NIH Adrenal Clinical Trials Updated 6/6/2011

Rank	Status	Study
1	Recruiting	Trial of Vasopressin and Epinephrine to Epinephrine Only for In-Hospital Pediatric Cardiopulmonary Resuscitation Conditions: Cardiopulmonary Arrest;   Cardiac Arrest Interventions: Drug: Vasopressin;   Drug: Epinephrine
2	Recruiting	Test Predicting Adrenal Insufficiency in Volunteers Under Prednisone Treatment Condition: Adrenal Gland Hypofunction Interventions: Procedure: adrenal insufficiency testing;   Drug: prednisone
3	Recruiting	The Bupivacaine Dose Sparing Effect of Intrathecal Epinephrine Condition: Spinal Anesthesia Interventions: Drug: Placebo;   Drug: epinephrine 25;   Drug: Epinephrine 50;   Drug: epinephrine 100;   Drug: Epi 200
4	Recruiting	SPARTACUS: Subtyping Primary Aldosteronism: a Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan. Condition: Hyperaldosteronism Intervention: Other: Ct-scan or adrenal vein sampling
5	Not yet recruiting	Intranasal Injection Versus Topical Administration of Epinephrin During Endoscopic Sinus Surgery Conditions: Hypertension;   Hypotension;   Tachycardia;   Bradycardia;   Arrhythmia Interventions: Drug: Epinephrin (Intranasal injection);   Drug: Epinephrin (Topical administration)
6	Recruiting	Adrenal Insufficiency in Septic Shock Conditions: Septic Shock;   Acute Adrenal Insufficiency Intervention: Drug: Corticosteroid
7	Recruiting	Performance of 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in the Diagnosis of Indeterminate Adrenal Tumors on Conventional Imaging: A French Prospective Multicentric Study Condition: Adrenal Gland Neoplasms Intervention: Other: FDG-PET scan
8	Unknown †	Prospective Study on the Incidence of Adrenal Crisis in Patients With Chronic Adrenal Insufficiency Condition: Adrenal Insufficiency Intervention:
9	Recruiting	Adrenal Function in Critical Illness Condition: Adrenal Insufficiency Intervention:
10	Recruiting	Adrenal Vein Sampling International Study (AVIS Study) Condition: Hyperaldosteronism Intervention:
11	Recruiting	Epinephrine Inhalation Aerosol USP: For Evaluation Of Efficacy And Safety In Asthma Patients Condition: Asthma Interventions: Drug: Epinephrine inhalation aerosol;   Drug: Placebo;   Drug: epinephrine inhalation aerosol
12	Unknown †	Adrenal Insufficiency in Critical Emergencies in Digestive Diseases Conditions: Digestive Diseases;   Adrenal Insufficiency;   Gastrointestinal Bleeding;   Variceal Bleeding;   Acute Pancreatitis Intervention:
13	Not yet recruiting	Prevalence Study of Adrenal Suppression After Corticosteroids During Chemotherapy. Condition: Adrenal Suppression Intervention: Other: Prevalence study only, no study intervention
14	Recruiting	Adrenal Hyperplasia Among Young People With PCOS Conditions: Adrenal Hyperplasia;   Polycystic Ovarian Syndrome;   Oligomenorrhea;   Obesity;   Hyperandrogenism Intervention:
15	Recruiting	Low-Dose Epinephrine Infusion Tests in Adolescent and Pediatric Patients Condition: Congenital Disorders Intervention: Drug: Epinephrine
16	Recruiting	Evaluation of Molecular Markers in Adrenal Tumors Condition: Adrenal Gland Neoplasms Intervention:
17	Unknown †	Adrenal Function After Living Kidney Donation Conditions: Addison Disease;   Hypoaldosteronism Intervention: Procedure: Laparoscopic hand-assisted donor nephrectomy
18	Recruiting	Adrenal Tumors - Pathogenesis and Therapy Conditions: Adrenal Tumors;   Adrenocortical Carcinoma;   Cushing Syndrome;   Conn Syndrome;   Pheochromocytoma Intervention:
19	Not yet recruiting	A Pilot Study of F-18 Paclitaxel (FPAC) PET for Evaluating Drug Delivery of Solid Tumors in Breast, Lung, Renal, and Adrenal Cancers Conditions: Breast Cancer;   Lung Cancer;   Renal Cancer;   Adrenal Cancer Intervention: Drug: F-18 Paclitaxel (FPAC)
20	Not yet recruiting	The Hemostatic and Hemodynamic Effects of Adrenaline During Endoscopic Sinus Surgery Condition: Chronic Sinusitis Interventions: Drug: 1% lidocaine with 1:100,000 adrenaline;   Drug: 1% lidocaine with 1:200,000 adrenaline

