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Adrenal Gland Scintigraphy

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Adrenal Gland Scintigraphy Adrenal Gland Scintigraphy Anca M. Avram, MD,* Lorraine M. Fig, MBChB, MPH,*,† and Milton D. Gross, MD*,† There is no question that high-resolution imaging techniques have revolutionized the approach to diagnostic imaging. Computed tomography (CT) and magnetic resonance imaging provide exquisite images of the adrenal glands and offer the best initial imaging approach in the evaluation of patients with suspected adrenal disease. However, an assessment of anatomy is only a portion of the diagnostic effort, which begins with a biochemical evaluation to establish the presence of adrenal gland dysfunction. With a confirmed biochemical diagnosis in hand, a logical and stepwise diagnostic approach can be tailored to a particular patient. Where scintigraphy fits in the evaluation of diseases of the adrenal cortex and medulla in the context of high-resolution imaging and which radiopharmaceuticals should be deployed has changed substantially during the last 2 decades. Adrenal functional imaging has evolved from classic planar scintigraphy to single-photon emission computed tomography (SPECT) and positron emission tomography (PET) using tracers that, by targeting specific metabolic or synthetic processes within the gland, have depicted adrenal pathophysiology. New PET/CT and SPECT/CT technologies integrate anatomic and functional information and redefine the radiotracer principle in the larger context of high resolution anatomic imaging. Semin Nucl Med 36:212-227 © 2006 Elsevier Inc. All rights reserved. drenal gland scintigraphy uses radiopharmaceuticals Magnetic resonance imaging (MRI) has value in high- Awith specific imaging characteristics for the adrenal resolution imaging and in tissue characterization and can cortex and adrenal medulla. These radiopharmaceuticals be used alone or in conjunction with other modalities to enter adrenal hormone synthetic pathways and act as pre- evaluate adrenal dysfunction (Table 2).3 Other modalities, cursor or precursor-like compounds, mimic native hor- such as adrenal vein hormone sampling, have value in mones, or demonstrate affinity for specific endocrine tis- selected cases in which neither anatomic nor functional sue receptors and, in doing so, provide information imaging can discern the site(s) of adrenal hormonal hyper- regarding target tissue endocrine function(s) (Table 1).1,2 secretion. Despite the sharp anatomic detail of CT or MRI, Integrating information obtained from anatomic and func- evaluation with adrenal scintigraphy in conjunction with tional imaging has always been essential for characteriza- hormonal analysis is used not only in defining the function tion of adrenal disease. Computed tomography (CT) is of adrenal lesions but also in the diagnosis and staging of currently the primary method of imaging the adrenals, and malignant neoplasms of adrenal origin (Table 3).1,4 the widespread use of CT technology in clinical practice Positron emission tomography (PET)/CT and single-pho- makes it an ideal instrument for evaluating adrenal gland ton emission computed tomography (SPECT)/CT are new 3 morphology (Table 2). In addition to imaging patients imaging techniques that permit the simultaneous acquisi- with abnormal adrenal function, the use of CT for general tion of anatomic and functional information, resulting in abdominal imaging has led to the incidental discovery of accurate localization and metabolic characterization of unsuspected adrenal masses (incidentalomas) that, in pathophysiological processes. The introduction of new ra- many patients, require further characterization. diopharmaceuticals and reintroduction of older radio- pharmaceuticals in the context of fused anatomic-func- *Department of Radiology, Division of Nuclear Medicine, University of tional imaging have considerably expanded the field of Michigan, Ann Arbor, MI. adrenal gland scintigraphy. In this review, we discuss ad- †Department of Veterans Affairs Health Systems, Ann Arbor, MI. renal gland imaging and recent developments in the field, Address reprint requests to Anca M. Avram, MD, Division of Nuclear Med- with the goal of demonstrating the importance and value icine, Department of Radiology, B1G 505G University Hospital, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109-0028. E-mail: of an approach that integrates the functional and anatomic [email protected] evaluation of adrenal disease. 