Case Report of Clitoral Hypertrophy inAnne-Laure 2 NerrExtremelyé, MD, Pierre Bétrémieux, MD, PrematureSylvie Nivot-Adamiak, MD

Girls With an Ovarian Cystabstract Neonatal clitoromegaly is mainly attributed to in utero androgen exposure secondary to congenital adrenal hyperplasia. We report on 2 extremely premature girls with clitoromegaly, increased androgen levels, no salt wasting syndrome, and ovarian cyst. In case 1, the cyst liquid was aspired during ovarian hernia surgery and revealed high androgen levels. After aspiration, serum androgen levels decreased, as did clitoral size. In case 2, an ovarian cyst was seen on pelvic ultrasound. Aspiration was not indicated. The cyst regressed spontaneously on iterative pelvic ultrasounds, and her clitoromegaly decreased. Case 1 demonstrates the ovarian origin of this transient virilization. Cyst formation seems to be linked to the physiologic maturation of the hypothalamic-pituitary-ovarian axis. Thirteen cases of clitoromegaly with hyperandrogenism, without salt Department of Pediatrics, University of Rennes 1, Rennes, wasting syndrome, have been reported in extremely premature infants. In France the context of clitoromegaly, we recommend ruling out in utero androgen Dr Nerré collected the clinical cases and drafted exposure, adrenal hyperandrogenism, and disorders of sex development. the initial manuscript; Dr Nivot-Adamiak carried out We further recommend affirming hyperandrogenism by androgen assay the initial analyses and reviewed and revised the and confirming ovarian origin with gonadotrophin assays and pelvic manuscript; Dr Bétrémieux treated the infants and critically reviewed the manuscript; and all authors ultrasound. Drug therapy abstention and clinical and ultrasound monitoring approved the final manuscript as submitted. are recommended because spontaneous regression of clitoral hypertrophy DOI: https://​doi.​org/​10.​1542/​peds.​2016-​1807 seems to be the most common outcome in the literature, as it was in our 2 Accepted for publication Feb 7, 2017 observations. Address correspondence to Anne-Laure Nerré, MD, Department of Pediatrics, Rennes Hospital, Hôpital sud, 16 Boulevard de Bulgarie, 35203 Rennes C dex, premature girls with clitoral é With the increased survival of very France. E-mail: [email protected] premature infants, there are new hypertrophy and ovarian cyst, PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, hospitalized in the NICU of the issues to consider in the identification 1098-4275). of clitoromegaly. This anomaly, with University Hospital of Rennes, France. Copyright 2017 by the American Academy of specific characteristics of posterior Hormonal assay methods at the © Pediatrics labial fusion and rugosity of the labial laboratory of University Hospital are FINANCIAL DISCLOSURE: The authors have skin, is mainly attributed to in utero described in Table 1. Assays carried indicated they have no financial relationships androgen exposure secondary to out in case 1 were obtained by relevant to this article to disclose. congenital adrenal hyperplasia (CAH) in radioimmunoassay after extraction 1 FUNDING: No external funding. female infants. We present 2 cases of and chromatographic separation at the POTENTIAL CONFLICT OF INTEREST: The authors laboratory of the University Hospital neonatal clitoromegaly associated with have indicated they have no potential conflicts of ovarian cyst and hyperandrogenism of Lyon, France. Consent for the interest to disclose. that decreased over time. collection of data was obtained from METHODS the parents of both children. To cite: Nerré A-L, Bétrémieux P, Nivot-Adamiak S. CASE PRESENTATIONS Case Report of Clitoral Hypertrophy in 2 Extremely Premature Girls With an Ovarian Cyst. Pediatrics. ’ Clinical and laboratory data were 2017;140(4):e20161807 retrospectively collected from the Patient A was born at 24 + 6 weeks medical records of 2 extremely gestation (WG) by vaginal delivery Downloaded from www.aappublications.org/news by guest on October 10, 2021 PEDIATRICS Volume 140, number 4, October 2017:e20161807 Case Report

