Patient Presentation
A 3-day-old 39 gestation female came to clinic for her first evaluation after discharge from the normal newborn nursery where she had an uneventful course. Her mother said she was feeding well every 2-3 hours and had been urinating and stooling frequency. She was very mildly jaundiced and her transcutaneous bilirubin was 7.2 mg/dL. Her pediatrician had received a notice that her newborn screening test did not have sufficient blood to be accurate and another needed to be drawn. The past medical history showed an uneventful pregnancy and vaginal delivery to a 28 year old G2P2 female. The family history was negative for any genetic abnormalities and there was some diabetes in older family members.
The pertinent physical exam showed a female who was 3.46 kg (75%, down 4.3% from birth weight), head circumference of 34.5 cm (50% unchanged) and 50 cm of length (50%) . She was mildly jaundiced in the face. Her examination was normal except that her genitalia did not appear as expected. The labia appeared fused posteriorly and her clitoris appeared larger than normal. When measured it had a length of 13 mm from the pubic ramus excluding the clitoral hood. The labia majora appeared darker in color than surrounding tissues but not excessively.
The diagnosis of of clitoromegaly was made and the pediatrician consulted a pediatric endocrinologist who agreed that more evaluation was needed right away because of the risk of congenital adrenal hyperplasia. The initial laboratory evaluation included initial testing with a slightly low serum sodium. Other testing including 17-hydroxyprogesterone, cortisol, ACTH and other hormones were pending. The patient was referred to the emergency room, where she was seen by the endocrinologist who confirmed clitoromegaly and posterior labial fusion without other abnormalities. Repeated testing had normal electrolytes at that time and she was discharged to followup in a few days with the endocrinologist. Repeat newborn screening eventually returned as normal as did the other hormones. The diagnosis of clitoromegaly without an obvious cause was made and the infant continued to be monitored by the pediatrician and endocrinologist and was doing well at 2 months of age.
Discussion
Clitoromegaly is the abnormal enlargement of the clitoris which may be congenital or acquired. The genital tubercle begins development at the 4th week of gestation and is recognizable by week 14. In the newborn, measurement of the clitorophallus should be from the pubic ramus to the tip of the structure without excess foreskin or clitoral hood tissue, with the clitorophallus stretched to the point of increased resistance. Normal values have a range in different populations. Normal values for the clitoris in females are a width of 2-6 mm and length < 9 mm is normal. Larger than these values is considered enlarged. For males the normal phallus width is 9 mm or greater and length is 2.5 cm or greater. Values less than these are considered a small phallus. Other abnormalities such as posterior fusion of the labia and palpable gonads should be noted on the examination as well.
Learning Point
Congenital adrenal hyperplasia is one of the most common causes of clitoromegaly, and the most common cause due to an enzymatic defect of the steroid pathway. Most cases are caused by 21-hydroxylase deficiency (autosomal recessive from CYP21A2 gene on chromosome 6) which causes the defective metabolism of 17-hydroxyprogesterone into 11-deoxycortisol. Therefore there will be an excess of 17-hydroxyprogesterone. The estimated incidence is 1/ 5-15,000 births. Patients are at risk for salt-wasting and adrenal crisis and may present with emesis, diarrhea, hypotension and shock. Neonatal screening identifies many of these infants.
The most common cause of clitoromegaly is due to excess androgen during fetal life, infancy or adolescence.
The differential diagnosis of clitoromegaly includes:
- Hormonal
- Congenital adrenal hyperplasia
- 5a-reductase deficiency
- Partial androgen insensitivity syndrome
- Chromosomal disorders such as mixed gonadal dysgenesis or hermaphroditis
- Steroid secreting tumor
- Luteoma of pregnancy
- Polycystic ovary syndrome
- Maternal exposure to hormonal medications including androgen, estrogen or progestins
- Various syndromes including Beckwith-Wiedemann, Klippel-Trenaunay, Proteus and Turner
- Non-hormonal
- Neurofibromatosis type 1
- Epidermal or simple cystic lesions
- Hemangiomas
- Pseudo-enlargement
- Appearance of enlargement in premature infants due to small fat pad
- Due to masturbation/manipulation in small children
- Idiopathic
Questions for Further Discussion
1. What does your local newborn screen test for?
2. How is a patient with potential intersex presentation evaluated?
3. What is the role of consultants such as endocrinology or radiology in the evaluation of a patient with possible clitoromegaly or other potential genitourinary abnormalities?
Related Cases
- Disease: Clitoromegaly | Endocrine Diseases | Birth Defects
- Symptom/Presentation: Genetic Disorder | Inborn Error of Metabolism | Syndromes
- Specialty: Endocrinology | Obstetrics / Gynecology
- Age: Newborn
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Endocrine Diseases and Birth Defect.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Iezzi ML, Lasorella S, Varriale G, Zagaroli L, Ambrosi M, Verrotti A. Clitoromegaly in Childhood and Adolescence: Behind One Clinical Sign, a Clinical Sea. Sex Dev. 2018;12(4):163-174. doi:10.1159/000489385
Hiers PS, Abi Younes RT, Haller MJ. Apparent Clitoromegaly in Healthy Female Newborn. Pediatrics In Review. 2021;42(Supplement_2):173-176. doi:10.1542/pir.2020-0043
Santi M, Graf S, Zeino M, et al. Approach to the Virilizing Girl at Puberty. J Clin Endocrinol Metab. 2020;106(5):1530-1539. doi:10.1210/clinem/dgaa948
Chan Y, Levitsky Lynne L. Evaluation of the infant with atypical genital appearance – difference of sex developent. UpToDate. Last updated March 22, 2023.
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa