Pathophysiology of Deoxycorticosterone-Secreting Adrenal Tumors*

Abstract

Two patients with hypermineralocorticoidism due to deoxycorticosterone (DOC) excess are described. The plasma 17-deoxysteroids of the zona fasciculata (ZF), namely DOC, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycorticosterone, were elevated. Plasma androgen concentrations were normal, and plasma aldosterone and renin levels were low. One patient, who had benign adrenocortical adenoma, had normal plasma cortisol levels. The other patient, who had metastatic adrenocortical carcinoma, had low plasma cortisol, presumably due to elevated plasma corticosterone levels. While tumors producing only 17-deoxysteroids are rare, they have provided new insights into the regulation of 17-deoxysteroid secretion by the ZF. Presumptive suppression of a non-ACTH factor by adenoma-produced DOC transiently impaired the early postoperative responses to ACTH of the ZF 17-deoxysteroids of the contralateral adrenal. The dissociation of 17-deoxysteroids from cortisol in normal subjects given either dexamethasone or DOC acetate provides additional evidence for such a factor.

A Case of Deoxycorticosterone-Producing Benign Adrenocortical Tumor

“…Excessive DOC is found in patients with 11 P-hydroxylase deficiency and 17a-hydroxylase deficiency syndromes and in those with DOC-producing tumors [6]. In this patient we excluded the 17a-hydroxylase defi ciency syndrome because her menstrual cycles were reg ular and sexual maturation was normal [7], Kondo et al [4] described a DOC-producing adrenal adenoma as being adrenocorticotropin-dependent.…”

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

“…Exceptions include patients who are habitually ingesting a low-sodium diet or receiving medications that can bring about increased renin production (see below and TABLE 1), or have "accelerated" or malignant hypertension (42,256,356), or concomitant renovascular hypertension (498). Lack of specificity, however, results from the possibility that renin levels may also be suppressed because of 1) treatment with agents (including ␤-adrenoceptor blockers, clonidine, or ␣-methyldopa) which reduce ␤-sympathetic stimulation of renin release (10,62,196,387) or with nonsteroidal anti-inflammatory agents which promote salt retention (331); 2) high dietary sodium intake (198); 3) the gradual fall in renin that occurs as renal function declines with advancing age (105, 301); 4) chronic renal impairment, in which renal reninproducing capacity is reduced and salt-retention contributes to renin suppression (324); and 5) the presence of other salt-dependent, low renin forms of hypertension (22,180,200,242,258,480,549,552,558,567). Among the latter conditions are 1) Liddle syndrome, caused by activation mutations of ENaC (552); 2) congenital or acquired (for example, through carbenoxolone administration or ingestion of licorice) deficiency of 11␤-HSD2, which permits cortisol to gain access to and activate the MR (480); 3) hypertensive forms of congenital adrenal hyperplasia caused by mutations in either the 11␤-hydroxylase or 17␣-hydroxylase genes, which bring about reductions in cortisol production, leading to feedback stimulation of ACTH, which in turn causes increased production of the mineralocorticoid deoxycorticosterone (DOC) (258, 558); 4) primary glucocorticoid resistance, which is again associated with ACTH simulation and excessive DOC production (22); 5) ectopic ACTH syndrome, in which mineralocorticoid hypertension is thought to result from a combination of DOC excess and "overload" of the 11␤HSD2 enzyme by very high levels of cortisol (549); 6) DOC-secreting tumors (242); 7) activating mutations of the MR (180); and 8) familial hyperkalemic hypertension (200), in which mutations in genes (WNK1, WNK4, CUL3, and KLCH3) regulating the NCC within the distal renal tubule are thought to lead to its activation and excessive retention of sodium and potassium (56,187,567).…”

11-Deoxycorticosterone-Producing Adrenocortical Carcinoma

“…DOC-producing tumors cause primary aldosteronism-like symptoms, show low plasma aldosterone but very high DOC levels. The DOC-producing tumor is very rare; to our knowledge since the first case was reported in 1974 [2], only 20 cases including the present case have appeared in the literature [3][4][5]. Of these, 8 cases were asymptomatic and the tumors were found by chance at medical checkups.…”