E2L26-27 Endocrine: Adrenal Pathoma

Question 1

What are the layers of the adrenal cortex and what do they produce?

Answer 1

Remember the mnemonic GFR and that it gets sweeter as you get deeper
1) Glomerulosa: mineralcorticoids–aldosterona
2) Fasciculata: glucocorticoids–cortisol
3) Reticularis: androgens–DHEA
All hormones are derived from cholesterol in a sequential enzymatic modification

Question 2

What enzyme deficiency would lead to an excess in androgens produced by the adrenal glands?

Answer 2

21-hydroxylase
This enzyme is needed to produce aldosterone and cortisol and without it all metabolites get pushed towards production of androgens

Question 3

What enzyme deficiency would lead to excess in aldosterone production by the adrenal glands?

Answer 3

17-hydroxylase

Question 4

Patient has a known deficiency in 21-hydroxylase enzyme. What hormone would be overproduced by the adrenal gland?

Answer 4

Androgens from DHEA

Question 5

Patient has deficiency in 17-hydroxylase enzyme. What hormone would be overproduced by adrenal gland?

Answer 5

Aldosterone

Question 6

What happens to the muscles of a patient with Cushing’s syndrome and why?

Answer 6

Cushing’s patients have muscle wasting and thin limbs because cortisol induces muscle breakdown for gluconeogenesis.

Question 7

Why would a cushings’s patient have thin limbs from muscle wasting and yet truncal obesity and deposition of fat throughout the body?

Answer 7

High cortisol causes high blood sugar. This induces high insulin which causes the body to store and make fat that is stored as central obesity, buffalo hump, moon facies.

Question 8

Why do cushing’s patients have thin skin and striae?

Answer 8

They have impaired collagen synthesis resulting in thin skin.

Question 9

What are the clinical features of Cushing’s Syndrome and why?

Answer 9

1) Muscle weakness and thin limbs: muscel used for gluconeogenesis
2) Fat deposition: high blood glucose leads to high insulin
3) Abdominal striae: impaired collagen synth. causes thin skin
4) HTN: cortisol up regulates alpha-1 receptors in vasculature
5) Osteoporosis
6) Immune suppression: inhibits phospholipase A2, and IL-2, prevents histamine release

Question 10

Patient is showing signs of hypercortisolism. Blood shows high Cortisol and low ACTH. What are the potential causes at this point and what should be done next to determine the final cause?

Answer 10

High cortisol and low ACTH indicates this is ACTH independent and has nothing to do with the pituitary.
Options are Exogenous glucocorticoids or primary adrenal adenoma/hyperplasia/carcinoma.
To differentiate, image the adrenals to assess the size. If exogenous glucocorticoids have been given both glands will be enlarged. If there is a primary tumor of some kind, only one gland will be enlarged and the other will have atrophied.

Question 11

Patient show signs of hypercortisolism. Blood shows high cortisol and high ACTH as well as androgens. What are some potential causes and what needs to be done next to reach a final diagnosis?

Answer 11

Having high ACTH despite high cortisol indicates a problem with the pituitary or there is some other source of ACTH. Potential causes are ACTH-secreting pituitary adenoma or ectopic ACTH secretion (cancer).
To differentiate, perform High-Dose dexamethasone test. ACTH suppressed in the adenoma, but not with ectopic production.

Question 12

Where does aldosterone act on the kidney, on what cells, and with what effect?

Answer 12

Distal tubule and collecting duct
Principle cells: absorb Na+, excrete K+
Alpha-intercalated: excrete H+

Question 13

What are the S/Sx of hyperaldosteronism and how do lab values differ between primary and secondary?

Answer 13

S/Sx: HTN, hypernatremia, hypokalemia, metabolic alkalosis

Labs: increased aldosterone, low renin (Primary), high renin (secondary)

Question 14

What are two drugs that are mineralcorticoid receptor antagonists?

Answer 14

Spironolactone

Eplerenone

Question 15

Patient has S/Sx of hyperaldosterone including HTN, hypokalemia, metabolic alkalosis but both aldosterone and renin are low. What is the diagnosis and treatment?

Answer 15

Liddle Syndrome
Mimics hyperaldosteronism because there is a decreased breakdown of Na channels in the distal tubules and collecting ducts.
Treated with K+ sparing diuretics like Amiloride or Triamterene

Question 16

What is the same between 21, 17, 11 hydroxylase deficiencies?

