17-hydroxylase and 17,20-lyase ( p450c17 ) are enzymes that convert pregnenolone and progesterone to 17-hydroxypregnenolone ( 17-ohpreg ) and 17-hydroxyprogesterone ( 17-ohp ) , which are precursors of sex steroids and cortisol . in cases of p450c17 deficiency , androgens , estrogens , and cortisol can not be produced . a compensatory increase in adrenocorticotrophic hormone ( acth ) , due to the failure of cortisol production , stimulates the production of 11-deoxycorticosterone and corticosterone , which have powerful mineralocorticoid activity . in turn , the excessive levels of these mineralocorticoids lead to volume expansion , hypertension , and electrolyte imbalances such as hypokalemia ( figure 1 ) . deficiency in sex steroids and excessive mineralocorticoid production cause characteristic symptoms and signs such as delayed puberty with primary amenorrhea and hypertension . congenital adrenal hyperplasia ( cah ) is an autosomal recessive disorder due to a defect in any of several enzymes involved in steroidogenesis ; different genotypes induce different phenotypes . 17-hydroxylase/17,20-lyase deficiency ( 17ohd ) is a rare type of cah that causes cortisol and sex hormone deficiency and aldosterone excess . here , we report the case of a 21-year - old woman who had been inadequately treated for 17-hydroxylase/17,20-lyase deficiency for a prolonged period of time . an 18-year - old female was transferred for evaluation of low serum potassium levels ( 2.6 mmol / l ) found incidentally during a preoperative workup for an appendectomy at a local medical center . then , the patient was referred to the cardiology department because she had constant high blood pressure , with a maximal reading of 180/110 mm hg . the patient was treated with an angiotension ii receptor antagonist ( telmisartan ) and a calcium channel blocker ( amlodipine ) . however , her blood pressure was still not well controlled and she was subsequently diagnosed with stage 1 hypertensive retinopathy . upon further investigation , it became apparent that the patient had had hypertension since the age of 15-year - old , when the patient visited her gynecologist . at that time , the patient was found to have primary amenorrhea and features of sexual infantilism . on physical examination , the patient was quite tall and slender , with a height of 166.2 cm and a body weight of 44 kg ( body mass index , 15.9 kg / m ) , and was phenotypically female . the patient 's breast development had only progressed to tanner stages 1 - 2 and pubic hair was underdeveloped . ultrasonography of the abdomen and pelvis demonstrated a hypoplastic uterine corpus , bilateral small multicystic ovaries , and a very thin endometrium . considering the patient 's history and clinical signs , hormone profiles and karyotype the patient 's karyotype was 46,xx and hormone studies showed a normal to hypergonadotropic hypogonadal state with low testosterone and dehydroepiandrosterone sulfate ( dhea - s ) levels ( table 1 ) . because there was a high suspicion of 17ohd , further evaluation was recommended ; however , the patient refused further investigation at this time . after a period of 4.5 years , the patient revisited the gynecology department with a complaint of persistent amenorrhea . upon physical examination a repeat hormone profile showed elevated levels of follicle - stimulating hormone ( fsh ) and luteinizing hormone ( lh ) with low levels of estradiol , indicating hypergonadotropic hypogonadism . studies also demonstrated very low cortisol , high acth , and low levels of both testosterone and dhea - s ( table 1 ) . with a clinical suspicion of an enzyme defect in steroidogenesis , particularly 17ohd , an acth stimulation test and the acth stimulation test showed no increase in 17-ohp after intravenous administration of synthetic acth ( synacthen 0.25 mg , dalim biotech , jecheon , korea ) when compared with the basal level ( table 2 ) , suggesting an impairment in the pathway catalyzed by 17-hydroxylase . genetic analysis showed a compound heterozygous mutation in exon 6 of the cyp17a1 gene ( c.985 - 987tac > aa and c.1118a > t ) . after being diagnosed with 17-hydroxylase deficiency , the patient stopped taking antihypertensive medication and started oral hydrocortisone ( rapison 30 mg daily , kolon pharmaceuticals , daejeon , korea ) , which is a cornerstone for the treatment for cah . in addition , the patient commenced oral estradiol and cyclic medroxyprogesterone ( progynova 2 mg daily , bayer , lys - lez - lannoy , france and provera 10 mg daily for 13 days each month , pfizer , tronto , italy ) in order to induce secondary sexual development and maintain cyclic uterine bleeding . after appropriate therapy , the patient 's blood pressure normalized without antihypertensive therapy , and five months later , follow up laboratory investigations revealed normal levels of acth ( 11.04 g / dl ) , progesterone ( 0.04 ng / ml ) and serum electrolytes . physical examination showed stage 2 tanner breast development with scanty pubic and axillary hair production , and the uterus was normal in size and shape upon ultrasonographic examination . 