Endogenous Cushing Syndrome Clinical Presentation

Updated: Oct 12, 2022
  • Author: Ha Cam Thuy Nguyen, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Patients with Cushing syndrome may complain of weight gain, especially in the face, supraclavicular region, upper back, and torso. Frequently, patients notice changes in their skin, including purple stretch marks, easy bruising, and other signs of skin thinning. Because of progressive proximal muscle weakness, patients may have difficulty climbing stairs, getting out of a low chair, and raising their arms.

Menstrual irregularities, amenorrhea, infertility, and decreased libido may occur in women related to inhibition of pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which likely is due to interruption of luteinizing hormone-releasing hormone (LHRH) pulse generation. In men, inhibition of LHRH and FSH/LH function may lead to decreased libido and impotence.

Psychological problems such as depression, cognitive dysfunction, and emotional lability may develop. New-onset or worsening of hypertension and diabetes mellitus, difficulty with wound healing, increased infections, osteopenia, and osteoporotic fractures may occur.

Signs and symptoms specifically associated with endogenous Cushing syndrome include the following:

  • Patients with an ACTH-producing pituitary tumor: Headaches, polyuria, nocturia, visual problems, or galactorrhea

  • Patients with tumor mass effect on the anterior pituitary: Hyposomatotropism, hypothyroidism, hyperprolactinemia or hypoprolactinemia, hypogonadism

  • Patients with an adrenal carcinoma as underlying cause of Cushing syndrome: Rapid onset of symptoms of glucocorticoid excess in conjunction with hyperandrogenism presenting as virilization in women or feminization in men


Physical Examination


Patients may have increased adipose tissue in the face (moon facies), upper back at the base of neck (buffalo hump), and above the clavicles (supraclavicular fat pads).

Central obesity may also appear as increased adipose tissue in the mediastinum and peritoneum, increased waist-to-hip ratio greater than 1 in men and 0.8 in women; and, upon CT scan of the abdomen, increased visceral fat is evident.


Facial plethora may be present, especially over the cheeks. Violaceous striae, often wider than 0.5 cm, are observed most commonly over the abdomen, buttocks, lower back, upper thighs, upper arms, and breasts. Ecchymosis may be present. Patients may have telangiectasia and purpura, cutaneous atrophy with exposure of subcutaneous vasculature tissue and tenting of skin may be evident. Glucocorticoid excess may cause increased lanugo facial hair. If glucocorticoid excess is accompanied by androgen excess, as occurs in adrenocortical carcinomas, hirsutism and male pattern balding may be present in women. Steroid acne, consisting of papular or pustular lesions over the face, chest, and back, may be present.

Acanthosis nigricans, which is associated with insulin resistance and hyperinsulinemia, may be present. The most common sites are axilla and areas of frequent rubbing, such as over elbows, around the neck, and under the breasts.

Cardiovascular and renal

Hypertension and possibly edema may be present due to cortisol activation of the mineralocorticoid receptor leading to sodium and water retention. Cushing syndrome is also associated with cardiac structural and functional changes. Left ventricular (LV) hypertrophy and impaired LV diastolic function have been described in patients with Cushing syndrome; however, these changes are reversed upon normalization of corticosteroid excess. [14]


Peptic ulceration may occur with or without symptoms. Particularly at risk are patients given high doses of glucocorticoids (rare in endogenous hypercortisolism).


Galactorrhea may occur when anterior pituitary tumors compress the pituitary stalk, leading to elevated prolactin levels.

Signs of hypothyroidism, such as slow deep tendon reflex relaxation, may occur from an anterior pituitary tumor whose size interferes with thyroid-stimulating hormone (TSH) synthesis and release. Similarly, other pituitary function may be impacted as well.

Low testosterone levels in men may lead to decreased testicular volume from inhibition of LHRH and LH/FSH function. In women, low level of LHRH and LH/FSH lead to menstrual irregularities or amenorrhea.


Proximal muscle weakness may be evident. Osteoporosis may lead to incident fractures and kyphosis, height loss, and axial skeletal bone pain. Avascular necrosis of the hip is also possible from glucocorticoid excess.


Patients may experience emotional lability, fatigue, and depression.

Visual-field defects, often bitemporal, and blurred vision may occur in individuals with large ACTH-producing pituitary tumors that impinge on the optic chiasma.

Adrenal crisis

Patients with cushingoid features may present to the emergency department in adrenal crisis. Adrenal crisis may occur in patients on steroids who stop taking their glucocorticoids or neglect to increase their steroids during an acute illness. It may also occur in patients who have recently undergone resection of an ACTH-producing or cortisol-producing tumor or who are taking adrenal steroid inhibitors.

Physical findings that occur in a patient in adrenal crisis include hypotension, abdominal pain, vomiting, and mental confusion (secondary to low serum sodium or hypotension). Other findings include hypoglycemia, hyperkalemia, hyponatremia, and metabolic acidosis