primary hyperaldosteronism is the most common cause of secondary hypertension , characterized by excessive production of aldosterone relatively independent of the renin - angiotensin system . patients with hyperaldosteronism typically present with one or more symptoms , including hypokalemia , muscle weakness and cramping , headaches , palpitations , polydipsia , polyuria , and nocturia . adrenal vein sampling is recommended for most patients requesting surgical treatment as a means of differentiating between unilateral and bilateral forms of primary hyperaldosteronism . the term " subclinical cushing syndrome " is used to describe autonomous cortisol secretion in patients who otherwise lack the typical signs and symptoms of hypercortisolism ( cushing syndrome ) . although difficult to detect clinically , 5% to 20% of all adrenocortical adenomas are responsible for the cortisol overproduction . although the likelihood of subclinical cushing syndrome progressing to overt cushing syndrome remains a topic of considerable debate , subclinical cushing syndrome alone represents an important clinical condition , as it is strongly associated with several cardiovascular risk factors , including obesity , arterial hypertension , type 2 diabetes mellitus , dyslipidemia , and osteoporosis . recent reports have suggested an increase in the frequency of synchronous excretion of aldosterone and cortisol from adrenal masses . although most of these reports describe solitary or multiple adrenocortical adenomas secreting both aldosterone and cortisol simultaneously , cases of independent secretion of each hormone from separate adenomas are extremely rare . herein , we report an extremely rare case of a patient presenting with primary hyperaldosteronism and subclinical cushing syndrome caused by bilateral adrenocortical adenomas , each secreting different types of hormones ( cortisol from the left adenoma and aldosterone from the right ) . a 31-year - old woman was diagnosed with hypertension by a private clinic in august 2013 , based upon a systolic blood pressure of 160 mm hg and she was prescribed antihypertensive drugs to treat the condition . initial therapy consisted of hydrochlorothiazide 12.5 mg and losartan 50 mg daily . after 1 week , her blood pressure was still high , so the doctor changed her medication to amlodipine 5 mg , losartan 100 mg , and indapamide 2.5 mg per day . five days after initiating this second regimen of drugs , she developed pretibial pitting edema , and thorough workup was done for the symptom . routine blood tests revealed the following : potassium 2.2 mmol / l , plasma renin activity ( pra ) 0.12 ng / ml / hr , plasma aldosterone concentration ( pac ) 16.76 ng / dl , and an aldosterone / renin ratio ( pac / pra ) > 30 , indicative of primary hyperaldosteronism . following her possible diagnosis of primary hyperaldosteronism , the patient was referred to our hospital for additional testing . at the time of admission , her blood pressure was 155/111 mm hg , height was 164.5 cm , and weight was 63.5 kg ( body mass index , 23.47 kg / m ) . pretibial pitting edemas were detected , but no physical signs of cushing syndrome were observed . a routine blood test at the time of admission showed the following : white blood cell 6,900/l , hemoglobin 13.5 g / dl , platelet 351,000/l , total protein 6.9 g / dl , albumin 4.1 g / dl , aspartate aminotransferase 76 u / l , alanine aminotransferase 126 u / l , blood urea nitrogen 7.3 mg / dl , creatinine 0.71 mg / dl , sodium 141 mmol / l , potassium 2.9 mmol / l , chloride 101 mmol / l , total cholesterol 210 mg / dl , triglyceride 104 mg / dl , high density lipoprotein 50 mg / dl , low density lipoprotein 141 mg / dl , and hemoglobin a1c 5.9% . biochemical evaluation of pheochromocytoma showed no excessive catecholamine production . the transtubular potassium concentration gradient was 12.64% , suggesting the possibility of hyperaldosteronism or hypercortisolism . pac and pra were 24.4 ng / dl and 0.76 ng / ml / hr , respectively , and the pac / pra ratio was 32.11 ( table 1 ) . after correcting for hypokalemia , a saline loading test was performed , which revealed no suppression of the aldosterone level after saline administration , consistent with a diagnosis of hyperaldosteronism ( the basal pac 24.4 ng / dl increased to 27.3 ng / dl after a 2 l saline infusion ) . dexamethasone suppression tests ( dsts ) resulted in no suppression of cortisol levels ( table 2 ) . adrenal ct demonstrated two bilateral adrenal masses in each of the adrenal glands , including a 1.6-cm mass on the right and a 2-cm mass on the left adrenal gland ( fig . an adrenal cortical scan using iodine-131 - 6-iodomethyl-19-norcholesterol ( np-59 ) showed focally increased radioactive uptakes in the bilateral adrenal gland areas , with a substantially higher uptake on the left side ( fig . bilateral adrenal venous sampling ( avs ) with adrenocorticotropic hormone ( acth ) stimulation ( table 3 ) revealed inadequate right adrenal venous blood sampling ( right adrenal vein cortisol level / peripheral blood cortisol level [ crt / cp ] < 10 ) , whereas the cortisol concentration in the left adrenal venous blood showed successful sampling on the left side . one explanation for this difference may be that the low level of crt was the result of suppressed cortisol secretion due to excessive cortisol secretion from the left adrenal mass . the left adrenal vein aldosterone / cortisol ( alt / clt ) ratio was lower than that of peripheral blood , implying the possibility of suppressed aldosterone secretion from this side caused by a contralateral adrenal mass which might secrete excessive aldosterone . four days after the first avs , a second avs was performed using low - dose dst but without acth infusion ( table 4 ) . this time , we also measured the epinephrine levels in the both adrenal veins and peripheral blood ; a large peripheral - to - adrenal gradient of epinephrine assured successful catheterization on both sides . clt / cp testing confirmed that the left adrenal mass was a cortisol - secreting adenoma . even though those two avs results appeared to provide clear evidence of the lateralization of functioning adrenal masses , such an independent functioning of bilateral masses was highly suspicious . we therefore concluded that sequential adrenalectomies , rather than concurrent operations , would be beneficial for making a definitive diagnosis . the first procedure was a laparoscopic partial adrenalectomy of the right adrenal gland to remove the putative aldosterone - producing mass , with the goal of controlling hypertension and hypokalemia . a firm , 1.5-cm ovoid , well - circumscribed , bright yellow tumor mass lacking necrosis or hemorrhage was arising from the cortex of the adrenal gland in the pathologic specimen . within 24 hours after surgery , the patient 's blood pressure had fallen to 110/80 mm hg without antihypertensive medication , serum potassium normalized at 4.5 mmol / l , and pac decreased to 3 ng / dl . these large postoperative changes strongly suggested that the right adrenal adenoma was producing excessive aldosterone . by day 3 , an overnight dst continued to show no cortisol suppression , indicating persistent secretion of corticosteroid from the left adrenal mass . to limit the likelihood of subclinical cushing syndrome progressing to overt cushing syndrome , we opted to completely remove the left adrenal gland as a means of controlling hypercortisolism . the patient began taking prednisolone 10 mg once a day for steroid replacement 1 day after the second surgery . by 2 months she had lost 5 kg of body weight . at that time , a rapid acth test revealed adrenal insufficiency ( table 5 ) . at 16 months after surgery , the patient has gradually reduced her prednisolone intake to 5 mg every other day . her blood pressure and serum potassium levels have remained within normal ranges , without the need for additional antihypertensive medications or potassium supplements . primary hyperaldosteronism is one of the main causes of secondary hypertension , characterized by an excessive production of aldosterone independent of the renin - angiotensin system and a lack of response to the sodium loading test . the prevalence of primary hyperaldosteronism in nonselected hypertensive patients and adrenal incidentaloma is 10% and 1.8% , respectively . the vast majority of patients with hyperaldosteronism exhibit either a unilateral aldosterone - producing adenoma or idiopathic bilateral adrenal hyperplasia ; in comparison , bilateral aldosterone - producing adenomas are rarely reported . relatively young patients presenting with functioning adrenocortical adenomas , particularly those producing aldosterone , are treated with surgical excision as a means of achieving symptom control , including hypertension and persistent hypokalemia . thus , recognizing the lateralization of aldosterone secretion in cases of bilateral adenomas is important . in these cases , avs is considered the gold standard for detecting aldosterone production in bilateral adrenal hyperplasia and for distinguishing the lateralization of aldosterone secretion . evidence of subclinical cushing syndrome in the presence of primary hyperaldosteronism has been reported in several studies , most of which described a solitary adrenocortical adenoma secreting both aldosterone and cortisol simultaneously . reported a case of bilateral adrenocortical adenomas in which the left adenoma secreted cortisol or both cortisol and aldosterone , while the right adenoma secreted both aldosterone and cortisol , as confirmed by avs and pathological studies using immunohistochemical stains . as primary hyperaldosteronism has