Episode Overview

Podcast: Endocrine News Podcast
Episode: ENP92: Pheochromocytomas
Host: Aaron Lohr (A)
Guest: Dr. Nikita Chandrasekhar (B), Endocrinologist
Date: October 2, 2024

This episode delves into the complexities of diagnosing and managing pheochromocytomas through a real-world case study presented at Endo 2024. Dr. Chandrasekhar shares clinical insights, lessons learned, and discusses management strategies for this rare but dangerous endocrine tumor.

Key Discussion Points and Insights

1. What are Pheochromocytomas?

• Tumors that secrete catecholamines (e.g., adrenaline), typically arising from adrenal medulla chromaffin cells.
• Can also be extra-adrenal (paragangliomas) originating from sympathetic ganglia, but focus is on adrenal pheochromocytomas.
• Prevalence: Occur in <0.2% of hypertensive patients, most common in fourth to fifth decade, equal gender distribution.
• Risks/Symptoms: Resistant hypertension, headaches, sweating, tachycardia, palpitations, pallor, panic-attack-like episodes.
• Crisis Presentation: “On rare occasions, patients can come in with something called the pheochromocytoma crisis...which can present with mental status changes, hypertension, hypotension, hyperthermia, and organ dysfunctions.” – Dr. Chandrasekhar (01:30)
• Metastasis: 10% are metastatic.
• Medication Confounders: Tricyclic antidepressants, SSRIs, SNRIs, etc., can interfere with lab diagnosis. Must be discontinued before biochemical testing.

2. Case Study Overview

• Patient: 28-year-old woman; history of hypertension, DVT, and stage 2 cervical cancer (chemotherapy/radiation-induced early menopause).
• Presentation: Admitted in circulatory shock—suspected Takotsubo’s cardiomyopathy, required intensive support (intubation, vasopressors, ECMO, CVVH).
• Initial Finding: Old CT showed a 3.6 cm, highly vascular right adrenal mass (23 Hounsfield Units). Labs: markedly elevated plasma normetanephrines and metanephrines.
  • “They consulted us due to concerns for underlying pheochromocytoma which may have led to her presenting symptoms.” (03:52)
• Problem: Lab interpretation confounded by critical illness, vasopressors, glucocorticoids, and psychoactive medications (quetiapine).
• Discharge Plan: Outpatient reevaluation off all interfering medications.

3. Critical Management Challenge

• Unfortunate Outcome: Discharged on metoprolol (beta-blocker) and hydralazine—led to life-threatening readmission.
• “This really highlights the importance of beta blocker avoidance when there’s any underlying...pheochromocytoma, which unfortunately happened in this case, which led to her readmission.” (08:41)
• Second Admission: Severe adrenergic spells (flash pulmonary edema, hypertensive emergency), repeated biochemical elevation, re-confirmed pheochromocytoma.

4. Unique Symptomatology and Treatment

• Observation: Adrenergic crises (spells of hypertension and palpitations) at night, triggered by menopausal hot flashes.
• “...the nighttime hot flashes precipitated these symptoms of catecholamine release, which came in the form of severe hypertension and palpitation.” (06:19)
• Standard blockade (alpha then beta) was insufficient; spells persisted.
• Innovative Solution:
  • Estrogen therapy (typical for chemo-induced menopause) contraindicated due to DVT history.
  • Used megesterol acetate (a progestin) and venlafaxine (an SNRI) to suppress hot flashes, which stopped the nocturnal adrenergic spells:
    • “...these were the only two agents that really controlled her symptoms and allowed for the adenolectomy.” (08:41)
• Outcome: Underwent adrenalectomy with stable perioperative course. Pathology confirmed pheochromocytoma (2.7 cm, no invasion/metastasis). Post-op, symptoms resolved and BP stabilized.

5. Lessons and Clinical Pearls

• Avoid Beta Blockers: Never use beta blockade first in suspected pheochromocytoma—can precipitate crisis.
• Hot Flashes as Triggers: Vasomotor menopausal symptoms can induce catecholamine release in patients with these tumors.
• Innovative Management: When estrogen is contraindicated, combined progestin and SNRI therapy may control hot-flash-triggered spells, a novel solution.
• Biochemical Testing Caveats: ICU drugs and stress can make catecholamine lab interpretation unreliable; rely on imaging and detailed history.
  • “...a thorough history and the phenotypic imaging that you see on the CT scans...will be key to establishing a diagnosis and initiating these lifesaving treatments since unfortunately, we cannot depend on the lab work.” (09:34)

6. Future Research Directions

• Uncharted Area: No documented case prior to this where magestrol acetate and venlafaxine controlled hot-flash-induced adrenergic spells in pheochromocytoma where estrogen was contraindicated.
  • “So it definitely highlights a need for more research in this area since this could be a lifesaving treatment in these specific cases.” (10:28)

Notable Quotes & Memorable Moments

• “Pheochromocytomas are actually catecholamines secreting tumors, and they arise from the chromaffin cells of the adrenal medulla.” – Dr. Chandrasekhar (00:48)
• “On rare occasions, patients can come in with something called the pheochromocytoma crisis, which...can present with mental status changes, hypertension, hypotension, hyperthermia, and organ dysfunctions.” – Dr. Chandrasekhar (01:30)
• “Unfortunately, she was discharged by her primary team on metoprolol and hydralazine...that led to her readmission.” – Dr. Chandrasekhar (04:57)
• “The hot flashes were precipitating her adrenergic spells....We ended up having to go with using magase or medesterol acetate and then venlafaxine. And actually this helped immediately.” – Dr. Chandrasekhar (07:17)
• “...this highlights the importance of beta blocker avoidance when there’s any underlying...pheochromocytoma...” – Dr. Chandrasekhar (08:41)
• “...it makes it very difficult to interpret these labs. And so in these cases a thorough history and the phenotypic imaging...will be key to establishing a diagnosis and initiating these lifesaving treatments...” – Dr. Chandrasekhar (09:34)

Timestamps for Important Segments

• 00:48 – Definition and classical presentation of pheochromocytomas
• 03:09 – Introduction of case study/patient background
• 03:52 – Initial evaluation and diagnostic challenge
• 04:38 – Why ICU and medications complicate lab interpretation
• 05:26 – Readmission and reevaluation; pattern recognition
• 06:19 – Hot flashes precipitating adrenergic crises
• 07:17 – Rationale behind alternative hot flash therapy; success
• 08:18 – Surgical outcome
• 08:41 – Three major take-home points for clinicians
• 10:12 – Implications for future research

Summary

This episode offers a vivid look at the nuanced management of pheochromocytoma, particularly when diagnosis is confounded by ICU interventions and biochemical interference. It underscores the value of clinical suspicion, the danger of mistimed beta blockade, and the untapped therapeutic potential of progestins/SNRIs for vasomotor-triggered crises when standard therapies are contraindicated. Dr. Chandrasekhar's case serves as a valuable primer on both the pathology and the art of managing rare endocrine emergencies.