21	Recruiting	Study of Intracameral Adrenaline for Pupil Dilation Without Topical Mydriatics in Refractive Cataract Surgery Condition: Cataract Intervention: Drug: adrenalin
22	Recruiting	Study of Adrenal Gland Tumors Condition: Adrenal Gland Neoplasm Intervention:
23	Recruiting	The Effects of Epinephrine in Endotoxemia in Normal Volunteers Condition: Immune System Interventions: Biological: Endotoxin, Lipopolysaccharide, LPS;   Biological: Endotoxin, Lipopolysaccharide, LPS /Epinephrine
24	Unknown †	Does Topical Steroid Treatment Impair the Adrenal Function? Conditions: Hypothalamus-Pituitary-Adrenal Axis Assessement;   Topical Steroid Therapy in Chronic Skin Diseases Intervention:
25	Recruiting	Combination Local Anesthetics Condition: Perioperative Pain Interventions: Drug: 1% Lidocaine with Epinephrine;   Drug: 0.25% Bupivacaine with epinephrine;   Drug: 1% Lidocaine + 0.25% Bupivacaine with Epinephrine;   Drug: 2% Lidocaine + 0.5% Bupivacaine with epinephrine
26	Recruiting	Study Comparing Peri-articular Injection of Bupivacaine With and Without Epinephrine Condition: Osteoarthritis Interventions: Procedure: Peri-articular injection of marcaine/epinephrine;   Procedure: Peri-articular injection of marcaine alone
27	Not yet recruiting	Gluing Lacerations Utilizing Epinephrine Condition: Lacerations Intervention: Drug: LET - Lidocaine Epinephrine Tetracaine
28	Recruiting	Use of Local Analgesia With Epinephrine During Total Hip Arthroplasty (THA) Condition: Arthroplasty, Replacement, Hip Intervention: Drug: ropivacaine, physical serum and adrenalin
29	Recruiting	Relative Adrenal Insufficiency in Preterm Very Low Birth Weight Infants With Shock Condition: Adrenal Insufficiency Intervention:
30	Unknown †	Adrenal Insufficiency in Cirrhotics With Ascites. Effects of Hydrocortisone on Renal and Haemodynamic Function Condition: Cirrhosis With Ascites Interventions: Drug: hydrocortisone;   Drug: dextrose solution 5%
31	Recruiting	Bronchiolitis, Optimal Treatment in Infants and Prognosis Condition: Bronchiolitis Interventions: Drug: Racemic adrenaline;   Drug: Isotonic saline
32	Recruiting	RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid Conditions: Pheochromocytoma;   Extra-Adrenal Paraganglioma;   Non-functioning Carcinoid Intervention: Drug: RAD001
33	Not yet recruiting	Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q4 Condition: Type 1 Diabetes Intervention: Drug: epinephrine
34	Recruiting	Effect of Epinephrine/ Phenylephrine for Preventing the Postreperfusion Syndrome During Reperfusion in Liver Transplantation Condition: Hypotension After Reperfusion in Liver Transplantation Interventions: Drug: phenylephrine;   Drug: epinephrine;   Drug: placebo control
35	Recruiting	Safety Study Evaluating the Adrenal Suppression Potential of Product 0405 in Pediatric Subjects With Atopic Dermatitis Condition: Atopic Dermatitis Intervention: Drug: Product 0405
36	Recruiting	Merits of Continuous Paravertebral Block in the Management of Renal/Adrenal Surgery by Laparotomy Condition: Patient Scheduled for Renal and/or Adrenal Surgery Intervention: Procedure: Continuous Paravertebral block
37	Not yet recruiting	Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome Condition: Adrenal Tumour With Mild Hypercortisolism Intervention: Procedure: Adrenalectomy
38	Unknown †	Role of the Protein Osteoprotegerin in the Bone Health of Women With Congenital Adrenal Hyperplasia Condition: Adrenal Hyperplasia, Congenital Intervention:
39	Recruiting	Gene Polymorphisms Influencing Steroid Synthesis and Action Conditions: Disorders of Sex Development;   Congenital Adrenal Hyperplasia;   Congenital Adrenal Hypoplasia;   Adrenal Insufficiency;   Mineralocorticoid Deficiency;   Intersex Intervention:
40	Recruiting	Adrenal Function and Use of Intralesional Triamcinolone Acetonide 10 mg/mL (Kenalog-10) in Patients With Alopecia Areata Condition: Alopecia Areata Intervention: Drug: Triamcinolone Acetonide 10 mg/mL (Kenalog-10)

Causes of secondary and tertiary adrenal insufficiency in adults

INTRODUCTION

Adrenal insufficiency can be caused by diseases of the adrenal gland (primary), interference with corticotropin (ACTH) secretion by the pituitary gland (secondary), or interference with corticotropin-releasing hormone (CRH) secretion by the hypothalamus (tertiary). This topic will review the major causes of the latter two disorders; the causes of primary adrenal insufficiency, and the clinical manifestations and approach to diagnosis are discussed separately. (See "Causes of primary adrenal insufficiency (Addison's disease)" and "Clinical manifestations of adrenal insufficiency in adults" and "Diagnosis of adrenal insufficiency in adults".)

