Molecular Pathology of Endocrine Diseases (eBook)

General Endocrine Molecular Pathology.- Molecular Oncogenesis.- Systematic Autoimmune Diseases.- MicroRNAs in Endocrine Diseases.- Thyroid Diseases.- Clinical Detection and Treatment of Thyroid Diseases.- Autoimmune Thyroid Diseases.- Benign Nodular Thyroid Disease.- Fine Needle Aspiration: Present and Future.- Well-Differentiated Papillary Thyroid Carcinoma.- Well-Differentiated Thyroid Follicular Carcinoma.- Poorly Differentiated and Undifferentiated Thyroid Carcinomas.- Medullary Thyroid Carcinoma.- Unusual Thyroid Tumors.- Hematopoietic Tumors of the Thyroid.- Parathyroid Diseases.- Clinical Detection and Treatment of Parathyroid Diseases.- Nonneoplastic Parathyroid Diseases.- Neoplastic Parathyroid Diseases.- Pituitary Diseases.- Clinical Detection and Treatment of Benign and Malignant Pituitary Diseases.- Nonneoplastic and Neoplastic Pituitary Diseases.- Adrenal Diseases.- Clinical Detection and Treatment of Adrenal Disease.- Benign and Malignant Pheochromocytomas and Paragangliomas.- Benign and Malignant Diseases of the Adrenal Cortex.- Pancreatic Neuroendocrine Tumors.- Clinical Detection and Treatment of Pancreatic Neuroendocrine Tumors.- Pancreatic Endocrine Neoplasms.- Other Neuroendocrine Lesions.- Gastrointestinal Neuroendocrine Tumors.- Head and Neck Neuroendocrine Tumors.- Merkel Cell Carcinoma.- Neuroendocrine Lung Tumors.

"Section 5 Adrenal Diseases (p. 196-197)

19 Clinical Detection and Treatment of Adrenal Disease

Adrian M. Harvey, Allan A. Siperstein, and Eren Berber

Introduction

Diagnosis and treatment of patients with adrenal lesions is both challenging and fascinating owing to the wide range of biologically important compounds produced by these small glands. Tumors of the adrenal cortex may produce mineralocorticoids, glucocorticoids, sex steroids or in specific cases, combinations of these. Tumors of the adrenal medulla may produce catecholamines and other related compounds making them particularly challenging to diagnose and treat. Malignant disease of the adrenal glands may also be hormonally active.

In this chapter, we review the work-up and treatment of benign, functional masses and malignant diseases of the adrenal cortex and medulla. The appropriate application and interpretation of biochemical and imaging tests in the setting adrenal disease are explored. The role of laparoscopic and open surgery and the outcomes in benign and malignant disease are also presented. In addition, medical therapies and their role in the preoperative and postoperative setting or as primary treatment of adrenal disease are touched on.

Hypercortisolism: Work-Up

The clinical manifestations of Cushings Syndrome (CS) include centripetal obesity, rounded face, abdominal striae, and muscle weakness.1 More recently however, the term Sub-Clinical Cushing’s (SCC) has been used to describe patients with adrenal incidentalomas, autonomous cortisol production but more subtle clinical and laboratory abnormalities including hypertension, impaired glucose tolerance, osteoporosis, depression and renal stones.2 If these patients are followed, approximately 12.5% will develop overt CS by 1 year.

The differential diagnosis of endogenous CS can be divided into ACTH dependent and independent causes. Overall, 80% of the patients will have an ACTH dependent etiology.1 Most of these will have a pituitary adenoma, (80%), producing ACTH with the remainder having an ectopic source.1 Tumors associated with ectopic ACTH production include small cell lung cancer, thymic and bronchial carcinoids, medullary thyroid cancer, pheochromocytoma, and pancreatic islet cell tumors.4 Those patients with ACTH independent CS have a primary adrenal source of cortisol production, with the two most common being unilateral adenoma, (60%) and adrenal cortical carcinoma, (40%).4 Rare causes include bilateral macronodular hyperplasia, primary pigmented nodular adrenal disease, and McCune–Albright Syndrome.

The incidence of endogenous CS is 1–2 per million per year.5 Patients with overt signs and symptoms of CS and those with adrenal incidentalomas should undergo screening tests. In addition, screening should be strongly considered in patients with osteoporosis, and poorly controlled diabetes as these populations are known to have a disproportionately high prevalence of this syndrome. Commonly utilized screening methods include 24-h urinary free cortisol and dexamethasone suppression tests.

Urinary measurements over four times the upper limit of normal are almost always indicative of CS.6 Pseudo-Cushing’s states such as depression, alcoholism, and chronic illness may produce lesser elevations. Other potential methods for the diagnosis of CS include an unsuppressed AM cortisol and late-night/midnight salivary. Salivary cortisol has received increasing attention because of its noninvasive nature and ease of repeating the test. Reference values are laboratory dependent, but the test has demonstrated sensitivity and specificity in excess of 90%.1,7 This test can be repeated up to three times when the index of suspicion is high as intermittent over-production may be missed.

Low dose dexamethasone suppression tests work on the principle that the hypothalamic–pituitary–adrenal (HPA) regulation is dysfunctional in patients with CS. Following administration of 1 mg of dexamethasone at 23:00, morning values less than 50 nmol/L, are considered normal.6 A 2-day, 2 mg form of the low dose suppression test is also used for screening purposes in some centers. Once the diagnosis has been made, measurement of serum"