Abstract
Introduction: Clitoromegaly presenting in childhood can be congenital or acquired. The most common cause is exposure to excess androgens in fetal or neonatal life. However, non-hormonal causes like neurofibromatosis type 1 (NF-1), epidermoid cysts, tumor syndromes have been reported. An asymmetric or irregular appearing clitoris is usually caused by a non-hormonal process. Clinical Case: A 6-year-old female with NF-1 and right-sided hemihypertrophy was referred to endocrinology due to progressive clitoromegaly since birth. NF-1 features included café-au-lait spots, bilateral optic nerve gliomas, plexiform neurofibroma, Lisch nodule, first degree relatives with NF-1 (sister and mother). At age 1.5, a hormonal work up was negative for hyperandrogenism. At age 2, patient was seen by genetics, and by urology for removal of a bladder neurofibroma, but did not return to these specialties for follow up. Lumbar spine MRI, obtained for back pain, revealed a large sciatic plexiform neurofibroma. She followed with oncology for cancer surveillance and due to parental concern for progressive clitoromegaly was referred to endocrinology at age 6. At the endocrinology visit, parents denied breast development, vaginal discharge or bleeding, axillary or pubic hair, body odor or acne. Her genital exam revealed a clitoris 3 x 1.5 cm in size, Tanner 1 pubic hair, no palpable gonads, no labial fusion but asymmetric labial sizes (right>left). A hormonal workup was normal including 41 ng/dL 17-hydroxyprogesterone (n ≤137 ng/dL), 20 ng/dL androstenedione (n ≤ 45 ng/dl), 42 ng/dL unconjugated DHEA (n ≤ 487 ng/dL), 11 mcg/dL DHEA Sulfate (n ≤ 34 mcg/dL), 3 ng/dL total testosterone (n ≤ 21 ng/dL) and pre-pubertal LH, FSH and estradiol levels. Patient was referred to a multi-disciplinary DSD (Disorders of Sexual Differentiation) clinic for further evaluation and potential surgical options. A pelvic ultrasound and subsequent pelvic MRI revealed that the large sciatic plexiform neurofibroma, detected on the prior MRI, had now extended into the clitoris and right labia. Uterus and ovaries were pre-pubertal in size. Surgical options were discussed in a multi-disciplinary approach. Since clitoral enlargement was contiguous with posterior bladder mass and vital organ functions were not affected, resection was not recommended. Clitoral reduction for cosmetic reasons had a potential risk of recurrence. Since benefits did not outweigh the risks, family chose to not pursue any surgical intervention. Conclusions: NF-1 is a rare but potential non-hormonal cause of clitoromegaly. In the absence of clinical evidence of hyperandrogenism, clitoromegaly in a patient with NF-1 does not warrant an extensive hormonal work up. Pelvic imaging should be pursued first, to search for local neurofibromas. Decision for surgical interventions requires a multi-disciplinary approach with detailed discussion of benefits vs. risks.