Clin Med Deck Adrenal disorders

Question 1

What are the three layers to the adrenal cortex?

Answer 1

Zona glomerulosa, Zona fasciculata, and zona reticularis

Question 2

What does the zona glomerulosa make? What do they do? Example?

Answer 2

Zona glomerulosa makes mineralcorticoids Mineralcorticoids regulate blood pressure and electrolyte homeostasis. An example of this is aldosterone.

Question 3

What does the zona fasciculata make? Example? What do they do?

Answer 3

Zona fasiculata produces glucocorticoids Glucocorticoids regulate the stress response, immune system, and metabolism. An example of this is cortisol, corticosterone, and cortisone.

Question 4

What does the zona reticularis make? What do they do? Example?

Answer 4

Zona reticularis produces androgens. These are converted to sex steroids such as testosterone, An example of this is DHEA - can be thought of as an intermediate to sex steroids.

Question 5

What’s a mnemonic to help remember the layers of the adrenal cortex?

Answer 5

Go find Rex - Zona Glomerulosa, Zona fasciculata, zona reticularis Make good sex - Mineralcorticoids, glucocorticoids, (sex hormones)/androgens

Question 6

What does the adrenal medulla make?

Answer 6

The adrenal medulla makes catecholamines such as epinephrine and norepinephrine. It also makes a small amount of dopamine

Question 7

What does aldosterone do? What is production stimulated by?

Answer 7

Aldosterone is mineralcorticoid. It is synthesized from cholesterol.

Aldosterone is secreted whenever there is an increase in potassium in the blood. It is also stimulated by angiotensin II whenever there is low blood volumes.

Aldosterone works on the distal convoluted tubules and collecting ducts and works to reabsorb sodium and excretes potassium and hydrogen. This effectively leads to water retention which would lead to increase in blood pressure. It works in the renin-angiotensin-aldosterone system.

Question 8

Describe the Renin-Angiotensin-Aldosterone system in steps

Answer 8

1) The Renin-Angiotensin-Aldosterone system is stimulated by a Sodium deficiency, dehydration, or hemorrhage
2) Na+ deficiency, hemorrhage, or dehydration all equate to decrease in blood volume
3) A decrease in blood volume equates to a decrease in blood pressure
4) A decrease in blood pressure is sensed by the juxtaglomerular cells of the kidney
5) In a response from the decrease in blood pressure, the juxtaglomerular cells will secrete renin.
6) Not only if renin produced but angiotensinogen is then also produced by the liver. Any angiotensinogen floating around in the blood stream is then turned into angiotensin 1 via renin.
7) Angiotensin 1 then goes to the lungs
8) The lungs have high amounts of angiotensin converting enzyme so they convert angiotensin 1 into angiotesin II.
9) Angiotensin II is one of the molecules that has effects on the body. It will directly cause vasoconstriction of arterioles increasing blood pressure, it will also go to the adrenal cortex to stimulate the release of aldosterone.
10) The release of aldosterone causes sodium reabsorption into the blood stream and then causes the excretion of potassium and hydrogen ions.
11) The increase in sodium in the bloodstream will effectly increase water reaborption which in turn increase blood volume. An increase in blood volume will increase blood pressure.
12) In summary, the Renin-angiotensin-aldosterone system works by detecting low amounts of sodium, dehydration, or hemorrhage and works to increase blood volume and blood pressure via angiotensin II - causing constriction of arterioles, and stimulating aldosterone which works by increasing sodium reabsorption and increasing blood volume in turn increasing blood pressure.

Question 9

What is the function of cortisol? When is it released? What does it do to glucose?

Answer 9

Cortisol is the main glucocorticoid in humans. Cholesterol is the precursor to cortisol

It is released in response to stress and low blood glucose. It effectively increases the circulating level of glucose via stimulating gluconeogenesis and playing a smaller role in glycolysis.

It decreasese the absorption of calcium in the GI tract, and decreases the capacity of osteoblasts to produce new bone tissue.

Cortisol also has the effect of supressing the immune system, and works as an anti-inflammatory.

