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Baseline Endocrine Workup for Suspected ACC

Hormonal Evaluation

Baseline endocrine workup for suspected adrenocortical carcinoma (ACC) is the initial biochemical assessment performed when an adrenal mass or endocrine syndrome raises concern for malignant adrenocortical disease. Within ACC evaluation, it complements imaging, staging, and surgical planning by identifying clinically significant hormone excess, defining secretory phenotype, and excluding biochemical mimics that alter procedural safety, especially pheochromocytoma.123

ACC may produce glucocorticoids, adrenal androgens, mineralocorticoids, estrogens, or multiple steroid precursors, and many tumors show mixed or inefficient steroidogenesis rather than a single classic endocrine syndrome.456 This broad endocrine range is part of the biological distinction between ACC and many benign adrenal adenomas, but routine hormonal assays do not by themselves establish malignancy with high certainty.17

The evidence base for baseline endocrine testing in suspected ACC remains limited. Most recommendations are derived from expert guidelines, retrospective series, adrenal incidentaloma cohorts with relatively few ACCs, and case reports describing uncommon secretory phenotypes.8910 As a result, biochemical testing is more reliable for detecting hormone excess that changes management than for definitively distinguishing carcinoma from adenoma, and negative or equivocal results do not exclude ACC.12

Broad endocrine assessment is therefore used as part of an integrated diagnostic pathway. In current practice, its main value is to uncover occult cortisol autonomy, androgen or precursor excess, selective mineralocorticoid syndromes, and mixed secretion patterns that may affect perioperative preparation, postoperative adrenal insufficiency risk, and longitudinal monitoring in hormonally active disease.1156

Diagnostic context

Baseline endocrine testing is generally undertaken when imaging or clinical presentation makes ACC a realistic possibility, including large or heterogeneous adrenal masses, rapidly progressive growth, virilization, hypercortisolism, resistant hypertension, hypokalemia, or otherwise unexplained sex steroid abnormalities.5123 A similar approach is often applied to adrenal incidentalomas because clinically subtle hormone excess can occur even in patients without overt endocrine signs, and a minority of ACCs present this way.13714

Endocrine evaluation complements rather than replaces radiologic and pathologic assessment. Its most dependable contribution is recognition of hormone-mediated risk and treatment implications; its least dependable contribution is etiologic discrimination between benign and malignant cortical tumors using standard single-analyte testing alone.12 Clinically, this supports a low threshold for comprehensive hormonal screening when suspicion for ACC is substantial, while avoiding overinterpretation of any isolated abnormality.

Core hormonal phenotypes

Cortisol autonomy

Assessment for autonomous cortisol secretion is a central part of the baseline workup. Current recommendations generally emphasize an overnight 1 mg dexamethasone suppression test, usually interpreted with morning ACTH, with additional tests such as urinary free cortisol used according to clinical phenotype and pretest probability.15214 Suppressed ACTH and loss of normal cortisol rhythmicity support adrenal, ACTH-independent hypercortisolism rather than pituitary-driven disease.161718

The most reliable implication of identifying cortisol autonomy is its effect on management rather than diagnosis. Even mild or clinically occult cortisol excess may influence perioperative glucocorticoid planning and the risk of postoperative adrenal insufficiency after adrenalectomy.11196 However, cortisol-based testing is not fully reliable for ACC phenotyping because some tumors secrete subtly, produce non-cortisol glucocorticoids or precursors, or show misleading ACTH results because of assay limitations.202122 In practice, abnormal cortisol physiology is meaningful when present, but nondiagnostic testing does not exclude a hormonally active ACC.

Androgen and steroid precursor excess

Measurement of adrenal androgens and steroid precursors is the other major component of baseline evaluation. DHEAS, androstenedione, testosterone, and 17-hydroxyprogesterone are commonly assessed, particularly in patients with virilization, rapid hyperandrogenism, or combined cortisol-androgen features.22324 Marked androgen excess, especially when mixed with cortisol autonomy, is more suggestive of ACC than of benign adenoma.2512

Across historical biochemical studies and newer mass spectrometry-based series, ACC tends to show broader and more precursor-rich steroid patterns than adenoma, with recurring signals involving 11-deoxycortisol, 11-deoxycorticosterone, pregnenolone-derived steroids, androstenedione, and DHEAS.26272829 This pattern is generally interpreted as disorganized steroidogenesis with partial enzymatic inefficiency rather than selective overproduction of a single end product.3031 The clinically useful conclusion is that multisteroid abnormalities may strengthen suspicion for ACC, whereas isolated findings such as DHEAS elevation alone are less specific and may also reflect benign lesions or assay interference.83233

Mineralocorticoid and selective phenotypes

Aldosterone-renin testing is usually performed selectively in patients with hypertension, hypokalemia, or other features suggestive of primary aldosteronism.34235 True aldosterone-producing ACC appears uncommon, but ACC may also produce mineralocorticoid precursors such as deoxycorticosterone, causing severe hypertension or hypokalemia despite low or normal aldosterone values.363738

These syndromes are supported mainly by case reports and small series, so their frequency and generalizability are uncertain. The practical implication is that extended precursor testing may be useful when standard aldosterone-based evaluation does not explain a severe mineralocorticoid picture in a suspicious adrenal mass.1139

Excluding mimics and ensuring procedural safety

After cortical hormone phenotyping, the workup also serves an important safety function by excluding alternative adrenal tumors. Pheochromocytoma should be biochemically excluded before biopsy, surgery, or other invasive procedures in any adrenal mass, including one suspected to be ACC.123 This step does not diagnose ACC, but it remains essential because imaging overlap and occasional discordant biochemical profiles can create diagnostic confusion.74041

This is one of the more reliable parts of the baseline pathway because the question is procedural safety rather than cortical malignancy discrimination. By contrast, unusual mixed hormonal profiles may still require reinterpretation in the context of imaging, pathology, and assay method.

Advanced steroid profiling

When available, serum or urinary steroid profiling is the most ACC-oriented extension of the baseline endocrine workup. GC-MS and LC-MS/MS studies consistently suggest that ACC is associated with multisteroid excess enriched for steroid precursors, in contrast to the narrower profiles more typical of adenoma.42543 Among the most recurrent candidate analytes are 11-deoxycortisol, androstenedione, DHEAS, 17-hydroxyprogesterone, and related multisteroid panels.28442945

Retrospective data suggest that steroid profiling may improve risk stratification for indeterminate adrenal masses, particularly when combined with tumor size and standard hormonal testing.4610 What is less certain is how broadly these results can be generalized across centers, assays, and clinical subtypes, because technical standardization and prospective validation remain incomplete.4710 At present, steroid profiling is best regarded as an adjunct that may sharpen suspicion for ACC rather than a replacement for conventional diagnostic pathways.

Pitfalls and interpretation limits

Several limitations recur across the literature. Hormone measurements may be affected by obesity, medications, circadian variation, preanalytical conditions, and immunoassay cross-reactivity, particularly for cortisol, ACTH, and androgen testing.48339 Dynamic endocrine responses may also be atypical in ACC, so preserved suppression, absent suppression, or unexpected stimulation responses do not behave consistently enough to serve as standalone markers of malignancy.4950

Older and indirect studies support the same broad caution: dynamic testing may help classify cortisol physiology, but it does not reliably separate carcinoma from adenoma by itself.515253 The practical implication is that borderline or internally inconsistent findings may warrant confirmation with more specific methods, ideally including mass spectrometry-based steroid measurement when available.474346

Role in management and research

In management, baseline endocrine workup helps identify hormone-mediated complications, guide preoperative preparation, anticipate postoperative glucocorticoid needs, and establish biochemical markers that may later be followed in hormonally active disease.54556 Compared with imaging alone, it may better identify occult cortisol excess and mixed secretion patterns that have immediate implications for patient safety and perioperative care.

