Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glycemic control during prolonged moderate-intensity exercise.

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

Epinephrine increases glucagon secretion and inhibits insulin secretion via adrenergic receptors.

“Epinephrine increases glucagon secretion and inhibits insulin secretion via adrenergic receptors (23).”

• cites [23] Samols, 1979, Adrenergic modulation of pancreatic A, B, and D cells. α-Adrenergic suppression and β-adrenergic stimulation of somatostatin secretion, α-adrenergic stimulation of glucagon secretion in the perfused dog pancreas., J Clin Invest sourceSupported

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

Decreased heart rate in response to exercise has been reported in adrenalectomized adults.

“Decreased heart rate in response to exercise has been reported in adrenalectomized adults (28).”

• cites [28] Howlett, 1999, Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans, J Physiol sourceSupported

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

Muscle glycogenolysis can occur in the absence of epinephrine.

“Although epinephrine increases energy metabolism of exercising muscles by stimulating muscle glycogenolysis during exercise, muscle glycogenolysis can occur in the absence of epinephrine (24).”

• cites [24] Kjaer, 2000, Adrenaline and glycogenolysis in skeletal muscle during exercise: a study in adrenalectomised humans, J Physiol sourceSupported

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

Exercise is natural, quantifiable in terms of workload and duration, and a known stimulus of the adrenal medulla and systemic sympathetic nervous system.

“Although several physical stressors are capable of eliciting physiological responses in the body, exercise is natural, quantifiable in terms of workload and duration, and a known stimulus of the adrenal medulla and systemic sympathetic nervous system (6).”

• cites [6] Wigal, 2003, Catecholamine response to exercise in children with attention deficit hyperactivity disorder., Pediatr Res sourceSupported

May combine two claims.

In patients with classic CAH, glucose showed a steady decline during exercise and increased during recovery.

“CAH patients showed a steady decline in glucose during exercise with an increase in glucose in the postexercise period.”

• Also stated in: § Results · plain

  “patients with CAH showed a steady decline in glucose during exercise with an increase in levels during recovery”

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

Patients and controls exercised at an energy expenditure rate comparable to brisk walking.

“Based on this scale, patients and controls exercised at an energy expenditure rate comparable to brisk walking (14).”

• cites [14] Ainsworth, 2000, Compendium of physical activities: an update of activity codes and MET intensities, Med Sci Sports Exerc sourceNot checked — no full text of the source

May combine two claims.

Glucose levels were comparable between CAH patients and controls early in exercise and at 30 min post exercise.

“whereas glucose levels were comparable between the two groups early in exercise and at 30 min (P ϭ 0.19) post exercise.”

May combine two claims.

CAH patients and controls had comparable cardiovascular parameters and perceived level of exertion.

“Patients with CAH and controls had comparable cardiovascular parameters and perceived level of exertion.”

• Also stated in: § Results · plain

  “Patients with CAH and healthy controls had comparable systolic (P ϭ 0.57) and diastolic (P ϭ 0.95) blood pressure and heart rate (P ϭ 0.63) throughout exercise and recovery”

• Also stated in: § Results · plain

  “Perceived levels of exertion based on the Borg scale (P ϭ 0.31) and VO 2 max (P ϭ 0.31) were similar between patients and controls.”

May combine two claims.

Insulin levels were slightly higher in CAH patients during the testing period, but the difference did not reach statistical significance (P = 0.17).

“insulin levels were slightly higher in CAH patients during the testing period (P ϭ 0.17)”

• Also stated in: § Results · plain

  “insulin levels were slightly higher in CAH patients during the testing period, but this difference failed to reach statistical significance (P ϭ 0.17)”

May combine two claims.

CAH patients did not have overt hypoglycemia at any point during exercise testing and did not experience glucopenic symptoms.

“CAH patients did not have overt hypoglycemia at any point during exercise testing and did not experience any glucopenic symptoms.”

• Also stated in: § Discussion · plain

  “hypoglycemia did not occur at any point during exercise or recovery.”

May combine two claims.

CAH patients experienced a decline in cortisol during exercise, whereas healthy controls experienced an increase in cortisol after 60 min of exercise.

“As expected, CAH patients experienced a decline in cortisol during exercise, whereas healthy controls experienced an increase in cortisol after 60 min of exercise”

May combine two claims.

Insulin levels were higher in patients with CAH despite lower glucose levels.

“Despite having lower glucose levels, insulin levels were higher in patients with CAH.”

May combine two claims.

Despite having a progressive decline in cortisol levels due to metabolism of exogenously administered hydrocortisone, CAH patients had a rise in blood glucose post exercise.

“However, despite having a progressive decline in cortisol levels due to metabolism of exogenously administered hydrocortisone, our patients had a rise in blood glucose post exercise.”

Probably not a substantial claim: may not pass S4 (based).

