Module 5: Endocrine: Adrenal Cortical Adenoma, Pheocyto

Question 1

First starting off, what is an adrenal cortical adenoma?

Answer 1

• -Unilateral
• -Non-functional (asymptomatic) called an incidentaloma
• -Benign neoplasm of the adrenal glands – is usually non functional but can be functional

Question 2

Describe the functional aspect of adrenal cortical adenoma

Answer 2

Zona Fasciculata — cortisol production —-Cushings (ACTH low due to negative feedback so contralateral adrenal atrophy)
Zona Glomerulosa – aldosterone (Conn’s syndrome) –primary hyperaldosteronism
Zona Reticularis– androgens
men: gynecomastia
women: virilization and hirsutism and FCC and endometrial cancer due to the excess estrogen made by the androgens

Question 3

What is the triad of symptoms if a patient develops Conn’s Syndrome in the Zona Glomerulosa?

Answer 3

1. Malignant Hypertension: resorption of sodium and water in the distal tubule; normal sodium levels and low renin levels (neg feedback)
2. Hypokalemia (muscle cramps and weakness)
3. Metabolic Alkalosis

Question 4

What is secondary aldosteronism?

Answer 4

From outside the adrenal gland

–renin and aldosterone are both elevated

Question 5

What are causes of secondary aldosteronism?

Answer 5

1. Hypoperfusion
2. Renal Artery Stenosis
3. Liver Cirrhosis (no albumin production– fluid trapped in tissues — hypoperfusion to kidneys –renin secretion)
4. Nephrotic Syndrome: albumin is lost in the urine (fluid trapped in tissues – hypoperfusion to kidneys–renin secretion)
5. Congestive Heart Failure

Question 6

Moving on to pheochromacytoma, what is the etiology?

Answer 6

Etiology: Tumor of adrenal medulla (chromaffin cells)
cell of origin: chromaffin neural crest cells (benign or malignant) (NOT ENTEROCHROMAFFIN thats GI)
Catecholamine production

Question 7

What is the rule of 10 in pheochromacytoma?

Answer 7

10% malignant
10% extraadrenal
10% in children
20-25% familial (MEN 2A, MEN 2B, VHL, Neurofibromatosis)
–what else do VHL? Retinal and Cerebellar Hemangioblastomas and Clear Cell Renal Carcinoma

Question 8

What is the presentation for a patient with pheochromocytoma?

Answer 8

Mimics hyperthyroidism and Graves

• -episodic malignant hypertension
• -anxiety
• -sweating
• -palpitations (most common cause of death)
• -diarrhea

Question 9

What makes the symptoms worsen in pheochromocytoma?

Answer 9

exercise 
Pressure on abdomen 
Stress
Surgery 
--all due to the release of catecholamines

Question 10

What investigations are done for pheochromocytoma?

Answer 10

Never do a CT first
Elevated catecholamines in the blood and urine
BMA and metanephrines in the urine are catecholamine metabolites
–VMA is catecholamine metabolite for neuroblastoma
–Metanephrine is catacholamine metabolite for pheochromocytoma
CT is next of adrenal to locate: 10% is extra adrenal and 90% is adrenal medulla.. what if you see nothing??
not found there—-MIBG (radioisotope scan) —Carotid Bodies typically (this is the most likely location of extra adrenal sites)

Question 11

What is seen on gross and histology for pheochromocytoma?

Answer 11

Gross: Brown is taking over the medulla (takes over the entire adrenal gland)
Histology: Nests of spindle shaped chromaffin cells separated by scanty vascularized stroma (Zellballen)

Question 12

What are the complications in pheochromocytoma?

Answer 12

HTN – atherosclerosis — hypertrophy of LV— LV failure — RV failure – mural thrombosis— atrial fibrilation – emboli stroke
Arrhythmias is the most common cause of death

Question 13

What should happen in surgery patients with pheochromocytoma?

Answer 13

Should be alpha blocked then beta blocked
–alpha receptors on blood vessels — vasoconstriction – stroke MI
alpha blocks allow vasodilation
beta receptors are located on the heart (if blocked first, all catecholamines would go to alpha receptors and cause massive vasoconstriction)

Question 14

The primary etiology of HTN in endocrine disorders is idiopathic. However, what are some secondary causes?

Answer 14

Acromegaly: GH upregulates alpha 1 receptors
Cushing’s Disease: cortisol is weak mineralcorticoid and upregulation of alpha 1 receptors
Pheochromocytoma: production of epinephrine and norepinephrine
Conn’s Syndrome: due to adrenal cortical adenoma affecting ZG

Question 15

Next we will briefly discuss neuroblastoma in kids. What is a neuroblastoma?

Answer 15

Poorly differentiated tumor of NCCs that normally give rise to the adrenal medulla and sympathetic ganglia due to germline mutation in ALK gene.
–second most common solid malignant tumor in children

Question 16

What is the presentation of a patient with Neuroblastoma?

Answer 16

less than 2 years old: mass in abdomen or mediastinum, fever, weight loss, and constipation
Older kids: signs of metastatic disease (bone pain, resp, GI symptoms)

Question 17

What investigations are done for neuroblastoma?

Answer 17

Gross calcification in 40-50%
Microscopy: neuropil (eosinophilic fibrillary material) and Homer-Wright Pseudorosettes (tumor cells arranged around neurophil with no lumen)
EM: neurosecretory granules
IHC: neuron-specific enolase and synaptophysin

Question 18

What are clues for diagnosis of a neuroblastoma?

