This document summarizes Cushing's syndrome, including its causes, signs and symptoms, screening tests, and diagnostic process. Cushing's syndrome can be ACTH-dependent or independent and is caused by excessive cortisol secretion. Screening tests include urine cortisol and low-dose dexamethasone suppression tests. If screening indicates Cushing's, further tests are needed to determine the source and guide treatment, such as MRI, PET, and bilateral inferior petrosal sinus sampling. Long-term complications include diabetes, high blood pressure, bone loss, and psychological issues if not treated.

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

5. First-line screening tests
1) Twenty-four-hour urinary free cortisol
(UFC)
2) Low-dose dexamethasone suppression tests
(DST)
3) Late-night salivary cortisol.

6.  Advantages :
- not affected corticosteroid-binding globulin
(CBG) levels
 Disadvantages :
- Affected by GFR
- Influenced by various metabolites of cortisol
and some synthetic glucocorticoids

7. 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)

8.  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 .

9.  most corticotroph adenomas respond
 Generally ectopic tumors are resistant to
feedback inhibition.
 Lack of suppression in adrenal in Cushing
syndrome

10.  increases ACTH secretion in 80 -90% of
patients with CD and only rarely in normal
individuals or patients with pseudo-CS.

11.  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

12.  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.

14.  Hypertension :
- severe hypercortisolism may present with
hypokalemia
- antihypertensive therapy may be only
partially effective

15.  increase hepatic glycogen and glucose
production and decreasing glucose uptake
and utilization by peripheral tissues.

16.  Central obesity
 there is an increase in circulating very low-
density lipoprotein and low-density
lipoprotein,

17.  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

18.  loss of cortical osteocytes
 decrease bone collagenous matrix synthesis
 inhibit calcium absorption from the gut
 Psychological alteration

19.  Somatotropic axis : reduces spontaneous GH
secretion
 Gonadal axis : may have gonadal dysfunction
 Thyroid axis : suppresses thyroid function