Aldosterone - Zona Glomerulosa

Cortisol - Zona Fasciculata

Androgens - Zona Reticularis

ALL ARE IN ADRENAL CORTEX.

♠ Increase gluconeogenesis

♣ Release amino acids through muscle catabolism

♥ Inhibit peripheral glucose uptake

♦ Stimulate lipolysis

END RESULT IS TO MAINTAIN ADEQUATE GLUCOSE FOR THE BRAIN

• Upregulate anti-inflammatory proteins

• Downregulate pro-inflammatory proteins

• Decrease leukocyte presence and function at sites of inflammation.

In Endocrine practice:

1) Diagnose Cushing's syndrome

2) Treat adrenal insufficiency and Congenital Adrenal Hyperplasia (CAH)

General use:

1) Treat inflammatory, allergic and immunological disorders. Must use supraphysiological dose.

1) Adrenocortical insufficiency (Addison's disease)

2) Cushing's syndrome

3) Congenital Adrenal Hyperplasia (CAH)

4) Aldosteronism (too much aldo)

CAUSE: Chronic or acute destruction of adrenal gland by means of the following processes: 1) Autoimmune adrenalitis (most common cause in West). 2) Infection (TB, fungal, CMV, HIV). 3) Hemorrhage (Waterhouse-Friderichsen) after meningococcal sepsis. 4) Metastatic tumor. 5) Infiltrations (amyloid, hemochromatosis [iron overload--hemosiderin inclusions]). 6) Adrenoleukodystrophies (inability to clear long chain FFAs, damages myelin and the adrenal gland somehow - Lorenzo's oil disease).

SYMPTOMS: Fatigue, NVD, salt craving, postural dizziness, anorexia.

SIGNS: Wt. loss, skin pigmentation, hypotension, vitiligo (depigmentation of sections of skin).

LABS: Hyponatremia, hyperkalemia, anemia, eosinophelia, azotemia.

CAUSE: 1) Glucocorticoid therapy. 2) Hypopituitarism secondary to pituitary tumors or surgery, pituitary apoplexy, granulomatous disease, metastatic tumor to pituitary (breast, bronchial), Sheehan's syndrome, radiation, isolated ACTH deficiency.

SYMPTOMS: Same as primary.

SIGNS: Same as primary except no hyperpigmentation (because ACTH not elevated).

Observe signs and symptoms.

Do Cosyntropin IV test: Take baseline cortisol level and then 30-60 mins after 250μg of cosyntropin.

NORMAL = Cortisol > 18

ABNORMAL = Cortisol < 18

Once insufficiency is confirmed: Primary is ↓ Cortisol, ↑ ACTH. Secondary is ↓ Cortisol, ↓ ACTH.

1) Glucocorticoid replacement (hydrocortisone) that mimics diurnal secretion. Increase dose during febrile illness. After trauma or severe stress. Before surgery/procedures.

2) Mineralocorticoid replacement. Also advise patient to intake salt liberally.

1) ACTH dependent - a) pituitary adenoma. b) ectopic ACTH production (small cell lung ca., bronchial carcinoid)

2) ACTH - independent - a) adrenal adenoma. b) adrenal carcinoma.

3) Pseudo-cushing's syndrome - caused by a) alcoholism. b) depression. c) obesity.

4) Iatrogenic - too much cortisol in hospital.

SYMPTOMS: Weight gain, hirsutism, psychiatric dysf., muscle weakness, fractures (osteoporosis).

SIGNS: Truncal obesity, moon facies, hypertension, abdominal striae, ankle edema, dorsocervical fat pad, diabetes, infections, cataracts.

USE: Cushing's treatment.

MECH: Blocks conversion of cholesterol to pregnenolone.

USE: Cushing's syndrome tmnt.

MECH: Antifungal imidazole derivative. Potent, nonselective inhibitor of adrenal and gonadal steroid hormone synthesis.

USE: Cushing's treatment.

MECH: Related to DDT insecticides. Nonselective cytotoxic action on adrenal cortex. Bad side effects!

USE: Cushing's treatment

MECH: Relatively selective inhibitor of 11-hydroxylation. Interferes with cortisol and corticosterone synth. (11-deoxycortisol---->Cortisol via 11β-hydroxylase)

RU-486 (abortion pill)

USE: glucocorticoid receptor antagonist--causes generalized glucocorticoid resistance.

Autosomal recessive mutations in enzymes involved in adrenal steroidogenesis.

Most common is 21-hydroxylase deficiency. Diverts pathway away from Aldosterone and Cortisol synthesis and towards Androgen and Estrogen pathway.

1) Steroids (dexamethazone).

2) Fludricortizosone for salt wasting.

SIGNS: ↑ Aldo, ↓ Renin, hypokalemia, hypertension.

CAUSES: Hyperaldosterone secretion due to 1) Aldo-producing adenoma. 2) Bilateral adrenal hyperplasia. 3) Aldo-producing adrenocortical carcinoma. 4) Primary unilateral adrenal hyperplasia.

Surgery for unilateral.

Use spironolactone or eplerenone (both aldo antagonists) for bilateral adrenal hyperplasia.