Answer 18

Increased blood catecholamines
Increased urine levels of catecholamine metabolites (VMA and HVA)
MIBG scintigraphy: concentrates in over 90% of tumors – used for assessment of spread and response to therapy

Question 19

What are the good prognostic factors for a neuroblastoma?

Answer 19

Stage 45 and increased expression of Tyrosine kinase receptor A

Question 20

What are the bad prognostic factors for a neuroblastoma?

Answer 20

Deletion distal 1p and gain of distal 17q; n-myc amplification and telomerase overexpression

Question 21

One of the etiologies for hypercalcemia is hyperparathyroidism, explain this

Answer 21

Primary: solitary adenoma
Secondary: reaction of parathyroid glands to a hypocalcemia
Tertiary: increased PTH to maintain normocalcemia in the setting of vit D deficiency — parathyroid hyperplasia occurs and PTH secretion becomes independent of calcium level
–part of MEN1 and MEN2 syndromes

Question 22

What are the other etiologies of hypercalcemia?

Answer 22

Malignant Disease
Excessive Vitamin D
Granulomas (TB, lymphoma, sarcoidosis): b/c they activated vit D
High Bone turn over: thyrotoxicosis and Pagets disease

Question 23

In about 50% of ppl become asymptomatic in hypercalcemia, explain the symptoms in each organ system

Answer 23

Renal: polyuria and thirst, stones, nephrocalcinosis and renal failure
Musculoskeletal: muscle weakness, osteitis fibrosa cystica
Neurological: psychiatric/neurological symptoms
GI: anorexia, constipation and ulcers

Question 24

What is treatment for hypercalcemia?

Answer 24

Correct dehydration, frusemide, biphosphonates and calcitonin

Question 25

Moving onto hypocalcemia, explain PTH related etiology

Answer 25

PTH-related: hypoparathyroidism, pseudo-hypoparathyroidism and hypomagnesemia
–pseudo-hypoparathyroidism/Albright’s Hereditary Osteodystrophy: decreased responsiveness of kidney due to defective PTH receptors — decreased calcium and increased phosphate

Question 26

What are other etiologies for hypocalcemia?

Answer 26

Hypoalbuminemia: decreased total plasma calcium but ionized calcium is normal
Chelation by EDTA
Defect in Vit D metabolism: rickets, osteomalacia, chronic renal failure and liver disease
Acute Pancreatitis

Question 27

What is the presentation for hypocalcemia?

Answer 27

Increased neuromuscular excitability: tetany, paresthesia, and cramps
Prolonged hypocalcemia: cataracts, mental retardation, psychosis, increased ICP and seizures

Question 28

What are some etiologies for hypophosphatemia?

Answer 28

Malabsorption
Increased cellular uptake: DKA, hyperalimentation, alkalosis
Increased excretion: hyperparathyroidism, hypomagnesemia, renal tubular defect and dialysis
Dilution: volume expansion
Chronic alcohol abuse

Question 29

What is the presentation for hypophosphatemia?

Answer 29

Muscle weakness
Hemolysis: depletion of 2,3 diphosphoglycerate
Resp Failure
Rhadomyolysis

Question 30

What are etiologies for hyperphosphatemia?

Answer 30

Artifact: hemolysis or delay in separation of blood samples
Chronic renal failure
Hypoparathyroidism

Question 31

What is the presentation for hyperphosphatemia?

Answer 31

High plasma calcium and phosphate – metastatic calcification (Deposition of calcium in previously normal tissues)

Question 32

What is the etiology for hypomagnesemia?

Answer 32

Etiology: malabsorption, malnutrition and alcoholism

Question 33

What is the presentation for hypomagnesemia?

Answer 33

Tetany 
Agitation 
Ataxia 
Tremors
Convulsions

Question 34

What is the etiology for hypermagnesemia?

Answer 34

Renal Failure

Question 35

What is the presentation for hypermagnesemia?

Answer 35

greater than 6mg/L – respiratory paralysis and cardiac arrest

Question 36

How do you tell the difference between benign and malignant pheochromocytoma?

Answer 36

They both invade

sooo mets

Question 37

Congenital adrenal hyperplasia (CAM) is caused by three enzyme deficiencies, each card will go through one. First is 21 alpha hydroxylase deficiency, what are some features

Answer 37

Most common form of CAM

• -partial and virtually complete deficiencies are known
• -mineralocorticoids and glucocorticoids are virtually absent (salt wasting or deficient)
• -overproduction of androgens leads to masculinization of external genitalia in females and early virilization in males

Question 38

The second cause of CAM is 11 Beta hydroxylase deficiency, what are some features?

Answer 38

Decrease in serum cortisol, aldosterone and corticosterone

• -increased production of deoxy-corticosterone causes fluid retention. because this hormone suppresses the renin/angiotensin system, it causes low renin HTN
• -overproduction of androgens causes masculinization and virilization as with 21 alpha hydroxylase deficiency

Question 39

The third cause of CAM is 17 alpha hydroxylase deficiency, what are some features?

Answer 39

Virtually no sex hormones or cortisol are produced

• -increased production of mineralocorticoides causes sodium and fluid retention and therefore HTN
• -patients have female like genitalia