Endocrinology - Adrenal Cortex and Adrenal Medulla

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What hormones are secreted by the adrenal glands?

Cortisol, aldosterone, and androgens, and catecholamines

What are the androgens?

DHEA, DHEAS, testosterone, and androstenedione

Which of the hormones are secreted from the inner medulla?

catecholamines

Which of the hormones is a glucocortoid hormone?

Cortisol

Which of the hormones is a mineralocorticoid?

Aldosterone

What does CRH (Corticotropin-releasing hormone) stimulate?

ACTH synthesis, Beta lipotrophin, Beta endorphins

In what situations is ACTH secreted?

Major illness, surgery, injury, exercise, hypoglycemia, starvation

What inhibits ACTH via negative feedback?

Cortisol

What time of day is highest amount of ACTH secreted?

early AM (0400-0600) in pulses

What time of day is the lowest amount of ACTH secreted?

night time

What is stimulated by increase in ACTH?

increase in cortisol, aldosterone and melanin secretion

What time of day is the greatest amount of cortisol secreted?

At wakening

What time of day is the lowest amount of cortisol secreted?

at bedtime

How does cortisol elevates blood glucose level?

Inhibits insulin secretion, inhibits glucose uptake by muscle and fat, increases protein breakdown for amino acid conversion to glucose and increases hepatic gluconeogenesis

How does cortisol affect fat metabolism?

increase lipolysis and quantity of free fatty acids

What is the name of group of glands that regulate the secretion of cortisol and adrenal androgens?

Hypothalamic-Pituitary-Adrenal Axis (HPA axis)

Is ACTH or the renin-angiotensin system the primary regulator of aldosterone secretion?

Renin-Angiotensin system

When cortisol inhibits glucose from being uptaken by muscles, what give muscles the energy to move?

Free fatty acids as a result of increased lipolysis, which was stimulated by cortisol

What is the major reason cortisol is used pharmacologically?

suppression of the immune system and inflammation

What are some effects of increased cortisol level?

Weight gain/truncal obesity
Inflammation/Immune System is suppressed
Sodium and water retention
growth failure in children
altered mood, behavior, and cognition
Suppresses bone formation and decreases calcium absorption (Osteoporosis)
Catabolic effects on bone, connective tissue, and muscle (loss of connective tissue, thin skin, easy bruising, development of abdominal striae, impaired wound healing)

What is the most common cause of Cushing's syndrome?

Long term use of high dose exogenous glucocorticoids

Name the glucocorticoids name in lecture.

Prednisone, dexamethasone, hydrocortisone

What is the 2nd most common cause of hypercorticolism?

ACTH-producing pituitary tumor

Do patients with Cushing's continue to have a diurnal rhythm of cortisol secretion.

No. Cortisol levels are high day and night.

Signs and Symptoms of Cushing's.

weight gain/truncal obesity, moon face, weakness, hypertension, abdominal stretch marks, easy bruising, osteoporosis, hyperglycemia/diabetes, buffalo hump, women-hirsutism and amenorrhea

Why would a patient with Cushing's have weak muscles?

Protein is being broken down to be converted to glucose.

Why would a patient with Cushing's have HTN?

Cortisol stimulates aldosterone which retains sodium and water, increases blood volume, and thus the blood pressure

Why would women develop hirsutism and amenorrhea?

Polycystic ovaries due to excess adrenal androgen production

What screening tests would you order if you suspect Cushing's syndrome?

24 hour UFC, 24 hour creatinine levels

How close should the results of the 24 hour creatinine levels be to confirm completeness of the urine collections?

within 10% of each other

What is the normal average level for 24 hour cortisol?

<55 mcg/24 h

What would be DDx of patient presenting with excess cortisol with an elevated ACTH level?

Pituitary tumor/adenoma, ectopic ACTH secretion

If there is an ectopic ACTH secretion, where is it most likely coming from?

small cell lung cancer

Can the normal regulatory mechanism control the ACTH released from an ectopic source?

No

What hormones does the small cell lung cancer usually secrete?

ACTH (Cushing's) and ADH (SIADH)

What lab results will you see in hypercortisolism with an ACTH-Independent cause?

High cortisol level and suppressed ACTH

What lab results will you see in hypercortisolism with an ACTH-dependent cause?

High cortisol level and elevated ACTH

What would be DDx of patient presenting with excess cortisol with an suppressed ACTH level?

Exogenous glucocorticoid use (duh!)
Adrenal adenoma or adrenal corticocarcinoma

What imaging test would confirm either an adrenal adenoma or adrenal corticocarcinoma?

