Figure 6 Axial T1 in-phase (A) and single-shot T2 (B) MR images of a left adrenal adenoma (arrow) seen in Figures 4 and 5, which is iso-intense on both sequences when compared to the liver (L). Figure 5 Axial T2 FSE (A) and single-shot (B) images of the same patient. In A the image is fat-suppressed, which increases the conspicuity of the adrenal lesion (arrow). The hepatic hemangioma is bright on both sequences (arrowheads). MRI of Endocrine Adrenal Tumors 347 wide variation in histological characteristics of both benign and malignant lesions (60–62), which contrib- utes to a wide range of T1 and T2 values as well as varying appearances on chemical shift techniques. In particular, larger adenomas, which may contain foci of calcification, cystic change, degeneration, and hemorrhage, may be impossible to different iate from carcinomas (63). Two other entities complicate the diffe- rentiation: collision tumor s where benign and malig- nant tumors coexist, and a zonal phenomenon where adjacent lipid-rich and lipid-poor regions abut one another (60,62). 5 SPECIFIC SYNDROMES 5.1 Cushing’s Syndrome Most patients with Cushing’s syndrome do not have a primary neoplasm of the adrenal cortex but have increased corticotrophin production by the pituitary Figure 7 Axial T1 in-phase (A) and single-shot T2 (B) MR images of a left adrenal mass (arrow) in a different patient which is also relatively iso-intense on both sequences when compared to the liver (L). In (A) the intensity of the adrenal is similar to that of the spleen (S). On the out-of-phase image (C), the adenoma loses signal in relation to the spleen, indicating the presence of intracellular lipid and, therefore, in keeping with an adenoma. Axial T1 with fat suppresion immediate postgadolinium image (D) shows minimal enhancement. Berning and Goldman348 gland (70–90%). Such patients may demonstrate hy- perplasia of both glands (64,65), which have the same signal characteristics as the normal adrenal gland. The other 10–30% of Cushing’s patients have a demon- strated focal mass, of which about 70% are adenomas (Fig. 10). Characteristically adenomas are intermediate in size (mean 3.3 cm) and are accompanied by atrophy of the nonneoplastic adrenal tissue. Other causes of Cushing’s syndrome include carcinoma or unilateral adrenal hyperplasia (66). Carcinomas are larger, with a mean size of 8.6 cm. The first line of investigation in Cushing’s syndrome, therefore, should be MR of the pituitary gland. If this examination is negative, then evaluation of the adrenals with MR may be performed to locate a possible adrenal mass. 5.2 Conn’s Syndrome Approximately two thirds of cases of Conn’s syndrome demonstrate an adrenal adenoma which is character- istically small (<2 cm) and homogeneous in appearance with the typical signal intensities described for adeno- mas (25,67). Alternatively, hormone hypersecretion may be due to unilateral adrenal hyperplasia or bilateral hyperplasia with no true adenoma (68,69). Adrenal vein sampling remains the gold standard for lateralization of function and cure by unilateral adrenalectomy. Fewer than 1% of cases are due to carcinoma. One study dem- onstrated decreased intracellular lipid in some adeno- mas, but this has not been shown to affect the signal intensity on chemical shift techniques. 5.3 Pheochromocytoma Pheochromocytoma arises from the adrenal medulla, can appear brighter than the adrenal cortex, but iso- or hypo-intense to liver on T1 (Fig. 12) and marked l y hyper-intense or bright on T2 (Fig. 13A). These tumors are hypervascular and show significant enhancement with gadolinium with a variable homogeneous/het- erogeneous pattern (70,71)(Fig. 13B). They may be complicated by hemorrhage, cystic degeneration, or necrosis, which can alter the imaging findings. Adrenal medullary hyperplasia, which may occur as a precursor to frank pheochromocytoma, has similar imaging, ap- pearance (72,73). Pheochromocytomas may be associated with a mul- tiple endocrine neoplasia (MEN), a neuroectodermal disorder, or with other inherited neoplastic syndromes. Extra-adrenal pheochromocytoma can occur anywhere along the sympathetic chain from the neck to the sacrum (74). However, b ecause 98% of tumors are subdia- phragmatic and 85–90% arise within the adrenal me- dulla, imaging the upper abdomen and adrenal area is usually adequate. Ten percent of pheochromocytomas are malignant, with the diagnosis usually made clinically based on the Figure 8 Axial T1 MR images demonstrating a moderate-to-large sized right adrenal mass (arrow), which is hypo-intense when compared to the liver (L) and shows no loss of signal on out of phase images (A) when compared to the in-phase images (B). Unfortunately, the patient has no spleen for comparison, so the liver is used instead. MRI of Endocrine Adrenal Tumors 349 presence of extensive local invasion or, more reliably, metastatic disease. Although nuclear pleomorphism and other findings suggestive of malignancy are present in some tumors, they do not correlate with malignant behavior. Metastases may occur in liver, bone, lymph nodes, brain, and lung and may be hormonally active. Metastases must be distinguished from multifocal tumors occurring elsewhere in areas of neural crest tis- sue (75), which occur in about 10% of cases. Although scintigraphy with iodine-labeled meta-iodobenzylgua- nidine (MIBG) offers the greatest specificity, it is not as sensitive as MR imaging, failing to visualize some tu- mors. In a recent study of 282 patients in which MR imaging, CT, and MIBG were compared, MR imaging was the most sensitive study for localizing adrenal and extra-adrenal pheochromocytomas (76). 5.4 Adrenocortical Carcinoma Adrenocortical carcinoma is rare. Thirty-eighty percent are functional lesions, usually small in size, most com- monly resulting in Cushing’s syndrome. Nonfunction- Figure 9 On the axial T2 MR images (A) the mass (arrow) is only mildly hyper-intense but shows quite significant enhancement with contrast (B–D). There is a central area of decreased intensity in keeping with hemorrhage or necrosis (arrowhead). This was histologically proven to be an adreno-cortical carcinoma. Berning and Goldman350 ing lesions are usually large (12–16 cm), show hetero- geneous enhancement, intermediate to high signal in- tensity on T2 and possibly high signal intensity on T1 if there is complicating hemorrhage. They do not lose signal on out-of-phase imaging and show progressive enhancement on delayed images (Figs. 8, 9). Local and distant metastatic spread may occur. Local invasion may involve the adrenal veins, IVC, and right atrium. Metastatic deposits occur in the liver, lungs, bone, and regional lymph nodes. 5.5 Differential Diagnoses 5.5.1 Metastases Adrenal metastatic masses may occur with a known or unknown primary source and may or may not be associated with a hormonal clinical syndrome. The lesions are characteristically intermediate in size (mean size 4 cm), show rapid growth, have ill-defined margins, and show heterogeneous signal intensity and variable enhancement. 5.5.2 Adrenal Myelolipoma These lesions demonst rate increased signal intensity relative to liver on T1 and T2 sequences, but appear- ances vary depending on the amount of fat they contain and the predominance of other tissue (77,78) (Fig. 14). 