A case of primary aldosteronism due to unilateral adrenal hyperplasia.

The case of a patient with primary aldosteronism due to unilateral adrenal hyperplasia (UAH) is reported. A 43-year-old man with an 8-year history of hypertension presented at our institution with hypokalemia, increased plasma aldosterone concentration (PAC), and suppressed plasma renin activity (PRA). An abdominal CT scan showed almost normal adrenal glands with slight enlargement in the left gland. 131I-Norcholesterol adrenal scintigraphy under dexamethasone suppression showed bilaterally decreased uptake. To rule out idiopathic hyperaldosteronism, an adrenal vein sampling before and after ACTH stimulation was performed and a left-sided lateralization of PAC was observed. A left adrenalectomy was performed, and the patient had a good clinical and biochemical response. Micronodular hyperplasia was discovered in the adrenal gland histologically, and in the immunohistochemical analysis, positive staining for 3beta-hydroxysteroid dehydrogenase in micronodular lesions confirmed the diagnosis of UAH. Although UAH is a rare subset of primary aldosteronism, it is surgically correctable as a unilateral autonomous aldosterone-producing lesion. Careful investigations, including bilateral adrenal vein sampling, should be performed for the diagnosis.     

A case of primary aldosteronism caused by multiple adrenocortical macronodules

A 60-year-old man presented with drug-resistant hypertension with hypokalemia, a high plasma aldosterone concentration (PAC) and suppressed plasma rennin activity (PRA). Imaging examinations showed multiple macronodules in the left adrenal gland. Endocrinological findings demonstrated autonomous aldosterone secretion and (131)I-adosterol scintigraphy demonstrated a left sided uptake. Laparoscopic left adrenalectomy normalized serum potassium levels and PAC, and substantially improved hypertension. Pathological and immunohistochemical analysis demonstrated that these nodules were positive for 3β-hydroxysteroid dehydrogenase (HSD3B) but not for CYP17. In addition, zona glomerulosa demonstrated "paradoxical hyperplasia", in which these cells were negative for HSD3B. All of these data indicated that the nodules in the left adrenal gland were mainly responsible for the autonomous aldosterone secretion. We conclude that the primary aldosteronism in this case was caused by multiple macronodules. This is a very rare case of primary aldosteronism caused by multiple adrenocortical macronodules.     

Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.     

A case with primary aldosteronism due to unilateral multiple adrenocortical micronodules

A 46-year-old male with long-term treatment-resistant hypertension and past history of cerebral hemorrhage was found to have suppressed plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) with aldosterone/renin ratio of 25.3. Furosemide plus upright test did not stimulate PRA, but computed tomography scan of the abdomen revealed no abnormal lesions in either adrenal gland. Selective adrenal venous sampling (SAVS) showed that PAC in the left and the right adrenal vein were 1000 ng/dl and 230 ng/dl, respectively, which increased to 1500 ng/dl and 620 ng/dl, respectively, after ACTH stimulation. Diagnosis of primary aldosteronism due to hypersecretion of aldosterone from the left adrenal gland was made, and laparoscopic left adrenalectomy was performed. Pathological examination of the 'apparently normal' adrenal tissue resected revealed the presence of poorly encapsulated multiple adrenocortical micronodules which showed positive immunoreactivity for 3beta-hydroxysteroid dehydrogenase by immunohistochemical study, but negative immunoreactivity in the hyperplastic zona glomerulosa consistent with paradoxical hyperplasia associated with primary aldosteronism. Postoperatively, PRA was normalized and his high blood pressure was well controlled with lower doses of antihypertensive drugs than those used before surgery. The clinicopathological features of our case are consistent with the diagnosis of unilateral multiple adrenocortical micronodules (UMN), a new subset of primary aldosteronism, in which SAVS proved to be a useful diagnostic tool for its localization.     

A case of normoreninemic aldosterone-producing adenoma associated with chronic renal failure: case report and literature review

