Clinical Application of Steroids

Hydrocortisone: brand names and routes of admin

Anusol-HC, Cortef, Solution-CORTEF, Vanicream, HC Cream

PO, IM, IV, PR, topical (cream, lotion, ointment)

Prednisolone: brand names and routes of admin

Millipred, Pediapred, Orapred ODT

PO, IV, IM, intra-articular, intradermal, ophthalmic

Prednisone: brand names and routes of admin

N/A

PO (tablet, solution)

Methylpredisolone: brand names and routes of admin

Medrol, SOLU-Medrol, DEPO-medrol

PO, IM, IV, intra-articular

Triamcinolone: routes of admin

External aerosol, IM, intra-articular, intradermal, intranasal, intrasynovial, soft tissue injection, topical (cream, lotion, ointment)

Dexamethasone: routes of admin

PO, IM, IV, ophthalmic

Betamethasone: routes of admin

Topical (cream, gel, lotion, ointment), intra-articular, intradermal, IM (off-label)

Fludrocortisone: routes of admin

PO

Corticosteroid dosing: life-threatening conditions

Large dose initially → if no response, double or triple the dose

corticosteroid dosing: chronic conditions

Start with small dose, then gradually increase until tolerable relief is achieved

OR

Start with high dose to resolve symptoms, then gradually decrease dose until tolerable relief is maintained

Corticosteroid dosing: Alternate day therapy (ADT)

Fewer adverse effects, less HPA suppression

Often not adequate for the control of many diseases

Considerations prior to initiation of steroids

History of DM, HTN, CV disease

History of PUD

Preexisting osteoporosis

History of psychological disorders

Disease states that influence steroid clearance

Hyperthyroidism increases clearance

Liver disease, age, pregnancy, hypothyroidism, anorexia nervosa, and protein-calorie malnutrition reduce clearance

Contraindications for steroid use

Absolute: AVOID STEROIDS until resolved or anti-microbial treatment is initiated → systemic fungal infection, active tuberculosis

Relative → active infection, glaucoma

AE of oral glucocorticoids: endocrine and metabolic

glucose intolerance, hyperglycemia, delayed growth in children

AE of oral glucocorticoids: GI

Increased appetite, indigestion, increased production of gastric acid and pepsin

AE of oral glucocorticoids: Immune system

Immunosupression, infections, delayed wound healing

AE of oral glucocorticoids: CV

Hypertension, edema

AE of oral glucocorticoids: Ocular

Cataracts, glaucoma

AE of oral glucocorticoids: CNS

Insomnia, nervousness, psychosis (high doses)

AE of oral glucocorticoids: Dermatologic

Hirsutism

iatrogenic Cushing’s syndrome

Occurs with steroid treatment with high dose for more than 2-3 weeks

Body habitus alterations: rounding/puffiness of face (moon facies), redistribution of fat to the face and trunk (buffalo hump), thin and atrophic skin, acne, hirsutism, purple striae

Steroid-induced osteoporosis

Risk with more than 2 weeks of therapy

• ADT does not prevent or lessen occurrence

Daily prednisone dose 1-5mg → relative risk 1.9x

Daily prednisone dose 5-10mg → relative risk 4.5x

Daily prednisone dose >10mg →relative risk 32x

Obtain BMD at baseline and the every 6-12 months during the first 2 years

Prevention: calcium, vitamin D, bisphosphonate

Patient counseling: oral steroids

Never discontinue without first consulting PCP

Take with food if GI upset occurs

Carry or wear a Medic Alert bracelet or ID if on chronic therapy

Dosage increase may be required at times (stress or emergency coverage)

Missed dose info

• once daily → take ASAP but skip if almost time for next dose (NEVER double dose)

• BID → if miss morning dose, can double up evening dose. If missed evening dose, go back to normal schedule

Be aware of potential long-term SE and complications

Steroid therapy: monitoring for AE

BP, weight, glucose, electrolytes (Na, K, Mg), eye exam, BMD/osteoporosis, growth and development (in children and adolescents

Hypersecretory cortisol disorders

Cushing’s disease: ACTH excess by pituitary gland (ACTH-secreting pituitary adenoma)

Cushing’s syndrome: excess cortisol production by the adrenals (adrenal adenomas and adrenal carcinomas) (Long-term therapy with glucocorticoids → iatrogenic)

Diagnosis of Cushing’s

Medication history

Establish presence of hypercortisolism

• 24-hour urine free cortisol

• 2-3x normal

Discover underlying etiology

• plasma ACTH concentration

• Inferior Petrosal sinus sampling

• MRI/CT of adrenal or pituitary gland

Tx of Cushing’s

Cushing’s disease: usually surgery since due to a tumor

Syndrome: surgery if due to adrenal adenoma, pharmacotherapy if not a surgical candidate/prior surgery/surgical failure

