CoChat
Sign Up
Cited by 24Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

Adrenomedullary Function in Patients with Nonclassic Congenital Adrenal Hyperplasia

Open access
Verma, S., Green-Golan, L., VanRyzin, C., Drinkard, B., Mehta, S. P., Weise, M., Eisenhofer, G., Merke, D. P.·2010·Hormone and Metabolic Research
DOI 10.1055/s-0030-1253385PMC PMC7473418
Open this paper in CoChat — free account

Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is classified into three types based on disease severity: classic salt-wasting, classic simple virilizing, and nonclassic. Adrenomedullary dysplasia and epinephrine deficiency have been described in classic CAH, resulting in glucose dysregulation. Our objective was to investigate adrenomedullary function in nonclassic CAH and to evaluate adrenomedullary function according to disease severity. Adrenomedullary function was evaluated in response to a standardized cycle ergonometer test in 23 CAH patients (14 females, age 9-38 years; 6 salt-wasting, 7 simple virilizing, 5 nonclassic receiving glucocorticoid treatment, 5 nonclassic not receiving glucocorticoid), and 14 controls (7 females, age 12-38 years). Epinephrine, glucose, and cortisol were measured at baseline and peak exercise. CAH patients and controls were similar in age and anthropometric measures. Patients with nonclassic CAH who were not receiving glucocorticoid and controls experienced the expected stress-induced rise in epinephrine, glucose, and cortisol. Compared to controls, patients with all types of CAH receiving glucocorticoid had impaired exercise-induced changes in epinephrine (salt-wasting: p=0.01;simple virilizing: p=0.01; nonclassic: p=0.03), and cortisol (salt-wasting: p=0.004; simple virilizing: p=0.006; nonclassic: p=0.03). Salt-wasting patients displayed the most significant impairment, including impairment in glucose response relative to controls (p=0.03). Hydrocortisone dose was negatively correlated with epinephrine response (r=-0.58; p=0.007) and glucose response (r=-0.60; p=0.002). The present study demonstrates that untreated patients with nonclassic CAH have normal adrenomedullary function. The degree of epinephrine deficiency in patients with CAH is associated with the severity of adrenocortical dysfunction, as well as glucocorticoid therapy.

Integrity signals

Registry

Crossref · 10.1055/s-0030-1253385

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 28 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Hydrocortisone dose was negatively correlated with epinephrine response (r = −0.58; p = 0.007).

    “Hydrocortisone dose was negatively correlated with epinephrine response (r = − 0.58; p = 0.007) and glucose response (r = − 0.60; p = 0.002).”
    • Also stated in: § Results · plain
      “For all CAH patients, hydrocortisone dose was inversely correlated with the exercise-induced change in epinephrine (r = − 0.58; p = 0.007) and glucose (r = − 0.60; p = 0.002).”
    Quote in the paperSubstantial claim
  • Findingown data

    Prior cortisol response to ACTH stimulation was similar between nonclassic patients receiving glucocorticoid treatment and those not receiving treatment.

    “Prior cortisol response to ACTH stimulation was similar between NC patients receiving glucocorticoid treatment and NC patients not receiving treatment.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Nonclassic CAH patients not receiving glucocorticoid and controls showed the expected stress-induced increases in epinephrine, glucose, and cortisol.

    “Patients with nonclassic CAH who were not receiving glucocorticoid and controls experienced the expected stress-induced rise in epinephrine, glucose, and cortisol.”
    Quote in the paperSubstantial claim
  • Findingown data

    Untreated patients with nonclassic CAH have normal adrenomedullary function.

    “The present study demonstrates that untreated patients with nonclassic CAH have normal adrenomedullary function.”
    • Also stated in: § Discussion · boosted
      “Our data demonstrate that patients with the mild or nonclassic form of CAH who are not receiving glucocorticoid therapy have normal adrenomedullary function.”
    Quote in the paperSubstantial claim
  • Findingown data

    The normal exercise-induced rise in glucose was blunted in all CAH patients receiving glucocorticoid.

