Endocrine #5 (Adrenal Disorders)

Question 1

In Addison’s Disease (Primary Chronic Adrenocortical Insufficiency), the adrenal gland is not making enough _______.

Causes of Addison’s Disease

Answer 1

Cortisol

Adrenal Gland Destruction (lack of cortisol AND aldosterone)
-Autoimmune (MC) in US
-Infection MC in developing countries
-Others: TB, Trauma, Ketoconazole, Rifampin, HIV

Question 2

Symptoms of Addison’s Disease

Answer 2

-Symptoms due to lack of cortisol
–Sparse axillary and pubic hair
–Fatigue, weakening
–Hypotension (orthostatic)
–Hyperpigmentation (in waist line, fat creases, ORAL 1st)
–Salt craving
–Loss of libido, amenorrhea, n/v, weight loss

Question 3

Explain the hypothalamus-pituitary-adrenal axis and how this affects cortisol

Answer 3

-Hypothalamus secretes CRH to stimulate pituitary gland to secrete ACTH to stimulate adrenals to secrete cortisol

Question 4

Therefore, what do labs show in PRIMARY adrenocortical insufficiency?

Answer 4

-Elevated ACTH
–8AM ACTH, cortisol, and renin levels
–Increased renin levels in primary

Question 5

However, in SECONDARY adrenocortical insufficiency, what labs are expected?

Answer 5

-Decreased ACTH

Question 6

What other labs are obtained in primary (Addison’s) adrenocortical insufficiency?

Answer 6

-Hypoglycemia
-Hyperkalemia
-Hyponatremia
-Metabolic Acidosis

Question 7

What is the effect of cortisol on blood sugar?

Answer 7

Cortisol raises blood sugar by releasing stored glucose.

Therefore, if cortisol is LOW, blood sugar will be low. Hypoglycemia is expected in Addison’s Disease.

Question 8

What labs are diagnostic for chronic adrenocortical insufficiency?

Answer 8

Low plasma cortisol, elevated ACTH

Question 9

What screening test can be done for primary adrenocortical insufficiency (Addison’s)?

Answer 9

High-dose ACTH Cosyntropin stimulation test
–Insufficiency (<18) or absent rise in serum cortisol after ACTH administration IV or IM

-Normal response is rise in serum cortisol

-Check after 60-90 minutes to determine if there is a rise or not

Question 10

Treatment for Addison’s Disease (Primary Adrenocortical Insufficiency)

Answer 10

-Glucocorticoid Replacement: Oral hydrocortisone
-Mineralocorticoid Replacement as well: Fludricortisone if positive for Addison’s

Question 11

Because cortisol is a stress hormone, people with chronic adrenal insufficiency must be treated with ______ and ________ before and after surgical procedures (mimicking the body’s natural response)

Answer 11

-IV Glucocorticoids and IV isotonic fluids

Question 12

What is Adrenal (Addisonian) Crisis?

Answer 12

-Acute adrenocortical insufficiency: sudden worsening of symptoms precipitated by stressful event (illness, surgery, trauma, MI, fever) or abrupt withdrawal of glucocorticoids (MC)

Normal response to stress is a 3-fold increase in cortisol, but these patients cannot meet the demand.

Question 13

Symptoms of Addisonian Crisis

Answer 13

-All the same symptoms of Addison’s Disease (salt craving, hyperpigmentation, muscle pain) + high fever, hypotension, hypovolemia (SHOCK)!!!!

Question 14

Although the labs are the same as in Addison’s Disease, what are they?

Answer 14

-Hyponatremia, hyperkalemia, hypoglycemia
–Cortisol and aldosterone confirms diagnosis

Question 15

Treatment for an Addisonian Crisis

Answer 15

-Isotonic fluids (normal saline or D5N5) + IV hydrocortisone or Dexamethasone
-Reversal of electrolyte disorders
-Fludricortisone

Question 16

Back to chronic adrenocortical insufficiency, explain a secondary cause pathology and what is low in this condition?

Answer 16

Pituitary failure of ACTH secretion (lack of cortisol only). Aldosterone intact due to renin angiotensin aldosterone system (RAAS)

Question 17

Primary Adrenocortical Insufficiency:

Secondary:

Answer 17

Lack of cortisol AND Aldosterone

Lack of cortisol only

Question 18

What is Cushing’s Syndrome?

Answer 18

Syndrome: symptoms and signs related to cortisol excess.

Question 19

There are exogenous causes of Cushing’s Syndrome and endogenous causes. Explain both.

Answer 19

Exogenous: long-term high dose glucocorticoid therapy

Endogenous:
-Cushing’s Disease (pituitary gland ACTH overproduction (pituitary adenoma) MCC)
-Ectopic ACTH-producing tumor (small cell lung cancer, etc.),
-Adrenal tumor (Adenoma) that secretes excess cortisol

Question 20

Symptoms of Cushing’s Syndrome

Answer 20

-Proximal muscle weakness
-Weight gain
-Fat Redistribution: Central obesity, moon facies, Buffalo hump, supraclavicular fat pads, thin extremities
-Skin Changes: Striae, acanthosis nigricans, easy bruising, poor wound healing
-Androgen Excess: hirsutism, acne, oily skin
-Hypertension

Question 21

What happens when the body recognizes there is low cortisol or experiencing stress?