CT

What imaging test would confirm a pituitary tumor?

MRI

What treatment has the greatest cure rate of pituitary tumor producing ACTH?

transsphenoidal surgery (90%)

What is a serious complication of radiation treatment of a tumor producing ACTH?

panhypopituitarism

If an MRI confirms a large pituitary tumor, what is your plan now?

Refer to neurosurgery

What is the life expectancy of patients with untreated Cushing's syndrome of moderate to severe degree?

Less than 5 years with death usually occurring from CV disease

If the tumor secreting ACTH cannot be resected or chemo is not effective, what is another alternative?

Pharmacologic therapy (metyrapone, aminoglutethimide or ketaconazole)

What is the most common cause of Addison's disease?

Autoimmune adrenalitis (80%)

What are causes of Addison's disease (besides autoimmune adrenalitis)?

TB, bilateral adrenal hemorrhage, congenital adrenal hypoplasia, or surgical removal of adrenal glands

Does the autoimmune adrenalitis affect the adrenal medulla?

No

How does the patient with Addison's present?

weakness, fatigue, HYPERPIGMENTATION, anorexia, n/v, orthostatic hypotension and anxiety

Why does hyperpigmentation present with Addison's?

Elevated ACTH stimulates melanocytes

What is primary adrenal insufficiency commonly called?

Addison's Disease (HYPOcortisolism)

Is Addison's often associated with other autoimmune endocrine disorders such as diabetes mellitus, Hashimoto's thyroiditis, and vitiligo?

Yes

What lab results do you expect to see in a patient with Addison's?

Low AM cortisol (<3 mcg/dl)
ACTH level is elevated (>200 pg/ml)
serum Na+ LOW
serum K+ elevated
(if chronic) chronic deficiency of cortisol and aldosterone

In which sex is Addison's more common?

Women

What causes the hyponatremia and hyperkalemia in patient with Addison's?

aldosterone deficiency

Will you see elevated or suppressed secretion of ACTH in Secondary Adrenal Insufficiency?

Suppressed ACTH

What is the most common cause of Secondary Adrenal Insufficiency?

Sudden/rapid withdrawal of long-term exogenous corticosteriod treatment

What are causes of Secondary Adrenal insufficiency?

Sudden/rapid withdrawal of long-term exogenous corticosteriod treatment
Pituitary tumors causing suppression of pituitary function
postpartum pituitary infarction
pituitary irradiation or surgery
head trauma

Will you see hyperpigmentation in Secondary Adrenal insufficiency?

No

Will you see electrolyte imbalance in Secondary Adrenal insufficiency?

No

What screening tests would you use on a patient you suspect of Primary Adrenal Insufficiency?

cosyntropin (ACTH) stimulation test

What is the normal response to the cosyntropin (ACTH) stimulation test?

increased cortisol level (>20 mcg/dl)

What result to the cosyntropin stimulation test would you expect to see in a pt with Addison's?

<20 mcg/dl increase in cortisol level

Can the cosyntropin stimulation test be given any time of day?

Yes

What result to the cosyntropin stimulation test would you expect to see in a pt with Secondary Adrenal Insufficiency?

increased cortisol level (>20 mcg/dl)

How do you treat Addison's Disease?

Replace mineralcorticoids and corticosteroids to physiologic levels with hydrocortisone, prednisone
Treat with Florinef.
Sick day rules - double glucocorticoid dose for a short time as possible for stress, acute illness, trauma, surgery
Emergency steroid kit
MedicAlert Bracelet - Adrenal Insuff - takes hydrocortisone

What is an important side effect of Florinef?

potent sodium-retaining effect

How do you treat secondary adrenal insufficiency?

Glucocorticoid (cortisone, dexamethasone, etc)
Treat the underlying pituitary disorder
Sick day rules - double glucocorticoid dose for a short time as possible for stress, acute illness, trauma, surgery
Emergency steroid kit
MedicAlert Bracelet - Adrenal Insuff

What are symptoms of the acute adrenal insufficiency (adrenal crisis)?

Extreme weakness, dehydration, hypotension, fever, nausea, vomiting, hypoglycemia, HA, confusion, coma

What tests must you order to make a diagnosis if you suspect your patient is having an adrenal crisis

Blood sample for immediate cortisol assay to distinguish adrenal insuff from other causes of shock.
Perform ACTH, electrolyte, BUN, creatinine and glucose assays
Administer a simplified cosyntropin stimulation test

Will the cosyntropin be able to stimulate a normal increase in serum cortisol in an adrenal crisis?

