Adrenal Gland Disorders

Question 1

What makes up the adrenal glands?

Answer 1

They are composed of two regions: Adrenal Cortex & Adrenal Medulla

Question 2

What cells make up the cortex?

Answer 2

3 Zones:

1. Zona glomerulosa
2. Zona fasiculata
3. Zona reticularis

Question 3

What cells make mineralocorticoids (aldosterone)?

Answer 3

Zona glomerulosa

Question 4

What cells make glucocorticoids (cortisol)?

Answer 4

Zona fasiculata

Question 5

What cells make androgens: androstenedione, DHEA and DHEA-S?

Answer 5

Zona reticularis

Question 6

What cells make catecholamines (epi and norepi)?

Answer 6

Medulla (10-20%)

Question 7

What is the site of action for aldosterone?

Answer 7

Distal nephrons of the kidneys

Question 8

What is the function of aldosterone?

Answer 8

• reabsorb Na+ and Cl-
• secrete K+ & H+
• water homeostasis

Question 9

Where is renin stored?

Answer 9

Renin is produced and stored in the juxtaglomerular cells surrounging the afferent arterioles of glomeruli in the kidneys.

Question 10

What does aldosterone help retain?

Answer 10

Aldosterone enhances renal sodium retention and thus results in expansion of the extracelular fluid volume thus dampening the stimulation for renin release.

Question 11

Describe the renin angiotensin pathway.

Answer 11

Renin acts on angiotensinogen (Alpha 2 globulin produced in the liver) in the kidney and peripherally to form angiotensin 1.

Angiotensin 1 is transformed by ACE (angiotensin converting enzyme-particularly present in the pulmonary vascular endothelium) to angiotensin 2. Angiotensin 2 is a potent pressor agent and exerts it’s action by direct effect on arteriolar smooth muscle.

Angiotensin 2 also stimulated production of aldosterone by the zona glomerulosa (adrenal cortex).

Question 12

What stimulates renin synthesis?

Answer 12

Renin synthesis occurs in the juxtaglomerular cells of the kidney and is released in response to:

• low sodium
• low renal blood flow
• high K
• increased sympathetic nerve stimulation

Question 13

What stimulates the release of cortisol and androgens?

Answer 13

Release stimulated by ACTH.

The release of ACTH, and thus of cortisol and androgens, occurs episodically throughout the 24 hour cycle in a circadian pattern.

Question 14

What stimulates the secretion of ACTH?

Answer 14

• stress (trauma, surgery, anxiety, emotional disturbance)

- low circulating levels of cortisol

Question 15

What inhibits the secretion of ACTH?

Answer 15

• high circulating levels of cortisol

- presence of synthetic glucocorticoids

Question 16

What are the physiological effects of gluccocorticoids?

Answer 16

• Stimulate gluconeogenesis
• Induce insulin resistance
• Increase release of amino acids and fatty acids
• Elevate RBC and platelet levels
• Maintain normal vascular response to vasoconstrictors
• Stimulation of PMN leukocytosis
• Depletion of circulating eosinophils and lymphocytes.
• Decrease macrophage adherence to endothelium

Question 17

What is Hyperaldosteronism (Conn’s Syndrome)?

Answer 17

Elevated levels of aldosterone causing HTN and hypokalemia

Question 18

What is the most common etiology of Hyperaldosteronism (Conn’s Syndrome)?

Answer 18

Aldosterone producing adenomas (60-70%)

Question 19

How is hyperaldosteronism diagnosed?

Answer 19

Screening: Measure 8 AM plasma aldosterone (PA) & plasma renin activity (PRA) levels. Obtain PA/PRA ratio.
Ratio 4-10 = normal
Ratio > 20 = primary aldosteronism

Confirmatory testing: Saline or salt loading test fails to suppress aldosterone. Aldosterone >10 ng/dL leads to a positive diagnosis.

Question 20

What are the types of adrenal insufficiency?

Answer 20

Primary (Addison’s disease): originates at the adrenal gland

Secondary: Pituitary problem (ACTH)

Question 21

What is the etiology of Primary Adrenal insufficiency (Addison’s disease)?

Answer 21

Autoimmune (most common cause), TB is another cause

Caused by the dysfunction or absence of the adrenal cortices. Characterized by a chronic deficiency of cortisol. ACTH levels are elevated.

Question 22

What are the clinical features of chronic adrenal insufficiency?

