Hormone-Excess Presentations in ACC

Clinical Presentation

Hormone-excess presentations in adrenocortical carcinoma (ACC) are clinical syndromes caused by autonomous secretion of cortisol, androgens, estrogens, aldosterone, or steroid precursors by a malignant adrenocortical tumor. Within the spectrum of ACC presentation, these syndromes are important because they may bring patients to attention before local mass effect becomes dominant, and they help define the endocrine phenotype of an otherwise rare adrenal malignancy.¹²³

Functioning ACC most commonly produces hypercortisolism, androgen excess, or mixed secretion, whereas feminizing and mineralocorticoid-dominant syndromes are less frequent but often clinically distinctive.¹⁴⁵ The distinction between functioning and nonfunctioning tumors is imperfect, however, because ACC often exhibits disordered steroidogenesis with secretion of multiple hormones or precursors, incomplete biochemical pathways, and variable clinical expression.⁶⁷⁸ As a result, some tumors that appear clinically silent show abnormal steroid profiles when tested, while some hormonally active tumors lack the classic external features expected from benign endocrine disorders.⁹¹⁰¹¹

Hormone excess in ACC is clinically useful but not pathognomonic of any single presentation pattern. Cortisol excess may be severe without a typical cushingoid appearance, androgen excess may coexist with or mask catabolic effects of hypercortisolism, and mineralocorticoid-like hypertension may be driven by steroid precursors rather than aldosterone itself.¹²¹³¹⁴ Moreover, hormonally active tumors are not necessarily detected at an earlier stage; many reported cases are already large, invasive, or metastatic at diagnosis despite overt endocrine manifestations.¹⁵¹⁶¹⁷

The evidence base is limited by the rarity of ACC and by reliance on retrospective cohorts, historical surgical series, and case reports. Reported phenotype frequencies vary across age groups, referral settings, and biochemical methods, so the literature is more dependable for broad clinical patterns than for precise incidence estimates, phenotype-specific prognosis, or comparative treatment effects.¹¹⁵¹⁸

Diagnostic context

ACC is commonly categorized as functioning or nonfunctioning, but this binary framework does not capture the frequency of partial, mixed, or clinically occult steroid excess.⁶⁷ In practice, endocrine activity exists on a spectrum, ranging from florid hormone syndromes to subtle biochemical abnormalities discovered only after targeted testing.⁹⁸ This is a relatively consistent finding across retrospective and case-based literature. The practical implication is that absence of a classic syndrome does not exclude biologically active ACC, particularly when an adrenal mass is large or clinically aggressive.

Age influences the dominant pattern of hormone excess. Pediatric ACC more often presents with virilization or other androgenic manifestations, whereas adult ACC more commonly shows mixed cortisol-androgen secretion; nonfunctioning presentations are reported more often in older adults.²¹⁹²⁰ These trends are reproducible across reviews, although exact proportions are uncertain. Clinically, age can sharpen suspicion but should not be used as a stand-alone discriminator.

This background helps frame the major hormone-excess phenotypes that recur across the ACC literature.

Major phenotypes

Hypercortisolism

Cortisol excess is the most commonly described endocrine presentation of ACC and usually manifests as ACTH-independent Cushing syndrome.¹²¹³ Typical features include weight gain, hypertension, diabetes or worsening hyperglycemia, hypokalemia, proximal myopathy, edema, bruising, striae, osteoporosis, and neuropsychiatric symptoms.²²²³²⁴ Retrospective data suggest that ACC-related hypercortisolism may be more rapid in onset and more metabolically severe than benign adrenal Cushing syndromes, but clinical overlap is substantial and no single symptom reliably distinguishes carcinoma from adenoma.²⁵²⁶

A recurring limitation of symptom-based recognition is that some cortisol-secreting ACCs do not have a classic cushingoid appearance despite marked biochemical excess and major systemic complications.¹²¹⁰¹¹ This is one of the more reliable practical lessons in the literature: clinicians may need to suspect occult cortisol excess when hypokalemia, resistant hypertension, diabetes, infection, thrombosis, or severe myopathy cluster around an adrenal mass.

Androgen excess and virilization

Androgen-secreting ACC usually presents with rapidly progressive hirsutism, acne, scalp hair loss, menstrual irregularity, amenorrhea, clitoromegaly, voice deepening, or precocious virilization in children.²⁷²⁸²⁹ In women, rapid onset and severity are more informative than isolated mild hyperandrogenic symptoms, because common disorders such as polycystic ovary syndrome create substantial diagnostic overlap.³⁰²⁸ The most reliable signal is marked adrenal androgen excess with clinical virilization developing over a short interval.

Mixed cortisol-androgen secretion is repeatedly described as particularly suggestive of malignancy, whereas pure androgen-secreting ACC appears less common, especially in adults.³¹⁴¹³³² This pattern is supported mainly by retrospective and case-based data rather than direct comparative studies. The practical implication is that virilization accompanied by adrenal-pattern biochemistry, especially with concurrent cortisol abnormalities, should prompt evaluation for ACC rather than routine management as a benign hyperandrogenic disorder.

Estrogen excess and feminization

Feminizing ACC is rare but distinctive. In men, the usual presentation includes gynecomastia, reduced libido, erectile dysfunction, testicular atrophy, and hypogonadotropic hypogonadism; in women, particularly after menopause, vaginal bleeding and breast enlargement are the main reported estrogenic manifestations.³³⁵³⁴ Across reviews and accumulated case literature, feminization in association with an adrenal mass is among the strongest endocrine clues to malignant adrenal cortical disease.⁴³⁵³⁶

The mechanism of feminization is variable and may involve direct estrogen secretion, mixed steroid production, or peripheral aromatization of tumor-derived androgens.³⁷⁵ That mechanistic uncertainty limits subtype-level biologic conclusions, but not the clinical implication: estrogenic presentation is uncommon yet highly suspicious for ACC and should prompt broad hormonal characterization.

Mineralocorticoid and mineralocorticoid-like excess

Mineralocorticoid-dominant ACC is uncommon and may result from aldosterone secretion or from accumulation of biologically active precursors such as deoxycorticosterone.³⁸³⁹¹⁴ Typical findings include severe or resistant hypertension, hypokalemia, metabolic alkalosis, weakness, and suppressed renin, while aldosterone concentrations may be elevated, normal, or low depending on the steroid profile.⁴⁰⁴¹⁴²

This phenotype may mimic ordinary primary aldosteronism, but atypical features such as a very large adrenal mass, marked hypokalemia, multihormonal secretion, or discordance between renin suppression and aldosterone level suggest a broader steroidogenic disorder.⁴³⁴⁴⁴⁵ The evidence is limited in volume and derived largely from isolated reports. Still, the practical implication is consistent: apparently mineralocorticoid-mediated ACC should not be excluded simply because aldosterone is not clearly elevated.

Cross-phenotype patterns and complications

Across hormone-excess phenotypes, several general patterns recur. Functioning ACC often shows rapid symptom evolution, multihormonal secretion, large tumor size, and a high frequency of locally advanced or metastatic disease at diagnosis.⁴⁶¹⁶¹⁷ These broad trends are more reliable than exact phenotype frequencies. Clinically, endocrine functionality may accelerate recognition, but it does not imply early-stage disease.

Hormone excess also contributes substantial morbidity independent of tumor burden, especially in cortisol-secreting disease. Reported complications include vertebral fractures, severe myopathy, opportunistic infection, thromboembolism, psychiatric decompensation, arrhythmia, cardiomyopathy, and hypertensive emergency.⁴⁷⁴⁸⁴⁹⁵⁰ Most evidence for these complications is observational, but the consistency of reported toxicity supports urgent endocrine stabilization alongside oncologic staging and treatment planning.

Atypical presentations are also described, including pseudopheochromocytoma-like episodes, hypoglycemia, ocular manifestations of severe hypercortisolism, inflammatory syndromes, and thrombotic events dominating the initial workup.⁵¹⁵²⁵³⁵⁴ Because these reports are mostly anecdotal, they are not reliable for defining phenotype frequency. Their main value is to illustrate that ACC can evade classic endocrine pattern recognition.

Role in management and research

Recognition of hormone excess has immediate implications for ACC management. Endocrine phenotyping helps confirm that an adrenal mass is biologically active, identifies urgent risks such as severe hypercortisolism or hypokalemic hypertension, and informs perioperative or pre-systemic supportive treatment.⁵⁵³⁵⁶ Compared with surgery, which remains the principal local treatment when feasible, hormone-directed therapy is usually adjunctive and temporizing rather than definitive.

