Cushing disease

Vignette says a 45 year old female presents to her primary care physician with chief complaints of irregular menstruation, weight gain, and fatigue over the past 8 months; Examination shows abdominal striae, facial hair and central obesity with thin extremities; Vital signs show blood pressure of 150/90 mm of Hg; Laboratory studies show random blood sugar of 258 mg/dL, elevated 24 hour urinary free cortisol levels, elevated serum ACTH levels and failure of suppression of cortisol with low dose dexamethasone whereas suppression of cortisol is evident with large dose dexamethasone; MRI shows pituitary mass; Diagnosis?

Diagnosis is Cushing’s disease; Cushing’s disease is characterized by increased ACTH production from the anterior pituitary gland.

Cushing’s syndorme

Etiologies:-

1. Iatrogenic:- MCC; Low ACTH and High Cortisol; Bilateral adrenal gland atrophy.

2. Adrenal Cushing’s:- 2nd MCC; Low ACTH and High Cortisol; Unilateral adrenal gland atrophy.

3. Pituitary Cushing’s:- MC endogenous cause; High ACTH and High Cortisol; Bilateral adrenal glands hyperplasia.

4. Ectopic Cushing’s:- Paraneoplastic ACTH secretion; High ACTH and High Cortisol; Bilateral adrenal glands hyperplasia.

Diagnosis:-

1. Screening tests to diagnose cushing's syndrome include elevated 24 hour urinary free cortisol levels, elevated level of salivary cortisol and inadequate suppression of cortisol on low dose dexamethasone test.

2. Differentiating tests for cause of cushing's syndrome (to r/o cushing's disease, ectopic ACTH secretion and adrenal tumors):-

a. Measure serum ACTH levels:- Decreased in adrenal tumors whereas Increased in ectopic ACTH secretion and cushing's disease (because they secrete ACTH independent of the HPA axis).

b. High dose dexamethasone test:- No suppression in ectopic ACTH secretion whereas adequate suppression in cushing's disease.

c. CRH stimulation test:- Increase in ACTH and cortisol in cushing's disease whereas no Increase in ACTH and cortisol in ectopic ACTH secretion.

Clinical Features:-

1. Redistribution of fat:- Central (truncal) obesity, moon facies, buffalo hump, supraclavicular fat pads with wasting of extremities or thin extremities (i.e. proximal myopathy; Increased CK levels).

2. Hypertension, hyperglycemia, hypokalemia.

3. Weight gain, osteoporosis, skin hyperpigmentation (due to increase in ACTH) with easy skin bruising and striae.

4. Acne, hirsutism, amenorrhea (these following symptoms are due to androgen excess).

5. Depression, insomnia, psychosis (these are mental symptoms of Cushing's syndrome).

Management:-

1. Cushing's disease (pituitary adenoma):- Transsphenoidal surgery (endoscopic transsphenoidal surgery is the mainstay of treatment); Radiation therapy if unresectable, surgery fails.

2. Ectopic ACTH-secreting:- Surgical removal of ectopic ACTH secreting tumors (e.g. resection of small cell carcinoma of lung).

3. Adrenal tumors:- Adrenalectomy is done in case of adrenal tumors. (e.g. ketoconazole, metyrapone may be used in inoperable patients (as it decreases cortisol production)).

4. Iatrogenic steroid therapy:- Gradual steroid taper (to prevent addisonian Crisis).

Lifelong glucocorticoid replacement therapy after transsphenoidal surgery whereas lifelong glucocorticoid and mineralocorticoid replacement therapy after surgical or medical bilateral adrenalectomy.