5.5.3 Hematoma (Adrenal Pseudocyst) Variation in appearance depending on the stage of he- moglobin degradation is seen in hematomas (79,80). Serial imaging, however, usually demonstrates an evolv- ing lesion that changes in signal intensity and may shrink or totally disappear over time (Fig. 15). There usually is minimal rim enhancement. Figure 10 Axial T1 in phase (A) and T2 fat-suppressed (B) MR images of a right adrenal mass (arrow) in a patient with increased cortisol production. The mass is relatively low signal on T1 and high signal on T2 in relation to the liver (L). Despite its large size and discrepant features, this proved to be a benign cortisol-secreting adenoma. Figure 11 Axial T1 fat-suppressed postcontrast MR image of the same patient demonstrates minimal enhancement (arrow). MRI of Endocrine Adrenal Tumors 351 Figure 12 Axial T1 in- (A) and out-of-phase (B) MR images of a moderate-sized right adrenal mass (arrow), which is relatively hypo-intense to the liver (L) and shows no signal loss in relation to the spleen (S) on the out-of-phase images. Figure 13 Axial T2 fat-suppressed (A) MR image demonstrates marked hyper-intensity of the adrenal mass (arrow), which is typical for a pheochromocytoma. The axial T1 postgadolinium (B) MR image shows minimal enhancement. Berning and Goldman352 5.5.4 Lymphoma and Adenomatoid Tumor Both of these may produce nonspecific findings approx- imating those of carcinoma or metastases (59,81). 5.5.5 Retroperitoneal Bronchogenic Cyst This lesion is rare but may present as a retroperito- neal lesion which is bright on T2 sequences and, therefore, may be mistaken for pheochromocytoma (82). 5.5.6 Congenital Adrenal Hyperplasia and Ectopic Adrena l Cortex Adrenals may be hyperplastic or ectopic but usually display signal intensities of normal adrenals (83,84). Figure 14 Axial T1 (A), single-shot T2 (B) and fat-suppressed postgadolinium MR images (C and D) of a right adrenal angiomyelolipoma (arrow). In A and B it is bright but loses signal on the fat-suppressed postgadolinium images, indicating the presence of fat. MRI of Endocrine Adrenal Tumors 353 6 CONCLUSION The choice of preoperative imaging will depend very much on the specific clinical problem, the local exper- tise, and the availability of imaging techniques. The chemical shift technique is undoubtedly extremely useful in identifying benign adrenal lesions, but the problem still remains of classifying indeterminate lesions. MR, however, should be the examination of choice in patien ts with renal disease and compromised renal function. ACKNOWLEDGMENT The authors would like to thank Dr. Emil Cohen for his assi stance with presenting the images. REFERENCES 1. Krebs TL, Wagner BJ. MR imaging of the adrenal gland: radiologic-pathologic correlation. Radiographics 1998; 18(6):1425–1440. 2. Francis IR, Korobkin M. Incidentally discovered adrenal masses. Magn Reson Imaging Clin North Am 1997; 5(1): 147–164. 3. Gilfeather M, Woodward PJ. MR imaging of the adrenal glands and kidneys. Semin Ultrasound CT MR 1998; 19(1):53–66. 4. Korobkin M, et al. The incidental adrenal mass. Radiol Clin North Am 1996; 34(5):1037–1054. 5. Megibow AJ, Lavelle MT, Rofsky NM. MR imaging of the pancreas. Surg Clin North Am 2001; 81(2):307– 320, ix-x. 6. Prince MR, Arnoldus C, Frisoli JK. Nephrotoxicity of Figure 15 Axial T1 pre- (A) and postgadolinium (B–D) MR images demonstrate a left adrenal mass (arrow), which is bright peripherally on T1 and shows no enhancement with contrast. This mass disappeared over a period of 3 months, in keeping with a resolving hematoma. Berning and Goldman354 high-dose gadolinium compared with iodinated contrast. J Magn Reson Imaging 1996; 6(1):162–166. 7. Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. Am J Roentgenol 1996; 167(4):847–849. 8. Dwamena BA, et al. Diagnostic evaluation of the adrenal incidentaloma: decision and cost-effectiveness analyses. J Nucl Med 1998; 39(4):707–712. 9. Semelka RC. Pancreatic disease: prospective compar- ison of CT,ERCP,and 1.5T MR imaging with dynamic gadolinium enhancement and fat suppression. Radiol- ogy 1991; 181: 785–791. 10. Siegelman ES, et al. Fat suppression by saturation/op- posed-phase hybrid technique: spin echo versus gradient echo imaging. Magn Reson Imaging 1995; 13(4):545– 548. 11. Ichikawa T, et al. Depiction of the normal adrenal gland evaluation with 0.5 tesla MRI. Nippon Igaku Hoshasen Gakkai Zasshi 1991; 51(8):906–911. 