Question 10

When is cortisol highest? What is the circadian rhythym of cortisol?

Answer 10

Cortisol is highest in the morning around 8 am. You can think of waking up as stimulating a lot of cortisol.

The lowest amount of cortisol is in the evening. This is due to the circadian rhythym of ACTH which is the hormone secreted from the pituitary gland that tells the adrenal cortex to secrete cortisol.

Question 11

Describe the hypothamic-pituitary-adrenal axis

Answer 11

The hypothalamus detects levels of cortisol in the body. Cortisol has a negative feedback on the hypothalamus. But when there are low levels of cortisol the hypothalamus will secrete cortiotropin-releasing hormone.

Corticotropin releasing hormone will go to the anterior pituitary and act on the ant pit to release ACTH. ACTH is then released and goes to the adrenal glands. Cortisol also has negative feedback on the anterior pituitary.

The ACTH acting on the adrenal glands works by causing the release of cortisol. If we remember, cortisol is a glucocorticoid and is released by the zona fasciculata.

Question 12

What does DHEA do? Where is it secreted?

Answer 12

DHEA (didehydroepiandrosterone) is produced from cholesterol and serves as the precursor for sex steroid hromone synthesis.

It is a steroid hormone that acts and binds to activate estrogen, testosterone and DHT.

It is secreted by the zona reticularis.

Question 13

What does epinephrine do? Where is it secreted?

Answer 13

Epinephrine is also known as adrenaline and is secreted from the medulla of the adrenal glands.

• It is a hormone that is an agonist of adrenergic receptors (sympathetic nervous system) and causes a vareity of differenet effects known as the fight or flight response.
  
  • These effects are increasing heart rate
  • increasing respiratory rate
  • stimulating glycogenolysis and lipolysis
  • Stimulating muscle contraction
  • vasoconstriction and vasodilation depending on where in the body.

Question 14

What does norepinephrine do? where is it secreted?

Answer 14

Norepinephrine is also known as norardenaline and is also secreted in the medula of the adrenal gland.

• It is a hormone and neurotransmitter that activates noradrenergic receptors and also plays a role in the fight or flight response
  
  • it serves to increase arousal and alertness in the brain
  • helps forming and retrieivng memories
  • increases restlessness and anxiety
  • it increases BP and heart rate.
  • It triggers the release of glucose from stores
  • it increases blood flow to skeletal muscle
  • it decreases gi motility, urination, and blood flow to the gi tract.

Question 15

What are the effects we would see in hyperaldosteronism?

Answer 15

Remember, aldosterone works to increase sodium reabsorption in the kidneys and works to increase secretion of potassium and hydrogen ions

Therefore, if there was too much we would see a decrease in potassium resulting in hypokalkemia, an increase in sodium resulting in hypernatremia, and an increase in blood pressure. “classic findings are hypokalemic, hypernatremic, metabolic alkalosis”

This is from an overproduction of aldosterone by the adrenal cortex. (specifically the zona glomerulosa). This may be primary or secondary.

Question 16

Hyperaldosteronism: Effects, Epidemiology, Pathophysiology. What causes primary and secondary?

Answer 16

Effects: hypokalemia, hypernatremia, and metabolic alklosis

epidemiology: This is up to 10% of people with hypertension. The peak age is between 30-50, so think about younger people with hypertension. There is usually a familial risk factor for hyperaldosteronism.

Pathophysiology:

• Primary hyperaldosternoism
  
  • one or both of the adrenal glands are hyperactive
    
    • can be idiopathic
    • adrenal adenoma
    • adrenal carcinoma
  • This is the majority cause: 60%. Problem is intrinsic to the organ or gland - primary
• Secondary hyperaldosteronism
  
  • Adrenal gland are overstimulated to secrete
    
    • Results in hyperkalemia, hyponatremia, hypotension, decreased renal perfusion
  • Problem is upstream - either from something like CHF, Cirrhosis etc.
• Familial hyperaldosteronism
  
  • Genetic component of producing too much aldosterone

Question 17

Adrenal Adenoma. Functional vs Nonfunctional. What are some things that functional adenomas secrete?

