DIAGNOSIS AND COMPLICATIONS OF

CUSHING’S SYNDROME

Namrata Dass

ETIOLOGY ACTH dependent : - pituitary corticotroph adenoma

[Cushing’s disease - extrapituitary tumor (ectopic ACTH- tumor secreting CRH ACTH independent :- adrenocortical tumors adrenal

hyperplasia or dysplasia

CLINICAL FEATURES central obesity , purple striae, proximal

muscle weakness, fatigue, high blood pressure,

glucose intolerance, acne, hirsutism, and menstrual

irregularity. Neuropsychological disturbances sleep disturbances, and cognitive

DIAGNOSES OF CUSHING SYNDROME First-line screening tests1) Twenty-four-hour urinary free cortisol

(UFC)2) Low-dose dexamethasone suppression

tests (DST)3) Late-night salivary cortisol.

TWENTY-FOUR-HOUR URINARY FREE CORTISOL

Advantages : - not affected corticosteroid-binding

globulin (CBG) levels Disadvantages :- Affected by GFR - Influenced by various metabolites of

cortisol and some synthetic glucocorticoids

LOW-DOSE DEXAMETHASONE SUPPRESSION TESTSLimitations :- interfering conditions causing an apparent

lack ofsuppression include: 1) decreased dexamethasone absorption, 2)drugs enhancing hepatic dexamethasone

metabolism (barbiturates, phenytoin, carbamazepine, rifampicin, mepro-

bamate, aminoglutethimide, methaqualone),

3)increased concentration of CBG (estrogen treatment, pregnancy)

DIFFERENTIAL DIAGNOSIS

ACTH measurement : - below 10 pg/ml : ACTH-independent - greater than 20 pg/ml : ACTH-

dependent - Between 10-20pg/ml : a CRH stimulation

test is indicated, with measurement of plasma ACTH.

CRH stimulation test : most pituitary tumors, and also a few ectopic ACTH-secreting tumors, respond .

HIGH-DOSE DST most corticotroph adenomas respond Generally ectopic tumors are resistant

to feedback inhibition. Lack of suppression in adrenal in

Cushing syndrome

DESMOPRESSIN TEST increases ACTH secretion in 80 -90% of

patients with CD and only rarely in normal individuals or patients with pseudo-CS.

PITUITARY MRI performed in all patients with ACTH

dependent Cushing syndrome Definitive diagnosis : - classic clinical presentation - dynamic biochemical studies compatible

with pituitary CS,- the presence of a focal lesion (6 mm)

on pituitary MRI

Bilateral inferior petrosal sinus sampling (BIPSS) : ACTH determination should be recommended in patients with ACTH-dependent CS whose clinical, biochemical, or

radiological studies are discordant or equivocal

If BIPSS confirms the lack of a pituitary ACTH gradient, CT and/or MRI of the neck, thorax, and abdomen should be performed.

COMPLICATIONS OF CUSHING SYNDROME Hypertension :- severe hypercortisolism may present

with hypokalemia- antihypertensive therapy may be only

partially effective

IMPAIRED GLUCOSE TOLERANCE AND DIABETES. increase hepatic glycogen and glucose

production and decreasing glucose uptake and utilization by peripheral tissues.

OBESITY AND HYPERLIPIDEMIA Central obesity there is an increase in circulating very

low-density lipoprotein and low-density lipoprotein,

COAGULOPATHY cortisol stimulate the synthesis of

several clotting factors, such as fibrinogen by the liver, and von Willebrand factor by endothelial cells.

Glucocorticoids also up-regulate the synthesis of plasminogen activator inhibitor type 1

OSTEOPOROSIS loss of cortical osteocytes decrease bone collagenous matrix

synthesis inhibit calcium absorption from the gut Psychological alteration

ALTERATION OF OTHER ENDOCRINE SYSTEMS Somatotropic axis : reduces

spontaneous GH secretion Gonadal axis : may have gonadal

dysfunction Thyroid axis : suppresses thyroid

function