Adrenal CIS

Question 1

Hormones Produced by the Adrenal Medulla

Answer 1

The adrenal medulla produces catecholamines (primarily epinephrine and small amounts of norepinephrine)
Epinephrine
- responder to stress such as hypoglycemia/exercise
- influences energy metabolism and cardiac output

Question 2

Synthesis of Catecholamines

Answer 2

Under control of the CRH-ACTH-cortisol axis
- ACTH stimulates synthesis of DOPA
- Cortisol increases PNMT enzyme
Release is triggered by CNS control

Question 3

Degradation of Catecholamines

Answer 3

COMT: catecholamine-O-methyltransferase
MAO: monoamine oxidase

Catecholamines, metanephrines, and
vanillylmandelic acid (VMA) can be measured in urine
To determine total catecholamine production

Question 4

alpha one receptor

Answer 4

increases IP3 and Ca, DAG.
Sympathetic postsynaptic nerve terminals
Increases vascular smooth muscle contraction

Question 5

alpha two receptor

Answer 5

decreases cAMP
sympathetic presynaptic nerve terminals; beta cell of pancreatic islets
Inhibits norepinephrine release; inhibits insulin release

Question 6

beta one receptor

Answer 6

increases cAMP
in the Heart
increases cardiac output

Question 7

beta two receptor

Answer 7

increases cAMP
in liver, smooth muscle of vasculature, bronchioles, and uterus
increases hepatic glucose output; decreases contraction of blood vessels, bronchioles and uterus (Epinephrine has higher affinity for beta 2)

Question 8

beta three receptor

Answer 8

increases cAMP
in liver, adipose tissue
increases hepatic glucose output; increases lipolysis

Question 9

pheochromocytoma

Answer 9

Pheochromocytoma- tumor of chromaffin tissue
-Produces excess catecholamines
-Symptoms sporadic
Hypertension

Question 10

hypertension breakdown in patients with pheochromocytomas

Answer 10

One half have sustained hypertension
One third have paroxysmal hypertension
And one fifth have normal blood pressure

Question 11

Differential for pheochromocytoma

Answer 11

Pheochromocytoma is a rare cause of hypertension

Question 12

For each of the following events determine which adrenoreceptor was responsible for the observed symptoms.

Pounding heart
Increased heart rate
Increased blood pressure
Cold hands and feet

Answer 12

heart: stimulation of beta 1 receptors

blood pressure and cold hands/ feet: alphareceptors

Question 13

What agent should be given first to pheochromocytoma patient to control blood pressure prior to surgery?

Answer 13

alpha-1 adrenergic antagonist

to control the blood pressure before dropping the heart rate.

Question 14

Hormones Produced by the Adrenal Cortex

Answer 14

Aldosterone (mineralocorticoid- regulates salt and water retention)
- functions in salt and water homeostasis

Cortisol (glucocorticoid- increases plasma glucose)

• released in response to stress
• influences glucose utilization, immune and inflammatory homeostasis

Androgens- dehydroepiandrosterone (DHEA)

Question 15

cortisol and glucose

Answer 15

cortisol increases glucose production

related to insulin resistance

Question 16

loss of 21 hydroxylase results in?

Answer 16

loss of cortisol and aldosterone, but there are adrenal androgens. No mineralocorticoids or glucocorticoids possible

Question 17

loss of 11 beta hydroxylase

Answer 17

lose cortisol and some aldosterone

Question 18

17 alpha hydroxylase loss results in?

Answer 18

no androgens or cortisol

Question 19

Congenital Adrenal Hyperplasia

Answer 19

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that involve a deficiency in either cortisol, aldosterone, or both due to impaired synthesis.

21 hydroxylase deficient? low glucocorticoids, low (salt-wasting) mineralocorticoid effects, androgenic effect: high virilizing

11 beta hydroxylase deficient? low glucocorticoids, moderate mineralocorticoid effects: hypertensive from excess DOC, high androgenic effect: virilizing

17 alpha hydroxylase deficient? low glucocorticoids, mineralocorticoid effect is excess: hypertensive, androgenic effect: low, feminizing

Question 20

21-Hydroxylase Deficiency

Answer 20

Mutation in CYP21A2
- Block in 11-deoxycorticosterone synthesis from progesterone
- Loss can be total or partial and the degree of loss effects onset of clinical symptoms
Total loss of glucocorticoid and mineralocorticoid activity
- Salt-wasting
- Hyponatremia
- Hyperkalemia
- Hypotension
- Cardiovascular collapse and possibly death
- Virilization- recognizable in females at birth but more difficult in males