12. Siegelman ES. MR imaging of the adrenal neoplasms. Magn Reson Imaging Clin North Am 2000; 8(4):769– 786. 13. Semelka RC, et al. Evaluation of adrenal masses with gadolinium enhancement and fat-suppressed MR imag- ing. J Magn Reson Imaging 1993; 3(2):337–343. 14. Bilal MM, Brown JJ. MR imaging of renal and adrenal masses in children. Magn Reson Imaging Clin North Am 1997; 5(1):179–917. 15. Tsushima Y, Ishizaka H, Matsumoto M. Adrenal mass- es: differentiation with chemical shift, fast low-angle shot MR imaging. Radiology 1993; 186(3):705–709. 16. Outwater EK, et al. Adrenal masses: correlation between CT attenuation value and chemical shift ratio at MR imaging with in-phase and opposed-phase sequences. Radiology 1996; 200(3):749–752. 17. Korobkin M, et al. Adrenal adenomas: relationship between histologic lipid and CT and MR findings. Radiology 1996; 200(3):743–747. 18. Heinz-Peer G, et al. Characterization of adrenal masses using MR imaging with histopathologic correlation. Am J Roentgenol 1999; 173(1):15–22. 19. Francis IR, et al. Integrated imaging of adrenal disease. Radiology 1992; 184(1):1–13. 20. Dunnick NR. Hanson lecture. Adrenal imaging: cur- rent status. Am J Roentgenol 1990; 154(5):927–936. 21. Dunnick NR. CT and MRI of adrenal lesions. Urol Radiol 1988; 10(1):12–16. 22. Berland LL, et al. Differentiation between small benign and malignant adrenal masses with dynamic incre- mented CT. Am J Roentgenol 1988; 151(1):95–101. 23. Szolar DH, Kammerhuber F. Quantitative CT eval- uation of adrenal gland masses: a step forward in the differentiation between adenomas and nonadenomas? Radiology 1997; 202(2):517–521. 24. Slapa RZ, Jakubowski W, Szopinski K. Magnetic resonance techniques used in the differentiation of adre- nal tumors. Pol Merkuriusz Lek 2000; 8(48):436–440. 25. Wang JH, et al. High resolution MRI of adrenal glands in patients with primary aldosteronism. Zhonghua Yi Xue Za Zhi (Taipei) 2000; 63(6):475–481. 26. Rossi GP, et al. Identification of the etiology of primary aldosteronism with adrenal vein sampling in patients with equivocal computed tomography and magnetic resonance findings: results in 104 consecutive cases. J Clin Endocrinol Metab 2001; 86(3):1083–1090. 27. Schultz CL, et al. Magnetic resonance imaging of the adrenal glands: a comparison with computed tomog- raphy. Am J Roentgenol 1984; 143(6):1235–1240. 28. Small WC, Bernardino ME. Gd-DTPA adrenal gland enhancement at 1.5 T. Magn Reson Imaging 1991; 9(3): 309–312. 29. Huch-Boni RA, Debatin JF, Krestin GP. Contrast- enhanced MR imaging of the kidneys and adrenal glands. Magn Reson Imaging Clin North Am 1996; 4(1):101–131. 30. Reinig JW, et al. MRI of indeterminate adrenal masses. Am J Roentgenol 1986; 147(3):493–496. 31. Chezmar JL, et al. Adrenal masses: characterization with T1-weighted MR imaging. Radiology 1988; 166(2):357– 359. 32. Chang A, et al. Adrenal gland: MR imaging. Radiology 1987; 163(1):123–128. 33. Leroy Willig A, et al. In vitro adrenal cortex lesions characterization by NMR spectroscopy. Magn Reson Imaging 1987; 5(5):339–344. 34. Mitchell DG, et al. Benign adrenocortical masses: diagnosis with chemical shift MR imaging. Radiology 1992; 185(2): 345–351. 35. Mayo-Smith WW, et al. Characterization of adrenal masses (<5 cm) by use of chemical shift MR imaging: observer performance versus quantitative measures. Am J Roentgenol 1995; 165(1):91–95. 36. Namimoto T, et al. Adrenal masses: quantification of fat content with double-echo chemical shift in-phase and opposed-phase FLASH MR images for differentiation of adrenal adenomas. Radiology 2001; 218(3):642–646. 37. Korobkin M, et al. Characterization of adrenal masses with chemical shift and gadolinium- enhanced MR imaging. Radiology 1995; 197(2):411–418. 38. Outwater EK, et al. Distinction between benign and malignant adrenal masses: value of T1-weighted chem- ical-shift MR imaging. Am J Roentgenol 1995; 165(3): 579–583. 