Psychological Symptoms of Pheochromocytoma: The Mind Under Catecholamine Storm

By

Pheochromocytoma is a rare, often underdiagnosed tumor that arises from chromaffin cells of the adrenal medulla. Its hallmark is the excessive and unregulated secretion of catecholamines—primarily epinephrine and norepinephrine. While its classic triad of symptoms includes headache, palpitations, and sweating, the effects of chronic catecholamine excess extend far beyond the physical. The central nervous system is significantly impacted, leading to a constellation of psychological and neuropsychiatric symptoms that can easily be mistaken for primary mental health disorders.

Psychological Symptoms of Pheochromocytoma Due to Excess Catecholamines

1. Anxiety / Panic Attacks

One of the most prominent psychological manifestations is acute anxiety, often resembling panic attacks:

  • Sudden, intense fear or discomfort.

  • Palpitations, chest tightness, and shortness of breath.

  • Often indistinguishable from true panic disorder.

  • Episodes are driven by catecholamine surges, not psychological triggers.

2. Irritability

  • Individuals often describe feeling "on edge" or chronically agitated.

  • This state of heightened arousal is linked to ongoing sympathetic nervous system activation.

3. Emotional Lability

  • Mood swings may be rapid and unpredictable.

  • Patients may shift between anxiety, anger, tearfulness, or irritability within minutes.

4. Insomnia

  • Difficulty initiating or maintaining sleep is common.

  • Hyperarousal due to elevated catecholamine levels interferes with normal sleep cycles.

5. Restlessness / Agitation

  • A physical and mental inability to relax.

  • Pacing, fidgeting, or feeling internally "revved up" are frequent complaints.

6. Depression

  • More likely in chronic, undiagnosed cases.

  • May co-occur with anxiety symptoms and contribute to significant functional impairment.

7. Cognitive Impairments

  • Problems with concentration and short-term memory are often reported.

  • Patients may describe episodes of “brain fog,” particularly during or after catecholamine surges.

Neurobiological Mechanisms Behind These Symptoms

Catecholamines play a central role in the fight-or-flight response, a critical survival mechanism. However, in pheochromocytoma, the constant and excessive release of epinephrine and norepinephrine leads to:

  • Overactivation of brain structures such as the locus coeruleus (arousal center), amygdala (fear processing), and hypothalamus (autonomic and emotional regulation).

  • Disruption of the hypothalamic-pituitary-adrenal (HPA) axis, contributing to both mood disturbances and cognitive dysfunction over time.

This overstimulation results in a brain caught in a perpetual state of stress, even in the absence of external threats.

Differential Diagnosis Considerations

Because the psychological presentation of pheochromocytoma can mimic psychiatric conditions, misdiagnosis is common. It is often confused with:

  • Generalized Anxiety Disorder (GAD)

  • Panic Disorder

  • Bipolar Disorder

  • Post-Traumatic Stress Disorder (PTSD)

Red Flags Suggesting Pheochromocytoma Instead of a Primary Psychiatric Disorder:

  • Paroxysmal episodes with sudden onset and spontaneous resolution.

  • Physical signs accompanying psychological symptoms: severe hypertension, tachycardia, sweating, tremors, pallor.

  • Lack of response to standard psychiatric medications or therapies.

  • A pattern of episodic symptoms linked to autonomic dysfunction rather than emotional triggers.

Diagnostic Workup for Pheochromocytoma

Biochemical Testing (First-Line)

  • Plasma Free Metanephrines
    The preferred initial screening test due to its high sensitivity and convenience. It's a simple blood test that detects elevated levels of metanephrine and normetanephrine—byproducts of catecholamines.

  • 24-Hour Urine Catecholamines & Metanephrines
    Measures epinephrine, norepinephrine, and their metabolites. Useful for confirming biochemical abnormalities or when plasma testing is equivocal.

  • Clonidine Suppression Test
    Used when plasma levels are mildly elevated to distinguish true pheochromocytoma from false positives. Clonidine suppresses sympathetic tone, but not tumor-derived catecholamine secretion.

  • Chromogranin A
    A supportive marker that may be elevated in neuroendocrine tumors, but has low specificity, so it is not used as a primary diagnostic test.

Imaging

  • ¹³¹I-MIBG Scintigraphy
    Performed after positive biochemical tests to localize the tumor. Helpful in identifying extra-adrenal or metastatic disease.

Genetic Testing and SDH-Related Pheochromocytoma

Approximately 30–40% of pheochromocytomas are linked to inherited mutations. Testing is especially important in patients with:

  • Early-onset disease

  • Bilateral tumors

  • Family history of pheochromocytoma or paraganglioma

Key Genetic Tests:

  • SDH Gene Panel (SDHB, SDHD, etc.)
    Identifies mutations in succinate dehydrogenase (SDH) genes, which predispose to hereditary pheochromocytoma.

