Pediatric Pheochromocytoma With Rapid Cyclic Blood Pressure Fluctuations: A Case Report

ABSTRACT

Cyclic blood pressure fluctuations in pheochromocytoma are extremely rare, and previously reported cases have been limited to adults. We report a 5‐year‐old boy with von Hippel–Lindau disease and a left adrenal pheochromocytoma who developed rapid cyclic blood pressure fluctuations immediately after tracheal intubation. Despite preoperative doxazosin (titrated from 0.5 to 3 mg/day over 27 days) and fluid loading, systolic blood pressure oscillated between 50 and 150 mmHg at approximately 7‐min intervals after tracheal intubation. The fluctuations were independent of surgical manipulation and refractory to phenylephrine and phentolamine. Plasma norepinephrine was markedly elevated before tumor manipulation. After tumor resection, profound vasoplegic hypotension required high‐dose norepinephrine, epinephrine, and vasopressin; hemodynamics gradually stabilized, and all vasoactive agents were discontinued on postoperative Day 3. This case demonstrates that pediatric pheochromocytoma can develop cyclic blood pressure fluctuations similar to those in adults and underscores the importance of individualized preoperative α‐blockade and strict postoperative hemodynamic management after tumor resection.

Key Clinical Message

Cyclic blood pressure fluctuations in pheochromocytoma are rare and have been reported only in adults. This pediatric case shows that comparable cyclic blood pressure fluctuations can occur in children, emphasizing individualized preoperative α‐blockade, preparedness for refractory circulatory instability, and strict hemodynamic management of severe vasoplegic hypotension after tumor resection.

1. Introduction

Pheochromocytomas and paragangliomas are catecholamine‐producing tumors, and their occurrence in childhood is rare, with an estimated annual incidence of approximately 0.5–2.0 cases per million children [1]. Hypertension may be persistent or paroxysmal and is often accompanied by features of catecholamine excess such as sweating, palpitations, pallor, or headache.

In contrast, pheochromocytoma showing rapid cyclic blood pressure fluctuations independent of external stimulation is extremely rare, and previous reports have been limited to adults [2, 3, 4, 5, 6, 7]. Here, we report a pediatric case of pheochromocytoma that developed rapid cyclic blood pressure fluctuations immediately after tracheal intubation, and we discuss important considerations for the perioperative management of this unusual hemodynamic presentation.

2. Case History / Examination

A 5‐year‐old boy (height, 105 cm; weight, 17 kg) had a family history of pheochromocytoma or paraganglioma in his paternal grandmother, father, and older brother. Genetic testing at 3 years of age established a diagnosis of von Hippel–Lindau disease. He had remained asymptomatic under regular follow‐up until 5 years of age, when he developed sweating and elevated systolic blood pressure in the 140 mmHg range.

Further evaluation revealed elevated plasma norepinephrine (14.93 ng/mL; reference range, 0.1–0.5 ng/mL) and urinary total metanephrines (6070 μg/day; reference range, 140–460 μg/day); the perioperative course of the catecholamines and metanephrines is shown in Table 1. Magnetic resonance imaging demonstrated a 32‐mm tumor in the left adrenal gland (Figure 1); left adrenal pheochromocytoma was diagnosed, and surgery was planned.

TABLE 1.

Perioperative catecholamine and metanephrine levels.

Parameter	Preoperative	Intraoperative (before manipulation)	Intraoperative (during manipulation)	Postoperative	Reference range
Plasma epinephrine (ng/mL)	0.05	0.04	0.08	0.09	≤ 0.1
Plasma norepinephrine (ng/mL)	14.93	51.22	78.34	0.34	0.1–0.5
Plasma dopamine (ng/mL)	0.11	0.16	0.24	≤ 0.01	≤ 0.03
Urinary epinephrine (μg/day)	3.2	—	—	10.1	3–41
Urinary norepinephrine (μg/day)	2426.6	—	—	90.4	31–160
Urinary dopamine (μg/day)	527.7	—	—	618.6	280–1100
Urinary total metanephrines (μg/day)	6070	—	—	230	140–460

Note: — not measured. Preoperative values were obtained 22 days before surgery. The intraoperative value before tumor manipulation was obtained after anesthesia induction. Postoperative values were obtained on postoperative Day 4.

FIGURE 1.

T2‐weighted magnetic resonance imaging of the left adrenal tumor. (A) Axial and (B) coronal images show a hyperintense tumor in the left adrenal gland (arrows).

The preoperative electrocardiogram showed sinus rhythm without ST‐segment changes or arrhythmia, and the chest radiograph showed no pulmonary abnormality or cardiomegaly. Preoperative serum sodium, potassium, and glucose were within normal limits, with no findings suggesting adrenocortical dysfunction.

3. Differential Diagnosis, Investigations, and Treatment

To stabilize blood pressure and intravascular volume, doxazosin was started 27 days before surgery at 0.5 mg/day and titrated under blood pressure monitoring (0.75 mg/day at 22 days before surgery, 1.5 mg/day at 8 days, 2 mg/day at 3 days, and 3 mg/day on the day before surgery). Preoperative fluid loading was initiated after admission, 3 days before surgery. Acetated Ringer's solution was started at 40 mL/h and increased to 50 mL/h at 2 days and 60 mL/h on the day before surgery. Preoperative blood pressure remained approximately 100–130/70–80 mmHg, with a heart rate of 90–120 beats/min.