 

SECONDARY ADRENAL INSUFFICIENCY

Any process that involves the pituitary and interferes with ACTH secretion can cause secondary adrenal insufficiency. The ACTH deficiency may be isolated, or occur in conjunction with other pituitary hormone deficiencies (panhypopituitarism).

 

Panhypopituitarism — Pituitary tissue can be destroyed and hormone secretion reduced by large pituitary tumors or craniopharyngiomas, infectious diseases such as tuberculosis or histoplasmosis, infiltrative diseases, lymphocytic hypophysitis, head trauma, and large intracranial artery aneurysms. Pituitary infarction can occur at the time of delivery if excessive blood is lost and hypotension occurs (Sheehan's syndrome), and hemorrhage may occur into a pituitary tumor (pituitary apoplexy). Pituitary metastases are frequently (about 5 percent) found in patients with disseminated cancer at autopsy; however, these metastases rarely reduce hormone secretion [1]. (See "Causes of hypopituitarism".)

 

ACTH deficiency due to genetic pituitary abnormalities is rare. ACTH and cortisol deficiency have been described in patients with multiple pituitary hormone deficiencies due to mutations in the PROP-1 (Prophet of Pit-1) gene, even though PROP-1 is not expressed in corticotropes. The onset of cortisol deficiency, which may be severe, ranges from childhood to late adulthood [2-5]. Mutations in other transcription factors involved in early pituitary development (HESX1, LHX4) also can result in variable degrees of hypopituitarism that include ACTH deficiency [6,7]. (See "Causes of hypopituitarism".)

 

Isolated ACTH deficiency — Isolated ACTH deficiency is a rare disorder [8]. The defect is probably at the pituitary level because there is no ACTH secretory response to CRH or vasopressin, as there usually is in hypothalamic disorders [9-11]. Occasional patients may have hypothyroxinemia and hyperprolactinemia that are corrected with glucocorticoid replacement [12,13].

 

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Incidentally-discovered Adrenal Masses

Author: Milton D Gross

Specialty: Radiology, Nuclear Medicine, Endocrinology
Institution: Division of Nuclear Medicine, Department of Radiology, University of Michigan
City: Ann Arbor; State/Province: Michigan; Postal Code: 48105; Country: United States

Author: Melvyn Korobkin

Specialty: Radiology
Institution: Division of Abdominal Imaging, Department of Radiology, University of Michigan Medical Center
City: Ann Arbor; State/Province: Michigan; Country: United States

 

Author: Wessam Bou-Assaly

Specialty: Radiology
Institution: Department of Radiology, University of Michigan Medical Center
City: Ann Arbor; State/Province: Michigan; Country: United States
Institution: Radiology Service, Department of Veterans Affairs Health System
City: Ann Arbor; State/Province: Michigan; Country: United States

Author: Domenico Rubello

Specialty: Radiology
Institution: Department of Nuclear Medicine, PET Center, and Medical Physics and Radiology, Santa Maria della Misericordia Hospital
City: Rovigo; Country: Italy

 

Abstract: Unanticipated adrenal masses are frequently encountered in modern, high resolution diagnostic imaging. Most often, these masses are benign adrenal adenomas, but when detected they necessitate a clinical evaluation sufficient to exclude subclinical endocrine disease, primary adrenal cancer, and remote metastases to the adrenal glands from other malignancies. These "incidentally-discovered" adrenal masses or so-called "adrenal incidentalomas" can be further evaluated with CT, MRI, and nuclear medicine imaging techniques. A substantial literature supports the use of each of these modalities to non-invasively characterize these neoplasms that have been considered by some as a 'disease' by modern imaging technology.

 

Introduction

Over the last 3 decades the more widespread use of high-resolution CT and MRI have seen the frequent, “incidental” discovery of clinically unsuspected masses of the adrenal glands. Detection of these masses raises the specter of malignancy and forces further diagnostic evaluation to determine their etiology and to distinguish benign masses from those that would substantially change the clinical approach to the patient.

 

In patients undergoing CT for reasons other than adrenal disease, adrenal masses are incidentally discovered in 0.4-4.5% (Kloos et al., 1995). The majority of adrenal masses, ranging from 7% to 94%, are benign and hormonally non-functional, while in patients with malignancy the incidence of unsuspected adrenal masses ranges from 7% to 68% (Kloos et al., 1995). Metastases from other cancers to the adrenal occur in up to 20% of patients without previously diagnosed cancers and in almost 75 % of patients harboring non-adrenal primary malignancies (Kloos et al., 1995) (Table 1).

