Elsevier

The Lancet

Volume 353, Issue 9161, 17 April 1999, Pages 1341-1347
The Lancet

Seminar
Mineralocorticoid hypertension

https://doi.org/10.1016/S0140-6736(98)06102-9Get rights and content

Summary

Hypertension with hypokalaemia and suppression of plasma renin activity is known as mineralocorticoid hypertension. Although mineralocorticoid hypertension accounts for a small number of patients labelled as having “essential” hypertension, it is a potentially reversible cause of high blood pressure. The most common cause of mineralocorticoid hypertension is probably primary aldosteronism; controlled posture studies to measure plasma renin activity and aldosterone concentrations, followed by adrenal imaging, will ensure the differential diagnosis between an aldosterone-producing adenoma and idiopathic adrenal hyperplasia in most cases. Three monogenic forms of mineralocorticoid hypertension have been described: glucocorticoid-suppressible hyperaldosteronism, Liddle's syndrome, and apparent mineralocorticoid excess, which have provided new insights into mineralocorticoid hormone action. Many patients with mineralocorticoid-based hypertension are now known to have normal serum potassium concentrations. Until the true prevalence of primary aldosteronism and monogenic forms of mineralocorticoid hypertension are defined, a high index of suspicion is needed in every hypertensive patient. Hypertensive patients with hypokalaemia, together with those with severe hypertension or a family history of hypertension or stroke, should be screened for mineralocorticoid excess.

Section snippets

Mineralocorticoid secretion and hormone action

Adrenal corticosteroids are classified as mineralocorticoid or glucocorticoid. Both types of hormone are secreted from the adrenal cortex-glucocorticoids in large amounts (cortisol 10–20 mg daily) from the zona fasciculata, mineralocorticoids in small amounts (aldosterone 100–150 μg daily) from the zona glomerulosa. In normal physiology, aldosterone secretion is principally controlled by the renin-angiotensin system and stimulates sodium transport across epithelial cells in the distal nephron,

Primary aldosteronism

First described by Conn,11 primary aldosteronism is likely to be the most common cause of mineralocorticoid hypertension. Prevalence rates of 0·5-2·0% have been reported in unselected patients with essential hypertension,12 but many of these studies relied on detection of hypokalaemia and underestimated true prevalence rates. By contrast, studies in specialist centres showed high prevalence rates of 5–12% in hypertensive populations,13 but these studies were subject to selection bias.

Symptoms

Monogenic hypertension

Hypertension is a phenotype of some well-documented gene mutations. 17α-hydroxylase deficiency and 11β-hydroxylase deficiency are forms of congenital adrenal hyperplasia in which mineralocorticoid excess occurs because of corticotropin-driven deoxycorticosterone excess. A similar process is thought to explain hypertension in patients with glucocorticoid resistance due to mutations in the glucocorticoid-receptor gene (panel). More recently, a significant advance in understanding of the molecular

Diagnosis of mineralocorticoid-based hypertension

Wherever possible, an explanation of the underlying basis of a patient's hypertension should be sought, so that appropriate therapy can be given. At present, the incidence of primary aldosteronism, glucocorticoid-suppressible hyperaldosteronism, Liddle's syndrome, and apparent mineralocorticoid excess in unselected community-based rather than hospital-based populations of patients with essential hypertension is unknown. Until this incidence is known, the decision on who should and should not be

References (65)

  • JL Arriza et al.

    Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor

    Science

    (1987)
  • JW Funder et al.

    Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated

    Science

    (1988)
  • JB Ferriss et al.

    Clinical, biochemical and pathological features of low renin (“primary”) hyperaldosteronism

    Am Heart J

    (1978)
  • RC Tarazi et al.

    Haemodynamic characteristics of primary aldosteronism

    N Engl J Med

    (1973)
  • JW Funder et al.

    Vascular type 1 aldosterone binding sites are physiological mineralocorticoid receptors

    Endocrinology

    (1989)
  • L Kornel

    Colocalization of 11β-hydroxysteroid dehydrogenase and mineralocorticoid receptors in cultured vascular smooth muscle cells

    Am J Hypertens

    (1994)
  • BR Walker et al.

    Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man

    Clin Sci (Colch)

    (1992)
  • ME Ullian et al.

    Carbenoxolone damages endothelium and enhances vasoconstrictor action in aortic rings

    Hypertension

    (1996)
  • EP Gomez-Sanchez et al.

    Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone

    Am J Physiol

    (1992)
  • JW Conn

    Primary aldosteronism, a new clinical entity

    J Lab Clin Med

    (1955)
  • JO Lund et al.

    Prevalence of primary aldosteronism

    Acta Med Scand

    (1981)
  • RD Gordon et al.

    High incidence of primary aldosteronism in 199 patients referred with hypertension

    Clin Exp Pharmacol Physiol

    (1994)
  • WF Young

    Primary aldosteronism: update on diagnosis and treatment

    Endocrinologist

    (1997)
  • K Hiramatsu et al.

    A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity

    Arch Intern Med

    (1981)
  • TJ McKenna et al.

    Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary aldosteronism

    J Clin Endocrinol Metab

    (1991)
  • MH Weinberger et al.

    The diagnosis of primary aldosteronism and separation of two major subtypes

    Arch Intern Med

    (1993)
  • L Barzon et al.

    Incidentally discovered adrenal tumours: endocrine and scintigraphic correlates

    J Clin Endocrinol Metab

    (1998)
  • EA White et al.

    Use of computed tomography in diagnosing the cause of primary aldosteronism

    N Engl J Med

    (1980)
  • MD Gross et al.

    Scintigraphic localisation of adrenal lesions in primary aldosteronism

    Am J Med

    (1984)
  • RG Fontes et al.

    Reassessment of the predictive value of the postural stimulation test in primary aldosteronism

    Am J Hypertens

    (1991)
  • WF Young et al.

    Primary aldosteronism: adrenal venous sampling

    Surgery

    (1996)
  • M Gagner et al.

    Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures

    Ann Surg

    (1997)
  • Cited by (161)

    • The adrenal gland in stress – Adaptation on a cellular level

      2019, Journal of Steroid Biochemistry and Molecular Biology
      Citation Excerpt :

      Furthermore, they express the aldosterone synthetase CYP11B2, which converts corticosterone to aldosterone [24,25]. Aldosterone, which is synthesized under the control of the renin angiotensin-aldosterone system (RAAS), is the most potent mineralocorticoid involved in maintenance of water and sodium homeostasis and subsequently blood pressure adjustments [26]. The zF is comparatively bigger than the zG, and the zF cells are larger and less densely packed than the zG cells with a highly abundant smooth ER.

    • Glucocorticoid metabolism and activation

      2018, Encyclopedia of Endocrine Diseases
    • Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system

      2015, Brain Research
      Citation Excerpt :

      One-way ANOVA revealed no significant changes in BDNF levels in the hippocampus of the clonidine treated rats. In the present study, the authors used the DOCA salt-induced hypertension model, a mineralocorticoid-based model of hypertension in rats which mimics "essential" hypertension in the clinical setting (Stewart, 1999; Hacioglu et al., 2003). The SBP, right kidney weight, heart weight and the heart index in DOCA salt-induced hypertensive rats were found to be significantly increased when compared to the sham operated group.

    • Primary Mineralocorticoid Excess Disorders and Hypertension

      2015, Endocrinology: Adult and Pediatric
    View all citing articles on Scopus
    View full text