Surgery was performed under combined general and epidural anesthesia. Immediately after anesthesia induction and tracheal intubation, rapid cyclic blood pressure fluctuations appeared, with systolic blood pressure oscillating between 50 and 150 mmHg at approximately 7‐min intervals (Figure 2); these fluctuations were independent of surgical manipulation. Bolus phenylephrine (10–20 μg per dose) and phentolamine (bolus and continuous infusion, up to 5 mg/h) were administered, but the cyclic blood pressure fluctuations could not be controlled. Plasma norepinephrine was markedly elevated, measuring 51.22 ng/mL before tumor manipulation and 78.34 ng/mL during tumor manipulation. After ligation of the adrenal vein, the periodicity gradually became irregular. Following tumor resection, profound hypotension developed, requiring norepinephrine (0.7 μg/kg/min), epinephrine (0.3 μg/kg/min), and vasopressin (2 U/h).

FIGURE 2.

Intraoperative arterial pressure record. Marked cyclic blood pressure fluctuations appeared immediately after tracheal intubation. After ligation of the adrenal vein, the cyclic blood pressure fluctuations gradually lost their regular periodicity, and following tumor resection, the patient developed prolonged hypotension. ABP, arterial blood pressure; HR, heart rate; NIBP, non‐invasive blood pressure; SpO2, peripheral oxygen saturation; T, temperature.

4. Outcome and Follow‐Up

High‐dose vasoactive support was continued after admission to the intensive care unit (ICU), where norepinephrine (0.3 μg/kg/min), epinephrine (0.25 μg/kg/min), and vasopressin (2 U/h) were required; hemodynamics improved gradually thereafter. The patient was extubated on postoperative day (POD) 2, and all vasoactive agents were discontinued on POD 3, when he was transferred to the general ward.

On POD 4, adrenocorticotropic hormone (ACTH) was 144 pg/mL (reference range, 7.2–63.3 pg/mL) and morning cortisol was 16.3 μg/dL, with no findings suggestive of adrenal insufficiency. Catecholamine and metanephrine levels normalized postoperatively: on POD 4, plasma norepinephrine was 0.34 ng/mL and urinary total metanephrines were 230 μg/day. The patient was discharged on POD 6.

The pathological diagnosis was pheochromocytoma. The Pheochromocytoma of the Adrenal gland Scaled Score (PASS) was 0, and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score was 2 (Ki‐67 labeling index, 3.6%). No recurrence has been observed over 2 years of postoperative follow‐up.

5. Discussion

The most important finding of this case is that short‐period cyclic blood pressure fluctuations, previously reported in adult pheochromocytoma, can also occur in a pediatric patient. Pheochromocytoma typically presents with persistent or paroxysmal hypertension, in which blood pressure surges are often triggered by tumor manipulation, anesthesia induction, tracheal intubation, pain, or stress. In the present case, however, systolic blood pressure oscillated between 50 and 150 mmHg at approximately 7‐min intervals after tracheal intubation, independent of surgical manipulation. Although a small number of adults with similar cyclic blood pressure fluctuations have been reported [2, 3, 4, 5, 6, 7], to our knowledge no pediatric case has been described. This case indicates that cyclic blood pressure fluctuations comparable to those in adults can occur in pediatric pheochromocytoma.

The mechanisms underlying cyclic blood pressure fluctuations remain unclear, but baroreflex‐mediated negative feedback and periodic changes in tumor perfusion may contribute [2, 3, 6]. An abrupt rise in blood pressure stimulates baroreceptors, suppressing sympathetic activity and producing a hypotensive phase; a subsequent increase in catecholamine secretion then restores the hypertensive phase [3]. Alternatively, severe vasoconstriction may transiently reduce tumor blood flow and suppress catecholamine release, with restoration of tumor perfusion leading to renewed catecholamine secretion [2]. In the present case, anesthesia induction, tracheal intubation, and positive‐pressure ventilation may have altered systemic and tumor hemodynamics, thereby triggering the cyclic fluctuations [6].

Pharmacological intervention with phenylephrine and phentolamine failed to control the cyclic blood pressure fluctuations. A correlation between cyclic blood pressure fluctuations and plasma catecholamine levels has been reported previously [2, 6]; in the present case, plasma norepinephrine had already risen to 51.22 ng/mL after anesthesia induction but before tumor manipulation—approximately 3.4 times the preoperative value. Conversely, abrupt catecholamine withdrawal after tumor resection produced marked vasodilation and hypotension, requiring prolonged high‐dose vasoactive support. Similarly, an adult case has been reported in which cyclic blood pressure fluctuations could not be controlled despite α‐blockade, and marked vasodilation occurred after control of the tumor vasculature [7]. These observations suggest that cyclic blood pressure fluctuations are accompanied by vigorous catecholamine release, and that circulatory management anticipating severe post‐resection hypotension is essential.

The international consensus statement on pediatric pheochromocytoma and paraganglioma recommends preoperative α‐blockade and/or calcium channel blockade, together with fluid intake of one to two times the weight‐based maintenance volume [1]. In the present case, despite preoperative α‐blockade with doxazosin, preoperative fluid loading, and generally stable preoperative blood pressure, rapid cyclic blood pressure fluctuations nonetheless appeared after tracheal intubation. This indicates that, in children, the adequacy of preoperative preparation cannot be judged by preoperative blood pressure stability alone; even when preoperative blood pressure is stable, individualized perioperative circulatory management—anticipating unexpected post‐induction hemodynamic instability and severe post‐resection hypotension—is essential in pediatric pheochromocytoma.

Author Contributions

Katsuaki Yamazaki: investigation, methodology, supervision, writing – original draft, writing – review and editing. Chika Maeda: investigation, methodology, writing – review and editing. Kaori Morikawa: data curation, writing – original draft. Naomi Okamoto: data curation, writing – original draft.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient's parents for publication of this case report and any accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data supporting the findings of this case report are available from the corresponding author upon reasonable request. The data are not publicly available due to ethical restrictions and the need to protect patient privacy.