Tx – ADRENAL AND THYROID DISEASE

Question 1

what class of steroid hormones does the zona glomerulosa of the adrenal cortex produce?

Answer 1

mineralocorticoids – aldosterone

Question 2

what class of steroid hormones does the zonae fasciculata/reticularis of the adrenal cortex produce?

Answer 2

glucocorticoids – hydrocortisone (cortisol)

adrenal androgens (converted to testosterone in other tissues)

Question 3

what is the primary function of glucocorticoids?

Answer 3

carbohydrate (glucose) metabolism

Question 4

what is the primary function of mineralocorticoids?

Answer 4

electrolyte-fluid (salt-water) homeostasis (balance)

Question 5

name the three adrenal cortical steroids

1.

2.

3.

Answer 5

1. glucocorticoids
2. mineralocorticoids
3. adrenal androgens

Question 6

what enzyme in the zona glomerulosa converts pregnenolone to aldosterone?

Answer 6

aldosterone synthase

Question 7

what are the two enzyme responsible for the conversion of pregnenolone to cortisol in the zona fasciculata/reticularis?

Answer 7

P450 17-alpha converts prenenolone to 17-alpha-OH-pregnenolone which is converted to cortisol by P450 11-beta

Question 8

what are the five prototype synthetic corticosteroids?

Answer 8

predninosone

prednisolone

dexamethasone

betamethasone

fludrocortisone

Question 9

what are the two events of glucocorticoid-mediated transcription and anti-inflammation

Answer 9

DNA-dependent regulation (upregulation of anti-inflammatory proteins)

Protein inference mechanisms (downregulation of inflammatory proteins)

Question 10

what adrenal cortical steroid receptor has wide-spread expression and broad effects, as well as a low affinity for aldosterone?

Answer 10

glucocorticoid receptor

Question 11

what adrenal cortical steroid receptor is expressed abundantly in renal distal tubules and collecting ducts, and is equally sensitive to both cortisol and aldosterone?

Answer 11

mineralocorticoid receptors

Question 12

how does stress affect the hypothalamus-pituitary-adrenal axis?

Answer 12

CRH (corticotropin-releasing hormone) is released onto the anterior pituitary by the hypothalamus in release to stress. ACTH (adrenocorticotropic hormone) is released, stimulating the production of cortisol

Question 13

how are adrenal insufficiency and addison’s disease diagnosed?

Answer 13

ACTH IV test.

ACTH is administered to assess the functioning of the adrenal glands stress response by measuring the adrenal response to ACTH

Question 14

how is pituitary function evaluated during the recovery from prolonged glucocorticoid exposure?

Answer 14

morning ACTH level assessment

Question 15

what percentage of circulating cortisol does corticosteroid-binding-globulin (CBG) bind?

Answer 15

80% of circulating cortisol is bound by CBG (unavailable)

< 20% of cortisol is free or loosely bound to albumin (available)

Question 16

what affinity does corticosteroid-binding globulin (CBG) have for aldosterone and dexamethasone?

Answer 16

CBG has no affinity for either aldosterone nor dexamethasone

Question 17

what are the short-acting corticosteroids that have considerable salt-retaining activity?

Answer 17

cortisol and cortisone

Question 18

what are the intermediate-acting corticosteroids responsible for intermediate anti-inflammatory and salt-retaining activities?

Answer 18

prednisone

prednisolone

methylprednisolone

Question 19

what are the long-acting corticosteroids responsible for maximal anti-inflammatory and minimal salt-retainning activities?

Answer 19

dexamethasone

betamethasone

Question 20

how do glucocorticoids affect gluconeogensis and glucose utilization in the periphery?

Answer 20

promote gluconeogensis in liver

inhibit peripheral glucose utilization

Question 21

do glucocorticoids promote catabolism/ anabolism of protein and fat?

Answer 21

increase protein and fat catabolism

Question 22

how do glucocorticoids affect calcium absorption, osteoblast formation and activity?