From a research perspective, hormone-excess presentations support the view that ACC commonly reflects disordered steroidogenic differentiation rather than simple overproduction of a single end-product hormone.⁷⁵⁷⁵⁸ This interpretation is plausible and repeatedly described, but current evidence is still largely descriptive. Practical use therefore remains strongest in clinical phenotyping and supportive management, rather than in validated biologic subclassification or treatment selection.

Included Articles

PMID 180740: This case report describes a rare feminising adrenocortical carcinoma in a postmenopausal woman presenting with vaginal bleeding, markedly elevated estradiol and androstenedione, suppressed gonadotropins, and rapid normalization of estradiol after adrenal tumor resection. The report highlights estrogen-secreting ACC as an uncommon endocrine presentation in adult females.⁵⁹

PMID 386679: In two female patients with adrenocortical carcinoma and increased adrenal androgen production, the article documents a hyperandrogenic clinical context that included menstrual abnormalities. These ACC cases were analyzed alongside other androgen-excess disorders, highlighting androgen excess as a presenting phenotype in female ACC.⁶⁰

PMID 465106: This case report describes ACC in a 47-year-old man presenting with flank pain, weight loss, fever, and a large left suprarenal mass without overt Cushingoid features. Cortisol levels were normal but failed to suppress with dexamethasone, and rapid postoperative spread to skin, brain, and ribs was observed.⁶¹

PMID 482186: This case report highlights feminizing ACC in a postmenopausal woman presenting with vaginal bleeding, elevated plasma estrogens and testosterone, and suppressed gonadotrophins. It emphasizes that, after exclusion of endometrial carcinoma and ovarian tumors, an estrogen-secreting adrenal tumor should be considered.⁶²

PMID 626558: This case report describes metastatic adrenocortical carcinoma in a 31-year-old man presenting with combined Cushing’s syndrome and rare feminization, with gynecomastia, elevated estrone and estradiol, and low testosterone. It also reports hypercalcemia attributed to pseudohyperparathyroidism from tumor or abdominal metastases.⁶³

PMID 686895: In this surgical series, the two reported ACC cases presented with hypercortisolism causing Cushing’s syndrome and already had liver metastases at diagnosis. Major presenting features included obesity, weakness, osteoporosis, depression, and in one case only mild Cushing’s syndrome despite bulky disease.⁶⁴

PMID 1179589: This case series describes a rare presentation of adrenocortical carcinoma as primary aldosteronism with mineralocorticoid excess, severe hypokalemia, and hypertension, often without overt glucocorticoid or androgen excess. It also notes that clinical improvement with spironolactone does not exclude underlying carcinoma.³⁸

PMID 1648874: This case describes endocrinologically active ACC presenting mainly with hypertension and headache rather than classic overt hormone-excess syndromes. Postoperative normalization of pregnenolone and urinary 17-ketosteroids, along with improved blood pressure, supported occult functional activity despite otherwise limited endocrine abnormalities.⁹

PMID 2555800: In Cushing’s syndrome caused by adrenal carcinoma, the tumor may grow very large before cushingoid symptoms appear because cortisol synthesis is inefficient. The article also notes frequent metastatic spread at presentation, common liver metastases, and that about half of tumors may be palpable, with calcification raising suspicion for malignancy.¹²

PMID 209063: In ectopic ACTH syndrome from bronchogenic oat-cell carcinoma, classic Cushingoid features were uncommon, while cachexia, edema, hypertension, hyperglycemia, and occasional proximal myopathy predominated. Ante mortem recognition relied mainly on hypokalaemia with metabolic alkalosis, and many cases were diagnosed only late or at necropsy.⁶⁵

PMID 2801388: This case report describes a functional adrenocortical carcinoma presenting with Cushing syndrome in a 45-year-old woman, with moon face, amenorrhea, and hypertension. The excerpt also notes that among endocrine-active malignant adrenal tumors, Cushing syndrome is reported as the most common presentation.⁶⁶

PMID 2822755: This case report describes metastatic adrenocortical carcinoma presenting with deoxycorticosterone-driven hypermineralocorticoidism, including hypertension, hypokalemia, suppressed renin and aldosterone, and markedly elevated 17-deoxysteroids. It highlights that ACC can rarely present with an unusual mineralocorticoid-secretory phenotype rather than classic cortisol or androgen excess.³⁹

PMID 2834927: This case report describes a virilizing ACC in a 36-year-old woman presenting with scant menses, hirsutism, weight loss, and a palpable abdominal mass. The tumor showed androgen excess with elevated testosterone and dehydroepiandrosterone, and virilization recurred within six months alongside suspected metastasis.⁶⁷

PMID 3047223: ACC can rarely first present as acute Budd-Chiari syndrome from tumor extension into the inferior vena cava and hepatic veins. In the reported case, the tumor was hormonally secreting but clinically nonfunctioning, without overt Cushingoid or virilizing features despite elevated steroid levels.⁶⁸

PMID 3051451: This review describes ACC as a rare adrenal cortical malignancy that may be hormonally silent or present with Cushing’s syndrome, virilization, or less commonly feminization in men. It notes that isolated virilization strongly suggests carcinoma and poor prognosis, and that venous invasion into the renal vein or vena cava can occur.⁶⁹

PMID 3074951: This pediatric case review describes a rare testosterone-secreting adrenocortical carcinoma presenting in a pubertal girl with isolated deepening of the voice, regular menses, and no hirsutism or Cushingoid features. It highlights that pediatric ACC can present with subtle virilization despite limited biochemical abnormalities.⁷⁰

PMID 3336072: Feminizing adrenocortical tumors in male patients can present with gynecomastia, impotence, and sometimes concurrent Cushingoid features from estrogen and cortisol excess. The report emphasizes that hormone patterns may shift over time in carcinoma and that recurrence may manifest with liver and lung metastases.⁵⁸

PMID 3608914: This case report describes ACC presenting with mineralocorticoid excess despite repeatedly normal aldosterone levels. Severe hypertension, low renin activity, mild hypokalemia, and biochemical elevation of weak mineralocorticoids such as 11-deoxycorticosterone, corticosterone, and related metabolites resolved after tumor resection.⁴¹

PMID 3674052: This case series shows that adrenocortical carcinoma can rarely present as an isolated primary aldosteronism syndrome without overt Cushingoid or virilizing features. Severe hypokalemia, marked aldosterone excess, and resistant hypertension characterized these presentations, highlighting a hormonally unusual ACC phenotype.⁴⁰

PMID 4057377: This case report describes feminizing ACC in a man presenting with progressive gynecomastia, diminished libido, impotence, testicular atrophy, and biochemical hyperestrogenism with low testosterone. It highlights that estrogen-secreting adrenal tumors should be considered in the differential diagnosis of male gynecomastia.⁷¹

PMID 4269508: This report describes a rare feminizing adrenocortical carcinoma in an adult postmenopausal woman presenting with recurrent vaginal bleeding, endometrial hyperplasia, and markedly elevated urinary estrogens despite gonadectomy. The case highlights ectopic estrogen production by ACC as an unusual endocrine presentation in women.⁷²

PMID 4292011: This case report describes a virilizing adrenocortical carcinoma in a 16-year-old girl presenting with hirsutism, deepened voice, clitoromegaly, and a palpable abdominal mass, with elevated plasma testosterone and markedly increased urinary 17-ketosteroids. The tumor later recurred with pulmonary metastases and evolving overt Cushing’s syndrome.⁷³

PMID 4362452: This case report describes adrenocortical carcinoma presenting with a mineralocorticoid excess phenotype driven by marked deoxycorticosterone secretion, causing severe hypertension, oedema, hypokalaemic alkalosis, and later recurrence with bone metastasis and renewed hormonal symptoms. It also notes associated hirsutism at relapse without overt Cushingoid features.⁷⁴

PMID 4669328: This case report highlights that adrenocortical carcinoma can present solely with hypermineralocorticoidism, including severe hypertension, hypokalemic alkalosis, muscular weakness, and renal potassium wasting, without overt Cushingoid features or virilization. The report emphasizes this uncommon presentation as an important differential diagnosis from primary hyperaldosteronism.⁷⁵

PMID 5394302: A 33-year-old woman with virilizing adrenocortical carcinoma presented with amenorrhea, hirsutism, deepened voice, breast atrophy, clitoromegaly, and elevated androgen-related steroid excretion. The report links this virilizing phenotype to markedly abnormal urinary and plasma steroid patterns that decreased after adrenalectomy.⁷⁶

