NP-59 Scintigraphy Research Articles

Diagnostic Accuracy of Adrenal Iodine-131 6-Beta-Iodomethyl-19-Norcholesterol Scintigraphy for the Subtyping of Primary Aldosteronism.

To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707-0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782-0.957]. The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.

An Occult Androgen-Secreting Ovarian Tumour Revealed by NP-59 Scintigraphy: a Case Report

An Occult Androgen-Secreting Ovarian Tumour Revealed by NP-59 Scintigraphy: a Case Report

NP-59 Scintigraphy for Primary Aldosteronism Lateralization in a Patient With Polycystic Kidney Disease

A 65-year-old-male presented to the endocrine clinic for further evaluation and treatment of primary aldosteronism (PA). His past medical history was notable for polycystic-kidney-disease (PCKD) leading to a kidney-transplantation at age 48, as well as a diagnosis of PA at the age of 52. The patient had initially elected for medical management of PA; thus, PA sub-type-classification was not pursued. Despite treatment with spironolactone and potassium supplements, subsequent blood-pressure control was poor, with progressive renal failure and persistent hypokalemia. Currently, the patient was being prepared for a staged-bilateral-nephrectomy to relieve some of the mass-effect from the giant polycystic-kidneys. The upcoming surgery gave rise to the option of a concomitant adrenalectomy as a potential cure for PA. However, at this point, PA-sub-type classification was quite challenging. Anatomically, the large cysts grossly distorted the retroperitoneum, hiding the adrenal glands from view on CT imaging ( Figure A). Biochemically, adrenal-vein-sampling (AVS) seemed both technically difficult due to the distorted vascular anatomy as well as potentially risky due to the expected prolonged exposure to radio-contrast in a kidney transplant patient pre-existing advanced chronic kidney disease (CKD). Following a multidisciplinary consultation, NP-59 SPECT/CT was performed (Figure B-D). Very few case reports of PA in patients with PCKD have been reported thus far ((1)Hoorn E.J. Hesselink D.A. Kho M.M. Roodnat J.I. Weimar W. Van Saase J.L. Van Den Meiracker A.H. Zietse R. A case of primary aldosteronism revealed after renal transplantation.Nature Reviews Nephrology. 2011; 7: 55-60Crossref PubMed Scopus (8) Google Scholar). In the setting of PCKD, a diagnosis of PA may be delayed or missed entirely due to pre-existing alternative explanations for resistant hypertension and CKD. Furthermore, adrenal adenomas may be overlooked on planar imaging due to their small size and distorted abdominal anatomy associated with PCKD. In general, AVS is considered the gold-standard For PA sub-type classification, but in complex cases such as with PCKD, alternative diagnostic methods may be useful. NP-59 (I-131-iodo-cholesterol) is a marker of adrenocortical cholesterol uptake. Dexamethasone-suppression NP-59 scintigraphy has been suggested for the differentiation of PA sub-types, but its use is limited by low resolution allowing for false negatives as well as limited tracer availability ((2)Nomura K, Kusakabe K, Maki M, Ito Y, Aiba M, Demura H. Iodomethylnorcholesterol uptake in an aldosteronoma shown by dexamethasone-suppression scintigraphy: relationship to adenoma size and functional activity. J Clin Endocrinol Metab. 1990 Oct;71(4):825-830. doi: 10.1210/jcem-71-4-825. PMID: 2401712.Google Scholar). The addition of SPECT/CT over planar imaging NP-59 scintigraphy, has been shown to increase sensitivity to 82%, including the detection of aldosterone producing adenomas smaller than 1.5 cm ((3)Yen R.F. Wu V.C. Liu K.L. Cheng M.F. Wu Y.W. Chueh S.C. Lin W.C. Wu K.D. Tzen K.Y. Lu C.C. TAIPAI Study Group131I-6β-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results.Journal of Nuclear Medicine. 2009; 50: 1631-1637Crossref PubMed Scopus (94) Google Scholar). In our patient, NP-59 SPECT/CT clearly identified a functional left-adrenal cortical adenoma (Figures B-D). Subsequent left adrenalectomy and nephrectomy resulted in normalization of potassium levels and improved blood-pressure control allowing for a reduction in the number of his anti-hypertensive medications. Pathological evaluation identified a 3cm cortical adenoma. Thus, NP-59 SPECT/CT should remain a part of the diagnostic armamentarium, especially for challenging cases of PA sub-type classification.