Answer 17

Adrenal adenomas are benign adenal tumors

Some are non-functional –> means they don’t secrete any hormones

Some are functional and can secrete a couple of different hormones

• Can secrete Aldosterone (zona glomerulosa) –> leads to Conn’s syndrome
• Can secrete cortisol (zona fasciculata) –> leads to cushings syndrome
• Can secrete androgens (hyperandrogenism)
• Approximately 1-10% of adrenal tumors are functional tumors.

Question 18

Adrenal Adenomas/Hyperaldosteronism - clinical features, testing, diagnosis, ddx, tx & prognosis

Answer 18

Symptoms

• Presenting symptoms are suually related to hypertension or hypokalemia
• If hypertension - it is hypertension that is hard to contorl
  
  • headaches are very common
  • vision impairment is common
• If hypokalemia
  
  • symptoms related to hypokalemia
  • Muscle weakness, and polyuria
• Hypernatremia and Metabolic alkalosis

Who should be tested?

• People with hypertension and hypokalemia
• HTN & spontaneous or low dose diuretic induced hypokalemia
• Severe or drug resistant HTN - usually still hypetensive after 3 drugs
• HTN & adrenal incidentaloma
• HTN & sleep apnea
• HTN and FH of early onset HTN or CVA less than age 40
• All hypertensive 1st degree relatives of someone with primary aldosteronism

Diagnosis

• 1st: labs –> Plasma aldosterone concentration (PAC), plasma renin activity (PRA)
• Will have abnormally high PAC - plasma aldosterone
• Aldosterone renin ratio (PAC/PRA ratio) very helpful in differentiating between primary and secondary.
  
  • High ratio - likely primary hyperaldosteronism –> this indicates high aldosterone and low renin
  • Low ratio - aldosterone and renin both elevated –> likely secondary hyperaldosteronism
• Confirm with aldosterone suppression tests: oral sodium loading or saline infusion test
• may check adrenal CT to look for adrenal abnormalities.

DDx -

• Renovasuclar hypertension – renal artery stenosis
• diuretic use
• liddle syndrome
• licorice consumption

Treatment

• If single adenoma or carcinoma or unilateral hyperplasia: Unilateral laproscopic adrenalectomy - remove the adrenal gland
  
  • MEasure plasma aldosterone the day after to asssess for cure
• If bilateral hyperplasia - or those who aren’t surgical candidates
  
  • spironolactone (aldactone) - 1st line
    
    • start with 12.5 mg PO daily with food
    • S/e hyperkalemia, gynecomastia and decreased libidio in men. Breast tenderness/menstural irregularities
  • Or Eplernone (inspra) if s/e from aldactone is too bad
    
    • Start with 25mg PO BID
    • S/e hyperkalemia, hypertriglyceridemia
• All need a close monitoring of BP and BNP
  
  • Want to watch for potassium and Na+ levels.

Prognosis/lifestyle changes/referral

• Higher ratse of cardiovascular related morbidity and mortality
• Tobacco avoidance is important –> mineralcorticoid levels related to tobacco
• Regular exercise, low sodium diet, maintenance of ideal body weight to help control HTN
• Referral to endocrinology.

Question 19

What is Hypoaldosteronism characterized by? Pathology?

Answer 19

Hypoaldosteronism refers to low levels of aldosterone. If we remember what aldosterone does - increases Na+, and excretes H+ and K+. So if we had low levels of that we wouldn’t get rid of K+ or H+. Characterized by hyperkalemia

Caused by an aldosterone deficiency or impairment of aldosterone function.