PMID 5410305: This case report describes feminizing ACC in a man presenting with marked gynecomastia, periareolar pigmentation, testicular atrophy, weight loss, and a large adrenal mass with lung metastases. The reviewed cases suggest estrogen-secreting ACC can produce a distinctive feminizing syndrome in men.⁷⁷

PMID 5587261: This surgical review outlines ACC-related hormone excess presentations, noting that adrenocortical carcinoma can present with Cushing syndrome, virilizing adrenogenital syndrome, mixed glucocorticoid-androgen excess, rarely primary aldosteronism, or as a hormonally inactive mass discovered by size or incidentally.⁷⁸

PMID 5636151: This case report describes a rare feminizing adrenocortical carcinoma in a 53-year-old man presenting with loss of libido, impotence, gynecomastia, edema, and small soft testes. Symptoms improved after tumor resection but gynecomastia persisted and recurrent feminization accompanied locally recurrent infiltrating tumor.⁷⁹

PMID 5653197: This case report describes feminizing ACC in a 31-year-old man presenting with hypertension, severe headaches, bilateral gynecomastia, testicular atrophy, reduced libido, and later metastatic pulmonary disease. It highlights that feminizing ACC can present with combined estrogenic features and hypertension.⁸⁰

PMID 5676087: This case report describes a nonfunctioning adrenocortical carcinoma presenting with adrenal insufficiency, including asthenia, weight loss, hypotension, hyperpigmentation, and absent cortisol and urinary 17-OHCS response to ACTH stimulation. It highlights an unusual presentation in which ACC lacked overt hormone-excess features yet was associated with adrenal failure.⁸¹

PMID 5775635: This case illustrates a possible ACC presentation dominated by severe hypokalemic metabolic alkalosis with edema, weakness, and progressive encephalopathy, while classic cushingoid features and hypertension were absent. The differential discussion highlights adrenocortical hormone excess, especially mineralocorticoid versus cortisol effects, as a diagnostic consideration.⁸²

PMID 6272575: In this single-center retrospective series, ACC commonly presented with Cushing’s syndrome often accompanied by virilization, while some tumors appeared clinically nonfunctional despite elevated cortisol and urinary steroid levels. Virilization-only presentations were seen particularly in women with carcinoma, and symptom duration before diagnosis was shorter for carcinoma than for adenoma.⁶

PMID 6312717: In isolated cells from a single cortisol-secreting adrenocortical carcinoma, basal steroidogenesis was very low, with small cortisol output, no measurable aldosterone production, and cortisol responsiveness to ACTH but not angiotensin II. The source case had mild Cushing’s syndrome that improved after surgery, then recurred before death from metastases.⁸³

PMID 6819236: In a rat ACC transplant model, steroid-producing tumor activity markedly increased corticosterone and progesterone and was associated with suppression of LH, FSH, and testosterone, along with reduced testes and accessory sex gland size. The findings support endocrine-mediated reproductive suppression as a consequence of hormonally active adrenocortical carcinoma.⁸⁴

PMID 7209968: This case report describes an 18-year-old woman with ACC presenting with overt Cushing’s syndrome, including moon face, obesity, hirsutism, amenorrhea, and markedly elevated urinary steroid excretion, followed by recurrent severe hypoglycemia with postoperative recurrence of a large steroid-producing tumor.⁸⁵

PMID 7776567: This case report describes a rare deoxycorticosterone-producing adrenocortical carcinoma presenting with hypokalemia and markedly elevated serum deoxycorticosterone but without hypertension. The review notes that weakly active steroid-producing ACCs may appear clinically nonfunctional or have minimal endocrine symptoms.⁸⁶

PMID 7930380: This case illustrates a rare feminizing presentation of ACC in a man, with gynecomastia and a large adrenal mass accompanied by mixed steroid excess including estrogens, androgens, mineralocorticoids, and biochemical glucocorticoid overproduction. The report emphasizes that estrogen excess may reflect both direct tumor production and peripheral aromatization of tumor-derived androgens.³⁷

PMID 8208649: This case report describes feminizing ACC presenting initially with isolated bilateral gynecomastia in a young man, without other obvious endocrine features. The tumor showed estrogen excess with suppressed testosterone, highlighting that hormonally active ACC can rarely present through gynecomastia alone and diagnosis may be delayed.⁸⁷

PMID 8364880: This case series describes virilizing adrenocortical tumors in adult women presenting with hirsutism, deep voice, amenorrhea, clitoromegaly, increased libido, and occasionally concurrent Cushing syndrome. It highlights that rare adrenal tumors may secrete testosterone alone with normal urinary 17-ketosteroids, mimicking an ovarian source.⁸⁸

PMID 8503331: This case report highlights virilizing ACC in an adult woman presenting after incidental adrenal mass detection with acne, hirsutism, clitoromegaly, and amenorrhea, alongside markedly elevated serum testosterone. The review notes adult virilizing ACC is very rare and commonly presents with androgen excess manifestations.⁸⁹

PMID 8731899: In this 20-case series, nonfunctional ACC occurred mainly in older adults and was often detected late because symptoms were nonspecific or absent, while functional ACC occurred predominantly in children and presented with hypercortisolism or virilizing features. Incidental imaging detection identified some smaller nonfunctional tumors with comparatively better prognosis.¹⁹

PMID 9366310: In adrenal Cushing’s syndrome, ACC can present with the same glucocorticoid-excess signs and symptoms seen in adrenal adenoma, with substantial overlap in hirsutism and mixed endocrine features. In this series, glucose intolerance was more frequent and androgen precursor elevations tended to be greater in carcinoma, but no specific symptom reliably distinguished malignancy.²⁵

PMID 9487478: This case report describes ACC presenting with androgenic features and cardiorespiratory symptoms caused by rapid tumor thrombus extension from a left adrenal primary through the inferior vena cava into the right atrium. Right atrial involvement produced edema, dyspnea, chest pain, and pulmonary embolic findings.⁹⁰

PMID 10679640: This review emphasizes age-dependent clinical presentation in adrenocortical carcinoma: children more often present with virilization and have fewer nonfunctioning tumors, whereas adults more commonly show mixed Cushing-virilizing syndromes, with nonfunctioning tumors occurring mainly in older adults and following a more aggressive course.²

PMID 10826873: This case report describes metastatic cortisol-secreting adrenocortical carcinoma presenting with overt Cushing syndrome, including cushingoid habitus, hypertension, edema, hyperglycemia, severe osteopenia with compression fractures, and opportunistic fungal skin infection. The report also notes suppressed ACTH and markedly elevated urinary free cortisol in the setting of a large adrenal mass.⁴⁷

PMID 11394339: This case report describes adrenocortical carcinoma presenting atypically with superior vena cava obstruction due to mediastinal nodal compression, alongside hypertension, severe hypokalaemia, ACTH-independent hypercortisolism, elevated adrenal androgens, an adrenal mass, and liver metastases. It underscores that ACC can mimic bronchial carcinoma when cortisol excess coexists with thoracic symptoms.⁹¹

PMID 11705136: This review emphasizes that about half of ACCs are functioning and present through hormone excess syndromes, especially rapidly progressive Cushing syndrome often accompanied by androgen excess, while the remainder are clinically silent until large enough to cause abdominal symptoms or metastases. It also outlines virilizing, feminizing, and rare aldosterone-producing presentations with their characteristic biochemical patterns.¹

PMID 11829861: This retrospective series describes ACC as either functional or nonfunctional, with functional tumors commonly presenting with Cushing syndrome and less often primary aldosteronism or virilization/feminization, while nonfunctional tumors presented with nonspecific symptoms such as abdominal pain, back pain, hypertension, or incidental discovery, contributing to delayed diagnosis and poor prognosis.¹⁵

PMID 11968809: This case illustrates hormonally active ACC presenting in a young woman with virilization, amenorrhea, hirsutism, clitoromegaly, abdominal pain, and elevated cortisol and testosterone. Endocrine manifestations resolved after resection, highlighting masculinization as a clinically important but uncommon adult presentation.⁹²

PMID 12002362: In ACC with inferior vena cava extension, presentation is often clinically nonfunctional despite advanced venous involvement. In this literature review, about half of ACC cases had obstructive symptoms such as lower-extremity edema or dyspnea, and only half were clinically hormonally functional, with clinical functionality more common in younger patients and females.⁹³

PMID 12954960: This case highlights hormone-secreting ACC presenting with rapidly developing Cushing’s syndrome and virilization, including hirsutism, amenorrhoea, weight gain, hypertension, and elevated testosterone. The report notes that raised androgen levels in a patient with Cushing’s syndrome can suggest a malignant adrenal tumor.³¹