PS-BPR01-7: CONCURRENT SOMATIC MUTATIONS IN CTNNB1 AND GNA11 IN AN ALDOSTERONE-PRODUCING ADENOMA

Background: Aldosterone-producing adenoma (APA) is a major subtype of primary aldosteronism (PA), a common form of secondary hypertension. In the past decade, there has been significant progress in the determination of genetic causes of APA. The use of next-generation sequencing (NGS) has led to the identification of somatic mutations in APA that cause excess aldosterone production. Most of the affected genes encode ion channels or transporters. Somatic activating mutations in CTNNB1 (β;-catenin) have also been detected in 2–5% of APA. As a possible pathogenesis, an association of CTNNB1-mutated APA with pregnancy and menopause has been proposed. A recent study reported double somatic mutations in CTNNB1 and GNA11/Q in APA. However, due to its rare incidence, characteristics of APA with these mutations are not well determined. Herein, we report a case of APA harboring somatic CTNNB1 and GNA11 mutations. Case presentation: A 46-year-old Japanese woman presented with hypertension and spontaneous hypokalemia. She had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation. Endocrine testing showed elevated plasma aldosterone concentration (677.5 pg/mL) under suppressed renin (plasma renin activity, 0.3 ng/mL/h). Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling indicated excess aldosterone production from the right adrenal gland. NP-59 scintigraphy further demonstrated increased tracer uptake in the right adrenal lesion. She underwent right laparoscopic adrenalectomy. Histologic diagnosis of the resected tumor was adrenocortical adenoma based on the Weiss criteria. Notably, Ki-67 labeling index was high (6% at hotspots). After surgery, her blood pressure and serum potassium both normalized. Based on the PASO (the primary aldosteronism surgical outcome) study criteria, PA remained clinically and biochemically cured at follow-up 18 months after surgery. Methods: Formalin-fixed, paraffin-embedded adrenal tumor tissue was used for immunohistochemical and genetic analysis. Results: Immunohistochemistry (IHC) showed high and diffuse expression of CYP11B2 (aldosterone synthase) within the tumor, whereas 11β;-hydroxylase (CYP11B1, a steroidogenic enzyme for cortisol biosynthesis) was mostly negative. VSNL1, a marker for the zona glomerulosa where physiologic aldosterone biosynthesis occurs, was highly expressed within the tumor. CYP11B2 IHC-guided targeted NGS identified concurrent somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations with similar variant allele frequencies (29.5% and 29.7%, respectively). Conclusions: To best of our knowledge, this is the first Asian case of APA with CTNNB1 and GNA11 mutations. Detailed clinical and histologic examination would provide useful information for better characterization of patients with PA due to these rare mutations.

Evaluation of standardized uptake value on 131I-6β-iodomethyl-19-norcholesterol scintigraphy for diagnosis of primary aldosteronism and correspondence with adrenal venous sampling.

Adrenal venous sampling (AVS) is a reliable method for lateralization of adrenal hormone secretion, which is important for discriminating between aldosterone-producing adenoma and bilateral adrenal hyperplasia, both of which cause primary aldosteronism (PA). The aim of this study was to evaluate the diagnostic accuracy of the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) of 131I-6β-iodomethyl-19-norcholesterol (NP-59) single-photon emission computed tomography (SPECT) for PA and its correspondence with AVS. Adrenal NP-59 scintigraphy was performed in 14 patients with suspected PA, and AVS was also performed in 7 of them. SUVmax and SUVmean of the adrenal lesions on the dominant side and their ratios to the values on the non-dominant side (SUVRmax and SUVRmean, respectively) were calculated on SPECT images using ordered-subset conjugate gradient minimization (OSCGM) and three-dimensional ordered-subset expectation maximization (3D-OSEM) reconstruction algorithms. SUVmax and SUVmean on NP-59 SPECT images were significantly higher for aldosterone-producing adenoma than for bilateral adrenal hyperplasia or non-functioning adenoma and slightly superior to SUVRmax and SUVRmean (P = 0.0475 and P = 0.0447 vs. P = 0.124 and P = 0.132, respectively, with OSCGM). The respective areas under the receiver-operating characteristic curve for SUV and SUVR were 0.933 and 0.725 with OSCGM and 0.844 and 0.750 with 3D-OSEM, while SUVmax and SUVRmax had exactly the same diagnostic accuracy as SUVmean and SUVRmean. SUV and SUVR were associated with the diagnostic features on AVS and consistent with lateralization by AVS in most patients. In this study, SUV on NP-59 SPECT helped in the diagnosis of PA and was consistent with the results of AVS in nearly all cases.

