Cushing' s syndrome is determined by the excess cortisol in blood and therefore, its signs and symptoms are the direct result of the action of  glucocorticoid hormones.

Cushing's syndome most common causes are: adrenal hyperplasia, adrenal macronodular hyperplasia, Carney's syndrome, adrenal neoplasia, prolonged use of glucocorticoids and prolonged use of ACTH. The ectopic ACTH syndrome is determined by tumors (nonpituitary) that secrete ACTH and determine adrenal hyperplasia. The symptoms of cushing's syndrome determined by the ectopic ACTH syndrome are subtle or even absent but the laboratory tests show many important changes in the biochemical values.

Cushing's syndrome most common symptoms are: truncal obesity, fatigue, hirsutism, hypertension, amenorrhea, edema, osteoporosis and purplish abdominal striae. The laboratory analysis of urine shows glucosuria.

The action of glucocorticoid hormones on the tissue metabolism determines muscle weakness and fatigability. decreased bone mineralization is very frequent among children and in adults osteoporosis, which is an important clinical issue since it can lead to fractures of the bones and to the colaps of vertebral bodies.

The increased gluconeogenesis (the body's production of glucose) and the increased resistance to insulin may reduce the glucose tolerance and therefore diabetus mellitus may occur (approximately in 20% cases).

Another common sign of Cushing's syndrome is the rapid weight gain, in which adipous tissue deposits in specific sites (lipodystrophy): the face ("moon face" aspect), the back of the head and the interscapular area ("the buffalo hump") and the mesenteric area, thus producing the "truncal obesity". The cause of this lipodystrophy is unknown , but it may be determined by by the elevated insulin levels and the insulin resistance.  The patient presents polydipsia (excessive thirst) excessive sweating and polyuria (large quantity of urine). The face is frequently plethoric (red face) even though the red cell count is normal. The massive weight gain causes the skin to stretch and therefore it can easily bruise or hemorrage, causing the purple striae( a frequent feature of Cushing's)

A common cardio-vascular manifestation of Cushing's syndrome is hypertension determined by the fact that epinephrine's vasoconstrictive effect is enhanced by cortisol. The hypertension and the hyperglicemia may also lead to different heart disease, increasing the mortality among the Cushing's syndrome patients. Cushing's syndrome may also have psychological manifestations such as profound emotional changes, irritability, depression, confusion, anxiety, emotional lability or even psychosis.

In women, cushing's syndrome may determine oligomenorhhea (reduced frequency and length of menstruation) hirsutism (male hair growth pattern in a woman) or dry, brittle hair and nails. Male patients may complain of reduced libido, impotence and infertility.Due to the fact that cortisol reduces the immune and the inflammatory response the wound healing is impaired and many patients may contact opportunistic infections.Other (less frequent symptoms of Cushing's syndrome are:acne, episternal fatty tumors and aching, sore joints (especially shoulders or lower back).