PMID 12985173: This case report describes feminizing ACC in a man presenting over years with gynecomastia, diminished libido, impotence, and later a large abdominal mass, with lung and liver metastases. The article emphasizes that estrogenic presentations are rare and may evolve slowly, potentially delaying recognition.⁹⁴

PMID 13098624: This case report describes a functional ACC in an elderly woman presenting with mixed hypercortisolism and virilization features, including obesity, facial plethora, diabetes, hypertension, edema, hirsutism, and elevated urinary 17-ketosteroids. The report also highlights acute perforated gastric ulcer as a terminal complication potentially related to glucocorticoid-like hormone excess.⁹⁵

PMID 13126484: This case report describes adrenal cortical carcinoma presenting with a pheochromocytoma-like syndrome, including paroxysmal severe hypertension, profuse sweating, hyperglycemia, and intense pain, without overt adrenogenital or Cushingoid features. It highlights that ACC may rarely mimic catecholamine-secreting tumors clinically.⁵¹

PMID 13449145: This case report and literature review describes feminizing ACC presenting in a young man with progressive gynecomastia, reduced libido and potency, testicular atrophy, and markedly increased urinary estrogen excretion. The review notes that gynecomastia often precedes other symptoms by many months in reported feminizing ACC cases.⁹⁶

PMID 13457493: This case report describes a hormone-producing adrenocortical carcinoma presenting initially with subtle hypercortisolism and mild virilizing features despite limited classic Cushingoid signs, followed after adrenalectomy by remission and later recurrence with marked virilization, hypertension, hepatomegaly, and widespread metastatic disease.⁹⁷

PMID 13472618: This case series describes predominantly functional adrenocortical carcinomas presenting with hyperadrenocorticism and frequent virilizing features, including hirsutism, clitoral enlargement, acne, amenorrhea, hypertension, obesity, moon facies, edema, glucose intolerance, and occasional feminization. The patients had advanced recurrent or metastatic disease, sometimes with hepatic, pulmonary, and vena caval involvement.⁹⁸

PMID 13493697: This case report describes an adrenocortical carcinoma presenting with extremely prolonged virilization beginning in childhood, including hirsutism, deepened voice, clitoromegaly, amenorrhea, and markedly elevated urinary 17-ketosteroids and pregnantriol before tumor resection.⁹⁹

PMID 13513730: This case report describes feminizing ACC in an adult man presenting with gynecomastia, breast tenderness, reduced libido, testicular softening, and a large abdominal mass, alongside markedly increased urinary estrogens and other steroid metabolites. Symptoms and estrogen excess improved after tumor resection.¹⁰⁰

PMID 14085320: This case report describes feminizing ACC in a man as a rare functional presentation marked by gynecomastia, loss of libido and potency, testicular atrophy, and markedly increased urinary estrogen excretion, often with concurrent androgen excess. The excerpt also notes generally poor prognosis for these feminizing adrenal cortical tumors.¹⁰¹

PMID 14204411: This review notes that adrenocortical carcinoma can cause Cushing’s syndrome, with urinary 17-ketosteroids often elevated in carcinoma compared with benign Cushing’s syndrome. It also outlines classic hypercortisolism features and highlights that abrupt, severe Cushingoid presentations with hypokalemic alkalosis may suggest an underlying malignancy.²⁶

PMID 14212075: This case report describes metastatic adrenocortical carcinoma in a young man presenting with feminization, later followed by hypertension, edema, and acne. Serial steroid studies linked these clinical features to marked estrogen excess and abnormal steroid precursor production rather than typical androgen or glucocorticoid overproduction.¹⁰²

PMID 14252287: This case report describes adrenocortical carcinoma presenting with Cushing’s syndrome, virilization, a large abdominal mass, and recurrent fasting hypoglycemia that resolved after tumor resection. The report highlights hypoglycemia as an uncommon paraneoplastic presentation in a steroid-secreting ACC.¹⁰³

PMID 14272374: This historical case discussion notes that marked estrogen hyperexcretion can accompany adrenocortical hyperactivity and cites prior reports of large urinary estradiol and estriol quantities in adrenal cancer. It highlights estrogen-related manifestations such as spider angiomata, periostitis, clubbing, arthropathy, and possible gynecomastia.¹⁰⁴

PMID 14449676: This case describes ectopic cortisol excess from bronchogenic carcinoma causing bilateral diffuse adrenocortical hyperplasia, with hypertension, diabetes or ketosis, profound hypokalemic metabolic alkalosis, and markedly elevated steroid levels despite absent classic Cushingoid features.¹⁰⁵

PMID 14564138: This case highlights ACC presenting with rapid-onset ACTH-independent Cushing syndrome plus virilization, hypertension, hypokalemia, edema, menstrual irregularity, hirsutism, and metastatic disease. The discussion notes that mixed cortisol-androgen excess is a common functional presentation in adults and often accompanies large tumors with advanced disease.⁴⁶

PMID 14668717: Pure androgen-secreting adrenal tumors are an uncommon cause of ACC presentation, especially in females, producing virilization with hirsutism, acne, clitoral enlargement, and menstrual disturbance without cortisol excess. In this series, about half of pure virilizing adrenal tumors were malignant, including pediatric and adult cases.²⁷

PMID 14834174: This case report describes ACC presenting with combined Cushingoid features and virilization in a 47-year-old woman, including florid facies, central obesity, hirsutism, amenorrhea, severe hypertension, and elevated urinary 17-ketosteroids. Surgical removal of a right adrenal cortical carcinoma was followed by biochemical decline in 17-ketosteroids and partial clinical improvement.¹⁰⁶

PMID 14920305: This case report describes androgen-secreting ACC in an adult man presenting with a large right adrenal mass, gynecomastia, markedly elevated urinary 17-ketosteroids, preserved libido and spermatogenesis, weight gain, polycythemia, hypertension, and later pulmonary and visceral metastases.¹⁰⁷

PMID 15049587: This review notes that patients with adrenocortical carcinoma often present with clinical signs of androgen excess, including hirsutism, male pattern baldness, and clitoral hypertrophy, though these may be absent. It also situates ACC within cortisol-producing presentations of Cushing’s syndrome and highlights the value of history, physical examination, and serial appearance changes.¹⁰⁸

PMID 15704782: This case describes ACC presenting after years of radiographic stability with abrupt onset of severe functional disease, including cortisol excess, hyperglycemia, hypokalemia, weakness, weight loss, and rapid clinical decline. The report highlights that multihormone secretion and rapidly evolving symptoms strongly suggest carcinoma even when an adrenal mass had previously seemed indolent.¹⁰⁹

PMID 15863951: This case illustrates ACC presenting with overt Cushing’s syndrome plus hyperandrogenism, including hirsutism and markedly elevated 17-hydroxyprogesterone and adrenal androgens. Imaging showed a large irregular adrenal mass with liver and lung metastases, highlighting that hormonally active ACC may present with combined steroid excess and advanced disease.¹¹⁰

PMID 16420869: This case describes ACC presenting with progressive abdominal distension and postprandial fullness together with amenorrhea and marked hirsutism, reflecting a virilizing endocrine syndrome from a very large adrenal mass with mass effect on adjacent organs.¹¹¹

PMID 16433936: This review notes that androgen-secreting adrenal tumors are part of the differential diagnosis of polycystic ovary syndrome in reproductive-age women presenting with hyperandrogenic features such as hirsutism, acne, menstrual irregularity, and biochemical androgen excess.³⁰

PMID 16596055: Feminizing ACC in adult men is described as a rare but highly aggressive functional variant characterized by gynecomastia, impotence, possible testicular atrophy, and marked estradiol excess with reduced testosterone. Tumors were typically very large and advanced at diagnosis, contributing to poor outcomes despite surgery and postoperative therapy.³³

PMID 20713337: This visual vignette highlights ACC presenting with mixed hormone excess in a postmenopausal woman, including hypercortisolism, marked hyperandrogenism, and very high estradiol. The report emphasizes that cosecretion of androgens and corticosteroids should raise suspicion for malignant adrenal disease.¹¹²

PMID 16618983: This case report describes a rare functional ACC in a young man presenting with mild gynecomastia from estrogen excess together with autonomous cortisol secretion causing subclinical Cushing’s syndrome, despite no overt Cushingoid features. Hormonal abnormalities normalized after tumor resection.¹¹³