Previous studies of healthy controls reveal a 10- to 20-fold increase in epinephrine during high-intensity exercise.

“Previous studies of healthy controls reveal a 10-to 20-fold increase in epinephrine during high-intensity exercise.”

May combine two claims.

CAH patients have altered metabolic and hormonal responses during prolonged moderate-intensity exercise comparable to brisk walking.

“Conclusion: CAH patients have defective glycemic control and altered metabolic and hormonal responses during prolonged moderateintensity exercise comparable to brisk walking.”

• Also stated in: § Discussion · boosted

  “our study demonstrates altered metabolic and hormonal response in CAH patients during a moderateintensity stressor equivalent to brisk walking.”

May combine two claims.

Patients with CAH and healthy controls were similar in age, height, weight, BMI, and pubertal stage.

“Patients with CAH and healthy controls were similar in age, height, weight, BMI, and pubertal stage (Table 1).”

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

In a previous short-term high-intensity exercise study, patients had a 5% lower peak heart rate than controls with a normal systolic and diastolic BP.

“In our previous short-term high-intensity exercise study, we reported that patients had a 5% lower peak heart rate than controls with a normal systolic and diastolic BP (2).”

• cites [2] Weise, 2004, Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise., J Clin Endocrinol Metab sourceNot checked — no full text of the source

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

Patients with CAH had decreased epinephrine secretion with a lack of the normal exercise-induced rise in blood glucose during high-intensity short-term exercise.

“We previously reported that patients with CAH had decreased epinephrine secretion with a lack of the normal exercise-induced rise in blood glucose during high-intensity short-term exercise (2).”

• cites [2] Weise, 2004, Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise., J Clin Endocrinol Metab sourceNot checked — no full text of the source

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

The small sample size of classic CAH patients and controls is a limitation to the study.

“The small sample size of classic CAH patients and controls is an obvious limitation to our study.”

May combine two claims.

Adrenomedullary abnormalities in classic CAH are most likely due to a deficit in adrenal cortical glucocorticoid secretion because glucocorticoid secretion is necessary for adrenomedullary organogenesis and adrenomedullary epinephrine synthesis.

“These adrenomedullary abnormalities are most likely due to a deficit in adrenal cortical glucocorticoid secretion because glucocorticoid secretion is necessary for adrenomedullary organogenesis and adrenomedullary epinephrine synthesis (3).”

• cites [3] Wurtman, 1971, Adrenocortical control of epinephrine synthesis in health and disease., Adv Metab Disord sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Diminished adrenomedullary output was not overcome with an extra dose of exogenous hydrocortisone.

“In this previous study, diminished adrenomedullary output was not overcome with an extra dose of exogenous hydrocortisone, suggesting that high intraadrenal glucocorticoid levels are needed for proper epinephrine synthesis (26)”

• cites [26] Weise, 2004, Stress dose of hydrocortisone is not beneficial in patients with classic congenital adrenal hyperplasia undergoing short-term, high-intensity exercise., J Clin Endocrinol Metab sourceNot checked — no full text of the source

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

Compared with controls, elevated diastolic BP was reported during exercise in children with isolated glucocorticoid deficiency due to ACTH unresponsiveness.

“Compared with controls, elevated diastolic BP was reported during exercise in children with isolated glucocorticoid deficiency due to ACTH unresponsiveness (16).”

• cites [16] Zuckerman-Levin, 2001, The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: a study in isolated glucocorticoid deficiency., J Clin Endocrinol Metab sourceNot checked — no full text of the source

May combine two claims.

Controls experienced more of a rise in glucagon and more of a decrease in insulin than patients with CAH, suggesting possible indirect effects of low epinephrine.

“Interestingly, controls experienced more of a rise in glucagon and more of a decrease in insulin than patients with CAH, suggesting possible indirect effects of low epinephrine.”

May combine two claims.

In the current study of moderate-intensity long-term (90 min) exercise, glucose progressively declined in patients with CAH, suggesting that the progressive decline in cortisol may have played a role.

“In our current study of moderate-intensity long-term (90 min) exercise, glucose progressively declined in patients with CAH, suggesting that the progressive decline in cortisol may have played a role.”

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

The lack of statistical significance between the two groups on measures of glucagon and insulin may have been due to the small sample size.

“The lack of statistical significance between the two groups on measures of glucagon and insulin may have been due to our small sample size.”

May combine two claims.

Previous exercise studies in patients with CAH and other exercise studies used comparable sample sizes to investigate similar parameters.

“However, previous exercise studies in patients with CAH (2,4,26) and other exercise studies used comparable sample sizes to investigate similar parameters.”