 

The incidence of clinically unsuspected adrenal masses increases with age greater than 30 years, regardless of gender. Clinically silent, hormonally active adrenal masses include tumors that produce hormones from all of the functional zones of the adrenal cortex and the adrenal medulla. As a result it is important that once discovered, and prior to any further imaging, a biochemical evaluation sufficient to exclude pheochromocytoma, normokalemic primary aldosteronism, and subclinical hypercortisolism be done as these conditions are optimally managed by surgical removal of the offending tumor (Young, 2007).

 

Methods of Adrenal Gland Imaging

Computed tomography is the most common imaging modality that identifies unsuspected adrenal masses in the evaluation of the chest and upper abdomen for diseases unrelated to the adrenal glands (Gross at al., 2005). Both CT and MRI can be used to differentiate normal from abnormal adrenal glands and MRI has been used to characterize incidentally discovered adrenal masses in clinical situations where CT is non-diagnostic (Gross et al., 2009) (Table 2).

 

Computed tomography and magnetic resonance imaging

 

Contemporary CT scanners using slice thicknesses of 3-5 mm will reliably depict the adrenal glands in virtually all patients. Comparison of non-contrast to contrast-enhanced CT can be used to distinguish adrenal masses and for evaluating retention and patterns of contrast washout as a means to differentiate adenomas from other adrenal neoplasms (Boland et al., 2008). MRI can be used to advantage in the evaluation of normal adrenal glands and adrenal masses. Gradient-echo, chemical shift MRI with in- and opposed-phrase imaging, and dynamic contrast-enhanced MRI detect lipid content in adrenal adenomas and, when combined with chemical shift ratios, depict the adrenal glands with an efficacy similar to CT (Dunnick et al., 2002). Hybrid scanners marrying CT, and perhaps in the near future MRI, with positron emission tomography (PET) and single photon emission tomography (SPECT) employing radiopharmaceuticals designed to target unique aspects of adrenal gland function(s) offer direct combination of anatomic and functional information that enhances diagnosis and differentiation of benign from malignant adrenal lesions (Gross et al., 2009).

 

Adrenal scintigraphy

The radiocholesterol analogs, ¹³¹I-6β-iodomethyl-19-norcholesterol (NP-59) and selenium-75-6β-iodomethyl-19-norcholesterol (Scintadren®) were some of the first successful radiopharmaceuticals used to image the adrenal cortex (Gross et al., 2007). Radiolabeled inhibitors of enzymes responsible for adrenal steroid hormone biosynthesis like the 11β-hydroxylase inhibitor, carbon-11-metomidate (¹¹C-MTO), can also be used to image neoplasms of adrenocortical origin. Other radiolabeled substrates depict metabolic processes such as the radio-fluorine-labeled ¹⁸F-fluorodeoxyglucose (FDG) to identify primary adrenal neoplasms and metastases to the adrenals, while ¹¹C-labeled acetate and ¹¹C- and ¹⁸F-labeled choline have been used to depict adrenal adenomas (Gross et al., 2007).

Radiolabeled metaiodobenzylguanidine (MIBG) has been used to identify the adrenal medulla and localize neoplasms of adrenomedullary origin by exploiting norepinephrine-re-uptake mechanisms into the catecholamine storage vesicles of adrenergic tissues.

 

Hydroxyephedrine, an analog of norepinephrine, can be labeled with ¹¹C or ¹⁸F, and is transported into adrenergic nerve terminals by these same mechanisms. The list of catecholamine-based PET radiopharmaceuticals used to image the adrenal medulla, related tissues, and tumors of sympathomedullary origin now includes ¹¹C-epinephrine, ¹¹C- or ¹⁸F-hydroxyepinephrine, ¹⁸F-fluorodopamine (FDA), and ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) (Shulkin et al., 2006). Alternatively, somatostatin receptor uptake of specific imaging agents can be used to image tissues that express somatostatin receptors, like the adrenal medulla and many other tissues and neoplasms. Octreotide, a long-acting somatostatin antagonist labeled with a variety of radioisotopes (¹¹¹Indium, ¹²³Iodine, ^99mTechnetium for SPECT, and ⁶⁸Gallium for PET imaging) can be used to accurately localize and stage primary and metastatic sympathomedullary tumors (Gross et al., 2007).

 

Imaging Incidentally-discovered Adrenal Masses

The differential diagnostic list of incidentally-discovered adrenal masses is long and a description of all but the most common is outside the scope of this short review. An extensive medical literature is available that describes the imaging characteristics of adrenal masses (Gross et al., 2005).

