I. Adrenal Background Information

The Adrenal

The adrenal gland is made up of two main compartments: the outer cortex and the inner medulla, both of which are encased in the adrenal capsule.

The outer cortex is made up of 3 zones, which are defined by their role in adrenal steroidogenesis.

  • Zona Glomerulosa (ZG) is the outer most zone, closest to the capsule.

  • Zona Fasciculata (ZF) is the middle zone.

  • Zona Reticularis (ZR) is the inner most zone, closest to the medulla.


The steroids that classify the zones of the adrenal cortex are the result of the segregated expression of steroidogenic enzymes and cofactors.

  • The ZG synthesizes the mineralocorticoid aldosterone.

  • The ZF produces the glucocorticoid cortisol.

  • The ZR produces adrenal-derived androgens and precursors.

Angiotensin II is the major agonist for the ZG, while adrenocorticotropic hormone (ACTH) is the primary stimulus for the ZF and ZR.

II. Adrenal Disorders

Primary Aldosteronism (PA)

PA is defined as inappropriately elevated aldosterone production in the setting of low plasma renin. PA is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist.

PA commonly presents itself as:

  • Aldosterone Producing Adenoma (APA)

  • Bilateral Hyperaldosteronism (BHA)

APA is a tangible form of disease and can be seen as nodules on the adrenal, while BHA is an elusive concept, which has lacked a pathophysiological mechanism for many years.

Congenital Adrenal Hyperplasia (CAH)

CAH is a term used collectively for a group of autosomal recessive genetic defects in cortisol biosynthesis.

  • 21-hydroxylase (CYP21A2) deficiency (21OHD) is the most common form of CAH, accounting for more than 90% of all CAH cases. Based on the presence or absence of cortisol insufficiency, diagnosis of 21OHD is routinely classified into classic and nonclassic forms, respectively.

  • Impaired cortisol production relieves negative feedback to the hypothalamus and the pituitary gland, which in response amplify the secretion of corticotropin-releasing hormone (CRH) and ACTH, respectively, resulting in hyperplasia of the adrenal cortex.

III. Adrenal Research

Adrenal Vein Sampling (AVS)

AVS is required to distinguish unilateral from bilateral aldosterone sources in primary aldosteronism, and cortisol is used for AVS data interpretation, but cortisol has several pitfalls. We are working to explore the utility of several other steroids in PA subtyping, both during AVS, as well as in peripheral serum. We have found 11β-hydroxyandrostenedione and 11-deoxycortisol to be superior to cortisol for AVS data interpretation. Single assay multi-steroid panels measured in peripheral serum are helpful in stratified PA subtyping and have the potential to circumvent AVS in a subset of patients with PA.

Turcu lab research is funded by :

Primary Aldosteronism Subtypes: Pathophysiology and Steroid Signatures

Project Number 1R01HL155834-01

The contemporary endocrinology of congenital adrenal hyperplasia

Project Number 5K08DK109116-02