• cites [2] Weise, 2004, Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise., J Clin Endocrinol Metab sourceNot checked — no full text of the source
• cites [4] Riepe, 2006, Absence of exercise-induced leptin suppression associated with insufficient epinephrine reserve in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency., Exp Clin Endocrinol Diabetes sourceNot checked — no full text of the source
• cites [26] Weise, 2004, Stress dose of hydrocortisone is not beneficial in patients with classic congenital adrenal hyperplasia undergoing short-term, high-intensity exercise., J Clin Endocrinol Metab sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

GH may have played a protective role in stimulating glucose production because of its ability to stimulate hepatic glucose synthesis.

“GH may have played a protective role in stimulating glucose production because of its ability to stimulate hepatic glucose synthesis.”

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

In general, catecholamines are thought to be most important under conditions of high metabolic stress, such as intense exercise, but less important in low intensity stress.

“In general, catecholamines are thought to be most important under conditions of high metabolic stress, such as intense exercise, but less important in low intensity stress (5).”

• cites [5] Coker, 2005, Glucoregulation during exercise: the role of the neuroendocrine system., Sports Med sourceNot checked — no full text of the source

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

The association between low resting plasma epinephrine levels and unfavorable survival may be a function of the lower levels of epinephrine in older individuals.

“One large population study suggests that low resting plasma epinephrine levels were associated with an unfavorable survival rate (17); this finding, however, may be a function of the lower levels of epinephrine in older individuals (18).”

• cites [18] Weise, 2002, Pubertal and gender-related changes in the sympathoadrenal system in healthy children., J Clin Endocrinol Metab sourceNot checked — no full text of the source

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

Exercise-induced changes in the pancreatic secretion of glucagon and insulin play an important role in the stimulation of hepatic glucose production during long-term exercise.

“Exercise-induced changes in the pancreatic secretion of glucagon and insulin play an important role in the stimulation of hepatic glucose production during long-term exercise, and both glucagon and insulin are influenced by catecholamines.”

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

Alterations in adrenomedullary development and structure may also play a role in the epinephrine deficiency of CAH.

“and alterations in adrenomedullary development and structure may also play a role (1).”

• cites [1] Merke, 2000, Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency., N Engl J Med sourceNot checked — no full text of the source

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

Under resting conditions, children with CAH have been reported to have elevated daytime systolic and diastolic blood pressure and to lack a normal dip in nocturnal systolic BP.

“Under resting conditions, children with CAH have been reported to have elevated daytime systolic and diastolic blood pressure (BP) and to lack a normal dip in nocturnal systolic BP (27).”

• cites [27] Roche, 2003, Blood pressure in children and adolescents with congenital adrenal hyperplasia (21-hydroxylase deficiency): a preliminary report., Clin Endocrinol (Oxf) sourceNot checked — no full text of the source

May combine two claims.

When given a longer time frame (90 min) of exercise, CAH patients were still unable to up-regulate the sympathetic nervous system to produce higher levels of norepinephrine, despite low levels of epinephrine.

“Thus, when given a longer time frame (90 min) of exercise, CAH patients were still unable to up-regulate the sympathetic nervous system to produce higher levels of norepinephrine, despite low levels of epinephrine.”

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

One large population study suggests that low resting plasma epinephrine levels were associated with an unfavorable survival rate.

“One large population study suggests that low resting plasma epinephrine levels were associated with an unfavorable survival rate (17); this finding, however, may be a function of the lower levels of epinephrine in older individuals (18).”

• cites [17] Christensen, 1994, Effect of psychosocial stress and age on plasma norepinephrine levels: a review., Psychosom Med sourceNot checked — no full text of the source
• cites [18] Weise, 2002, Pubertal and gender-related changes in the sympathoadrenal system in healthy children., J Clin Endocrinol Metab sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

Discrepancy of results may be due to different patient populations, different testing protocols, or different treatment practices.

“Discrepancy of results may be due to different patient populations, different testing protocols, or different treatment practices.”

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

The hormone assays used had specified sensitivities and coefficients of variation.

“The cortisol assay has a sensitivity of 1 g/dl and has interassay coefficients of variation (CV) of 11.1, 7.5, and 10% at 3.3, 22.4, and 35.6 g/dl, respectively.”

• Also stated in: § Assays · plain

  “The insulin assay has a sensitivity of 2 U/ml and CV of 6.2 and 4.9% at 8.13 and 61.7 U/ml, respectively.”

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

Catecholamines were log transformed for analysis because they are known to be nonnormally distributed in the general population.

“Catecholamines, known to be nonnormally distributed in the general population, were log transformed for analysis.”

Classified as probably not a substantial claim.

The VO2 max and AT levels obtained from the d-1 maximal test were used to standardize the d-2 90-min exercise test and to ensure that each subject exercised at the same level of intensity.

“The VO 2 max and AT levels obtained from the d-1 maximal test were used to standardize the d-2 90-min exercise test and to ensure that each subject exercised at the same level of intensity (comparable to brisk walking).”