 

Adrenal adenoma

Adrenal adenomas are depicted on CT with density values expressed as Hounsfield units (HU) that are similar to normal adrenal tissues and depending upon their lipid content may express HU values similar to tissue water density (Korobkin et al., 1996). Furthermore, adenomas demonstrate increasing density, so-called “enhancement,” after intravenous CT contrast with more rapid loss of contrast — “washout” as compared to adrenal metastases (Korobkin et al., 1998). Like CT, MRI characteristics of adenomas are also similar to normal adrenal tissues. Signal intensity of adenomas is low on T2-weighted MR imaging sequences, but there is overlap (20-30%) with the signal intensity of metastases to the adrenal. Chemical-shift imaging is useful to depict tissue lipid content and is often employed to differentiate adenomas from metastases to the adrenal (Dunnick et al., 2002).

 

Pheochromocytoma

Pheochromocytomas are often clinically silent and present on high resolution anatomic imaging as incidentally-discovered adrenal masses. These neoplasms show enhancement with intravenous contrast agents in a fashion similar to malignant adrenal masses and occasionally may mimic contrast washout characteristics of benign adrenal adenomas. The imaging uncertainty posed by pheochromocytomas demands a biochemical evaluation sufficient to exclude catecholamine hypersecretion in suspect patients. Concerns over the potential of intravenous contrast-induction of hypertensive crisis have recently been allayed with nonionic contrast agents. Like CT, pheochromocytomas are usually hyperintense on T2-weighted imaging; however, there is overlap and about 30% are hypointense on T2-weighted imaging sequences (Blake et al., 2004).

 

Adrenal carcinoma

Adrenal carcinoma is a rare neoplasm (~ 2/10⁶ patients) that usually presents late in the course of disease. Adrenal carcinoma is often imaged as a large, heterogeneous abdominal mass with central necrosis, calcification, and tumor venous extension on contrast enhanced CT (Gross et al., 2009). On MRI these neoplasms are hyperintense on both T1- and T2-weighted imaging sequences from intra-tumor hemorrhage and central necrosis.

 

Adrenal metastases

Adrenal glands are common sites of remote metastases from cancers of the lung, breast, and melanoma. Adrenal metastases can be unilateral, bilateral, and variable in size. CT and MRI are nonspecific. Small metastases are often homogeneous on contrast CT or MRI, while large metastases are heterogeneous as a result of intra-metastasis necrosis and hemorrhage.

 

Distinguishing benign from malignant adrenal masses

Figure 1. An adrenal mass (arrow) is identified on CT (panel A) with characteristics of an adenoma with a non-contrast CT density (panel B) of 9.8 HU.

 

CT can be used to distinguish adrenal adenomas from metastases since most adenomas demonstrate non-contrast densities that are lower than metastases to the adrenal. The highest diagnostic efficacy for diagnosis of adrenal adenomas is obtained by selecting a threshold density value of 10 HU on non-contrast CT, as HU values for adenomas and adrenal hyperplasia are typically lower than those of metastases to the adrenal and pheochromocytomas (Figures 1 and 2).

 

Chemical-shift MRI also differentiates adrenal adenomas from metastases. By exploiting the different resonant frequencies of hydrogen in tissue water and lipid molecules, chemical-shift MRI detects a loss of signal intensity of tissues with high lipid and water content. Using gradient-echo imaging techniques, signal intensity loss on opposed-phase as compared to in-phase images differentiates tissues that contain lipids with high sensitivity and specificity. As lipids are common components of adrenal adenomas that are usually absent in metastases, this difference in lipid content can be exploited for the differentiation of adenomas vs. metastases to the adrenals (Figures 3 and 4).

Figure 2. Abdominal CT of bilateral adrenal masses (arrows) shows persistent enhancement of the right adrenal gland after intravenous contrast at 1.5 (panel B) and 5 min (panel C) after contrast injection in a pattern compatible with metastases to the adrenals.

 

In a combined histological CT and MRI study of adrenal adenomas there was an inverse relationship between lipid-containing cells and unenhanced CT, and a positive correlation with the relative change in signal intensity on opposed-phase MRI confirming that non-contrast CT and chemical-shift MRI might not necessarily complement each other in the evaluation of adrenal adenomas (Outwater et al., 1996). Contrast-enhanced CT images of the adrenals are obtained about 1 minute after a bolus intravenous injection of contrast and at this time point the attenuation values of adenomas and metastases are nearly identical (Figure 2B and Figure 5C). However, over time adenomas demonstrate loss of contrast enhancement and attenuation values on contrast enhanced CT of < 30-40 HU at 10-15 minutes post contrast injection can be used to distinguish, with few exceptions, adenomas from other adrenal masses (Gross el al., 2009).

 

Figure 3. MRI of a right adrenal nodule (arrows) demonstrates post-contrast enhancement on T1-weighted imaging (panel C) and displays loss of signal on out-of-phase (panel B) compared to in-phase imaging (panel A) confirming the mass as an adrenal adenoma.