131I-6β-iodomethyl-19-norcholesterol adrenal scintigraphy as an alternative to adrenal venous sampling in differentiating aldosterone-producing adenoma from bilateral idiopathic hyperaldosteronism.

To assess the correlation value between adrenal venous sampling (AVS) and I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy in differentiating aldosterone-producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (BHA), and the use of NP-59 scintigraphy as an alternative to AVS. Overall, 29 patients with APA or BHA who underwent AVS and dexamethasone-suppression NP-59 scintigraphy were included between 2010 and 2017. The correlation value between AVS and dexamethasone-suppression NP-59 scintigraphy was assessed using each lateralisation index (LIAVS and LI1NP-59). Tumour presence and size were evaluated using computed tomography. The sensitivity and specificity of dexamethasone-suppression NP-59 scintigraphy for APA according to each lateralisation index threshold were calculated. Of 29 patients, 12 presented with APA and 17 with BHA according to AVS. The correlation value between LIAVS and LI1NP-59 was 0.63 (P < 0.001). If the cut-off points were 2.55 and 1.80 in all cases, the sensitivity and specificity were 0.33 and 1.00 as well as 0.58 and 0.94, respectively. In adrenal microtumours (maximum diameter ≤10 mm), no cases revealed a cut-off point of >1.8. However, in adrenal macrotumours (maximum diameter >10 mm), the cut-off point of 2.55 represented the best compromise (sensitivity: 0.44; specificity: 1.00). NP-59 scintigraphy can be used as an alternative to AVS if there is a strong lateralisation on NP-59 scintigraphy and adrenal macrotumours observed on the computed tomography when AVS is technically challenging, particularly in the right adrenal vein cannulation, and if contraindications, such as allergy to contrast materials and renal failure, are observed.

Taiwan mini-frontier of primary aldosteronism: Updating detection and diagnosis

To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols. When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management. With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients.

Diagnostic value of adrenal iodine-131 6-beta-iodomethyl-19-norcholesterol scintigraphy for primary aldosteronism: a retrospective study at a medical center in North Taiwan.

BackgroundPrimary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are, bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of iodine-131 6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish BAH from APA.Patients and methodsPatients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 postunilateral adrenalectomy and seven postradiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal scintigraphy prior to surgery. The accuracy of the NP-59 adrenal scintigraphy was confirmed by the pathologic findings and postoperative outcomes.ResultsAmong 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and seven bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity, and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3, 44.4, and 92.3%, respectively. Moreover, single-photon emission computed tomography/computed tomography scan increased the sensitivity and specificity, but not the positive predictive value (85.0, 60.0, and 89.5%) of NP-59 scintigraphy in this study.ConclusionNP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

NP-59 test for preoperative localization of primary hyperaldosteronism.

Adrenal venous sampling is generally considered the gold standard to identify unilateral hormone production in cases of primary hyperaldosteronism. The aim of this study is to evaluate whether the iodine-131-6-β-iodomethyl-19-norcholesterol (NP-59) test may represent an alternative in selected cases. Patients submitted to laparoscopic adrenalectomy for suspected primary hyperaldosteronism (n=27) were retrospectively reviewed. When nuclear medicine tests were preoperatively performed, their results were compared with the histopathologic findings and clinical improvement. Nuclear medicine tests were realized in 13 patients. In 11 (84.6%), a planar anterior and posterior NP-59 scintigraphy was performed and a SPECT/TC in two (15.4%). Scintigraphy indicated a preoperative lateralization in 12 out of 13 patients (92.3%). When the value of NP-59 tests was based on pathologic results, it showed a sensitivity of 90.9% and a positive predictive value of 83.3%. When the nuclear medicine test's performance was based on postoperative blood pressure control, both sensitivity and positive predictive value were 91.6%. Nuclear medicine tests represent a useful tool in the preoperative localisation of primary hyperaldosteronism with a high sensitivity and positive predictive value. In patients with contraindications to adrenal venous sampling like contrast allergies, or when it is inconclusive, scintigraphy can represent a useful and non-invasive alternative.