Tx Cushing’s: ketoconazole

Decreases cortisol production by inhibition of 11- and 17- hydroxylase

SE: gynecomastia, GI discomfort, increased LFTs

Tx Cushing’s: Mitotane

MOA: inhibits 11-hydroxylase but also ha some direct andrenolytic activity

SE: anorexia, ataxia, GI discomfort, lethargy

Tx Cushing’s: Etomidate

MOA: 11-hydroxylase inhibitor

IV only: reserved for rapid control or if patient is NPO

SE: injection site pain, nausea, vomiting, myoclonus

Tx Cushing’s: Metyrapone

MOA: inhibition of 11-beta-hydroxylation of precursors in the adrenal cortex

SE: hypertension, hypoadrenalism, HA, GI, hirsutism, acne

Tx Cushing’s: Mifepristone

MOA: glucocorticoids receptor antagonist,controls hyperglycemia associated with Cushing’s

SE: HTN, hyperadrenalism, HA, nausea, vomiting

Adrenal Insufficiency

Primary (Addison’s disease)

• >90% destruction of the adrenal gland

• Autoimmune disease is the most common etiology

• Can also be due to cancer, TB, HIV

Secondary → disorder of the HPA system

• hypopituitarism

• Rapid withdrawal of glucocorticoids

Clinical features of adrenal insufficiency (AI)

• flu-like syndrome with fatigue, malaise, anorexia, abdominal pain, arthralgia, and postural dizziness

• Progressive symptoms (depending on severity): vomiting, fever, hypotension, shock

• Increased skin pigmentation and vitiligo

• Hyponatremia, hyperkalemia, hypercalcemia, hypoglycemia, eosinophilia

• Hemodynamic instability and dependency on catecholamines despite control of infection should lead to suspect AI

Diagnosis of AI

Cortisol level: random, free

ACTH stimulation test

• high dose

  • 250mcg IM or IV, measure at 0, 30 min (and sometimes 60) after dose

  • Relative AI defined as increase of cortisol < 9 mcg/dL from baseline, measured at 30 or 60 minutes after administration

• Low dose

  • 1mcg IM or IV only

  • Potentially more sensitive

  • Not a lot of evidence to support

Adrenal Insufficiency: chronic treatment

The only disease state that steroids “cure” (other uses of steroids are more symptomatic relief)

Prednisone 5mg/day plus fludrocortisone 0.005-0.2mg/day

AI: Tx of acute adrenal crisis

• Hydrocortisone 100mg IV push STAT, then continuous infusion of 10mg/hr or 50mg IV q6h for the first 24 hours

• fluid replacement with D5NS to maintain BP

• Day 2: reduce IV dose to 100mg in divided doses

• Once stable, hydrocortisone 25mg PO q6-8h for 48h then taper to patient’s chronic replacement needs

Clinical uses of steroids

• Addison’s disease/AI

• Respiratory disorders: COPD, Asthma, ARDS, COVID

• RA

• Systemic lupus erythematus

• Sepsis/septic shock

• Allergic reactions/anaphylaxis

• Organ transplant

• Pneumocystis jiroveci pneumonia (PCP)

• Dermatologic uses

Clinical uses of steroids: Respiratory disorders

• Asthma

  • Inhaled corticosteroids are preferred treatment for all patients with persistent asthma

  • Oral are reserved for severe asthma

• COPD

  • Inhaled corticosteroids are added on to long-acting B2 agonists for patients at high risk

• Exacerbations

  • Give “burst” of oral steroids

  • IV steroids reserved for acute situations with severe airway obstruction

Clinical uses of steroids: Rheumatoid arthritis

• steroid use does not alter the course of the disease. Bone and cartilage destruction continues while inflammation is decreased

• used as a bridge therapy or during acute flairs

• Intra-articular injections may be helpful to alleviate panful symptoms and when successful are preferred over increasing the dose of oral steroids

• ADT often not useful because patients are symptomatic on the off days

Clinical uses of steroids: Systemic lupus erythematous

Acute flairs: prednisone 1 mg/kg/day up to 60mg

Mild disease: prednisone 10mg/day for 4-6 weeks; maintenance therapy with ADT dosing may be used for chronic therapy

Clinical uses of steroids: Sepsis/septic shock

• steroid use has been controversial and has mixed date in the literature

• Surviving sepsis guidelines state that steroids can be used in patients who are unresponsive to fluids and vasopressors