In research, the field is moving from single-analyte testing toward integrated steroid metabolomics that more closely reflects ACC as a disorder of dysregulated steroidogenesis.282945 Even so, the optimal minimal baseline panel is not fully standardized, and current evidence still supports a pragmatic approach: broad initial hormonal assessment for suspected ACC, cautious interpretation of any single marker, and integration of endocrine data with imaging, pathology, and clinical course.23

Included Articles

  • PMID 144263: This article describes glass capillary gas chromatography for simultaneous measurement of 26 urinary C19 and C21 steroid metabolites and illustrates its use in a child with virilizing adrenal carcinoma. The report supports urinary steroid pattern analysis as a tool for studying steroid production and metabolism in adrenal disease.42
  • PMID 180041: This pediatric endocrine study reports that serum dehydroepiandrosterone sulfate can serve as a practical indicator of abnormal adrenal androgen secretion, with markedly elevated levels in a child with adrenal carcinoma and persistence despite dexamethasone unlike congenital adrenal hyperplasia.56
  • PMID 182566: In six cortisol-secreting adrenocortical tumors causing Cushing syndrome, an 8-hour intravenous ACTH test distinguished ACTH-responsive from unresponsive tumors; unresponsive lesions included two black adenomas and one carcinoma and were associated with more severe clinical features and higher urinary 17-ketosteroid excretion.57
  • PMID 223357: Frequent plasma cortisol sampling in hypercortisolism showed that adrenal adenoma produced relatively flat, non-episodic cortisol secretion with near-zero ACTH, whereas Cushing’s disease retained pulsatile cortisol and ACTH patterns. The authors suggest short 6-hour cortisol profiling may help differentiate ACTH-dependent from adrenal autonomous cortisol excess when standard tests are equivocal.16
  • PMID 223356: In four women with Cushing’s syndrome from adrenocortical carcinoma, detailed blood and urinary steroid profiling showed patient-specific but longitudinally stable secretion patterns, including cortisol excess with suppressed ACTH and markedly increased urinary free deoxycorticosterone in all cases. Testosterone and estradiol elevations paralleled virilization, while urinary aldosterone tracked hypertension severity.58
  • PMID 710647: This tissue-based steroid microdetermination study found that cortisol-producing adrenal carcinoma had markedly low intratumoral aldosterone, cortisol, and corticosterone compared with adenomas, suggesting low steroid content per unit tissue despite clinical hormone excess. The report also highlights heterogeneity in steroid content across adrenal regions and between sides.59
  • PMID 1327327: In outpatient evaluation of suspected Cushing’s syndrome, 24-hour urinary free cortisol showed markedly better diagnostic performance than urinary 17-hydroxycorticosteroids, with less overlap against obese controls. The study also notes that very high cortisol excretion can occur in adrenal carcinoma but does not establish etiology without further ACTH testing and localization studies.60
  • PMID 2742414: In patients with primary adrenal hypercortisolism, the report describes a diagnostic pattern of elevated 24-hour urine free cortisol and 17-hydroxycorticosteroids, usually undetectable plasma ACTH, lack of suppression with high-dose dexamethasone, and generally absent ACTH or cortisol response to oCRH, supporting pituitary-independent disease.17
  • PMID 2152930: In a cortisol-secreting adrenocortical carcinoma case within a mixed Cushing syndrome cohort, dispersed tumor cells secreted very little cortisol per cell and were unresponsive to ACTH, cholera toxin, and forskolin. The study also showed that precursor steroid responses may persist despite weak cortisol output, highlighting discordance between cortisol production and upstream steroidogenesis.61
  • PMID 2854760: Two functioning adrenocortical carcinoma cases showed detectable, biologically active plasma ACTH despite hypercortisolism, indicating that measurable ACTH does not exclude an adrenal primary. Urinary steroid profiling demonstrated multiple steroid excess patterns characteristic of ACC and helped support tumor recurrence detection after surgery.62
  • PMID 2967899: In patients with Cushing’s syndrome and an adrenal mass, peripheral steroid profiling showed ACC had markedly higher 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, testosterone, and 11-deoxycortisol, with a higher 11-deoxycortisol-to-cortisol ratio than adenoma. These findings suggest disordered steroidogenesis and may help preoperative biochemical differentiation of carcinoma from adenoma.26
  • PMID 2986563: In Cushing’s syndrome caused by adrenocortical tumors, endocrine testing showed loss of normal diurnal cortisol variation, elevated urinary 17-hydroxycorticosteroids, resistance to high-dose dexamethasone suppression, and suppressed plasma ACTH. Preoperative clues favoring carcinoma included ACTH-stimulation nonresponse and markedly elevated urinary 17-ketosteroids, often above 40 mg per 24 hours.63
  • PMID 3551152: This review outlines biochemical evaluation of adrenocortical tumors, emphasizing screening and etiologic testing for Cushing’s syndrome with urinary free cortisol, dexamethasone suppression, plasma ACTH, and metyrapone. It also notes that markedly elevated urinary 17-ketosteroids and very high DHEA or DHEAS can suggest malignant adrenal cortical tumors.25
  • PMID 4024084: In a Cushing syndrome case caused by adrenocortical carcinoma, marked elevation of androgens and steroid precursors, absent ACTH responsiveness, and abnormal tissue steroid patterns were presented as clues supporting malignancy beyond routine histology. The report recommends detailed preoperative steroid studies alongside adrenal CT.64
  • PMID 4236096: A semiquantitative thin-layer chromatography method for urinary neutral 17-ketosteroid fractionation identified eight steroid compounds and showed diagnostically distinct excretion patterns across endocrine disorders. In one histologically confirmed adrenocortical carcinoma with Cushing syndrome, dehydroepiandrosterone was the predominant urinary 17-ketosteroid and appeared to drive the markedly increased total excretion.65
  • PMID 4247013: This pediatric ACC case links virilization to markedly increased urinary androgen metabolites, especially dehydroepiandrosterone, androsterone, aetiocholanolone, and unusual C19-delta16 steroids that were not normally detected in infants and fell markedly after tumor resection. The report illustrates how perioperative steroid profiling can document a functioning adrenal carcinoma.66
  • PMID 4251155: A pediatric virilizing ACC showed marked androgen and precursor excess, with very high urinary 17-ketosteroids and elevated plasma pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, androstenediol, testosterone, and multiple steroid sulfates. Adrenal vein sampling demonstrated higher concentrations of most precursors and sulfates than peripheral blood, supporting adrenal tumor secretion and complex peripheral conversion of testosterone.67
  • PMID 4260320: In a small pediatric series of adrenocortical disorders including four carcinomas, 24-hour urinary dehydroepiandrosterone excretion was elevated before surgery and declined toward normal three months postoperatively. The study suggests urinary dehydroepiandrosterone measurement may help biochemical diagnosis and postoperative assessment of steroid-secreting adrenocortical disease.68
  • PMID 4296070: This study describes a competitive protein-binding radioassay for 24-hour urinary cortisol and reports that all measured values in Cushing’s syndrome exceeded 120 ug/24 hr, while healthy and several non-Cushing groups were generally below this threshold. The assay was presented as a rapid, specific tool for detecting adrenocortical hyperfunction.69
  • PMID 4299351: In a small operative series of adrenocortical hyperfunction including two carcinomas, biochemical testing suggested that nighttime plasma cortisol is a useful screening measure, while combined urinary steroid profiling and dynamic testing improved differential diagnosis. Elevated baseline tetrahydro S and lack of 17-KS/17-KGS rise with metopirone, plus absent dexamethasone suppression, were associated with tumor cases.70
  • PMID 4306479: This study reports that reduced efficiency of adrenal 11 beta-hydroxylation, estimated by the cortisol to cortisol-plus-11-deoxycortisol ratio, was observed in patients with adrenocortical carcinoma, while ratios were generally normal in controls, after ACTH stimulation, and in nontumorous Cushing syndrome.30
  • PMID 4322562: This case report describes a metastatic cortisol-secreting adrenocortical carcinoma with unusual endocrine behavior, showing marked ACTH responsiveness and suppression of urinary steroid excretion with high-dose dexamethasone. The report cautions that these dynamic test results do not exclude ACC and may mimic bilateral adrenal hyperplasia.49
  • PMID 4326521: In this small 1971 series of Cushing syndrome cases, urinary delta5-pregnenetriol and pregnanetriol measured by gas chromatography were markedly elevated in adrenal carcinoma, especially delta5-pregnenetriol, while values in adrenal adenoma and hyperplasia were generally within or near normal ranges.71
  • PMID 4327689: This case report describes a virilizing ACC with markedly elevated urinary 17-ketosteroids and steroid precursors, including pregnanetriol and tetrahydro compound S, suggesting disordered steroidogenesis. The authors also note that precursor metabolite excess may help distinguish carcinoma from other adrenal causes of androgen excess.72
  • PMID 4597949: This review outlines endocrine workup for adrenal causes of hypertension relevant to ACC, emphasizing that cortisol-secreting adrenal carcinomas can cause severe hypertension with hypokalemic alkalosis. It describes dexamethasone suppression testing for Cushing syndrome and renin-aldosterone based evaluation of hypokalemic hypertensive patients.34