Hormonal, Radiological, NP-59 Scintigraphy, and Pathological Correlations in Patients With Cushing's Syndrome Due to Primary Pigmented Nodular Adrenocortical Disease (PPNAD).

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing's syndrome that may occur in an isolated form or as part of Carney complex. The diagnosis of this disease can be difficult preoperatively because computed tomography (CT) scan can be normal or suggest unilateral adrenal lesion, which can impede the correct diagnosis of bilateral adrenal disease. The aim of our study was to describe the results of preoperative imaging (adrenal [6β-(131)I]iodomethyl-19-norcholesterol] [NP-59] scintigraphy and standard adrenal CT scan) and their correlations with clinical, pathological, and genetics investigations in patients with PPNAD. Seventeen patients with ACTH-independent syndrome due to PPNAD were investigated with a standard adrenal CT scan and NP-59 scintigraphy. Hormonal, pathological, and genetics data were analyzed. Four males and 13 females (median age, 27 y) were included. PPNAD was isolated in 11 patients (with PRKAR1A mutation, n = 7; and without PRKAR1A mutation, n = 4) and was associated with extra-adrenal manifestations of Carney complex in six patients (with PRKAR1A mutation, n = 4; and without PRKAR1A mutation, n = 2). Standard adrenal CT scan revealed micronodules in 11 patients, macronodules in three patients, and was normal in three patients. All patients demonstrated bilateral adrenal radiocholesterol uptake. Adrenal uptake was asymmetrical in 10 of 17 patients (59%). Asymmetrical uptake correlated with the presence of macronodules at pathological analysis (P = .03). Standard adrenal CT scan most often reveals micronodules but there is no specific CT imaging. NP-59 scintigraphy always shows a bilateral adrenal uptake confirming the bilateral nature of the disease, but asymmetrical scintigraphic uptake can be observed in patients with macronodules.

Prognostic value of semiquantification NP-59 SPECT/CT in primary aldosteronism patients after adrenalectomy

Primary aldosteronism (PA), characterized by an excessive production of aldosterone, affects 5-13 % of patients with hypertension. Accurate strategies are needed for the timely diagnosis of PA to allow curability and prevention of excessive cardiovascular events and related damage. This study aimed to evaluate the usefulness of semiquantification of (131)I-6β-iodomethyl-norcholesterol (NP-59) single photon emission computed tomography (SPECT)/CT in differentiating aldosterone-producing adenoma (APA) from idiopathic adrenal hyperplasia (IAH) and in predicting clinical outcomes after adrenalectomy. We retrospectively reviewed 49 PA patients who had undergone adrenalectomy after NP-59 SPECT/CT within 1 year. A conventional visual scale (VS) and two semiquantitative parameters generated from SPECT/CT, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON), with cutoff values calculated by receiver-operating characteristic (ROC) analysis, were compared with pathology results and postsurgical outcomes to determine the accuracy. An ALR cutoff of 1.84 and a CON cutoff of 1.15 showed an ability to distinguish adenoma from hyperplasia similar to VS (p = 0.2592 and 0.1908, respectively). An ALR cutoff of 2.28 and a CON cutoff of 1.11 yielded the highest sensitivity and specificity to predict postsurgical outcomes, and an ALR of 2.28 had an ability superior to VS (p = 0.0215), while a CON of 1.11 did not (p = 0.1015). Patients with either ALR or CON greater than the cutoff had a high probability of positive postsurgical outcomes (n = 36/38), while patients with both ALR and CON less than the cutoff had a low probability of positive postsurgical outcomes (n = 2/11). Semiquantification of NP-59 scintigraphy has an ability similar to VS in differentiating APA from IAH, but an excellent ability to predict postsurgical outcomes of adrenalectomy. An ALR or CON greater than the cutoff strongly suggests benefits from adrenalectomy, and both ALR and CON less than the cutoff implies a reduced chance of improvement in postsurgical outcome.

