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Food-dependent Cushing's syndrome: from molecular characterization to therapeutical results

N M Albiger1, G Occhi, B Mariniello

  • 1Department of Medical and Surgical Sciences Endocrinology Unit, University of Padua, via Ospedale 105, 35128 Padua, Italy. nalbiger@yahoo.com

European Journal of Endocrinology
|December 7, 2007
PubMed
Abstract

Insights

Aberrant G-protein-coupled receptor expression, specifically glucose-dependent insulinotropic polypeptide (GIP) and LH-receptor, was identified in ACTH-independent macronodular adrenal hyperplasia (AIMAH). This finding may enable targeted therapies and supports unilateral adrenalectomy as an initial treatment option.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Surgical Oncology

Background:

  • ACTH-independent macronodular adrenal hyperplasia (AIMAH) is characterized by cortisol hypersecretion, often managed by bilateral adrenalectomy.
  • Aberrant expression of G-protein-coupled receptors on adrenal glands is implicated in AIMAH pathophysiology.
  • Investigating specific receptor profiles can reveal therapeutic targets and inform treatment strategies for AIMAH.

Observation:

  • A patient with AIMAH exhibited cortisol and androgen excess, with bilateral adrenal macronodules.
  • In vivo stimulation tests revealed abnormal cortisol responses to meals and glucose.
  • In vitro studies on adrenal tissue demonstrated overexpression of glucose-dependent insulinotropic polypeptide (GIP) and LH receptors.

Findings:

  • Octreotide therapy partially blunted cortisol response and improved urinary free cortisol (UFC) levels.
  • Unilateral adrenalectomy confirmed AIMAH and revealed coexisting GIP and LH-receptor overexpression in adrenal nodules and adjacent cortex.
  • Post-surgery, UFC and androgen levels normalized, leading to clinical improvement.

Implications:

  • Coexistence of GIP and LH-receptor expression in AIMAH influences the disease's phenotype, suggesting potential for targeted pharmacological interventions.
  • Specific receptor profiling may guide personalized medical treatments for AIMAH.
  • Unilateral adrenalectomy presents a viable initial surgical option for asymmetric bilateral adrenal hyperplasia, preserving adrenal function where possible.

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