Adrenal gland and paraganglia
Adrenocortical adenoma
Tumors associated with adrenogenital syndrome

Author: Carmen Perrino, M.D. (see Authors page)

Revised: 1 March 2016, last major update February 2014

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Adrenogenital syndrome[title] adrenocortical tumor
General
  • Adrenal cortical tumor (ACT, includes adenoma and carcinoma) resulting in precocious puberty, feminization, or virilization
Epidemiology
  • Rare lesions
    • 0% to 11% of reported adrenal tumors are virilizing (Surgery 2004;136:1192)
    • Feminizing adrenocortical adenoma (ACA) less clearly quantified and are even rarer
    • Feminization is more commonly associated with adrenocortical carcinoma (ACC), comprises 1-2% of ACC (J Clin Oncol 2011;29:e127)
  • Androgen-secreting adrenal tumors more common in childhood, with ACTs most commonly presenting with virilization with/without Cushing syndrome
Sites
  • Adrenal cortex
Pathophysiology
  • Virilization: ↑DHEA, ↑DHEA-sulfate (DHEA-S), ↑androstenedione, ↑testosterone, ↑DHT → ↑urinary 17-ketosteroids (metabolic product)
  • Feminization: ↑androgens → aromatization → ↑estrogen, ↑estradiol → ↑urinary 17-ketosteroids (metabolic product)
Etiology
  • Neoplastic proliferation of adrenal cortical cells
Clinical Features
  • Virilization: occurs in women due to androgen excess
    • Hirsutism, amenorrhea, increased libido, male pattern baldness, deep voice, acne, male musculature, clitoromegaly
  • Feminization: occurs in men due to estrogen excess
    • Gynecomastia, testicular atrophy, impotence, diminished libido
  • Isosexual precocious puberty: early onset development of appropriate sexual characteristics for a patient's sex (in women due to increased estrogen, in men due to increased androgens)
Diagnosis
  • ACT in the context of appropriate laboratory and clinical findings consistent with precocious puberty, virilization, or feminization
  • May have concomitant increased secretion of mineralocorticoids or glucocorticoids as well
Laboratory
  • Virilizing:
    • ↑ serum dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androstenedione, testosterone
    • ↑ urine 17-ketosteroids (sex steroid metabolites)
    • May have relative ↓ 11β-hydroxylase with compensatory ↑ deoxycorticosterone
  • Feminizing:
    • ↑ plasma and urine estrogens
    • ↑ plasma adrenal androgens (DHEA, DHEA-S)
    • ↑ urine 17-ketosteroids (sex steroid metabolites)
    • ↓ plasma gonadotropins
    • No response to gonadotropin-releasing hormone (GnRH) stimulation because ACA produces sex steroids independently of GnRH feedback cycle
      • Normal GnRH feedback cycle: hypothalamus releases GnRH → anterior pituitary releases LH/FSH → ovaries release estrogen/progesterone OR testes release testosterone → estrogen/progesterone or testosterone inhibits release of GnRH and LH/FSH
      • GnRH stimulation test:
        • Central precocious puberty: GnRH administration → ↑ LH/FSH → ↑ estrogen/progesterone or testosterone
        • Peripheral precocious puberty (i.e. adrenal gland): GnRH administration → unchanged LH/FSH, estrogen/progesterone, and/or testosterone levels
Radiology Description
  • Computed tomography (CT) shows a well-defined, solid mass
  • Contrast shows homogeneous enhancement (Clin Nucl Med 2002;27:741)
  • Magnetic resonance imagine (MRI) shows well-defined, solid mass
  • Low signal on T1-weighted image and high signal on T2-weighted image (Intern Med 1994;33:790)
Radiology Images

Images hosted on other servers:

18 year old woman with androgen producing ACA

Right adrenal mass

Multiple pulmonary nodules

Prognostic Factors
  • Adrenogenital syndrome is indicative of malignancy; 70% (7/10) of patients in one study over a 30 year period (Cancer 1993;72:1997) and 88% (7/8) over a 28 year period with adrenogenital syndrome had ACC (Am J Med 1981;71:855)
  • Like other adrenal cortical lesions, difficult to distinguish benign from malignant cases, multiple systems have been proposed including Weiss and Modified Weiss Criteria (see Adrenocortical carcinoma topic)
Case Reports
Treatment
  • Surgical resection
Clinical Images

Images hosted on other servers:

18 year old woman with androgen producing ACA, hirsutism

Gross Description
Gross Images

Cut section of tumor

Micro Description
  • Well-defined lesion in adrenal cortex surrounded by pseudocapsule or the fibrous capsule of the adrenal gland
  • Architectural patterns include: nesting, alveolar, cords, trabeculae
  • Comprised of cells with compact, eosinophilic cytoplasm with/without admixed cells with clear, vacuolated cytoplasm
  • Nuclei are uniform, round to oval, with rare mitoses, however occasional nuclear pleomorphism and prominent nucleoli may be identified
  • Cannot predict biochemical behavior based on histology alone
Micro Images

Images hosted on other servers:

Moderate pleomorphism - H&E

Abundant eosinophilic cytoplasm - H&E

Vascular invasion - H&E

Bizarre nuclei - H&E

Thick trabecular patterns - H&E

Inhibin positivity

Cytology Description
  • Rare lesion, no reported cases with described cytologic findings
Positive Stains
  • Usually positive: α-inhibin, MelanA/Mart1, steroidogenic factor-1 (SF-1), calretinin
  • Sometimes positive: synaptophysin, neuron specific enolase (NSE), low molecular weight cytokeratin (AE1/AE3, CAM5.2)
  • Rarely positive: vimentin (Am J Pathol 1990;136:1077)
  • Low Ki-67 index (usually <5%)
Negative Stains
  • EMA, CEA, B72.3, S100
  • Chromogranin (stains adrenal medulla), vimentin, carbonic anhydrase IX (CAIX)
Electron Microscopy Description
  • Rare lesion, no reported cases with described electron microscopy findings
Molecular / Cytogenetics Description
  • Given rarity of this diagnostic entity, molecular/cytogenetics not well-established
Differential Diagnosis