Deoxycorticosterone (DOC)

Deoxycorticosterone (DOC) is a C-21 (21 carbon atoms) steroid hormone synthesized in the zona fasciculata (ZF) and zona glomerulosa (ZG) of the adrenal gland and is a precursor for the synthesis of cortisol and aldosterone (see the image below).

The reference range for DOC can be seen in the table below.

Table 1. Deoxycorticosterone Reference Range (Open Table in a new window)

 

DOC is an intermediate in the biosynthesis of the major corticosteroids and not a major adrenal secretory product. Therefore, elevated serum DOC levels are clinically important in only a few disease states that involve enzymatic deficiencies, generalized adrenal hyperfunction, or direct adrenal tumor production. Decreased serum DOC levels occur in enzymatic deficiencies “upstream” from DOC synthesis or generalized adrenal hypofunction.

Congenital adrenal hyperplasia (CAH) due to 11β-hydroxylase (CYP11B1) and 17α-hydroxylase deficiency

As a result of the enzymatic defects, the adrenocorticotropic hormone (ACTH) level increases because of the absence of the cortisol negative feedback; this increase in the ACTH leads to the accumulation of cortisol precursors proximal to the enzymatic deficiency. These precursors can be converted to adrenal androgen, leading to virilization in females and premature adrenarche in both genders. In the case of 11-hydroxylase and 17-hydroxylase deficiency, the cortisol precursor is DOC, which can act as a mineralocorticoid leading to low-renin hypertension and hypokalemia (see image below). For further reading, please see the Medscape Drugs & Diseases topic C-17 Hydroxylase Deficiency.

Clinical presentation

• CAH due to aldosterone synthase (CYP11B2) causes a decrease in aldosterone level without affecting cortisol levels.

• DOC-producing tumor may exist.

• Primary cortisol resistance syndrome, due to defects in glucocorticoid receptors and characterized by increases in ACTH, cortisol, and cortisol precursors (including DOC), can lead to hypertension and hypokalemia.

• Severe ACTH-dependent Cushing syndrome may exist.

• Levels may be elevated during pregnancy and the first week of life.

Serum DOC is decreased in the following:

• CAH due to 21-hydroxylase deficiency, 3-beta-steroid dehydrogenase deficiency, or steroidogenic acute regulatory protein (StAR) deficiency.

• Primary or secondary adrenal insufficiency

Patient instruction: No need for fasting, morning sample preferred

Collection tube: Red-top tube

Unacceptable conditions: Hemolyzed specimens

Specimen preparation: Separate serum from cells and transfer to transport tube.

Storage/transport temperature: Frozen

Stability: Refrigerated 7 days; frozen 14 days

Panels: None

Description

Deoxycorticosterone (DOC) is a C-21 (21 carbon atoms) steroid hormone synthesized in zona fasciculata (ZF) and zona glomerulosa (ZG) of the adrenal gland and is a precursor for the synthesis of cortisol and aldosterone (see the image below).

DOC is produced from progesterone under the effect of 21-hydroxylase (other name: 21-hydroxyprogesterone). ^{[1, 2, 3, 4]}

In the ZG, under the effect of aldosterone synthase (CYP11B2), DOC is converted to aldosterone through a process including other precursor (corticosterone and 18-hydroxycorticosterone); CYP11B2 gene transcription is under control of angiotensin II.

In the ZF, under the effect of the 17α-hydroxylase, DOC is converted to 11-deoxycortisol and then later is converted to cortisol by the 11β-hydroxylase (CYP11B1), an enzyme mainly available in the ZF that is under the effect of ACTH.

Although CYP11B1 and CYP11B2 share 95% homology, the former regulates the final steps in cortisol synthesis, whereas the latter regulates the final steps in aldosterone synthesis.

History

DOC was one of the earliest corticosteroids to be synthesized and later isolated from bovine adrenal glands (1938). Synthetic DOC acetate was the first corticosteroid shown to be effective in treating Addison disease.

Biologic activity

Authoritative texts dismiss DOC as a weak mineralocorticoid (MC) and negligible glucocorticoid (GC). The bulk of the evidence, however, supports the concept that DOC is a potent MC, which in excess, can produce sodium retention, low-renin hypertension, and kaliuresis. Although DOC binds less avidly to GC receptors than cortisol, it is an effective GC replacement in the treatment of Addison and postadrenalectomy patients.

Table 2. Relative Blood Levels, Production Rates, and Bioactivity of DOC, Aldosterone, and Cortisol (Open Table in a new window)

Indications/Applications

DOC should be measured in conjunction with other hormone as part of the work up for the following:

• Low renin hypertension

• CAH due to 11β-hydroxylase (CYP11B1)

• CAH due to aldosterone synthase (CYP11B2; not associated with low cortisol)

• Adrenocortical carcinoma

At birth, the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis are activated, and all adrenal steroids are high, including mineral corticoids and sex steroids and their precursors. In preterm infants, elevations can be even more pronounced due to illness and stress. In doubtful cases, when the initial test was performed on a just-born baby, repeat testing a few days or weeks later is advised.

Elevated serum DOC level is not diagnostic for any disease, and it should be measured with other hormones, including 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, and cortisol measurements.

Serum DOC level can be measured as part of the high-dose ACTH stimulation to confirm the presence of a mild cases of 11β-hydroxylase deficiency.

As discussed in a case report/literature review by Asla et al, the 11-deoxycorticosterone–producing adrenal lesion, a very rare entity taking the form of a tumor or hyperplasia, occurs most often in middle-aged women. The investigators state that it typically has a clinical presentation like that of primary aldosteronism, with patients frequently demonstrating high blood pressure, moderate to severe hypokalemia, and/or nonspecific symptoms—muscle weakness and paresthesia—primarily related to hypokalemia. Histologically, the study’s lesions most commonly existed as a carcinoma or an adenoma. ^[5]