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Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma

Giuseppe Reimondo1, Soraya Puglisi2, Barbara Zaggia1

  • 1Internal Medicine 1Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.

European Journal of Endocrinology
|August 7, 2017
PubMed
Abstract

Insights

Mitotane treatment for adrenocortical cancer (ACC) may suppress ACTH at the pituitary level, complicating adrenal insufficiency assessment. This study shows mitotane affects the HPA axis broadly, requiring multiple biomarkers.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Mitotane is a key treatment for adrenocortical cancer (ACC), inhibiting steroidogenesis and potentially causing adrenal insufficiency.
  • In vitro studies suggest mitotane directly impacts pituitary function, warranting further investigation in patients.

Purpose of the Study:

  • To evaluate the hypothalamic-pituitary-adrenal (HPA) axis function in patients with ACC undergoing mitotane treatment.
  • To investigate the potential pituitary-level inhibitory effects of mitotane on ACTH secretion.

Main Methods:

  • Prospective study of 16 ACC patients on adjuvant mitotane therapy.
  • Standard hormone evaluation and human corticotropin-releasing hormone (h-CRH) stimulation tests were performed.
  • A control group of 10 patients with primary adrenal insufficiency (PAI) was included for CRH test comparison.

Main Results:

  • A significant correlation was observed between cortisol-binding globulin (CBG) and plasma mitotane levels.
  • ACTH levels were significantly lower in ACC patients compared to PAI patients, both at baseline and after CRH stimulation (P < 0.05).
  • No correlation was found between cortisone acetate dosage and ACTH or cortisol levels.

Conclusions:

  • Lower ACTH levels in mitotane-treated ACC patients suggest a pituitary inhibitory effect of mitotane on ACTH secretion.
  • Mitotane influences the HPA axis at multiple levels.
  • Assessing adrenal insufficiency in ACC patients on mitotane requires a multi-biomarker approach.

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