document: congenital adrenal hyperplasia ( cah ) is caused by defects in various enzymes necessary for cortisol synthesis . 
   90 - 95% of cah cases are caused by 21-hydroxylase deficiency ( 21-ohd ) . in patients with 21-ohd , 
   some of these precursors are shunted into the androgen synthetic pathway , causing signs and symptoms of androgen excess , including ambiguous genitalia in females and rapid somatic growth with accelerated skeletal maturation in both sexes1 ) . since the discovery of cortisone in the 1950s , cah has been managed effectively , and the clinical course of the disease has markedly improved2 ) . 
   typical medical treatment consists of oral glucocorticoid and mineralocorticoid administration in order to compensate for adrenal steroid deficiencies and to suppress adrenal androgens . 
   herein , we report four cases of patients who were diagnosed as having cah . they have been managed with hydrocortisone and fludrocortisone . 
   thereafter , adrenal masses were found by abdominal computed tomography ( ct ) scan in all four cases . 
   recent reports reveal a high apprearance of small tumors in patients with untreated cah and most adrenal masses in children with cah are benign3 - 5 ) . 
   two of our four cases were managed with adrenalectomy because of increasing adrenal mass size and virilization . 
   a male neonate who presented with severe vomiting at 15 days of life was brought to medical attention . 
   however severe vomiting recurred after he was discharged and he was brought to kyunghee medical center . 
   laboratory evaluation revealed a ph level of 7.36 , hco3 13 meq / l , base excess -10 meq / l , and na 109 meq / l . 
   electrolytes were normalized and vomiting was resolved . thereafter the level of na was normalized . 
   however at the age of 20 years , his height was 145 cm ( less than 3 percentile ) . 
   abdominal ct performed at the age of 18 years ( july 30 , 2004 ) revealed the presence of multiple bilateral adrenal masses ( possibly adenoma ) . 
   the size of his right adrenal mass was 2.41.3 cm and the size of left adrenal masses were 2.71.7 cm and 2.31.9 cm with adrenal hyperplasia . 
   follow - up abdominal ct was performed at the age of 20 years ( fig . 
   1 ) . abdominal ct showed that both adrenal masses on both sides were increasing in size . 
   the size of his right adrenal mass was 3.01.8 cm , and the size of his left adrenal masses were 3.32.4 cm and 3.02.6 cm . 
   bilateral adrenalectomy was performed at the age of 20 years . a female neonate presented with ambiguous genitalia at birth suggesting salt - losing cah . 
   when she was at the age of 3 years , vaginoplasty and clitoroplasty were performed . at the age of 11 
   abdominal ct performed at the age of 11 years showed a 3.54.0 cm mass in her right adrenal gland ( fig . 
   hydrocortisone and fludrocortisone administration was carried out during follow - up and vaginoplasty and clitoroplasty were performed at the age of 4 years . 
   when she was 11 years old and 12 years old , abdominal cts were performed due to her virilization including hirsuitism and masculine voice . 
   a male neonate was admitted to medical attention at 1 month of age with poor oral intake and diarrhea . 
   he was admitted to kyunghee medical center at 5 months of age with poor oral intake and vomiting . 
   laboratory evaluation revealed a ph level of 7.35 , hco3 14 meq / l , base excess -9 meq / l , and na 119 meq / l . during follow - up , he was diagnosed with cah . 
   after his medication had begun , the level of na was normalized . during follow - up , 
   medication was stopped on his parents ' request and since the age of six , he showed secondary growth such as hyperpigmentation , hirsuitism , large penis , and pubic hair . 
   abdominal ct performed at the age of 14 years revealed the presence of adrenal masses ( left adrenal gland : 2.01.4 cm & 1.21.3 cm , right adrenal gland : 1.11.2 cm ) . since there was no change in the size of adrenal mass , adrenalectomy was not performed . 
   a male neonate who presented with severe vomiting at 15 days of life was brought to medical attention . 
   however severe vomiting recurred after he was discharged and he was brought to kyunghee medical center . 
   laboratory evaluation revealed a ph level of 7.36 , hco3 13 meq / l , base excess -10 meq / l , and na 109 meq / l . 
   electrolytes were normalized and vomiting was resolved . thereafter the level of na was normalized . 
   however at the age of 20 years , his height was 145 cm ( less than 3 percentile ) . 
   abdominal ct performed at the age of 18 years ( july 30 , 2004 ) revealed the presence of multiple bilateral adrenal masses ( possibly adenoma ) . 
   the size of his right adrenal mass was 2.41.3 cm and the size of left adrenal masses were 2.71.7 cm and 2.31.9 cm with adrenal hyperplasia . 
   follow - up abdominal ct was performed at the age of 20 years ( fig . 
