Adrenal Pathology

Question 1

What is the 2 basic components of the adrenal gland?

Answer 1

Composed of the cortex, which secretes cholesterol derived hormones, and adrenal medulla which secretes the catecholamines.

Question 2

What are the three components of the adrenal cortex?

Answer 2

GFR, Glomerulosa, Fasiculata and Reticularis.

Question 3

What are the different hormones produced by the adrenal cortex that are derived from cholesterol?

Answer 3

In the glomerulosa of the AC, Mineralocorticouids (like aldosterone, for salt maintenance) is made, in the Fasciculata makes glucocorticoids (like cortisol for sugar maintenance among others) and in the reticularis the sex steroids are made. “It gets sweeter as you get deeper,” i.e. from salt (aldesterone) to cortisol (sugar) to sex (deeper?)

Question 4

What is the basic problem of hyperaldosteronism?

Answer 4

Too much aldosterone production by the adrenal cortex, specifically by the Granulosa of the AC.

Question 5

How would hyperaldosteronism present?

Answer 5

Increased Na, decreased K, and metabolic alkalosis. Also HTN due to water retention.

Question 6

Where does aldosterone work?

Answer 6

Late Distal Tubule and Collecting duct, where 2 cell types are found: principal cells and alpha intercalated cells.

Question 7

What do the principal cells and alpha intercalated cells do to respond to aldosterone? How does this manifest?

Answer 7

Principal cells will reabsorb Na but dump K back into the tubules thereby excreting them. Alpha intercalated cells will dump H+ and excrete that. Net result: increased Na and HTN results, decreased K and hypokalemia results, and decreased H+ so metabolic alkalosis results.

Question 8

What is the main reason and two lesser reason for primary hyperaldosteronism?

Answer 8

Most commonly due to adrenal adenoma, but also sporadic hyperplasia and carcinoma can cause this as well.

Question 9

How is primary hyperaldosteronism characterized by in terms of hormones?

Answer 9

High aldosterone, which increases body fluids that will be detected by the juxtaglomerular cells of the kidney, and they respond by lowering renin because there is no need to raise BP when there is so much fluid.

Question 10

What defines a secondary hyperaldosteronism?

Answer 10

High aldosterone however not due to the adrenal, but due to the RAS activation.

Question 11

Why does the RAS activate in young women?

Answer 11

Fibromuscular dysplasia, which will thicken the walls of the BV’s of renal arteries, making the JG cells detect low blood flow and respond by secreting renin to increase blood flow.

Question 12

Why does the RAS activate in older men?

Answer 12

Atherosclerosis of the renal artery, which will basically block the blood flow into the kidneys and the JG will think there is low blood flow, respond with renin secretion.

Question 13

What is secondary hyperaldosteronism characterized by hormone wise?

Answer 13

High aldosterone, high renin (because the JG’s detect low blood flow and tries to compensate by raising BP, and does so by secreting renin which converts angiotensiongen to angiotension I, which turns into angiotensiotensin II, which makes adrenal gland make aldosterone.

Question 14

What is the reasoning behind “Congenital adrenal Hyperplasia?”

Answer 14

Excess sex steroids with hyperplasia of both adrenal glands, as a result of congenital abnormalities.

Question 15

What is the most common enzyme deficiency that causes the congenital adrenal hyperplasia?

Answer 15

21-hydroxylase deficiency.

Question 16

Why is the enzyme 21-hydroxylase important?

Answer 16

It is necessary to convert pregnenolol into mineralocorticoids or to cortisol.

Question 17

What does a congenital adrenal hyperplasia with 21-hydroxylase deficiency result in?

Answer 17

Since no 21-hydroxylase is available, no conversion of pregnenolol to cortisol or mineralocorticoids happen, so all the pregnenolol gets converted to the third pathway, conversion of sex hormones. This results in enlarged clit for females, precocious puberty for males. Low cortisol will result in life threatening hypotension (because cortisol hits the alpha 1 vascular receptors to maintain vascular tone). Also low cortisol makes AP think it needs more cortisol so it secretes excess ACTH, resulting in b/l adrenal hyperplasia.

Question 18

Congenital adrenal hyperplasia has this consequence in mineralocorticoids if due to 21-hydroxylase deficiency:

Answer 18

No conversion of pregnenolol into mineralocorticoids, no aldosterone = salt wasting (hyponatremia) and retension of K (hyperkalemia), as aldosterone would retain Na and excrete K if it were present. Also can cause hypovolumia because no water retention due to aldosterone.

Question 19

If it is not a 21 hydroxylase deficiency induced congenital adrenal hyperplasia, and there is no salt wasting hypovolumia or hyperK, what is it? How would this present?

