cushing syndrome
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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
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