The diagnosis of aldosterone-producing adenoma (APA) is challenging for endocrinologists, as APA does not always present with the typical constellation of clinical and laboratory features, such as hypertension, hypokalemia, suppressed plasma renin activity (PRA), and high plasma aldosterone concentration (PAC). Very recently, several studies have indicated that APA can be discovered even in normokalemic subjects with normal PRA more frequently than previously considered. Here we report a case of APA associated with chronic renal failure, which showed normokalemia and normal PRA. The patient was referred to our clinic for evaluation of an incidentally discovered adrenal mass with abnormally high PAC. After 6 yr, it was found that the right adrenal tumor showed a marked increase in size. Endocrinological examinations indicated normal PRA and markedly high PAC. Aldosterone showed a better response to the upright posture test than that to ACTH stimulation test. The diagnosis of APA was made based on the markedly high PAC to PRA ratio and the adrenocortical scintigraphy, which showed unequivocal uptake into the tumor. Right laparoscopic adrenalectomy was performed, revealing a right adrenocortical adenoma with massive hemorrhage. Histopathological examinations revealed the presence of two independent adrenocortical adenomas, one APA with predominant clear tumor cells and few c17 (17alpha-hydroxylase) immunoreactivity and the other, cortisol producing adenoma with compact cytoplasm and abundant C17 immunoreactivity. This case indicates a difficulty of diagnosis of “normoreninemic APA” with renal failure. This case is in line with the recent concept that APA is a continuous condition in which only a minority of patients have the classical clinical picture of primary aldosteronism such as hypokalemia. It is possible that normokalemic APA constitutes the most common presentation of the disease.     

Primary hyperaldosteronism in childhood due to unilateral macronodular hyperplasia. Case report

We present the first report of primary hyperaldosteronism in childhood due to unilateral macronodular hyperplasia. A 10-year-old white boy with severe hypertension (150/100 mm Hg), hypokalemia (1.4 mEq/liter), and suppressed plasma renin activity (PRA) (less than 0.1 ng/ml/hr) demonstrated fixed PRA and aldosterone (aldo) levels that did not change with alteration of dietary sodium. The paradoxical decrease in serum aldo on assumption of upright posture suggested a tumor. Prolonged ACTH administration produced a continuous rise in blood pressure, but a transient rise in aldo. A minimal decrease in urinary aldo during dexamethasone administration was noted, excluding dexamethasone-suppressible hyperaldosteronism. Blood pressure normalized with spironolactone. Computerized transaxial tomography, iodocholesterol scanning, and adrenal venography were not diagnostic of a discrete adrenal lesion. Although hyperplasia is more common than an adenoma as a cause of hyperaldosteronism in childhood, a tumor was predicted, since adrenal vein hormone sampling with ACTH stimulation lateralized aldosterone secretion unequivocally to the left adrenal gland. However, left adrenalectomy revealed macronodular hyperplasia. Postoperatively, there was reversal of hypertension, hypokalemia, and hyperaldosteronism. Thus, in childhood, unilateral hypersecretion of aldosterone may result from nodular hyperplasia, rather than a discrete adenoma.     

Adrenal adenoma with bilateral adrenocortical nodular change in a patient with Cushing's syndrome

We report a 57-year-old male patient with adrenocorticotrophin (ACTH)-independent Cushing's syndrome and long-standing hypertension. Both abdominal computed tomographic scan and magnetic resonance imaging revealed bilateral adrenal enlargement with the presence of a tumour in the left adrenal. Marked uptake of ¹³¹I-6β-iodomethyl-19-norcholesterol was observed only in the left adrenal gland. Left adrenalectomy and biopsy of the right adrenal gland were subsequently performed. Histological examination revealed the presence of an adrenocortical adenoma in the left adrenal with multiple adrenocortical nodules in both left and right non-neoplastic adrenals. Peri- and intraadrenal arteries and arterioles demonstrated marked arteriosclerotic vascular changes. Immunoreactivity for several steroidogenic enzymes was present in the tumour and markedly diminished in the non-neoplastic adrenals. This patient with Cushing's adenoma is considered to have developed adrenocortical nodules in the non-neoplastic adrenal possibly as a result of localized compensatory overgrowth of adrenocortical cells in response to ischaemic changes due to arteriopathy. When examining patients with Cushing's syndrome and bilateral adrenal enlargement, the possibility of concomitant adenoma and adrenocortical nodule formation should also be considered in the differential diagnosis.     

Pheochromocytoma due to unilateral adrenal medullary hyperplasia

We describe two male patients, aged 17 and 47 years, with clinical and biochemical features of pheochromocytoma. Both patients had normal-sized adrenal glands on abdominal CT scan and abnormal unilateral uptake of I-123 metaiodobenzylguanidine (MIBG) on scintigraphy. The surgical adrenalectomy revealed normal macroscopic glands in both patients. Histological examination showed adrenal medullary hyperplasia with adrenal cortico-medullary ratios of 2 : 1 and 4 : 1. Unilateral adrenalectomy resulted in amelioration of symptoms and normalization of catecholamines excretion. DNA examination for RET proto-oncogene revealed no mutations in exons 10, 11, 13, 14 and 16. Our results suggest that diffuse adrenal medullary hyperplasia may be the initial pathological change in the adrenal gland leading, subsequently, to the development of nodular hyperplasia and adrenal medullary tumor. These results indicate that the syndrome of pheochromocytoma may occur as an unilateral adrenal medullary hyperplasia in patients without evidence for multiple endocrine neoplasia.     

