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  • 1. Namrata Dass
  • 2.  ACTH dependent : - pituitary corticotroph adenoma [Cushing’s disease - extrapituitary tumor (ectopic ACTH - tumor secreting CRH  ACTH independent : - adrenocortical tumors adrenal hyperplasia or dysplasia
  • 3.  central obesity , purple striae, proximal muscle  weakness, fatigue, high blood pressure, glucose intolerance,  acne, hirsutism, and menstrual irregularity.  Neuropsychological disturbances  sleep disturbances, and cognitive
  • 4. First-line screening tests 1) Twenty-four-hour urinary free cortisol (UFC) 2) Low-dose dexamethasone suppression tests (DST) 3) Late-night salivary cortisol.
  • 5.  Advantages : - not affected corticosteroid-binding globulin (CBG) levels  Disadvantages : - Affected by GFR - Influenced by various metabolites of cortisol and some synthetic glucocorticoids
  • 6. Limitations : - interfering conditions causing an apparent lack of suppression include: 1) decreased dexamethasone absorption, 2)drugs enhancing hepatic dexamethasone metabolism (barbiturates, phenytoin, carbamazepine, rifamp icin, mepro- bamate, aminoglutethimide, methaqualone), 3)increased concentration of CBG (estrogen treatment, pregnancy)
  • 7.  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 .
  • 8.  most corticotroph adenomas respond  Generally ectopic tumors are resistant to feedback inhibition.  Lack of suppression in adrenal in Cushing syndrome
  • 9.  increases ACTH secretion in 80 -90% of patients with CD and only rarely in normal individuals or patients with pseudo-CS.
  • 10.  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
  • 11.  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.
  • 12.  Hypertension : - severe hypercortisolism may present with hypokalemia - antihypertensive therapy may be only partially effective
  • 13.  increase hepatic glycogen and glucose production and decreasing glucose uptake and utilization by peripheral tissues.
  • 14.  Central obesity  there is an increase in circulating very low- density lipoprotein and low-density lipoprotein,
  • 15.  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
  • 16.  loss of cortical osteocytes  decrease bone collagenous matrix synthesis  inhibit calcium absorption from the gut  Psychological alteration
  • 17.  Somatotropic axis : reduces spontaneous GH secretion  Gonadal axis : may have gonadal dysfunction  Thyroid axis : suppresses thyroid function