L23- Endocrine Pathology IV (adrenal)

Question 1

Primary Hyperaldosteronism = (1):

• (2) causes
• results in (3)

Answer 1

1- Conn’s syndrome

2- idiopathic, adenoma, carcinoma

3- Na retention (+ H2O in exchange for K+/H+) –> HTN, hypokalemia, metabolic alkalosis

Question 2

Secondary hyperaldosteronism:

• (1) activity is increased in response to (2)
• (2) may result from (3)

Answer 2

1- RAAS

2:

i) dec effective blood volume
ii) dec renal blood flow

3:

i) liver cirrhosis, HF, nephrotic syndrome
ii) HTN

Question 3

Hyperaldosteronemia:

• (1) are the initial results to indicate a screening test
• the screening test is then conducted with (2) results

Answer 3

1- HTN, hypokalemia, metabolic alkalosis (inc HCO3-)

2- inc aldosterone : renin (inc ARR / aldosterone renin ratio)

Question 4

list the confirmatory tests for hyperaldosteronemia after intial screening tests

Answer 4

(many tests)
-Oral Na loading test

-FST = fludrocortisone suppression test: administer aldosterone like drug in order to cause low urinary / plasma aldosterone levels in normal people (positive if it remains elevated)

Question 5

Hyperaldosteremia testing:

• (1) is the results or purpose of CT scan
• (2) describe the purpose adrenal venous sampling

Answer 5

1- Unilateral / Bilateral micro-/macro- adenoma OR bilateral hyperplasia

2- lateralizing the aldosterone source (R or L adrenal)

Question 6

CAH:

• (1) definition
• (2) type of inheritance
• (3) is a specific change seen in cortisol deficiency

Answer 6

(congenital adrenal hyperplasia)
1- partial or total enzyme deficiency in synthesis of adrenal steroids

2- AR

3- inc ACTH secretion (hyperpigmentation) –> adrenal hyperplasia

Question 7

list the main enzymes affected in CAH (deficiencies)

Answer 7

(congenital adrenal hyperplasia)

• 21-hydroxylase (90%)
• 11β-hydroxylase
• 17α-hydroxylase

Question 8

21-hydroxylase deficiency clinical presentations (CAH)

Answer 8

1) simple virilizing (non-salt wasting)
2) Adrenal crisis / salt-wasting
3) late-onset CAH

Question 9

describe the Simple Virilizing presentation of 21-hydroxylase deficiency (CAH)

Answer 9

(non-salt wasting, partial enzyme deficiency)
-generates sufficient mineralocorticoid to prevent salt-wasting ‘crisis’

Girls- ambiguous genitalia (= enlarged clitoris +/- labial fusion)

Boys- normal at birth –> penile enlargement, early pubic hair, rapid growth (height) when 4-5 yrs old

Question 10

describe the Adrenal Crisis presentation of 21-hydroxylase deficiency (CAH)

Answer 10

(salt-wasting, severe enzyme deficiency)
-no aldosterone production => hyperkalemia, hyponatremia, hypotension (, metabolic acidosis)

-Females: virilization

Question 11

describe the late-onset presentation of 21-hydroxylase deficiency (CAH)

Answer 11

• hirsutism

- infertility

Question 12

21-hydroxylase deficiency Dx:

• (1) is found in blood (indicate timing)
• (2) is performed in borderline cases
• (3) is useful in measuring degradation products

Answer 12

1- high 17α-hydroxyprogesterone; morning sample

2- short synacthen test (administer ACTH-like drug for 15-30 mins, measure adrenal response –> should induce x2-5 hormone release in normal people)

3- urinary steroid profile

Question 13

describe screening for 21-hydroxylase deficiency

Answer 13

1) Neonatal screening: measure 17α-hydroxyprogesterone in blood spot

2) Prenatal diagnosis:
- mutational analysis via chorionic villous sampling or amniocentesis
- mothers treated with dexamethasone

Question 14

list the effects of 11β-hydroxylase deficiency

Answer 14

1) Androgen excess:
- Females: ambiguous genitalia (enlarged clitoris), virilization
- Males: precocious puberty (by age 5-6)

2) 11-deoxycorticosterone:
(some aldosterone / mineralocorticoid activity)
-mild HTN
-dec circulating angiotensin II
-varying degree of hypokalemia, alkalosis

Question 15

list the effects of 17α-hydroxylase deficiency

Answer 15

Males- ambigous genitalia

Females: delayed puberty, absent secondary sex characteristics OR primary amenorrhea

-Excess mineralocorticoid –> varying degrees of HTN, hypokalemia (note- no elevated aldosterone b/c controlled by angiotensin II)

Question 16

briefly describe the adrenal neoplasms

Answer 16

• benign Adenoma or malignant Carcinoma
• functional or non-functional

Functional:

• Zona Glomerulosa –> hyperaldosteronism
• Zona Fasiculata –> hypercortisolism (Cushing syndrome)
• Zona Reticulata –> virilizing (females) or feminizing (males)

Question 17

Adrenal Adenoma:

• (benign/malignant)
• (2) route of diagnosis
• (3) indicates clinical significance
• (4) morphology

Answer 17

1- benign
2- incidental upon imaging (incidentalomas)
3- hormone production (functional adenoma)

4- small, yellow, very well differentiated

Question 18

Adrenocortical Carcinoma:

• (1) describe prevalence
• (2) morphology
• (3) metastasis method

Answer 18

1- rare, sporadic, rare inherited (Li Fraumeni, Beckwith-Wiedemann)

2- large, hemorrhage, necrosis, anaplastic

3- (common) invades adrenal vein

Question 19

Adrenal Medulla:

• (1) cells
• (2) are the most important diseases

Answer 19

1:

• chromaffin cells (neuroendocrine, neural crest cells)
• supporting / sustentacular cells

2:

• chromaffin cell neoplasm / pheochromocytoma
• neuronal neoplasm / neuroblastoma

Question 20

describe the 10% rule

Answer 20

(Pheochromocytoma, everything below is ~10%)

• 10% extra-adrenal
• 10% malignant
• 10% bilateral
• 10% childhood
• 10% component of MEN2a/2b (multiple endocrine neoplasia)
• 10% not associated with HTN

**-10% inherited (old rule, now up to 25%)

Question 21

describe the clinical features of pheochromocytoma

Answer 21

Episodic:

• HTN, HA
• anxiety, palpitations
• excess sweating (diaphoresis)
• cardiac arrhythmias

Question 22

describe the Pheochromocytoma investigations

Answer 22

• Plasma Metaephrines testing (more sensitive)
• 24hr urinary catecholamines / metanephrines (during episode, more specific)

Imaging:

• MRI, CT scan
• MIBG = I(123)-metaiodobenzylguanidine scinigraphy (if MRI, CT fail, and biochemical testing is positive)

Question 23

(1) is the most common childhood tumor, affecting (2). (3) is the most common product of (1), represented mostly by (4) in blood/urine. (5) is the main method of investigation.

Answer 23

1- neuroblastoma
2- mostly adrenal glands, occasionally SNS chain
3- dopamine
4- HVA, VMA (homovanillic acid, vanillylmandelic acid)
5- I(123)-metaiodobenzylguanidine scintigraphy: concentrate in >90% of tumors –> assesses spread of tumor and response to therapy