Epidemiology, RF

• Hyporeninemic hypoaldosteronism is most common in those 50-70
• Diabetes
• Nephropathy
• Medication Use
  
  • NSAIDs, aldactone, heparin, beta blockers
• Family history for familial forms

Pathology

• Aldosterone deficiency/reduced production
  
  • From decreased renin secretion (Aka hyporeninemic hypoaldosteronism)
    
    • Renal disease (most common: diabetic nephropathy), NSAIDs
  • ACEI, ARB, heparin therapy
  • adrenal insuffiency/primary hypoaldosteronism
    
    • adrenal cortex isn’t secreting aldosterone
  • Inherited disorders
• Decreased response to aldosterone
  
  • Medications causing aldosterone resistance
    
    • spironolactone, antibiotics (Bactrim)
  • Psuedohypoaldosteronism
    
    • Renal aldosterone receptors aren’t responsive to aldosterone

Question 20

Hypoaldosteronism, Symptoms, dx, tx

Answer 20

symptoms

• people are often asymptomatic
• Hyperkalemic –> often induced byself
  
  • But need to consider in patient with persistant hyperkalemia where there doesn’t seem to be any obvious cuase
• Mild hyperchlomeric metabolic acidosis
  
  • AKA Type 4 renal tubular acidosis (RTA4)

dx

• BMP
  
  • shows hyperkalemia. May see hyponatremia
  • Hypercholermic metabolic acidosis
  • May have increased BUN/Cr 2/2 renal disease
• Plasma renin activity, serum aldosterone
  
  • Hyporeninemic hypoaldosteronism –> low renin and low aldosterone
  • End organ is refracotry to aldosterone: High renin and low aldosterone
  • Adrenal gland abnormalitiy: High renin and low aldosterone.

tx:

• Primary adrenal insufficiency
  
  • Mineralcorticoid replacement therapy
    
    • Fludrocortison (Florinef) 0.05 -0.1mg daily to start + glucocorticoid
• Hyporeninemic hypoaldosteronism
  
  • Fludrocortisone (florinef) 0.2-1mg day
    
    • Not often used in these patients becasuse they often have HTN and edema
  • Low potasssium diet and loop or thiazide diuretic
    
    • avoid meds that cause/worsen hyperkalemia.

Question 21

Adrenal Insuffiency, What is it? Epidemiology, Pathophys

Answer 21

When the adrenal glands don’t produce enough steroid hormones such as cortisol and aldosterone.

Can be life threatening if not treated.

Epidemiology

• About 5 in 10,000
• female:male is 2:1
• Rare overall

Patho

• Primary adrenal insufficiency aka Addison’s disease
  
  • Autoimmune adrenalitis
  • Genetic
  • infection andreanalitis: TB, HIV, disseminated fungal infections
  • Meds
  • Adreanl hemorrhrage
  • Metastases to the adrenal glands
• Secondary adrenal insufficiency
  
  • Lack of ACTH stimulation from the pituitary
    
    • could be froma pituitary lesion or tumor or treatment of one
• Tertiary adreanl insufficiency
  
  • lack of CRH from the hypothalamus
    
    • could be from a hypothalamic lesion or tumor or treatment of one.
• Abrupt withdrawl of steroid treamtent
  
  • Pituitary takes some time to reccur its funciton. Stop steriods slow.

Question 22

Adrenal insufficiency: clinical features, dx, ddx, tx

Answer 22

clinical features

• General s/s: Weakness, fatigue, hairloss, lightheadedness, GI symptoms, anorexia, weight loss, hypotension, emotinal changes, scant axillary and pubic hair. Decrease in libidio in women, hypoglycemia, myalgias
• Primary adrenal insuffiency symptoms (addison’s disease)
  
  • Both cortisol and aldosterone are affected
  • Hyponatremia –> leads to hypotension
  • Hyperkalemia
  • Hyperpigmentation of the skin and mucous membranes
    
    • Bronzing, tanning, freckling
  • Salt craving
• Secondary or tertiary adrenal insufficiency
  
  • No hyperpigmentation
    
    • Becuase ACTH secretion isn’t increased
  • No hyperkalemia
    
    • becuase aldosterone is still produced
  • No dehydration
    
    • hypotension is less prominent
  • Hypoglycemia more common in Addison’s
  • GI symptoms less common
• Clinical features of adrenal crisis. (acute adrenal insuffienciency Addisonian crisis)
  
  • Hypotension –> hypovolemic shock
  • May mimic acute abdomen: tenderness, n/v, fever
  • May have decreased responsiveness, stupor or coma
  • can be triggered by an acute illness, surgery, or other stress