Adrenal Cortical Imaging With I-131 NP-59 SPECT-CT

The purpose of this article is to present our initial experience with hypersecretory adrenal syndromes investigated with radioiodinated I-6-B-iodomethyl-19-norcholesterol (NP-59) and SPECT-CT. Illustrative cases are presented of patients being investigated for adrenal hypersecretory syndromes, with or without adrenal nodules, using NP-59 scintigraphy with SPECT-CT imaging, representing a spectrum of diagnoses. Clinical and imaging data are reviewed to evaluate whether additional information derived from near-simultaneous anatomic localization aids study interpretation. The final diagnoses reached are hyperfunctional and nonfunctioning adrenal nodules, physiological bowel activity, and bilateral adrenal hyperplasia. SPECT-CT assisted study interpretation by localizing focal uptake to the adrenal glands, allowing direct assessment of function within adrenal nodules, and distinguishing physiological bowel activity from adrenal uptake. SPECT-CT provided additional information to planar and SPECT imaging, which improved confidence of study interpretation. Utilization of SPECT-CT with NP-59 scintigraphy allows precise localization of the functional activity to anatomic structures improving diagnostic interpretation.

The role of radiologic studies in the evaluation and management of primary hyperaldosteronism

Surgical treatment of primary hyperaldosteronism (PHA) requires demonstration of unilateral adrenal hypersecretion. Optimal methods for interpretation of imaging and invasive testing are still in development. A retrospective review from 1996-2007 of 106 patients with PHA was undertaken. Patient demographics, biochemical studies, radiologic imaging, operative reports, and pathology were reviewed and comparisons made. Optimal ratios for adrenal vein sampling were tested with regard to sensitivity and specificity. Preoperative and postoperative medication requirements and blood pressures were compared among different treatment groups. Seventy-eight patients (62 surgically treated) met criteria for inclusion. Median arterial blood pressure at diagnosis was 150/86 mm Hg while taking 3 antihypertensive medications. 69.2% required potassium supplementation. Median aldosterone:renin ratio was 107.0. Forty-two AVS procedures changed the management of 15 patients (35.7%) when compared to CT results. AVS accuracy was 96.6 vs 88.9% for NP-59 scintigraphy. Operative patients remained on fewer antihypertensive medications (1 vs 3), and mean systolic pressure was lower (130 vs 146 mm Hg) compared with medically managed patients. When used together, pre-ACTH aldosterone ratios, normalized A/C:A/C ratios, ratios to define contralateral suppression, and post-ACTH stimulated values allowed for capture of episodically secreting tumors and subtle unilateral or bilateral hyperaldosteronism.

The Role of Adrenal Scintigraphy in the Preoperative Management of Primary Aldosteronism

Differentiation between the two major subgroups of primary aldosteronism, bilateral hyperplasia and aldosterone producing adenoma is essential since therapy in the former is medical and in the latter surgical. The aim of the present study was to evaluate the clinical utility of adrenocortical scintigraphy in the management of primary aldosteronism. [131I] norcholesterol (NP-59) scintigraphy with dexamethasone suppression for subclassification and lateralization of primary aldosteronism was evaluated in 49 patients with long-term follow-up after diagnosis and treatment. Thirty-three patients with the diagnosis of aldosterone producing adenoma were operated with adrenalectomy. Preoperative scintigraphy showed lateralized isotope uptake in 27/33 patients while 6 showed no uptake. Twenty-two were cured and three significantly improved. Thus, in 25/33 (76%), scintigraphy showed the correct side as the patients benefited of surgery. Two patients did not improve. Fourteen patients with a probable diagnosis of bilateral hyperplasia had normal scintigraphies. In the present retrospective study we found limited sensitivity of NP-59 scintigraphy. However, when a lateralized scintigraphic uptake is achieved it has a high accuracy. Scintigraphy may be used as an adjunct in cases where adrenal venous sampling is inconclusive.

Indications for laparoscopic adrenalectomy for non‐functional adrenal tumor with hypertension: Usefulness of adrenocortical scintigraphy

