Clonidine suppression testing for pheochromocytoma in neurofibromatosis type 1

Correspondence to Dr WingYee Wan, [email protected]

Background

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an increased risk of pheochromocytoma, which is an adrenal gland tumour that releases catecholamines. Diagnosis of this tumour may be challenging due to its variable presentation and testing limitations. Biochemical false positives frequently occur secondary to certain medications, metabolic abnormalities and systemic illness. Most pheochromocytomas are sporadic but 10%–15% are hereditary in diseases such as NF1, multiple endocrine neoplasia type 2, von Hippel-Lindau disease and familial carotid body tumours.^1–6

The incidence of pheochromocytoma in normotensive patients with NF1 is 1%–5.7%.⁶ In hypertensive NF1 patients, the rate increases to 20%–50%.^{7 8} Though our NF1 patient was initially normotensive, the higher incidence of pheochromocytoma in this population led to further testing for pheochromocytoma. To assess for false positive testing, the clonidine suppression test was performed. The ultimate result of testing led to appropriate adrenalectomy.

Case presentation

A 48-year-old woman without a personal history of hypertension or NF1 presented in 2015 with panic attacks and occasional tachycardia for several years. Her family history was significant for NF1 in her father and two sons. On physical examination, she had multiple neurofibromas, café au-lait spots, axillary and inguinal freckling and iris hamartomas (Lisch nodules) (figure 1). Given her family history and physical examination findings, she met the National Institutes of Health Consensus Conference criteria for NF1. Upon review of her previous imaging, a non-contrast chest CT from February 2012 noted an incidental right adrenal mass, measuring 1.24 cm (figure 2A). Her urinary metanephrine levels, by high-pressure liquid chromatography (HPLC), were above the upper limit of normal in May 2015 (table 1).

Table 1

Urine metanephrines over time

	Metanephrine (74–297 mcg/24 hours)	Normetanephrine (105–354 mcg/24 hours)	Total metanephrine (179–651 mcg/24 hours)
May 2015 On cyclobenzaprine	414	449	863
February 2017 On cyclobenzaprine	507	753	1260
August 2017 Off cyclobenzaprine	610	821	1431

She had persistent palpitations and anxiety, as well as increasing urinary metanephrine levels in February 2017 (table 1). She had a dedicated adrenal CT in March 2017 that revealed growth of the right adrenal mass, now measuring 2.6 cm (figure 2B). The mass had an unenhanced Hounsfield unit attenuation of 44 units, with an absolute washout of 29.5% (<60%...