Diagnosis

• BMP
  
  • hyperkalemia (primary), hyponatremia, hypoglycemia
• Simplified cosyntropin test (ACTH stimulation test) is diagnostic
  
  • ACTH given –> serum cortisol level should rise
  • Standard version is 250mcg high dose test
• 8 am plasma cortisol level and plasma ACTH
  
  • Low cortisol + High ACTH - primary disease
  • Low cortisol + low ACTH - secondary dz.

ddx:

• Sepsis
• hypovolemic shock
• major depression
• chronic infeciton
• acute abdomen
• anorexia nervosa
• gi malignancy

tx

• Acute adrenal insufficiency (addison crisis)
  
  • Aggressive IV fluids
  • Glucocorticoid replacement
    
    • high doses
      
      • Hydrocortisone 100mg IV bolus ASAP, then hydrocortisone 100-200mg over 24 hours continous infusion
      • Dexamethasone 4mg IV Bolus ASAP
  • treatment of underlying cause (ie. sepsis, or hemorrhage)
  • Don’t delay teatment while waitig for results of plasma cortisol levels.
• General principles
  
  • Need to periodically montior BMP, vital signs, body weight
  • Liberal sodium intake
  • Patients should have a medical alert bracelet and emergency syringe iwth 100mg hydrocortisone
  • Regular bone density monitoring.

Treatment

• Primary adrenal insufficiency (addisons)
  
  • Mineralocorticoid replacement (florinef) + glucocorticoid replacement (hydrocortisone or prednisone)
    
    • Fludrocortisone (Florinef) - 0.05mg -0.01mg PO daily
    • Hydrocortisone 2-3x a day (1st choice)
      
      • 2x/day 2/3 in the morning and 1/3 in the afeternoon
      • 3x a day Morning> early afternoon> later afternoon (ie. 10/5/2.5)
  • DHEA supplementation is controversial
    
    • Not indicated for men
    • But in women may help with sexuality and mood and quality of life
      
      • 25-50mg daily to start.
• Illness or surgery
  
  • Cortisol secretion normally increases with stress from illness or surgery –> patients in these situations should be given extra
  • Illness: a patient can increase glucocorticoid dose to 2-3x the usual dose for 3 days (the 3x3) rule without consulting provider
    
    • if not improving after 3 days, should see provider
  • surgery
    
    • minor: extra 25 mg hydrocortisone on the day of surgery
    • moderate: 50-75 mg of hydrocortisone (divided doses) POD 0 & 1
    • Major: extra 100-150mg hydrocortisone (divided doses) for 2-3 days.

Prognosis

• poor prior to glucocorticoid availability
  
  • 80% died within 2 years of dx
• Now: discrepancies in studies
  
  • some show twofole increase in mortality
  • some show no difference in lifespan
• Many have imparied quality of life and self-reported decreased function

Question 23

What is Cushing’s syndrome? Pathophysiology, epidemiology

Answer 23

Cushings syndrome is a syndrome that results from prolonged exposure to excess cortisol.

Patho

• Iatrogenic - from long term steroid treatment
• Primary - Oversecretion from one or both of the adrenal glands
• Secondary - Cushing’s disease, overstimultaion of the adrenal glands by an ACTH secreting tumor in the pituitary.
• Ectopic tumor - overstimulation of the adrenal glands by an ectopic ACTH producing tumor. SCLC is most common.

Epidemiology/RF

• Iatrogenic: most common but underreported
• primary: Women>men. Adrenal tumors have bimodal age distribution: small peaks in the 1st decade of life and large pekas at 50 years for adenomas and 40 years for carcinomas
• Secondary: Cushing’s disease, an ACTH secreting tumor. Affects women more than men. Mainly ages 25-45.
• Ectopic ACTH syndrome: 2nd most ocmmon. Also underdiagnosed. Increases after age 50. More common in men.

