Pair glands and located above the kidney

2 distinct organs

1. Cortex--secretes steroids
2. Medulla--secretes Neuropeptides

Zona Glomerulosa--mineralcorticoids (aldosterone)

Zona Fasiculata--Glucocorticoids (cortisol)

Zona Reticularis--Adrenal Androgens (DHEA)

Corticotropin Releasing hormone(CRH)--released by hypothalamus to stimulate Pituitary

Adrenocorticotropin Hormone (ACTH)--released by the pituitary to stimulate cortex of adrenal gland

Controls secretion of cortisol and adrenal androgens

--As part of the R-A-A-S controls aldosterone levels

at the DCT it causes K+ excreation and Na+ rabsorption

-protect against hypovolemia and hyperkalemia

Major atually occuring glucocorticoid

Glucocorticoid

(Function)

--Gluconeogenisis

--Anti-insulin effect

--Protein Catabolism

--Inhibits Lipogenisis

--Induces Lipolysis

Glucocorticoid

(Anti-infalmmatory effects)

--Mast cell stabilization

--Stabelize lysosomal membranes

--decrease capillary permiability

--Supresses T-cell activation

--Redistribution of leukocyte differential

Glucocorticoid

(other MISC. effects)

bone

Psych

GI

pituitary

Skin

bone--osteoporosis

Psych/CNS--mood changes

GI--increased pepsin production

Pituitary--decrease TSH and FSH

Skin--thinning

DHEA is the major androgen secreted

Androstenedione--secreted in small amounts

Testosterone--secreted in small amounts(more important in females)

1. Cushing's Syndrome--adrenal hyperfunciton
2. Addison's Disease--adrenal hypofunction
3. Tumor of Medulla--pheochromocytoma

--Acute Adrenal Insufficiency

• Can occur with a stressor
• Corticoids stopped too quickly
• Sudden destruction of pituitary
• Thyroid hormone given to hypoadrenal patient
• Adrenal insult
• Infections (ie Waterhouse-Friderichsen)

§Headache

Acute Adrenal Failure

(labs)

 §Hyponatremia

1. Cosyntropin (synthetic ACTH)--parenteral dose of .25 mg given to patient and measure serum cortisol.

• Normal patient--see an increase in cortisol
• Hypoadrenalism--see a decrease in cortisol

*must stop hydrocortisone 8 hrs prior to test*

1. Hydrocortisone IV push and maintain 10mg/hr via infusion
2. IV fluids
3. Volume Exanders--normal saline, lactated ringers, plasmanate(saline and protein)
4. Fludrocortisone--replace aldosterone--not urgent

Chronic Addison's Disease

(etiologies)

1. Autoimmune adrenal insufficiency--80% USA
2. HIV--most common infectious in USA
3. Tuberculosis--most common worldwide

Chronic Addison's Disease

(S/S)

§Weakness, easily fatigued

Chronic Addison's Disease

(Lab Evaluation)

 §Na+ - may be decreased

Chronic Addison's Disease

(Diagnosis)

--Plasma cortisol levels decreased to <3mcg/dL at 8am

--ACTH level is elevated

--DHEA <1000 ng/mL

Cosyntropin shows inadequate adrenal response

Chronice Addison's Disease

(treatement)

1. Hydrocortisone--po (2/3 dose AM) (1/3 dose PM)
2. Fludrocortisone--po QD
3. Dehydroepiandrosterone--po QD
4. NaCL--(counter act the salt wasting)

--double the usual steroid dose.

--wean to the baseline steroid dose when the stress is controlled

--during surgery give hydrocortison loading dose and wean over 2-3 days

--identical to cortisol

dose--5-30mg/d

MOA--see glucocorticoids

Precautions--TB, fungal infections, hepatic/renal impariment, seizures, osteoporosis

Adverse Reactions--Cushingoid effect

PREG--C

1/2 life--8-12 hrs

Mineral corticoid substitute for aldosteron

Dose--.05-.2 mg QD

MOA--same as aldosterone

Cautions--TB, fungal infections, hepatic/renal impairment, seizures, osteoporosis

Adverse Reactions--cushingoid, suppressed adrenal, CHF

PREG--C

1/2 life- 18-36 hrs

Dehyrdroepiandrosterone

(DHEA)

This is identical to the adrenal androgen.