Nerré et al 2017 ROUGH GALLEY PROOF Case Report of Clitoral Hypertrophy in 2 https://doi.org/10.1542/peds.2016-1807 October 2017 Extremely Premature Girls With an Ovarian Cyst 4 140 Pediatrics TABLE 1 Hormonal Assay Methods Assay Method Manufacturer Hormones an AKI (related to fetal distress and Radioimmunoassay Beckman-Coulter, Villempinte, DHEAS, aldosterone ibuprofen treatment), and patent France Radioimmunoassay CisBio, Codolet, France Estradiol ductus arteriosus. The first days of Radioimmunoassay after ether Beckman-Coulter, Villempinte, 17OHP, testosterone, life were marked by hyponatremia, extraction France androstenedione which corrected quickly, and Enzymoimmunoassay Beckman-Coulter, Villempinte, AMH hyperkalemia, treated with calcium France gluconate and furosemide related to Immunoradiometric assay CisBio, Codolet, France ACTH, renin ADVIA-Centaur Chemiluminescent Healthcare Diagnostics, Saint- Cortisol transient AKI. The patient had a bifid immunoassay Denis, France turgid clitoris that measured 10 mm Cobas electrochemiluminescene Roche, Meylan, France FSH, LH in length and 15 mm in width. There immunoassay was no posterior labial fusion with DHEAS, dehydroepiandrosterone sulfate. an anogenital ratio <0.5. A uterus was seen on the first PUS, performed × at 37 + 5 WG. The right ovary was in the right iliac fossa, measuring 21 in the context of chorioamnionitis. with a uterus/cervix ratio <1. The 9 mm with follicles of >5 mm. The × Antenatal management included right ovary was in place and had the left ovary presented a fluid-filled administration of corticosteroids. expected multifollicular aspect. The × cyst measuring 18 23 mm with Apgar scores were 3 at 1 and 5 left ovary was in the inguinal position other small follicles in the periphery. × minutes. Intubation was necessary with a size of 19 8 mm and normal Control at 39 + 1 WG found a left × at birth. Birth weight was 660 g. echogenicity with the presence of ovary measuring 25 26 mm with an There was no family pathology, few follicles. Ovarian vascularization increased cyst of 20 25 mm. There consanguinity, or drug exposure was normal. Karyotype was 46XX. ü was no sediment or thickening at the during pregnancy. She was included Hormonal assays (Table 2) periphery of the cyst. Steroid assays in the protocol for2 the PREMILOC indicated a low anti-M llerian (Table 3) at 38 + 3 WG found high trial study group. Ventilatory hormone (AMH) level, confirming testosterone and androstenedione support was required for 91 days. the absence of Sertoli tissue and and nonelevated 17OHP. No Neonatal complications included an high androgen levels. A new dosage hormonal treatment was initiated. Bacteroidesepisode of acute ureolyticus pulmonary edema of steroids was given at 39 + 4 By 41 + 3 WG, PUS confirmed that resolved with furosemide, a WG by column chromatography – spontaneous mild regression of the maternal- (Table 2). 17-hydroxyprogesterone cyst. The length of the uterus was fetal infection, a catheter line (17OHP) was routinely measured 27 mm with a uterus/cervix ratio <1. × associated infection, and retinopathy for CAH exclusion, and no therapy At 41 + 3 WG, the clitoris measured I. Significant fluid and electrolyte was initiated. Clinical ovarian 10 10 mm. disorders were present, requiring hernia surgery was performed at 41 × DISCUSSION large fluid and salt intake, followed WG, during which an ovarian cyst by sodium and water restriction. measuring 15 10 mm was aspired. With diuresis, hyperchloremia and The withdrawn liquid revealed high hypernatremia resolved, and sodium androgen levels. One week later, We report 2 cases of clitoral restriction was necessary. Transient serum androgen levels decreased. By hypertrophy with serum acute kidney injury (AKI) occurred. 48 WG, the clitoris size regressed to hyperandrogenism without salt By day 15, fluid intake decreased, and 12 mm in length and 8 mm in width. wasting syndrome in 2 extremely premature infants. salt supplementation was stopped. Patient B was born at 27 + 2 WG Possible clitoromegaly was reported after a trichorionic triamniotic Clitoral hypertrophy was probably at birth without any other sign of triplet pregnancy conceived by present at birth. Clitoral size is virilization. At 36 WG, the clitoris in vitro fertilization. The mother determined by precise measurements measured 15 mm in length and 10 received 1 dose of antenatal of corpus cavernosum. Normal mm in width. The vulva was normal corticosteroids. Birth weight was clitoral width ranges from 2 to 6 mm, 3 without posterior labial fusion. The 960 g, and Apgar scores were 3, 8, and length is <10 mm in term infants. anogenital ratio was <0.5. At that and 10 at 3, 5, and 10 minutes of Normal clitoral index (product of ± time, serum sodium, average blood life, respectively. Hyaline membrane the longest sagittal and transverse2 4 pressure, and weight gain were disease necessitated surfactant clitoris) is 15.1 1.4 mm . There normal. Pelvic ultrasound (PUS) therapy and ventilatory support for are few references for premature confirmed the presence of a uterus 51 days. Neonatal complications girls, but in our present cases, and 2 ovaries. The uterus was normal included a pulmonary hemorrhage, measurements were made at term. Downloaded from www.aappublications.org/news by guest on October 10, 2021 2 Nerré et al