    “Although the normal exerciseinduced rise in glucose was blunted in all CAH patients receiving glucocorticoid, the difference in the glucose levels between baseline and peak exercise was significantly different from controls for the SW group only (p = 0.03; Fig. 1b).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Findingown data

    The control group had an overall rise in cortisol in response to exercise, while this was not observed in any CAH patients on medication, including nonclassic patients.

    “As expected, the control group did have an overall rise in cortisol level in response to exercise, while this was not observed in any of the CAH patients on medication, including the NC patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    CAH patients in good clinical control on glucocorticoid therapy, including those with nonclassic CAH, have decreased epinephrine reserve and reduced epinephrine response to high-intensity, short-term exercise.

    “However, CAH patients in good clinical control on glucocorticoid therapy, including those with NC CAH, have decreased epinephrine reserve and reduced epinephrine response to high-intensity, short-term exercise.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All treated patients were on hydrocortisone, and nonclassic patients received lower hydrocortisone doses than classic patients (p < 0.01; SW vs. SV vs. NC means: 14.6 ± 0.6 vs. 16.6 ± 1.2 vs. 9.6 ± 1.2 mg/m2/day).

    “All patients receiving treatment were on hydrocortisone and overall, NC patients were receiving lower doses of hydrocortisone than classic patients (p < 0.01) [SW vs. SV vs. NC (mean ± SEM): 14. 6 ± 0.6 vs. 16.6 ± 1.2 vs. 9.6 ± 1.2mg/m2/day] (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Salt-wasting patients had the lowest epinephrine levels, followed by simple virilizing and then nonclassic patients.

    “The SW patients had the lowest epinephrine levels followed by the SV and NC patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Eight nonclassic patients had cortisol measured during ACTH stimulation at diagnosis or in the untreated state, and cortisol levels were slightly below normal in most of them.

    “Eight NC patients had cortisol measured during an ACTH stimulation test at the time of diagnosis or in the untreated state, and cortisol levels were slightly below normal in the majority of patients (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Nonclassic patients not receiving glucocorticoid did show a rise in cortisol that was somewhat less than in healthy controls, but the difference did not reach statistical significance (p = 0.08).

    “The NC patients not receiving glucocorticoid treatment did show a rise in cortisol level that was somewhat less than in the healthy controls, but this difference failed to reach statistical significance (p = 0.08).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared with controls, patients with all types of CAH receiving glucocorticoid had impaired exercise-induced changes in epinephrine (salt-wasting p = 0.01; simple virilizing p = 0.01; nonclassic p = 0.03).

    “Compared to controls, patients with all types of CAH receiving glucocorticoid had impaired exercise-induced changes in epinephrine (salt-wasting: p = 0.01; simple virilizing: p = 0.01; nonclassic: p = 0.03), and cortisol (saltwasting: p = 0.004; simple virilizing: p = 0.006; nonclassic: p = 0.03).”
    • Also stated in: § Results · plain
      “The increase in epinephrine in response to exercise was significantly different between all CAH groups receiving treatment and the control group (SW: p = 0.01; SV: p = 0.01; NC-treated: p = 0.03; Fig. 1a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Salt-wasting patients showed the most significant impairment, including impaired glucose response relative to controls (p = 0.03).

    “Salt-wasting patients displayed the most significant impairment, including impairment in glucose response relative to controls (p = 0.03).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    CAH patients and controls were similar in age and anthropometric measures.

    “CAH patients and controls were similar in age and anthropometric measures.”
    • Also stated in: § Results · plain
      “All subjects undergoing the standardized exercise study were similar in age and anthropometric measures (Table 2).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Treated CAH patients were on conventional hydrocortisone and fludrocortisone therapy and were in good clinical control based on physical examination and laboratory evaluation within two months before exercise testing.

