Adrenal Dysfunction

Question 1

Contrast the venous drainage of left and right adrenals.

Answer 1

left adrenal vein drains into the left renal vein, the right adrenal vein drains directly into the IVC

Question 2

When are levels of cortisol highest?

Answer 2

highest around 6-9am and lowest around 2p, there is variability in pulses but the pattern is generally biphasic

Question 3

What enzyme does the zona glomerulosa lack?

Answer 3

17-hydroxylase (also not in the placenta?)

Question 4

What are the clinical features of primary adrenocortical insufficiency?

Answer 4

glucocorticoids: weakness, fatigue anorexia, weight loss, GI disturbances
mineralcorticoids: hypotension, salt craving, postural symptoms, hyperkalemia
excess ACTH/MSH: hyperpigmentation

Question 5

What are the common a rare causes of primary adrenocortical insufficiency?

Answer 5

major: autoimmune (80%), TB (20%)
rare: adrenal hemorrhage, infarction, fungal infections, metatastic disease, amyloidosis, sarcoid, HH, radiation, surgical adrenalectomy

Question 6

How do the symptoms of secondary adrenal insufficiency differ from those of primary insufficiency?

Answer 6

similar but usually less pronounced (serum cortisol may be normal or low) esp. those symptoms related to low mineral corticoids because those are normally maintained by RAAS in absence of ACTH

hyponatriemia can be due to ADH/ACTH ratio

(acute syndrome can be caused by pituitary apoplexy)

Question 7

What is Waterhouse Friedricksen Syndrome?

Answer 7

caused by infarction of the adrenal gland often accompanies meningococcal infection

Question 8

What is a distinguishing symptom of adrenal hemorrhage.

Answer 8

usually commonly associated with pain, whereas chronic damage is unlikely to present with pain (flank/abdomen) as well as other symptoms shared with low levels of glucocorticoids

Question 9

How do you distinguish between primary or secondary adrenocortical insufficiency from lab tests.

Answer 9

start with a serum cortisol (check when they are naturally low if concerned about hyposecrtion)

secondary test include rapid ACTH stimulation test (and measure cortisol) to determine if the adrenal gland is working

Question 10

Name an iatrogenic cause of secondary adrenocortical insufficiency.

Answer 10

giving steroids (stop ACTH stimulation with negative feedback)

Question 11

What are medical treatments for maintenance of therapy for adrenocortical insufficiency?

Answer 11

hydrocortisone (identical to cortisol), higher dose in AM
fludrocortisone- mineralcorticoid properties PO in AM
+/- DHEA
patient education re: ID bracelet and cortisol dose adjustment

monitor weight, blood pressure, electrolytes

Question 12

What are features of Cushing’s syndrome?

Answer 12

central obesity
facial plethora
hirsutism
menstrual disorders
hypertension
muscular weakness
back pain
striae
acne
psychologic symptoms

Question 13

Contrast Cushing Syndrome and Cushing disease.

Answer 13

Cushing disease is specifically the condition of pituitary dysfunction causing low levels of glucocorticoids and cushingoid features

Cushing’s syndrome can have many causes

Question 14

Contrast ACTH dependent and independent causes of Cushing syndrome.

Answer 14

dependent: (central-ish) Cushing disease, ectopic corticotropin syndrome, ectopic CRH syndrome
independent: (adrenal-ish) adrenal adenoma, adrenal carcinoma, macro nodular hyperplasia

Question 15

What types of tumors cause ectopic ACTH syndrome?

Answer 15

small cell carcinoma of the lung (50%)
pancreatic islet tumors
thymoma
carcinoid tumors
pheochromocytoma

(can present with sudden onset DM, HTN, very high ACTH and hypercalemia)

Question 16

How do you differentiate between pituitary and ectopic causes of excess CRH/ACTH?

Answer 16

pituitary tumors often show suppression when dexamethasone is administered (some overlap)

ectopic tumors will not respond to CRH stimulation where as those with Cushing disease do respond

pituitary tumors present with a gradient if bilateral simultaneous blood sampling of inferior petrosal sinuses is performed (**with CRH stimulation)

Question 17

What are different ways you can detect excess cortisol?

Answer 17

24hr. cortisol urine collection

salivary cortisol around midnight (after low-key evening)

Question 18

How does the level of ACTH secretion vary with whether the ectopic source of ACTH is benign or malignant?

Answer 18

much higher levels are see in malignant tumors v. benign

Question 19

What treatments are indicated for Cushing’s disease?

Answer 19

TSS, pituitary irradiation and total bilateral adrenalectomy (in that order)

caution: removal of adrenal gland can sometimes remove negative feedback and lead to expansion of tumor and Nelson’s syndrome (hyper pigmentation)

Question 20

What treatments are indicated for adrenal tumor?

Answer 20

surgical resection of tumor, for carcinomas, cure is often not possible, +/- adrenal enzyme inhibitors

Question 21

What treatments are indicated for ectopic sources of excess glucocorticoids?

Answer 21

surgical resection if tumor can be found, octreotide scans helpful (often difficult with NET), adrenal enzyme inhibitors may be used in malignant disease and indolent tumors may be related by medical or surgical adrenalectomy

Question 22

What DNA segment does the GR receptor bind to within the nucleus after being activated?

Answer 22

GR translocates, dissociated from HSP and binds to GRE segments of gene to regulate transcription.

Question 23

How do steroids interfere with the immune system?

Answer 23

GR binding creates a product that slows the metabolism of INFkB binding protein, INFkB protein is inactive when bound to the carrier protein, reducing inflammatory response

Question 24

What is unique about the pharmacology of fludrocortisone?

Answer 24

potent mineral corticoid activity with negligible glucocorticoid actions

Question 25

What are the most potent forms of glucocorticoids?

Answer 25

dexamethasone (strongest, no MR activity)
methylprednisolone
prednisone/prenisolone
cortisol/hyrocrotisone

Question 26

Describe the specificity of mineral corticoid receptors.

Answer 26

MR are often paired with 11-B-hydroxysteroid dehydrogenase and converts cortisol to cortisone (inactive) to minimize its action at MR

if levels of cortisone are high enough, the enzyme will be overwhelmed, this enzyme can also be suppressed by consumption of licorice