title: Ovarian hyperthecosis in the setting of portal hypertension.
abstract: Hepatocellular dysfunction and perturbed portal hemodynamics alter steroid metabolism. Men with liver disease have gynecomastia, although women similarly affected rarely show virilization. We report a 10-yr-old girl with portal hypertension and shunting associated with precocious puberty and ovarian hyperandrogenism. This was one of premature twin girls; neither had clitoromegaly or genital ambiguity. In one child, neonatal respiratory problems led to umbilical vein catheterization with subsequent development of portal hypertension. Pubic hair was first noted at age 6 yr, breasts at 7 yr, and severe acne and clitoromegaly at 10 yr. Baseline sex hormones were elevated: androstenedione (A), 413 ng/dL; testosterone (T), 226 ng/dL; and estradiol (E2), 160 pg/mL. Liver transaminases were within the normal range, however, the coagulation profile was mildly abnormal. Cosyntropin adrenal stimulation revealed no steroidogenic defect. Dexamethasone suppression reduced A and T slightly. LH-releasing hormone stimulation produced a pubertal rise in LH and FSH. Pelvic sonography showed a large right ovary with numerous follicles. Surgical exploration revealed symmetrically enlarged ovaries with dense capsules. Histology of ovarian wedge resections showed hyperthecosis; immunohistochemistry showed stromal cells expressing steroidogenic enzymes and proteins. One month postoperatively, A and T were unchanged from baseline, whereas E2 decreased to 56 pg/mL. A single dose of depot leuprolide acetate significantly reduced T. Subsequent treatment with oral contraceptives reduced T to 50 ng/dL, and cyclical menses occurred. We conclude that precocious puberty and ovarian hyperthecosis were induced in this young girl by elevated circulating levels of sex hormones, a consequence of portasystemic shunting and impaired hepatic steroid metabolism.
authors.affiliation: Department of Pediatrics, North Shore University Hospital, New York University School of Medicine, Manhasset 11030, USA. speiser@nshs.edu
authors.forename: P W
authors.initials: PW
authors.lastname: Speiser
authors.forename: M
authors.initials: M
authors.lastname: Susin
authors.forename: H
authors.initials: H
authors.lastname: Sasano
authors.forename: S
authors.initials: S
authors.lastname: Bohrer
authors.forename: J
authors.initials: J
authors.lastname: Markowitz
mesh_terms: D000735:Androstenedione / Q000097:blood; D002648:Child; D003276:Contraceptives, Oral / Q000627:therapeutic use; D004200:Diseases in Twins; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006975:Hypertension, Portal / Q000150:complications*; D007150:Immunohistochemistry; D016729:Leuprolide / Q000627:therapeutic use; D010049:Ovarian Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011629:Puberty, Precocious / Q000209:etiology; D013739:Testosterone / Q000097:blood; D013799:Theca Cells / Q000473:pathology*
chemical_list: D003276:Contraceptives, Oral; D012739:Gonadal Steroid Hormones; D013739:Testosterone; D000735:Androstenedione; D016729:Leuprolide