Question 24

Cushings Syndrome, clinical features, dx, ddx, tx

=]

Answer 24

clincal features:

• Progressive central/truncal obesity
  
  • involves face, neck, trunk, abdomen
  • moon face
  • buffalo hump; dorsocervical fat pad
  • neck appers short and thick from fat depositon in supraclavicular fossae
• Dermatologic features
  
  • Skin atrophy -> slow wound healiing
  • easy bruistability
  • striae
    
    • wide and common on abdomen, flank, breasts
  • Fungal infections
  • Hyperpigmentation from ACTH
  • May see acanthosis nigricans
• Menstural abnormalities
• Signs of adrenal androgen excess in women
  
  • hirsutism
  • oily skin and acne on face, neck, shoulders
  • increased libido
  • virilization
  • males may have premature puberty
• Proximal muscle weakness and wasting
• Bone loss
  
  • vertebral compression fractures 75% of patients
  • pathologic rib and long bone fractures
  • osteonecrosis of femoral heads
  • low back pain
• glucose intolerance –> cortisol stimulates gluoneogenesis \
• Cardiovascular disease
  
  • Increase in risk of death from MI, CVA, and VTE
    
    • due to glucocorticoid increasing clotting factors
• Impaired cognition
  
  • learning, cognition, memory
• psychiatric disease
  
  • emotional lability
  • depression
  • irritabitlity
  • anxiety
  • panic attakcs
  • mild paranoia
  • insomnia is first signs
• increased infection rate
• HTN

Diagnosis

Step 1: show increase in cortisol

• Low dose dexamethasone suppression test (DST)
  
  • Overnight
    
    • patient given 1mg dex PO between 11pm and 12am. Fasting plasma cortisol measured between 8 am and 9 am the next day
  • 48 hour
    
    • 0.5 mg dex given PO Q6H for 8 total doses. Serum cortisol measured between 8 am and 9 am on days 2 and 3
• Late night salivary cortisol
  
  • saliva sample collected between 11pm and 12 am on 2 seperate nights
• 24 hour urinary free cortisol excretion
  
  • 24 hour urine collection: 2 Measurements.

Step 2 of dx: determine the cause

• Measure plasma ACTH
  
  • ACTH low –> likely adrenal tumor b/c negative feedback on ant pit
    
    • check CT of adrenal glands next
  • ACTH high –> pituitary or ectopic site of ACTH production
    
    • High dose dex suppressio test can distinguish between the two
      
      • Lower ACTH after high dex –> pit tumor, do a pituitary MRI
      • No change in ACTH after high dex –> ectopic tumor –> CT C/A/P
  • ACTH intermediate (5-20): Less definitive, but likely a pituitary or ectopic aCTH production
    
    • CRH stimulation test helpful
  • Bilateral inferior petrosal sinus sampling (BIPSS)
    
    • Most accurate method to differentitae between pituitary and ACTH ectopic secreting tumor.
  • Make sure to refer this patients to endocrinology

ddx

• pseudo-cushing syndrome
• visceral obsesity
• polycystic ovarian syndrome
• pregnancy
• famililal partial lipodystrophy type i
• chronic alcoholism

tx

• iatrogenic - stop the corticosteroid (taper)
• primary adreanl disease - surgical resection
• cushing’s disesae - transphenoidal resection. Irradiation may also be option
• Ectopic ACTH producing tumor - find it, then surgical resection
• Pharmacologic
  
  • often sued pre-surgery, in those who aren’t good candidtaes, or those who have failed surgeyr and radiation
  • Mitotane, metyrapone, ketoconazole suppress hypercortisolism

Prognosis

• Almost always curable in current times but patients have residual cognitive and phsyical impairment, osteoporosis, weakness, and poorer quality of life
• Untreated - often fatal
  
  • most deaths from cardiovascular, thromboembolic, or hypertensive complicatoins
• Benign adnreal adenoma - 95% 5 year survival rate
  
  • similar for pituitary adenoma
  • 15-20% recur, even in those with complete remission
• pronosos of ectopic ACTH producting is often poor
  
  • if source is unknown, 5 year survival is 65%

Question 25

What is MEN (Multiple endocrine neoplasia)? What are the different types?

