Dwipayana I. M. P, Sudjana K, Semadi S, Suastika K, Saraswati M. R, Gotera W. Simple Virilization Type of Classic Congenital Adrenalhyperplasia: Case Report. Biomed Pharmacol J 2018;11(3).

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Manuscript received on :11-Jul-2018
Manuscript accepted on :31-July-2018
Published online on: 16-08-2018

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Reviewed by: Kulvinder Kaur 
Second Review by: Abhinav Kanwal

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I Made Pande Dwipayana^1,2, Karismayusa Sudjana³, Siswadi Semadi¹, Ketut Suastika¹, Made Ratna Saraswati¹ and Wira Gotera¹

¹Division of Endocrinology and Metabolism, DepartmentofInternal Medicine, Facultyof Medicine, Udayana University-Sanglah General Hospital Denpasar Bali.

²Doctoral Programme in Medical Science, Facultyof Medicine, Udayana University Denpasar Bali.

³Internal Medicine Programme, Facultyof Medicine, Udayana University-Sanglah General Hospital Denpasar Bali.

Corresponding Author E-mail: pande_dwipayana@unud.ac.id

DOI : https://dx.doi.org/10.13005/bpj/1497

Abstract

We have reported a case of 21 year old patient with congenital adrenal hyperplasia that manifestated with ambiguous genitalia and other signs of androgen excess. Chromosome analysis revealed 46 XX. Laboratory examination and imaging showed high level of 17-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. It was planned to give glucocorticoid therapy to the patient to suppress androgen level, genital reconstruction surgery and psychosexual therapy to reared as a woman, but she refused all suggestions because she wanted to be considered a man.

Keywords

Androgen excess, Congenital Adrenal Hyperplasia, Genital reconstruction, Glucocorticoid therapy

Introduction

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 wasa 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 pimpleson 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 5×2 cmin size. There was no hymen found from rectal toucher examination. Urethra was under the clitoris, the labia majoralooked 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.

Figure 1: Picture of the patient   Click here to View figure

Laboratory examination revealed increase in 17-Hydroxyprogesterone (743. 53ng/dL), increase in dehydroepiandrosterone sulfate 667mcg/dL (80-350mcg/dL), normal range for testosterone and estradiol, decrease in folicle stimulating hormone 4.85mIU/mL (5-20mIU/mL), decrease in luteinizing hormone 1.45mIU/mL (5-20mIU/mL), and patient’s chromosome analysis result was 46 XX.

Trans abdominal ultrasonography and computed tomography showed undeveloped uterus, two ovaries with follicles, notesticles, noprostate, and massatupperside of both kidney with irregular border.

Figure 2: Contrast CT scan abdomen showed undeveloped uterus and right ovarium   Click here to View figure

Figure 3: Contrast CT scan abdomen showed bilateral upper kidney mass.   Click here to View figure

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

CAHis a group of autosomal recessive genetic disorders. CAH caused by deficiency of enzymes needed in adrenal steroid biosynthesis;21-hydroxylase, 11β-hydroxylase, 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase or P450 oxidoreductase.^2,3

Figure 4: Adrenal steroidogenesis process   Click here to View figure

21-hydroxylase enzyme deficiency is the most common cause of CAH (90-95%).^2,3,5 21-hydroxylase turns 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol and progesterone to deoxycorticosterone, a precursor of cortisol and aldosterone.^2,3 Steroidogenesis process in CAH can be viewed in picture 6. Failure of cortisol synthesis will increase ACTH from anterior pituitari and causes adrenal hyperplasia.^6,7

There are two types of CAH, classic and non classic. The classic type consist of salt wasting type (75%) and simple virilization type (25%). 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.^8,9

Clinical 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^2-5,10

Figure 5: Steroidogenesis in CAH caused by21-hydroxylase enzyme deficiency.3   Click here to View figure

Table 1: Clinical and hormonal manifestation in CAH ¹¹

In our case clinical manifestations are caused by androgen excess, such as short stature, ambiguous genital, acne, and amenorrhea. Our patient 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).^9,10,12-15

Table 2: Medication used in CAH¹²