Nerré et al 2017 ROUGH GALLEY PROOF Case Report of Clitoral Hypertrophy in 2 https://doi.org/10.1542/peds.2016-1807 October 2017 Extremely Premature Girls With an Ovarian Cyst 4 140 Pediatrics TABLE 2 Biochemical Hormonal and PUS Results for Patient A at Corrected Gestational Age Results WG 34 + 2 35 + 6 36 + 4 37 + 5 39 + 4a 41b 42 Hormonal assays 170HP (nmol/L) <9–term 34.5 16 12.3 23.5 7.4 — 6.1 17-liydroxypregneaolone (nmol/L) — — — — 22.8 — — Progesterone (nmol/L) 0.5–1.3 — — — 1.6 — — — 11-deoxycortisol (nmol/L) 2.1 ± 1.6 — — — — 2.1 — — Testosterone (nmol/L) 0.35–1.24c — — 6.1 — 3 67.4 3.8 Delta4A (nmol/L) 0.38–3.22c — — 31.5 — 10.5 196.6 18.1 Estradiol (nmol/L) — — — — — 18.9 — DHEAS (pmol/L) <3.8 — — — 5.2 — — — DHEA (nmol/L) 10.5 ± 3 — — — — 38.2 — — 21-desoxycortisol (pmol/L) — — — — <30 — — AMH (pmoTL) <75 — — 8.6 7.5 — — — Corticotropin (pmol/L) — — — 126.9 — — — Cortisol (nmol/L) — — — 7.9 — — — Aldosterone (nmol/L) — — — 5.3 — 1.2 — Renin (pmol/L) — — — — — 0.3 — PUS/surgery Right ovary — — — — — — — Left ovary — — Multifollicular — — Ovarian cyst — ovarian hernia, 19 × 8 mm Cyst — — No — — Yes, — aspiration

DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; —, no value. a Radioimmunoassay after extraction and chromatographic separation. b Hormonal assay in the ovarian cyst withdrawn liquid. c Serum values.

TABLE 3 Biochemical Hormonal Results and Pelvic Ultrasound Results for Patient B at Corrected Gestational Age WG 37 + 5 38 + 3 39 + 1 41 + 3 Hormonal assays 17OHP (nmol/L) <9 to term — 7.5 — 4.2 Testosterone (nmol/L) 0.35–1.24 — 2.8 — 1.3 Delta4A (nmol/L) 0.38–3.22 — 9.6 — 5.3 DHEAS (μmol. L) <3.8 — 4.4 — 2.5 Estradiol (pmol/L) <9.9 — 99.1 — 88.1 FSH (mUI/mL) — 6.9 — 4.6 LH (mUI/mL) — 4.8 — 3.5 AMH (pmol/L) <74.81 — — — 24.9 PUS First — Second Third Right ovary 21 × 9 mm — 15 × 17 mm 23 × 7 mm Left ovary Cyst — 25 × 26 mm cyst — Uterus Present — Present 27 mm length Cyst 18 × 23 mm — 20 × 25 mm 19 × 20 mm —, no value.

The absence of a posterior labial dehydroepiandrosterone sulfate). are routinely ruled out with a fusion (anogenital ratio <0.5) In utero androgen exposure (eg, normal baseline 17OHP level and 3 ’ suggests recent virilization. maternal history, virilization signs a normal 11-deoxycortisol level, during pregnancy) and adrenal respectively. Huysman s study Further investigations are origin for hyperandrogenism showed significantly higher 17OHP needed. First, biological must be determined. If there are levels and lower cortisol/17OHP in hyperandrogenism can be no specific clinical indications ventilated very premature infants β confirmed by hormonal assays of CAH, 21-hydroxylase and compared with nonventilated (testosterone, androstenedione, 11 -hydroxylase deficiency preterm infants as well as in more Downloaded from www.aappublications.org/news by guest on October 10, 2021 PEDIATRICS Volume 140, number 4, October 2017 3

