ENP92: Pheochromocytomas

Summary

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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.

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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)

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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)

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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

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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.

Transcript

[A]

Hello, I'm Aaron Lohr and this is the Endocrine News Podcast. Today we're talking about pheochromocytomas as we walk through a very interesting case study presented at Endo 2024. Joining me is the presenter of that study, Dr. Nikita Chandrasekhar. She just finished her endocrinology fellowship at University Hospital's Case Western Reserve in Cleveland, Ohio. Thank you for being here today.

[B]

Thank you so much for having me.

[A]

We're talking about pheochromocytomas. What can you tell us about them? What are they?

[B]

Pheochromocytomas are actually catecholamines secreting tumors, and they arise from the chromaffin cells of the adrenal medulla. There are actually even extra adrenal pheochromocytomas or paradangliomas that we call them, which are also catecholamine secreting tumors, but they arise from the sympathetic ganglia. But today we'll be focusing mainly on the pheochromocytomas.

[A]

And when we're thinking about these, what do we know about their prevalence or what risks they pose to our health?

[B]

They occur in less than 0.2% of patients with hypertension, and they can occur at any age. But they're most commonly seen in the fourth to fifth decade of life, and they're equally common in males and females.

[A]

What are the risk factors that pheochromocytomas have?

[B]

The risks that generally come with the pheocytoma is that patients would have issues with resistant hypertension. They can present with headaches, sweating and tachycardia. Some patients have palpitations paler. They can come in with panic attack like symptoms. And on rare occasions, patients can come in with something called the pheochromocytoma crisis, which is which can present with mental status changes, hypertension, hypotension, hyperthermia, and organ dysfunctions. One of those organ dysfunctions can be cardiomyopathy, which is from the catecholamine excess. And it's similar to Takotsubo's or stress induced cardiomyopathy. And it can present with pulmonary edema when patients are given beta blockades during their admission. And 10% of all catecholamine secreting tumors are actually metastatic. So a lot of the times the lab work that you perform for pheochromocytomas, they can have a lot of confounding factors. When alternate medications are being taken, like tricyclic antidepressants, patients who are taking medications like antidepressant medications like SSRIs, SNRIs. You have to make sure that those medications are stopped weeks before actually doing these fytoma labs in fear that they would interfere with the actual lab result. And our case that we're presenting today is just an example of that where in the ICU there are so many factors that play in and this can actually lead to difficulties with the biochemical interpretation of the pheochemothytoma.

[A]

Lab. You recently presented an intriguing case study at Endo 2024. Can you tell us about the patient and what they presented upon their visit to the hospital?

[B]

So this was the case of a 28 year old female. She had a past medical history of hypertension, she had a history of a deep vein thrombosis and unfortunately had invasive stage 2 cervical cancer and had underwent chemotherapy and radiation which led to symptoms of early menopause. And she presented to the hospital in circulatory shock from what they thought was Takatsubo's cardiomyopathy. And during this admission she required intubation, use of vasopressors. She was ultimately placed on CVVH and ecmo. So she's very sick in the ICU when they ultimately consulted.

[A]

So now endocrinology gets involved in what happened next.

[B]

The reason that they consulted us was because they looked over some of her previous CT imaging and found that she had a highly vascular 3.6 cm 23 Hounsfield unit right Adrenal mass on a CT abdomen that was done months prior to her admission. They subsequently checked plasma Normanphrines and they were elevated at 15 nanomoles per liter. And her plasma metanephrines were also elevated at 1.5 nanomoles per liter. @ the time of the consult, her urinary metanephrines and normanpherens were still in process. So they consulted us due to concerns for underlying pheochromocytoma which may have led to her presenting symptoms.

[A]

And so now endocrinology is involved and they got some good data and now they're going to take some next steps. And what were those?

[B]

With the data that was presented to us with her acute illness and her recent use of venous suppressors along with glucocorticoids. And she was also on quetiapine for her anxiety. I was found, though the labs couldn't be accurately interpreted. And so after she had been extubated and come off ECMO and CBDH and she was ready to be discharged home, we Recommended that she see us as an outpatient when she was off all of these confounding medications and out of the critical illness, and we could recheck her labs as an outpatient. Unfortunately, she was discharged by her primary team on metoprolol and hydralazine for her management. Subsequently, that led to her readmission.

[A]

So she was discharged now, readmitted. Why was there readmission and what was learned at this time?

