Clinical Information

Corticosterone is a steroid hormone and a precursor molecule for aldosterone. It is produced from deoxycorticosterone, further converted to 18-hydroxycorticosterone, and ultimately to aldosterone in the mineralocorticoid pathway.

The adrenal glands, ovaries, testes, and placenta produce steroid hormones, which can be subdivided into 3 major groups: mineralocorticoids, glucocorticoids, and sex steroids. Synthesis proceeds from cholesterol along 3 parallel pathways, corresponding to these 3 major groups of steroids, through successive side-chain cleavage and hydroxylation reactions. At various levels of each pathway, intermediate products can move into the respective adjacent pathways via additional, enzymatically catalyzed reactions (see Steroid Pathways).

Corticosterone is the first intermediate in the corticoid pathway with significant mineralocorticoid activity. Its synthesis from 11-deoxycorticosterone is catalyzed by 11-beta-hydroxylase 2 (CYP11B2) or by 11-beta-hydroxylase 1 (CYP11B1). Corticosterone is in turn converted to 18-hydroxycorticosterone and finally to aldosterone, the most active mineralocorticoid. Both reactions are catalyzed by CYP11B2, which, unlike its sister enzyme CYP11B1, also possesses 18-hydroxylase and 18-methyloxidase (also known as aldosterone synthase) activity.

The major diagnostic utility of measurements of steroid synthesis intermediates lies in the diagnosis of disorders of steroid synthesis, in particular congenital adrenal hyperplasia (CAH). All types of CAH are associated with cortisol deficiency with the exception of CYP11B2 deficiency and isolated impairments of the 17-lyase activity of CYP17A1 (this enzyme also has 17 alpha-hydroxylase activity). In cases of severe illness or trauma, CAH predisposes patients to poor recovery or death. Patients with the most common form of CAH (21-hydroxylase deficiency, which accounts for >90% of cases), the third most common form of CAH (3-beta-steroid dehydrogenase deficiency, which accounts for<3% of cases), or the extremely rare StAR (steroidogenic acute regulatory protein) or 20,22 desmolase deficiencies may also suffer mineralocorticoid deficiency, as the enzyme blocks in these disorders are proximal to potent mineralocorticoids. These patients might suffer salt-wasting crises in infancy. By contrast, patients with the second most common form of CAH (11-hydroxylase deficiency, which accounts for <5% of cases) are normotensive or hypertensive, as the block affects either CYP11B1 or CYP11B2 but rarely both, thus ensuring that at least corticosterone is still produced. In addition, patients with all forms of CAH might suffer the effects of substrate accumulation proximal to the enzyme block. In the 3 most common forms of CAH, the accumulating precursors spill over into the sex steroid pathway, resulting in virilization of female patients or, in milder cases, hirsutism, polycystic ovarian syndrome, or infertility, as well as in possible premature adrenarche and pubarche in both sexes.

Measurement of the various precursors of mature mineralocorticoid and glucocorticoids, in concert with the determination of sex steroid concentrations, allows diagnosis of CAH and its precise type and serves as an aid in monitoring steroid replacement therapy and other therapeutic interventions.

Measurement of corticosterone is used as an adjunct to 11-deoxycorticosterone and 11-deoxycortisol (also known as compound S) measurement in the diagnosis of:

-CYP11B1 deficiency (associated with cortisol deficiency)

-The less common CYP11B2 deficiency (no cortisol deficiency)

-The rare glucocorticoid responsive hyperaldosteronism (where expression of the gene CYP11B2 is driven by the CYP11B1 promoter, thus making it responsive to corticotropin [previously adrenocorticotrophic hormone: ACTH] rather than renin)

-Isolated loss of function of the 18-hydroxylase or 18-methyloxidase activity of CYP11B2

For other forms of CAH, the following tests might be relevant:

21-Hydroxylase deficiency:

-OHPG / 17-Hydroxyprogesterone, Serum

-ANST / Androstenedione, Serum

-21DOC / 21-Deoxycortisol, Serum

3-Beta-steroid dehydrogenase deficiency:

-17PRN / Pregnenolone and 17-Hydroxypregnenolone, Serum

17-Hydroxylase deficiency or 17-lyase deficiency (CYP17A1 has both activities):

-17PRN / Pregnenolone and 17-Hydroxypregnenolone, Serum

-PGSN / Progesterone, Serum

-OHPG / 17-Hydroxyprogesterone, Serum

-DHEA_ / Dehydroepiandrosterone (DHEA), Serum

-ANST / Androstenedione, Serum

 Cortisol should be measured in all cases of suspected CAH.

When evaluating for suspected 11-hydroxylase deficiency, this test should be used in conjunction with measurements of 11-deoxycortisol, 11-corticosterone, 18-hydroxycorticosterone, cortisol, renin, and aldosterone.

When evaluating infants with positive newborn screening results for congenital adrenal hyperplasia, this test should be used in conjunction with 11-deoxycortisol and 11-deoxycorticosteorone measurements as an adjunct to 17-hydroxyprogesterone, aldosterone, and cortisol measurements.