(H-P-A axis)

Answer 21

Hypothalamus releases CRH that stimulates the pituitary to release ACTH to stimulate adrenal gland to secrete cortisol

Question 22

What vision changes are expected with Cushing’s Syndrome?

Answer 22

Bitemporal vision changes

Question 23

What are three screening tests for Cushing’s Syndrome?

Answer 23

-24 hour urinary free cortisol (most specific)
-Nighttime salivary cortisol
-Low dose (1mg) overnight Dexamethasone suppression test

Question 24

What is expected on the Dexamethasone suppression test if the patient has Cushing’s?

Answer 24

-Elevated cortisol or no suppression with low dose Dexamethasone

Question 25

How do you differentiate Cushing’s Disease from other causes of Cushing’s Syndrome?

Answer 25

Baseline ACTH + High Dose Dexamethasone suppression test

–Increased ACTH + suppression of cortisol on high dose.

Question 26

What is expected on high dose dexamethasone suppression test if the Cushing’s Syndrome is due to ectopic ACTH producing tumor or adrenal tumor or steroid use?

Answer 26

Ectopic ACTH tumor: increased ACTH + no suppression

Adrenal tumor and steroids: decreased ACTH + no suppression

Question 27

What other labs are expected in Cushing’s?

Answer 27

-Hyperglycemia (high cortisol –> pulls glucose out)
-Leukocytosis
-Hypokalemia
-Metabolic alkalosis

Question 28

Treatment for Cushing’s Syndrome

Answer 28

-If due to corticosteroid steroid: gradual taper to prevent Addisonian crisis
-if Cushing Disease: Transsphenoidal resection
-Adrenal Tumor: tumor excision
-Ectopic tumor: resection

Question 29

What is a pheochromocytoma?

What is it associated with?

Answer 29

Catecholamine secreting adrenal tumor (chromaffin cells)

MEN Syndrome II

Question 30

A pheochromocytoma secretes _____, _______, and _______ autonomously and intermittently from triggers including surgery, exercise, pregnancy, meds (TCA, opiates, histamine, glucagon)

Answer 30

Serotonin
Norepi
Epi

Question 31

Symptoms of a pheochromocytoma (PHE)

Answer 31

-HYPERTENSION**

-Palpitations
-Headache
-Excessive Sweating

Question 32

What diagnostic can be done to diagnose a pheochromocytoma?

Answer 32

-Plasma fractionated metanephrines confirmed by 24 hour urinary fractionated catecholamines including metabolites (increased metanephrines and vanillylmandelic acid)

Question 33

Treatment for a pheochromocytoma

Answer 33

-Nonselective alpha blockade: Phenoxybenzamine or Phentolamine for 1-2 weeks, then Beta Blockers or CCB to control BP prior to surgery

-Complete adrenalectomy after 1-2 weeks of medical therapy

Question 34

Primary hyperaldosteronism occurs renin-independently. What are some causes of this?

Answer 34

-Idiopathic or bilateral adrenal hyperplasia (MC)
-Conn Syndrome: adrenal aldosteronoma

Question 35

On the other hand, what is secondary hyperaldosteronism?

Answer 35

-Due to increased renin (from the kidneys), via the RAAS.
–Renal artery stenosis MCC of secondary

Question 36

Symptoms of hyperaldosteronism

Answer 36

-Usually asymptomatic
-Triad of hypertension + hypokalemia + metabolic alkalosis
–Hypokalemia: proximal muscle weakness, polyuria, decreased DTR’s
–Hypertension: headache, flushing

Question 37

True or False: Primary hyperaldosteronism is a cause of secondary hypertension?

Answer 37

True!

Suspect in patients who develop hypertension at extremes of age (<30 or >60), not controlled on 3 blood pressure medications, or with classic triad

Question 38

What is a screening test that can be done for hyperaldosteronism?

Answer 38

-Plasma renin and aldosterone levels: aldosterone to renin ratio: ARR > 20:1.
–High aldosterone and low renin levels = primary
–High plasma renin levels = secondary

Question 39

Confirmatory tests for hyperaldosteronism include…

Answer 39

Oral sodium loading test: high urine aldosterone = primary

Saline infusion test: no suppression of aldosterone levels = primary

CT or MRI to look for adrenal mass or extra-adrenal mass

Question 40

Treatment for bilateral hyperplasia of adrenals (primary cause)

Answer 40

-Spironolactone or Eplerenone (they block aldosterone), ACE inhibitors, CCB

Question 41

Treatment for Conn Syndrome

Answer 41

-Surgical Excision + Spironolactone (blocks aldosterone)