Laparoscopic adrenalectomy is currently indicated for biochemically and clinically functional adrenal tumors and potentially malignant tumors of the adrenal glands. Non-functional adenomas greater than 5 cm in diameter of the adrenal gland are generally considered to represent potentially malignant tumors. The present study shows indications of laparoscopic adrenalectomy for non-functional adrenal tumors with hypertension in a retrospective fashion. Between 1994 and 2004, 110 laparoscopic adrenalectomies were performed at Tokushima University Hospital. All 110 patients underwent detailed endocrinological examination before surgery. Medical and operative records of these 110 patients (57 men, 53 women), including operative parameters, histopathological findings and pre- and postoperative hypertension, were reviewed. Forty-five patients underwent laparoscopic adrenalectomy for non-functional adrenal tumors, and [(131)I]6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol (NP-59) scintigraphy was performed for patients with preoperative hypertension. Mean patient age was 55.0 years (range, 22-77 years). Mean maximum tumor diameter was 42 mm (range, 20-105 mm). All adrenal tumors were removed successfully by laparoscopic surgery. Hypertension was postoperatively improved in seven of the 11 patients with preoperative hypertension, without subclinical Cushing syndrome. Importantly, all patients who improved hypertension after adrenalectomy displayed strong accumulation in adrenal tumors with visualization of the contralateral gland on NP-59 scintigraphy. Conversely, blood pressure did not improve in four patients for whom scintigraphy yielded negative results. The indication of laparoscopic adrenalectomy for non-functional adrenal tumors is generally considered for lesions more than 5 cm diameter. However, the present study suggests that laparoscopic surgery should be considered even in patients with tumors less than 5 cm in diameter, if both hypertension and accumulation in tumors on NP-59 scintigraphy are present.

Adrenal tumors: how to establish malignancy ?

Discerning malignancy in adrenal tumors largely influences disease management and is, therefore, of utmost importance to both patient and physician. Clinical presentation (e.g. virilization) and baseline hormonal evaluation (e.g. high serum DHEAS) are occasionally of great value but usually provide only limited help in predicting malignancy. The probability of malignancy is clearly related to tumor size, as almost all lesions <3 cm are benign whereas a diameter of >6 cm indicates a high risk of malignancy. Computed tomography (CT) and magnetic resonance imaging (MRI) both contribute significantly to the characterization of adrenal masses. If the attenuation of a homogeneous mass with smooth border is 10 Hounsfield units or less in unenhanced CT the diagnosis of a lipid rich adenoma is established. Similarly, enhancement washout of more than 50% in CT at 10-15 min suggests a benign lesion. In MRI both rapid contrast enhancement after gadolinium followed by rapid washout and signal intensity loss using opposed-phase image in chemical shift analysis also indicate the presence of an adenoma. In contrast, adrenal carcinomas--but also pheochromocytomas--typically present as inhomogeneous lesion with intermediate-to-high intensity on T2 images in MRI. Margins and enhancement after contrast media in CT are irregular in adrenal carcinoma. Other imaging techniques either offer little additional information (NP-59 scintigraphy) or have not yet been fully established (positron emission tomography). Fine needle aspiration/cut biopsy is at present restricted to patients with a known extra-adrenal malignancy and suspected adrenal metastasis as the only evidence of disseminated disease. Adrenal tumors classified as benign undergo follow-up imaging to assess tumor growth. If an increase in diameter of >1 cm is seen, surgical removal is recommended. Even after tumor removal the diagnosis of dignity may remain difficult. Diagnostic scores together with new immunohistological markers are the methods of choice to assess malignancy. In conclusion, an interdisciplinary approach with a structured use of available diagnostic tools is needed to classify adrenal tumors correctly.

Diagnostic dilemma of small incidentally discovered adrenal masses: role for 131I-6beta-iodomethyl-norcholesterol scintigraphy.

Incidentally discovered adrenal masses are detected in 0.35% to 5. 00% of patients imaged with computed tomography (CT) for reasons other than suspected adrenal pathology. Most small adrenal masses are benign, although malignant tumors </= 3 cm in diameter are well described. In the setting of normal adrenal hormonal secretion, the preferential accumulation of 131I-6beta-iodomethyl-norcholesterol (NP59) by adrenocortical tissues allows the distinction of adenomas from other space-occupying or destructive lesions, with diagnostic images being obtained in 100% of lesions > 2 cm. Although some lesions </= 2 cm have yielded nondiagnostic images, the frequency of this phenomenon and thus the utility of NP59 scintigraphy for the evaluation of small adrenal lesions has remained incompletely characterized. Between January 1976 and December 1994 a total of 166 patients with nonhypersecretory unilateral adrenal masses </= 3 cm in maximal diameter, discovered incidentally during CT examinations of the abdomen or chest for reasons other than clinically suspected adrenal disease, were studied with NP59 scintigraphy. Nonhypersecretory masses </= 1 cm, > 1 to </= 2 cm, and > 2 to </= 3 cm yielded diagnostic images in 52%, 89%, and 100% of patients, respectively. Lesions other than adenomas, including malignancies, > 1 to </= 2 cm and > 2 to </= 3 cm were present in 9% and 10% of patients, respectively. These findings emphasize the need to determine the nature of small incidentally discovered adrenal masses whose management may alter patient care and confirm the utility of NP59 scintigraphy to evaluate nonhypersecretory adrenal masses regardless of size.