Answer 22

inhibit calcium absorption, osteoblast formation/activity

Question 23

describe the anti-inflammatory effects of glucocorticoids

1. (T cells/ cytokines)
2. (inflammatory mediators)
3. (lymphocytes, monocytes, eosinophils, basophils)
4. (leukocytes and macrophages)

Answer 23

1. suppress T cell activation/ cytokine production
2. inhibit inflammatory mediator release
3. reduce circulating lymphocytes, monocytes, eosinophils, basophils
4. inhibit function of leukocytes and macrophages

Question 24

how do glucocorticoids effect gastric acid and pepsin?

Answer 24

stimulate production of gastric acid and pepsin

Question 25

what are the three therapeutic uses of glucocorticoids?

Answer 25

1. **hormone replacement therapy** for adrenocortical insufficiency 2. **anti-inflammation and immunosuppression** 3. evaluate the function of the **HPA-axis (hypothalamus-pituitary-adrenal)**

Question 26

what are the primary and secondary therapeutic indications for HRT?

Answer 26

* **Primary indication: Addison's disease** (all adrenal steroids are low) * **Secondary indication: suppression of the HPA-axis** (low cortisol and androgens, but normal aldosterone)

Question 27

what is the therapeutic treatment for acute Addison's disease?

Answer 27

hydrocortisone (cortisol) IV

Question 28

what is the glucocorticoid therapeutic treatment for chronic Addison's disease?

Answer 28

hydrocortisone (cortisol) replacement therapy mimicing the natural circadian secretion

Question 29

what is the clinical indicator for addison's disease vs suppression of HPA-axis?

Answer 29

addison's disease = reduced production of all adrenal steroids HPA-axis suppression = low cortisol and androgens, but normal aldosterone

Question 30

what are the therapeutic anti-inflammatory/immunosuppression indications of glucocorticoids? 1. 2. 3. 4.

Answer 30

1. **allergy**: bee sting, drug rxns, contact dermititis 2. **bronchial asthma, infant respiratory distress** 3. **inflammation and autoimmune disorders**: arthritis, multiple sclerosis, systemic lupus 4. **prevent organ refection in transplantation**

Question 31

what is the glucocorticoid therapeutic treatment for anti-inflammation and immunosuppression?

Answer 31

**intermediate-acting corticosteroids** (predinsone, prednisolone, methylprednisolone) and **long-acting corticosteriods** (dexamethasone, betamethasone)

Question 32

how does cushing's syndrome present on a HPA-axis evaluation?

Answer 32

increased urine cortisol level failure of low-dose dexamethasone suppression test

Question 33

how does a pt with cushing's syndrome present physically?

Answer 33

full moon face, trunk obesity, buffalo hump, muscle waste and thinning of skin, osteoporosis (excessive exposure to glucocorticoids)

Question 34

definition: used to assess adrenal gland function by measuring how cortisol levels change in response to an injection to dexamethasone. typically used to diagnose cushing's syndrome (increased cortisol production)

Answer 34

dexamethasone suppression test (DST)

Question 35

what are the adverse effects and clinical problems that present upon withdrawal of steroids?

Answer 35

acute adrenal insufficiency due to suppression of HPA axis, and flare up of underlying disease

Question 36

what are the pharmacological effects of mineralocorticoid administration?

Answer 36

**salt-retaining activity**: promoting reabsorption of sodium, secretion of potassium

Question 37

what are the therapeutic uses of mineralocorticoids?

Answer 37

tx of adrenal insufficiency

Question 38

what is the most widely used therapeutic mineralocorticoid?

Answer 38

fludrocortisone

Question 39

what adverse effects can mineralocorticoids produce?

Answer 39

increased salt-retention and hypertension

Question 40

how does aminoglutethimide block adrenal corticol steroid synthesis?

Answer 40

inhibits the conversion of cholesterol to pregnenolone

Question 41

how is aminoglutethimide used as a therapeutic?

Answer 41

in the case of andrenal and/or pituitary adenoma

Question 42

how does spironolactone inhibit the action of aldosterone?

Answer 42

spironolactone is an antagonist for mineralocorticoid receptors, thus inhibiting activation by aldosterone

Question 43

how is spironolactone used therapeutically?

