What are the consequences of adrenal insufficiency due to glucocorticoid (cortisol) deficiency?

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From the Guidelines

Glucocorticoid insufficiency can lead to life-threatening adrenal crisis, and prompt treatment with hydrocortisone is essential to prevent morbidity, mortality, and improve quality of life. The consequences of adrenal insufficiency due to glucocorticoid (cortisol) deficiency are severe and can affect multiple body systems.

Primary Effects

The primary effects of glucocorticoid insufficiency include:

  • Profound fatigue, weakness, weight loss, and hypotension, which can progress to life-threatening adrenal crisis if untreated
  • Gastrointestinal symptoms like nausea, vomiting, and abdominal pain
  • Metabolic changes, such as hypoglycemia due to impaired gluconeogenesis, alongside electrolyte abnormalities including hyponatremia and hyperkalemia
  • Cardiovascular effects, including decreased cardiac output and vascular tone, leading to orthostatic hypotension and reduced stress response

Secondary Effects

Patients may also develop:

  • Skin hyperpigmentation (in primary adrenal insufficiency)
  • Decreased stress tolerance
  • Psychological symptoms like depression, anxiety, and irritability
  • Laboratory findings typically show low serum cortisol, elevated ACTH (in primary insufficiency), hypoglycemia, hyponatremia, and hyperkalemia

Treatment

Treatment requires prompt glucocorticoid replacement, typically with hydrocortisone 100 mg by intravenous (i.v.) injection at induction of anaesthesia, followed by a continuous infusion of hydrocortisone at 200 mg.24 h-1, until the patient can take double their usual oral glucocorticoid dose by mouth, as recommended by 1.

Dose Adjustments

Dose adjustments may be necessary during illness or stress, and patients should be closely monitored for signs of adrenal crisis, as reported in 1 and 1.

Mineralocorticoid Replacement

Mineralocorticoid replacement with fludrocortisone should be restarted when the hydrocortisone dose falls to <50 mg day-1, as suggested by 1.

Quality of Life

Overall, glucocorticoid insufficiency can have a significant impact on a patient's quality of life, and prompt treatment is essential to prevent morbidity, mortality, and improve quality of life, as emphasized by the guidelines from the association of anaesthetists, the royal college of physicians and the society for endocrinology uk 1.

From the FDA Drug Label

In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy, should be carefully observed for signs of hypoadrenalism.

The consequences of adrenal insufficiency due to glucocorticoid (cortisol) deficiency may include hypoadrenalism, which can occur in infants born to mothers who have received substantial doses of corticosteroids during pregnancy 2.

From the Research

Consequences of Adrenal Insufficiency

The consequences of adrenal insufficiency due to glucocorticoid (cortisol) deficiency can be severe and life-threatening. Some of the key consequences include:

  • Adrenal crisis, which is a life-threatening condition that requires prompt treatment with hydrocortisone 3, 4, 5, 6, 7
  • Hypotension, weight loss, and fatigue, which are nonspecific symptoms that can make diagnosis difficult 3, 4
  • Increased risk of bleeding, particularly in patients with underlying conditions such as immune thrombocytopenia (ITP) 3
  • Misinterpretation of symptoms, particularly abdominal and gastrointestinal symptoms, which can lead to delayed diagnosis 3, 4

Diagnosis and Treatment

Diagnosis of adrenal insufficiency can be challenging due to the nonspecific nature of the symptoms. Some of the key diagnostic tests and treatments include:

  • Stimulation tests, such as the ACTH test, to diagnose glucocorticoid-induced adrenal insufficiency 5
  • Measurement of morning cortisol concentrations to diagnose primary adrenal insufficiency 4
  • Treatment with hydrocortisone and fludrocortisone to replace deficient hormones 3, 4, 7
  • Education and empowerment of patients to manage their condition and prevent adrenal crisis 5, 7

Clinical Implications

The clinical implications of adrenal insufficiency are significant, and include:

  • Risk of life-threatening adrenal crisis, particularly in patients with unrecognized chronic adrenocortical failure 6
  • Impact on quality of life, which can be improved with appropriate treatment and management 7
  • Need for close collaboration between patients and healthcare providers to manage the condition and prevent complications 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol - Early Manifestation of Addison's Disease.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2024

Research

Approach to the Patient With Glucocorticoid-induced Adrenal Insufficiency.

The Journal of clinical endocrinology and metabolism, 2022

Research

The management of glucocorticoid deficiency: Current and future perspectives.

Clinica chimica acta; international journal of clinical chemistry, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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