Nerré et al 2017 ROUGH GALLEY PROOF Case Report of Clitoral Hypertrophy in 2 https://doi.org/10.1542/peds.2016-1807 October 2017 Extremely Premature Girls With an Ovarian Cyst 4 140 Pediatrics g — 4.8 6.9 Current Study —— OH OC 5.2 4.3 Yes Yes Asp No 15 × 10 10 × 15 i 50 4.7 31.5 9.6 46XX 46XX Florinef HC and f i —— — —— 50 Florinef Ref 5 HC and i No No No ——— 32 Florinef e NoNo No No No No No No ————— ——— ————— 19 3 434 205 128 123 7.5 Ref 1 Normal Normal — — — No 6.2 5.6 27.1 Normal d Ref 9 — — 6.5 ′ >35 >35 11.8 2 2.6 1 1.6 10.8 3.5 3.4 4.4 6.1 2.8 No OH 91.8 170 41.5 68.5 46XX 46XX 46XX 46XX 46XX 46XX 111.9 162 33.3 86.4 10 × 4 10 × 4 10 × 4 10 × 4 18 × 13 Patient 1 Patient 2 Patient 3 Patient 4 MS Patient 1A Patient 1B Patient 2 Patient A Patient B — — —— — c Patient 2 Patient Ref 6 1 No No No No No No No HC and —— —— 3.6 9 26.6 b No Yes ——————— 7.9 1.8 9.6 ′ 10.4 3.4 Lg 12 Ref 8 Normal OC — — — — —— ; Lg = length. 2 a Ref 7 31 35 31.4 36 34 27 29 35 36 36.4 27.1 28 35.4 36.6 38.4 24 27 25 31 29 26.7 29 25 25 25.7 25 25 24 24.9 27.3 No No No —— —————————— —— —————————— 6.8 0.5 640 1056 490 1556 1400 575 900 635 700 775 550 880 760 660 960 hernia 1990 1990 2003 2004 2004 2008 2008 2008 2008 2009 2012 2012 2012 2017 2017 46XX 46XX 46XX surgery Case 1 Case 2 Case Patient Inguinal

h

h  Summary Data of the 15 Literature Cases

( μ mol/L) (nmol/L) 27.2 22 2.5 5 13.8 21.2 14.3 8.6 a h (UI/L) h (UI/L) h publication syndrome (nmol/L) (nmol/L) h Year of Clitoris size (mm) Salt wasting Ovarian cyst Karyotype DHEAS WG Birth wt (g) 170HP PUS CYP21 FSH Androstenedione LH Treatment HC, plastic Testosterone WG At first investigations. Reference values for reference 8 not reported. <20; testosterone, <0.3; androstenedione, 0.22 – 2.4; DHEAS, <10; FSH, <167; LH, <54. Reference values for reference 9: 17OHP, Reference values for reference 7 not reported. <9; testosterone, 0.35 – 1.2; androstenedione, 0.38 3.2; DHEAS, <3.8; FSH, and LH not reported. Reference values for current study: 17OHP, Reference values for reference 1: 17OHP, 3.2 – 22; testosterone, <0.22 2.8; androstenedione, not reported; DHEAS, 0.14 – 3.01; FSH and LH not reported. Reference values for reference 1: 17OHP, Reference values for reference 6: 17OHP, <20; testosterone, <0.5; androstenedione, <1; DHEAS, <0.5; FSH and LH, not reported. <20; testosterone, <0.5; androstenedione, <1; DHEAS, Reference values for reference 6: 17OHP, Reference values for reference 5: 17OHP, <10; testosterone, <1; androstenedione, <2.1; DHEAS, FSH, and LH not reported. <10; testosterone, <1; androstenedione, <2.1; DHEAS, FSH, Reference values for reference 5: 17OHP, Clitoral index, normal range =15.1 ± 1.4 mm e f g h i TABLE 4 Asp, aspiration of ovarian cyst; DHEAS, dehydroepiandrosterone sulfate; HC, hydrocortisone; OC, ovarian cyst; OH, hernia; — , no value. a b c d