PMID 16778409: This case report describes a nonfunctioning ACC presenting with symptoms from local and vascular tumor burden, including dyspnea, weight loss, and poor intake, with a large right adrenal mass showing direct extension through the inferior vena cava into the right atrium. The report notes that nonfunctioning ACC commonly presents with mass-effect symptoms rather than hormone excess.¹¹⁴

PMID 16974107: This case report describes a rare feminizing ACC that secreted estradiol and inhibin B, causing gynecomastia, loss of libido, and a distinctive endocrine pattern of markedly elevated estradiol with selective suppression of basal and GnRH-stimulated FSH despite normal LH. Inhibin B and estradiol fell after resection and rose again with early local recurrence.¹¹⁵

PMID 17534556: In this tertiary-center Cushing’s syndrome series, 13 patients had cortisol-secreting adrenocortical carcinoma without distant metastases at presentation, indicating ACC can present through overt hypercortisolism rather than metastatic symptoms. Despite biochemical control after adrenalectomy, survival in the ACC subgroup remained poor.⁵⁵

PMID 18128432: This case report describes a male patient with metastatic adrenocortical carcinoma associated with markedly increased urinary gonadotropin excretion and a positive Friedman test, without clear feminization. The report highlights that ACC can present with unusual endocrine manifestations beyond more typical virilizing or feminizing syndromes.¹¹⁶

PMID 18363988: This case report describes a functional adrenocortical carcinoma presenting with severe mineralocorticoid-like manifestations, including profound hypokalemia, kaliuresis, metabolic alkalosis, hypertension, and paresis, alongside hypercortisolism. Aldosterone was low while deoxycorticosterone was increased, and these abnormalities resolved after adrenalectomy.¹⁴

PMID 18912706: This historical case report describes pediatric virilizing adrenocortical carcinoma presenting with progressive hirsutism, deepened voice, primary amenorrhea, clitoromegaly, and a large abdominal mass, with unusually severe metabolic disturbance including profound recurrent hypoglycemia and seizures.¹¹⁷

PMID 19742438: This case report describes aldosterone-secreting adrenocortical carcinoma presenting with severe hypertension, persistent hypokalemia, and ventricular fibrillation causing resuscitated sudden cardiac death. It highlights that unexplained persistent hypokalemia after sudden death should prompt evaluation for adrenal causes, including ACC.⁴³

PMID 20266235: This case-based review describes hormone-producing adrenal cortical carcinoma as presenting with variable endocrine syndromes, most often Cushing-like features, while noting that manifestations depend on the steroid profile and patient sex and age and may be atypical or incomplete.⁷

PMID 20467160: This case report describes a rare feminizing ACC in a man presenting with gynecomastia, reduced libido, elevated estrone and estradiol, and hypogonadotropic hypogonadism, with concurrent subclinical ACTH-independent hypercortisolism. It highlights estrogen-secreting ACC as an uncommon but important cause of male hypogonadotropic hypogonadism and feminizing symptoms.¹¹⁸

PMID 20668603: This case highlights metastatic ACC presenting with virilization and bone pain in a postmenopausal woman, with markedly elevated androgen levels, only marginal cortisol elevation, and skeletal plus hepatic metastases. The report emphasizes that virilization and androgen-secreting phenotypes can signal malignant adrenal cortical disease.¹¹⁹

PMID 21167382: This review highlights the uncommon clinical presentations of androgen- and estrogen-secreting adrenocortical cancers, including virilization, hirsutism, menstrual irregularity, precocious puberty, gynecomastia, and hypogonadism. It emphasizes that cortisol-androgen co-secretion is highly suggestive of malignancy and that feminization in a patient with an adrenal tumor is considered almost pathognomonic of malignant disease.⁴

PMID 21720063: This case report highlights feminizing ACC as a rare functional presentation in men, with gynecomastia, poor libido, erectile dysfunction, marked hyperestrogenemia, elevated DHEA-S, and low testosterone. The excerpt also notes selective FSH suppression with relatively preserved LH, suggesting unusual hormone secretion beyond estrogen alone.¹²⁰

PMID 21806824: This case report highlights that nonfunctioning ACC can rarely present with testicular pain, unilateral varicocele, acute kidney injury, and renal vein or inferior vena cava thrombosis rather than endocrine symptoms. It emphasizes abdominal and retroperitoneal evaluation when varicocele is accompanied by atypical features or signs of venous obstruction.¹²¹

PMID 22039980: In a dog with functional adrenocortical carcinoma causing hyperadrenocorticism, severe polyuria and polydipsia improved after tumor removal. The study supports cortisol excess as a driver of polyuria through impaired renal response to vasopressin rather than suppressed vasopressin release.¹²²

PMID 22461853: This case describes adrenocortical carcinoma presenting with Cushing’s syndrome together with non-islet cell hypoglycaemia mediated by big IGF-II. It highlights a rare hormonally complex presentation of ACC beyond typical single-hormone excess patterns.⁵²

PMID 22689603: This case report describes feminizing adrenocortical carcinoma presenting with marked gynecomastia in a middle-aged man, with very high estradiol, suppressed gonadotropins, low testosterone, and concurrent Cushingoid features. The report emphasizes that ACC is a rare but important cause of gynecomastia in older men without an obvious medication cause.¹²³

PMID 22784838: This case describes ACTH-independent Cushing’s syndrome and initial hyperandrogenism from an adrenal cortical tumor, followed four years later by recurrent Cushing’s caused by cortisol-secreting pulmonary metastases without local adrenal recurrence. It highlights that late ACC metastases can remain hormonally functional while changing their steroid output profile.⁵⁷

PMID 22937299: This case report describes feminizing ACC in a man presenting with gynecomastia, decreased libido, erectile dysfunction, and markedly elevated estradiol, alongside possible cardiac manifestations including heart failure, QT prolongation, and ventricular arrhythmia that improved after adrenalectomy.¹²⁴

PMID 23152728: This case report describes a rare pseudopheochromocytoma presentation of adrenocortical carcinoma, with episodic hypertension, palpitations, sweating, postural symptoms, and elevated urinary VMA despite absent Cushingoid or virilizing features. It highlights that ACC can rarely mimic pheochromocytoma clinically and biochemically.¹²⁵

PMID 23204580: This veterinary case describes a functioning unilateral adrenocortical carcinoma presenting with mineralocorticoid-excess features, notably severe hypertension and refractory hypokalemia, despite normal aldosterone testing. The report highlights that active steroid precursors such as deoxycorticosterone can produce this phenotype and that symptoms resolved after adrenalectomy.¹²⁶

PMID 23404608: This case series describes ACC presenting predominantly with hormone-excess syndromes, especially hypercortisolism causing Cushingoid features, hypertension, hypokalemia, edema, and ascites, with one woman showing virilization. The reported tumors were large and often advanced or unresectable, with venous compression or invasion and liver metastases.¹⁶

PMID 23424707: This case report highlights a very rare presentation of adrenocortical carcinoma as acute abdomen with hemodynamic instability from spontaneous tumor rupture and retroperitoneal hemorrhage. It also contrasts this with more typical ACC presentations driven by hormone excess or nonspecific mass effect symptoms.¹²⁷

PMID 23498718: A case report describes a left adrenocortical tumor discovered during evaluation of mediastinal and hilar sarcoid-like granulomatous adenopathy, with concurrent hypercortisolism and hyperglycemia that resolved after tumor resection. The authors present this as an unusual, previously unreported presentation associated with corticosurrénalome.¹²⁸

PMID 23565436: In a case series of adrenal incidentalomas, one patient had androgen-secreting ACC presenting with amenorrhea and mild hirsutism that had been misattributed to menopause. The review notes that androgen-secreting ACC is rare and may present with hirsutism, virilization, male-pattern baldness, and oligo/amenorrhea.¹²⁹

PMID 23924534: This case report highlights severe symptomatic hypoglycemia as a rare presentation of adrenocortical carcinoma, occurring with suppressed insulin and C-peptide and concurrent hyperandrogenic and cortisol-excess features. Clinical and biochemical abnormalities improved after tumor resection, supporting non-islet cell tumor hypoglycemia as an unusual ACC manifestation.¹³⁰

PMID 24083069: This case report highlights that functioning ACC can present with overt Cushing’s syndrome yet still have advanced disease, including inferior vena cava tumor thrombus with extension into the right atrium. Reported symptoms included flank pain and multiple hypercortisolism features despite a hormonally active tumor.¹³¹

