Hyperglucocorticism - classification, etiology, pathogenesis, and clinical manifestations.
Hyperglucocorticism refers to excess levels of glucocorticoids (especially cortisol) in the body.
- Clinically manifests as Cushing syndrome.
Classification
- 1 According to source of cortisol excess
Etiology
ACTH- dependent
- Cushing disease: pituitary adenoma producing ACTH (most common endogenous cause).
- Ectopic ACTH production: from non-pituitary tumors (e.g., small cell lung carcinoma, bronchial carcinoid).
ACTH- independent
- Adrenal adenoma or carcinoma: autonomous cortisol secretion.
- Adrenal hyperplasia (less common).
Iatrogenic (exogenous)
- Most common overall cause: prolonged high-dose corticosteroid therapy (e.g., for autoimmune diseases).
Pathogenesis
- Increased cortisol levels, regardless of source.
- Metabolic effects of excess cortisol:
- Increased gluconeogenesis → hyperglycemia → insulin resistance → diabetes mellitus.
- Increased protein catabolism → muscle wasting, skin thinning.
- Increased lipolysis with abnormal fat redistribution.
- 3 Mineralocorticoid effects (at high levels):
- Sodium and water retention → hypertension.
- Hypokalemia (in some cases).
- 4 Inhibition of immune and inflammatory responses:
- Increased susceptibility to infections.
- Impaired wound healing.
Clinical manifestations
General appearance
- Central (truncal) obesity.
- Moon face (rounded face).
- Buffalo hump (fat pad on upper back/ neck).
- Thin extremities (due to muscle wasting).
Skin changes
- Thin, fragile skin.
- Easy bruising.
- Purple striae (stretch marks), especially on abdomen.
- Poor wound healing.
Musculoskeletal
- Proximal muscle weakness (e.g., difficulty climbing stairs, rising from chair).
- Osteoporosis → fractures.
Metabolic
- Hyperglycemia, diabetes mellitus.
- Hyperlipidemia.
Cardiovascular
- Hypertension (due to sodium retention and vascular sensitivity).
Neuropsychiatric
Mood swings, irritability.
Depression, psychosis.
Reproductive system
Women: menstrual irregularities, hirsutism (due to adrenal androgen excess).
Men: decreased libido, impotence.
Immune system
Increased susceptibility to infections.