Endocrinology

Question 1

Cortisol Physiology

žLevel of serum cortisol

• begins to rise at _____

ž- reaches a peak at _____

ž- then _____

• In Cushing’s _____

Answer 1

3 AM

8 AM

Falls for the rest of the day, to very low levels when the person is unstressed and asleep at midnight

In Cushing’s syndrome: loss of late night cortisol nadir

Question 2

Types of Cushing’s

Answer 2

ACTH Dependent

• Cushing’s disease—pituitary (most common)
• Ectopic ACTH

— Small cell carcinoma

— Neuroendocrine tumors of pancreas, thymus

— Bronchial carcinoid

— Medullary thyroid cancer

• Ectopic CRH

Exogenous ACTH

ACTH Independent

• Exogenous glucocorticoids
• Adrenal adenomas, carcinomas
• Bilateral adrenal hyperplasia
• Bilateral adrenal micronodular hyperplasia

Question 3

What are some of the symptoms that patients with Cushing’s syndrome/disease present with?

Answer 3

• Most common:
  
  • Decreased libido
  • Weight gain
  • Menstrual changes
  • HTN, hyperglycemia
  • Hirsutism
• Less common
  
  • Striae
  • Edema
  • Proximal muscle weakness
  • Osteopenia/osteoporosis
  • Recurrent infections

Question 4

What are the lab abnormalities associated with Cushing’s? How are these explained in regards to the underlying pathophysiology?

Answer 4

• High serum cortisol overwhelms the ability of the kidneys to convert cortisol to cortisone resulting in activation of the mineralcorticoid receptors.
• Causing*
• Hyperglycemia
• Hypokalemia
• Metabolic alkalosis
• +/- Hypernatremia (ACTH can stimulate aldosterone, and mineralcorticoid effects of cortisol)

Question 5

In what patients should you consider screening patients for Cushings?

Answer 5

• Patients with obvious findings of Cushing’s (purple striae, facial plethora, proximal myopathy).
• HTN or osteoporosis in young patients
• Unexplained/resistant HTN
• Adrenal incidentalomas

However before you test, need to rule out other causes of high cortisol:

• PCOS
• Pregnancy
• Physical stress
• Malnutrition, amenorrhea

Question 6

What tests can you perform to tests for Cushings?

Answer 6

• Low dose: Dexamethasone supression test
  
  • Administer 1 mg of Dex at 11 p.m.
  • Check ACTH, Dex and Cortisol levels at 8 a.m.
  • Can use anytime of the day
  • If cortisol levels remain high in the morning suspect Cushings syndrome or Cushings disease
• High dose: Dexamethasone supression test
  
  • Administer 8 mg of dexamethasone similar to above
  • Check ACTH, dex, and cortisol levels in the morning

Question 7

How do you interpret low and high dose dexamethasone supresion tests?

Answer 7

• The normal response to the low dose dexamethasone test is for ACTH and cortisol to be supressed, if elevated need to pursue high dose supression test
• If ACTH and Cortisol supressed by the high dose suspect Cushings disease, as there appears to be feedback control on the pituitary.
• If ACTH is low and Cortisol remains high, suspect Cushings syndrome as this is due to cortisol being secreted by a non-dependent ACTH process
• If ACTH and Cortisol both remain elevated, suspect ectopic secretion of ACTH

Question 8

How do you treat Cushing’s disease (increased secretion of ACTH)?

Answer 8

• Transsphenoidal removal if a microadenoma is present
  
  • Most patients will be hypoadrenal for months and will require glucocorticoid replacement.
  • While waiting for surgery can use cabergoline (dopamine receptor agonist)
• Metastatic disease; no cure