been shown to coexist with hypercortisolism , patients should also be tested for hypercortisolism in cases of suspected primary hyperaldosteronism . however , cases of multiple simultaneous adrenocortical adenomas secreting each hormone independently are extremely rare , particularly when those adenomas are located in different adrenal glands . as far as we can find from the database of pubmed and koreamed , only four cases have been reported in english , japanese , and korean . the first such case in korea was reported by choi et al . , who described a patient having primary hyperaldosteronism and cushing syndrome with bilateral adrenal masses . avs testing was unsuccessful in this patient , leading to simultaneous removal of the bilateral adrenal masses . as the removal of these masses was performed together , the identities of hormones secreted from each mass were unclear . in contrast , our sequential surgical approach was able to identify discrete secretory functions for each mass . this case is therefore the first report in korea describing bilateral adrenocortical adenomas functioning independently that resulted in subclinical cushing syndrome and primary hyperaldosteronism . a similar report by onoda et al .   described a case of synchronous cushing syndrome and primary hyperaldosteronism with multiple adrenocortical adenomas secreting each hormone individually . avs showed excess secretion of cortisol and aldosterone from the right and left tumors , respectively . a bilateral laparoscopic partial adrenalectomy was performed , followed by in situ hybridization for mrnas in each pathologic specimen so as to demonstrate independent production of cortisol ( both hsd3b2 and cyp17a1 mrnas expression ) and aldosterone ( both hsd3b2 and cyp11b mrnas expression ) . to our knowledge , this is the first case in korea describing the co - presence of a corticosteroid - producing left adrenal adenoma and an aldosterone - producing right adrenal adenoma , which was demonstrated biochemically and clinically by avs and the sequential removal of adrenal masses . based upon the findings described here , avs may be useful for accurately diagnosing patients with hypercortisolism accompanied by bilateral adrenal masses . in the second round of avs testing using low - dose dst and without acth stimulation , an elevated clt / cp ratio revealed autonomous cortisol production by the left adrenocortical adenoma . a combination of a basal hormone test in conjunction with avs results confirmed the coexistence of excessive cortisol and aldosterone secretion . while a few reports have demonstrated adenomas producing cortisol and aldosterone using cyp11b1/b2 immunohistochemical staining , our analyses were limited to standard clinical and biochemical tests due to a lack of the availability of immunohistochemical tests in korea . 2 ) were compatible with features of both aldosteronomas ( often a small and solitary mass , a transverse section demonstrating a lipid - rich , bright yellow color ) and adenomas causing cushing syndrome ( well defined with apparent encapsulation , the cut surface appearing as yellow or irregular mottled areas or showing diffuse pigmentation ) . in conclusion diagnoses were confirmed by avs and postoperative changes in clinical features and laboratory tests , which demonstrated the co - presence of a cortisol - producing left adrenal adenoma and an aldosterone - producing right adrenal adenoma . such cases of bilateral adrenocortical adenomas with independent production of different hormones are extremely rare , and in this regard , this case report is the first important finding of this disease in korean patients .
a 31-year - old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of cushing syndrome . 
 the serum aldosterone / renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level , consistent with a diagnosis of primary hyperaldosteronism . overnight and low - dose dexamethasone suppression tests showed no suppression of serum cortisol , indicating a secondary diagnosis of subclinical cushing syndrome . adrenal vein sampling during the low - dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass . 
 a partial right adrenalectomy was performed , resulting in normalization of blood pressure , hypokalemia , and high aldosterone level , implying that the right adrenal mass was the main cause of the hyperaldosteronism . 
 a total adrenalectomy for the left adrenal mass was later performed , resulting in a normalization of cortisol level . 
 the final diagnosis was bilateral adrenocortical adenomas , which were secreting aldosterone and cortisol independently . 
 this case is the first report of a concurrent cortisol - producing left adrenal adenoma and an aldosterone - producing right adrenal adenoma in korea , as demonstrated by adrenal vein sampling and sequential removal of adrenal masses .