Adrenal insufficiency resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayeesha Kattubadi, M.B.B.S[2]

Overview

Adrenal insufficiency is a clinical state where there is reduced production of adrenocortical hormones. The adrenal cortex is divided into three zones- zona glomerulosa, zona fasciculata and zona reticularis producing mineralocorticoids, glucocorticoids and androgens respectively. Adrenal insufficiency can cause glucocorticoid and mineralocorticoid deficiency. It is classified as primary, secondary and tertiary. Its presentation depends on the rapidity and degree of hormone depletion. It can present acutely as adrenal crisis, especially when the body is under stress due infections, trauma etc. If it presents chronically, it is called Addison's disease. The common causes include chronic glucocorticoid use and autoimmune adrenalitis. It is diagnosed using serum basal cortisol measurement and ACTH stimulation test. Treatment consists of lifelong glucocorticoid and mineralocorticoid replacement.

Causes

Life-Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

• Adrenal crisis

Common Causes

Common causes of adrenal insufficiency may include:

• Primary adrenal insufficiency: Autoimmune adrenalitis
• Central adrenal insufficiency: Chronic glucocorticoid use.

Less common causes:

• Infections:
  • Tuberculosis
  • Fungal infections(histoplasma)
  • Cytomegalovirus
  • HIV
• Adrenal hemorrhage
• X-linked adrenoleukodystrophy
• Trauma
• Metastasis

Diagnosis

Shown below is an algorithm summarizing the diagnosis of adrenal insufficiency.

Adrenal Insufficiency suspected

Serum basal cortisol

<5 µg/dL

5-18 µg/dL

>18 µg/dL

Confirms Adrenal Insufficiency

Dynamic tests

Rules out Adrenal Insufficiency

Primary Adrenal Insufficiency suspected

Secondary Adrenal Insufficiency suspected

ACTH stimulation test

ACTH stimulation test

Serum cortisol <18 µg/dL

Serum cortisol >18µg/dL

Serum cortisol <18 µg/dL

Serum cortisol 18-23µg/dL

Serum cortisol >23 µg/dL

Confirms Adrenal Insufficiency

Rules out Adrenal Insufficiency

Confirms Adrenal Insufficiency

Indeterminate

Rules out Adrenal Insufficiency

Insulin hypoglycemic test

Serum cortisol <18µg/dL

Serum cortisol >18µg/dL

Confirms Adrenal Insufficiency

Rules out Adrenal Insufficiency

Treatment

Shown below is an algorithm summarizing the treatment of adrenal insufficiency.

Primary adrenal insufficiency

Secondary adrenal insufficiency

Lifelong Glucocorticoid and Mineralocorticoid replacement therapy

Lifelong Glucocorticoid replacement therapy

Mineralocorticoid replacement therapy: 9 α-Fludrocortisone 0.05-0.2 mg/day PO single dose in the morning

Glucocorticoid replacement therapy: 1. Hydrocortisone 15-25mg PO in two or three divided doses 2. Cortisone acetate 20-25mg PO single dose in the morning

Dos

• In the diagnosis of Adrenal insufficiency plasma cortisol to be measured between 8:00-9:00 AM, after the early morning peak which happens between 6:00-8:00 AM.
• Hydrocortisone (preferred glucocorticoid) to be given in two or three divided doses to mimic the circadian rhythm.
• Glucocorticoid dose to be titrated based on symptom improvement. The least possible dose of glucocorticoid has to be used.
• Mineralocorticoid dose to be titrated based on symptom improvement (salt craving, postural hypotension, edema) and electrolytes.
• After adjusting the dose, follow-up to be continued annually.
• Patients should be educated on how to self increase the dose of glucocorticoid in the presence of other illnesses like fever, wounds.
• Patients should be educated on carrying steroid emergency and medical alert identification in the event of adrenal crisis for early detection and treatment.
• Patients should be educated on carrying and injecting glucocorticoid in case of an emergency.

Don'ts

• Insulin hypoglycemic test not be used in the diagnosis of adrenal insufficiency in patients age >60 Y, cardiovascular disease, hypertension, epilepsy and pregnancy.
• Glucocorticoid replacement not to be given after 6 PM.
• ACTH and Serum Cortisol levels not to be used for monitoring treatment efficacy.
• In patients on fludrocortisone who develop hypertension, the drug should not be discontinued. Instead, first reduce the dose of fludrocortisone. If hypertension remains uncontrolled, add anti hypertensive.