Answer 16

All prevent the production of cortisol and therefore there is no feedback to the pituitary and there are high serum levels of ACTH and bilateral adrenal hyperplasia

Question 17

Patient is a female neonate with life-threatening hypovolemia, hyponatremia, hyperkalemia, and clitoral enlargement. What is the diagnosis and what hormone levels will be expected?

Answer 17

Classic form of 21-hydroxylase deficiency (neonate)
21-OHase is needed to produce mineralcorticoids and glucocorticoids therefore these are lacking in this patient.
Low aldosterone causes salt wasting and dilute urine leading to hypovolemia.
Androgens will be elevated causing the enlarged clitoris.

Question 18

10y male presents with mature sex characteristics, hyponatremia, hyperkalemia, and bilat. adrenal hyperplasia. Diagnosis? How would this present in a female?

Answer 18

Nonclassic form of 21-OHase deficiency (later presentation)
Enzyme deficiency prevents formation of aldosterone and cortisol and shunts metabolites to androgen production causing precocious puberty in males and hirsutism with menstrual irregularities in females.

Question 19

Features of 11-hydroxylase deficiency

Answer 19

Similar to 21-OHase deficiency in that cortisol will be low and androgens will be high but different in that there will be some mineralcorticoid action causing HTN instead of hypovolemia and only mild hypokalemia.
Renin and aldosterone levels will be low whereas renin would be elevated in a 21-OHase deficiency.

Question 20

What are the expected hormone abnormalities assoc. with a 17-OHase deficiency?

Answer 20

Low cortisol and androgens
High weak mineralcorticoids causing HTN and mild hypokalemia
Low renin and aldosterone!

Question 21

What hydroxylase deficiency can lead to primary amenorrhea and lack of pubic hair in females or pseudohermaphroditism in males?

Answer 21

17-OHase

Question 22

How do you screen for congenital adrenal hyperplasia (CAH)?

Answer 22

Serum 17-hydroxyprogesterone levels
Increased in 21 or 11-hydroxylase deficiency
Decreased in 17

Question 23

What is Conn syndrome?

Answer 23

adrenal adenoma causing primary hyperaldosteronism

Question 24

What is the relationship between cortisol and BP and pigmentation?

Answer 24

BP: cortisol upregulates alpha-1 receptors and is therefore essential in maintaining vascular tone, too much=HTN, not enough=hypotension

Pigmentation: cortisol feeds back to the hypothalamus/pituitary and decreases production of ACTH, ACTH is derived from POMC which also can become MSH (melanocyte stimulating hormone). This means that low levels of cortisol stimulates increased production of ACTH as well as MSH which causes hyperpigmentation classically in the oral mucosa (sign of Addison’s disease)

Question 25

What can happen if you abruptly withdraw glucocorticoid meds?

Answer 25

Acute adrenal insufficiency leading to weakness and hypotension

Question 26

Patient’s adrenal gland found to be full of blood. What is the classic cause of this, and presentation?

Answer 26

Waterhouse-Friderichsen syndrome characterized by hemorrhagic necrosis of the adrenal glands
Usually caused by DIC occurring in young children with a N meningitidis infection
Causes acute adrenal insufficiency causing low cortisol which can lower BP and worsen the DIC and lead to shock and death

Question 27

What are the most common causes of Addison’s disease?

Answer 27

Autoimmune (most common in the West)
TB (most common in developing world)
Metastatic carcinoma (generally from the lung)

Question 28

Patient shows hyperpigmentation in the oral mucosa and on the skin, hypotension, hyponatremia, hypovolemia, hyperkalemia, metabolic acidosis, weakness. What is the likely diagnosis?

Answer 28

Addison’s disease

Question 29

Patient has episodic hypertension, headache, palpitations, tachycardia, and sweating. Episodes last 15 min. What is the likely diagnosis and treatment?

Answer 29

Pheochromocytoma–tumor of chromaffin cells in the adrenal medulla making too much catecholamines
Diagnosed by serum metanephrines and increased 24 hour urine metanephrines and VMA
Treatment is surgical excision after drug Phenoxybenzamine used to irreversibly block alpha receptors in case of inadvertent squeezing of the gland and Epi release which could cause HTN and death

Question 30

Patient reports palpitations, sweating, nervousness after urination. Diagnosis?

Answer 30

Pheochromocytoma that is extramedullary in the bladder wall. This is a common location.

Question 31

What disease follows the rule of tens and what are they?

Answer 31

Pheochromocytoma
10% Bilateral
10% Familial
10% Malignant
10% Outside adrenal medulla