Bilateral pheochromocytomas in Von Hippel-Lindau disease
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction
Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary condition that significantly increases the risk of various tumors, including pheochromocytomas, which are neuroendocrine tumors arising from the adrenal glands. In children, pheochromocytomas can sometimes be the first manifestation of VHL disease, with delayed onset of other typical manifestations, such as hemangioblastomas or retinal angiomas. VHL-related pheochromocytomas is often bilateral and can present with sustained hypertension, rather than the episodic symptoms typically seen in adults.
Case Presentation
We describe the clinical characteristics, biochemical findings, genetic diagnosis and treatment outcome of a child with bilateral pheochromocytomas due to VHL. Genetic testing was performed using whole exome sequencing. A 14-year-old boy was found to have hypertension of 145/110 mmHg without headache, blurred vision, nausea, or vomiting. He has no edema, no hyperpigmentation, no weight loss or Cushing signs. Twenty-four-hour urinary test showed high nor-adrenaline, high dopamine, high VMA, and high HVA. Abdominal ultrasound showed a solid, heterogeneous mass with some small fluid cysts inside on both adrenal glands with the sizes of 65x52 mm and 78x67 mm, respectively. Abdominal MSCT with contrast showed both adrenal masses with the size of 64x57x57 mm and 62x59x68 mm, respectively. Whole exome sequencing showed a dominant heterozygous pathogenic variant of VHL gene: c. 414A>G (p.Pro138=). This variant was not detected in his parents.
Diagnostic Workup
He was diagnosed with bilateral pheochromocytomas due to VHL disease.
Treatment and Management
He was treated with carduran and embolizing before surgery to remove the tumors. Both tumors were removed safely and the right adrenal gland was preserved
Outcome and Follow-Up
Complete resolution of hypertension was achieved gradually after surgery for 3 days. After that, the child was supplemented with hydrocortisone at a dose of 12.5 mg/m²/day and has been undergoing regular follow-ups every three months. Currently, two years post-surgery, there are no signs of Cushing’s syndrome, blood pressure remains normal, and puberty is progressing as expected. Abdominal ultrasound, testicular ultrasound, and brain MRI results are normal. Eye and vision examinations also show normal.
Discussion
In cases of bilateral pheochromocytomas, adrenalectomy remains the only curative treatment for the disease. Preoperative preparation is important in pheochromocytoma surgery as induction of anesthesia, manipulation of the tumor, or other stimulation can cause a massive outpouring of catecholamines from the tumor, resulting in hypertensive crisis, stroke, arrhythmias, or myocardial infarction. In this case, the risk will be higher because of bilateral pheochromocytomas with the large size. So we decided on embolization of the two tumors before removing them. The standard treatment for pheochromocytoma is adrenalectomy. However, for bilateral pheochromocytoma tumors, possible options include removing both adrenal glands or attempting to remove only the tumors to preserve adrenal hormonal function. Severe burdens accompany bilateral total adrenalectomy as it causes permanent adrenal insufficiency, requiring lifelong corticosteroid replacement therapy reduced quality of life for patients, and higher mortality. For this reason, we decided to preserve the right adrenal gland. After surgery, we gave him a hydrocortisone injection to prevent acute adrenal insufficiency. The dose of hydrocortisone was gradually reduced and the patient was taken a low dose before discharge from our hospital.
Conclusion
Genetic testing and molecular analysis, including sequencing of the VHL gene, are crucial for diagnosing VHL and identifying children at risk of additional tumors.
Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary condition that significantly increases the risk of various tumors, including pheochromocytomas, which are neuroendocrine tumors arising from the adrenal glands. In children, pheochromocytomas can sometimes be the first manifestation of VHL disease, with delayed onset of other typical manifestations, such as hemangioblastomas or retinal angiomas. VHL-related pheochromocytomas is often bilateral and can present with sustained hypertension, rather than the episodic symptoms typically seen in adults.
Case Presentation
We describe the clinical characteristics, biochemical findings, genetic diagnosis and treatment outcome of a child with bilateral pheochromocytomas due to VHL. Genetic testing was performed using whole exome sequencing. A 14-year-old boy was found to have hypertension of 145/110 mmHg without headache, blurred vision, nausea, or vomiting. He has no edema, no hyperpigmentation, no weight loss or Cushing signs. Twenty-four-hour urinary test showed high nor-adrenaline, high dopamine, high VMA, and high HVA. Abdominal ultrasound showed a solid, heterogeneous mass with some small fluid cysts inside on both adrenal glands with the sizes of 65x52 mm and 78x67 mm, respectively. Abdominal MSCT with contrast showed both adrenal masses with the size of 64x57x57 mm and 62x59x68 mm, respectively. Whole exome sequencing showed a dominant heterozygous pathogenic variant of VHL gene: c. 414A>G (p.Pro138=). This variant was not detected in his parents.
Diagnostic Workup
He was diagnosed with bilateral pheochromocytomas due to VHL disease.
Treatment and Management
He was treated with carduran and embolizing before surgery to remove the tumors. Both tumors were removed safely and the right adrenal gland was preserved
Outcome and Follow-Up
Complete resolution of hypertension was achieved gradually after surgery for 3 days. After that, the child was supplemented with hydrocortisone at a dose of 12.5 mg/m²/day and has been undergoing regular follow-ups every three months. Currently, two years post-surgery, there are no signs of Cushing’s syndrome, blood pressure remains normal, and puberty is progressing as expected. Abdominal ultrasound, testicular ultrasound, and brain MRI results are normal. Eye and vision examinations also show normal.
Discussion
In cases of bilateral pheochromocytomas, adrenalectomy remains the only curative treatment for the disease. Preoperative preparation is important in pheochromocytoma surgery as induction of anesthesia, manipulation of the tumor, or other stimulation can cause a massive outpouring of catecholamines from the tumor, resulting in hypertensive crisis, stroke, arrhythmias, or myocardial infarction. In this case, the risk will be higher because of bilateral pheochromocytomas with the large size. So we decided on embolization of the two tumors before removing them. The standard treatment for pheochromocytoma is adrenalectomy. However, for bilateral pheochromocytoma tumors, possible options include removing both adrenal glands or attempting to remove only the tumors to preserve adrenal hormonal function. Severe burdens accompany bilateral total adrenalectomy as it causes permanent adrenal insufficiency, requiring lifelong corticosteroid replacement therapy reduced quality of life for patients, and higher mortality. For this reason, we decided to preserve the right adrenal gland. After surgery, we gave him a hydrocortisone injection to prevent acute adrenal insufficiency. The dose of hydrocortisone was gradually reduced and the patient was taken a low dose before discharge from our hospital.
Conclusion
Genetic testing and molecular analysis, including sequencing of the VHL gene, are crucial for diagnosing VHL and identifying children at risk of additional tumors.
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