Answer 25

MEN stands for multiple endocrine neoplasia (MEN)

• Several syndrome sthat have tumors of endocrine glands
• Autosomal dominant or sporadic
• Can be diagnosed by
  
  • clinical features- 2 or more of associated tumors
  • familial pattern (an associated tumor in patient who has a 1st degree relative with the syndrome)
  • genetic testing

There are several types. MEN I, MEN 2a, MEN 2B, MEN 4

Question 26

What is MEN 1? Where do the tumors usually occur?

Answer 26

MEN 1 is also called wermer syndrome. It is multiple endocrine tumors.

The tumors most commonly occur in the parathyroid, anterior pituitary, and the pancreas

• Can also have: adrenal cortical tumors, carcinoid tumors (Usu, foregut), meningiomas, facial angiofibromas, collagenomas, lipomas
• Primary hyperparathyroidism is most common feature
• Assocaited with earlier mortality
  
  • COD usually a malignant tumor
  • occult mets more common
  • more likely to have, multiple, larger, more aggressive/resistant treatment tumors

Question 27

What is MEN 2a, Where do the tumors usually occur?

Answer 27

MEN2a is also called sipple syndrome - also another multiple endocrine neoplasia disease

• tumors most commonly occur in the parathyroid, pheochromocytoma, and medullary thyroid carcinoma

May be associated with cutaneous lichen amyloidosis, often upper back, intensie pruritis that improves with sun exposure, worsens with stress

May be assocaited with hirchsprung dz

Medullary thyroid carcinoma is most common feature.

• if known to have RET mutation, should have prophylactic thyroidectomy.

Question 28

What is MEN 2b? Where do they tumors usually occur?

Answer 28

AKA MEN3, but another neoplasia disorder

• Tumors and symptoms are
  
  • Marfanoid body habitus, pheochromocytoma, medullary thyroid carcinoma

Also mucosal nueromas of the lips, tongue, and eyelids, intestinal autonomic dysfunction causing multiple diverticulae and megacolon, thickened corneal nerves.

More aggressive than 2a.

Medullary thyroid carcinoma most common feature. If known to have RET mutation should have prophylactic thyroidectomy.

Question 29

What is Men 4? What is the most common tumors?

Answer 29

Another multiple neoplasia endocrine disorder

• Most common tumors are parathyroid adenomas, pituitary adenomas, pancreatic neuroendocrine tumors in association with
  
  • gonadal tumors
  • adrenal tumors
  • renal tumors
  • thyroid tumors
    *

Question 30

What is congential adrenal hyperplasia (CAH)? What causes it? Symptoms and treatment?

Answer 30

Congenital Adrenal hyperplasia (CAH) is a group of disorders caused by enzyme defects in synthesizing adrenal steroids. It is an autosomal recessive gene defect.

• These defects cause a decrease in cortisol production
  
  • There is less negative feedback –> get high levels ACTH
  • Increased ACTH during development causes hyperplasia of the adrenal glands and accumulation of cortisol precursors
    
    • Can cause androgen excess and or aldosterone deficiency –> females can have virilization and present with clitoromegaly.
• Most common defect is cause of 21-hydroxylase deficiency

Symptoms

• skin hyperpigmentation,
• females with ambiguous genitalia and masculinization.
• Salt wasting variants: Acute crisis early in life with hyponatremia and hyperkalemia, vomiting, dehydration, cardiac arrhythmias
• Severe refractory acne
• Short stature
• Body odor
• Male pattern baldness in females
• delayed menarche in females, subfertility in both sexes

tx

• Salt wasting crisis: fluid resuscitation, immediate hydrocortisone, correction of electrolyte disturbances, and mineralcorticoid replacement
  
  • requires hospital admission
• chronic tx: corticosteroids and mineralcorticoids
  
  • indefinite
• reconstructive surgery for girls with masculine external genitalia between 2-6 months
• may need counseling.

Question 31

What is a Pheochromocytoma? RF? Patho?

Answer 31

A pheochromocytoma is a rare catecholamine producing tumor that commonly occurs in the andrenal medulla. It secretes mostly norepinephrine but also epinephrine.

