[Cortisol]_trough

[Cortisol]_peak

midnight

~8:00am

--> ~ [Cortisol binding globulin]

elevated [cortisol]_serum

with loss of diurnal variation

DDx

Cushing syndrome

False +: stress, depression, chronic alcoholism

[Free cortisol]_urine /24hrs

--> invalid in renal insufficiency

--> if - => cannot r/o Cushing

Effect of Dexamethasone

in a Pt with normal endocrine function

suppression --> CRF, ACTH & cortisol

--> no crossreaction with cortisol assays

Hypercortisolism

High-dose DST

Pt-1.Results: suppresion => Dx

Pt-2.Results: no suppression => DDx

1.Pituitary adenoma --> Cushing disease

2. ectopic ACTH / 1⁰ adrenal hypercortisolism

Metyrapone stimulation test

Results: no increase in[Cortisol]_serum

Impaired pituitary ACTH production

Metyrapone--> ^- cortisol <-- 11,deoxycortisol

=> + ACTH_pituitary

The best screening test for Cushing syndrome

100% specificity

~90% sensitivity

Late-night (1:00pm) salivary cortisol

--> free cortisol that crosses into the saliva

-->independent of salivary flow rates

-->stable up to 1 week

Pituitary microadenoma of basophilic cells

B/L adrenal hyperplasia

elevated [ACTH] and [Cortisol]

DX

Cushing disease

~70% of hypercortisolism cases

Actopic ACTH production

Most common association

1⁰ adrenal hypercortisolism

Causes

B/L adrenal hyperplasia, Adenomas1 ,Carcinomas²

Adults¹⁼² , children^2>1

Cortosyn stimulation test

 1.Pt- no response

2. Pt- good response, low [ACTH]_serum

1.1⁰ adrenal insufficiency (Addison disease)

2. 2⁰ adrenal insufficiency

Cortosyn = ACTH analog

Pt with altered mental status, weakness, hypotension, hypoglycemia, hyponatremia, hyperkalemia w metabolic acidosis & Diffuse hyperpigmentation of the skin

Dx

Addison disease (1⁰ adrenal insufficiency)

--> co-hypersecretion of MSH

Conn syndrome

Causes

hyperaldosteronism, 1⁰ - Adrenal adenoma

2⁰ - Renal artery stenosis, juxtaglomerular cell tm --> renin -->⁺ Production_aldosteron

Enzyme deficiencies--> autosomal recessive

1. 21-hydroxylase--> gene conversion

2. 11-hydroxylase

[17-hydroxyprogesterone] = > 242nmol/L (high)

in a randomly timed blood sample

Dx