212 0001-2998/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.semnuclmed.2006.03.004 Adrenal gland scintigraphy 213 Table 1 Radiopharmaceuticals for Adrenal Gland Imaging Target(s)/Mechanism(s) of Radiopharmaceutical Metabolic Activity Uptake 131I-19-iodocholesterol Uptake mediated by LDL receptor Adrenal cortex via the LDL-receptor 131I-6-iodocholesterol ++ 131I-6␤-iodomethylnorcholesterol ++ 75Se-selenomethylnorcholesterol ++ 131I, 123I, 111In, 99mTc-low density lipoproteins ++ 123I-tyr3-octreotide Somatostatin analog Neuroendocrine via somatostatin- receptor 111In-/111In- DOTA-tyr3-octreotide*† ++ 90Y-DOTA-tyr3-octreotide*† ++ 86Y-DOTA-tyr3-octreotide*† ++ 114mIn-octreotide* ++ 90Y-DOTA-lanreotide*† ++ 111In-/111In-DOTA-lanreotide† ++ 99mTc-HYNIC-tyr3-octreotide† ++ 123I-vasoactive intestinal peptide (123I-VIP) Hormone Neuroendocrine via VIP-receptor 123I-metaiodobenzylguanidine (123I-MIBG) Neuronal blocker Neuroendocrine via active transport into neurosecretory granules 131I-metaiodobenzylguanidine (131I-MIBG)† ++ 125I-metaiodobenzylguanidine (125I-MIBG)† ++ 131I-aminoiodobenzylguanidine (131I-AIBG)† ++ 11C-epinephrine Catecholamine + 11C-hydroxyephedrine (11C-HED) Catecholamine analog + 11C-phenylephrine Catecholamine analog + 18F-dopamine Catecholamine + 18F-fluorodeoxyglucose (18F-FDG) Glucose analog Adrenal cortex as a metabolic intermediate 11C-acetate TCA intermediate* + 11C-etiomidate Enzyme inhibitor Adrenal cortical enzyme inhibitor 11C-metiomate ++ 131I-metyrapone ++ Reprinted with permission from Gross et al.4 LDL, low-density lipoprotein. *Therapeutic or potential therapeutic radiopharmaceutical. †Tricarboxcylic acid cycle intermediate. Physiological Basis of through a receptor-mediated process.5 Once located within the adrenal cortex, the 19-norcholesterol derivatives are es- Functional Adrenal Imaging terified, like native cholesterol, but are not further metabo- The adrenal glands are paired retroperitoneal endocrine lized. In the syndromes of excess production of glucocorti- structures localized superior and medial to the kidneys. The coids, mineralocorticoids, and adrenal androgens, NP-59 adrenal glands consist of 2 embryologically, morphologi- uptake is facilitated by adrenocorticotrophic hormone cally, and functionally distinct units: the adrenal cortex, (ACTH) in the inner zones of the cortex and the rennin– which is of mesodermal origin and secrets steroid-derived angiotensin system in the outer cortex and has been shown to hormones, and the medulla, which is of neural crest origin be quantitatively related to steroid hormone output.5,6 Drugs and secretes norepinephine and epinephrine. The adrenal and conditions that interfere with adrenocortical uptake of cortex contains 2 regions: the subcapsular zona glomerulosa, NP-59 are listed in Table 4. which secretes mineralocorticoids (principally aldosterone) The adrenal medulla synthesizes catecholamines (norepi- and the deeper zona fascicularis and reticularis, which se- nephrine and epinephrine) that are stored in membrane- cretes glucocorticosteroids (principally cortisol) and weak bound storage vesicles in association with soluble proteins androgens (dehydroepiandrosterone [DHEA], dehydroepi- (chromogranins) and nucleotides forming the neurosecre- androsterone sulfate [DHEA-S], and androstenedione). tory granules. Under neural or humoral (eg, angiotensin, se- Steroid hormone biosynthesis starts with cholesterol de- rotonin, histamine) stimulation, catecholamines are released livered to the adrenal cortical cells by circulating low-density from the vesicles by exocytosis and diffuse into the circula- lipoproteins. Cholesterol analog, like 131I-6␤-iodomethyl- tion. Within the medulla, catecholamines are recycled and 19-norcholesterol (NP-59), are incorporated in low-density restored in secretory vesicles by an energy-dependent type I lipoproteins and accumulated by adrenocortical cells uptake mechanism specific to the adrenal medulla and sym- 214 A.M. Avram, L.M. Fig, and M.D. Gross Table 2 Adrenal Gland Anatomic Imaging Techniques Technique Principle Advantages Disadvantages Comments Ultrasound Reflection of ultrasound, Widely available, no Limited resolution. Interference Limited utility depicts anatomy radiation exposure by fat and bowel gas Angiography X-ray attenuation with Detailed depiction Invasive (arterial puncture). Generally obsolete for iodinated contrast, of vascular Technically demanding. May adrenal localization depicts vascular anatomy cause adrenal hemorrhage or anatomy infarction. Risks of contrast reaction CT X-ray attenuation, Highest spatial May fail in postoperative or Very widely used anatomy based resolution. X-ray very thin patients. Radiation (iodinated contrast attenuation and exposure. may be used) washout of contrast can be quantified MRI Radiofrequency signal High spatial Limited specificity of tissue Limited advantages over by protons in resolution. No characterization. Resolution CT. Modes of tissue magnetic field ionizing radiation. < CT in routine adrenal characterization may following Some degree of imaging applications. be useful. radiofrequency tissue stimulus characterization pathetic
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