  • PMID 5462077: This case report describes hormonally active ACC presenting with Cushing syndrome and marked steroid excess, including very high urinary 17-ketosteroids and 17-hydroxycorticosteroids, increased DHEA, tetrahydro-compound S, pregnanetriol, and pregnanediol, with no response to ACTH, dexamethasone suppression, or metyrapone testing.73
  • PMID 6649220: In Cushing syndrome caused by adrenal tumors, peripheral steroid profiling may help distinguish ACC from adrenal adenoma, with markedly higher 17-hydroxyprogesterone, testosterone, androstenedione, dehydroepiandrosterone, and 11-deoxycortisol in ACC. The report also notes that cortisol measurement should preferably follow chromatographic separation from 11-deoxycortisol because assay cross-reactivity can falsely elevate apparent cortisol levels.31
  • PMID 7093917: A case report describes adrenocortical carcinoma initially appearing clinically nonfunctioning, then later developing marked cortisol and androgen hypersecretion with Cushingoid features and virilization. The report argues that all ACC patients should undergo broad steroid assay surveillance because apparent nonfunctioning status may change during progression or recurrence.74
  • PMID 7139973: In aldosterone-producing adrenocortical carcinoma, plasma deoxycorticosterone was reported as consistently elevated, alongside high aldosterone and often elevated 18-hydroxycorticosterone, despite normal cortisol. The excerpt suggests this steroid pattern may help identify a primary adrenal zona glomerulosa abnormality and distinguish it from idiopathic hyperaldosteronism.36
  • PMID 7584693: A small 1995 study describes a 24-hour intravenous dexamethasone suppression test for differential diagnosis of Cushing’s syndrome. Cortisol did not suppress in patients with autonomous adrenal adenoma or primary adrenocortical nodular dysplasia, contrasting with transient suppression in pituitary ACTH-dependent disease and sustained suppression in controls.50
  • PMID 7951578: In patients with non-hyperfunctioning adrenal cortical adenomas, standard endocrine testing showed suppression on 1 mg dexamethasone testing and negative provocative evaluation for occult pheochromocytoma, while tissue steroid analysis suggested preserved steroidogenesis with relatively reduced aldosterone production and increased 17alpha-hydroxylase activity in tumor tissue.75
  • PMID 8612460: In a prospective series of 85 adrenal incidentalomas, subclinical hypercortisolism was identified in 6% using inadequate suppression on a 2 mg dexamethasone test plus low plasma ACTH despite absent Cushing stigmata. The report supports routine endocrine screening of incidental adrenal masses because hormonal abnormalities may be clinically inapparent.13
  • PMID 9005978: In a series of adrenal incidentalomas, structured endocrine testing identified occult functional lesions including pheochromocytoma and preclinical Cushing’s syndrome, one of the latter proving to be cortisol-secreting adrenocortical carcinoma after surgery. The study also noted low DHEA-S and exaggerated ACTH-stimulated 17-hydroxyprogesterone responses in many patients, supporting comprehensive hormonal assessment of incidental adrenal masses.76
  • PMID 9100554: In a small ACC cohort, preoperative plasma DHEAS levels showed marked variability, with some tumors having elevated values unlike adrenal adenomas, while higher DHEAS values were associated with more frequent death from ACC. The study suggests DHEAS may have limited diagnostic discrimination but possible prognostic relevance.8
  • PMID 9167966: In a large multicenter adrenal incidentaloma cohort, endocrine testing identified unsuspected hormone excess, with overnight 1 mg dexamethasone suppression appearing most useful for subclinical hypercortisolism and urinary catecholamines outperforming VMA for occult pheochromocytoma. Most clinically silent adrenocortical carcinomas showed no major hormonal abnormality, though elevated DHEAS occurred in a minority.7
  • PMID 10426568: This case report describes ACC presenting with preclinical Cushing’s syndrome and elevated adrenal androgen output, including high DHEA-S, androstenedione, and urinary 17-ketosteroids despite subtle clinical findings. The authors suggest adrenal androgen assessment may help characterize adrenocortical neoplasms when autonomous cortisol secretion is present.77
  • PMID 10449234: This veterinary case highlights that a deoxycorticosterone-secreting adrenocortical carcinoma can present with severe hypokalemia, metabolic alkalosis, and hypertension despite undetectable aldosterone and normal cortisol testing. It illustrates the diagnostic value of extended steroid profiling with deoxycorticosterone measurement when standard endocrine evaluation is nonrevealing.78
  • PMID 10915006: This review outlines a diagnostic endocrine approach for Cushing’s syndrome relevant to cortisol-secreting ACC: confirm hypercortisolism with 24-hour urinary free cortisol and low-dose dexamethasone suppression testing, then use plasma ACTH, high-dose dexamethasone, CRH testing, and steroid hormone profiling to define etiology.15
  • PMID 11767922: This case report describes adrenocortical carcinomas associated with hyperadrenocorticoid-like clinical features despite low or subnormal cortisol responses to ACTH, where excess adrenal sex hormones and low endogenous ACTH supported hormonally active tumors. It highlights steroid profiling beyond cortisol, including progesterone, 17-hydroxyprogesterone, estradiol, androstenedione, testosterone, and DHEAS.20
  • PMID 11809538: This review emphasizes that suspected adrenal hormone excess should be confirmed biochemically before radiologic localization, and that all adrenal masses require screening for occult secretion, especially pheochromocytoma, hypercortisolism, and aldosteronism. It also notes the lack of valid biochemical markers of malignancy in inactive adrenal tumors.1
  • PMID 13092810: In a masculinizing adrenocortical carcinoma, urinary steroid testing showed marked predominance of 17-ketosteroid excretion over corticoids, matching the virilizing phenotype. After resection, both normalized within 48 hours, and later rises in urinary steroids preceded clinically evident recurrence with metastases.54
  • PMID 13163152: In a woman with metastatic adrenocortical carcinoma and virilizing features, urinary steroid analysis identified tetrahydro compound S, suggesting tumor secretion of its parent steroid, 17-alpha-hydroxy-11-desoxycorticosterone. The report highlights that unusual steroid metabolites can reveal ACC hormone production beyond routine cortisol-focused testing.79
  • PMID 13529241: In a patient with ACC causing Cushing syndrome and virilization, markedly elevated urinary 17-hydroxycorticoids and 17-ketosteroids did not increase with ACTH stimulation and did not suppress with fluorohydrocortisone. The report presents these hormonal patterns as distinctive diagnostic clues favoring adrenocortical carcinoma over hyperplasia or most adenomas.80
  • PMID 13601844: In a small series of patients with proven adrenocortical carcinoma, increased urinary tetrahydro S was found in those with elevated Porter-Silber chromogens, while cases with isolated 17-ketosteroid elevation had low tetrahydro S. The findings suggest steroid metabolite profiling may reveal abnormal cortisol precursor handling in some ACCs.81
  • PMID 13654492: In a small 1959 series of 10 adrenocortical carcinoma cases, urinary pregnanetriolone was undetectable across virilizing, Cushingoid, and clinically nonfunctional presentations, whereas pregnanetriol, corticoids, and 17-ketosteroids were variably elevated and not diagnostically reliable. The authors propose absent detectable urinary pregnanetriolone as a clue favoring adrenal tumor over adrenal hyperplasia, with acknowledged assay sensitivity limits.82
  • PMID 13702528: In a patient with metastatic cortisol-secreting adrenocortical carcinoma, detailed urinary steroid analysis during SU-4885 treatment showed marked reduction of 11-oxygenated C19 and C21 steroids with a corresponding rise in 11-deoxy metabolites. The findings illustrate ACC steroidogenic responsiveness and the value of comprehensive steroid metabolite profiling.83
  • PMID 14065877: This review emphasizes that many ACCs are biochemically functional even without obvious endocrine syndromes, with frequent elevations of urinary 17-ketosteroids and often 17-hydroxycorticoids. It highlights steroid-pattern clues such as increased DHEA and tetrahydro substance S, while noting imperfect correlation between biochemical excess and clinical virilization or Cushingoid features.4
  • PMID 14465754: In 10 patients with histologically proven functional metastatic ACC, urinary steroid metabolite profiling showed frequent excess tetrahydro Substance S, dehydroepiandrosterone, androsterone, and etiocholanolone, suggesting inefficient 11β-hydroxylation and other steroidogenic blocks with overproduction of pregnenolone and abnormal steroid metabolism.27
  • PMID 14794698: In urine from a boy with adrenocortical carcinoma, investigators identified unusual steroid metabolites including delta 5-pregnenetriol-3 beta, 17 alpha, 20 alpha and related delta 5-3 beta-stenols, suggesting marked tumor-associated alteration of steroid excretion patterns. The report highlights adrenal tumor origin of abnormal urinary steroids and a shift away from normally predominant 3 alpha-stanols.84
  • PMID 15218335: This case report describes ACC presenting with primary hyperaldosteronism and severe hypokalemia, while dexamethasone testing also revealed autonomous cortisol secretion despite no overt Cushingoid features. It emphasizes performing broad preoperative adrenal hormonal testing in adrenal masses to detect clinically silent cortisol excess and guide perioperative steroid coverage.11
  • PMID 15421996: A historical biochemical study of urine from a boy with adrenocortical carcinoma identified unusual steroid excretion products, including delta 5-pregnenetriol-3 beta, 17 alpha, 20 alpha, supporting adrenal tumor origin and illustrating altered steroidogenesis with predominance of delta 5-3 beta-stenol metabolites.85
