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INTRODUCTION

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ACTH Adrenocorticotropic hormone
ADH Antidiuretic hormone (vasopressin)
AIRE Autoimmune regulator gene
APS Autoimmune polyendocrine syndrome
ARMC5 Armadillo-repeat containing 5
AVP Arginine vasopressin
BMAH Bilateral macronodular adrenal hyperplasia
CBG Corticosteroid-binding globulin
CRH Corticotropin-releasing hormone
DAX1 Dosage-sensitive sex reversal-adrenal hypoplasia gene product
DHEA Dehydroepiandrosterone
DOC Deoxycorticosterone
ELISA Enzyme-linked immunosorbent assay
GH Growth hormone
GIP Glucose-dependent insulinotropic peptide/Gastrointestinal inhibitory polypeptide
GnRH Gonadotropin-releasing hormone
HLA Human leukocyte antigen
HPA Hypothalamic-pituitary-adrenal
HPLC High-performance liquid chromatography
HSD Hydroxysteroid dehydrogenase
HSP Heat shock protein
ICMA Immunochemiluminometric assay
IL Interleukin
IPSS Inferior petrosal sinus sampling
IRMA Immunoradiometric assay
LC/MS/MS Liquid chromatography tandem mass spectroscopy
LH Luteinizing hormone
PMN Polymorphonuclear neutrophil
PRA Plasma renin activity
PRKACA Protein kinase A catalytic subunit
PRL Prolactin
PTH Parathyroid hormone
RANK Receptor activator of nuclear factor kappa B
SF-1 Steroidogenic factor-1a
SHBG Sex hormone–binding globulin
StAR Steroidogenic acute regulatory protein
TRH Thyrotropin-releasing hormone
TSH Thyroid-stimulating hormone (thyrotropin)
VLCFA Very long chain fatty acid

The adrenal cortex produces many steroid hormones of which the most important are cortisol, aldosterone, and the adrenal androgens. Disorders of the adrenal glands lead to classic endocrinopathies such as Cushing syndrome, Addison disease, hyperaldosteronism, and the syndromes of congenital adrenal hyperplasia. This chapter describes the physiology and disorders of the glucocorticoids and the adrenal androgens. Disorders of aldosterone secretion are discussed in Chapter 10 and congenital defects in adrenal hormone biosynthesis in Chapters 10 and 14. Hirsutism and virilization (which reflect excess androgen action) are discussed in Chapter 13.

Advances in diagnostic procedures have simplified the evaluation of adrenocortical disorders; in particular, the assay of plasma glucocorticoids, androgens, and adrenocorticotropin (ACTH) has allowed more rapid and precise diagnosis. Recent discoveries have also begun to elucidate the genetic basis for many disorders of the adrenal cortex, and advances in surgical and medical treatment have improved the outlook for patients with these disorders.

EMBRYOLOGY AND ANATOMY

Embryology

The adrenal cortex is of mesodermal origin and derives from a single cell lineage characterized by expression of certain transcription factors such as steroidogenic factor-1 (SF-1). At 2 months’ gestation, the cortex, already identifiable as a separate organ, is composed of a fetal zone and a definitive zone similar to the adult adrenal cortex. The adrenal cortex then increases rapidly in size; at mid gestation, it is considerably larger than the kidney and much larger than the adult gland in relation to total body mass. The fetal zone makes up the bulk of the weight of the adrenal cortex at this time. Several genes encoding transcription factors are important in adrenal development and differentiation. These include SF-1 and the product of the dosage-sensitive sex reversal–adrenal hypoplasia gene (DAX1), among others; mutations of the DAX1 gene are associated with congenital adrenal hypoplasia.

The fetal adrenal is under the control of ACTH ...

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