Clinical Report: Cortisol Secretion's Impact on Pheochromocytomas and Paragangliomas
Overview
This study found that approximately one-quarter of patients with pheochromocytomas and paragangliomas (PPGLs) exhibit autonomous cortisol secretion, identified by nonsuppressive cortisol levels after a 1-mg dexamethasone suppression test. These patients had larger tumors, higher prevalence of diabetes, elevated catecholamine metabolites, and increased perioperative complications compared to those with suppressive cortisol responses.
Background
Pheochromocytomas and paragangliomas are tumors characterized by excessive catecholamine secretion, which increases cardiometabolic risks including hypertension and insulin resistance. Some PPGLs may also secrete other hormones, including cortisol, potentially leading to mild autonomous cortisol secretion (MACS) without overt Cushing syndrome. MACS is associated with metabolic complications such as diabetes and cardiovascular disease, which may exacerbate the clinical profile of PPGL patients. Understanding the prevalence and impact of cortisol secretion in PPGLs is critical for optimizing perioperative management and improving outcomes.
Data Highlights
Parameter
Suppressive Group
Nonsuppressive Group
P Value
Number of patients
80 (75.5%)
26 (24.5%)
–
Median age (years)
56
66
< .001
Female (%)
48.8%
84.6%
= .001
Tumor size (cm)
4.0
5.2
< .05
Diabetes prevalence before surgery (%)
26.8%
50.0%
< .05
Diabetes prevalence after surgery (%)
12.7%
33.3%
< .05
Urinary and plasma metanephrine concentrations
Lower
Higher
–
DHEAS concentrations
Higher
Lower
–
Perioperative complications
Less frequent
More frequent
< .05
Key Findings
24.5% of patients with PPGLs showed nonsuppressive cortisol levels post-1-mg DST, indicating mild autonomous cortisol secretion.
Nonsuppressive patients were older (median 66 vs 56 years) and predominantly female (84.6% vs 48.8%).
Tumors were significantly larger in the nonsuppressive group (5.2 cm vs 4.0 cm).
Diabetes prevalence was higher both before (50.0% vs 26.8%) and after surgery (33.3% vs 12.7%) in the nonsuppressive group.
Nonsuppressive patients had higher urinary and plasma metanephrine levels and lower DHEAS concentrations.
Perioperative complications, including blood loss, conversion to open surgery, and prolonged hospitalization, were more common in the nonsuppressive group.
Clinical Implications
Routine screening for autonomous cortisol secretion using the 1-mg dexamethasone suppression test in patients with PPGLs may identify those at higher risk for metabolic and perioperative complications. Recognizing mild autonomous cortisol secretion can guide preoperative optimization, including management of diabetes and cardiovascular risks, potentially improving surgical outcomes. Awareness of larger tumor size and elevated catecholamine metabolites in this subgroup may also influence surgical planning and postoperative care.
Conclusion
Mild autonomous cortisol secretion occurs in a significant subset of patients with PPGLs and is associated with adverse metabolic profiles and increased perioperative risk. Incorporating cortisol screening into the diagnostic workup may enhance patient management and prognosis.
References
European Society of Endocrinology Guidelines 2016 -- Diagnosis and management of cortisol excess
Karolinska University Hospital and University Hospital Krakow Study 2005-2023 -- Cortisol secretion in PPGLs