    “Treated patients with CAH who underwent the exercise study were on conventional therapy with hydrocortisone and fludrocortisone (latter in classic patients only) and were in good clinical control based on physical examination and laboratory evaluation done within 2 months prior to the exercise testing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Epinephrine secretion was normal in the nonclassic untreated patients, suggesting that intra-adrenal cortisol secretion was not relevantly reduced.

    “Epinephrine secretion was normal in our NC-untreated patients, suggesting that intra-adrenal cortisol secretion was not relevantly reduced.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Plasma metanephrine is an accurate measure of CAH phenotype among classic patients, supporting a correlation between adrenomedullary impairment and clinical phenotype in CAH.

    “Plasma metanephrine, the O-methylated metabolite of epinephrine, has been found to be an accurate measure of CAH phenotype amongst classic patients [19], supporting a correlation between adrenomedullary impairment and clinical phenotype in CAH.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Patients with classic CAH have adrenomedullary hypoplasia and impaired epinephrine secretion.

    “Patients with classic CAH have been found to have adrenomedullary hypoplasia and im paired epinephrine secretion [6].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    This impairment was attributed mainly to epinephrine deficiency and was not corrected by doubling the hydrocortisone replacement dose before exercise.

    “This impairment was attributed mostly to epinephrine deficiency and could not be corrected by doubling the replacement dose of hydrocortisone prior to exercise [7].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    CAH is divided into three clinical forms: classic salt-wasting, classic simple virilizing, and nonclassic.

    “There is a range of clinical severity and three types of CAH can be distinguished by clinical and molecular genetic criteria: classic salt-wasting (SW), classic nonsalt-wasting or simple virilizing (SV), and nonclassic (NC) forms [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Healthy volunteers were matched to patients by age, sex, and BMI group.

    “Healthy volunteers were age-, sex- and BMI-group-matched.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Normal glucocorticoid secretion from the zona fasciculata is required for adrenomedullary organogenesis, and a developmental defect in adrenal medulla formation has been shown in salt-wasting CAH.

    “Normal glucocorticoid secretion by the zona fasciculata of the adrenal cortex is also necessary for adrenomedullary organogenesis, and a developmental defect in the formation of the adrenal medulla has been shown in patients with SW CAH [6].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Standardized exercise testing has previously been used to assess adrenomedullary reserve in patients with classic CAH.

    “Standardized exercise testing has been used in the past to evaluate adrenomedullary reserve in patients with classic CAH [7 – 10].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [7]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [8]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [9]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [10]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    The degree of epinephrine deficiency in patients with CAH is associated with the severity of adrenocortical dysfunction and with glucocorticoid therapy.

    “The degree of epinephrine deficiency in patients with CAH is associated with the severity of adrenocortical dysfunction, as well as glucocorticoid therapy.”
    • Also stated in: § Discussion · plain
      “Thus, the degree of epinephrine deficiency in patients with CAH is associated with the severity of adrenocortical dysfunction, as well as glucocorticoid therapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All patients had a genotype that corresponded to the expected clinical phenotype.

    “All patients had a genotype that corresponded to the expected clinical phenotype.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In adults, epinephrine counters hypoglycemia, although this compensation is not believed to be critical if glucagon and insulin secretion are intact.

    “In adults, epinephrine counters hypoglycemia, although this compensation is not believed to be critical if glucagon and insulin secretion is intact [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Miscarriage risk was recently found to be significantly lower in glucocorticoid-treated nonclassic CAH women than in untreated nonclassic CAH women, suggesting that the mild hormone imbalances of nonclassic CAH may have subtle clinical implications.

    “Miscarriage risk was recently found to be significantly lower in glucocorticoid treated NC CAH women than in untreated NC CAH women [34], suggesting that the mild hormone imbalances characteristic of NC CAH may indeed have subtle clinical implications.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The sample size is acceptable for an exercise study, and statistical significance was found with limited analyses.

    “However, this sample size is acceptable for an exercise study, and statistical significance was found with limited analyses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A limitation of the study is its small sample size.