Diagnostic accuracy of adrenal venous sampling in comparison with other parameters in primary aldosteronism

This retrospective study was aimed 1) to compare the difference of the findings between adrenal CT scan and adrenal venous sampling (AVS) in 35 cases with definite primary aldosteronism (PA) for assessment of the diagnostic efficacy of PA subgroup (unilateral and bilateral adrenal hypersecretion: UAH and BAH), and 2) to determine the clinical and biochemical parameters as potential predictors for PA subgroup. There were significant discordant results based on AVS and CT scan in subgrouping PA; 9 of 17 BAH patients (53%) had unilateral lesion on CT scan, while 4 of 18 UAH patients (22%) had no apparent or bilateral lesions on CT scan. Among three diagnostic criteria, absolute values of plasma aldosterone concentration (PAC) in both adrenal veins, lateralized and contralateral ratios of aldosterone/cortisol after ACTH stimulation during AVS to determine the laterality, none of them showed 100% diagnostic accuracy if applied alone. Among several clinical and biochemical parameters, hypokalemia (<3.4 mEq/l), younger age (<52 y) and poor response of PAC (<1.45) after furosemide-upright posture, proved to be significant predictors for UAH, with higher specificities (100%, 88%, 94%, respectively). Therefore, despite AVS as a gold standard method to determine the laterality of aldosterone hypersecretion in PA, our study shows that no single criterion could provide definite diagnostic value for its laterality by AVS. It is also suggested that most PA patients, if not all, with a distinct unilateral adrenal lesion on CT accompanied by hypokalemia, younger age and poor aldosterone response to renin stimulation, could undergo adrenalectomy without prior AVS.     

Pheochromocytoma combined with pre-clinical Cushing's syndrome in the same adrenal gland

Pheochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. In most of them, ectopic adrenocorticotropic hormone (ACTH) produced by PHEO resulted in bilateral adrenocortical hyperplasia. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report on a patient and discuss the peculiar diagnostic aspects of this entity. A 52-yr-old Turkish woman was hospitalized at Farabi Hospital for further examinations of a right adrenal mass that was incidentally discovered by abdominal ultrasonography during examinations for abdominal bloating and "gas" in other hospital. The patient had a history of palpitations, nervousness, sweating and heat intolerance. On admission, her blood pressure was 140/90 mmHg. A physical examination revealed no signs of an excessive production of adrenocortical steroids such as in CS. Tension Holter monitoring revealed paroximal hypertension attacks (183/105 mmHg). Urinary catecholamines were markedly increased. Her serum cortisol concentrations ranged from 5 to 17 microg/dl, whereas ACTH levels were undetectable. Cortisol was not suppressed on the overnight 1 mg oral dexamethasone suppression test (DST), 2-day low-dose dexamethasone suppression test (DST). Abdominal computed tomography and magnetic resonance imaging studies revealed a solid round tumor approximately 4 cm in diameter, located in the right adrenal gland. A 131 lodine-metaiodobenzylguanidine (131 I-MIBG) scan revealed uptake within tumor in the right adrenal gland. Right adrenalectomy was performed; the surgical specimen revealed PHEO and adrenocortical hyperplasia. To our knowledge, the present report is a rare case of PHEO combined with PCS in the same adrenal gland.     

Gastric diverticulum simulating left adrenal incidentaloma in a hypertensive patient

A 46-year-old Japanese male with hypertension was referred for examination of left adrenal tumor incidentally detected by computed tomography (CT) scan. The patient had a 4-month history of hypertension. Abdominal CT demonstrated a low-density mass 2.5 cm in diameter in the left adrenal region that was observed as a high-intense lesion with T2-weighted magnetic resonance imaging. (131) I-adosterol scintigraphy showed normal uptake of bilateral adrenals. The adrenocortical hormone levels were within normal ranges; however, urinary noradrenaline excretion was slightly elevated, likely due to concurrent sleep apnea syndrome. Based on the observation of a very tiny bubble in the ventral portion of the adrenal mass by careful review of CT images examined at a previous hospital, a restudy of abdominal CT with oral contrast was performed. In this restudy abdominal CT we observed positive enhancement of the left adrenal mass, indicating that the adrenal mass was a diverticulum derived from posterior gastric fornix. The present case study reinforces that preoperative differentiation from mimic adrenal tumors is necessary in cases of cystic adrenal mass in the left adrenal region.     