  • PMID 15626289: In a cohort of patients with confirmed Cushing syndrome, adrenal carcinoma cases had very low basal ACTH levels similar to adrenal adenoma, supporting ACTH as a tool to distinguish ACTH-independent adrenal hypercortisolism from ACTH-dependent causes. The study reported high diagnostic accuracy overall and proposed an intermediate ACTH zone of 8 to 22 pg/mL.18
  • PMID 15891961: This case report describes a rare aldosterone-producing ACC presenting as primary aldosteronism with hypokalemic hypertension. It emphasizes careful endocrine workup of adrenal masses, including assessment for cortisol co-secretion and consideration of markedly elevated 18-hydroxycortisol as a clue to ACC in uncertain primary aldosteronism.86
  • PMID 15906564: This veterinary case highlights that an adrenocortical carcinoma can secrete non-cortisol glucocorticoids together with aldosterone, producing hypercorticoid features despite normal or subnormal cortisol responses. Expanded steroid testing identified markedly elevated corticosterone and aldosterone when routine cortisol-based evaluation was misleading.21
  • PMID 17649795: This case report describes a functional ACC in which serial serum and urinary cortisol levels paralleled recurrence and metastatic progression, normalizing after adrenalectomy and hepatic metastasectomy and declining again after treatment of a solitary sacral metastasis. It suggests that small cortisol rises in cortisol-secreting ACC may prompt targeted evaluation for relapse when interpreted alongside imaging and clinical findings.55
  • PMID 17669719: This case report highlights that ACC can rarely cosecrete cortisol, androgens, and 11-deoxycorticosterone, producing Cushing syndrome, hyperandrogenism, hypertension, and refractory hypokalemia despite low aldosterone. It recommends measuring 11-deoxycorticosterone when mineralocorticoid excess is suspected with suppressed aldosterone levels.37
  • PMID 18482927: A metastatic cortisol- and androgen-secreting ACC case showed that markedly elevated DHEA-S can cause misleading testosterone results on some direct immunoassays. The report highlights the need for cautious interpretation of androgen testing and consideration of assay-specific interference or mass spectrometry-based confirmation in suspected ACC.33
  • PMID 18589890: In a mixed adrenal incidentaloma cohort that included one adrenocortical carcinoma, baseline 17-hydroxyprogesterone and DHEA-S did not distinguish lesion groups, while ACTH-stimulated 17-hydroxyprogesterone and DHEA were higher in adenoma and hyperplasia than in other tumors. Exaggerated 17-hydroxyprogesterone responses were not linked to germline CYP21 mutations, suggesting this finding may reflect altered intratumoral steroidogenesis rather than true 21-hydroxylase deficiency.87
  • PMID 18708508: This case report describes an adrenocortical carcinoma presenting with severe ACTH-independent hypercortisolism, elevated plasma renin, androgen excess, and normal aldosterone, with postoperative normalization and recurrence-associated re-elevation of renin and cortisol. It highlights that ACC can rarely co-secrete renin alongside cortisol and androgens.88
  • PMID 18985457: This case illustrates that ACC can present with hypertension, hypokalemia, and amenorrhea despite normal aldosterone, cortisol, and androgen end products because of excess steroid intermediates such as DOC, 18-hydroxy-DOC, progesterone, and pregnenolone. Urinary steroid profiling and enzyme-pattern assessment identified disorganized steroidogenesis with multiple partial biosynthetic defects, and steroid abnormalities normalized after resection.38
  • PMID 19037697: In patients undergoing unilateral adrenalectomy for lesions considered nonfunctioning by routine morning serum and 24-hour urinary cortisol testing, postoperative adrenal insufficiency occurred in 22%, suggesting occult cortisol autonomy may be missed by standard screening. Larger tumor size, diabetes, hypertension, and obesity were associated with higher risk, supporting more sensitive preoperative cortisol evaluation and routine early postoperative cortisol measurement.19
  • PMID 19722132: This case report describes bilateral adrenocortical carcinomas with undetectable cortisol on ACTH stimulation and dexamethasone suppression testing, but markedly elevated progesterone, showing that steroid precursor and sex hormone assessment can reveal hormonally active ACC when cortisol-based testing is misleading.89
  • PMID 20126340: In a cohort of obese patients without overt Cushingoid features, screening with 24-hour urinary free cortisol followed by a 1-mg overnight dexamethasone suppression test identified occult Cushing’s syndrome in 9.33% of cases, including one adrenocortical carcinoma. The study highlights the false-positive rate of urinary free cortisol alone and supports confirmatory dexamethasone suppression testing before etiologic imaging.48
  • PMID 20181215: This case report highlights that suspected ACC warrants comprehensive hormonal assessment, as multimodal steroid secretion including cortisol, androgens, and the rare aldosterone excess may signal malignancy. Postoperative normalization of the hormonal profile supported the tumor as the source of combined hormone overproduction.90
  • PMID 20281620: In urine from a boy with an adrenocortical tumor, the authors isolated unusual steroid metabolites including 45-pregnenediol-3(β),17(β)-one-20 and noted a very high dehydroisoandrosterone titer, supporting abnormal adrenal steroid excretion patterns in ACC. The report also cautions that some detected compounds may arise artifactually during fractionation.91
  • PMID 21648291: This pediatric ACC case emphasizes a structured endocrine workup for combined Cushing syndrome and virilization, including baseline serum and urine testing before dynamic studies. It highlights urinary steroid profiling as a useful diagnostic and monitoring tool, with excess cortisol, androgen metabolites, tetrahydro-11-deoxycortisol, and unusual steroid metabolites supporting ACC.92
  • PMID 21980052: This case report shows that thorough endocrinologic testing can identify metastatic ACC even when presentation mimics another primary cancer. Concurrent autonomous cortisol secretion and confirmed primary hyperaldosteronism, highlighted by severe hypokalemia and suppression testing, pointed to a functioning adrenal primary.93
  • PMID 25097323: This case report describes an exceptionally rare ACC co-secreting aldosterone and cortisol, presenting with hypertension, severe hypokalemia, hyperglycemia, and facial puffiness. It emphasizes that patients evaluated for primary hyperaldosteronism should also undergo cortisol assessment when overlapping features suggest hypercortisolism, to guide perioperative steroid management and avoid postoperative adrenal crisis.39
  • PMID 25554619: The review outlines recommended biochemical evaluation for suspected ACC, including testing for glucocorticoid, sex steroid, and mineralocorticoid excess plus exclusion of pheochromocytoma. It also highlights urinary steroid profiling as a useful tool to distinguish ACC from other adrenal lesions and to monitor for postoperative recurrence.5
  • PMID 26165270: This consensus statement emphasizes comprehensive preoperative endocrine testing in suspected ACC, noting that many tumors secrete glucocorticoids, mineralocorticoids, sex steroids, or steroid precursors even without overt symptoms. It outlines a minimal workup including dexamethasone suppression testing, DHEAS and 17-OH progesterone, selective androgen or estrogen assays, and metanephrine testing.2
  • PMID 27797672: In patients with adrenal incidentalomas, an age- and sex-adjusted low DHEAS ratio was reported as a highly sensitive and more specific screening marker for subclinical ACTH-independent hypercortisolism than the 1 mg overnight dexamethasone suppression test, while urinary free cortisol performed less well.94
  • PMID 28980338: In postmenopausal hyperandrogenism, adrenal androgen-secreting tumors usually show elevated DHEA or DHEAS, while autonomous adrenal co-secretion of cortisol and testosterone indicates high risk of adrenocortical carcinoma. Baseline ACTH, low-dose dexamethasone testing, and urine steroid metabolomics are described as tools to help distinguish adrenal from ovarian androgen excess.23
  • PMID 29260252: This review outlines functional endocrine testing relevant to adrenal tumors, emphasizing the 1 mg dexamethasone suppression test as the recommended initial screen for autonomous cortisol secretion and for excluding cortisol excess in patients with an adrenal incidentaloma.14
  • PMID 29264444: This case report describes metastatic ACC with ACTH-independent hypercortisolism and marked inhibin B secretion causing selectively suppressed and GnRH-blunted FSH despite normal LH. It suggests measuring inhibin B when an adrenal tumor is accompanied by low FSH with preserved LH, and notes inhibin B may track treatment response in some ACCs.95
  • PMID 29342266: In women evaluated for androgen excess, simultaneous measurement of DHEAS, androstenedione, and testosterone identified distinct patterns associated with ACC. ACC cases consistently showed androstenedione elevation, and in postmenopausal women severe DHEAS or severe androstenedione excess was exclusively due to ACC, supporting steroid-pattern analysis to guide further investigation.24
  • PMID 29653933: This reply discusses serum LC-MS/MS steroid panel development for ACC detection, emphasizing that intermediates such as 11-deoxycortisol, 17-hydroxypregnenolone, and pregnenolone may help distinguish ACC from other adrenal lesions. It also notes that ionization method should be optimized per instrument rather than assuming APPI is universally superior to APCI.47
  • PMID 29743239: Experimental work in adrenocortical NCI-H295R1 cells shows that DHEA sulfation depends specifically on PAPSS2 interacting with SULT2A1, whereas PAPSS1 does not compensate. The findings clarify a mechanistic basis for altered DHEA sulfate production and androgen excess biology relevant to adrenal steroid metabolism.96