PMID 24103295: This case report highlights that cortisol-secreting ACC can initially present with severe hypokalemia and hypertension that mimic primary hyperaldosteronism despite normal aldosterone and renin levels. The report emphasizes covert hypercortisolism without classic Cushingoid features in rapidly progressive metastatic disease.¹¹

PMID 24251173: This case report highlights that pure androgen-secreting ACC in adult women is extremely rare and may present with longstanding amenorrhea, marked hirsutism, virilization, and a large adrenal mass. The report also notes an unusual coexistence with non-classical congenital adrenal hyperplasia.¹³²

PMID 24375435: This case report highlights that nonfunctional ACC can present through severe mass effect rather than hormone excess, including acute kidney injury from near-total inferior vena cava compression. Renal function improved after tumor resection and worsened again with rapid local recurrence causing repeat caval compression.¹³³

PMID 24622271: This case highlights androgen-secreting ACC as a virilizing presentation in an adult woman, with hirsutism, scalp hair loss, menstrual irregularity, abdominal pain, and an adrenal mass accompanied by elevated testosterone and DHEAS despite otherwise unremarkable endocrine testing.¹³⁴

PMID 24642180: This case report describes nonfunctioning adrenocortical carcinoma presenting solely as bilateral pitting leg edema due to direct tumor invasion of the adrenal vein, inferior vena cava, and right atrium. It highlights vascular extension as an unusual but potentially lifesaving diagnostic clue when common edema causes are excluded.¹³⁵

PMID 24654754: This case illustrates that ACC can present with estrogen excess causing true gynecomastia in an older man. Estradiol normalized promptly after adrenalectomy, supporting a feminizing ACC phenotype, while coexisting late-onset 21-hydroxylase deficiency complicated interpretation of steroid precursor abnormalities.¹³⁶

PMID 25332762: This case report highlights feminizing ACC as a rare estrogen-secreting presentation in men, where gynecomastia may be the initial clue, often accompanied by testicular atrophy, low testosterone, and possible concurrent hypercortisolism. It emphasizes that sex hormone excess, particularly feminization, strongly suggests adrenal malignancy rather than adenoma.³⁵

PMID 25425660: This review notes that cortisol-producing ACC can present as adrenal Cushing’s syndrome, typically with moderate-to-severe hypercortisolism of rapid onset and possible virilisation. It places ACC among the major adrenal causes of ACTH-independent Cushing’s syndrome in surgical series.²¹

PMID 26425231: This case report highlights that ACC can present as a very large androgen-secreting adrenal mass with minimal clinical virilization despite markedly elevated DHEA-S and testosterone. The patient had abdominal pain and flushing, but no metastases were detected and postoperative androgen levels normalized after resection.¹³⁷

PMID 26537284: This case report describes a functioning ACC presenting with rapidly progressive ACTH-independent Cushing syndrome after bariatric surgery, with acne, hirsutism, proximal muscle weakness, severe hypertension, and diabetes worsening over three months. The report notes that many ACCs are hormonally active and may present with Cushing syndrome with or without virilization.¹³⁸

PMID 26825939: This case illustrates functional ACC presenting in a young woman with combined hypercortisolism and virilization, including Cushingoid features, amenorrhea, hirsutism, acne, hypertension, and elevated cortisol and testosterone. The report also notes that many ACCs are functional at presentation and that mixed Cushing’s syndrome with virilization is a recognized phenotype.¹³⁹

PMID 26833526: This case report illustrates that cortisol-secreting ACC can present with overt Cushing’s syndrome and already disseminated disease, including vertebral metastases causing cauda equina compression. The report emphasizes weight gain, amenorrhea, hirsutism, proximal myopathy, and progressive back pain as a potentially unifying presentation.¹⁴⁰

PMID 27672796: This case report describes adrenocortical carcinoma presenting with endogenous hypercortisolism and severe steroid-induced proximal myopathy, alongside rapid weight gain, hirsutism, diabetes, and low ACTH with markedly elevated 24-hour cortisol. Functional recovery remained limited despite medical control of cortisol excess.⁴⁸

PMID 27927710: This case report describes ACC presenting as secondary hypertension with severe hypokalemia and metabolic alkalosis from hyperaldosteronism, alongside marked cortisol and androgen excess. It highlights that aldosterone-secreting ACC is rare and may present with resistant blood pressure elevation and metastatic disease at diagnosis.⁴⁴

PMID 28095038: Pure androgen-secreting adrenal tumors are a rare functional adrenocortical tumor phenotype that can include ACC and typically present with virilization in females or sexual precocity in children, with elevated testosterone and sometimes DHEAS but without cortisol excess. In this series, one patient had ACC with lung metastases and another had local recurrence after initial resection.³²

PMID 28639924: This review notes that ACC can present as ACTH-independent Cushing syndrome through autonomous cortisol secretion. It states that about 40% of ACCs are hormonally functioning, most commonly secreting cortisol, with functioning tumors linked to greater morbidity and worse survival than nonfunctioning tumors.³

PMID 28804590: This case report describes a rare feminizing ACC in a 44-year-old man with mixed steroid secretion, showing that estrogen-secreting ACC can present without gynecomastia despite markedly elevated estradiol. The article emphasizes abdominal pain, metastatic disease, and absent classic feminization signs as a possible atypical presentation.¹⁴¹

PMID 29144800: This case highlights virilizing ACC presenting with a large adrenal-region mass, marked clitoromegaly, facial hair growth, and hyperandrogenic symptoms. It also illustrates that prominent clitoromegaly on routine CT or MRI can provide an overlooked clinical clue to androgen-secreting ACC.¹⁴²

PMID 29264142: This case report describes a functional giant adrenocortical carcinoma presenting with overt Cushingoid features alongside symptoms and biochemical findings suggestive of pheochromocytoma. It highlights that combined Cushing syndrome and pheochromocytoma-like presentation can occur in ACC, although reported as exceptionally rare.¹⁴³

PMID 29667589: This case report highlights cortisol-producing ACC presenting as abrupt worsening of metabolic syndrome, with severe hypertension, hyperglycemia, hypokalemic metabolic alkalosis, proximal muscle weakness, edema, and bruising. It emphasizes that clustered or rapidly progressive Cushingoid features may signal functional ACC, often already advanced at diagnosis.²²

PMID 29752041: This report highlights that ACC can rarely present with distant bone metastasis to the foot, alongside a large adrenal mass and pulmonary metastases. It also illustrates a hormonally functional tumor with estrogen and androgen excess in a man, where gynecomastia was the main endocrine clue despite otherwise limited symptoms.¹⁴⁴

PMID 30053001: This study characterizes feminizing ACC as a rare functional subtype presenting with estrogen excess, including gynecomastia, hypaphrodisia, and postmenopausal bleeding, often with concurrent hypercortisolism. In this cohort, estrogen-producing tumors normalized hormonal abnormalities and clinical features after surgery.⁵

PMID 30123413: This case report highlights that aldosterone-producing ACC is exceptionally rare but can present with severe or resistant hypertension and hypokalemia, including at recurrence from metastatic disease. Recurrent hyperaldosteronism after prior adrenalectomy may signal metastatic ACC and can accompany pulmonary metastases.⁴⁵

PMID 30290908: This case report describes metastatic, hormone-secreting ACC presenting with severe secondary hypertension, hypokalemia, ascites, amenorrhea, and signs of cortisol and androgen excess. The authors emphasize that hypertension is an unusual revealing presentation and may be multifactorial in cortisol-secreting ACC.¹⁴⁵

PMID 30333277: This case report describes an extremely rare ectopic hepatic adrenocortical carcinoma presenting in a young woman with longstanding virilization, including hirsutism, alopecia, deepened voice, menstrual arrest, and markedly elevated testosterone and dehydroepiandrosterone sulfate. It emphasizes that functioning ectopic ACC can mimic adrenal ACC clinically, with virilization or Cushingoid features.¹⁴⁶

PMID 30505399: This case report describes ACC presenting with heart failure from reversible dilated cardiomyopathy in a young woman with virilization, hypertension, and biochemical cortisol and androgen excess. Cardiac dysfunction resolved after adrenalectomy, highlighting an uncommon presentation of hormone-secreting ACC that may delay diagnosis.¹⁴⁷

PMID 30527206: This case report highlights that ACC can rarely present as a feminizing, multi-hormone secreting tumor with concurrent Cushing syndrome and hyperestrogenism, causing gynecomastia, testicular atrophy, loss of libido, and metastatic disease at diagnosis. It emphasizes that progressive gynecomastia in men can signal malignant adrenal hormone excess.¹⁴⁸