A rare case of ACTH-independent macronodular adrenal hyperplasia associated with aldosterone-producing adenoma

A 52-year-old man was evaluated for incidentally discovered bilateral adrenal masses. He had drug-resistant hypertension but lacked Cushingoid features. Endocrinological tests revealed autonomous secretion of cortisol and aldosterone with suppressed plasma ACTH and renin activity. A selective adrenal venous sampling demonstrated aldosterone hypersecretion from the left adrenal vein. The clinical diagnosis of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) associated with primary aldosteronism was made, and he underwent left adrenalectomy; the resected adrenal lesion was consistent with the pathological diagnosis of AIMAH coexistent with aldosterone-producing adenoma (APA). This is a very rare case of AIMAH with concomitant unilateral APA, whose hypertension improved after surgery.     

Unilateral adrenalectomy improves insulin resistance and polycystic ovaries in a middle-aged woman with virilizing adrenocortical adenoma complicated with Cushing's syndrome

A benign virilizing adrenal adenoma is rare among adrenal neoplasms in middle-aged women. A 39-yr-old Japanese woman who presented with hirsutism, obesity, diabetes mellitus and hypertension was admitted. Plasma concentrations of testosterone and DHEAS were high. While the basal level of plasma ACTH was suppressed, serum cortisol level was high and its circadian rhythm was absent. Serum cortisol level was not suppressed with the low- and high-dose overnight dexamethasone suppression test. Abdominal computed tomography showed a left adrenal tumor, and an adrenocortical scintigraphy revealed uptake of the tracer on the left side. Polycystic ovaries were also found and bone mineral density revealed osteoporosis. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma. Immunoreactivity of all the steroidogenic enzymes was apparent in the tumor cells and particularly dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was markedly expressed. Cortical atrophy and reduced expression of DHEA-ST were detected in the cortex of the adjacent non-neoplastic adrenal gland. Plasma testosterone, DHEAS and cortisol levels returned to normal after surgery, concomitantly with the disappearance of polycystic ovaries. This is a very rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome (CS).     

Association of adrenal medullar and cortical nodular hyperplasia: a report of two cases with clinical and morpho-functional considerations

Arterial hypertension of adrenal etiology is mainly attributed to primary hyperaldosteronism. However, subtle expressions of hyperadrenergic or glucocorticoid excess can also generate arterial hypertension. The present report describes two hypertensive patients cataloged as resistant essential hypertensives, in whom adrenal masses were found incidentally, who highlight the need to recognize these tenuous clinical or laboratory presentations. Case 1 was a 50-yr-old female with hyperadrenergic hypertension associated to a left adrenal node, normal cortisol and aldosterone:renin ratio, marginally increased urinary normetanephrine, and a positive 131I MIBG radioisotope scan. Adrenalectomy normalized blood pressure and urinary metanephrines. Pathology showed a hyperplastic adrenal medulla associated to a multinodular cortical hyperplasia. Case 2 was a 62- yr-old female with progressive hypertension, a slight Cushing phenotype, non-suppressible hypercortisolism, normal urinary metanephrines, and bilateral adrenal nodes. Bilateral adrenalectomy and subsequent replacement normalized blood pressure and phenotypic stigmata. Pathology demonstrated bilateral cortical multinodular hyperplasia and medullary hyperplasia. The clinical study in both patients was negative for MEN. The apparently rare association of cortical and medullary lesions presented by both patients is probably overlooked in routine pathology exams, but should be meticulously searched since the crosstalk between the adrenal cortex and medulla may prompt dual abnormalities.     

A case of aldosterone-producing adrenocortical adenoma associated with a probable post-operative adrenal crisis: histopathological analyses of the adrenal gland.

We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent.     

Right adrenal recurrence of pheochromocytoma discovered 24 years after ablation of two ectopic pheochromocytomas

The classical localisation of chromaffin cell tumours is intra-adrenal. Ectopic or multiple tumours are not rare and are commonly observed in children. The authors report a case of ectopic pheochromocytoma with a double localisation in a 14 year old child (renal pedicle and right retropleural space), in which surgical ablation resulted in an immediate and sustained correction of the hypertension. Hypertension recurred 24 years later and a classical right adrenal pheochromocytoma was demonstrated by methyl-iodo-benzylguanidine (M.I.B.G.) scintigraphy and abdominal CT scan. Right adrenalectomy resulted in normalisation of the hypertension once again without antihypertensive therapy with a follow-up of three years. Regular follow-up is necessary after ablation of a pheochromocytoma, especially in children, even in the absence of a phacomatosis or multiple endocrine neoplastic syndromes.     