No.

What will the cosyntropin stimulation test indicate in an adrenal crisis?

If the patient has primary adrenal disease (ACTH will be >200 pg/ml

How do you treat an adrenal crisis?

High doses of glucocorticoid
Broad-spectrum antibiotics (empiric therapy)
Treat the cause of the underlying stress if possible

Would you use Florinef with secondary adrenal insufficiency?

No. (Aldosterone should not be affected.)

What hormones increase in a normal HPA axis?

CRH, ACTH, and cortisol

What stimulates normal aldosterone release?

Increase in plasma potassium concentration
low renal perfusion pressure due to either hypovolemia or renal artery stenosis
Increased SNS activity
Eating real licorice
Taking oral contraceptives

What symptoms would clue you in to hyperaldosteronism?

HTN
Not taking diuretics
hypernatremia
hypokalemia (unexplained)
Metabolic acidosis

What might cause excessive aldosterone production from the adrenal gland?

unilateral adrenocortical adenoma
bilateral adrenal hyperplasia
adrenal cancer

T/F. Excessive ACTH production causes adrenal hyperplasia.

True

What are secondary causes of hyperaldosteronism?

Most common cause - renal artery stenosis
Excess renin production by the kidneys
hypovolemia and CHF

What differentiates primary hyperaldosteronism from secondary hyperaldosteronism?

Plasma renin activity (primary-suppresses and secondary involves excessive)

How would you treat a unilateral adrenocortical adenoma?

unilateral adrenalectomy

How would you treat a bilateral adrenal hyperplasia?

Aldactone (aldosterone antagonist and diuretic)

How would you treat renal artery stenosis?

Angioplasty
Revascularization procedures

What are common etiologies of hypoaldosteronism?

diabetic nephropathy
hypertensive nephrosclerosis

Are deficiencies of adrenal androgens in adults clinically important?

No

What symptoms occur as a result of excess adrenal androgens?

acne, hirsutism, and virilization

Pheochromocytoma

Catecholamine-secreting tumor of chromaffin cells arising from the adrenal MEDULLA or any location along the sympathetic nervous chain (paragangliomas)

Is pheochromocytoma rare?

Yes

What ages is peak prevalence of pheochromocytoma?

30-40 year olds with HTN

What are the rule of the 10s for pheochromocytoma?

10% are NOT associated with HTN
10% are extra-adrenal
10% are extra-abdominal
10% are malignant
10% occur in children
10% are bilateral adrenal tumors
10% are familial

What is the classic symptom triad for pheochromocytoma?

HA, sweating, and palpitation
***HTN (sustained or paroxysmal) is number one symptom but not in the triad

Clinical presentation of pheochromocytoma

HTN (sustained or paroxysmal)
HA, sweating, and palpitation
Anxiety/nervousness
Tremor
Facial pallor with mottled CYANOSIS, then flushing
Tachycardia with or without precordial pain
Angina
N/V
Abdominal pain

What may cause intermittent catecholamine release?

Exertion/postural change
Meals, alcohol use, smoking
Urination/straining at stool
Emotional stress, trauma, pain
GENERAL ANESTHESIA and barbiturates
Hormones/drugs: glucagon, ACTH, histamine

What tests would you order if you suspect your patient has pheochromocytoma?

Get labs on free T4, TSH, CBC, ESR, glucose
24 hr Urine for catecholamines
24 hr urine for metanephrines (metabolites of catecholamine) - VMA

When is the best time to obtain urine samples in a patient you suspect of having pheochromocytoma who is experiencing paroxysmal episodes?

During or immediately following an episode

Should you order direct blood and urine assays for epi and norepi if the patients is experiencing PAROXYSMAL hypertension?

No. Likely to be abnormal

Should you order plasma free metanephrine or plasma free catecholamines if the patients is experiencing PAROXYSMAL hypertension?

No. Likely to be abnormal

What are some complications from pheochromocytoma?

stroke and/or sudden blindness
cardiomyopathy
cardiac arrhythmias

How would you treat pheochromocytoma?

TOC - Surgery (laparoscopic removal)
Pre-op alpha blocker or calcium channel blocker
Use beta blocker for persistent tachy or arrhythmias
For the HTN crisis: IV labetalol, Na nitroprusside or phentolamine

Why do you have to use a beta blocker AFTER an alpha blocker has been administered?

Use of a beta-blocker can initially INCREASE the blood pressure

How would you treat pheochromocytoma if you cannot operate on pheochromocytoma or it is metastatic?

Metyrosine (reduces catecholamines synthesis)

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