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Nerré et al 2017 ROUGH GALLEY PROOF Case Report of Clitoral Hypertrophy in 2 https://doi.org/10.1542/peds.2016-1807 October 2017 Extremely Premature Girls With an Ovarian Cyst 4 140 Pediatrics severely ill infants. This suggests The pituitary gonadal axis is an ovarian origin. Unfortunately, an insufficient adrenal response active during the last trimester gonadotrophins were not to stress in sick, ventilated, very of pregnancy. At birth, levels analyzed in patient A. This cyst preterm infants. The adrenals of gonadotrophins rise rapidly formation seems to be linked to increase the production of between 2 and 4 months of age in the physiologic maturation of the

17OHP without being5 able to response to the postnatal fall of hypothalamic-pituitary-ovarian convert it to cortisol. The elevated estrogens. This latency is attributed axis in these extremely premature 17OHP levels may indicate a to immaturity of the hypothalamic- girls. β relative deficiency of 21- and/or pituitary-ovarian axis. The axis CONCLUSIONS 11 -hydroxylase enzymes, then becomes sensitive to the

leading to increased6 androgen negative feedback of low levels of production. sex steroids, resulting in the fall of In cases of clitoromegaly, we 7 follicle-stimulating hormone (FSH) recommend ruling out in utero In 2004, Greaves et al reported 2 and luteinizing hormone (LH) to androgen exposure, adrenal similar cases and concluded that 11 prepubertal levels. hyperandrogenism (17OHP, hyperandrogenism was exclusively 11-deoxycortisol), and disorders of due to a prolonged activation of Fetal follicles and ovarian cyst sex development (karyotype, AMH, the fetal adrenal cortex based formation are stimulated by fetal and PUS). We also recommend on the results of urinary steroid gonadotrophins and maternal affirming hyperandrogenism metabolite levels. However, it is 12 hormones. Because of a shortened with hormonal assays difficult to conclude that there gestation, the expected third (testosterone, androstenedione, was an exclusively adrenal origin trimester dips in gonadotrophins dehydroepiandrosterone sulfate) because there was no PUS nor levels do not occur, allowing and confirming ovarian origin with gonadotrophin assays performed gonadotropin-releasing hormone, gonadotrophin assays (LH, FSH) in their second patient. Moreover, FSH, and LH to remain at high and PUS to determine if there is an the presence of an ovarian cyst levels and stimulate the ovarian ovarian cyst. Cysts should not be in their first patient was not 13 follicles,​ which may lead to aspirated as a routine procedure considered a possible cause of ovarian cyst formation and in these patients because they transient hyperandrogenism. hyperandrogenism. often regress spontaneously. If Gonadal origin, particularly a aspiration is required, testosterone disorder of sex development, must 10 Greaves et al in 2008 described 4 and androstenedione should be be ruled out with a XX karyotype, similar cases. The clitoromegaly was assayed from cyst fluid. Drug the absence of testicular tissue (low associated with high ex utero levels therapy abstention and clinical AMH), and multifollicular ovaries of LH and androgens for a few weeks. and ultrasound monitoring are and uterus present on ultrasound. The LH levels were significantly recommended because spontaneous Ultrasound can also reveal an higher compared with other infants regression of clitoral hypertrophy ovarian cyst. of similar gestational13 age without and ovarian cysts seems to be the An ovarian cyst was present in clitoromegaly. This significant most common outcome in these both of our cases. In patient A, high difference in the serum levels of observations. androgen levels in the cyst liquid pituitary hormones for extremely confirmed the ovarian origin of the preterm infants compared with those hyperandrogenism. In patient B, for late preterm and full-term infants14 Abbreviations clitoral hypertrophy and the ovarian was confirmed by Greaves et al cyst decreased simultaneously. The in 2015. The authors assumed that absence of a posterior labial fusion this higher LH/FSH ratio caused the 17OHP: 17-hydroxyprogesterone suggests later exposure to androgens, biological hyperandrogenism and ü AKI: acute kidney injury which may have come from the therefore the transient virilization. AMH: anti-M llerian hormone ovarian cyst. In the literature Androgens were probably produced CAH: congenital adrenal reviewed since 1990, we found 13 by the ovaries, but only 2 of 4 hyperplasia similar cases, but the link with an patients had a PUS, and no ovarian FSH: follicle-stimulating ovarian cyst was never reported. cyst was found. An adrenal origin was hormone Only 1 ovarian cyst was found on 7 excluded. LH: luteinizing hormone PUS performed in these 13 patients. ’ – PUS: pelvic ultrasound ‍Table 4 provides a summary of these Patient A demonstrates that this 1,6​ 10 WG: weeks gestation data. ‍ ‍‍ transient hyperandrogenism had Downloaded from www.aappublications.org/news by guest on October 10, 2021 PEDIATRICS Volume 140, number 4, October 2017 5