39. Boraschi P, et al. Diagnosis of adrenal adenoma: value of central spot of high-intensity hyperintense rim sign and homogeneous isointensity to liver on gadolinium- enhanced fat-suppressed spin-echo MR images. J Magn Reson Imaging 1999; 9(2):304–310. 40. Outwater EK, et al. Detection of lipid in abdominal tissues with opposed-phase gradient- echo images at 1.5 T: techniques and diagnostic importance. Radiographics 1998; 18(6):1465–1480. 41. Mitchell DG, et al. Fatty tissue on opposed-phase MR images: paradoxical suppression of signal intensity by MRI of Endocrine Adrenal Tumors 355 paramagnetic contrast agents. Radiology 1996; 198(2): 351–357. 42. Teeger S, Papanicolaou N, Vaughan ED Jr. Current concepts in imaging of adrenal masses. World J Urol 1999; 17(1):3–8. 43. Weishaupt D, Debatin JF. Magnetic resonance: evaluation of adrenal lesions. Curr Opin Urol 1999; 9(2):153–163. 44. Mantero F, Arnaldi G. Investigation protocol: adrenal enlargement. Clin Endocrinol (Oxf) 1999; 50(2):141– 146. 45. Ogita M, et al. Magnetic resonance imaging of the adrenal gland. Nippon Igaku Hoshasen Gakkai Zasshi 1991; 51(12):1431–1441. 46. Dunnick NR, Korobkin M, Francis I. Adrenal radiology: distinguishing benign from malignant adre- nal masses. Am J Roentgenol 1996; 167(4):861–867. 47. Bilbey JH, et al. MR imaging of adrenal masses: value of chemical-shift imaging for distinguishing adenomas from other tumors. Am J Roentgenol 1995; 164(3): 637– 642. 48. Peppercorn PD, Reznek RH. State-of-the-art CT and MRI of the adrenal gland. Eur Radiol 1997; 7(6):822– 836. 49. Outwater EK, Mitchell DG. Differentiation of adrenal masses with chemical shift MR imaging. Radiology 1994; 193(3):877–878. 50. Chung JJ, Semelka RC, Martin DR. Adrenal adeno- mas: characteristic postgadolinium capillary blush on dynamic MR imaging. J Magn Reson Imaging 2001; 13(2):242–248. 51. Krestin GP, Steinbrich W, Friedmann G. Adrenal masses: evaluation with fast gradient-echo MR imaging and Gd-DTPA-enhanced dynamic studies. Radiology 1989; 171(3):675–680. 52. Ichikawa T, et al. Adrenal adenomas: characteristic hyperintense rim sign on fat-saturated spin-echo MR images. Radiology 1994; 193(1):247–250. 53. Krestin GP, et al. Evaluation of adrenal masses in oncologic patients: dynamic contrast- enhanced MR vs CT. J Comput Assist Tomogr 1991; 15(1):104–110. 54. Krestin GP, Lorenz R, Steinbrich W. Magnetic reso- nance tomography of adrenal gland tumors. Detection and differentiation using fast gradient echo sequences and dynamic contrast media studies. Radiology 1990; 30(5):228–234. 55. Reinig JW, et al. Differentiation of adrenal masses with MR imaging: comparison of techniques. Radiology 1994; 192(1):41–46. 56. Schwartz LH, et al. Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies. Am J Roentgenol 1997; 168(6):1575–1578. 57. Zimmermann GG, Debatin JF, Kr estin GP. The differentiation of adrenal gland tumors: an improvement in accuracy by a combination of fat-sensitive, T2-weight- ed and contrast-enhanced MR sequences. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1997; 167(2): 153–159. 58. Korobkin M, et al. Differentiation of adrenal adenomas from nonadenomas using CT attenuation values. Am J Roentgenol 1996; 166(3):531–536. 59. Rodrigo Gasque C, et al. MR imaging of a case of adenomatoid tumor of the adrenal gland. Eur Radiol 1999; 9(3):552–554. 60. Ramsay JA, et al. Lipid degeneration in pheochromo- cytomas mimicking adrenal cortical tumors. Am J Surg Pathol 1987; 11(6):480–486. 61. Cotran RS, Kumar V, Robbins SL, eds. Robbins Path- ological Basis of Disease. Philadelphia: WB Saunders. 62. Custodio CM, et al. Adrenal neuroblastoma in an adult with tumor thrombus in the inferior vena cava. J Magn Reson Imaging 1999; 9(4):621–623. 63. Newhouse JH, et al. Large degenerated adrenal adeno- mas: radiologic-pathologic correlation. Radiology 1999; 210(2): 385–391. 