Adrenal Gland 2 Flashcards
What is adrenocortical insufficiency?
Characterized by failure to produce adrenocortical hormones
What is Primary Adrenocortical Insufficiency (Addison Disease)?
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
What are the consequences of aldosterone deficiency?
Hyponatremia and polyuria
Hypotension and dehyrdation
Hyperkalemia
What are the consequences of cortisol deficiency?
Inability to handle stress
Hypoglycemia
Fatigue
Hypotension
Weight loss
Anemia
Hyperpigmentation
GI discomfort
What are the consequences of androgen deficiency?
Loss of pubic and axillary hair in females
What is secondary adrenocortical insufficiency?
Insufficient production of ACTH, associated with pituitary lesion (panhypopituitarism) and renin insufficiency
Key point: Aldosterone and Cortisol production are regulated differently
What is pseudohypoaldosteronism?
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
What is Cushing Syndrome?
Characterized by excessive cortisol production
Symptoms:
Obesity - especially around trunk
Hypertension
Glucose intolerance
Hirsutism (male-pattern hair growth in females)
Amenorrhea
Purple striae
Osteoporosis
What are the major causes of Cushing Syndrome?
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
What is Primary Aldosteronism?
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
What is Secondary aldosteronism?
Caused by an inappropriate activation of the renin-angiotensin system
What is congenital adrenal hyperplasia (CAH)?
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
What is the most frequent block in CAH?
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
What is the adrenal medulla?
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
What is the rate-limiting step of catecholamine synthesis?
Conversion of tyrosine to dihydroxyphenylalanine (DOPA)
What is VMAT?
Catecholamine-H exchanger that transports dopamine into a secretoy granule where it is converted into norepinephrine
What occurs to norepinephrine in epinephrine-secreting chromaffin cells?
Exits the secretory granule where it is converted into epinephrine in the cytoplasm
Epinephrine is transported back into a chromaffin granule via VMAT
How are catecholamines stored?
In chromaffin granules in a complex with ATP, Ca and chromogranin
What is the regulation of catecholamine synthesis and release by the nervous system?
Sympathetic Nervous system activation
ACh release by preganglionic fibers promotes secretion and transcription of rate-limiting step enzyme (tyrosine hydroxylase)
How do glucocorticoids regulate the secretion of catecholamines?
Cortisol promotes the conversion of NE to epinephrine
Prevents chromaffin cells from developing into postganglionic neurons
What are the two catecholamine-degrading enzymes present in tissues?
Monoamine oxidase (MAO)
Catecholamine-o-methyltransferase (COMT)
Adrenal catecholamines are rapidly cleared from circulation
What are the major classes of metabolites resulting from the inactivation of catecholamines?
Metanephrines
Vanillylmandelic acid
Determination of urinary levels of these metabolites can measure total catecholamine production
What are the actions of catecholamines?
Actions are dependent on the adrenergic receptor type that is activated
In general, they activate responses that enable one to cope with emergency situations
What are pheochromocytomas?
Catecholamine-producing tumors of chromaffin cells of the adrenal medulla
Hypertension is most common feature
Other symptoms: Tachycardia, tremors, sweating, anxiety
