Hypothalamic-Pituitary Relationships pt2

Question 1

Describe the HPA axis

Answer 1

Hypothalamus releases CRH
Anterior pituitary releases ACTH
Adrenal cortex releases cortisol
Cortisol = negative feedback to anterior pituitary and hypothalamus

Question 2

What are the main functions of cortisol?

Answer 2

Immune suppression, gluconeogenesis in liver to increase BGL, protein catabolism in muscle, lipolysis in adipose tissue

Question 3

When is cortisol secreted at its highest level?

Answer 3

High in the morning, low at night. Pulsatile secretion

Question 4

What stimulates aldosterone release by the adrenal gland?

Answer 4

Low BP/Na+ and angiotensin II

Low BP leads to Renin increase, which forms Angiotensin 1…which continues to II… then eventually increases water/Na+ reabsorption and raises BP by making Aldosterone

Question 5

What glucocorticoid is elevated in Cushing’s syndrome?

Answer 5

Cortisol

Question 6

What is the dexamethasone suppression test?

Answer 6

Dexamethasone suppresses ACTH
Low-dose- differentiates CS vs not CS (no suppression=CS+)
High-dose- differentiates Cushing’s disease (Decreased ACTH=pituitary ACTH-secreting tumor) vs CS of other cause (no ACTH change=ectopic ACTH-secreting tumor)

Question 7

What are consequences of excess glucocorticoids?

Answer 7

Short-term cortisol = lipolysis, but long term = adipocyte formation, increased BGL, breakdown of protein impairs CT/collagen formation, antagonist of ADH = HTN

Question 8

What different types of Cushing’s syndrome are there?

Answer 8

• Adrenal tumor that secretes cortisol (neg feedback causes low ACTH)
• Pituitary tumor secreting ACTH (causes high cortisol) “Cushing’s Disease”
• Ectopic ACTH-secreting tumor (causes increased cortisol which causes decrease of pituitary secretion of ACTH)—high dose test has no ACTH effect
• Iatrogenic- excess exogenous glucocorticoids causes decreased CRH and ACTH due to negative feedback

Question 9

Describe the HPA axis in Addison’s disease

Answer 9

Decreased cortisol output from adrenal gland, so high CRH from hypothalamus and high ACTH from pituitary—basically the excess ACTH must find other means of dispersement (one of which is the pigment increase)

Question 10

What is the primary action of aldosterone?

Answer 10

Renal sodium reabsorption

Question 11

Explain hyperpigmentation seen in

Addison’s disease

Answer 11

High levels of ACTH activate receptors in melanocytes which causes skin darkening—ACTH and alpha-MSH lead to increased Melanin synthesis

Question 12

Explain primary vs secondary/tertiary adrenal insufficiency

and review the cosyntropin stimulation test for determining which

Answer 12

Primary - adrenal cortex not secreting cortisol or aldosterone
Secondary/tertiary - decreased ACTH means adrenal cortex not secreting cortisol, but renin/angiotensin system still allows for aldosterone secretion

CST: only used if 8am cortisol level is between 3-15 micro g/dL

• greater than 15= AI is ruled out
• less than 3= definite insufficiency (can skip the test and measure ACTH straight for type-determining)

give dose of cosyntropin (synthetic acth)… wait 30 min… if there is less than 18 micro g/dL after time, you then measure ACTH levels to determine type (elevated levels=Primary AI///Low/normal levels=secondary or tertiary

Question 13

What is Conn’s syndrome?

Answer 13

Primary hyperaldosteronism - excessive release of aldosterone from adrenal cortex (can be due to adenoma)

Question 14

What is secondary hyperaldosteronism?

Answer 14

Excessive renin secretion by kidney = high aldosterone levels

Question 15

What is hypoaldosteronism?

Answer 15

Inadequate stimulation of aldosterone secretion, can be due to destruction of adrenal cortex or defects in aldosterone synthesis

Question 16

In the pathways for synthesizing adrenal steroid hormones, what are the common key enzymes?

Answer 16

Aldosterone- 21B, 11B
Cortisol- 17a, 21B, 11B
Androgens- 17a

A deficiency is one of these will increase the production of the other paths, which explains the symptoms that will present in the case

Question 17

Congenital adrenal enzyme deficiencies are characterized by what?

Answer 17

Enlargement of both adrenal glands (adrenal hyperplasia) due to increased ACTH stimulation (bc of decreased cortisol)

Question 18

What is a pheochromocytoma?

Answer 18

Benign, unilateral adrenal tumor that causes an increase in BP by stimulating alpha/beta adrenergic receptors with elevated levels of catecholamines

• it is a rare and dangerous cause of hypertension
• presents commonly with headaches, palpitations (heart), and sweating

Question 19

What are the layers of the Adrenal Glands?

Answer 19

Cali Girls F Real Men
Capsule
Glomerulosa (Salt)
Fasciculata (Sugar)
Reticularis (Sex)
Medulla (chromaffin cells)

Question 20

Application of exogenous glucocorticoid does what?

Answer 20

Same negative feedback as cortisol, but over time can atrophy the adrenal cells that actually produce cortisol

Question 21

Some major causes of Primary adrenal insufficiency (Addison’s disease)

Answer 21

• Autoimmune disease that destroys the Adrenal Gland
• Adrenal Hemorrhage (secondary effects to Meningitidis or caused by anticoagulant treatment)
• infection from Tuberculosis or Meningitidis
• Tumor metastases to the AG

Question 22

Cortisol upregulates what enzyme, that does what?

Answer 22

PNMT- turns Norepinephrine–>Epinephrine

Karius would be proud

Also Ach is the signal for secretion of Catecholamines in case that also was punted after the last neuro exam

Question 23

Catecholamine action lasts about how long?

What degrades them?

Answer 23

about 10 seconds

COMT and MAO