Elevated urinary 19-Nor-deoxycorticosterone glucuronide in Cushing's syndrome

Area of Science:

• Endocrinology
• Nephrology
• Cardiovascular Medicine

Background:

• Hypertension is a frequent comorbidity in Cushing's syndrome (CS).
• The underlying mechanisms contributing to hypertension in CS remain incompletely understood.
• Excess production of nonaldosterone mineralocorticoids, specifically 19-nor-deoxycorticosterone (19-Nor-DOC), is a potential contributing factor.

Purpose of the Study:

• To investigate the role of 19-nor-deoxycorticosterone (19-Nor-DOC) in the pathogenesis of hypertension associated with Cushing's syndrome (CS).
• To quantify urinary 19-Nor-DOC glucuronide excretion in patients with different forms of CS and essential hypertension compared to healthy controls.

Main Methods:

• Measurement of urinary 19-Nor-DOC glucuronide excretion in normal subjects, patients with pituitary-dependent CS, adrenal CS, and essential hypertension.
• Subjects were maintained on a controlled metabolic diet (128 meq Na+, 80 meq K+/day) during 24-h urine collection.
• 19-Nor-DOC glucuronide was purified via extraction and chromatography, followed by radioimmunoassay (RIA) quantification.

Main Results:

• Urinary 19-Nor-DOC glucuronide excretion was significantly elevated in both pituitary CS and adrenal CS groups compared to normal subjects.
• Excretion levels of 19-Nor-DOC glucuronide were comparable between the two CS groups.
• Patients with essential hypertension also exhibited higher urinary 19-Nor-DOC glucuronide levels than controls, though lower than in CS patients.

Conclusions:

• This study demonstrates excessive production of the nonaldosterone mineralocorticoid 19-Nor-DOC in patients with pituitary or adrenal CS.
• Elevated 19-Nor-DOC may play a significant role in the development of hypertension in CS.
• These findings suggest a potential link between 19-Nor-DOC excess and the pathophysiology of certain hypertensive disorders.