{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:01:11Z","timestamp":1790290871721,"version":"4.1.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The most severe form of congenital adrenal hyperplasia (CAH) is lipoid CAH. It was once thought that this disease was due to mutations in the cholesterol side-chain cleavage enzyme system, thus eliminating the ability to convert cholesterol to pregnenolone, causing a complete absence of steroid hormone production. We recently showed that lipoid CAH is due to mutations in the steroidogenic acute regulatory (StAR) protein, thus preventing acutely stimulated adrenal and gonadal responses to tropic stimulation. However, this lesion may permit low levels of StAR-independent steroidogenesis to persist until the accumulation of intracellular lipid deposits destroys steroidogenic capacity. This model would predict that the steroidogenic cells of the ovaries of affected 46,XX females should remain undamaged until puberty, at which time low levels of StAR-independent estrogen biosynthesis should be detectable. We describe a 15.5-yr-old 46,XX female with a classic history of lipoid CAH who underwent spontaneous feminization and cyclical vaginal bleeding beginning at age 13. Genetic analysis of the patient and her parents showed that she was homozygous for the novel StAR frameshift mutation 261delT. This is the first adolescent female with lipoid CAH who has undergone spontaneous feminization and who has been analyzed genetically. Finding an inactive StAR gene in this patient confirms our two-hit model of the pathogenesis of lipoid CAH, in which loss of StAR activity initially preserves StAR-independent steroidogenesis, which is lost only after cells undergo chronic tropic stimulation and subsequent damage from accumulation of cholesterol esters.<\/jats:p>","DOI":"10.1210\/jcem.82.5.3962","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:45Z","timestamp":1389200505000},"page":"1511-1515","source":"Crossref","is-referenced-by-count":7,"title":["Spontaneous Feminization in a 46,XX Female Patient with Congenital Lipoid Adrenal Hyperplasia Due to a Homozygous Frameshift Mutation in the Steroidogenic Acute Regulatory Protein*"],"prefix":"10.1210","volume":"82","author":[{"given":"Himangshu S.","family":"Bose","sequence":"first","affiliation":[{"name":"Department of Pediatrics (H.S.B., W.L.M.), San Francisco, California 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ora Hirsch","family":"Pescovitz","sequence":"additional","affiliation":[{"name":"The Department of Pediatrics (O.H.P.), Indiana University Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (H.S.B., W.L.M.), San Francisco, California 94143;"},{"name":"the Metabolic Research Unit (W.L.M.), University of California San Francisco, San Francisco, California 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071615355702800_R1","first-page":"397","article-title":"Das Syndrom des Pseudohermaphroditismus masculinus bei kongenitaler Nebennierenrindenhyperplasie ohne Androgenuberproduktion (adrenaler Pseudohermaphroditismus masculinus).","volume":"10","author":"Prader","year":"1955","journal-title":"Helv Paediatr Acta"},{"key":"2020071615355702800_R2","first-page":"569","article-title":"Nebenniereninsuffizienz bie kongenitaler Lipoidhyperplasie der Nebennieren.","volume":"12","author":"Prader","year":"1957","journal-title":"Helv Paediatr Acta"},{"key":"2020071615355702800_R3","first-page":"305","article-title":"Hochgradige Verfettung der Nebenniere eines Sauglings.","volume":"16","year":"1913","journal-title":"Verh Dtsch Ges Pathol"},{"key":"2020071615355702800_R4","first-page":"203","article-title":"Hochgradige Lipoidhyperplasie beider Nebennieren mit herdformigen Kalkablagerunger bei einem Fall von Hypospadiasis penisscrotalis und doppelseitigem Kryptorchismus mit unechter akzessorischer Nebenniere am rechten Hoden (Pseudohermaphroditismus masculinus externus).","volume":"24","year":"1920","journal-title":"Frankf Z Pathol"},{"key":"2020071615355702800_R5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1136\/adc.30.154.538","article-title":"A form of lipoidosis of the adrenal cortex 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