known or suspected CAH due to 21-hydroxylase deficiency, 11- hydroxylase deficiency, or 3-beta-hydroxysteroid dehydrogenase deficiency and males with known or suspected FMPP may be eligible for this study. Patients with both classic and non-classic CAH are eligible, and patients with androgen excess of unknown cause may be eligible. Participants undergo the following procedures: * Medical history and physical examination. * Fasting blood tests for analysis of hormones, blood chemistries including blood sugar and cardiovascular risk factors such as lipids. * Oral glucose tolerance test for patients with elevated insulin levels. For this test, a catheter (plastic tube) is placed in a vein in the patient's arm. The patient drinks a sugar-containing fluid and blood samples are collected through the catheter at intervals starting with drinking the solution, and then 30, 60 and 120 minutes after drinking the solution. * 24-hour urine collection to measure hormone levels in the urine. * DNA testing for patients with 21-hydroxylase deficiency to help identify the type of genetic mutation responsible for the disease. * X-ray of the left hand to measure bone age in growing children. The x-ray is used to determine how far into puberty the child is and how much growth potential is left in the bones. * A pelvic ultrasound in females and testicular ultrasound in males to evaluate the size and development of the gonads (ovaries in females and testes in males). * Cognitive and psychological tests, including an IQ test and evaluation of memory, achievement and behavior. * Other tests and evaluations based on medical need. The schedule for these procedures varies. In a part of the study involving only patients with CAH, growing children are evaluated twice (once in childhood and once after reaching adult height), and adults are evaluated once. In another part of the study involving patients with CAH and FMPP, growing children are seen twice a year, and adults and children who have reached adult height may be seen annually. Additional visits may be scheduled if medically indicated. In this part of the study, females are asked to keep a record of their periods after their first menstrual cycle.

Neonatal salt loss can be caused not only by infections but also by rare endocrine disorders that resemble 21-hydroxylase deficiency but are not detected by neonatal screening. This study examines how often these conditions occur and describes their main clinical, genetic, and treatment features.

This is a multicenter study designed to assess the effects of groundbreaking CAH therapies on a spectrum of clinical and biochemical outcomes, with a special emphasis on reproductive and sexual health. Fertility is a profound concern for individuals with CAH, given the high prevalence of gonadal dysfunction that arises from the hormonal derangements that characterize this complex disease. At our endo-ERN accredited center for rare diseases at Policlinico Umberto I, addressing these fertility issues in CAH patients represents a daily commitment. The revolution of the pharmacological management of CAH is one of the most debated topics to date. Data on the effects of novel management options for CAH on fertility are scarce, but the anecdotal improvements in sperm count and menstrual regularity reported in the latest clinical trials have significantly motivated us to design the CALLIOPE study. Thus, we aim to delve deeper into the fertility and sexual function of CAH patients, employing advanced seminal parameter evaluations, multiparametric gonadal ultrasound, and sophisticated hormonal analyses in both females and males performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Beyond fertility, the CALLIOPE trial aspires to provide further understanding of therapy's effects on body composition, metabolism, immune function, coagulation, and quality of life, among other factors. We will explore the immunological impact of novel CAH therapies by quantifying Peripheral Blood Mononuclear Cells (PBMCs) and analyzing transcriptomic profiles to unveil gene expression patterns and identify biomarkers that could signal therapeutic targets or disease management strategies in CAH. Moreover, seminal plasma will be used to assess the expression of adrenal miRNAs regulating steroidogenesis and metabolism. The research will be conducted at our rare disease referral center (Policlinico Umberto I, Sapienza University of Rome) in collaboration with leading centers across Italy: Modena (Università degli Studi di Modena e Reggio Emilia), Naples (Università Federico II), Rome (Ospedale Sant'Andrea) and Bologna (Alma Mater Studiorum - Università di Bologna). https://isidorilab.com/home