Nerré et al 2017 ROUGH GALLEY PROOF Case Report of Clitoral Hypertrophy in 2 https://doi.org/10.1542/peds.2016-1807 October 2017 Extremely Premature Girls With an Ovarian Cyst 4 140 Pediatrics REFERENCES 5. Huysman MW, Hokken-Koelega AC, De appearance in some extremely Ridder MA, Sauer PJ. Adrenal function preterm female infants may be the 1. Dumont T, Black AY, Ahmet A, Fleming in sick very preterm infants. Pediatr result of foetal programming causing NA. Isolated transient neonatal Res. 2000;48(5):629 633 a surge in LH and the over activation clitoromegaly with hyperandrogenism – of the pituitary-gonadal axis. Clin of unknown etiology. J Pediatr Adolesc 6. Couch R, Girgis R. Postnatal virilization Endocrinol (Oxf). 2008;69(5):763–768 Gynecol. 2009;22(5):e142–e145 mimicking 21-hydroxylase deficiency in 3 very premature infants. Pediatrics. 11. Brandt ML, Helmrath MA. Ovarian cysts 2. Baud O, Maury L, Lebail F, et al; 2012;129(5):e1364 e1367 in infants and children. Semin Pediatr PREMILOC trial study group. Effect – Surg. 2005;14(2):78 85 of early low-dose hydrocortisone on 7. Greaves R, Kanumakala S, Read A, – survival without bronchopulmonary Zacharin M. Genital abnormalities 12. Dolgin SE. Ovarian masses in the dysplasia in extremely preterm mimicking congenital adrenal newborn. Semin Pediatr Surg. infants (PREMILOC): a double-blind, hyperplasia in premature 2000;9(3):121–127 infants. J Paediatr Child Health. placebo-controlled, multicentre, 13. Greaves RF, Hunt RW, Chiriano AS, 2004;40(4):233 236 randomised trial. Lancet. – Zacharin MR. Luteinizing hormone and 2016;387(10030):1827–1836 8. Midgley PC, Azzopardi D, Oates N, follicle-stimulating hormone levels in 3. Houk CP, Levitsky LL. Evaluation of Shaw JC, Honour JW. Virilisation of extreme prematurity: development the infant with ambiguous genitalia. female preterm infants. Arch Dis Child. of reference intervals. Pediatrics. 2013. Available at: www.​uptodate.​com/​ 1990;65(7 spec no):701–703 2008;121(3). Available at: www.​ contents/​evaluation-​of-​the-​infant-​with-​ 9. Akçam M, Topaloglu AK. Extremely pediatrics.​org/​cgi/​content/​full/​121/​3/​ ambiguous-genitalia.​ Accessed July 12, immature infant who developed e574 2015 clitoromegaly during the second 14. Greaves RF, Pitkin J, Ho CS, Baglin 4. Sane K, Pescovitz OH. The clitoral month of her postnatal life probably J, Hunt RW, Zacharin MR. Hormone index: a determination of clitoral due to frequent whole blood modeling in preterm neonates: size in normal girls and in girls with transfusion from an adult male. establishment of pituitary and abnormal sexual development. Pediatr Int. 2003;45(3):347–348 steroid hormone reference J Pediatr. 1992;120(2 pt 1): 10. Greaves R, Hunt RW, Zacharin M. intervals. J Clin Endocrinol Metab. 264–266 Transient anomalies in genital 2015;100(3):1097–1103

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Nerré et al 2017 ROUGH GALLEY PROOF Case Report of Clitoral Hypertrophy in 2 https://doi.org/10.1542/peds.2016-1807 October 2017 Extremely Premature Girls With an Ovarian Cyst 4 140 Pediatrics Case Report of Clitoral Hypertrophy in 2 Extremely Premature Girls With an Ovarian Cyst Anne-Laure Nerré, Pierre Bétrémieux and Sylvie Nivot-Adamiak Pediatrics originally published online September 20, 2017;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2017/09/18/peds.2 016-1807 References This article cites 13 articles, 3 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2017/09/18/peds.2 016-1807#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Endocrinology http://www.aappublications.org/cgi/collection/endocrinology_sub Fetus/Newborn Infant http://www.aappublications.org/cgi/collection/fetus:newborn_infant_ sub Neonatology http://www.aappublications.org/cgi/collection/neonatology_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

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