Clinical Chemistry

[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

 

Which test reflects the amount of free cortisol and is independent of diurnal variation of [cortisol]serum?

[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

=> + ACTHpituitary

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

Small cell carcinoma of the Lung

10 adrenal hypercortisolism

Causes

B/L adrenal hyperplasia, Adenomas1 ,Carcinomas2

Adults1=2 , children2>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 –>+ Productionaldosteron

Most common cause of congenital adrenal hyperplasia

Enzyme deficiencies–> autosomal recessive

1. 21-hydroxylase–> gene conversion

2. 11-hydroxylase

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

in a randomly timed blood sample

Dx

21-hydroxylase deficiency