Simple Virilization Type of Classic Congenital Adrenal Hyperplasia: Case Report

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Udayana University-Sanglah General Hospital Denpasar Bali. 2Student of Doctoral Programme in Medical Science, Faculty of Medicine, Udayana University Denpasar Bali. 3Student of Internal Medicine Programme, Faculty of Medicine, Udayana University-Sanglah General Hospital Denpasar Bali. *Corresponding author E-mail: pande_dwipayana@unud.ac.id

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic disorders.CAH is caused by deficiency of enzymes needed in adrenal steroid biosynthesis, this will result in increased production of adrenocorticotropic hormone (ACTH) and will further enlarge the adrenal gland.According to Office of Rare Diseases (ORD) from National Institutes of Health (NIH), CAH is a rare disorder, in United States of America the incidence is less than 200.000 of total population.Indonesia recorded 292 patients with CAH from 2009-2014, this data was gained by pediatric endocrinologists because no case has been detected in adult patients 1 .

Case Report
Patient was a 21 year old, a Balinese, unmarried, consulted from Obstetric and Gynecology Department with ambiguous genitalia.Her urine flows from her women's part of her genital, and she wanted to be able to urinate in standing position like a man.She has always felt that she is a man, but her family treated her as a girl since she was born.During childhood she had taller figure compared to her friends, but her growth has been slowed down since adolesence.She also easily got pimples on her face.She had never ejaculated and also has never gotten menarche.Agreement to do and take picture of physical examination especially genital examination were given by herself.Physical examination revealed short stature 133 cm, normal vital signs, tanner I breasts, penile gland-like enlarged clitoris with 5x2 cm in size.There was no hymen found from rectal toucher examination.Urethra was under the clitoris, the labia majora looked like scrotum, testicles were unpalpable, and there was vagina, 4 cm depth from vaginal sondage examination.Speculum examination cannot be performed because of the small size of vagina.
Trans abdominal ultrasonography and computed tomography showed undeveloped uterus, two ovaries with follicles, no testicles, no prostate, and mass at upper side of both kidney with irregular border.
We assessed this patient with congenital adrenal hyperplasia simple virilization type, primary amenorrhea, bilateral adrenal tumour probably myelolipoma, and transexualism.Our multi dicipline team decided to keep the female identity of the patient with glucorticoid, hormonal therapy, genital reconstruction, and supportive psychotherapy.How ever the patient refused our recommendation because she still wanted to be identified as male.

DISCUSSION
CAH is a group of autosomal recessive genetic disorders.CAH caused by deficiency of enzymes needed in adrenal steroid biosynthesis;21hydroxylase, 115ØÃÞ-hydroxylase, 175ØÂÞh y d r o x y l a s e , 3 5 Ø Ã Þ -h y d r o x y s t e r o i d dehydrogenase or P450 oxidoreductase. 2,31-hydroxylase enzyme deficiency is the most common cause of CAH (90-95%). 2,3,51-hydroxylase turns 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol and progesterone to deoxycorticosterone, a precursor of cortisol and aldosterone. 2,3Steroidogenesis process in CAH can be viewed in picture 6.Failure of cortisol synthesis will increase ACTH from anterior pituitari and causes adrenal hyperplasia. 6,7g. 1.Picture of the patient In salt wasting type, there is no 21-hydroxylase, so both aldosterone and cortisol synthesis will be disrupted .In simple virilization type, a small part of the enzyme still can function normally so disruption only happens in cortisol synthesis. 8,9linical manifestations in CAH are caused by cortisol and aldosterone deficiency and excess of androgen production.Hormonal examination can help us to differentiate type of CAH, but the gold standard is molecular genetic analysis [2][3][4][5]10 In our case clinical manifestations are caused by androgen excess, such as short stature, ambiguous genital, acne, and amenorrhea. Oupatient didn't have hirsutism though, this can be caused by insensitivity of hair follicle to androgen, so the pilosebaceous unit differentiate to sebaceous gland.11,12,13 Treatment goals for CAH in adults are to prevent side effect from long term adrenal replacement therapy and to keep patient's fertility.5,10,14,17 Modalities used in treatment can be seen at table 3. The corner stone of CAH treatment is glucocorticoid; hydrocortisone (15-45 mg/day) , prednisone (5-7.5 mg/ day), and dexamethasone (0.25-0.5 mg/day).9,10,[12][13][14][15] Fertility impairment in CAH cannot be treated only by steroid but also surgery for genital reconstruction and psychosexual therapy.Our  patient refused the treatment recommendation to suppress androgen because she wanted to be identified as a man and wanted to do genital reconstruction surgery to be a man.Our team refused her request because currently there is no legal law about gender changing in Indonesia.Abundant androgen exposure since intrauterine period was very likely that contributed to her desire to be a man.
One of the complication from CAH is adrenal gland tumor, usually detected accidentally during imaging examination.This tumor is caused by long term high ACTH exposure.Our patient had non contrast enhancement tumor from her imaging, so we assumed that her tumor is myelolipoma.

CONCLUSION
We have reported case of patient with congenital adrenal hyperplasia that manifestated in ambiguous genitalia and other signs of androgen excess.Altough chromosome analysis revealed 46 XX, patient has always identified herself as a man because of her high level of androgen.Laboratory examination and imaging which resulted in high level of17-Hydroxyprogesterone, undeveloped uterus, two ovaries with follicles, no testicles, no prostate, and mass at upper side of both kidney with irregular border confirmed the diagnosis.Patient was planned to be given glucocorticoid therapy to suppress androgen level, genital reconstruction surgery and psychosexual therapy to be a woman, but she refused all suggestions because she wanted to be a man.
Published by Oriental Scientific Publishing Company © 2018This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC-BY).