Long term treatment of mineralocorticoid excess syndrome
Division of Endocrinology, University of Padua, Italy. Steroids
(Impact Factor: 2.64).
02/1995; 60(1):81-6. DOI: 10.1016/0039-128X(94)00018-8
Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here present the results of a prolonged clinical follow-up (from 1 to 20 years) of a large number of patients with mineralocorticoid excess syndromes (MES), including over 100 patients with primary aldosteronism (PA), 3 cases with dexamethasone-suppressible aldosteronism (DSA), 3 cases of apparent mineralocorticoid excess (AME) Type II, and 4 patients with 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 1982, and the second of 37 patients studied between 1983 and 1992; 33 further cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, 1 primary hyperplasia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hypertension. Forty-three patients with either adenoma (APA) or idiopathic aldosteronism (IHA) received long-term spironolactone treatment. Among them, 13 required the addition of thiazide and/or beta-blockers, while 13 were switched to an amiloride/thiazide combination (+/- beta blockers) due to side-effects to spironolactone (gynecomastia 6/20 males, menstrual upset or breast pain in 7/23 females). In group II, 12 patients underwent surgery (11 adenoma, 1 primary hyperplasia) with a similar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (11) or Ca++ channel blockers (14) with or without KCl supplementation; in 8 cases these two drugs were combined according to blood pressure levels achieved during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Available from: Paolo Ferrari
- "The disease is inherited as an autosomal recessive trait, and various mutations in the HSD11B2 gene have subsequently been shown to cause 11βHSD2 deficiency. Signs and symptoms of the syndrome can be partially or fully reversed by treatment with the MR-antagonist spironolactone [4,575859 or kidney transplantation , evidence for the crucial role of the renal 11βHSD2 in MR protection [26,27]. Normally plasma cortisol levels are in the sub-micromolar range, while aldosterone levels are sub-nanomolar; even in 11βHSD protected cells intracellular levels of glucocorticoid are ∼10 × those of aldosterone . "
[Show abstract] [Hide abstract]
ABSTRACT: Cortisol and aldosterone have the same in vitro affinity for the mineralocorticoid receptor (MR), although in vivo only aldosterone acts as a physiologic agonist of the MR, despite circulating levels of cortisol in humans and corticosterone in rodents being three orders of magnitude higher than aldosterone levels. In mineralocorticoid target organs the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) inactivates 11-hydroxy steroids, to their inactive keto-forms, thus protecting the nonselective MR from activation by glucocorticoids. The gene is highly expressed in all sodium-transporting epithelia, particularly in the kidney and colon, but also in human placenta and vascular wall. Mutations in the HSD11B2 gene cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, compromised 11βHSD2 enzyme activity results in activation of the MR by cortisol, causing sodium retention, hypokalaemia, and salt-dependent hypertension. Whereas mutations or inhibition of 11βHSD2 by licorice have been clearly shown to produce a congenital or acquired syndrome of mineralocorticoid excess, the questions remaining are the extent to which subtle abnormalities in MR/11βHSD2 mechanisms may contribute to essential hypertension. Studies in patients with essential hypertension showed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites, suggesting a deficient 11βHSD2 activity. These abnormalities may be genetically determined, as suggested by the association of a microsatellite flanking the HSD11B2 gene with hypertension in black patients with end-stage kidney disease and with salt sensitivity of blood pressure in healthy subjects. These findings indicate that variants of the HSD11B2 gene may contribute to the enhanced blood pressure response to salt and possibly to hypertension in humans.
Available from: Vasilios Gabriel Athyros
- "It is apparent that laparoscopic adrenalectomy alone is not sufficient to achieve BP control in a significant proportion of patients. In addition, surgery is not without risks (Mantero et al. 1995, Ghose et al. 1999). Therefore, long-term medical therapy might represent an attractive alternative approach for the treatment of PA. "
[Show abstract] [Hide abstract]
ABSTRACT: Primary aldosteronism (PA) and, in particular, its two commonest subtypes (i.e. idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA)) have been recognized as the most common cause of secondary hypertension. While 'conservative' medical treatment with aldosterone receptor antagonists is the therapeutic approach of choice in controlling blood pressure in patients with PA due to IHA, the more invasive (laparoscopic) adrenalectomy seems to be the most suitable therapy for patients with APA. In this review, we focus on the medical approach for the management of APA in cases where surgical excision of the adrenal is not possible.
Available from: tsim.org.tw
[Show abstract] [Hide abstract]
ABSTRACT: Background: 17α-hydroxylase deficiency is a rare cause of congenital adrenal hyperplasia and endocrine hypertension. Only around 124 cases were reported in literature. Case: A 35-year-old Taiwanese female presented with severe hypertension (220/130 mmHg), absence of secondary sexual characteristics and primary amenorrhea. Chromosome study revealed 46XX karyotye. The laboratory data revealed hypokalemia, suppressed plasma renin activity, low level of sex steroids with high gonadotropin, morning cortisol level: 1.8µg/dl and ACTH: 235 pg/ml. Her plasma level of aldosterone (sitting position) was at high level of normal (23.6 ng/dl). We made the diagnosis of 17α-hydroxylase deficiency. Plasma aldosterone level was suppressed in most of the reported ca-ses while normal or elevated levels were also described in a considerable number. Her uterus was found to be rudimentary, which was reported in only one genetic female case before. Conclusion: We report a case of 17α-hydroxylase deficiency in genetic female with normal le-vel of plasma aldosterone and rudimentary uterus. ( J Intern Med Taiwan 2002;13: 141-146 )
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.