64. Miyajima A, et al. ACTH-independent bilateral macro- nodular adrenocortical hyperplasia caused Cushing’s syndrome. Urol Int 1997; 58(4):259–261. 65. Doppman JL, et al. Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism. Radiology 2000; 216(3): 797–802. 66. Otsuka F, et al. Cushing’s syndrome due to unilateral adrenocortical hyperplasia. Intern Med 1998; 37(4):385– 390. 67. Sohaib SA, et al. Primary hyperaldosteronism (Conn syndrome): MR imaging findings. Radiology 2000; 214(2): 527–531. 68. Haenel LCt., Hermayer KL. A case of unilateral adrenal hyperplasia: the diagnostic dilemma of hyper- aldosteronism. Endocr Pract 2000; 6(2):153–158. 69. Otsuka F, et al. Hormonal characteristics of primary aldosteronism due to unilateral adrenal hyperplasia. J Endocrinol Invest 1998; 21(8):531–536. 70. Garritano A, et al. Pheochromocytoma. A case report. Minerva Chir 1999; 54(4):283–286. 71. Neumann K, Langer R. Imaging methods in diagnosis of pheochromocytoma. Zentralbl Chir 1997; 122(6):438– 442. 72. Yung BC, et al. Sporadic bilateral adrenal medullary hyperplasia: apparent false positive MIBG scan and expected MRI findings. Eur J Radiol 2000; 36(1):28–31. 73. Fink IJ, et al. MR imaging of pheochromocytomas. J Comput Assist Tomogr 1985; 9(3):454–458. 74. Dahnert WF. Dahnert’s Radiology Review Manual. 4th ed. Williams and Wilkins, 1999. 75. Walther MM, Keiser HR, Linehan WM. Pheochromo- cytoma: evaluation, diagnosis, and treatment. World J Urol 1999; 17(1):35–39. 76. Jalil ND, et al. Effectiveness and limits of preoperative imaging studies for the localisation of pheochromocyto- mas and paragangliomas: a review of 282 cases. French Association of Surgery (AFC), and The French Associ- Berning and Goldman356 [...]... corticosteroids (8) C-14 has no gamma emission and is therefore not suitable for imaging Many attempts to label cholesterol with I-131 were Table 1 Imaging Radiopharmaceuticals for Adrenal Cortical 19-Iodocholesterol 6- h-Iodomethyl-19-norcholesterol (NP-59) 6- Iodocholesterol Se-75 methyl-selenocholest-5 (6) en-3-beta-ol Se-75 6- h-methyl-selenomethyl-19-norcholest-5(10)en-3-h-ol Se-75 methyl-cholesterol I-131 norcholesterol... such as 6- iodocholesterol, side chain modifications, or labeling various esters or stigmasterol were not successful In the United States, NP-59 can be obtained from the radiopharmacy of the University of Michigan as an investigating radiopharmaceutical requiring individual IND from the FDA In Europe, selenium (Se-75) methyl-selenocholest-5 (6) en-3-h-ol and (Se-75) 6- hmethyl-selenomethyl-19-norcholest-5(10)en-3-h-ol,... FDG C-11 metomidate unsuccessful until 19-iodocholesterol was synthesized (Fig 1a) After 8 days of injection, the adrenal-to-liver ratio of 19-iodocholesterol was 200:1, and uptake in tissues other than adrenal was largely cleared (17,18) Later, the contaminant from 19-iodocholesterol synthesis, 6- h-iodomethyl-19-norcholesterol (NP-59) (Fig 1b) was found to have 5–10 times higher uptake than 19-iodocholesterol... syndrome Unknown source of ACTH ACTH-independent Cushing’s syndrome Adrenal adenoma Adrenal carcinoma Nodular adrenal hyperplasia Pseudo-Cushing’s syndrome Major depressive disorder Alcoholism Study 1a (n=302) Study 2b (n=3 06) Study 3c (n =63 0) 66 .0 7.1 >1 n.a 68 .3 10.5 n.a 5.2 68 12 . Cortical Imaging 19-Iodocholesterol 6- h-Iodomethyl-19-norcholesterol (NP-59) 6- Iodocholesterol Se-75 methyl-selenocholest-5 (6) en-3-beta-ol Se-75 6- h-methyl-selenomethyl-19-norcholest-5(10)en-3-h-ol Se-75 methyl-cholesterol I-131. radiopharmaceutical requiring indi- vidual IND from the FDA. In Europe, selenium (Se-75) methyl-selenocholest-5 (6) en-3-h-ol and (Se-75) 6- h- methyl-selenomethyl-19-norcholest-5(10)en-3-h-ol, which has a biodistribution. (17,18). Later, the contaminant from 19-iodocholesterol syn- thesis, 6- h-iodomethyl-19-norcholesterol (NP-59) (Fig. 1b) was found to have 5–10 times higher uptake than 19-iodocholesterol in the adrenals