The Enigmatic Dance of Androstenedione in Cushing’s Syndrome

December 21, 2023by Dr. S. F. Czar0

The Enigmatic Dance of Androstenedione in Cushing’s Syndrome

Patient: Sarah, a 34-year-old woman, presented with a constellation of symptoms suggestive of Cushing’s syndrome. Over the past two years, she experienced weight gain, particularly around the trunk and upper back, accompanied by the development of facial hair and acne. Additionally, she reported irregular menstrual cycles and excessive fatigue-Androstenedione

Initial Evaluation:

  • Physical examination revealed central obesity, facial and abdominal striae, and mild hirsutism.
  • Laboratory tests:
    • Elevated serum cortisol levels, confirming hypercortisolism.
    • Elevated ACTH levels, pointing towards ACTH-dependent Cushing’s syndrome.
    • Elevated serum androstenedione levels, significantly higher than the reference range for women.
    • Normal DHEA-S and testosterone levels.

Further Investigation:

  • Imaging studies: A pituitary MRI revealed no evidence of pituitary tumor, suggesting ectopic ACTH syndrome as a potential diagnosis.
  • An abdominal CT scan identified a small nodule on the left adrenal gland, raising suspicion of an adrenal cortical adenoma.


Based on the clinical presentation, laboratory findings, and imaging results, Sarah was diagnosed with ACTH-dependent Cushing’s syndrome likely due to an adrenal cortical adenoma. The elevated androstenedione levels, despite normal DHEA-S and testosterone levels, were consistent with findings in patients with ectopic ACTH syndrome, suggesting a distinct pattern of steroidogenesis compared to pituitary ACTH-dependent cases.

Treatment Plan:

  • Laparoscopic adrenalectomy was performed to remove the left adrenal adenoma.
  • Postoperative monitoring:
    • Serum cortisol levels normalized, confirming successful management of hypercortisolism.
    • Androstenedione levels significantly decreased and approached the normal range within three months after surgery.
    • Other symptoms, such as weight gain, hirsutism, and fatigue, gradually improved over time.


This case highlights the multifaceted role of androstenedione in Cushing’s syndrome, particularly in the context of ectopic ACTH secretion. The independent elevation of androstenedione suggests a different regulatory pathway for adrenal steroidogenesis in this variant of the disease.

  • Clinical Significance: Monitoring androstenedione levels alongside other hormones can provide valuable insights into the subtype of Cushing’s syndrome and potentially guide treatment decisions.
  • Future Research: Understanding the specific mechanisms underlying the altered androstenedione production in ectopic ACTH syndrome could pave the way for targeted therapies aimed at normalizing hormonal imbalances and improving clinical outcomes.


This case emphasizes the importance of considering the complete hormonal picture in Cushing’s syndrome, beyond just cortisol. Androstenedione, although often overlooked, can offer valuable clues for diagnosis and potentially play a more significant role in the disease process than previously recognized. Further research exploring its intricacies may hold the key to unlocking new insights and therapeutic strategies for managing this complex disorder.

Disclaimer: This case study is for educational purposes only and should not be used for self-diagnosis or treatment. Please consult a healthcare professional for any medical concerns.

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