PMID 30557981: This case report highlights that ACTH-independent Cushing’s syndrome can rarely arise from an ectopic cortisol-secreting adrenocortical adenoma in the renal hilum, with symptoms including weight gain, amenorrhea, easy bruising, acne, and striae. It emphasizes considering ectopic adrenal tissue when adrenal glands are atrophic and a perirenal mass is present.¹⁴⁹

PMID 30859743: This pediatric case report describes testosterone-secreting ACC presenting with virilization and erythrocytosis, with polycythemia preceding overt hirsutism. After adrenalectomy, testosterone and hemoglobin normalized and virilization improved, supporting erythrocytosis as a potential early manifestation of severe androgen excess in young patients.¹⁵⁰

PMID 31440735: This case report describes a rare functional ACC presenting with primary aldosterone excess causing profound hypokalemia, ventricular arrhythmia, and cardiac arrest, with concurrent biochemical cortisol excess despite no Cushingoid features. It highlights aldosterone-secreting ACC as an unusual but important presentation of hormonally active disease.⁴²

PMID 31600093: This case report highlights feminizing ACC as a rare cause of acute gynecomastia, loss of libido, erectile dysfunction, and hypogonadotropic hypogonadism in a man with marked hyperestrogenemia. It notes that isolated estradiol-secreting ACCs are exceptionally uncommon and may present without other adrenal hormone excess.¹⁵¹

PMID 31620613: This case highlights estrogen-secreting ACC as a rare functional presentation in men, where gynecomastia, abdominal discomfort, and reduced gonadotropin and testosterone levels accompanied elevated estradiol and cortisol. The report emphasizes feminizing adrenal tumors as an uncommon but important endocrine phenotype of ACC.¹⁵²

PMID 31892624: This case highlights ACC presenting as rapidly progressive hirsutism with mixed cortisol and androgen excess, where androgenic features can partially mask classic antianabolic signs of Cushing syndrome. The excerpt emphasizes that cortisol-androgen cosecretion is a particularly suggestive presentation pattern for ACC.¹³

PMID 32231811: This case report describes ACC presenting with two exceptionally rare endocrine manifestations: IGF-II-mediated non-islet cell tumor hypoglycemia and ACTH-dependent Cushing syndrome from aberrant ACTH production by tumor cells. It highlights that ACC can rarely produce unusual paraneoplastic and hormonal syndromes beyond the usual ACTH-independent cortisol excess.¹⁵³

PMID 33075802: In a nationwide Korean cohort of adrenal Cushing syndrome, 72 of 1199 cases were malignant adrenal Cushing syndrome attributed to adrenocortical carcinoma. The study highlights persistent cardiovascular, metabolic, and psychiatric comorbidity burdens after adrenalectomy, reflecting the clinical impact of cortisol-secreting malignant adrenal tumors.⁴⁹

PMID 33568404: This case report describes ACC presenting atypically as persistent right shoulder pain, likely referred from phrenic nerve irritation caused by a large right adrenal mass with extension into the liver, inferior vena cava, and right atrium. The tumor was cortisol-secreting despite symptoms being dominated by mass effect and metastatic spread.¹⁵⁴

PMID 33652108: In a single-center Cushing syndrome cohort, the 7 patients with ACC often lacked classic Cushingoid appearance despite cortisol excess. Clinical suspicion triggered testing in 57.1% of ACC cases, with weight gain common and hirsutism particularly frequent among affected women.¹⁰

PMID 33664034: This case highlights functioning ACC presenting as severe Cushing syndrome in a woman under 40 with resistant hypertension, hypokalaemia, metabolic alkalosis, oedema, weight gain, hirsutism, acne, oligomenorrhea, proximal muscle wasting, and purple striae. It underscores that cortisol-secreting ACC can mimic other causes of secondary hypertension and may already be advanced at diagnosis.²³

PMID 33845455: This case report highlights that estrogen-secreting ACC, although exceedingly rare in women, can present in postmenopausal patients with bilateral breast enlargement, genital bleeding, and mixed estrogen-androgen secretion, sometimes with biochemical cortisol nonsuppression despite no overt Cushingoid features. The report emphasizes feminization in the setting of an adrenal tumor as a strong clue to malignancy.¹⁵⁵

PMID 33959434: This case report highlights functional cortisol-secreting ACC presenting with Cushing syndrome and a large heterogeneous adrenal mass with tumor thrombus extending through the renal and gonadal veins into the inferior vena cava. It underscores that hormone-excess symptoms may accompany locally advanced vascular invasion at diagnosis.¹⁵⁶

PMID 34083198: This case highlights that isolated virilising ACC in adults is uncommon but can present with rapidly progressive hyperandrogenic features such as hirsutism, deepening voice, clitoromegaly, and menstrual irregularities, together with abdominal mass effect and constitutional symptoms. Markedly elevated androgens with normal cortisol supported an isolated androgen-secreting phenotype.¹⁵⁷

PMID 34221746: This case report highlights that ACC can rarely present with isolated bone metastasis to the mandible ramus, producing a painless progressive parotid-region swelling without overt hormone-excess symptoms. It reinforces that although lung, liver, and lymph nodes are typical metastatic sites, unusual skeletal presentations can be the initial manifestation.¹⁵⁸

PMID 34307221: This report describes a rare virilizing functional ACC in a 33-year-old woman presenting with hirsutism, amenorrhea, and a large palpable abdominal mass, with elevated testosterone and mildly increased cortisol. It highlights that androgen-secreting ACC can present through hormonal manifestations and mass effect even when metastases are absent.¹⁵⁹

PMID 34307612: This case report describes androgen-secreting ACC in a postmenopausal woman presenting with hirsutism, a giant adrenal mass, and unusual cardiac manifestations including atrial flutter, dilated cardiomyopathy, and heart failure that resolved after tumor resection. It highlights virilization and rare cardiovascular complications as possible presentations of functional ACC.¹⁶⁰

PMID 34497994: This case report highlights estrogen-secreting ACC as a rare functional presentation in a postmenopausal woman with vaginal bleeding, elevated estradiol and testosterone, and symptom resolution after adrenalectomy. It emphasizes that feminization should raise suspicion for malignant adrenal disease and prompt broad hormonal evaluation.³⁴

PMID 34726762: This clinical image case highlights ACC presenting with overt ACTH-independent hypercortisolism, including hypokalemia, osteoporosis with multiple vertebral fractures, and metabolic comorbidities. It emphasizes considering ACC when a large adrenal mass is accompanied by manifestations of Cushing syndrome.⁵⁶

PMID 34779264: This case report highlights virilizing ACC as a rare functional presentation marked by progressive hirsutism, deepening voice, male pattern baldness, amenorrhea, and markedly elevated androgen precursors and testosterone. Menstrual function returned after tumor resection, illustrating reversibility of endocrine manifestations.¹⁶¹

PMID 35042562: In a cystic fibrosis case series, one 22-year-old woman with adrenocortical carcinoma presented with Cushing’s syndrome. She underwent complete tumor resection without metastases initially, but developed rapid local recurrence and lung and bone metastases within 10 months and died 15 months after diagnosis.¹⁶²

PMID 35078872: This case report highlights that recurrent ACTH-independent Cushing syndrome shortly after R0 adrenalectomy can rarely result from cortisol-secreting distant ACC metastases in the liver and lungs, even when there is no evidence of locoregional recurrence. It emphasizes that metastatic ACC may retain fully functional steroidogenesis.¹⁶³

PMID 35349173: In women with androgen excess, ACC should be suspected when symptoms have rapid onset, include virilization, or show severe biochemical disturbance with preferential elevation of adrenal androgen precursors such as DHEAS. The review notes that clinically active ACC may also cosecrete cortisol and present with Cushingoid features.²⁸

PMID 35580936: This case report describes iliac vein deep vein thrombosis as an atypical initial presentation of metastatic adrenocortical carcinoma in a young woman. It emphasizes that ACC may present through cancer-associated thrombosis related to hypercoagulability, cortisol excess, or tumor mass effect rather than classic endocrine or local compressive symptoms.¹⁶⁴

PMID 35637536: This case report highlights microscopic hematuria as a rare initial presentation of adrenocortical carcinoma, likely related to vascular invasion, preceding more typical manifestations of cortisol and androgen excess. The patient later developed rapid Cushingoid features, hypokalemia, and hirsutism before adrenalectomy confirmed ACC.¹⁶⁵

