- In response to low serum cortisol or stress the hypothalamus secretes corticotropin releasing factor (CRF).
- In response to CRF the pituitary releases adrenocorticotropic hormone (ACTH). In response to
- In response to ACTH the adrenal glands secrete cortisol
- In response to elevated cortisol levels the hypothalamus decreases production of CRF.
- If you are unclear about how a negative feedback loop works, here is a link to a video with that might help. (I couldn’t find anything great and despite how much I would like to, there is no way I’m adding video to the site right now.)
Cortisol is produced by the adrenal glands in a reaction to stress. Its main functions are to suppress the immune response and increase available energy by increasing blood sugar levels and promoting the breakdown of fat and protein.
- Cushing’s syndrome = excessive cortisol production
- Addison’s disease = low cortisol production
- Hyperfunction comes from one of several places
- Cushing’s disease
- Pituitary adenoma with hypersecretion of ACTH stimulating cortisol production in the adrenals. Women have a three times greater chance of having this than men.
- Adrenal tumor producing an increase in cortisol
- Ectopic production of ACTH – most commonly a small cell lung cancer
- Long term use of corticosteroids usually in treatment of another disease
- Obesity – fat is centrally located but the limbs are skinny. Buffalo hump and moon faces!
- Proximal muscle weakness – one of the most specific signs
- Pigmented striae – one of the most specific signs. Found on thigh, breast and abdomen
- Sexual issues
- Oligomenorrhea or amenorrhea
- erectile dysfunction
- poor wound healing
- superficial skin infections
- Thirst and polyuria
- Problems with calcium including kidney stones, osteoporosis, avascular necrosis
- Mental – there is a spectrum from decreased concentration up through frank psychosis
Labs and Studies:
- Glucose elevated
- Cortisol is elevated
- ACTH may be high, normal or low.
- elevated – pituitary or ectopic adenoma
- low – adrenal tumor
- Overnight dexamethasone suppression test. Patient gets 1mg of dexamethasone at 12pm. 8 am plasma cortisol should be < 5 µg/dl. Positive test is > 10 µg/dl.
- Best dx made with a 24 hour urine collection. Free cortisol > 125 µg/dl is diagnostic
- MRI, CT and plain Chest Film all have a role in locating a adenomas.
- For Cushing’s disease (pituitary adenoma) transsphenoidal resection
- Surgical removal of tumors causing the problem is the best option in all cases were that is possible, otherwise chemotherapy or radiation therapy is a possibility
- If tumor cannot be destroyed or removed – metyrapone and ketoconazole may suppress hypercortisolism. Parenteral octreotide may suppress ACTH
- Often patients treated for Cushing’s syndrome will go into cortisol withdraw, Addison’s disease, and require hydrocortisone or prednisone.