Pathology of Cushing's syndrome Animated lecture: etiology, diagnosis, signs and symptoms and management
Cushing's syndrome occurs due to an excess of glucocorticoids in circulation over a period of time. The most common cause is iatrogenic, including the use of topical and inhaled glucocorticoids. The endogenous causes of Cushing's syndrome can be divided into adrenocorticotrophic (ACTH) dependent and non-dependent ACTH. ACTH-dependent disease arises when there is an increase in ACTH either from the pituitary gland (Cushing's disease) or from an ectopic tumor producing ACTH. The non-ACTH-dependent disease occurs due to adrenal adenomas or adrenal carcinomas.
Cushing's disease accounts for two-thirds of all cases of endogenous Cushing's syndrome and is caused by excessive secretion of the hormone ACTH by a pituitary microadenoma. This leads to an increased secretion of cortisol (secondary adrenal hypercortisolism) of the adrenal cortex, as well as an increase in androgen levels. The typical characteristics of Cushingoids observed in patients with Cushing's syndrome arise due to the excess of glucocorticoids. These Cushingoid features are due in part to the redistribution of fat and typical changes in the skin.
The changes in the skin in Cushing's syndrome are multiple. The skin becomes thin and translucent, and ecchymosis occurs after minor trauma. The thinning of the epidermis also leads to the plethoric appearance of the skin. Hyperpigmentation of the skin can be observed, but it is more common in the pituitary or ectopic production of ACTH. Although widespread, it tends to occur in areas exposed to the sun. Addison's disease also produces a similar pattern of hyperpigmentation in areas exposed to the sun, but it also occurs in the following areas: palmar folds, areas of friction, vermilion border, genital skin, and oral mucosa.
Acne, hirsutism and menstrual irregularities, whether oligomenorrhea or amenorrhea, arise due to increased androgen levels.
The hypersecretion of cortisol also predisposes to hypertension, peripheral edema, glucose intolerance, gonadal dysfunction, osteoporosis and proximal muscle weakness. Psychiatric symptoms may be present in the vast majority of patients (more than 70%), and the severity of symptoms varies from anxiety to mania, depression and frank psychosis. Insomnia occurs early in the disease.
Ectopic ACTH production can also lead to Cushing's syndrome. In these patients, due to the sudden onset of Cushing's syndrome, there is no time to develop the characteristic clinical features. In contrast, these patients will have hypertension, edema, glucose intolerance and sudden onset hypokalemia. Seventy-five percent of these tumors are small cell lung carcinomas. Ectopic ACTH is produced by bronchial carcinoids, thymic or pancreatic carcinoids, thymic neuroendocrine tumors, medullary carcinoma of the thyroid or pheochromocytomas.
Patients with carcinoid tumors or pheochromocytomas generally have the typical characteristics of Cushingoids, as they develop over a longer period of time. Due to the immunosuppressive effects of glucocorticoids, these patients commonly develop cutaneous infections due to staphylococci, candidiasis and superficial fungi. The incidence of pituitary-dependent hypophysary adrenal hyperplasia is more frequent in women three times, with an average age of onset in the third and fourth decades.
Mortality increases 4 times compared to the general population, and cardiovascular disease is the leading cause of death.
Although it is rare in children, obesity and delayed growth may be a presenting characteristic.
Video credits to Dr.G.Bhanu Prakash – Usmle , FMGE and Neet PG YouTube channel