Epi

• Rare, annual incidence 2-8 cases per million
• Peak incidence in the 30s and 40s
• Equal frequency in men and women
• Familial autosomal dominant disorders
  
  • MEN TYPE 2 (MEN2)
  • Von-Hippel-Lindau disease (VHL)
  • Neurofibromatosis type I (NF1)

Patho

• Arise from chromaffin cells of the adrenal medulla
  
  • 10-15% are extraadrenal –> called paragangliomas
• Etiology of sporadic pheochromocytomas is unknown
• inherited versions: germline mutations
• excessive levels of the catecholamines cause the symptoms that are seen
  
  • stimulate alpha and beta receptors
• about 10% are malignant

Question 32

Pheo Clinical featuers, Dx, tx

Answer 32

Clinical features

• Usually up to 50% are asymptomatic
  
  • usually paroxysmal when symptomatic
• Classic triad: Headache, sweating, tachycardia
  
  • Most don’t have this though
• common symptoms
  
  • sustatined or paroxysmal hypertension
    
    • most common sign
  • Headache is very common
  • palpitations
  • hyperhidrosis
    
    • most evident during paroxysmal attacks of HTN
• Spells/Paroxysms
  
  • Variable from patient to patient but tend to be sterotypical for an individual
  • may be infrequent or several times a day
  • typically last 15-20 minutes
  • May be spontaneous or preceipiated by meds, exercise, increased intra-abdominal pressure, anxiety, postural change, urination
  • May start with a rush into the chest, followed by SOB, palpitations, then a throbbing headahce
    
    • sounds like anxiety attacks as well.
• Crisis
  
  • Could lead to
    
    • Acute respiratory distress syndomre (ARDS)
    • acute heart failure
    • pulmonary edema
    • severe hypotension
    • kidney failure
    • liver failure
    • ICH
    • Death

ddx

• anxiety disorder
• thyrtoxicosis
• amphetamine or cocaine abuse
• essential hypertension
• carcinoid

Who should be tested?

• Classic triad patients - headache, sweating, tachycardia
• Hyperadrenergic spells
• early onset HTN less than 20 years old, resistant HTN, or HTN with new onset or atypical diabetes
• FH of pheochromocytoma
• Adreanal incidentaloma
• MEN2, NF1, or VH1 genetic mutations.

diagnosis

• Need to first confirm catecholamine oversecretion, then identify tumor on imaging
• Detect with either
  
  • 24 hour urine fractionated metanephrines and catecholamines or
  • plasma fractionated metanephrines
    
    • high false positive rate, person needs to lay down for at least 30 minutes before measuring
• If positive for hypersecretion of catecholamines –>imaging
  
  • ct or mri would be appropriate
• if normal and patient has spells, should be repeated during a spell

treatment

• All patients should have medical preparation, then surgical resection
• Preoperative stabilization
  
  • Alpha blocker -AND-
    
    • phenoxybenzamine, prazosin, doxazosin, or terazosin
  • Beta blocker -AND-
  • Liberal salt and fluid intake
  • May also have caclium channel blockers added
• Avoid beta blockers for several days until adequate alpha blockade has been established
  
  • This is to avoid hypertensive crisis from unopposed alpha stimulation.
• Considered a high risk surgery b/c getting rid of catecholamines

Follow up

• Mestastases might become apparent years laters –> lifetime follow up is needed
• check BP and plasma metaneprhines 4-6 weeks postop and every 6 months for at least 5 years, then yearly for life.
• Need endocrinology follow up
  
  • surgery and oncology referrals would be helpful too if malignant

Prognosis

• In pregnancy, can cause death of fetus and mother
• may develop catecholamine-induced cardiomyopathy
• malignant arrhythmia leading to cardiac arrest, CVA, blindness, ARDS, or any other complicatoin of severe HTN are all possible outcomes
• 5 year survival for those with malignant pheo is less than 50%
  
  • about half have indolent disease, life expectancy is decreaed by 20%
  • The other half have rapidly progressive dz
• Recurrence in 16% after resection
• Surgery fatalities are very high, lethal hypertensive crisis, and arrythmia