18F-FDOPA PET/CT accurately identifies MEN1-associated pheochromocytoma

Abstract

Summary: Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO. Although the patient was normotensive and asymptomatic, routine screening imaging with CT demonstrated bilateral adrenal masses. The left adrenal mass grew from 2.5 to 3.9 cm over 4 years with attenuation values of 9 Hounsfield units (HU) pre-contrast and 15 HU post-contrast washout. Laboratory evaluation demonstrated an adrenergic biochemical phenotype. Both 18F-fluorodeoxyglucose (18F-FDG) PET/CT and 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy demonstrated bilateral adrenal uptake. In contrast, 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT demonstrated unilateral left adrenal uptake (28.7 standardized uptake value (SUV)) and physiologic right adrenal uptake. The patient underwent an uneventful left adrenalectomy with pathology consistent for PHEO. Post-operatively, he had biochemical normalization. A review of the literature suggests that adrenal tumors >2 cm may be at higher risk for pheochromocytoma in patients with MEN1. Despite a lack of symptoms related to catecholamine excess, enlarging adrenal nodules should be biochemically screened for PHEO. 18F-FDOPA PET/CT may be beneficial for localization in these patients.

Learning points: 18F-FDOPA PET/CT is a beneficial imaging modality for identifying pheochromocytoma in MEN1 patients. Adrenal adenomas should undergo routine biochemical workup for PHEO in MEN1 and can have serious peri-operative complications if not recognized, given that MEN1 patients undergo frequent surgical interventions. MEN1 is implicated in the tumorigenesis of PHEO in this patient.

Keywords: 2020; Adrenal; Adrenal function; Adrenal scintigraphy; Adrenalectomy; Adrenaline; Adult; CT scan; Calcium (serum); Chromogranin A; Cortisol; Cortisol, free (24-hour urine); DNA sequencing; Dexamethasone suppression; Epinephrine (plasma); Gastrin; Haematoxylin and eosin staining; Haemoglobin A1c; Histopathology; Hypercalcaemia; Hyperparathyroidism (primary); Laparoscopic adrenalectomy; Lipoma*; MEN1; MRI; Male; March; Metanephrines; Metanephrines (plasma); Metanephrines (urinary); Molecular genetic analysis; Noradrenaline; Norepinephrine; Normetanephrine; Novel diagnostic procedure; PET scan; PTH; Pancreatic cysts*; Parathyroidectomy; Phaeochromocytoma; Phosphate (serum); Polymerase Chain Reaction; Radionuclide imaging; S100*; United Kingdom; United States; White.

Figure 1

Patient’s family tree spanning across three generations. The patient’s three sons range from 42 to 45 years of age; arrow indicates the MEN1 index case. A&W indicates alive and well.

Figure 2

Imaging studies and surgical pathology of the pheochromocytoma. (A) CT demonstrating the left adrenal mass measuring 3.9 cm (15 Hounsfield unit (HU) post-contrast) and right adrenal mass measuring 2.5 cm. (B) ¹²³I-mIBG demonstrating abnormal uptake corresponding to the right and left adrenal masses. (C) ¹⁸F-FDG-PET/CT demonstrating bilateral adrenal uptake (6.4 SUVmax on the left and 4.4 SUVmax on the right). (D) ¹⁸F-FDOPA PET/CT demonstrating increased uptake in the left adrenal gland (SUVmax 28.7) compared to the right. (E) S100 highlights sustentacular cells, 20×. (F) Hematoxylin and eosin staining, 60×. (G) Chromogranin A staining, 20×.

Figure 3

Loss of heterozygosity (LOH) at the MEN1 locus (chromosome 11q13) in the patient’s tumor DNA. A diagram indicating the location of chromosome 11q13 markers near the MEN1 gene is shown based on UCSC hg19 in silico PCR with published primers (27, 28). LOH was detected at two markers, D11S4945 and D11S449, in the patient’s tumor DNA compared to his blood DNA (PCR products resolved in 1× TBE 6% polyacrylamide gels).