17-hydroxylase deficiency is a rare form of cah , with an estimated incidence of 1 in 50,000 to 100,000 , and accounts for about 1% of all cah cases . the most common enzyme defect causing cah is 21-hydroxylase deficiency ( 21-ohd ) , followed by 11-hydroxylase deficiency ( 11-ohd ) . clinically , these enzyme deficiencies are characterized by hyperandrogenism or heterosexual precocious puberty in females ; however , clinical features of 17-hydroxylase deficiency differ from those of 21-ohd or 11-ohd in that there is no hyperandrogenism , but rather , sexual infantilism . the gene encoding the enzyme p450c17 is cyp17a1 , which is located at chromosome 10q24.3 . human 17-hydroxylase deficiency involving a loss of only 17-hydroxylase or 17,20-lyase has been observed , but in most affected patients , both enzymes are deficient . blockage of the pathway catalyzed by 17-hydroxylase enhances the mineralocorticoid pathway , resulting in overproduction of 11-doc , corticosterone and aldosterone . this also causes a decline in 17-ohpreg , 17-ohp , 11-deoxycortisol , cortisol , dhea , androstenedione , and testosterone . high levels of 11-doc induce sodium and fluid retention and loss of potassium and hydrogen , and consequently hypertension , because of its potent mineralocorticoid effect . affected males have ambiguous or female external genitalia due to a deficiency in androgen synthesis . female patients have normal genitalia but show immature sexual development and primary amenorrhea caused by a deficiency of estrogen in adolescence . once diagnosis is made , immediate adequate intervention should be initiated in order to prevent complications such as hypertension or hypokalemia and to induce sexual development at the appropriate time . the diagnosis of 17ohd is based on clinical , biochemical , and molecular features . in our case , biochemically , there were decreased concentrations of dhea , androstenedione , testosterone , estradiol , and cortisol , and increased concentrations of 11-doc and acth . since clinical and biochemical features are diverse , depending on the type of mutations in the cyp17a1 gene , genetic analysis is critical for confirmative diagnosis . some genetic abnormalities such as point mutations by single base substitution , small duplications , and large deletions have been reported in 17ohd . in our case , compound heterozygous mutations in exon 6 of the cyp17a1 gene ( c.985 - 987tac > aa and c.1118a > t ) were detected . the substitution of the tac codon at 329 with aa is assumed to induce a frameshift variation such that consequently , the codon at 418 becomes a stop codon ; additionally , a missense mutation is developed via the substitution of histidine with leucine at codon 373 . these mutations are some of the frequently reported mutations of the cyp17a1 gene in asian countries such as korea , japan , and china . of the mutations reported among the korean population , h373l mutation ( c.1118a > t ) was the most common ; additional mutations are also reported ( table 3 ) . because 17ohd is an autosomal recessive disorder , we investigated the family history . while there were no affected individuals apparent from the clinical history , we recommended genetic analysis of the patient 's parents ; however , this was not performed due to a lack of consent . glucocorticoids are administered in order to decrease and normalize the blood levels of 11-doc and acth . glucocorticoid therapy can normalize blood pressure and serum electrolyte levels . generally , dexamethasone ( 0.25 - 1.0 mg / day ) , prednisone ( 2 - 5 mg / day ) , or equivalents are recommended . sex hormone replacement is required for breast and uterus development and maintenance of female sexual characteristics . estrogen and progestin agents are required in patients with a 46,xx karyotype to induce cyclic withdrawal bleeding and to prevent endometrial hyperplasia . our patient had not been managed appropriately for a prolonged period prior to consultation with us . the patient had received intermittent potassium replacement and antihypertensive treatment following the incomplete diagnosis of her clinical condition . after administration of glucocorticoid ( hydrocortisone 10 mg three times daily ) and sex steroids ( estradiol valerate 2 mg once daily and medroxyprogesterone acetate 10 mg once daily for 13 days per month ) , the patient 's blood levels of renin , aldosterone , acth , and progesterone were normalized . patients with 17ohd can not produce their own mature oocytes because of failed follicular development due to the irreversible defect in steroidogenesis , and therefore can not conceive spontaneously or via endocrinologic intervention . theoretically , assisted reproductive technology using in vitro maturation of immature oocytes is the only way for these female patients to have their own genetic offspring . almost all patients present for the evaluation of delayed puberty and may not complain of symptoms until the time of puberty , thus an early diagnosis is difficult to make prior to this clinical phase . some patients may visit the hospital at an earlier age for evaluation of hypertension that comes from increased 11-doc before menarche . for early diagnosis and adequate management , 17ohd should be considered when a girl or a young woman presents with poor sexual development and hypertension , because hypertension is uncommon in young age .
17-hydroxylase and 17,20-lyase are enzymes encoded by the cyp17a1 gene and are required for the synthesis of sex steroids and cortisol . in 17-hydroxylase deficiency , there are low blood levels of estrogens , androgens , and cortisol , and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone . in turn , the excessive levels of mineralocorticoids lead to volume expansion and hypertension . females with 17-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty , with accompanying hypertension . 
 affected males usually have female external genitalia , a blind vagina , and intra - abdominal testes . 
 the treatment of this disorder is centered on glucocorticoid and sex steroid replacement . in patients with 17-hydroxylase deficiency who are being raised as females , 
 estrogen should be supplemented , while genetically female patients with a uterus should also receive progesterone supplementation . here 
 , we report a case of a 21-year - old female with 17-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time . 
 we also include a brief review of the recent literature on this disorder .