Detecting and treating primary aldosteronism: primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies, using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. Idiopathic bilateral adrenal hyperplasia (IHA) and aldosterone-producing adrenal adenoma (APA), are the leading causes of primary aldosteronism. Glucocorticoid-remediable aldosteronism (GRA), also called familial hyperaldosteronism type I, familial hyperaldosteronism type II and carcinomas are rare causes of PA. Patients with hypertension and hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with medication-resistant hypertension should be screened for PA using the PAC/PRA ratio. If a high ratio is found, a sodium loading test or a captopril test is warranted to confirm the diagnosis. Adrenal gland imaging is important in subtype differentiation (APA vs IHA). Adrenal venous sampling should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA. Surgery is considered the treatment of choice for patients with APA, while bilateral hyperplasia subtypes are treated medically. Normalization of aldosterone levels or aldosterone receptor blockade are necessary to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage.     

Cyclical Cushing syndrome presenting in infancy: an early form of primary pigmented nodular adrenocortical disease, or a new entity?

Cushing syndrome is uncommon in childhood and rare in infancy. We report the case of a 3-yr-old child who presented with symptoms of Cushing syndrome beginning shortly after birth. Her hypercortisolemia was cyclical, causing relapsing and remitting symptoms, which eventually led to suspicions of possible Munchausen syndrome by proxy. Investigation at the National Institutes of Health excluded exogenous administration of glucocorticoids and indicated ACTH-independent Cushing syndrome. Paradoxical response to dexamethasone stimulation (Liddle's test) suggested a diagnosis of primary pigmented nodular adrenocortical disease (PPNAD).After bilateral adrenalectomy, both glands showed micronodular adrenocortical hyperplasia, but histology was not consistent with typical PPNAD. DNA analysis of the coding sequences of the PRKAR1A gene (associated with PPNAD and Carney complex) and the GNAS gene (associated with McCune-Albright syndrome) showed no mutations.We conclude that hypercortisolemia in infancy may be caused by micronodular adrenocortical hyperplasia, which can be cyclical and confused with exogenous Cushing syndrome. A paradoxical rise of glucocorticoid excretion during Liddle's test may delineate these patients. Infantile micronodular disease has some features of PPNAD and may represent its early form; however, at least in the case of the patient reported here, micronodular hyperplasia was not caused by coding mutations of the PRKAR1A or GNAS genes or associated with typical histology or any other features of Carney complex or McCune-Albright syndrome and may represent a distinct entity.     

Variant of pre-clinical Cushing's syndrome: hypertension and hypokalemia associated with normoreninemic normoaldosteronism.

The case of a 48-year-old woman with a left adrenocortical adenoma and showing hypokalemia, hypertension and normoreninemic normoaldosteronism is reported. Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol levels were within the reference ranges. The patient's plasma cortisol level decreased insufficiently at night, and was insufficiently decreased by nighttime administration of dexamethasone. She showed no Cushingnoid stigmata. Iodocholesterol scintigraphy revealed tumor-sided uptake alone. The plasma dehydroepiandrosterone-sulfate level was low-to-normal for her age. Metabolic alkalosis and increased potassium clearance after sodium thiosulfate loading were revealed. The plasma aldosterone level was within the normal range, but it was statistically higher than the range for patients with pre-clinical Cushing's syndrome. However, peripheral plasma renin activity (PRA) increased normally after the patient resumed an upright posture following furosemide administration. After adenomectomy the hypokalemia and hypertension were resolved, and the plasma ACTH, cortisol, and PRA remained within the reference ranges. The plasma aldosterone level decreased slightly, but also remained within the reference range after adenomectomy. Paradoxical hyperplasia in the non-neoplastic adrenal glomerulosa zone, which indicates primary aldosteronism, and slight atrophy of the non-neoplastic adrenal cortex, which indicates pre-clinical Cushing's syndrome, were demonstrated. These findings satisfied the criteria of pre-clinical Cushing's syndrome, but did not completely satisfy those of primary aldosteronism. However, the level of CYP11 B2 mRNA in the tumor was in the lower-limit of the range for adenomas associated with primary aldosteronism and was higher than the ranges for adenomas associated with pre-clinical Cushing's syndrome and overt Cushing's syndrome. Based on these results, this case was suspected to constitute a variant of pre-clinical Cushing's syndrome with slight hypersecretion of aldosterone.