In the Spotlight

Elizabeth Connor, MS4, awarded Endocrine Society Outstanding Abstract Travel Award. 

April 2, 2017

Elizabeth O'Connor, fourth-year medical student on the Savannah Campus, presented her work (abstract below) in the Endocrine Society Annual Meeting in Orlando, Florida, in April 2017.  Elizabeth O'Connor was the recipient of an Endocrine Society Outstanding Abstract Award, a travel award, to present this work at this meeting. 

Vaginal Vault Prolapse and Bilateral Adrenal Hyperplasia in a 46, XY Infant with a Homozygous Mutation of the CYP11A1 Gene, Ambiguous Genitalia and Adrenal Insufficiency

Elizabeth O'Connor1, Jasmeet Kaur, PhD1, Alan Michael Rice, MD1, Anil Piya, MD1, Bradley Buckler, MD2 and Himangshu S Bose, Ph.D.3,

(1) Laboratory of Biochemistry, Mercer University School of Medicine, Savannah, GA, (2) Department of Pediatrics, Mercer University School of Medicine, Savannah, GA, (3) Department of Biomedical Sciences, Mercer University, Savannah, GA.

The presence of adrenal enlargement has been considered to be inconsistent with the presence of cholesterol side-chain cleavage enzyme (SCC) deficiency. In spite of multiple reports of adrenal imaging studies of individuals with SCC deficiency revealing only small or normal size adrenal glands, the term “congenital adrenal hyperplasia” has been used when describing individuals with clinical manifestations of SCC deficiency. To our knowledge, this is the first time that adrenal hyperplasia has been confirmed in a patient with an adrenal insufficiency-inducing mutation of the gene encoding SCC, CYP11A1. The proband’s mother had a history of two spontaneous abortions, and another child, thought to be female, died 10 days after birth at 23-weeks and 5-days gestational age (GA). Due to the prior miscarriages and extremely premature live-born infant, the mother received weekly 17-alpha hydroxyprogesterone caproate (17P) injections from the 16 to the 35 week of the pregnancy with the proband. Shortly after a C-section due to a placental abruption at 36-weeks and 1-day GA, the infant was found to have generalized hyperpigmentation, a urethral opening at the ventral base of a 5-mm wide phallic structure, a prolapsed vaginal vault prolapse with partial posterior labial-scrotal fusion, no palpable gonads, clinical and laboratory evidence of adrenal failure, and a 46, XY karyotype. Prior to onset of glucocorticoid and mineralocorticoid replacement, circulating levels of corticoadrenal steroids were low, and an adrenocorticotropic hormone level was elevated. A pelvic and abdominal MRI revealed large adrenal glands and absence of Müllerian structures. By three months of age, the phallic structure was smaller and the vaginal vault was no longer protruding. Because of the enlarged adrenal glands, lipoid congenital adrenal hyperplasia due to a StAR gene mutation was initially suspected. However, StAR gene abnormalities were not identified. Subsequent analysis of CYP11A1, however, revealed that the patient’s adrenal insufficiency and ambiguous genitalia were due to a homozygous mutation in exon 5 of CYP11A1 that resulted in a truncated protein of 286 amino acids as compared to wild-type protein that has 521 amino acids (W286X). Analysis of parental CYP11A1 revealed that both parents were carriers of the mutation. So this patient’s ambiguous genitalia and adrenal insufficiency were due to impaired conversion of cholesterol to Pregnenolone by SCC in mitochondria. Our findings reveal that patients with SCC deficiency can present with adrenal hyperplasia and vaginal vault prolapse. Our findings also raise the possibility that maternal 17P therapy during the pregnancy may alter the clinical presentation of SCC deficiency.

For pictures from the meeting, see our Facebook page