Spironolactone-reversible rickets associated with 11β-hydroxysteroid dehydrogenase deficiency syndrome

Batista, Marcelo C.; Mendonça, Berenice Bilharinho; Kater, Cláudio E.; Arnhold, Ivo Jorge Prado; Rocha, Antonino dos Santos; Nicolau, Wilian; Bloise, W

doi:10.1016/s0022-3476(86)80282-7

Cited by 31 publications

(16 citation statements)

References 15 publications

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“…In our report (90), all 14 patients studied had characteristic signs of a severe 11␤-HSD2 defect, which were consistent with patients reported worldwide (56,57,59,75,(88)(89)(90)(91)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111): birth weights were lower than in their unaffected sibs, and the patients were short, underweight, and hypertensive for age. Damage of one or more organs (kidneys, retina, heart, and central nervous system) because of hypertension was found in all of the patients except one.…”

Section: Biochemical Features Adrenal Steroidogenesis and Fetal Devesupporting

confidence: 89%

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

New

Wilson

1999

Proc. Natl. Acad. Sci. U.S.A.

147

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Our research team and laboratories have concentrated on two inherited endocrine disorders, congenital adrenal hyperplasia (CAH) and apparent mineralocorticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficiency (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21-OHD, is the most common autosomal recessive disorder in humans, and occurs in 1͞27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified that cause both classical and nonclassical CAH. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre-and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11␤-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-renin hypertension.

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Section: Biochemical Features Adrenal Steroidogenesis and Fetal Devesupporting

confidence: 89%

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

New

Wilson

1999

Proc. Natl. Acad. Sci. U.S.A.

147

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“…Apparent mineralocorticoid excess is caused by a deficiency of 11β-hydroxysteroid dehydrogenase, the enzyme responsible for the interconversion of hormonally active cortisol into inactive cortisone [80]. Bone disease was reported in two affected cases, possibly as a result of increased mineralocorticoid activity [81,82].…”

Section: Mineralocorticoidsmentioning

confidence: 99%

Steroid hormone receptor expression and action in bone

BLAND

2000

Clinical Science

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The skeleton is a complex tissue, and hormonal control of bone remodelling is elaborate. The important role that steroid hormones play in bone cell development and in the maintenance of normal bone architecture is well established, but it is only relatively recently that it has become possible to describe their precise mechanism of action. This review focuses not only on the steroid hormones (oestrogens, corticosteroids, androgens and progesterone), but also on related hormones (vitamin D, thyroid hormone and the retinoids), all of which act via structurally homologous nuclear receptors that form part of the steroid/thyroid receptor superfamily. By examining the actions of all of these hormones in vivo and in vitro, this review gives a general overview of the current understanding of steroid hormone action in bone. In addition, a comprehensive review of steroid hormone receptor expression in bone cells is included. Finally, the role that future developments, such as steroid hormone receptor knockout mice, will play in our understanding of steroid hormone action in bone is considered.

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“…Mineralocorticoids were previously shown to induce hypercalcuria (37). The occurrence of hypercalcuria in the syndrome of apparent mineralocorticoid excess is suggested by the high incidence of nephrocalcinosis in previous reports (3,(38)(39)(40) and in patient E. A relationship between hypercalcuria, demineralization, and mineralocorticoid excess was demonstrated in a child with the type 1 variant of the syndrome and rickets (41). Spironolactone was effective in correcting the hypertension and hypokalemic alkalosis as well as the hypercalcuria and also led to healing of the rickets and resumption of linear growth.…”

Section: Mineralocorticoids and Calcium Balancementioning

confidence: 73%

“…There has been ample confirmation of the clinical and biochemical features of the type 1 variant (3,18,40,41,(46)(47)(48)51). Of the earlier cases (38,52,53), by clinical criteria two (38) were subsequently defined biochemically (18), and one (52) was attributed to a gas chromatographic peak considered to represent an unknown steroid.…”

Section: Incidencementioning

confidence: 98%

Pathogenesis of the Type 2 Variant of the Syndrome of Apparent Mineralocorticoid Excess*

Ulick

Tedde

Mantero

1990

The Journal of Clinical Endocrinology & Metabolism

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The syndrome of apparent mineralocorticoid excess, which is not a primary disorder of the adrenal cortex, describes the association of an unexplained hypermineralocorticoid state with a decreased rate of peripheral 11 beta-hydroxydehydrogenation of cortisol to cortisone. Studies in this syndrome have led to the hypothesis that peripheral cortisol inactivation is the normal mechanism permitting specific mineralocorticoid recognition. This view reconciled developing evidence that the mineralocorticoid receptor itself could not distinguish between mineralocorticoids and glucocorticoids. The syndrome occurs in two forms. In both forms there is decreased turnover of a normal level of plasma cortisol, consistent with the view that delayed removal of the glucocorticoid from strategic receptor sites unmasks its potential mineralocorticoid agonism. In the type 1 variant, impaired 11 beta-hydroxydehydrogenation is reflected by an elevated cortisol/cortisone metabolite ratio. In three patients with the type 2 variant, this ratio was normal, suggesting that the rate of 11 beta-hydroxydehydrogenation was unimpaired. The hypertension and hypokalemic alkalosis of both forms are improved by spironolactone, but patients with the type 2 variant have responded somewhat better to the suppression of cortisol by dexamethasone.

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Spironolactone-reversible rickets associated with 11β-hydroxysteroid dehydrogenase deficiency syndrome

Cited by 31 publications

References 15 publications

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

Steroid hormone receptor expression and action in bone

Pathogenesis of the Type 2 Variant of the Syndrome of Apparent Mineralocorticoid Excess*

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