Incidentally Discovered Adrenal Masses*

Independently, endocrinology, radiology, and nuclear medicine can not optimally differentiate the etiology of the incidental adrenal mass. Rather, the insight necessary for this task must be contributed by all three disciplines. Incidentally discovered adrenal masses are being detected at an increasing rate. This trend is expected to continue based on the incidence of adrenal masses in autopsy series and the increasing use of high resolution abdominal imaging techniques. CT and MRI are able to definitely characterize only a minority of these lesions (simple cyst, myelolipoma, obvious local malignant invasion). Biochemical screening for hormone excess is essential regardless of a nonsuggestive complete history and physical examination. An argument may be made for not further pursuing nonhypersecreting lesions with the typical features of a benign adenoma on CT scan and an attenuation value of 0 HU or less. Adrenocortical scintigraphy is recommended in all patients with normal biochemical screening tests, especially those with CT attenuation values greater than 0 HU. In this setting, we believe that the functional and anatomical information provided by NP-59 and [75Se]selenomethylnorcholesterol scintigraphy allows one to noninvasively, accurately, and less expensively (Table 9) categorize adrenal masses as benign nonhypersecretory adenomas (the vast majority) vs. a possibly malignant lesion (the minority). In the presence of normal biochemistry, a concordant NP-59 imaging pattern is diagnostic of a nonhypersecretory benign adrenal adenoma and requires no immediate therapeutic intervention. Conversely, patients with discordant patterns of NP-59 scintigraphy have lesions that carry a significant risk for malignancy, and the pursuit of a tissue diagnosis is indicated, usually by means of FNA. Normal adrenocortical tissue on cytological studies in this setting may represent inadvertent sampling of adjacent normal adrenocortical tissues or the presence of a well differentiated adrenocortical carcinoma. In patients with lesions larger than 2 cm in whom NP-59 scintigraphy is nonlateralizing, the possibility of a periadrenal or pseudoadrenal mass is likely and should prompt review, or perhaps even repeat, of high resolution adrenal imaging (occasionally angiography may be helpful). In lesions shown to be 2 cm or less in size with a nonlateralizing NP-59-scan, there is a possibility of a periadrenal or pseudoadrenal mass; however, once this is excluded it must be recognized that benign and malignant lesions, because of the limitations of scintigraphy, cannot always be clearly distinguished by this method when masses are small.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone-secreting adrenal cortical adenoma in an 11-year-old child and collective review of the literature

We report a rare case of primary hyperaldosteronism due to a unilateral adrenal cortical adenoma in an 11-year-old female patient. The patient presented with hypertension, hypokalaemia and metabolic alkalosis, associated with inappropriate kaliuresis. The diagnosis was supported by the following laboratory findings: elevated plasma aldosterone, suppressed plasma renin activity, nonsuppressible aldosterone secretion following saline infusion and absent plasma aldosterone response to ambulation. MRI revealed a 1 cm-diameter adrenal tumour on the left side. Even though the NP-59 scintigraphy showed the negative result, laparotomy with left adrenalectomy was performed. Pathological examination confirmed an adenoma in the adrenal cortex. The patient's blood pressure and biochemical laboratory data normalized postoperatively within 2 days. We recommend that in hypertensive children with hypokalaemia and metabolic alkalosis, primary aldosteronism should be considered.

The Association of Aldosterone-Producing Adrenal Adenoma in a Patient With Autosomal Dominant Polycystic Kidney Disease

We report a young female with autosomal dominant polycystic kidney disease associated with right adrenal adenoma. Refractory hypertension and hypokalemia were the findings that led to this diagnosis. The diagnostic approach included plasma potassium and aldosterone levels, plasma renin activity, captopril test, saline infusion test, NP-59 scintigraphy, computed tomography, and magnetic resonance imaging. Adrenalectomy completely normalized hypertension and hypokalemia in this patient.