A Hormonal Storm Behind the Heart: ACTH-Producing Pheochromocytoma Presenting with Acute Coronary Syndrome and Diabetic Ketoacidosis

Abstract

Background

Clinical manifestations of pheochromocytoma can be highly variable and life-threatening, particularly affecting the endocrine and cardiovascular systems. We report an unusual case of adrenal pheochromocytoma.

Case Description

A 54-year-old woman with long-standing diabetes and prior cardiovascular events presented with episodic chest pain and labile blood glucose levels. Imaging revealed a left adrenal mass and biochemical studies confirmed excessive catecholamine and adrenocorticotropic hormone (ACTH) secretion, with failure of cortisol suppression. Adrenalectomy confirmed pheochromocytoma with ectopic ACTH production. Postoperatively, the patient achieved complete biochemical remission and glycemic stability on metformin monotherapy.

Conclusion

This case highlights the diagnostic complexity of pheochromocytoma with atypical presentations. ACTH cosecretion can mimic Cushing's syndrome and precipitate metabolic crises such as diabetic ketoacidosis. Early recognition and surgical intervention are essential for improving clinical outcomes and achieving long-term stability.

 

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Keywords

pheochromocytoma - ACTH secretion - diabetic ketoacidosis - acute coronary syndrome - adrenal tumor - endocrine disorders

Introduction

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells, primarily located within the adrenal medulla. Although they typically present with episodic hypertension, palpitations, and headaches, atypical or silent manifestations are not uncommon.[1] [2] [3] In some cases, PPGLs may appear as adrenal incidentalomas or precipitate acute cardiovascular and metabolic emergencies, including acute coronary syndrome (ACS), Takotsubo cardiomyopathy, and hypertensive crises. Notably, approximately 5% of adrenal incidentalomas are later diagnosed as pheochromocytomas, often remaining asymptomatic until significant complications occur.[4] [5] [6] [7]

In rare instances, pheochromocytomas can secrete ectopic adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone, leading to Cushing's syndrome (CS) and further complicating the clinical picture with hyperglycemia, hypokalemia, and immune dysfunction. When ACTH and catecholamine excess coexist, patients may present with overlapping endocrine emergencies, posing a diagnostic challenge.[8] [9] [10] This hormonal interplay can precipitate severe metabolic instability, including diabetic ketoacidosis (DKA), even in individuals with type 2 diabetes.[11] Our case highlights this diagnostic complexity, demonstrating how cardiovascular instability, metabolic decompensation, and excess hormone production can converge due to an ACTH-producing pheochromocytoma.

 

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Case Description

A 54-year-old woman with type 2 diabetes mellitus presented with episodes of chest discomfort, dyspnea, and frequent glucose fluctuations. Her medical history included multiple non-ST elevation myocardial infarctions, heart failure with preserved ejection fraction, and two episodes of DKA.

Despite normal findings on coronary angiography, the recurrence of cardiovascular events raised suspicion for an alternative etiology. Her glycated hemoglobin (HbA1c) remained persistently elevated (> 10%) despite triple oral hypoglycemic therapy. Contrast-enhanced computed tomography ([Fig. 1]) revealed a heterogeneous, rounded left adrenal mass measuring 4.4 × 4.3 × 4.8 cm, with cystic degeneration and central necrosis. Biochemical evaluation showed markedly elevated plasma metanephrine (16.59 nmol/L; reference 0–0.5) and normetanephrine (5.53 nmol/L; reference 0–1) consistent with a pheochromocytoma. Further assessment of adrenal hormone secretion revealed a morning cortisol level of 580.2 nmol/L and ACTH level of 67.5 ng/L, with inadequate cortisol suppression following dexamethasone testing (152 nmol/L; reference: < 50), indicating ACTH-dependent hypercortisolism ([Table 1]). A pituitary magnetic resonance imaging was scheduled to localize the ACTH source; however, the patient opted to proceed with treatment of the pheochromocytoma first.

Table 1 Hormonal and glycemic profile: pre- and postoperative comparison

Hormone/Test	Preoperative	Postoperative	Reference range
Morning cortisol (nmol/L)	580.2	321.1	133–537
ACTH (ng/L)	67.5	30.8	7.2–63.3
Metanephrine (nmol/L)	16.59	< 0.10	< 0.50
Normetanephrine (nmol/L)	5.53	0.84	< 1.00
HbA1c (%)	10.2	5.9	Target < 7.0

Abbreviations: ACTH, adrenocorticotrophic hormone; HbA1c, glycosylated hemoglobin.

Fig. 1 Computed tomography (CT) scan showing a left adrenal mass with heterogeneous enhancement and central necrosis (red arrowhead).

Patients with pheochromocytoma typically require preoperative preparation with alpha-adrenergic blockade—using phenoxybenzamine, doxazosin, or prazosin—followed by the cautious introduction of beta-blockers after adequate alpha-blockade to prevent unopposed alpha-adrenergic activity.[12]

Preoperative management in this case included alpha-blockade with prazosin, insulin therapy, and continuation of oral hypoglycemics ([Table 2]). The patient subsequently underwent a left adrenalectomy. Histopathological examination confirmed pheochromocytoma, with immunohistochemical staining positive for synaptophysin, chromogranin, and S-100 protein. The Ki-67 index was < 1% and the pheochromocytoma of the Adrenal Gland Scaled Score was 0. Unfortunately, our center could not perform ACTH immunostaining due to unavailability.

