Exaggerated adrenarche and altered cortisol metabolism in Type 1 diabetic children

Remer, Thomas; Maser-Gluth, Christiane; Boye, Kai R; Hartmann, Michaela F.; Heinze, E.; Wudy, Stefan A.

doi:10.1016/j.steroids.2006.02.005

Cited by 35 publications

(45 citation statements)

References 48 publications

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“…Remer et al (17) described an increased urinary excretion of 6b-hydroxycortisol and a reduced 5a-reductase activity in lean children with type 1 diabetes. In our study, we found a higher urinary 5a-THF excretion and a higher relative 5a-reduction (5a-THF/F) in lean boys compared with lean girls.…”

Section: Discussionmentioning

confidence: 99%

“…The urinary steroid metabolite profile was analyzed using a gas chromatography-mass spectrometry (GC/MS) as previously reported (16,17), measuring free and conjugated F metabolites. Total cortisol metabolites (tetrahydrocortisone (THE), tetrahydrocortisol (THF), 5a-tetrahydrocortisol (5a-THF), a-cortolone, b-cortolone, a-cortol, and b-cortol) were used as an index of total cortisol excretion (18).…”

Section: Methodsmentioning

confidence: 99%

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Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys

Wiegand

Richardt²,

Wudy³

et al. 2007

eur j endocrinol

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Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11b-hydroxysteroid dehydrogenase type 1 enzyme (11b-HSD1) regenerates active cortisol from inactive cortisone. Altered 11b-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis. Design, patients, and methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis. Results: 11b-HSD1 activity (urinary tetrahydrocortisol (THF)C5a-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11b-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11b-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11b-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index. Conclusions: In conclusion, our findings strongly suggest that 11b-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys

Wiegand

Richardt²,

Wudy³

et al. 2007

eur j endocrinol

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“…Conversely, some investigators have defined PA very strictly as the biochemical detection of a premature increase in circulating adrenal androgens irrespective of the clinical presentation (52). The additional use of the term 'exaggerated adrenarche' has created further confusion, as it has been used to describe adrenal androgen levels above the pubertal range in children of pre-pubertal age (53,54) but also as a definition for the presence of exaggerated clinical features of androgen action associated with physiological, normal-timed adrenarche (55).…”

Section: Pa: Definitions and Differential Diagnosismentioning

confidence: 99%

Premature adrenarche: novel lessons from early onset androgen excess

Idkowiak

Lavery

Dhir

et al. 2011

European Journal of Endocrinology

110

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Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

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“…The 24-h UFF excretion serves as an integrated measure of blood free cortisol concentrations during the entire day (1 ). Increasing evidence suggests that simultaneous measurements of more than 1 analyte in the same sample material will bring more confidence to the acceptance or rejection of specific diagnoses (2)(3)(4). Accordingly, clear advantages have been reported regarding the identification of hypercortisolism, e.g., in patients with confirmed Cushing syndrome (2 ) and type1 diabetes mellitus (4 ), with simultaneous measurements of UFF and urinary free cortisone (UFE) compared with UFF alone.…”

Section: Simultaneous Measurements Of Urinary Free Cortisol and Cortimentioning

confidence: 99%

“…Variations in activity of 11␤-hydroxysteroid dehydrogenase type2, a highly expressed enzyme in the human kidney that inactivates cortisol to cortisone, can confound renal cortisol output (UFF). Accordingly, the usual renal 24-h UFE excretion is about twice that of UFF (2)(3)(4).…”

Section: Simultaneous Measurements Of Urinary Free Cortisol and Cortimentioning

confidence: 99%

Exaggerated adrenarche and altered cortisol metabolism in Type 1 diabetic children

Cited by 35 publications

References 48 publications

Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys

Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys

Premature adrenarche: novel lessons from early onset androgen excess

Simultaneous Measurements of Urinary Free Cortisol and Cortisone for the Assessment of Functional Glucocorticoid Activity

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