 

Adrenal gland contrast washout as a percentage of initial enhancement is another parameter that can be used to identify adenomas from other adrenal masses. Adrenal adenomas have characteristic washout percentages of ~ 60% at 15 minutes post contrast administration corresponding to a sensitivity of 88% and a specificity of 96% for diagnosis of adenoma (Korobkin et al., 1998) (Figure 5). Further, so-called “lipid-poor” adenomas with unenhanced CT attenuation of >10 HU have contrast enhancement washout values that are nearly identical to those of lipid-rich adenomas confirming the value of differential washout as a means to identify adrenal adenomas from other adrenal masses (Caoili et al., 2000).

 

Distinguishing adrenal adenoma from carcinoma

Figure 4. MRI of a right adrenal mass demonstrates heterogeneous post-contrast enhancement (panel C) with no signal loss on out-of-phase imaging (panel B) vs. in-phase imaging (panel A) confirming the mass to be an adrenal metastasis.

 

Any adrenal mass larger than 5 to 6 cm in diameter is considered suspicious for an adrenocortical carcinoma. Large, non-secreting pheochromocytomas, adrenal carcinoma, or adrenal metastases may be indistinguishable by CT and MRI. Size criteria for resection of adrenal masses varies widely from 3.5 to 6 cm, and while there is controversy concerning the approach to smaller masses there is general agreement that masses > 6 cm, regardless of their imaging characteristics, should be removed.

 

Scintigraphy of adrenal masses

There are a host of scintigraphic imaging agents, with each targeting a unique characteristic of adrenal gland function that can be used to assess the etiology of incidentally-discovered adrenal masses. Adrenal adenomas can be depicted with iodocholesterol with positive and negative predictive values of 89% and 100%, respectively, and the lateralization of tracer uptake to one gland may be predictive of the development of future functional autonomy.

 

Metaiodbenzylguanidine images masses of adrenomedulla origin with positive and negative predictive values of 83% and 100%, respectively, while ¹⁸F-FDG separated benign from malignant adrenal lesions with 100% sensitivity and specificity (Maurea et al., 2001). As a result, if functional imaging is to be used to evaluate adrenal masses in patients with no history of cancer, radiocholesterol scintigraphy should be the first imaging procedure to identify the most common incidentally-discovered adrenal mass, a benign adrenal adenoma, followed by MIBG to identify clinically silent pheochromocytomas. Should MIBG be non-diagnostic, ¹⁸F-FDG is to be used to identify a potentially malignant adrenal mass or remote metastasis to the adrenal. Conversely, in patients with a prior history of cancer, ¹⁸F-FDG would be the most optimal first imaging study in the search for metastatic disease to the adrenal followed in sequence by iodocholesterol and MIBG.

Figure 5. A left adrenal gland mass (arrow) with a density of 1.5 HU on non-contrast CT (panels A and B) increases after intravenous contrast administration to 50 HU on early post-contrast enhanced images (panel C), and falls to 4 HU on the delayed images (panel D). The calculated washout of 95% is compatible with a lipid rich, adrenal adenoma.

 

¹⁸F-FDG-PET can differentiate benign from malignant adrenal lesions and metastases to the adrenal (Figure 6). In a study of 150 patients with adrenal masses, ¹⁸F-FDG-PET had a sensitivity of 98.5% and a specificity of 92% at a standardized uptake value (SUV) threshold of 3.1 and with the addition of CT to FDG-PET specificity increased to 98% with all masses correctly characterized as benign or malignant (Metser et al., 2006). While in 50 patients with known or suspected malignancy, ¹⁸F-FDG-PET had a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%, and by using the liver as a ‘normal’ comparison tissue it improved the sensitivity of ¹⁸F-FDG for detecting malignant adrenal lesions without sacrificing sensitivity (Yun et al., 2001). More recently ¹⁸F-FDG-PET was shown in a prospective multicenter trial to accurately differentiate adrenocortical adenomas from adrenal carcinomas and in particular a subgroup of masses with indeterminate findings on CT (Groussain et al., 2009).

 

In comparative studies of the 11β-hydroxylase inhibitor, ¹¹C-MTO, and ¹⁸F-FDG in incidentally-discovered masses, ¹¹C-MTO identified lesions of adrenocortical origin with the highest SUV in adrenocortical carcinoma, followed by hypersecretory adrenal cortical adenomas and non-hypersecretory adenomas, although ¹¹C-MTO-PET did not distinguish benign adrenocortical neoplasms from adrenocortical carcinoma (Hennings et al., 2006). ¹⁸F-FDG can be also used to image pheochromocytomas and adrenocortical carcinoma and to differentiate these neoplasms from other non-hypersecreting and most hypersecreting adrenal adenomas.