[B]

She actually bounced back to the CICU two days later with flash pulmonary edema and hypertensive emergency. And when we got involved during the second admission, we kind of posed more questions to her and teased out that she actually had longstanding hypertension for the past 10 years, which was pretty resistant to medications. And she did endorse having these intermittent episodes of headaches, palpitations, and vomiting, which was all the more concerning for Theo. When we ultimately repeated her labs and they continued to show elevations of her normedinescence and medinesin levels. And her urinary metanephrines and normaninephrines that were checked during the prior admission did come back elevated as well. So she was admitted and prepped for adrenalectomy because there was a concern that that right adrenal mass was indeed a feeo. So ultimately, when during her admission, we started to notice that she would have hot flashes, which she always had even previously prior to the admission. But the nighttime hot flashes precipitated the these symptoms of catecholamine release, which came in the form of severe hypertension and palpitation. And the symptoms that she had, which were precipitated initially by these hot flashes, were only present in the night. And during the day she would be completely fine. But during the night we would see these adrenergic spells. So despite being adequately alpha blockade and then subsequently beta blockade, and we she was on Prezosan almost 6 milligrams every six hours. And despite being on these high doses, and she was still having these release of symptoms which were triggered by the hot flashes at night, which we had not seen.

[A]

So you mentioned an adrenalectomy. Was that the next course of action or there other elements that were part of the next course of action?

[B]

In order to reach the stage of performing the adrenalectomy, we need to make sure that they're, well, alpha and B blockaded, that they don't have any symptoms of catecholamine release, so that when they undergo the surgery, they're not having release of all of these hormones, and it doesn't cause A crisis. So we ultimately had to start her on a medication called magestrel acetate and venlafaxine to control these hot flashes, because the hot flashes were precipitating her adrenergic spells. Usually for hot flashes in women who have early menopause from chemotherapy, we could go with using estrogen therapy, but in her case, she had a history of a deep vein thrombosis. Estrogen therapy would be contraindicated in her case, given the risk for clotting. So we ended up having to go with using magase or medesterol acetate and then the facade. And actually this helped immediately. And the hot flashes came down after a few days, and all of her adrenergic cells were controlled. We did not change the dose of her prazosin or her labetalol. And she went in for her right adrenalectomy subsequently and did great. Intraoperatively, her blood pressure was very well controlled. Post op, she had resolution of all her symptoms and her blood pressure stabilized. And it.

[A]

Well, after all this, and things are seeming to go well. Did you find anything else?

[B]

Yeah. So ultimately, the pathology came back as a 2.7 centimeter pheochromocytoma with no local invasion or distant metastases.

[A]

This is a fascinating case, and I'm sure there's something here for others to learn. So what are some key takeaways for other healthcare providers?

[B]

Some of the key takeaways is that, you know, this really highlights the importance of beta blocker avoidance when there's any underlying for pheochromocytoma, which unfortunately happened in this case, which led to her readmission. Another part, which is kind of interesting to our case, is that the patient had these triggering menopausal hot flashes, which ended up being controlled with the acetate, which is a progestational agent, and venofaxine, which is an snri. And this preempted the adrenergic spells during her admission, and we were able to control it with these two agents. Despite having adequate alpha and beta blockade, she continued to have release of the adrenergic spells. So these were the only two agents that really controlled her symptoms and allowed for the adenolectomy. So that's the second point that's very important. And the third point, I think, would just highlight the importance of how difficult it is sometimes to interpret pheochromocytoma labs in the ICU setting, given the number of interfering agents. So there are confounders in this case, like the vasopressors and intrinsic stress of critical illness and the catiapine which increase your catecholamine levels and it makes it very difficult to interpret these labs. And so in these cases a thorough history and the phenotypic imaging that you see on the CT scans or any imaging that you have prior will be key to establishing a diagnosis and initiating these life saving treatments. Since unfortunately we cannot depend on the lab work.

[A]

And did this case illuminate some possible areas for future research?

[B]

Prior case reports have described vasomotor menopausal symptoms, masquerading pheochromocytoma symptoms and midestrel acetate has been shown to substantially decrease the frequency of hot flashes in men and women. But to our knowledge, there's no known case report that documented its use to control hot flashes and catecholamine release in pheochromocytomas when estrogen specifically is contraindicated. So it definitely highlights a need for more research in this area since this could be a lifesaving treatment in these specific cases.

[A]

Well, this has been wonderful. What an interesting case. I hope folks who are listening enjoyed hearing about this and have something to take away from it. Thank you so much for taking the time to talk to us today.

[B]

Thank you so much for having me.

[A]

And that's all for this episode. I hope you enjoyed it. If you love hearing about case studies like this one, I invite you to check out the Endocrine Society's journal entitled J.C.E.M. case Report. J.C.E.M, case Reports is an online only open access journal that publishes original clinical cases covering the entire spectrum of endocrinology worldwide. I think you'll enjoy it and if you have a case study to publish, JCEM Case Reports is welcoming submissions and offers some lovely authored benefits. We'll link to the journal in today's episode Description we'll be back soon with another fascinating dive into to the world of endocrinology. Until then, thanks for listening. Endocrine News Podcasts are a free service of the Endocrine Society. To learn more or to become a member, visit the society's website at www.endocrine.org.