Adrenal Disorders Pharamcology

Question 1

Anatomic parts of adrenal gland with hormones it produces

Answer 1

Outer cortex

• cortisol
• vasopressin
• aldosterone
• DHEA

Inner medulla
- catecholamines (NE and epinephrine)

Question 2

Cortisol and aldosterone effects

Answer 2

Cortisol

• Raises plasma glucose levels and stimulates gluconeogenesis
• inhibits glucose uptake except in the brain
• Promotes protein catabolism
• Promotes lipolysis and fat redistribution in the body
• enhances catecholamine effects on blood vessels (HTN)
• decreases osteogenesis and promotes osteoporosis
• immunosupression and anti-inflammation

Aldosterone

• alters sodium and water in the renal collecting duct
• synthesis and secretion regulated by angiotensin 2 at AT1 receptors on zona glomerulosa cells

Question 3

Cushing syndrome

Answer 3

Excess glucocorticoids
(especially cortisol)

Symptoms:

• obesity
• hyperglycemia and HTN
• osteoporosis
• muscle weakness
• hirsutism
• buffalo hump and strain on abdomen
• poor wound healing
• moon-like facies

Treatment:

• surgical adrenal tumor with HRT therapy (hydrocortisone and cortisone)
• can also use: metyrapoine, aminoglutethimide, ketoconazole

Question 4

3 drugs used to treat Cushing syndrome

Answer 4

On top of hydrocortisone or cortisone treatment

1) metyrapone:
- 11-B hydroxylase enzyme inhibitor

2) aminoglutethimide
- inhibits conversion of cholesterol -> pregneolone (chemical adrenalectomy)

3) ketoconazole
- inhibits synthesis of all hormones in testes and adrenal cortex

Question 5

Primary hyperaldosteronism

Answer 5

Excess aldosterone secretion caused by adrenal tumors

Symptoms:

• edema
• fluid/electrolyte disturbances
• HTN

Treatment:

• surgical adrenal resection with fludrocortisone HRT
• Also can use spironolactone (antagonizes aldosterone)

Question 6

Addison’s disease

Adrenal hormone deficiency

Answer 6

Caused by multiple causes but all result in insufficiency of cortisol and aldosterone levels

Symptoms:

• weakness
• emanciation
• hypoglycemia
• hyperpigmentation of skin
• hyperkalemia
• hyponatremia
• hypotension

Treatment: HRT with hydrocortisone/cortisone and fludrocortisone

Question 7

What is the diurnal rhythm of cortisol release

Answer 7

Highest levels are in the morning/waking up

Lowest levels found at night

very closely related to sleep-wake cycle

Question 8

How does stress regulate cortisol release

Answer 8

The Stress descending central pathways increases CRH release from the hypothalamus.

Question 9

How does angiotensin 2 affect aldosterone secretion

Answer 9

Angiotensin 2 binds to AT1 receptors on zona glomerulosa cells

1) Regulates conversion of cholesterol -> pregneolone Via desmolase enzyme activity
2) Regulates conversion of corticosterone -> aldosterone via aldosterone synthase

Aldosterone effects are increase sodium reabsorption and potassium excretion via Na/K exchanger

Question 10

DHEA

Answer 10

Produced by the zona reticularis in the adrenal cortex

In males = produces testosterone and is primary androgen throughout life

In females = induces puberty effects but under normal conditions is clinically insignificant after puberty

Question 11

Glucocorticoid receptors (GRs)

Answer 11

Nuclear receptor family of transcription factors
- reside in the cytoplasm in an inactive form until steroid binding occurs (then it translocates to the nucleus to up-regulate transcriptions of glucocorticoid responsive elements (GREs). This upregulates glucocorticoid production while also inhibiting cycloxygenase 2, nitric oxide and inflammatory cytokine production

Question 12

Mineralcorticoid receptors (MRs)

Answer 12

Ligand-activated transcription factors and bind to very similar hormone responsive elements
- are expressed in epithelial tissues involved in electrolyte transport (kidney,colon, salivary glands, etc) and in the heart, vasculature and adipose tissue

Question 13

What is the purpose of the dexamethasone test

Answer 13

Diagnosing Cushing syndrome

Inject a patient with dexamethasone (contains potent glucocorticoid action but little Mineralcorticoid action)
- administer in the evening before bed and then measure in the morning

Normal functional HPA axis = ACTH release and cortisol levels are suppressed

Cushing syndrome = ACTRH levels are suppressed but cortisol levels will remain elevated

Question 14

Corticosteroid toxicity

Answer 14

Occurs with cessation of chronic steroid use of acute high dose use

If abruptly stopped, results in acute Addison’s disease
- because of this tapered dose is required instead of going cold turkey (requires several weeks to months to taper off and minor ACTH and cortisol levels)

Withdrawal syndrome symptoms:

• fever
• myalgia
• arthralgia
• malaise
• *Continued use of high dose corticosteroids in high doses
• fluid electrolytes
• HTN
• hyperglycemia
• increased susceptibility to infections
• peptic ulcers, osteoporosis
• myopathy
• cataracts and growth arrest

Question 15

What are the three most common characteristics of physical signs associated with excess glucocorticoid use

Answer 15

Fat redistribution (buffalo hump)

Striae (collagen rearrangement)

Ecchymoses (poor wound healing)