Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). A common sign is the growth of fat pads along the collar bone and on the back of the neck (buffalo hump) (known as a lipodystrophy) and a round face often referred to as a "moon face". Other symptoms include excess sweating, telangiectasia (dilation of capillaries), thinning of the skin (which causes easy bruising and dryness, particularly the hands) and other mucous membranes, purple or red striae (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth). In rare cases, Cushing's can cause hypercalcemia, which can lead to skin necrosis. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, reduced libido, impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety are also common.[3]
Cushing's syndrome may present with striking and distressing skin changes including hyperhidrosis, dryness, fragility of the skin, facial acne, susceptibility to superficial dermatophyte and malassezia infections, a plethora over the cheeks, anterior neck, and V of the chest, and the characteristic purplish, atrophic striae on the abdomen.[4]:500
Other signs include polyuria (and accompanying polydipsia), persistent hypertension (due to cortisol's enhancement of epinephrine's vasoconstrictive effect) and insulin resistance (especially common in ectopic ACTH production), leading to hyperglycemia (high blood sugar) which can lead to diabetes mellitus. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation, such as acanthosis nigricans in the axilla. This is due to Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Pro-opiomelanocortin (POMC). Cortisol can also exhibit mineralcorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, gastrointestinal disturbances, opportunistic infections and impaired wound healing (cortisol is a stress hormone, so it depresses the immune and inflammatory responses). Osteoporosis is also an issue in Cushing's syndrome since, as mentioned before, cortisol evokes a stress-like response. Consequently, the body's maintenance of bone (and other tissues) becomes secondary to maintenance of the false stress response. Cushing's syndrome may also elicit hirsutism (male-pattern hair growth in a female, and/or cause hair to become extremely dry and brittle) and oligomenorrhea (decreased frequency of menstruation) due to elevations in androgens (male sex hormones), normally at low levels in women. Additionally, Cushing's may cause sore and aching joints, particularly in the hip, shoulders, and lower back.
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