Dosage:  20-50 mg/d for replacement

Mode of Action:  Precursor to testosterone and estrogen

Precautions:  Cancer, endometriosis or fibroids, mood disorders, hepatic impairment

Adverse Reactions:  Potential problem in cancer

Cushing's DZ

VS

Cushing's Syndrome

DZ--hypercortisolism due to pituitary (pituitary adenoma) hypersecretion of ACTH

Syndrome--caused by exogenous steroid administration, ectopic steroid production, or adrenal overproduction

Account for 32% of Cushing's syndrome

1. Adenomas--small and b9 (secrete coritsol)
2. Carcinomas--Cortisol and androgens (large)
3. Macronodular Adrenal hyperplasia

Causes 10% of the cushing's syndrome

--ie small cell lung carcinoma with ectopic ACTH production

Moon face

Buffalo hump

supraclavicular fat pads

MANY OTHERS

NA+ normal

K+ decreased

Diabetes Mellitus

Polyuria

Leukocytosis

Cushing's

(Diagnostic testing)

24 hr urine for free cortisol and creatine

Dexamethasone suppression test (give at 11pm and if cortisol is elevated the following morning it is this DZ)

Pituitary  

Surgery

External beam radiation

Ketoconazole or Metyrapone

Adrenal neoplasm

surgery

Metastatic Adrenal Carcinomas

mitonane, ketoconazole, metyrapone

Ectopic ACTH-secreting tumor

surgery

OFF label use

dose--200mg po QD

precaution--do not use with PPI or H2 blockers, hepatotoxic

Adverse reaction--elevated LTF's, nausea, dcreased libido, gynecomastia

Preg--C

1/2 life--8  hrs

interrupts cortisol syntheis by blocking 11-beta-hydroxylase

--Adrogen and other precussors are increased--> hirsutism, ACNE, HTN

Inhibits 11-beta-hydroxylase and cholesterol side chain enzymes

--primary hyperaldosteronism

increased adrenal production of aldosterone seen in women 30-60yoa

Primary Hyperaldosteronism

(s/s)

• HTN
• Hypokalemia(muscle weak, tetany, HA, arrythmia)
• Low plasma RENIN

Primary Hyperaldosteronism

(LABS)

Na+ - slight elevation.

K+ - can be decreased.

Aldosterone elevated in plasma or

      in a 24 hour urine collection.

May have impaired glucose tolerance

Sampling from adrenal vein.

Primary Hyperaldosteronism

(Cause and treatment)

C--73% due to unilateral adrenocortical adenoma

T--Surgery

C--27% due to bilateral cortical hyperplasia

T--Medicinal

Give spironolactone 400 mg Q day X 4 days.  Check K and if it increases, presume hyperaldosteronism.  Significant decrease in K with discontinuation of spironolactone is consistent with diagnosis.

Spironolactone

(aldactone)

Dosage: 100-400 mg/day

Action: Works at the distal convoluted tubule.  Na resorption is blocked.  There is sparing of K.

Precautions: Use in hyperkalemia.  Use with caution hepatic or renal impairment.

Adverse Reactions: *Hyperkalemia*, anaphylaxis, agranulocytosis, hepatic or renal failure.

Pregnancy: Category D

Half-life: 1.5 to 2 hours

Catecholamine producing tumor

90% in medulla

male = female

30-60 yoa

Pheochromocytoma

(s/s)

5P's

1. pressure (HTN)
2. Pain (chest, abdominal, head)
3. Perspiration
4. Palpitation
5. Pallor

--Suspicion

--Elevated Metanephrine and VMA

--MRI

Pheochromocytoma

(treatment)

Pheochromocytoma

(pre-op treatment)

--Phenoxybenzamine--controlling BP

--Propranolol

--Phentolamine or nitroprusside for HTN crisis

Dosage: 10 mg QD to 40 mg BID/TID to control BP prior to surgery.

Action: alpha-adrenergic antagonist

Precautions: Cardiovascular or renal disease.

Other Indications: Neurogenic bladder.

Adverse Reactions: Hypotension and shock; CHF

Pregnancy: Category C

Half-life: 24 hours

Phentolamine

(Regitine)

Dosage: 5 mg 1-2 hours prior to surgery.  May repeat during and after surgery. 

Action: Alpha-adrenergic antagonist

Precautions: CVD, CAD

Adverse Reactions: CVA, MI, hypotension, orthostasis, arrhythmias, priapism, fatigue, GI pain, miosis, nasal congestion

Pregnancy: Category C

Half-life: 19 minutes