• Hydrocortisone 50mg IV q6h ± fludrocortisone

Clinical uses of steroids: Allergic reaction/anaphylaxis

• mild: medrol dosepak or prednisone dosepak

• Severe (secondary treatment):

  • Hydrocortisone 200-300mg IV

  • methylprednisone 1-2 mg/kg (max of 125mg x 1)

Clinical uses of steroids: Organ transplant

• steroids used liberally to prevent rejection and during transplant rejection

• Does are started high (prednisone 20-240mg/day) and tapered to maintenance of 5-30 mg/day around 3months post-transplant, further tapered to 5-10mg/day at 12-18 months post-transplant

Clinical uses of steroids: Pneumocystis jiroveci pneumonia

• in AIDS patients, addition of steroid to PCP treatment lessens the severity of the course

• PO2 </= 70mmHg: 40mg prednisone PO BID, taper to 20mg PO daily over 3 weeks

Steroids: Dermatologic uses

psoriasis, vitiligo, atopic dermatitis, radiation-induced dermatitis, eczema, lichen sclerosis

Topical steroids: potency

• low to medium potency agents are usually effective for treating thin, acute, inflammatory skin lesions

• High or ultra high potency agents are often required for treating chronic, hyperkeratotic, or lichenified lesions

• For face and intertriginous areas, use low potency agent (or high potency for short duration)

• For palms of hands or soles of feet, use high or ultra high potency agents

Topical steroid vehicles: ointment

Useful for thick,dry, hyperkeratotic areas

Shouldn’t be used ion hairy or intertriginous areas

Topical steroid vehicles: cream

Useful in intertriginous areas and for acute exudative inflammation

Topical steroid vehicles: lotion

Useful for hairy areas

Topical steroid vehicles: gel

Useful for exudative inflammation, can use on hairy areas

Topical steroids: duration of use

• daily use of high or ultra-high potency topicals should not exceed 2-3 weeks

• For longer duration, low potency is preferred

• Cycling or intermittent therapy may be referable to long-term continuous therapy

• Estimate amount of topical corticosteroid based on treatment area and duration of of use

Topical steroids: AE

Percutaneous absorption, skin atrophy, rebound papular dermatitis after medium-high potency, striae formation, systemic absorption can occur with high and ultra-high potency

Topical steroids: patient counseling

• Apply sparingly and only to areas of skin affected by skin disease

• apply only as often as prescribed

• Once the disease is under control, application of therapy may be reduced or discontinued

• Washing hands after each application helps to avoid topical corticosteroid contact with eyes

Steroids: HPA axis suppression

• Degree and duration of HPA axis suppression depends on the dose and duration of therapy

• After chronic steroid therapy stopped, takes at least 2-3 months for pituitary and adrenals to become responsive

• Pituitary recovers before adrenals

• If therapy is to be stopped, steroid dosage should be tapered

• If dose is reduced too quickly, acute or chronic adrenal insufficiency could occur

Tapering: general steps

1. Consolidation

2. Rapid taper

3. Slow taper

4. If symptoms worsen

Tapering Step 1 (consolidation)

Convert multiple daily doses to once daily dose in the AM

Tapering Step 2 (rapid taper)

Taper to physiologic doses: decrease dose by 2.5 to 5 mg prednisone every 3-7 days until physiologic doses (5mg/day of prednisone) is reached

Tapering step 3 (slow taper)

Decrease dose by 1mg prednisone or equivalent per week

Tapering step 4 (if symptoms worsen)

Slow the taper or increase dose if symptoms of disease exacerbation or adrenal insufficiency occurs

Stress replacement of corticosteroids

• Required for patients taking more than 5 mg prednisone or
  equivalent

  • During times of moderate to severe physical stress (febrile illness or injury)-should double dose

  • For surgery

Stress coverage for patients on chronic steroids

For patients on >5mg prednisone

• Minor surgery

  • 25 mg hydrocortisone at induction on day of induction only

• Moderate surgery

  • Hydrocortisone 25 mg at induction, plus 50-100 mg hydrocortisone per day for 24 hours

  • Taper quickly over 1-2 days to usual dose

• Major surgery

  • Hydrocortisone 25 mg at induction plus 100-150 mg hydrocortisone per day for 48-72 hours

  • Taper quickly over 1-2 days to usual dose

Stress coverage for patients recently off steroids

• If the patient has been off chronic steroids for <3 months, treat as if the patient was still taking steroids

• If patient has been off steroids greater than 3 months, no stress dose steroids are needed

• For patients on prednisone 5 mg or less, no additional steroids are needed for stress coverage