Issue: March 2011
March 01, 2011
2 min read

Clitoromegaly: A rare clinical finding in extremely premature infants

Issue: March 2011
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Canadian Pediatric Endocrine Group

TORONTO — Researchers at the University of Calgary have reported four cases of clitoromegaly of unknown etiology in extremely premature infants that appears to resolve spontaneously.

Four babies were born at 24 to 28 weeks gestation with normal genital anatomy and developed clitoromegaly about 10 weeks after birth.

“They had isolated clitoromegaly with no other signs of puberty,” Munier Nour, MD, a pediatric endocrinology fellow in the department of pediatric endocrinology at Alberta Children's Hospital, University of Calgary, said. “It was a transient process. All the cases eventually resolved on their own.”

Nour noted that clitoromegaly in the extremely premature infant is extremely rare. He and his colleagues found just two other documented cases of transient-acquired clitoromegaly in the medical literature. The cases were associated with significantly elevated androgen levels and spontaneous resolution.

According to the researchers’ review, there were no common characteristics of the mothers, except all were aged between 30 and 35 years. Common medications were administered, including ampicillin, caffeine, gentamicin, fluconazole, iron and furosemide.

The researchers noted several unifying features, such as birth weight less than 750 g, treated sepsis, prophylactic fluconazole use, PDA requiring medical or surgical closure and treatment in the same nursery.

According to laboratory results, all patients had the 46,XX karotype, elevated androstenedione (27.3 nmol/L to 35 nmol/L) and normal 17-hydroxyprogesterone. In addition, estradiol and gonadotropin levels, specifically luteinizing hormone (24 U/L to 42 U/L) and follicle-stimulating hormone (126 U/L to 146 U/L), were elevated in three of the four cases.

A “striking” observation of elevated androgen levels was observed in the four cases, with testosterone measuring 4.9 nmol/L to 11.8 nmol/L.

“There is nothing significant that unifies these patients other than significantly elevated androgens,” Nour told Endocrine Today.

One patient was treated with Lupron, but Nour said it is unlikely that the treatment was related to resolution of clitoromegaly. In all cases, there was normalization of androgen and gonadotropin levels with resolution of the condition.

“We have no idea what caused it," Nour said. To date, no unifying diagnosis has been identified for clitoromegaly. Nour said some speculation has been an endocrine disruptor in the form of commonly used medications or medical apparatus.

The researchers said further study is needed to understand the pathophysiology and projected clinical course.

“We want to look at the entire NICU population and test biochemical profiles at similar gestational age and see if there are silent cases we are missing,” Nour said – by Louise Gagnon

For more information:

Disclosure: Dr. Nour reports no relevant financial disclosures.


The question is if it is a real elevation in androstenedione or is it what we know about premature babies, that we tend to get higher values on assays because of interfering substances. It may be real, but it may be over-read because the androstenedione values were very high. It's important that they follow their patients.

Diane Wherrett, MD, FRCPC

Associate Professor, Department of Pediatrics
University of Toronto, The Hospital for Sick Children

Disclosure: Dr. Wherrett is a member of an advisory board or equivalent with Eli Lilly and has received a grant or honorarium from Medtronic.

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