What are the risks of adrenal insufficiency and effects on red blood cells in a patient with autoimmune disease (Autoimmune Disease) treated with chronic oral corticosteroids (Oral Steroids)?

From the Guidelines

Patients on chronic oral steroids for autoimmune diseases are at risk for adrenal insufficiency due to suppression of the hypothalamic-pituitary-adrenal axis, and treatment for adrenal insufficiency involves glucocorticoid replacement, typically with hydrocortisone 15-25 mg daily divided into 2-3 doses (higher morning dose), or prednisone 5-7.5 mg daily 1. Adrenal insufficiency occurs when the body cannot produce adequate cortisol, resulting in symptoms like fatigue, weakness, weight loss, hypotension, and electrolyte abnormalities.

• Symptoms of adrenal insufficiency include:
  • Fatigue
  • Weakness
  • Weight loss
  • Hypotension
  • Electrolyte abnormalities During stress or illness, patients need to increase their steroid dose ("stress dosing"), often doubling or tripling their maintenance dose 1.
• Stress dosing is crucial to prevent adrenal crisis, and patients should carry a steroid emergency card and wear medical alert identification. For acute adrenal crisis, immediate treatment with hydrocortisone 100 mg IV is necessary, along with fluid resuscitation using normal saline 1.
• Acute adrenal crisis requires prompt treatment to prevent morbidity and mortality. When discontinuing chronic steroids, gradual tapering is essential to allow the adrenal glands to recover, typically reducing by 10-20% every 1-2 weeks 1.
• Gradual tapering of steroids is necessary to prevent adrenal insufficiency and other complications. Regarding red blood cells, chronic steroid use can lead to polycythemia (increased red blood cell production) due to enhanced erythropoietin production 1.
• Chronic steroid use can also cause increased red blood cell size (macrocytosis) and affect iron metabolism, potentially leading to iron deficiency anemia in some patients. Regular monitoring of complete blood counts is important for patients on long-term steroid therapy 1.
• Monitoring of complete blood counts can help detect potential complications of chronic steroid use, such as polycythemia and iron deficiency anemia.

From the FDA Drug Label

Hypothalamic-pituitary adrenal (HPA) axis suppression. Cushing's syndrome, and hyperglycemia. Monitor patients for these conditions with chronic use. Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted

Adrenal Insufficiency may occur in patients on chronic oral steroid doses due to HPA axis suppression. To minimize the risk of adrenal insufficiency, a gradual reduction of dosage is recommended when discontinuing treatment. Treatments for adrenal insufficiency include hormone therapy, which should be reinstituted in situations of stress occurring after discontinuation of corticosteroids. There is no information in the provided drug labels about changes to red blood cells with chronic long-term use of oral steroids 2 2.

From the Research

Adrenal Insufficiency

• Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production 3.
• The most prevalent form of AI is tertiary AI (TAI) owing to exogenous glucocorticoid use 3.
• Symptoms of AI are non-specific, often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors, and aldosterone (especially in primary AI) 3.
• Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones, and stimulation tests 3.

Treatment of Adrenal Insufficiency

• The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs 3.
• Therapy options for AI include glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises 4.
• Multiple GC replacement formulations are available, comprising short-acting, intermediate, long-acting, and novel modified-release hydrocortisone, as well as subcutaneous formulations 4.

Chronic Oral Steroid Use and Adrenal Insufficiency

• Long-term oral glucocorticoid use can lead to adrenal suppression upon discontinuation of the medication and adrenal insufficiency after utilizing supraphysiologic doses for more than one month 5.
• Better management of the quantity and frequency of exogenous corticosteroid use, as well as better education before starting its use, is needed to prevent patients from unwanted signs and symptoms of adrenal insufficiency 5.

Red Blood Cell Changes with Chronic Oral Steroid Use

• There is no direct information available in the provided studies regarding changes to red blood cells with chronic long-term use of oral steroids.

Autoimmune Adrenal Insufficiency

• Autoimmune adrenal insufficiency is caused by an autoimmune organ-specific destruction of the cells in the adrenal cortex by an autoreactive process of activated immune cells directed against the steroid-synthesising enzyme 21-hydroxylase 6.
• Determination of 21-hydroxylase autoantibodies permits early diagnosis before a complete adrenocortical destruction has occurred, allowing for a window of opportunity for an early immunomodulatory intervention therapy 6.