  • Succinate:Fumarate Ratio
    Elevated succinate relative to fumarate can suggest a functional SDH deficiency, supporting the presence of an SDH mutation.

  • Immunohistochemistry (IHC)
    Loss of SDH complex expression in tumor tissue (e.g., SDHB-negative staining) confirms SDH dysfunction.

Conclusion

Pheochromocytoma, though rare, should be part of the differential diagnosis when psychological symptoms are episodic, intense, and accompanied by signs of autonomic overactivity. The unregulated release of epinephrine and norepinephrine creates a physiological environment that mimics psychiatric illness, making diagnosis challenging.

A high index of clinical suspicion is essential—especially in patients presenting with unexplained anxiety, panic, or mood changes, alongside symptoms such as hypertension and palpitations.

Definitive diagnosis involves:

  • Biochemical testing: plasma free metanephrines (high sensitivity).

  • Imaging studies: CT or MRI of the adrenal glands or MIBG scanning if needed.

Timely diagnosis and treatment can not only reverse life-threatening cardiovascular effects but also resolve the debilitating psychological symptoms that so often dominate the clinical picture.

Keywords: pheochromocytoma, catecholamines, epinephrine, norepinephrine, anxiety, panic attacks, neuropsychiatric symptoms, adrenal tumor, HPA axis, sympathetic nervous system.

References:

Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma
https://www.nature.com/articles/s41436-018-0106-5

Understanding the Krebs Cycle, Adrenal Gland Function, and Pheochromocytoma: A Look into Catecholamine-Secreting Tumors
https://swaresearch.blogspot.com/2025/12/understanding-krebs-cycle-adrenal-gland.html

© 2025-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9  

Comments

Post a Comment

Popular posts from this blog

Schnitzler Syndrome: A Rare Autoinflammatory Disorder

By
Schnitzler syndrome is a rare, chronic autoinflammatory disease characterized by chronic urticaria (hives), recurrent fever, joint pain, and monoclonal gammopathy (abnormal proteins in the blood). First described by Dr. Liliane Schnitzler in 1972 , this condition is often misdiagnosed, leading to years of untreated symptoms before a correct diagnosis is made. The case report, " A 58-Year-Old Woman With Urticaria, Fever, and Joint Pain " , describes a case that closely aligns with my own experience with this challenging disorder. Key Features of Schnitzler Syndrome Schnitzler syndrome presents with a characteristic set of symptoms, though not all patients experience them in the same way: Chronic Urticaria (Hives) – Persistent, non-itchy or mildly itchy red patches that do not respond to antihistamines. Monoclonal Gammopathy (IgM or IgG type) – Abnormal monoclonal immunoglobulin detected in the blood (most commonly IgM ). Recurrent Fever – Unexplained fever episodes, often...
Read more

Acute Flaccid Myelitis (AFM): Understanding the “Polio-like” Illness Affecting the Spinal Cord

By
Acute flaccid myelitis (AFM) is a rare but serious neurological disorder that primarily affects children and results in sudden weakness or paralysis in the limbs. Often referred to as a “polio-like” illness, AFM has drawn growing attention over the past decade due to its similarities with poliomyelitis and its seasonal spikes in reported cases. While AFM remains uncommon, its potential severity—and the uncertainty surrounding its causes—make it an important condition for clinicians, parents, and public health officials to understand. What Is Acute Flaccid Myelitis? AFM is a condition that affects the gray matter of the spinal cord , where it damages motor neurons responsible for muscle movement. This leads to acute, flaccid paralysis , meaning muscles become limp and weak, often without warning. The condition can progress rapidly, and in some cases, the weakness can become long-lasting or even permanent. Although its symptoms resemble those of poliovirus infection, AFM is not cau...
Read more

Dysferlin Protein: Key Roles, Genetic Locations

By
Image
The purpose of this article is to share and discuss the details of a new discovery, which is highlighted within: CRISPR-Cas9: A Breakthrough Tool to Repair the DYSF Gene The dysferlin protein plays an essential role in maintaining the integrity of muscle cell membranes, particularly in tissues that endure significant mechanical stress, such as skeletal and cardiac muscles . Encoded by the DYSF gene , dysferlin is indispensable for repairing damaged cell membranes after injury caused by muscle contraction or external forces. This article explores the main locations where dysferlin is produced, its role in muscle repair, and supportive nutritional and therapeutic strategies for individuals with dysferlin deficiency, such as those affected by dysferlinopathies (e.g., Limb-Girdle Muscular Dystrophy Type 2B or Miyoshi Myopathy). Currently, there is no definitive answer as to why the severity of dysferlin protein expression or depletion varies. Do pathogens play a role in the methylation o...
Read more