The Adrenal Gland

Question 1

• The zona glomerulosa secretes _
• The zona fasciculata secretes _
• The zona reticularis secretes _
• The adrenal medulla secretes _ and _ (which is the main product?)

Answer 1

• Mineralcorticoids (EX: Aldosterone)
• Glucocorticoids (Cortisol) and Androgens (to a lesser extent)
• Androgens and Glucocorticoids to a lesser extent
• Epi (main prod) and NE

Question 2

• The adrenal cortex is derived from _ germ layer
• The adrenal medulla consists of _ cells derived from what germ layer?

Answer 2

• Mesoderm
• Chromaffin (Neural Crest)

Question 3

• Cortisol exerts negative feedback on the hypothalamus (preventing _ release) and the anterior pituitary (preventing _ release)

Answer 3

• CRH, ACTH (from corticotroph cells)

Question 4

• What are the main stimuli of cortisol secretion?
• What are the main effects of cortisol on the following organs/systems:
  
  • Immune
  • Liver
  • Muscle
  • Adipose Tissue

Answer 4

• Stress (ex: exercise or psychological stress) and Circadian Rhythms (regulated by SCN)
• Suppresses Immune Response
• Gluconeogenesis in the liver
• Protein catabolism in muscle
• Lipolysis in adipose tissue

Overall goal is to increase glucose levels in the blood so the body has energy to fight/flee from stimulus

Question 5

• Cortisol is secreted in a _ manner
• Secretory rates are highest _ and lowest during _

Answer 5

• Circadian Rhythm/Pulsatile
• Early morning, late evening

Question 6

• How do exogenous glucocorticoids exert negative feedback?

Answer 6

• Exert negative feedback in the same way cortisol does
• Exogenous glucocorticoids inhibit CRH release from the hypothalamus and ACTH release from the anterior pituitary

Question 7

• What is the main stimulus for the secretion of aldosterone?
• Which cells/layer of the renal cortex are responsible for the production of aldosterone?

Answer 7

• Main stimuli
  
  • Increased K+ or Decreased Na+ in blood
  • Decreased blood volume and/or blood pressure
• Zona glomerulosa

Question 8

• What is the primary function of aldosterone?
• How does aldosterone accomplish this?

Answer 8

• Increase Na+ reabsorption and increase K+ excretion
• Transcription of the following transporters on the following membranes
  
  • APICAL
    
    • K+ channels
    • eNAC channels
  • BASOLATERAL
    
    • Na+/K+ ATPase

Question 9

• Signs and Symptoms of Cushing’s Syndrome (Hypercortisolism)

Answer 9

• Truncal obesity
• Moon face
• Buffalo Hump
• Easy bruising
• Purple striae
• HTN
• Edema
• Weakness
• Osteoporosis
• Hirsutism
• Acne
• Virilization
• Diabetes
• Immunosuppression
• Cognitive Effects

Question 10

• How does the low dose dexamethasone suppression test work?

Answer 10

• Dexamethasone is an exogenous glucocorticoid
• Low dose test differentiates patients who have CS from patients who do not​
• Upon administration of low dose, if patient:
  
  • Does not have ACTH suppression, they are positive for CS (of some type)

Question 11

• How does the high dose dexamethasone suppression test work?

Answer 11

• Helps distinguish between types of Cushing’s Diseases (from pituitary or ectopic tumor)
• Patient given high dose of dexamethosone:
  
  • Decrease in ACTH (pituitary tumor-mediated by negative feedback on pituitary)
  • No Change in ACTH (ectopic tumor-no negative feedback effect)

Question 12

• What happens to CRH, ACTH, and Cortisol levels if a tumor in the adrenal gland is the underlying source for Cushing’s Disease?
• What happens to CRH, ACTH, and Cortisol levels if a tumor in the anterior pituitary is causing Cushing’s disease?
• What happens to CRH, ACTH, and Cortisol levels with an ectopic ACTH secreting tumor?
• What happens to CRH, ACTH and Cortisol levels with exogenous glucocorticoid drug administration (in excess)?