Table 2 Medications pre- and postadrenalectomy

Medication	Dose	Frequency	Indication	Status/Notes
Metformin	1000 mg	TID	T2D	Currently on 500 mg; good glycemic control (last HbA1c 5.9%)
Gliclazide	120 mg	OD	T2D	Previously on; stopped after adrenalectomy
Sitagliptin	100 mg	OD	T2D	Previously used, stopped after adrenalectomy
Prazosin	1 mg	BID	Hypertension, pheochromocytoma prep	Used prior to adrenalectomy, stopped postop
Aspirin	81 mg	OD	ACS	Continued
Atorvastatin	40 mg	OD	ACS	Continued

Abbreviations: ACS, acute coronary syndrome; BID, twice daily; HbA1c, glycosylated hemoglobin; OD, once daily; T2D, type 2 diabetes; TID, three times daily.

Postoperatively, the patient's hormonal profile normalized ([Table 2]). Glycemic control improved significantly, allowing the transition to metformin monotherapy (500 mg daily). Her most recent HbA1c was 5.9%, indicating sustained metabolic stabilization. She remains under regular multidisciplinary follow-up, including quarterly endocrine reviews, annual plasma metanephrine assessments, and periodic imaging to monitor for biochemical recurrence, optimize glycemic control, and evaluate long-term cardiovascular outcomes.

 

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Discussion

This case underscores the diagnostic complexity of pheochromocytoma, particularly when it presents with atypical and multifaceted clinical features. While excess catecholamines are well known to trigger hypertensive crises, myocardial ischemia, and stress cardiomyopathy, the cosecretion of ACTH by pheochromocytomas is a rare yet clinically significant phenomenon. The combined effects of catecholamine and ACTH excess can lead to profound metabolic and cardiovascular decompensation, necessitating a high index of suspicion in complex or unexplained cases.[4] [5] [6] [7] [12] [13]

The patient's hyperglycemia and recurrent episodes of DKA likely resulted from the synergistic impact of cortisol-induced insulin resistance and catecholamine-driven lipolysis and ketogenesis. Her multiple episodes of ACS, despite normal coronary angiography, are consistent with previous reports of catecholamine-induced vasospasm and myocardial injury, hallmarks of a pheochromocytoma crisis.[5] [6] Moreover, ACTH-secreting pheochromocytomas have been associated with higher rates of metabolic derangements, including diabetes mellitus, hypokalemia, and severe hypertension.[9] [10]

Preoperative alpha-adrenergic blockade remains the cornerstone of management, ensuring hemodynamic stability and adequate volume expansion before surgical intervention. Selective alpha-blockers such as prazosin or doxazosin help minimize intraoperative risks, while beta-blockers are introduced only after sufficient alpha-blockade to avoid unopposed alpha-adrenergic stimulation. Laparoscopic adrenalectomy remains the preferred definite surgical approach for most benign pheochromocytomas, offering a favorable balance between efficacy and safety.[2]

Postoperatively, normalization of cortisol and catecholamine levels, along with marked glycemic improvement, confirmed the tumor's central role in the patient's multisystem dysfunction. Her dramatic metabolic recovery following adrenalectomy highlights the curative potential of timely surgical intervention. Clinicians should maintain a high level of vigilance for functional adrenal tumors in patients presenting with unexplained metabolic crises, cardiovascular instability, or features suggestive of CS to ensure prompt diagnosis and optimal management.

 

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Conclusion

This case highlights the importance of recognizing pheochromocytoma in patients with overlapping cardiovascular, endocrine, and metabolic abnormalities. The patient's clinical course—from recurrent episodes of ACS and DKA to biochemical evidence of hypercortisolism—demonstrates the tumor's capacity to mimic multiple life-threatening conditions simultaneously. Although ACTH-secreting pheochromocytomas are rare, they should be considered when hypercortisolism coexists with biochemical or clinical evidence of catecholamine excess.

Timely diagnosis and surgical resection led to complete biochemical remission, resolution of cardiac symptoms, and marked improvement in glycemic control. This case underscores the vital role of a multidisciplinary approach—encompassing endocrinology, cardiology, radiology, and surgery—in effectively managing complex adrenal tumors. Greater awareness of such atypical presentations can facilitate earlier diagnosis, prevent complications, and ultimately improve long-term outcomes.

 

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Conflict of Interest

None declared.

Patient's Consent Statement

The patient gave informed consent for the publication of this case report and accompanying images. The report was anonymized to protect the patient's identity.

Authors' Contributions

A.A.R., I.A., S.A.G.: Conceptualization, data collection, clinical management, manuscript writing, and final approval.

Ethical Considerations

No prior ethical approval is required for single case reports and small series.

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Publication History

Article published online:
29 July 2025