Figure 6. PET/CT scans of adrenal masses (white arrows). An ¹⁸F-FDG scan (panel A) shows no appreciable tracer accumulation in a left adrenal mass seen on CT (panel B) compatible with an adrenal adenoma. An adrenal metastasis from lung cancer (black arrows) is depicted on an ¹⁸F-FDG scan (panel C) as an intense focus of tracer uptake in a small left adrenal mass on CT (panel D).

 

Pheochromocytomas can be reliably imaged with ¹²³I- or ¹³¹I-MIBG with PET/CT using ¹⁸F-dopamine or ¹⁸F-DOPA (Shulkin et al., 2006) (Figure 7). In a comparison of the efficacy of ¹⁸F-FDA, ¹²³I-MIBG, and ¹¹¹In-octreotide, ¹⁸F-FDA demonstrated the highest sensitivity in the localization of intra-adrenal and metastatic pheochromocytomas, followed by ¹²³I-MIBG and ¹¹¹In-octreotide for intra-adrenal pheochromocytoma, while the efficacy of ¹⁸F-FDA and ¹²³I-MIBG were equivalent (Ilias et al., 2008). If catecholamine analogs are not successful in imaging, the neoplasm may have experienced malignant dedifferentiation, and ¹⁸F-FDG or ¹¹¹In-octreotide can be used to localize metastases and guide subsequent therapy.

 

Summary

Incidentally-discovered adrenal masses are commonly encountered in modern high-resolution imaging. The list of differential diagnostic possibilities of incidentally-discovered adrenal masses is large, but fortunately, most are benign and non-hyperfunctioning adenomas. The first consideration in the evaluation of an incidentally-discovered adrenal mass is its functional status and should include a biochemical evaluation sufficient to exclude clinically-silent endocrine disease. CT, MRI, and scintigraphy can be used to characterize incidentally-discovered adrenal masses and distinguish adrenal adenomas from metastases to the adrenals and other adrenal neoplasms. An understanding of the imaging techniques used to distinguish benign from malignant and other incidentally-discovered adrenal masses speeds diagnosis, optimizes therapy, and decreases costs in the evaluation of these neoplasms.

Figure 7. A small, left adrenal mass (arrow) on CT (panel A) demonstrates intense ¹⁸F-DOPA uptake (panel B) in a patient with hypertension and a prior negative ¹²³I-MIBG scan who was later shown to have elevated catecholamines compatible with a pheochromocytoma.

 

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Boland GW. Blake MA. Hahn PF. Mayo-Smith WW. Incidental adrenal lesions: principles, techniques, and algorithms for imaging characterization. Radiology 249(3):756-75, 2008.

Caoili EM. Korobkin M. Francis IR. Cohan RH. Dunnick NR. Delayed enhanced CT of lipid-poor adrenal adenomas. Am J Roentgenol 175(5):1411-5, 2000.

Dunnick NR and Korobkin M. Imaging of adrenal incidentalomas: current status. Am J Roentgenol 179(3):559-68, 2002.

Gross MD, Korobkin M, Hussain H, Cho KJ, Bui C. “Adrenal Gland Imaging” Chapter 126. Endocrinology, 5^th Edition. JL. Jameson and LJ. Degroot, Eds. W.B. Saunders, Philadelphia, USA, pp. 2425-2453, 2005.

Gross MD, Avram A, Fig LM, Rubello D. Contemporary adrenal scintigraphy. European J Nucl Med Mol Imaging 34:547-57, 2007.

Gross MD, Korobkin M, Bou Assaly W, Dwamena B, Djekidel M. Contemporary imaging of incidentally discovered adrenal masses. Nat Rev Urol 6:363-73, 2009.

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[Discovery Medicine, Volume 9, Number 44, January 2010. Pre-published.]

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From http://www.discoverymedicine.com/Milton-D-Gross/2010/01/04/incidentally-discovered-adrenal-masses/

Laparoscopic management of adrenal lesions larger than 5 cm in diameter - Abstract

Monday, 11 January 2010

Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India.

Laparoscopic adrenalectomy remains a controversial procedure for large tumors. The incidence of adrenocortical carcinoma increases and technical difficulty of adrenalectomy increases as the size increases. We examined the outcome and complications of laparoscopic adrenalectomy for such lesions.

 

Twenty-nine patients underwent laparoscopic adrenalectomy, of whom 19 had tumors larger than 5 cm in diameter, having a median tumor size of 7.0 cm. They were compared with patients whose adrenal tumors were smaller than 5 cm.

 

Patients with small tumors (< 5 cm) had a significantly shorter median operative time of 90 minutes as compared to 145 minutes in those with large tumors (> 5 cm). There was no significant difference in the median hemoglobin drop (1.05 g/dL versus 1.30 g/dL), time for starting oral intake (24 hours in both groups) or hospital stay (3.5 days versus 4.0 days) between patients with small and large tumors, respectively. There were no intra-operative complications except for 1 incidence of supraventricular tachycardia in a patient with a large pheochromocytoma. There were no major complications seen in any of the patients and no open conversions. Histopathology of large tumors revealed 16 benign tumors (8 pheochromocytomas, 4 adenomas, 2 ganglioneuromas, 1 pseudocyst, and 1 myelolipoma) and 3 malignancies, of which 1 was primary adrenocortical carcinoma and 2 were metastatic renal cell carcinoma.