  • PMID 31445667: This review emphasizes that hormonal workup of adrenal incidentalomas, including cases in which ACC is a consideration, is vulnerable to circadian, age-related, preanalytical, analytical, and medication-related assay interference. It highlights that false hormone results can misclassify lesions and that method choice and proper sampling conditions are essential for interpretation.9
  • PMID 31492730: In a patient with an incidental 16 mm adrenal lesion, low-dose overnight dexamethasone testing identified ACTH-independent hypercortisolism despite no clinical features of Cushing’s disease. The report also states that complete adrenal workup for incidentalomas includes assessment of cortisol, aldosterone, catecholamines, and metanephrines.97
  • PMID 31499501: This review notes that androgen profiling may help distinguish ACTH-dependent Cushing syndrome from adrenal cortisol-secreting tumors: DHEA, DHEA-S, and androstenedione are generally elevated or high-normal in ACTH-dependent disease but lower in adrenal causes. It also highlights emerging plasma and urinary steroid profiling by LC-MS/MS or GC-MS as a promising diagnostic tool, including for adrenal tumors such as carcinoma.98
  • PMID 31543330: In this discussion of ACC, tumor functionality was defined only after complete biochemical evaluation, with nonfunctional cases excluding patients lacking a full workup. Assessment for Cushing syndrome included serum cortisol, 24-hour urinary cortisol, ACTH, and a 1 mg dexamethasone suppression test.99
  • PMID 32195126: This case report highlights that isolated DHEA-S excess from an adrenal neoplasm is exceedingly rare but can occur, with otherwise normal androgen, cortisol, aldosterone, estrogen, and metanephrine testing. In an incidental adrenal mass, androgen production and marked DHEA-S elevation supported surgical management because of concern for ACC, even though pathology proved adenoma.32
  • PMID 33340399: This study shows that patients with adrenocortical carcinoma can have elevated circulating 11-oxygenated androgens, but the corresponding 11-oxygenated estrogens were not detectable in serum despite in vitro aromatization. The findings support interpreting these steroids primarily as androgens rather than contributors to circulating estrogen excess.100
  • PMID 34665854: In adrenal incidentaloma, plasma steroid profiling by LC-MS/MS identified an ACC-associated pattern with elevations in 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, and DHEAS. Combining selected steroids with plasma metanephrines and tumor size markedly improved ACC discrimination compared with hormonal assessment alone.28
  • PMID 34673545: This case highlights that persistent testosterone elevation despite adequate gonadotropin suppression should prompt adrenal hormonal workup, including DHEA-S and androstenedione, plus exclusion of pheochromocytoma and assessment for cortisol autonomy. In an adrenal mass, androgen excess favored a functioning primary ACC over metastatic disease.101
  • PMID 35130566: In cortisol-secreting adrenal tumors, plasma ACTH measured by the Siemens Immulite assay was often spuriously unsuppressed, particularly in ACC, creating a risk of misclassifying adrenal Cushing syndrome as ACTH-dependent disease. The study emphasizes cautious ACTH interpretation and confirmation with more accurate assays when results are borderline or discordant.22
  • PMID 35910411: This article validates a targeted LC-MS/MS assay for 11 urinary steroids and shows prolonged pre-analytical stability of 24-hour urine samples, supporting urinary steroid profiling as a practical adjunct in differentiating benign from malignant adrenal tumors, including ACC, during hormonal workup.43
  • PMID 36262492: This case highlights hormonal workup for suspected ACC presenting with severe hypokalemic metabolic alkalosis, showing ACTH-independent hypercortisolism with failure to suppress on dexamethasone testing, elevated DHEA-S and 17-hydroxyprogesterone, and exclusion of primary hyperaldosteronism and pheochromocytoma before biopsy.102
  • PMID 37150696: In a retrospective comparison of adrenocortical carcinoma and adrenal cortical adenoma, LC-MS/MS serum steroid profiling found larger tumor size and higher androstenedione associated with ACC, while lower 11-ketotestosterone/11-ketoandrostenedione and 11-ketoandrostenedione/11-hydroxyandrostenedione ratios also correlated with ACC.44
  • PMID 38169194: This review highlights mass spectrometry-based steroid profiling as a promising extension of hormonal workup for adrenal masses, including ACC. It notes that initial ACC screening should include dexamethasone suppression test cortisol, DHEAS, testosterone, aldosterone, and renin, and that multisteroid panels with machine learning may help distinguish ACC from adenoma.46
  • PMID 38864873: This review emphasizes that suspected ACC warrants comprehensive hormonal testing even when tumors appear clinically nonfunctional. Recommended preoperative evaluation includes dexamethasone suppression testing with ACTH, androgen and steroid precursor assays, selective aldosterone-renin testing, and use of hormonal findings to guide management and anticipate postoperative adrenal insufficiency risk.6
  • PMID 39232900: This case report highlights that ACC can rarely present with a striking multihormonal profile, including excess steroid hormones and precursors, discordant catecholamine measurements, non-suppressed ACTH despite hypercortisolism, and probable IGF-2-mediated non-insulin hypoglycemia, creating major diagnostic confusion with pheochromocytoma or mixed corticomedullary tumors.41
  • PMID 39238157: This case report describes a ruptured ACC with concurrent hypercortisolism, hyperaldosteronism, and elevated normetanephrine, highlighting that ACC can mimic pheochromocytoma while secreting multiple cortical hormones. It supports comprehensive biochemical testing of adrenal masses, including cortisol, aldosterone-renin assessment when indicated, and metanephrines.40
  • PMID 39279304: These national ACC guidelines recommend urgent endocrine workup of suspected cases, including testing for cortisol, sex steroid and precursor excess, mineralocorticoid abnormalities when indicated, and mandatory exclusion of pheochromocytoma before surgery. They also highlight mixed hormonal secretion and expanded blood or urine steroid profiling as supportive clues to ACC.3
  • PMID 39359414: In a matched retrospective cohort comparing ACC with adrenocortical adenoma, LC-MS/MS serum steroid profiling identified 11-deoxycortisol as the most consistent discriminator across sex and functional-status subgroups. A model combining tumor diameter, 11-deoxycortisol, and BMI showed high diagnostic accuracy, while interpretation of other steroids varied by sex and hormonal function.29
  • PMID 39620173: This case report highlights that ACC can rarely co-secrete cortisol and aldosterone, producing concurrent Cushing’s syndrome and primary hyperaldosteronism. In a unilateral adrenal mass with resistant hypertension and hypokalemia, endocrine workup should include cortisol testing, aldosterone-renin ratio with aldosterone level, and pheochromocytoma exclusion before surgery.35
  • PMID 40250889: This review notes that ACC can present with androgen hypersecretion causing hirsutism, virilization, abdominal fullness, and satiety, and lists a biochemical workup including testosterone, DHEAS, DHEA, androstenedione, cortisol, plasma or urine metanephrines, and aldosterone with aldosterone-renin ratio.12
  • PMID 40270996: This case highlights rare IGF-2-mediated non-islet cell tumor hypoglycemia in ACC alongside steroid hormone excess. It supports a structured endocrine workup using supervised fast samples with suppressed insulin, C-peptide, and proinsulin plus an IGF-2:IGF-1 ratio greater than 10 as the preferred diagnostic marker for IGF-2 hypersecretion.103
  • PMID 40380878: This editorial emphasizes that serum profiling of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone helped distinguish ACC from non-ACC adrenal masses, particularly in indeterminate lesions. It recommends this limited, clinically available steroid panel mainly for indeterminate adrenal masses and notes the need for multicenter prospective validation.10
  • PMID 41544796: In adults with unilateral indeterminate lipid-poor adrenal masses at least 3 cm, serum LC-MS/MS steroid profiling identified androstenedione, 11-deoxycortisol, and DHEAS as the best discriminator set for ACC, with an AUC of 0.923 and 83.8% sensitivity and 96% specificity at the reported cutoff.45
  • PMID 32685047: Case report of a benign adrenal adenoma with autonomous cortisol secretion identified during workup of ipsilateral renal cell carcinoma. Indirectly relevant to suspected ACC because it reinforces the need to test for subtle cortisol autonomy in adrenal masses even without overt Cushingoid features and even when another malignancy is present.104
  • PMID 6277837: A veterinary series of cortisol-producing adrenocortical tumors found that many neoplasms, including carcinomas, still showed normal or exaggerated cortisol responses to exogenous ACTH, with some variability on repeat testing. While indirect for human ACC, the report reinforces caution against overinterpreting ACTH stimulation patterns as tumor-specific.51
  • PMID 8756877: A prospective veterinary study found that low-dose dexamethasone testing helped distinguish pituitary-dependent hypercortisolism from adrenal tumor hypercortisolism, but high-dose suppression patterns were not absolute because rare adrenal tumors showed borderline suppression. Although indirect to human ACC, this supports cautious interpretation of dexamethasone suppression responses in adrenal tumor evaluation.52
  • PMID 1850483: A canine retrospective study found that ACTH stimulation and other routine endocrine tests overlapped with pituitary-dependent hypercortisolism and did not reliably distinguish adrenocortical tumors; metastatic lesions, rather than endocrine test patterns, were the main discriminator between adenoma and carcinoma. This indirectly supports the note’s caution about limited interpretability of ACTH stimulation responses in suspected ACC.53

