Pharmacological Treatment of Adrenal and Thyroid Disease

Question 1

Zona Glomerulosa

Answer 1

Mineralocorticoids

Question 2

Zonae Fasciculata/Reticularis

Answer 2

Glucocorticoids

Adrenal androgens

Question 3

Glucocorticoids

Answer 3

carbohydrate metabolism

Major type: hydrocortisone/cortisol

Question 4

Mineralocorticoids

Answer 4

electrolyte-water homeostasis

Major type: aldosterone

Question 5

ACTH i.v. test

Answer 5

stimulate cortisol secretion, diagnosis of adrenocortical insufficiency

Question 6

Morning ACTH level

Answer 6

evaluate pituitary function during the recovery from prolonged glucocorticoids exposure

Question 7

Corticosteroid-binding-globulin (CBG): availability

Answer 7

bind greater than 80% of circulating cortisol (unavailable)
<20% cortisol is free or loosely bound to albumin (available)
Aldosterone dose not bind CBG, has short half-life
Dexamethasone dose not bind CBG, thus is 100% active

Question 8

Pharmacokinetics Corticosteroids

Answer 8

short-acting: cortisol and cortisone - Salt-retaining
intermediate-acting: prednisone
Intermediate anti-inflammatory and salt-retaining activity
long-acting: dexamethasone and betamethasone
Maximal anti-inflammatory and minimal salt-retaining activity

Question 9

Glucocorticoid Metabolic effects

Answer 9

Promotes gluconeogenesis in liver and inhibits glucose utilization in periphery
Increased protein and fat catabolism
Inhibits Calcium absorption, osteoblast formation and activity

Question 10

Glucocorticoid Anti-inflammatory effects

Answer 10

Suppress activation of T cells and production of cytokines
Prevent release of inflammation mediators
Reduce circulating lymphocytes, monocytes, eosinophils, and basophils
Inhibit the function of leukocytes and macrophages
stimulate gastric acid and pepsin production

Question 11

Glucocorticoids Therapeutic Uses

Answer 11

Primary: Addison’s disease
Acute: emergency, hydrocortisone i.v.
Chronic: replacement therapy, mimic the circadian secretion
All adrenal steroids are reduced
Secondary
Often caused by suppression of the HPA axis
Low cortisol and androgens, but normal aldosterone
Drug selection: cortisol (hydrocortisone)

Question 12

Glucocorticoids Therapeutic Uses 2

Answer 12

Anti-inflammation and immunosuppression
Allergy: bee sting, drug reactions, contact dermatitis
Brochial asthma, infant respiratory distress
Inflammation and autoimmune disorder: arthritis,
multiple sclerosis, systemic lupus
Prevent organ rejection in transplantation
Drug selection: intermediate- and long-acting; maximal anti-inflammatory and minimal salt-retaining activity for severe cases

Question 13

Glucocorticoids Therapeutic Uses 3

Answer 13

Evaluate the function of hypothalamus-pituitary-adrenal axis
Cushing’s Syndrome
Increased urine cortisol level
Fail in low-dose dexamethasone suppression test
For all types of Cushing’s syndrome: failure in suppression of serum cortisol to < 5 mg/dL by a low dose of dexamethasone.

Question 14

Cushing Syndrome

Answer 14

full moon face and trunk obesity
muscle waste and thinning of skin
osteoporosis

Question 15

Glucocorticoids Adverse Effects and Clinical Problems

Answer 15

Withdrawal of steroids
Acute adrenal insufficiency, due to suppression of HPA axis
Flare-up of underlining disease

Question 16

Mineralocorticoids Pharmacological effects and therapeutic uses

Answer 16

Pharmacological effects:
Salt-remaining activity: promoting reabsorption of sodium, secretion of potassium.
Therapeutic uses:
Adrenal insufficiency
Fludrocortisone is the most widely used mineralocorticoid.
Adverse effects: salt-retention and hypertension

Question 17

Aminoglutethimide

Answer 17

Inhibits the conversion of cholesterol to pregnenolone.

Therapeutic Uses: adrenal and/or pituitary adenoma

Question 18

Spironolactone

Answer 18

Antagonist for mineralocorticoid receptor.

Uses: aldosteronism, such as adrenal adenoma

Question 19

Mifepristone (RU486)

Answer 19

Antagonist for glucocorticoid receptor

Also acts as an antagonist for progesterone receptor

Question 20

Hypothyroidisim

Answer 20

Causes: destruction of thyroid
Autoimmune : Hashimoto’s thyroiditis
Surgery or lithium over dose

Question 21

Levothyroxine

Answer 21

Synthroid, L-T4

Question 22

Liothyronine

Answer 22

L-T3

Acute Severe Hypothyroidism

Question 23

Hyperthyroidisim

Answer 23

Grave’s disease: Autoimmune antibody binds TSH receptor and mimics hormone
Hyperfunction goiter
Clinical symptoms:
Increased metabolic rate
Irregular heart beat/rapid pulse
Increased appetite with dramatic weight loss
Protruding eyes (bug eye), and Goiter

Question 24

Thioureylene
Propylthiouracil (PTU)
Methimazole (Tapazol)

Answer 24

Inhibits peroxidase reactions in iodination of
TG and coupling of MIT/DIT
PTU also inhibits the conversion of T4 to T3
control of symptoms prior to surgery or RIA

Question 25

Iodide or KI (Lugol’s) solution/tablet: >6 mg/day

Answer 25

Inhibits TH formation and release

Application: thyroid storm, preoperative thyroidectomy given after thioureylene

Question 26

Radioactive iodide (131I) and surgery

Answer 26

Mechanisms: 131I emits beta-rays that kills surrounding thyroid cells
Application: severe hyperthyroidism/thyroid tumor, combined with life-long therapy with Synthroid

Question 27

Propranolol

Answer 27

Beta blocker to reverse tachycardia during thyroid storm.

Used in combination with thioureylene