 

In experienced hands, laparoscopic adrenalectomy is safe and feasible for large functioning adrenal tumors. Large adrenal tumors suspicious of harboring malignancy with no peri-adrenal involvement can be tackled laparoscopically.

 

Written by:
Sharma R, Ganpule A, Veeramani M, Sabnis RB, Desai M.   Are you the author?

 

Reference:
Urol J. 2009 Fall;6(4):254-9.

PubMed Abstract
PMID:20027553

UroToday.com Adrenal and Retroperitoneum Section

 

From http://www.urotoday.com/57/browse_categories/adrenal_and_retroperitoneum/laparoscopic_management_
of_adrenal_lesions_larger_than_5_cm_in_diameter__abstract01112010.html

Diagnosis and Treatment of Adrenal Tumors: A Single-Center Experience with 238 Cases

Abdul-Monem Gomha, Yasser Osman, Mohsen El-Mekresh, Mohamed Abou El-Ghar, Ibrahim Eraky
Urology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

Address of Corresponding Author

Urol Int 2009;83:433-437 (DOI: 10.1159/000251184)

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 Key Words

• Adrenal mass
• Adrenalectomy

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 Abstract

Objective: It was the aim of this study to review and analyze clinical data on the diagnosis and management of patients with adrenal masses.

 

Patients and Methods: Between 1976 and 2005, 238 patients admitted to our institute with adrenal masses were reviewed. Incidence, clinical features, imaging technique findings, surgical approaches, morbidity and mortality, as well as pathological diagnoses were reported.

 

Results: The series comprised 134 males and 104 females (mean age 33.3 ± 20.3 years). Right-sided masses were more common (63.4%), with a mean size of 7.7 ± 4 cm. Pain was the most frequent presenting symptom (53.4%), while 62 (26%) had a functional tumor. Incidentaloma was diagnosed in 49 patients (20.6%). Both computed tomography and magnetic resonance imaging showed a high diagnostic yield (sensitivities of 98.9 and 100%, respectively). Open adrenalectomy was performed in 153 patients (64.3%), while a laparoscopic approach was employed in 53 patients (22.3%). The intraoperative complication rate was 14.7%, the postoperative complication rate 6.1% and perioperative mortality 1.7%. Most of the excised masses were pheochromocytomas (26.4%). Conclusions: Computed tomography is recommended as the first diagnostic modality to define and characterize adrenal masses. Laparoscopic adrenalectomy is currently replacing open surgery as the standard surgical management of adrenal masses.

Copyright © 2009 S. Karger AG, Basel

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 Author Contacts

Yasser Osman, MD
Urology and Nephrology Center
Mansoura University
Mansoura (Egypt)
Tel. +20 50 226 2222, Fax +20 50 226 3717, E-Mail y_osman99@yahoo.com

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 Article Information

Received: October 20, 2008
Accepted: December 9, 2008
Published online: December 08, 2009
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 3, Number of References : 20

 

From http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=251184&Ausgabe=253627&ProduktNr=224282

ACTH-producing pheochromocytoma: Clinical considerations and concise review of the literature

M.F. Nijhoffab, O.M. Dekkersac, L.J. Vlemingb, J.W.A. Smita, J.A. Romijna, A.M. Pereiraa

Received 5 May 2009; received in revised form 9 July 2009; accepted 10 August 2009. published online 01 September 2009.

Abstract

We present a patient with a rare cause of ectopic ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma. The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent Cushing's syndrome. It clearly demonstrates that the relative contributions of clinical, biochemical, and radiological clues in establishing the correct underlying cause of Cushing's syndrome may differ considerably between Cushing's disease and Cushing's syndrome due to ectopic overproduction of ACTH. In addition, the literature concerning ACTH-producing pheochromocytomas is reviewed.

 

Keywords: Pheochromocytoma, Adrenocorticotropic hormone, Cushing's syndrome, ACTH syndrome, Ectopic

a Department of Endocrinology & Metabolism, C4-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands

b Department of Internal Medicine, HAGA, location Leyenburg, Leyweg 2752545 CH the Hague, The Netherlands

c Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

Corresponding author. Tel.: +31 71 6263082; fax: +31 71 524 8146.

PII: S0953-6205(09)00159-9

doi:10.1016/j.ejim.2009.08.002

© 2009 European Federation of Internal Medicine. Published by Elsevier Inc All rights reserved.

 

From http://www.ejinme.com/article/PIIS0953620509001599/abstract?rss=yes