cushing syndrome
TRANSCRIPT
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DIAGNOSIS AND COMPLICATIONS OF
CUSHING’S SYNDROME
Namrata Dass
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ETIOLOGY ACTH dependent : - pituitary corticotroph adenoma
[Cushing’s disease - extrapituitary tumor (ectopic ACTH- tumor secreting CRH ACTH independent :- adrenocortical tumors adrenal
hyperplasia or dysplasia
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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
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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.
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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
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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)
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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 .
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HIGH-DOSE DST most corticotroph adenomas respond Generally ectopic tumors are resistant
to feedback inhibition. Lack of suppression in adrenal in
Cushing syndrome
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DESMOPRESSIN TEST increases ACTH secretion in 80 -90% of
patients with CD and only rarely in normal individuals or patients with pseudo-CS.
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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
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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.
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COMPLICATIONS OF CUSHING SYNDROME Hypertension :- severe hypercortisolism may present
with hypokalemia- antihypertensive therapy may be only
partially effective
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IMPAIRED GLUCOSE TOLERANCE AND DIABETES. increase hepatic glycogen and glucose
production and decreasing glucose uptake and utilization by peripheral tissues.
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OBESITY AND HYPERLIPIDEMIA Central obesity there is an increase in circulating very
low-density lipoprotein and low-density lipoprotein,
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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
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OSTEOPOROSIS loss of cortical osteocytes decrease bone collagenous matrix
synthesis inhibit calcium absorption from the gut Psychological alteration
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ALTERATION OF OTHER ENDOCRINE SYSTEMS Somatotropic axis : reduces
spontaneous GH secretion Gonadal axis : may have gonadal
dysfunction Thyroid axis : suppresses thyroid
function