Answer 12

• Low CRH, Low ACTH, High Cortisol
• Low CRH, High ACTH, High Cortisol
• Low CRH, Low ACTH (from anterior pituitary) and high cortisol
• Low CRH, Low ACTH (exogenous glucocorticoids inhibit ACTH release from anterior pituitary), Low cortisol

Question 13

• Etiologies of Cushing’s Syndrome

Answer 13

Question 14

ACTH is derived from _ and is a peptide hormone

It is important because it helps with secretion of _ and synthesis of _ in non pituitary tissues

Answer 14

• POMC
• Alpha-MSH, melanin

Question 15

• Why does hyperpigmentation occur in Addison’s Disease?

Answer 15

• In Addison’s disease, there is lack of cortisol production, and hyperpigmentation results from increased ACTH levels that act as a result of feedback mechanisms in the HPA axis

Question 16

• How is cosyntropin (synthetic ACTH) stimulation test used to diagnose adrenal gland insufficiency (Addisons)

Answer 16

• Measure 8 am cortisol levels:
  
  • If > 15, AI is ruled out
  • If between 3-15, administer 30 min cortisol during cosyntropin stimulation test, and if >18, rule out AI, if < 18, can confirm AI and measure ACTH
  • If <3 during 8 am cortisol levels, can confirm AI, measure ACTH
  • Low or normal ACTH: Secondary or Tertiary AI (pituitary or thyroid)
  • High ACTH: Primary AI (problem with adrenal glands themselves)

Question 17

• Primary adrenal insufficiency
  
  • ​Causes?
    
    • How are CRH, ACTH, Cortisol and Aldosterone Levels affected?
    • Treatment?

Answer 17

• Causes: AID, Adrenal hemorrhage, Infection, Tumor metasteses to adrenal gland
• CRH and ACTH increased, Cortisol (zona fasciculata/reticularis) and Aldosterone levels decreased (zona glomerulosa)
• Cortisol-replaced with corticosteroid
• Aldosterone-replaced with a mineralcorticoid

Side note: since Aldosterone levels are decreased, you will often see an increase in renin (d/t feedback within RAAS system)

Question 18

• Secondary or tertiary adrenal insufficiency
  
  • How are levels of CRH, ACTH, Cortisol, and Aldosterone affected?
  • Treatment?

Answer 18

• CRH is increased, ACTH is decreased, Cortisol is Decreased, Aldosterone is NORMAL (dependent on RAAS system)
• Treat with corticosteroid (normally don’t need mineralcorticoid hormone to replace aldosterone since secretion of aldosterone is usually normal)

Question 19

• All congenital adrenal enzyme deficiencies are characterized by _ of the adrenal glands d/t _ in ACTH stimulation (d/t _ cortisol)

Answer 19

• Enlargement
• Increase, Decrease

Question 20

• Identify how the levels of the following would change given the disease state

Answer 20

Question 21

• _ is a rare but extremely dangerous cause of HTN
• Also leads to what symptoms?

Answer 21

• Pheochomocytoma (most are benign, unilateral)
• Headaches, Palpitations, Sweating
• Excess secretion of catecholamines that activate alpha and beta adrenergic receptors

Question 22

• The adrenal medulla contains _ cells that secrete _ and _
• What are the functions of the primary hormone secreted by the adrenal medulla?

Answer 22

• Chromaffin cells-Epi (80%) and NE (20%)
• Respond to stress-hypoglycemia/exercise
• Influences energy metabolism and CO

Question 23

• Synthesis of catecholamines is under control of what axis?
• _ stimulates synthesis of DOPA and NE
• _ increases PNMT activity
• Release is triggered by CNS contro.

Answer 23

• CRH-ACTH-cortisol axis
• ACh
• Cortisol

Question 24

• What is the rate limiting step in this reaction?

Answer 24

• Hormones (from top to bottom)
  
  • ACh
  • ACh
  • Cortisol
• Enzyme (from top to bottom)
  
  • Tyrosine hydroxylase
  • Dopamine beta hydroxylase
  • PNMT

Rate limiting step-Conversion of Tyrosine to Dopa via Tyrosine Kinase

Question 25

* NE is synthesized in the _ and E is synthesized in the \_

Answer 25

* Nucleus, Cytosol

Question 26

* ***How are catecholamines degraded?***

Answer 26

* **COMT enzyme** * **MOA**

Question 27

* Catecholamine receptors: * _ and _ receptors respond better to NE than Epi * _ receptor responds equally to NE and E * E is more potent than NE for _ receptor

Answer 27

alpha, beta 3 beta 1 beta 2

Question 28

* Major physiologic actions of NE and Epi (summary)

Answer 28