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Toronto Notes 2019
Adrenal Cortex
Endocrinology E31
Table 22. Physiological Effects of Glucocorticoids
Stimulatory Effects
Stimulate hepatic glucose production (gluconeogenesis) Increase insulin resistance in peripheral tissues Increase protein catabolism
Stimulate leukocytosis and lymphopenia
Increase cardiac output, vascular tone, Na+ retention Increase PTH release, urine calcium excretion
Androgens
Inhibitory Effects
Inhibit bone formation; stimulate bone resorption
Inhibit fibroblasts, causing collagen and connective tissue loss Suppress inflammation; impair cell-mediated immunity
Inhibit growth hormone axis
Inhibit reproductive axis
Inhibit vitamin D3 and inhibit calcium uptake
• sexsteroidsregulatedbyACTH;primarilyresponsibleforadrenarche(growthofaxillaryandpubichair)
• principaladrenalandrogensare:dihydroepiandrosterone(DHEA),androstenedione,and
11-hydroxyandrostenedione
• proportionoftotalandrogens(adrenaltogonadal)increasesinoldage
Adrenocortical Functional Workup
STIMULATION TEST
• purpose:diagnosisofhormonedeficiencies
• method:measuretargethormoneafterstimulationwithtropic(pituitary)hormone
1 . Tests of Glucocorticoid Reserve
• Cosyntropin(ACTHanalogue)StimulationTest
■ give 250 μg cosyntropin IV, and measure plasma cortisol levels at time 0 and 60 min ■ physiologic response: stimulated plasma cortisol of >500 nmol/L
■ inappropriate response: inability to stimulate increased plasma cortisol
• insulintoleranceisthegoldstandardtestusedtodiagnoseadrenalinsufficiency(seePituitaryGland,E16)
SUPPRESSION TESTS
• purpose:diagnosisofhormonehypersecretion
• method:measuretargethormoneaftersuppressionofitstropic(pituitary)hormone
1 . Tests of Pituitary-Adrenal Suppressibility
• Dexamethasone(DXM)SuppressionTest
■ principle: DXM suppresses pituitary ACTH, plasma cortisol should be lowered if HPA axis is
normal
■ Screening Test: Overnight DXM Suppression Test
◆ oral administration of 1 mg DXM at midnight, then measure plasma cortisol levels the following day at 8 am
◆ physiologic response: plasma cortisol <50 nmol/L, with 50-140 nmol/L being a “grey zone” (cannot be certain if normal or not)
◆ inappropriate response: failure to suppress plasma cortisol
◆ <20% false positive results due to obesity, depression, alcohol, other medications
■ Confirmatory Test: other testing is used to confirm the diagnosis, such as:
◆ 24 h urine free cortisol (shows overproduction of cortisol)
◆ midnight salivary cortisol (if available), shows lack of diurnal variation
– inappropriate response: remains high (normally will be low at midnight)
2 . Tests of Mineralocorticoid Suppressibility
• screenforprimaryaldosteronismwithelevatedaldosterone:reninratioandhighaldosterone
• confirmwithlackofsuppression:withexpansionofextracellularfluidvolume(ECFV),plasma
aldosterone should be lowered if HPA axis is normal
• ECFVExpansionwithNormalSaline(NS)
■ IV infusion of 500 mL/h of NS for 4 h, then measure plasma aldosterone levels
■ plasma aldosterone >277 pmol/L is consistent with primary hyperaldosteronsim, <140 pmol/L is
normal
■ inappropriate response: failure to suppress plasma aldosterone