References

Footnotes

  1. Adrenocortical tumors: clinical symptoms and biochemical diagnosis.. Eur J Radiol. 2002. PMID: 11809538. Local full text: 11809538.md ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  2. Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE).. J Endocrinol Invest. 2016. PMID: 26165270. Local full text: 26165270.md ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9

  3. Polish diagnostic and therapeutic recommendations for adrenocortical carcinoma.. Endokrynol Pol. 2024. PMID: 39279304. Local full text: 39279304.md ↩ ↩2 ↩3 ↩4 ↩5

  4. CLINICAL AND PATHOPHYSIOLOGIC ASPECTS OF ADRENOCORTICAL CARCINOMA.. Am J Med. 1963. PMID: 14065877. Local full text: 14065877.md ↩ ↩2

  5. Adrenocortical cancer (ACC) - literature overview and own experience.. Endokrynol Pol. 2014. PMID: 25554619. Local full text: 25554619.md ↩ ↩2 ↩3 ↩4 ↩5

  6. [Adrenal tumors: current standards in clinical management].. Inn Med (Heidelb). 2024. PMID: 38864873. Local full text: 38864873.md ↩ ↩2 ↩3 ↩4 ↩5

  7. Adrenal incidentaloma: an overview of hormonal data from the National Italian Study Group.. Horm Res. 1997. PMID: 9167966. Local full text: 9167966.md ↩ ↩2 ↩3 ↩4

  8. Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery.. Eur J Endocrinol. 1997. PMID: 9100554. Local full text: 9100554.md ↩ ↩2 ↩3

  9. Pharmacological and analytical interference in hormone assays for diagnosis of adrenal incidentaloma.. Ann Endocrinol (Paris). 2019. PMID: 31445667. Local full text: 31445667.md ↩ ↩2 ↩3

  10. Response to Letter to the Editor From Li and Lu: “Serum Steroid Profiling in the Diagnosis of Adrenocortical Carcinoma: A Prospective Cohort Study”.. J Clin Endocrinol Metab. 2025. PMID: 40380878. Local full text: 40380878.md ↩ ↩2 ↩3 ↩4

  11. Co-secretion of aldosterone and cortisol by an adrenocortical carcinoma.. Horm Res. 2004. PMID: 15218335. Local full text: 15218335.md ↩ ↩2 ↩3 ↩4

  12. Review of Adrenal Androgen Synthesis, Hypersecretion, and Blockade.. Urol Clin North Am. 2025. PMID: 40250889. Local full text: 40250889.md ↩ ↩2 ↩3

  13. [Subclinical hypercortisolism in incidentally detected adrenal adenoma].. Dtsch Med Wochenschr. 1996. PMID: 8612460. Local full text: 8612460.md ↩ ↩2

  14. [Functional diagnostics in endocrinology].. Internist (Berl). 2018. PMID: 29260252. Local full text: 29260252.md ↩ ↩2 ↩3

  15. Pathophysiology and diagnosis of Cushing’s syndrome.. Biomed Pharmacother. 2000. PMID: 10915006. Local full text: 10915006.md ↩ ↩2

  16. Plasma cortisol profiles in Cushing’s syndrome.. Acta Endocrinol (Copenh). 1979. PMID: 223357. Local full text: 223357.md ↩ ↩2

  17. Primary adrenal causes of Cushing’s syndrome. Diagnosis and surgical management.. Ann Surg. 1989. PMID: 2742414. Local full text: 2742414.md ↩ ↩2

  18. Value of assessing adrenocorticotropic hormone (ACTH) levels in differential diagnosis of hypercorticism.. Med Pregl. 2004. PMID: 15626289. Local full text: 15626289.md ↩ ↩2

  19. Unrecognized adrenal insufficiency in patients undergoing laparoscopic adrenalectomy.. Surg Endosc. 2009. PMID: 19037697. Local full text: 19037697.md ↩ ↩2

  20. Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs.. J Am Vet Med Assoc. 2001. PMID: 11767922. Local full text: 11767922.md ↩ ↩2

  21. Corticosterone- and aldosterone-secreting adrenocortical tumor in a dog.. J Am Vet Med Assoc. 2005. PMID: 15906564. Local full text: 15906564.md ↩ ↩2

  22. Clinical Spectrum of Adrenal Cushing’s Syndrome and the Caution for Interpretation of Adrenocorticotrophic Hormone: A Single-Center Experience.. Horm Metab Res. 2022. PMID: 35130566. Local full text: 35130566.md ↩ ↩2

  23. Clinical Case Seminar: Postmenopausal androgen excess-challenges in diagnostic work-up and management of ovarian thecosis.. Clin Endocrinol (Oxf). 2018. PMID: 28980338. Local full text: 28980338.md ↩ ↩2

  24. Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited Women.. J Clin Endocrinol Metab. 2018. PMID: 29342266. Local full text: 29342266.md ↩ ↩2

  25. Diagnosis and treatment of functioning and nonfunctioning adrenocortical neoplasms including incidentalomas.. Surg Clin North Am. 1987. PMID: 3551152. Local full text: 3551152.md ↩ ↩2

  26. Steroid content of the peripheral and adrenal vein in Cushing’s syndrome due to adrenocortical adenoma and carcinoma.. J Urol. 1988. PMID: 2967899. Local full text: 2967899.md ↩ ↩2