Answer 22

Weakness, Weight loss, small heart
Anorexia, nausea 
Abdominal pain, Diarrhea or constipation
Postural hypotension – dizziness, syncope
Salt craving
Skin hyperpigmentation

Question 23

What causes hyperpigmentation?

Answer 23

Increase of ACTH

Question 24

Where do we see hyperpigmentation in Primary AI?

Answer 24

dorsal surface and palmar creases, elbows and knees

Question 25

What causes Iatrogenic Adrenal Insufficiency?

Answer 25

Caused by: chronic exogenous steroid use Degree of suppression depends on dosage, schedule, and duration of administration suppression rarely occurs with dosages of HC (or its equivalent) of <21 days usually do not result in adrenal insufficiency

Question 26

What is adrenal crisis?

Answer 26

Acute adrenal insufficiency is an emergency caused by insufficient cortisol. Crisis may occur in the course of treatment of chronic insufficiency, or it may be the presenting manifestation of adrenal insufficiency. Can occur during stress or in withdrawal of adrenocortical hormone.

Question 27

What are the clinical features of adrenal crisis?

Answer 27

Headache, N/V, abdominal pain, and often diarrhea. BP is low. May see sparse axillary hair (if hypogonadism is also present). Hyponatremia, hyperkalemia No hyper-pigmentation in acute failure

Question 28

How is adrenal crisis treated?

Answer 28

Treat with hydrocortisone, glucose and IV saline immediatley, with out waiting for results.

Question 29

How is adrenal insufficiency diagnosed?

Answer 29

Cosyntropin stimulation test, Anti adrenal antibodies are present in 50% of patients.

Question 30

How is primary adrenal insufficiency treated?

Answer 30

Combination of corticosteroid and mineralcorticoid. Hydrocortisone is the drug of choice with fludrocortisone acetate. Alert bracelet

Question 31

What is cushings syndrome?

Answer 31

The term Cushings refers to the manifestations of excessive corticosteroids commonly dure to supraphysiologic doses of corticosteroid drugs and rarely due to spontaneous production of excessive corticosteroids by the adrenal cortex. 40% due to ACTH hypersecretion by pituitary

Question 32

How is cushings syndrome different from cushings disease?

Answer 32

Cushing’s disease: Pituitary source of high ACTH Cushing’s syndrome: Adrenal source of high cortisol levels

Question 33

What causes cushings syndrome?

Answer 33

Ectopic source: ACTH or CRH production by tumors Exogenous steroids: Most common

Question 34

What are the clinical findings for cushings syndrome?

Answer 34

``` Central obesity Muscular weakness,proximal Moon facies and facial plethora Buffalo hump, Purple straie Hirsutism, Acne ``` ``` Polyuria, nocturia Hypertension DM or Impaired glucose tolerance (IGT) Osteoporosis Avascular bone necrosis ```

Question 35

What is Ectopic ACTH syndrome?

Answer 35

Marked wasting and skin pigmentation are present

Question 36

How is cushings diagnosed?

Answer 36

Dexamethasone Suppression Test

Question 37

Determining ACTH-dependent vs. ACTH-independent.

Answer 37

Check plasma ACTH level. Suppressed (200) then suggests an ectopic source.

Question 38

What is Pheochromocytoma?

Answer 38

Chromaffin tumors that usually arise in the adrenal medulla, can be extra-adrenal, along the sympathetic chain in the abdomen, thorax, or neck, and rarely in sympathetic tissue in the walls of the urinary bladder.

Question 39

What are the clinical features of Pheochromocytoma?

Answer 39

Headaches occur in 80% of cases Other common symptoms: excessive perspiration (70%) palpitations (64%) tremors (30%) Catecholamine excess often causes pallor (due to vasoconstriction) and not flushing (due to vasodilation)

Question 40

How is Pheochromocytoma diagnosed?

Answer 40

Urinary measurements of: free catecholamines urinary metabolites-- metanephrines, and VMA. Diagnostic yield increased significantly if obtained after or during paroxysm

Question 41

How is Pheochromocytoma treated?

Answer 41

Surgical excision of the tumor is curative Medical treatment: preoperatively (to decrease perioperative morbidity and mortality) and on a chronic basis in surgical failures α – adrenergic blockade-cornerstone of medical therapy Should be instituted as soon as the diagnosis is made Phenoxybenzamine is the drug of choice ß-blockade to control tachyarrhythmias use only after adequate α –blockade

Question 42

How is Cushings treated?

Answer 42

Best treated with transsphenoidal selective resection of the pituitary adenoma. Give hydrocortisone/ prednisone until return to normal functioning.