Adrenal Gland 2

Question 1

What is adrenocortical insufficiency?

Answer 1

Characterized by failure to produce adrenocortical hormones

Question 2

What is Primary Adrenocortical Insufficiency (Addison Disease)?

Answer 2

Caused by a defect within the adrenal gland

Destruction, autoimmune, or inborn errors of steroid hormone synthesis

Clinical features due to deficient production of cortisol, aldosterone, and adrenal androgens

Question 3

What are the consequences of aldosterone deficiency?

Answer 3

Hyponatremia and polyuria

Hypotension and dehyrdation

Hyperkalemia

Question 4

What are the consequences of cortisol deficiency?

Answer 4

Inability to handle stress

Hypoglycemia

Fatigue

Hypotension

Weight loss

Anemia

Hyperpigmentation

GI discomfort

Question 5

What are the consequences of androgen deficiency?

Answer 5

Loss of pubic and axillary hair in females

Question 6

What is secondary adrenocortical insufficiency?

Answer 6

Insufficient production of ACTH, associated with pituitary lesion (panhypopituitarism) and renin insufficiency

Key point: Aldosterone and Cortisol production are regulated differently

Question 7

What is pseudohypoaldosteronism?

Answer 7

Caused by a loss of function mutation in the mineralcorticoid receptor

Severe salt wasting in the neonate, hyperkalemia, metabolic acidosis and failure to respond to mineralcorticoid treatment

Question 8

What is Cushing Syndrome?

Answer 8

Characterized by excessive cortisol production

Symptoms:

Obesity - especially around trunk

Hypertension

Glucose intolerance

Hirsutism (male-pattern hair growth in females)

Amenorrhea

Purple striae

Osteoporosis

Question 9

What are the major causes of Cushing Syndrome?

Answer 9

Ingestion of pharmacological doses of glucocorticoids

Excessive secretion of ACTH by pituitary (Cushing Disease)

Ectopic, non-endocrine, ACTH-secreting tumors

Tumors of the adrenal cortex

Question 10

What is Primary Aldosteronism?

Answer 10

Caused by autonomous secretion of aldosterone, usually by an adenoma arising from the zona glomerulosa

Symptoms: Hypertension, Hypokalemia, metabolic alkalosis (H secretion)

Plasma renin levels are depressed due to fluid retention

Question 11

What is Secondary aldosteronism?

Answer 11

Caused by an inappropriate activation of the renin-angiotensin system

Question 12

What is congenital adrenal hyperplasia (CAH)?

Answer 12

Group of genetically transmitted enzymatic deficiencies in the biosynthetic pathway for adrenal steroids

Decrease in negative feedback inhibition from cortisol deficiency leads to a rise in ACTH, then adrenal gland hyperplasia

Steroid intermediates behind the enzymatic block build up

Question 13

What is the most frequent block in CAH?

Answer 13

21-hydroxylase enzyme

Block characterized by a virilizing syndrome due to excess androgen production

Females - fusion of labia and clitoral hypertrophy (pre 12 weeks), Breads development and menstruation do not occur

Males - Early somatic growth; premature closure of epiphyseal plate; early maturation of genitalia and secondary sexual characteristic development

Question 14

What is the adrenal medulla?

Answer 14

Specialized sympathetic ganglion containing chromaffin cells that secrete catecholamines into the blood stream

80% secrete epinephrine, the rest secrete norepinephrine

Catecholamine is important in the acute response to stress

Question 15

What is the rate-limiting step of catecholamine synthesis?

Answer 15

Conversion of tyrosine to dihydroxyphenylalanine (DOPA)

Question 16

What is VMAT?

Answer 16

Catecholamine-H exchanger that transports dopamine into a secretoy granule where it is converted into norepinephrine

Question 17

What occurs to norepinephrine in epinephrine-secreting chromaffin cells?

Answer 17

Exits the secretory granule where it is converted into epinephrine in the cytoplasm

Epinephrine is transported back into a chromaffin granule via VMAT

Question 18

How are catecholamines stored?

Answer 18

In chromaffin granules in a complex with ATP, Ca and chromogranin

Question 19

What is the regulation of catecholamine synthesis and release by the nervous system?

Answer 19

Sympathetic Nervous system activation

ACh release by preganglionic fibers promotes secretion and transcription of rate-limiting step enzyme (tyrosine hydroxylase)

Question 20

How do glucocorticoids regulate the secretion of catecholamines?

Answer 20

Cortisol promotes the conversion of NE to epinephrine

Prevents chromaffin cells from developing into postganglionic neurons

Question 21

What are the two catecholamine-degrading enzymes present in tissues?

Answer 21

Monoamine oxidase (MAO)

Catecholamine-o-methyltransferase (COMT)

Adrenal catecholamines are rapidly cleared from circulation

Question 22

What are the major classes of metabolites resulting from the inactivation of catecholamines?

Answer 22

Metanephrines

Vanillylmandelic acid

Determination of urinary levels of these metabolites can measure total catecholamine production

Question 23

What are the actions of catecholamines?

Answer 23

Actions are dependent on the adrenergic receptor type that is activated

In general, they activate responses that enable one to cope with emergency situations

Question 24

What are pheochromocytomas?

Answer 24

Catecholamine-producing tumors of chromaffin cells of the adrenal medulla

Hypertension is most common feature

Other symptoms: Tachycardia, tremors, sweating, anxiety