  27. Adrenocortical cancer: steroid biosynthesis and metabolism evaluated by urinary metabolites.. J Clin Endocrinol Metab. 1962. PMID: 14465754. Local full text: 14465754.md ↩ ↩2

  28. Plasma Steroid Profiling in Patients With Adrenal Incidentaloma.. J Clin Endocrinol Metab. 2022. PMID: 34665854. Local full text: 34665854.md ↩ ↩2 ↩3 ↩4

  29. Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma.. Front Endocrinol (Lausanne). 2024. PMID: 39359414. Local full text: 39359414.md ↩ ↩2 ↩3 ↩4

  30. Studies on the efficiency of adrenocortical 11 beta-hydroxylation in the human subject.. J Clin Endocrinol Metab. 1969. PMID: 4306479. Local full text: 4306479.md ↩ ↩2

  31. Peripheral blood steroid levels in Cushing syndrome due to adrenocortical carcinoma or adenoma.. Urology. 1983. PMID: 6649220. Local full text: 6649220.md ↩ ↩2

  32. Isolated DHEAS production by an adrenal neoplasm: Clinical, biochemical and pathologic characteristics.. Urol Case Rep. 2020. PMID: 32195126. Local full text: 32195126.md ↩ ↩2

  33. A rare cause of Cushing’s syndrome demonstrates analytical discrepancies between the Roche E170 and Bayer Centaur testosterone assays.. Ann Clin Biochem. 2008. PMID: 18482927. Local full text: 18482927.md ↩ ↩2 ↩3

  34. Adrenal causes of hypertension.. Arch Intern Med. 1974. PMID: 4597949. Local full text: 4597949.md ↩ ↩2

  35. Diagnosis and Management of Adrenocortical Carcinoma with Co-secretion of Cortisol and Aldosterone: A Case Report.. J ASEAN Fed Endocr Soc. 2024. PMID: 39620173. Local full text: 39620173.md ↩ ↩2

  36. The mineralocorticoid hormone pathways in hypertension with hyperaldosteronism.. Clin Exp Hypertens A. 1982. PMID: 7139973. Local full text: 7139973.md ↩ ↩2

  37. Concomitant secretion of glucocorticoid, androgens, and mineralocorticoid by an adrenocortical carcinoma: case report and review of literature.. Endocr Pract. 2007. PMID: 17669719. Local full text: 17669719.md ↩ ↩2

  38. Close examination of steroidogenesis disorders in a DOC- and progesterone-producing adrenocortical carcinoma.. Endocrine. 2009. PMID: 18985457. Local full text: 18985457.md ↩ ↩2

  39. Aldosterone and cortisol co-secreting bifunctional adrenal cortical carcinoma: A rare event.. Indian J Urol. 2014. PMID: 25097323. Local full text: 25097323.md ↩ ↩2

  40. Ruptured triple hormone-secreting adrenal cortical carcinoma with hyperaldosteronism, hypercortisolism, and elevated normetanephrine: a case report.. J Yeungnam Med Sci. 2024. PMID: 39238157. Local full text: 39238157.md ↩ ↩2

  41. A puzzling malignant adrenal tumor.. Ann Endocrinol (Paris). 2024. PMID: 39232900. Local full text: 39232900.md ↩ ↩2

  42. Application of glass capillary gas chromatography to the study of urinary steroid excretion in normal children and in patients with various endocrinopathies.. Padiatr Padol Suppl. 1977. PMID: 144263. Local full text: 144263.md ↩ ↩2

  43. Targeted metabolic profiling of urinary steroids with a focus on analytical accuracy and sample stability.. J Mass Spectrom Adv Clin Lab. 2022. PMID: 35910411. Local full text: 35910411.md ↩ ↩2 ↩3

  44. [Comparison the characteristics of serum adrenocortical hormone profile in patients with adrenal cortical carcinoma and adrenal coritcal adenoma].. Zhonghua Yi Xue Za Zhi. 2023. PMID: 37150696. Local full text: 37150696.md ↩ ↩2

  45. Serum steroid profiling by LC-MS/MS in distinguishing adrenocortical carcinoma from other indeterminate adrenal masses.. J Steroid Biochem Mol Biol. 2026. PMID: 41544796. Local full text: 41544796.md ↩ ↩2 ↩3

  46. Steroid profiling in adrenal disease.. Clin Chim Acta. 2024. PMID: 38169194. Local full text: 38169194.md ↩ ↩2 ↩3

  47. In Reply.. Clin Chem. 2018. PMID: 29653933. Local full text: 29653933.md ↩ ↩2 ↩3

  48. Screening for Cushing’s syndrome in obese patients.. Clinics (Sao Paulo). 2010. PMID: 20126340. Local full text: 20126340.md ↩ ↩2

  49. ACTH-responsive, dexamethasone-suppressible adrenocortical carcinoma.. N Engl J Med. 1971. PMID: 4322562. Local full text: 4322562.md ↩ ↩2

  50. Single intravenous bolus of dexamethasone for the differential diagnosis of Cushing’s syndrome.. J Pediatr Endocrinol Metab. 1995. PMID: 7584693. Local full text: 7584693.md ↩ ↩2

  51. Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia.. J Am Vet Med Assoc. 1982. PMID: 6277837. Local full text: 6277837.md ↩ ↩2

  52. Use of low- and high-dose dexamethasone tests for distinguishing pituitary-dependent from adrenal tumor hyperadrenocorticism in dogs.. J Am Vet Med Assoc. 1996. PMID: 8756877. Local full text: 8756877.md ↩ ↩2

  53. Canine hyperadrenocorticism due to adrenocortical neoplasia. Pretreatment evaluation of 41 dogs.. J Vet Intern Med. 1991. PMID: 1850483. Local full text: 1850483.md ↩ ↩2

  54. Urinary steroids in adrenocortical tumor; excretion of corticoids and 17-ketosteroids on admission, after ACTH, following resection, after withdrawal of ACTH, and upon recurrence of masculinizing carcinoma.. Ann Surg. 1953. PMID: 13092810. Local full text: 13092810.md ↩ ↩2

  55. Cortisol as a possible marker of metastatic adrenocortical carcinoma: a case report with 3-year follow-up.. Anticancer Res. 2007. PMID: 17649795. Local full text: 17649795.md ↩ ↩2

  56. Dehydroepiandrosterone sulfate (DS) levels, a rapid test for abnormal adrenal androgen secretion.. J Clin Endocrinol Metab. 1976. PMID: 180041. Local full text: 180041.md ↩

  57. [Studies on the responsiveness of human adrenocortical tumors to ACTH the clinical and experimental observations (author’s transl)].. Nihon Naibunpi Gakkai Zasshi. 1975. PMID: 182566. Local full text: 182566.md ↩

  58. Cushing’s syndrome due to adrenocortical carcinoma - a comphrensive clinical and biochemical study of patients treated by surgery and chemotherapy.. Acta Endocrinol (Copenh). 1979. PMID: 223356. Local full text: 223356.md ↩

  59. [Microdetermination of corticosteroids in adrenocortical zones in various adrenal diseases (author’s transl)].. Nihon Naibunpi Gakkai Zasshi. 1978. PMID: 710647. Local full text: 710647.md ↩

  60. Urinary free cortisol versus 17-hydroxycorticosteroids: a comparative study of their diagnostic value in Cushing’s syndrome.. Clin Investig. 1992. PMID: 1327327. Local full text: 1327327.md ↩

  61. Characterization of adrenal autonomy in Cushing’s syndrome: a comparison between in vivo and in vitro responsiveness of the adrenal gland.. J Clin Endocrinol Metab. 1990. PMID: 2152930. Local full text: 2152930.md ↩

  62. Inappropriate ACTH concentrations in two patients with functioning adrenocortical carcinoma.. Clin Endocrinol (Oxf). 1988. PMID: 2854760. Local full text: 2854760.md ↩

  63. Tumors of the adrenal cortex and Cushing’s syndrome.. Ann Surg. 1985. PMID: 2986563. Local full text: 2986563.md ↩

  64. Particular cases of Cushing’s syndrome—one with adrenocortical carcinoma and the other with double adenomas.. Tohoku J Exp Med. 1985. PMID: 4024084. Local full text: 4024084.md ↩

  65. [Pattern of urinary neutral 17-ketosteroids on the basis of thin layer chromatography].. Z Klin Chem Klin Biochem. 1967. PMID: 4236096. Local full text: 4236096.md ↩