PMID 35865995: This case highlights that ACC can present in an older woman with vague abdominal discomfort, weight loss, and subtle hyperandrogenic features despite limited overt Cushingoid signs. The report also reiterates that many ACCs are functional, commonly causing mixed cortisol and androgen excess, while nonfunctional tumors may present through mass effect or incidental discovery.¹⁶⁶

PMID 36037151: This case report highlights that cortisol-producing ACC can present predominantly with psychiatric symptoms, including panic attacks, hallucinations, and psychosis, alongside hyperadrenergic features such as paroxysmal hypertension, tachycardia, flushing, and sweating that may mimic pheochromocytoma.²⁴

PMID 36134572: This case-based review highlights avascular necrosis of the femoral heads as a rare presenting complication of cortisol-secreting ACC. In patients with unexplained femoral head osteonecrosis and cushingoid features, endogenous hypercortisolism should prompt hormonal evaluation for an adrenal source.¹⁶⁷

PMID 36140452: In the differential diagnosis of female hyperandrogenism, rapidly progressive manifestations such as hirsutism should raise suspicion for an androgen-secreting adrenocortical carcinoma rather than polycystic ovary syndrome. The review frames ACC as an adrenal cause to consider when evaluating virilizing presentations.²⁹

PMID 36526356: This case report describes stage IV cortisol- and androgen-secreting ACC presenting with melena from upper gastrointestinal bleeding, alongside hypokalemia, hirsutism, and increased libido. The report highlights an unusual presentation linked to gastric wall infiltration and coexisting ulcer risk factors in the setting of hypercortisolism.¹⁶⁸

PMID 36578899: This case report highlights a rare presentation of cortisol-secreting ACC with overt ACTH-independent Cushing syndrome and extensive venous tumor thrombus involving the inferior vena cava, renal, adrenal, and iliac venous systems. It emphasizes that ACC may present with marked hormone excess plus unusual large-vessel invasion at advanced stage.¹⁶⁹

PMID 37124098: This case report highlights ACC as an uncommon cause of secondary hypertension in a young adult, presenting with severe persistent hypertension alongside weight gain, edema, acne, and biochemical evidence of cortisol excess. It emphasizes that functional ACC may declare itself through Cushing syndrome features rather than incidental imaging alone.¹⁷⁰

PMID 37229033: This case report highlights metastatic ACC presenting with overt hormone excess, including severe hypertension, hypokalaemia, Cushingoid features, elevated cortisol with suppressed ACTH, markedly elevated DHEAS, and gynecomastia. It reinforces that rapid multi-hormonal excess can be a key clinical clue to ACC, even in a young man.¹⁷¹

PMID 37605388: This case report describes cortisol-producing metastatic ACC presenting as resistant hypertension with hypertensive emergency, hypokalemic metabolic alkalosis, and overt Cushingoid features, complicated by myocardial injury and acute heart failure. It underscores that severe hypercortisolism from functional ACC can dominate presentation even when mass-effect symptoms are minimal.⁵⁰

PMID 38109708: In a small prospective series of patients with cortisol-secreting ACC causing Cushing syndrome, 16% had CSC-like fundus abnormalities, including serous retinal detachment and ellipsoid/interdigitation zone disruption. Ocular structural changes improved after adrenalectomy as cortisol normalized.¹⁷²

PMID 38192879: This case highlights gynecomastia from hyperestrogenism as a rare presentation of estrogen-secreting ACC in men. The report emphasizes that estrogen excess with an indeterminate adrenal mass should raise suspicion for malignancy, and recurrent gynecomastia may signal metastatic relapse years after adrenalectomy.¹⁷³

PMID 38406134: This case report describes ACC presenting as an adrenal incidentaloma with rapid-onset hypercortisolism, hyperandrogenic features, and subsequent pulmonary embolism. It highlights pulmonary embolism as a rare presenting manifestation alongside more typical clues such as virilization and Cushingoid symptoms.¹⁷⁴

PMID 39004684: This case report describes an exceptionally rare clinical presentation of ACC with ACTH-dependent Cushing’s syndrome due to ectopic ACTH production by the carcinoma itself, alongside hyperandrogenism, hypokalemia, and a large invasive adrenal mass with liver metastases.¹⁷⁵

PMID 39171930: This case report describes primary unilateral macronodular adrenal hyperplasia presenting during pregnancy as a large unilateral adrenal mass with severe ACTH-independent cortisol excess, androgen excess, and a urinary steroid pattern typically considered suggestive of ACC. It highlights a rare benign mimic of ACC in the differential diagnosis of hormonally active adrenal masses.¹⁷⁶

PMID 39626096: This case report describes metastatic, cortisol-secreting adrenocortical carcinoma presenting through bilateral chronic multifocal central serous chorioretinopathy. Ocular findings prompted endocrine evaluation that showed ACTH-independent Cushing syndrome, highlighting an unusual symptomatic presentation linked to hypercortisolism.⁵³

PMID 39894501: This case report describes adrenocortical carcinoma presenting as persistent fever of unknown origin without obvious hormone-excess symptoms, associated with markedly elevated IL-6 and inflammatory markers. Fever and systemic inflammatory abnormalities resolved rapidly after adrenalectomy, supporting IL-6-producing ACC as a rare inflammatory presentation.¹⁷⁷

PMID 40032570: This case report describes oncocytic adrenocortical carcinoma presenting atypically with refractory hypertension, decompensated metabolic syndrome, hypokalaemia, new insulin-requiring diabetes, and psychotic delirium. Postoperative resolution of psychiatric symptoms and improved blood pressure suggested occult hormonal activity despite largely non-diagnostic standard endocrine testing.⁸

PMID 40270176: This case report describes metastatic ACC with simultaneous cortisol and androgen secretion in a 62-year-old man, producing Cushingoid features, refractory hypertension, hypokalemia, edema, fatigue, and altered mental status. The report highlights that dual-secretory ACC can present with mixed endocrine manifestations and advanced disease with lung metastases.¹⁷

PMID 40375728: This case series and review highlights that ACC may present either with hormone-related syndromes such as hypercortisolism, virilisation, hirsutism, and weight loss or as an adrenal incidentaloma detected on imaging. Three of five reported cases were incidentalomas, underscoring that ACC can be asymptomatic or minimally symptomatic at discovery.¹⁸

PMID 40746503: A 17-year-old female with ACC presented with isolated androgen excess causing progressive virilization, amenorrhea, and markedly increased athletic performance. The case highlights hyperandrogenism as a distinctive presentation of ACC in young patients, with rapid biochemical normalization after adrenalectomy.¹⁷⁸

PMID 41133658: This case report and literature review highlight feminizing ACC in men as a rare estrogen-secreting presentation marked by persistent gynecomastia, suppressed gonadotropin function, and possible infertility, often accompanied by a large adrenal mass and abdominal symptoms. Estradiol normalized and gonadal function recovered after resection.³⁶

PMID 41415212: This case report describes ACC presenting through ischemic stroke workup, with multifocal infarcts leading to discovery of a large cortisol-secreting adrenal mass. It highlights that hypercortisolism and malignancy-associated hypercoagulability can contribute to thrombotic cerebrovascular presentation before ACC is otherwise recognized.⁵⁴

PMID 41797592: This pediatric ACC case highlights that marked extensive striae and amenorrhea can be presenting clues to cortisol-secreting ACC even without obvious virilization, obesity, moon facies, or hypertension. The review notes that isolated Cushing syndrome is uncommon in children, where virilization is usually the dominant presentation.²⁰

PMID 6289791: A 1982 veterinary case report describes a functioning adrenocortical carcinoma with hypercortisolism and hepatic metastases in a dog. Indirectly, it supports the broader pattern that hormonally active adrenocortical carcinomas may be clinically overt but already advanced, and that endocrine testing helps separate adrenal tumor secretion from other hypercortisolism etiologies.¹⁷⁹

Quartz 4

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hormone_excess_presentations_in_acc

Hormone-Excess Presentations in ACC

Diagnostic context

Major phenotypes

Hypercortisolism

Androgen excess and virilization

Estrogen excess and feminization

Mineralocorticoid and mineralocorticoid-like excess

Cross-phenotype patterns and complications

Role in management and research

Included Articles

References

Graph View

Table of Contents

Backlinks

Quartz 4

Explorer

hormone_excess_presentations_in_acc

Hormone-Excess Presentations in ACC

Diagnostic context

Major phenotypes

Hypercortisolism

Androgen excess and virilization

Estrogen excess and feminization

Mineralocorticoid and mineralocorticoid-like excess

Cross-phenotype patterns and complications

Role in management and research

Included Articles

References

Footnotes

Graph View

Table of Contents

Backlinks