Question 21

11 beta-Hydroxylase Deficiency

Answer 21

Mutation in the CYP11B1 gene that results in a loss of activity and a block in the conversion of 11-deoxycortisol to cortisol
Loss of negative feedback inhibition and ACTH-mediated adrenal androgen excess is observed
Mineralocorticoid activity is attributed to deoxycorticosterone (DOC) and increased secretion is postulated to be responsible for the observed hypertension in these patients
Cortisol is absent

Question 22

17 alpha-Hydroxylase Deficiency

Answer 22

Autosomal-recessive mutation of the CYP17 gene
Impaired sex steroid and cortisol biosynthesis
Excess intermediary steroids with mineralocorticoid activity leads to varying degrees of hypertension and hypokalemia
No androgen activity
- Females fail to develop secondary sexual characteristics
- Males develop ambiguous external genitalia

Question 23

what does ringing in the ears indicate?

Answer 23

can be hypertension

Question 24

cortisol- excess and deficiency

Answer 24

excess: cushing’s
deficiency: Addison’s disease and hypocortisolism

Question 25

Aldosterone- excess and deficiency

Answer 25

excess- Conn's syndrome | deficiency- addison's disease and hypoadrenalism

Question 26

sex steroid excess

Answer 26

hirsutism/ virilization

Question 27

approach to adrenal pathophysiology

Answer 27

Is the clinical presentation consistent with an excess or deficiency in one or more of the adrenocortical hormones? Can a deficiency be stimulated or an excess be suppressed (biochemical diagnosis)? What is the etiology of the disorder (imaging)?

Question 28

causes of cushing's syndrome

Answer 28

ACTH-dependent ACTH-independent Factitious (taking excess glucocorticoids)

Question 29

cortisolemia (cushing's) symptoms

Answer 29

striae, weakness and fatigue, red cheeks, muscle weakness, high fasting glucose

Question 30

cortisolemia biochemical findings in the case study

Answer 30

Cushing syndrome is suspected based on the patient’s clinical presentation. Urine free cortisol levels were 300 µg (nl, 20-90) After an overnight dexamethasone suppression test, 8 am plasma cortisol levels were 25 µg/dL (nl, 20) Imaging studies revealed an adrenal mass on the left adrenal gland

Question 31

What can cause fals positives for overnight dexamethasone suppression test?

Answer 31

acute and chronic illness, obesity, sleep apnea, PCOS, high estrogen, alcoholism, anorexia, renal failure, drugs, and depression.

Question 32

Corti had increased central obesity, muscle wasting, and striae. What are the biological effects of cortisol that are responsible for each of these physical findings?

Answer 32

Hyperglycemia--> Increased gluconeogenesis Catabolic effect - Muscle weakness - Degradation of elastin→ fragile skin and easy bruising - Thinning of blood vessels→ redness Hypertension- due to increased levels of circulating cortisol (upregulates alpha adrenergic receptors on vascular smooth muscle) and cross-reactivity with mineralocorticoid receptors- possible increased levels of aldosterone excess glucocorticoids --> bone density goes down

Question 33

Cortisol Biologic Effects

Answer 33

Increases gluconeogenesis, protein catabolism, lipolysis, and decreases glucose utilization and insulin sensitivity Anti-inflammatory effects Suppresses immune responses Maintain vascular responsiveness to catecholamines Maintains normal blood pressure ↓ cortisol → hypotension Inhibition of bone formation Increases glomerular filtration rate (GFR) Decreases REM sleep (psychosis)

Question 34

Primary Hyperaldosteronism

Answer 34

Primary hyperaldosteronism is characterized by excessive production of aldosterone. It is a term for a group of disorders. - Bilateral hyperplasia of the zona glomerulosa (idiopathic hyperaldosteronism [IHA]) - Solitary aldosterone-producing adenoma - Adrenal carcinoma - Glucocorticoid-remediable aldosteronism

Question 35

Findings in primary aldosteronism

Answer 35

hypertension hypokalemia metabolic alkalosis hypomagnesemia

Question 36

Causes of primary adrenal insufficiency (Addison's disease)

Answer 36

``` Autoimmune Metastatic disease Adrenalectomy Infectious adrenalitis - Tuberculosis - Disseminated fungal infections - HIV Adrenoleukodystrophy Hemorrhagic infarction Infiltrative Drugs Congenital adrenal hyperplasia ```

Question 37

distinguishing primary from secondary adrenal insufficiency

Answer 37

Primary usually presents with hyperpigmentation

Question 38

Why hyperpigmentation in primary adrenal insufficiency?

Answer 38

MC2R receptors are on the surface of the adrenal gland and ACTH binds these receptors. At high levels, ACTH can cross-react with MC1R receptors on melanocytes, thereby increasing pigmentation.