Pheochromocytoma: A Genetic and Diagnostic Update

Leilani B. Mercado-Asis, MD, PhD, MPH; Katherine I. Wolf; Ivana Jochmanova, MD; David Taïeb, MD


Endocr Pract. 2018;24(1):78-90. 

In This Article

Advances in Functional Imaging

After PPGL is biochemically proven, anatomical imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is performed. Upon CT or MRI lesion confirmation, the patient's biochemical phenotype and tumor size, as well as metastatic potential, plays a determining role in whether further imaging with functional studies is required.[53,54] PPGL patients with a single epinephrine- or MN-secreting adrenal mass <5 cm, will most likely not benefit from functional imaging, since these tumors are confined to the adrenal gland and have a low risk of metastasis.[53] However, the metastatic potential is much higher for lesions greater than 5 cm, secreting norepinephrine or NMN, located extra-adrenally, or associated with a hereditary tumor syndrome such as SDHB, and functional imaging is necessary to determine the extent of disease.[53,54]

PPGLs overexpress somatostatin receptors (SSTRs),[55–58] which has shifted focus to newly developed imaging modalities targeting SSTRs. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) peptides, particularly 68Ga-DOTA(0)-Tyr(3)-octreotate (68Ga-DOTATATE), are quickly emerging as the gold standard of PPGL functional imaging. While 18F-FDOPA PET/CT was previously found to be the most sensitive radiopharmaceutical in the detection of metastatic PPGL,[59–61] 68Ga-DOTATATE PET/CT showed a significantly superior lesion detection rate over other functional and anatomical imaging modalities, as well as demonstrated a 100-fold higher affinity for SSTR2 than the previous first-line SSTR scintigraphy 111In-DTPA-octreotide (Octreoscan).[62] Tan et al found that utilizing different radiotracers provides imaging of real disease extension, but this practice is time-consuming, impractical, and not cost effective, which lead to their recommendation that 68Ga-DOTATATE PET/CT become standard of care in determining tumor extent and evaluating metastatic disease.[63] Furthermore, avid enhancement on 68Ga-DOTATATE PET/CT could indicate the potential for an additional systemic treatment option with peptide receptor radionuclide therapy (PRRT).[62,64]

While 68Ga-DOTATATE PET/CT surpassed 18F-FDOPA PET/CT as the functional imaging modality of choice, particularly in sporadic and SDHB-related meta-static disease, as well as in head and neck paragangliomas (HNPGLs),[62,65–67] Darr et al recently described the superiority of 18F-FDOPA PET/CT in detecting multifocality/metastases in somatic HIF2A gain-of-function mutation patients.[68]

In a recent report from Archier et al, 68Ga-DOTATATE PET/CT failed to detect an SDHx-related, small pheochromocytoma in the adrenal gland,[65] which again brings attention to the high physiologic 68Ga-DOTATATE uptake by healthy adrenal glands.[66] In contrast, 18F-FDOPA PET/CT has minimal physiologic uptake in the adrenals and might be beneficial for patients with small, hereditary pheochromocytomas routinely associated with MEN2 and NF1.[65]

While the aforementioned functional imaging modalities, particularly 68Ga-DOTATATE PET/CT, are currently unmatched in detection of metastatic disease, their availability is limited (Figure 3). On the other hand, 18F-FDG PET/CTs are widely accessible and are the preferred imaging modality for patients with metastatic disease compared to 131I-MIBG, with sensitivities of 80% and 49%, respectively.[28,69–71] In SDHx- and VHL-related lesions, 18F-FDG PET/CT showed exceptional metastatic localization.[69,70] Until widespread availability of specific radiotracers like 68Ga-DOTATATE and 18F-FDOPA, 18F-FDG PET/CT still offers an inexpensive, high-sensitivity option for patients with metastatic disease.

Figure 3.

Comparison of functional imaging modalities. A 39-year-old male patient presented with SDHB-related metastatic pheochromocytoma. 68Ga-DOTATATE PET/CT (A) showed multiple, extensive, metastatic skeletal lesions; a large necrotic mass adjacent to the right adrenalectomy bed; 2 metastatic liver lesions; and a focal increased uptake in the left lower lung of uncertain significance. 18F-FDOPA PET/CT (B) showed multiple skeletal abnormalities, demonstrating mild uptake suggestive of metastatic disease with mild peripheral uptake in the right upper abdomen, while 18F-FDA PET/CT (C) revealed nonspecific uptake in the region of the right atrium, with multiple areas of abnormal increased fluorodopamine uptake. On 18F-FDG PET/CT (D), innumerable metastatic bone lesions were detailed, as well as a tiny subpleural focus at the periphery of the left lower lobe, a metastatic liver lesion, and a large, right retroperitoneal mass abutting and displacing several nearby abdominal organs—most of which were silent on 18F-FDOPA PET/CT and 18F-FDA PET/CT. The patient was evaluated for 131I-MIBG treatment with 123I-MIBG scintigraphy (E), which showed that most metastatic bone lesions had mild to moderate activity, the left adrenal gland had intense MIBG uptake, and the large periportal mass had only minimal MIBG activity. MIBG = metaiodobenzylguanidine; PET/CT = positron emission tomography/computed tomography.