   1 ) . abdominal ct showed that both adrenal masses on both sides were increasing in size . 
   the size of his right adrenal mass was 3.01.8 cm , and the size of his left adrenal masses were 3.32.4 cm and 3.02.6 cm . 
   when she was at the age of 3 years , vaginoplasty and clitoroplasty were performed . at the age of 11 
   abdominal ct performed at the age of 11 years showed a 3.54.0 cm mass in her right adrenal gland ( fig . 
   hydrocortisone and fludrocortisone administration was carried out during follow - up and vaginoplasty and clitoroplasty were performed at the age of 4 years . 
   when she was 11 years old and 12 years old , abdominal cts were performed due to her virilization including hirsuitism and masculine voice . 
   a male neonate was admitted to medical attention at 1 month of age with poor oral intake and diarrhea . 
   he was admitted to kyunghee medical center at 5 months of age with poor oral intake and vomiting . 
   laboratory evaluation revealed a ph level of 7.35 , hco3 14 meq / l , base excess -9 meq / l , and na 119 meq / l . during follow - up , he was diagnosed with cah . 
   hydrocortisone and fludrocortisone medication was initiated . after his medication had begun , the level of na was normalized . during follow - up , 
   medication was stopped on his parents ' request and since the age of six , he showed secondary growth such as hyperpigmentation , hirsuitism , large penis , and pubic hair . 
   abdominal ct performed at the age of 14 years revealed the presence of adrenal masses ( left adrenal gland : 2.01.4 cm & 1.21.3 cm , right adrenal gland : 1.11.2 cm ) . since there was no change in the size of adrenal mass , adrenalectomy was not performed . 
   cah describes a group of autosomal recessive condition in which deletions or mutations of the cytochrome p450 21-hydroxylase gene result in glucocorticoid and/or mineralocorticoid deficiency6 ) . in 95% of cases , 
   epidemiology , genetics , pathophysiology , clinical features , and the management of cah will be reviewed as follows . 
   the overall incidence of classical 21-ohd is 1:10,000 - 1:15,000 in most reported populations8 ) . 
   the 21-hydroxylase gene cyp21a2 is located on chromosome 6p21.3 within the hla histocompatibility complex9 ) . 
   two highly homologous 21-hydroxylase genes exist ; cyp21a2 and cyp21a1p , of which cyp21a2 codes for the active 21-hydroxlyase and cyp21a1p is an inactive pseudogene . 
   more than 90% of mutations of the active cyp21a2 gene are generated by recombinations between the active and the inactive pseudogene10 ) . 
   the pathophysiology of cah due to 21-ohd is closely linked to the degree of enzyme deficiency6 ) . 
   the biosynthesis of cortisol is regulated by negative feedback on hypothalamic corticotropin - releasing hormone ( crh ) and pituitary adrenoconticotrophic hormone ( acth ) secretion . 
   a defect in cortisol biosynthesis leads to a compensatory increase in hypothalamic and pituitary secretion of crh and acth . 
   this stimulates the adrenal cortex and results in the pathological correlative of hyperplastic adrenal glands . 
   the consequence of 21-ohd is a state of hypocortisolism , hypoaldosteronism , and hyperandrogenism combined with catecholamine deficiency and several metabolic disturbances . 
   endogenous glucocorticoids are essential for the development and continuing regulation of the adrenal medulla , synthesizing epinephrine and norepinephrine . without cortisol , 
   the organogenesis of the adrenal medulla is severely disturbed and the consequence is catecholamine deficiency , mainly comprising a lack of epinephrine11 ) . 
   cah is classified as classic , the severe form , or non - classic , the mild or late - onset form . 
   classic cah is subclassified as the salt - losing or non - salt - losing ( simple virilizing ) . 
   non - classic cah is subclassified as the late - onset form or cryptic form . 
   salt - losing cah is a severe form with a concurrent defect in aldosterone biosynthesis . 
   non - classic cah may be asymptomatic or may be associated with signs of androgen excess developing during childhood or at puberty . 
   the classic forms are characterized by a congenital decrease of cortisol and aldosterone secretion and an increase in androgen biosynthesis . 
   all female infants with classic cah due to 21-ohd typically have ambiguous genitalia at birth because of exposure to high concentrations of androgens in the uterus . 
   the internal genitalia are normal , including uterus , fallopian tubes , and ovaries ; wolffian duct structures are not present . 
   boys with classic cah have no signs of cah at birth , except subtle hyperpigmentation and possible penile enlargement . 
   thus , the age at diagnosis in boys varies according to the severity of aldosterone deficiency . 
   up to 2/3 of patients suffering from classic 21-ohd have insufficient aldosterone biosynthesis leading to salt - losing episodes after birth and later on12 ) . 
   boys with the salt - losing form typically present at 7 - 14 days of life with vomiting , weight loss , lethargy , dehydration , hyponatraemia , hyperkalaemia , and can present shock . 
