Adrenal Glands Therapeutics

Adrenal gland location

A triangular gland located at the top of each kidney encased in a fibrous capsule

Adrenal gland structure

Composed of cortex (~90%) and medulla (~10%)

Adrenal cortex zones

Zona fasciculata, zona reticularis, zona glomerulosa

Zona fasciculata function

Produces glucocorticoid cortisol

Zona reticularis function

Produces androgens such as DHEA

Zona glomerulosa function

Produces mineralocorticoid aldosterone

Adrenal medulla function

Produces catecholamines norepinephrine and epinephrine

HPA axis

Hypothalamus releases CRH → pituitary releases ACTH → adrenal cortex releases cortisol

ACTH role

Primary regulator of cortisol and androgen production

Aldosterone regulation

Controlled mainly by RAAS and potassium levels

Circadian rhythm cortisol

Cortisol peaks around 8am and is lowest around midnight

Stress response cortisol

Stress increases ACTH and cortisol up to 10x normal levels

Cortisol function

Supports metabolism and energy needs during stress

Cortisol metabolic effects

Stimulates gluconeogenesis, permits lipolysis, inhibits protein synthesis

Cortisol CNS effects

Can cause euphoria, insomnia, irritability, confusion, or psychosis

Cortisol connective tissue effects

Decreases collagen leading to thin skin, bruising, poor healing

Cortisol bone effects

Inhibits osteoblasts and increases bone resorption

Cortisol eye effects

Increases risk of cataracts and glaucoma

Aldosterone function

Acts on distal tubule causing sodium reabsorption and potassium excretion

Aldosterone excess effects

Hypertension, hypokalemia, metabolic alkalosis

Aldosterone deficiency effects

Hypotension, hyperkalemia, metabolic acidosis

Adrenal androgens

DHEA and androstenedione are precursors to testosterone

Adrenal insufficiency definition

Inadequate production of cortisol for physiologic function or stress

Addison disease definition

Primary adrenal insufficiency due to destruction of adrenal cortex

Addison cause

Most commonly autoimmune destruction of adrenal cortex

Addison pathology

All three cortex zones destroyed causing cortisol, aldosterone, androgen deficiency

Addison symptoms

Muscle weakness, hyperpigmentation, weight loss, hypotension

Hyperpigmentation cause

Low cortisol leads to high ACTH which increases melanin

Addison labs

Low cortisol and abnormal electrolytes

Morning cortisol test

Low

Cosyntropin test

Synthetic ACTH used to test cortisol response

Cosyntropin result

Cortisol <18 mcg/dL suggests adrenal insufficiency

Hydrocortisone equivalent

20 mg hydrocortisone equals 5 mg prednisone equals 0.75 mg dexamethasone

Glucocorticoid potency

Dexamethasone has highest anti-inflammatory potency

Fludrocortisone

Used as mineralocorticoid replacement therapy

Addison treatment goals

Improve symptoms, avoid over treatment, prevent adrenal crisis

Hydrocortisone dosing

2/3 dose in morning and 1/3 later in day

Fludrocortisone effects

Causes sodium and water retention and potassium loss

Fludrocortisone monitoring

Monitor blood pressure, edema, sodium, potassium

Stress dosing glucocorticoids

Increase dose during illness, trauma, or surgery

Androgen replacement women

DHEA may improve libido and mood but is controversial

Adrenal crisis definition

Sudden lack of adrenal hormones during stress

Adrenal crisis symptoms

Hypotension, hypoglycemia, nausea, dehydration

Adrenal crisis treatment

IV fluids and IV hydrocortisone

Secondary adrenal insufficiency cause

Lack of ACTH from pituitary

Secondary adrenal

Aldosterone normal so no hyperkalemia or severe hypotension

Secondary adrenal treatment

Glucocorticoid replacement only no fludrocortisone

Cushing syndrome definition

Chronic glucocorticoid excess

Cushing most common cause

Iatrogenic from chronic glucocorticoid therapy

Cushing features

Central obesity, moon facies, buffalo hump, hypertension

Cushing metabolic effects

Hyperglycemia and diabetes

Cushing skin effects

Striae, bruising, thin skin

Cushing psychiatric effects

Anxiety, euphoria, insomnia, psychosis

Cushing causes

Excess ACTH, adrenal tumor, or glucocorticoid drugs

Cushing disease

Pituitary adenoma causing excess ACTH

Ectopic ACTH syndrome

Tumor produces ACTH causing high cortisol

Adrenal tumor cortisol

Cortisol high but ACTH low due to feedback

Cushing screening

Late night cortisol, 24 hour urine cortisol, dexamethasone suppression test

Dexamethasone suppression test

In normal patients cortisol suppressed, in Cushing it is not

Cushing treatment

Remove tumor or reduce glucocorticoid use

Steroidogenesis inhibitors

Mitotane, metyrapone, aminoglutethimide, ketoconazole

Ketoconazole MOA

Inhibits CYP enzymes reducing cortisol production

HPA suppression factors

Dose, duration, route, and patient factors

HPA suppression threshold

Prednisone >7.5 mg for >3 weeks may suppress axis

Tapering glucocorticoids

Must be gradual to prevent adrenal insufficiency

Primary aldosteronism definition

Excess aldosterone production

Primary aldosteronism symptoms

Hypertension and hypokalemia

Spironolactone MOA

Aldosterone antagonist and treatment of choice

Spironolactone side effects

Hyperkalemia, gynecomastia, decreased libido

Amiloride

Used to correct hypokalemia

Licorice effect

Inhibits cortisol metabolism causing pseudo-hyperaldosteronism

Pheochromocytoma definition

Catecholamine producing tumor of adrenal medulla

Pheochromocytoma symptoms

Severe hypertension and catecholamine excess

Pheochromocytoma diagnosis

24 hour urine catecholamines and imaging

Pheochromocytoma treatment

Surgical removal after BP stabilization

Phenoxybenzamine

Irreversible nonselective alpha blocker used first

Beta blocker rule

Must block alpha before beta to avoid severe hypertension