Answer 43

aldosteronism, such as adrenal adenoma

Question 44

how does mifepristone (RU486) inhibit adrenal cortical steroid

Question 45

describe the action of thyroid hormones:

Answer 45

T4:T3 = 4:1 → converted to T3 → Bind surface receptor → internalize and bind nuclear receptor

Question 46

what are the physiological effects of thyroid hormones?

Answer 46

increased metabolic activity, appetite, activity of sympathetic nervous system, blood flow and heart rate decreased body weight

Question 47

describe the control of TH release by the CNS

Answer 47

hypothalamus produces thyrotropin releasing hormone (TRH) pituitary produces thyroid-stimulating hormone (TSH) (thyrotropin) thyroid produces thyroxin (T4) and thiiodothyronine (T3)

Question 48

hypothyroidism is caused by what?

Answer 48

destruction of the thyroid by either an autoimmune disease (hashimoto's thyroiditis), surgery or lithium overdose

Question 49

how does hypothyroidism present clinically in adults?

Answer 49

myxedema/myxedema coma

Question 50

symptoms include: dry waxy sweelin skin and edema reduced metabolic rate and appetite with weight gain reduced cardiac output, slow pulse

Answer 50

myxedema

Question 51

how does hypothyroidism present clinically in infants?

Answer 51

cretinism

Question 52

symptoms include: impaired CNS development/ mental retardation short stature and coarse facial features

Answer 52

cretinism

Question 53

what hormones are used in replacement therapy for hypothyroidism?

Answer 53

**levothyroxine** (synthroid, L-T4) – most widely used **liothyronine** (L-T3) – for acute severe hypothyroidism (myxedema coma)

Question 54

what two disease states causes hyperthyroidism?

Answer 54

grave's disease hyperfunction goiter

Question 55

how does grave's disease cause hyperthyroidism?

Answer 55

autoimmune antibody binds TSH receptor and mimics hormone

Question 56

symptoms: increased metabolic rate irregular heart beat/rapid pulse increased appetite with dramatic weight loss protruding eyes (bug eye) and goiter

Answer 56

hyperthyroidism

Question 57

what is the treatment for hyperthyroidism?

Answer 57

thiourea drugs iodide or KI (lugol's) solution/tablet (\>6mg/d) radioactive iodide (¹³¹I) and surgery beta adrenergic blockers for acute thyroid storm

Question 58

which antithyroid/thiourea drug is contraindicated for pts with liver dysfunction?

Answer 58

propylthiouracil (PTU)

Question 59

which antithyroid/thiourea drug is contraindicated for pts in the early stages of pregnancy?

Answer 59

methimazole (tapazol)

Question 60

describe the mechanism of action of thiourea drugs

Answer 60

inhibits peroxidase rxns in iodination of the thyroid gland and coupling of MIT/DIT (to form T3) PTU also inhibits the conversion of T4 to T3

Question 61

what is the most common application of thiourea drugs?

Answer 61

control of hyperthyroididic symptoms prior to surgery

Question 62

describe the mechanism of action of iodide/KI (Lugol's) solution

Answer 62

inhibits TH formation and release

Question 63

what are the most common applications of iodide/Lugol's solution?

Answer 63

thyroid storm preoperative administration before thyroidectomy to reduce intraoperative blood loss

Question 64

describe the mechanism of action of radioactive iodide

Answer 64

¹³¹I emits beta-rays that kills surrounding thyroid cells

Question 65

what is the most common application of radioactive iodide?

Answer 65

severe hypothyroidism/thyroid tumor combined with life-long synthroid (levothyroxine) therapy

Question 66

definition: life-threatening crisis characterized by tachycardia, fibrillation, shock, and heart failure

Answer 66

acute thyroid storm

Question 67

what is the drug of choice for acute thyroid storm?

Answer 67

propranolol

Question 68

what is the mechanism of action of propranolol?

Answer 68

blocks activation of sympathetic nervous system and reverses tachycardia

Question 69

what is the most common application of propranolol?

Answer 69

administered in combination with thiourea drugs and a large dose of iodide for rapid treatment of acute thyroid storm