    “A limitation of our study is the small sample size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Patients with isolated glucocorticoid deficiency display low baseline epinephrine and minimal adrenomedullary response to physical stress.

    “For example, patients with isolated glucocorticoid deficiency display a low baseline epinephrine and minimal adrenomedullary response to physical stress [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent study by Bao et al. showed that prior exposure to elevated cortisol resulted in reduced epinephrine response to exercise in patients with type 1 diabetes.

    “A recent study by Bao et al. [27] showed that prior exposure to elevated cortisol resulted in reduced epinephrine response to exercise in patients with type 1 diabetes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Patients with classic CAH mostly have an inborn epinephrine deficiency, whereas nonclassic CAH patients mostly develop epinephrine deficiency under glucocorticoid replacement.

    “It appears that patients with classic CAH mostly have an inborn epinephrine deficiency, whereas NC CAH patients mostly develop epinephrine deficiency under glucocorticoid replacement.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Children are more prone to hypoglycemia than adults, and much of their glycemic control appears to depend on epinephrine secretion.

    “Children are known to be more prone to hypoglycemia than adults [22], and much of their glycemic control appears to depend on epinephrine secretion [23 – 26].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [22]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [23]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [24]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [26]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

28 of 28

  • The paper relies on this without support.

    Adrenomedullary function had not been evaluated in patients with nonclassic CAH before this study.

    “Adrenomedullary function has not been evaluated in patients with NC CAH.”

  • The paper relies on this without support.

    During development, intra-adrenal cortisol secretion is expected to be normal or near normal in patients with nonclassic CAH.

    “During development, intra-adrenal cortisol secretion is expected to be normal or near normal in patients with NC CAH.”

  • The paper relies on this without support.

    Glucocorticoid secretion is necessary for the induction of phenylethanolamine N-methyltransferase, the enzyme that converts norepinephrine to epinephrine.

    “Glucocorticoid secretion is necessary for the induction of phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine.”

  • The paper relies on this without support.

    Exercise is a potent stimulator of epinephrine release from the adrenal medulla.

    “Exercise is a potent stimulator of epinephrine from the adrenal medulla.”

  • The paper relies on this without support.

    The aberrant adrenomedullary development seen in salt-wasting CAH is due to a lack of intra-adrenal cellular interactions and impaired cortical-chromaffin crosstalk.

    “the aberrant adrenomedullary development found in patients with salt-wasting CAH is due to lack of intra-adrenal cellular interactions and impaired cortical-chromaffi n crosstalk.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Verma, S., Green-Golan, L., VanRyzin, C., Drinkard, B., Mehta, S. P., Weise, M., Eisenhofer, G., & Merke, D. P.
Affiliations
  • National Institutes of Health (US)
  • Federal Institute for Drugs and Medical Devices (DE)
  • University Hospital Carl Gustav Carus (DE)
ORCID
Venue
Hormone and Metabolic Research
Publisher
Georg Thieme Verlag KG
Published
2010-05-05
Volume
42
Issue
08
Pages
607-612
ISSN
  • 0018-5043 (ISSN-L)
  • 1439-4286
DOI
10.1055/s-0030-1253385
PMC
PMC7473418
OpenAlex
W2085359400
Cited by
24
References
2
Citations by year
2026: 3 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2019: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
0.91
Type
journal article
Language
en
Open access
Locations
  • Hormone and Metabolic Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99CL999999)
  • NIH Clinical Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
non-classical congenital adrenal hyperplasia, 21-hydroxylase deficiency, adrenomedullary function, exercise stress response, glucocorticoid therapy, hydrocortisone dose, cortisol response, glycemic response, disease severity, salt-wasting CAH, simple virilizing CAH
MeSH terms
Adolescent, Adrenal Hyperplasia, Congenital, Adrenal Medulla, Adult, Blood Glucose, Child, Epinephrine, Exercise Test, Female, Humans, Hydrocortisone, Male, Case-Control Studies, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review