title: Case report: Adrenal LH/hCG receptor overexpression and gene amplification causing pregnancy-induced Cushing's syndrome.
abstract: Transient pregnancy-induced Cushing's syndrome (CS) is extremely rare, with only several cases reported in the literature. Ectopic LH/hCG-receptors (LHCGR) in the adrenal gland have been suggested to be involved in the pathogenesis of this condition. We report the clinical, molecular, and genetic features of a patient with pregnancy-induced CS. A 29-year-old female patient developed CS during multiple pregnancies, leading to repeated miscarriage. Signs and symptoms of hypercortisolism resolved soon after delivery or abortion, only to recur in subsequent pregnancies. In the non-pregnant state, hCG stimulation testing resulted in elevated cortisol levels. Serum cortisol was not suppressible with dexamethasone. The adrenals exhibited bilateral adrenal cortical nodular hyperplasia. Quantitative RT-PCR revealed a 2-fold increase in LHCGR and progesterone receptor mRNA expression and decreased estrogen receptor-beta expression in the patient's adrenal tissue relative to normal adrenals. Higher intensity of immunostaining for LHCGR was observed, particularly within the nodular lesions, compared to controls. Quantitative PCR revealed a LHCGR-to-beta-actin ratio of 1.5 in genomic DNA from adrenal and peripheral leukocytes, suggesting the presence of a germline duplication of the LHCGR gene. LHCGR overexpression resulting from germline gene duplication may be a potential pathogenic mechanism underlying this case of pregnancy-induced CS.
authors.affiliation: Department of Pathology, University Health Network, Toronto, ON, Canada M5G 2C4.
authors.forename: Michael Herman
authors.initials: MH
authors.lastname: Chui
authors.forename: Michael
authors.initials: M
authors.lastname: Herman Chui
authors.forename: Nese Colak
authors.initials: NC
authors.lastname: Ozbey
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.forename: Yersu
authors.initials: Y
authors.lastname: Kapran
authors.forename: Yesim
authors.initials: Y
authors.lastname: Erbil
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology; D000302:Adrenal Cortex / Q000473:pathology*; D000311:Adrenal Glands / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000315:Adrenalectomy; D000328:Adult; D006063:Chorionic Gonadotropin; D003480:Cushing Syndrome / Q000209:etiology* / Q000601:surgery; D003907:Dexamethasone; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006965:Hyperplasia; D007962:Leukocytes / Q000737:chemistry; D011247:Pregnancy; D011248:Pregnancy Complications; D012333:RNA, Messenger / Q000032:analysis; D018043:Receptors, Corticotropin / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006063:Chorionic Gonadotropin; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D011974:Receptors, LH; D011980:Receptors, Progesterone; D003907:Dexamethasone; D006854:Hydrocortisone
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