Answer 19

Due to a deficiency in 11ß Hydroxylase. Pregnenolol turns into a weak mineralocorticoid via 21 hydroxylase, and that product is converted to a strong mineralocorticoid via 11ß hydroxylase. Also 11ß hydroxylase is needed to turn pregnenolol into cortisol (second step after 21 hydroxylase). This results in the same cortisol induced problems, but there will be some mineralocorticoids so no salt wasting, no hyper K, no hypovolumia, but yes b/l adrenal hyperplasia, life threatening hypovolumia, enlarged clit/precocious puberty.

Question 20

What would happen if there is a 17 hydroxylase deficiency instead for congenital adrenal hyperplasia?

Answer 20

17 Hydroxylase is needed to initiate both the cortisol and sex steroid pathways (before 21 and 11 can come into play). Deficiency in 17 hydroxylase will result in increased mineralocorticoids with no sex steroids or cortisol, thus still resulting in adrenal hyperplasia, along with probably hypervolumia, hypo K and hyper Na, as well as late puberty and late development of female clit.

Question 21

What is the classic disease for inducing adrenal insufficiency?

Answer 21

Waterhouse-Friderichsen syndrome. This is due to lack of adrenal hormones.

Question 22

What is the progression of Waterhouse-Friderichsen syndrome?

Answer 22

Occurs in a young child with Neisseria Meningitidis infection, which then develops into DIC, and gets b/l necrosis of both adrenal glands. Results in acute lack of cortisol, and thus exacerbate the hypotension.

Question 23

How would acute adrenal insufficiency and Waterhouse-Friderichsen syndrome present?

Answer 23

The adrenal glands will look like a “sac of blood.”

Question 24

What is chronic insufficiency and what causes it?

Answer 24

Progressive and slow destruction of adrenal glands, can be caused by 3 things: autoimmune, TB, or metastatic carcinoma, particularly lung cancer.

Question 25

Where does lung cancer love to metastasize?

Answer 25

It loves to go to the adrenals.

Question 26

What are the clinical features of Adrenal insufficiency?

Answer 26

Hypotension, hyponatremia, hyper K, hypovolumia. Weakness, hyperpigmentation of oral mucosa and skin, and vomitting, diarrhea.

Question 27

Why would chronic insufficiency present as hyperpigmentation?

Answer 27

Lack of cortisol will result in the AP secreting ACTH, which is derived from POMC. POMC also produces melanocyte simulating hormone (MSH), which stimulates the melanocytes to induce hyperpigmentation.

Question 28

Where is the adrenal medulla derived from?

Answer 28

Neural crest derived.

Question 29

What is the adrenal medulla composed of?

Answer 29

Chromaffin cells.

Question 30

What 2 hormones are secreted by the adrenal medulla?

Answer 30

Epi and NorEpi.

Question 31

What is “Pheochromocytoma?”

Answer 31

A tumor of the chromaffin cells of the adrenal medulla.

Question 32

What color does pheochromocytoma present as?

Answer 32

It will be a brown tumor because the adrenal medulla is brown, as compared to the adrenal cortex which will be yellow.

Question 33

What are the clinical features of Pheochromocytoma and what causes it?

Answer 33

All the symptoms are caused due to Epi and NorEpi production, which results in episodic HTN, headaches, palpitations, tachycardia and sweating.

Question 34

How would we diagnose Pheochromocytoma?

Answer 34

Increased serum metanephrines and increased 24 hr urine metanephrines and VMA.

Question 35

How is Pheochromocytomas Tx-ed? What must be administered before tx?

Answer 35

Surgical excision. Must administer phenoxybenzamine before tx, which is an irreversible blocker of alpha receptors, thus when the tumor is removed there is a potential for a massive release of epi and norepi. Phenoxybenzamine will block the alpha receptors so no effect of that will take place.

Question 36

How are both Epi and NorEpi metabolized?

Answer 36

Epinephrine gets metabolized into metanephrine, norepi turns into normetanephrine. Both of these compounds get further converted into VMA due to the Monoamine Oxidase (MAO).

Question 37

What are the 4 rule of 10’s in relation to pheochromocytoma?

Answer 37

10% are b/l, 10% familial, 10% (90% benign) malignant and 10% located outside the medulla (90% in medulla).

Question 38

What is a classic site of pheochromocytoma if it is outside of the medulla?

Answer 38

In the bladder wall.

Question 39

What is Pheochromocytoma associated with?

Answer 39

MEN2A (medulla carcinoma of thyroid, pheychromocytoma and parathyroid adenoma) and 2B (Medullary Carcinoma of thyroid, Pheochromocytoma, mucosal ganglio neuromas esp in oral mucosa) VHL disease, and NF type I.

Question 40

What is Von Hippel Lindau disease (VHL disease)?

Answer 40

AD condition where VHL tumor suppressor is lost, resulting in an increased risk of hemangioblastoma of cerebellum, renal cell carcinoma, and Pheochromocytoma.