   patients with non - classic cah do not have cortisol deficiency , but instead have manifestations of hyperandrogenism , generally later in childhood or in early adulthood13 , 14 ) . 
   manifestations include premature pubarche , tall stature , advanced bone age , menstrual irregularities , infertility , hirsutism and acne . 
   cah due to 21-ohd can be diagnosed in newborn screening programs by screening for 17-hydroxyprogesterone in dried blood spots . today , most cases of classical 21-ohd are diagnosed with this tool . 
   a high concentration of 17-hydroxyprogesterone in a randomly timed blood sample is diagnostic of classic 21-ohd . 
   the gold standard for diagnosis of cah is a corticotropin stimulation test , with measurement of 17-hydroxyprogesterone at 60 min . a stimulated concentration of 17-hydroxyprogesterone higher than 45 nmol / l is diagnostic of 21-ohd . 
   the aim of medical treatment in 21-ohd is to suppress adrenal androgens sufficiently without impairing growth , while allowing for normal pubertal development and fertility . in classic cah 
   , glucocorticoids are given in doses sufficient to suppress excessive secretion of crh and acth without total suppression of the hypothalamic - pituitary - adrenal . 
   physiological cortisol secretion rates are about 6 - 8 mg / m / day15 - 17 ) . to achieve these goals , the glucocorticoid doses have to exceed the physiological cortisol secretion rate , using doses of 12 - 18 mg / m 
   fludrocortisone was administered in cases of salt - losing manifestation and elevated plasma renin activity , to decrease glucocorticoid doses , or according to the genotype19 ) . 
   the use of fludrocortisone in patients with non - salt - losing classic cah allows management with lower doses of glucocorticoid and improves linear growth18 - 20 ) . 
   infants with the salt - losing form of 21-ohd require mineralocorticoid ( fludrocortisone , usually 0.1 - 0.2 mg ) and sodium chloride supplements ( 1 - 2 g daily ; 1 g nacl contains 17 meq of sodium ) in addition to glucocorticoid treatment . 
   treatment is indicated only for those with symptoms and aims to reduce hyperandrogenism18 - 20 ) . 
   cah constitutes a continuum of disorders that affect patients throughout their lives ( table 2 ) . 
   a variety of clinics involving close interaction between paediatric , reproductive , adult endocrinologists , and clinical psychologists experienced in psychosexual counselling will be necessary for patients with cah21 - 24 ) . 
   the development of adrenal adenoma or carcinoma in patients with cah is rare ; the etiology is not clear . 
   however , the incidence of adrenal masses appears to be higher in cah patients and in heterozygotes than in the general population3 ) . 
   recent reports have revealed a high prevalence of small adrenal tumors in patients with untreated 21-ohd cah3 , 4 ) . 
   histological types of adrenal tumor include adenoma , myelolipoma , and hemangioma25 ) . rarely , virilizing adrenal carcinoma has been found in patients with cah , but most adrenal masses in children with cah are benign5 ) . 
   the pathogenesis of adrenal tumor in patients with 21-ohd cah is thought to be related to a consequence of acth hypersecretion , which results from the lack of glucocorticoid synthesis26 ) . 
   avoidance of high steroid dose is likely to result in insufficient suppression of corticotropin stimulation27 ) . 
   chronic poor compliance to therapy appears to be associated with the development of the tumor . 
   therefore patients with 21-ohd cah should maintain steroid medication to avoid the appearance of adrenal tumor . 
   follow - up imaging may help to discover the appearance of adrenal tumor in patients with long - term management of 21-ohd cah . 
   there has been much improvement during the past 50 years in the understanding of cah , and the management with cah continues to improve . furthermore new medical strategies that offer the prospect of an improved outcome continue to evolve . 
   however , patients with 21-ohd cah should maintain steroid medication to avoid the appearance of adrenal tumor , to improve its symptoms , and to normalize electrolyte disorder , particularly hyponatremia .
summary: congenital adrenal hyperplasia ( cah ) caused by 21-hydroxylase deficiency is an autosomal recessive disease , which leads to cortisol and aldosterone deficiency and hyperandrogenism . 
   typical medical treatment includes oral glucocorticoid and mineralocorticoid administration to suppress adrenal androgens and to compensate for adrenal steroid deficiencies . 
   however , some patients stopped taking medicine without the doctor 's consent . among these patients , 
   four cases of cah patients showing the presence of hyponatremia as an initial electrolyte disorder were found with adrenal adenoma . 
   hypersecretion of adrenocorticotrophic hormone and chronic poor compliance to therapy appears to be associated with the development of the adrenal tumor . 
   two cases were managed with adrenalectomy because of increasing adrenal tumor size and virilization . whereas the other two cases did not increase in size and were observed without adrenalectomy . 
   therefore , it is important that patients with cah maintain steroid medication to avoid the appearance of adrenal tumor .