  66. Steroid excretion and biosynthesis with special reference to C19-delta16-steroids in an infant with a virilizing adrenocortical carcinoma.. Acta Endocrinol (Copenh). 1970. PMID: 4247013. Local full text: 4247013.md ↩

  67. Studies of androgens and their precursors in adrenocortical virilizing carcinoma.. J Clin Endocrinol Metab. 1971. PMID: 4251155. Local full text: 4251155.md ↩

  68. Urinary excretion of dehydroepiandrosterone in normal children and in patients with adrenocortical disorders.. Clin Chim Acta. 1972. PMID: 4260320. Local full text: 4260320.md ↩

  69. Clinical evaluation of urinary cortisol determinations by competetive protein-binding radioassay.. J Clin Endocrinol Metab. 1968. PMID: 4296070. Local full text: 4296070.md ↩

  70. Steroid determinations in six cases of hyperplasia and three cases of tumour of the adrenal cortex.. Acta Med Scand. 1968. PMID: 4299351. Local full text: 4299351.md ↩

  71. [Gas chromatographic estimation of urinary delta5 pregnenetriol and pregnanetriol in adrenocortical disease and male hypogonadism].. Nihon Hinyokika Gakkai Zasshi. 1971. PMID: 4326521. Local full text: 4326521.md ↩

  72. Profile and possible origin of an adrenocortical carcinoma.. J Clin Endocrinol Metab. 1971. PMID: 4327689. Local full text: 4327689.md ↩

  73. [Adrenocortical carcinoma causing Cushing’s syndrome: report of a case].. Hinyokika Kiyo. 1970. PMID: 5462077. Local full text: 5462077.md ↩

  74. Development of Cushing’s syndrome and virilization after presentation of a nonfunctioning adrenocortical carcinoma.. Cancer. 1982. PMID: 7093917. Local full text: 7093917.md ↩

  75. Steroid contents and cortical steroidogenic enzymes in non-hyperfunctioning adrenal adenoma.. Endocr J. 1994. PMID: 7951578. Local full text: 7951578.md ↩

  76. Evaluation of hormonal function in a series of incidentally discovered adrenal masses.. Metabolism. 1997. PMID: 9005978. Local full text: 9005978.md ↩

  77. A patient with preclinical Cushing’s syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.. Endocr J. 1999. PMID: 10426568. Local full text: 10426568.md ↩

  78. Deoxycorticosterone-secreting adrenocortical carcinoma in a dog.. J Vet Intern Med. 1999. PMID: 10449234. Local full text: 10449234.md ↩

  79. Isolation of pregnane-3-alpha, 17-alpha, 21-triol-20-one (tetrahydro compound S) from the urine of a woman with metastatic adrenocortical carcinoma.. J Clin Endocrinol Metab. 1954. PMID: 13163152. Local full text: 13163152.md ↩

  80. Cushing’s syndrome secondary to adrenocortical carcinoma.. South Med J. 1958. PMID: 13529241. Local full text: 13529241.md ↩

  81. Excretion of pregnan-3 alpha, 17 alpha, 21-triol-20-one (tetrahydro S) by patients with adrenocortical carcinoma.. Proc Soc Exp Biol Med. 1958. PMID: 13601844. Local full text: 13601844.md ↩

  82. Urinary steroids in 10 cases of adrenal carcinoma, with special reference to pregnane-3 alpha, 17 alpha,20 alpha-triol-11-one.. J Clin Endocrinol Metab. 1959. PMID: 13654492. Local full text: 13654492.md ↩

  83. Studies with an adrenal inhibitor in adrenal carcinoma.. J Clin Endocrinol Metab. 1960. PMID: 13702528. Local full text: 13702528.md ↩

  84. Steroid excretion in a case of adrenocortical carcinoma. V. delta 5-Pregnenetriol-3 beta, 17 alpha, 20 alpha.. J Biol Chem. 1950. PMID: 14794698. Local full text: 14794698.md ↩

  85. Steroid excretion in a case of adrenocortical carcinoma. IV. delta 5 pregnenetriol-3 beta, 16 alpha, 20 alpha.. J Biol Chem. 1950. PMID: 15421996. Local full text: 15421996.md ↩

  86. Steroid profile in an adrenocortical carcinoma producing aldosterone.. Exp Clin Endocrinol Diabetes. 2005. PMID: 15891961. Local full text: 15891961.md ↩

  87. The prevalence of 21-hydroxylase deficiency in adrenal incidentalomas - hormonal and mutation screening.. Exp Clin Endocrinol Diabetes. 2008. PMID: 18589890. Local full text: 18589890.md ↩

  88. Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol.. Endocr Relat Cancer. 2008. PMID: 18708508. Local full text: 18708508.md ↩

  89. [Hyperprogesteronism due to bilateral adrenal carcinomas in a cat with diabetes mellitus].. Schweiz Arch Tierheilkd. 2009. PMID: 19722132. Local full text: 19722132.md ↩

  90. Adrenocortical carcinoma secreting cortisol, androgens and aldosterone: a case report.. Cases J. 2009. PMID: 20181215. Local full text: 20181215.md ↩

  91. Steroid excretion in a case of adrenocortical carcinoma; the isolation of delta 5-pregnenediol-3(beta), 17(beta)-one-20 and of 17a-methyl-5D-homoandrostenediol-3(beta), 17a (alpha)-one-17.. J Biol Chem. 1947. PMID: 20281620. Local full text: 20281620.md ↩

  92. A 12-year-old chinese girl with Cushing syndrome and virilization due to adrenocortical carcinoma.. J Pediatr Endocrinol Metab. 2011. PMID: 21648291. Local full text: 21648291.md ↩

  93. Metastatic adrenocortical carcinoma presenting simultaneously with Cushing’s and Conn’s syndromes: a case report.. Jpn J Clin Oncol. 2011. PMID: 21980052. Local full text: 21980052.md ↩

  94. Low DHEAS: A Sensitive and Specific Test for the Detection of Subclinical Hypercortisolism in Adrenal Incidentalomas.. J Clin Endocrinol Metab. 2017. PMID: 27797672. Local full text: 27797672.md ↩

  95. Reversal of a Blunted Follicle-Stimulating Hormone by Chemotherapy in an Inhibin B-Secreting Adrenocortical Carcinoma.. J Endocr Soc. 2017. PMID: 29264444. Local full text: 29264444.md ↩

  96. Human DHEA sulfation requires direct interaction between PAPS synthase 2 and DHEA sulfotransferase SULT2A1.. J Biol Chem. 2018. PMID: 29743239. Local full text: 29743239.md ↩

  97. Simultaneous presentation of parathyroid carcinoma, papillary thyroid cancer and ACTH-independent hypercortisolism due to benign cortical adenoma.. BMJ Case Rep. 2019. PMID: 31492730. Local full text: 31492730.md ↩

  98. Androgens in Cushing’s Syndrome.. Front Horm Res. 2019. PMID: 31499501. Local full text: 31499501.md ↩

  99. Discussion.. Surgery. 2020. PMID: 31543330. Local full text: 31543330.md ↩

  100. 11-Oxygenated Estrogens Are a Novel Class of Human Estrogens but Do not Contribute to the Circulating Estrogen Pool.. Endocrinology. 2021. PMID: 33340399. Local full text: 33340399.md ↩

  101. Castration failure in prostate carcinoma due to a functioning adrenocortical carcinoma.. Endocrinol Diabetes Metab Case Rep. 2021. PMID: 34673545. Local full text: 34673545.md ↩

  102. Diagnosis of Adrenocortical Carcinoma with Hypercortisolism in a Patient Presenting with Hypokalemic Metabolic Alkalosis.. J Community Hosp Intern Med Perspect. 2022. PMID: 36262492. Local full text: 36262492.md ↩

  103. Adrenocortical Carcinoma With 2 Distinct Syndromes From Secretion of Insulin-Like Growth Factor 2 and Steroid Hormones.. JCEM Case Rep. 2025. PMID: 40270996. Local full text: 40270996.md ↩

  104. ADRENAL ADENOMA WITH AUTONOMOUS CORTISOL SECRETION ACCOMPANIED BY HOMOLATERAL RENAL CELL CARCINOMA: A CASE REPORT.. Acta Endocrinol (Buchar). 2020. PMID: 32685047. Local full text: 32685047.md ↩

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