Adrenocortical insufficiency, or adrenal insufficiency, is a state in which the adrenal tissue is incapable of generating sufficient steroid hormones, particularly cortisol. Cortisol has many imperative roles in the body, including the body’s stress response, metabolism, and immune system regulation. 

Types of Adrenocortical Insufficiency 

Primary Adrenal Insufficiency (Addison’s Disease): 

This is due to the direct damage to the adrenal glands. 

Some causes include autoimmune destruction of the gland, infections such as Tuberculosis, and Adrenal hemorrhage. 

Secondary Adrenal Insufficiency: 

Consequently, this is due to substandard secretion or non-secretion of ACTH by the pituitary gland. 

May be caused by pituitary disorders that include tumours or taking corticosteroids during a long-term treatment. 

Tertiary Adrenal Insufficiency: 

It develops from the hypothalamus disorder, which implies the decreased secretion of corticotropin-releasing hormone (CRH). 

The predisposing factor is usually observed in patients with long-term usage of exogenous steroids. 

Importance of Screening 

Hence, the early diagnosis of adrenocortical insufficiency is essential to avoid adverse complications like adrenal crisis, which is a severe condition involved hypotension, hypoglycemia and shock. Screening tests in high-risk individuals make it easier to diagnose and treat the diseases. 

Primary Adrenocortical Insufficiency (Addison’s Disease) 

• Destruction of Adrenal Cortex: Mainly caused by autoimmune adrenalitis but can be caused by various diseases such as Infections e.g. Tuberculosis, metastases, adrenal hemorrhage and congenital adrenal hyperplasia. 
• Deficiency of Cortisol and Aldosterone: This results in high levels of ACTH due to the lack of negative feedback inhibition. 

Secondary Adrenocortical Insufficiency: 

• Pituitary or Hypothalamic Dysfunction: Because of brain or pituitary gland tumors, infections, radiation, or surgery on the adrenocorticotropic hormone. 
• Deficiency of ACTH: These lead to decreased secretion of cortisol while secretion of aldosterone is generally spared because its secretion is affected more by renin-angiotensin mechanism. 

Tertiary Adrenocortical Insufficiency: 

• Chronic Suppression of Hypothalamic CRH: Sometimes because of Cushing syndrome after the administration of glucocorticoids that inhibits the release of cortisol from the adrenal cortex by suppressing the HPA axis. 

Primary adrenal insufficiency also known as Addison’s disease involves the adrenal glands in the body’s lower abdomen producing inadequate amounts of adrenal hormones termed cortisol and aldosterone. 

• Autoimmune Adrenalitis: The leading type prevailing in developed nations, autoimmune disease in which the body’s immune system targets the adrenal cortex. 
• Infections: This can be evidenced by Tuberculosis, HIV, some fungi, and others that affect the adrenal glands. 
• Metastatic Disease: The cases of cancer that reach the adrenal glands. 
• Genetic Disorders: For example, if there were a condition such as congenital adrenal hyperplasia or adrenoleukodystrophy. 
• Medications: These include ketoconazole, which acts as cortisol synthesis inhibitor. 

Secondary Adrenocortical Insufficiency 

• Pituitary Disorders: Tumors, surgery, radiation or trauma of the pituitary gland, this leads to a low production of ACTH. 
• Exogenous Glucocorticoids: Medical corticosteroids can also cause inhibition of ACTH release and the adrenal glands; therefore, the withdrawal of corticosteroids often precipitates adrenal insufficiency. 

Researchers reported higher mortality of patients with primary AI and identified adrenal crisis as one of the vital causes of death among those patients, which requires educating the patients on AA. This study provides data about the observation of primary adrenal insufficiency that indicates that the quality of life of the patients is still poor even with the adequate replacement dose, which appears to depend on the time required in diagnosing the condition. 

Age group 

Primary Adrenal Insufficiency (Addison’s Disease): 

• Adults and Older Adults: The screening may be required by symptoms that include the following, weight loss without apparent cause, fatigue, and muscle weakness, low BP. Autoimmune disease sufferers are at higher risk. 
• Children: If there is a family history of Addison’s disease or manifested signs, screening may be carried out. 

Secondary Adrenal Insufficiency: 

• Adults: Usually performed in patients with the history of pituitary disease, the history of long-term steroid treatment, or with the clinical signs of adrenal failure. 
• Children: Given a pituitary or hypothalamic disorder or when on long-term steroids. 

Laboratory Tests 

Serum Cortisol 

ACTH Stimulation Test 

Electrolytes 

Blood Glucose 

Renin and Aldosterone Levels 

Imaging Studies 

• CT or MRI 

Activity and Functional Assessment 

• Functional Status 
• Quality of Life 

• Autoimmune Diseases 
• Infections 
• Genetic Conditions 
• Secondary Adrenal Insufficiency 

Hormone Replacement Therapy (HRT) 

Glucocorticoids: 

• Hydrocortisone: More often prescribed because of its similar profile to cortisol used commonly in the body. 
• Prednisone or Prednisolone: Hydrocortisone has shorter-lasting forms; however, longer-lasting forms are available. 

Mineralocorticoids: 

• Fludrocortisone: It’s used in the treatment of primary adrenal insufficiency also known and as Addison’s disease, as a replacement for aldosterone. 

Treatment of Acute Adrenal Insufficiency 

An acute adrenal crisis is a life-threatening emergency requiring immediate treatment: 

Intravenous Hydrocortisone: Deliverable in large volume/ Larger volumes are used. 

• Intravenous Fluids: To correct hypotension, dehydration, and electrolyte imbalance and to improve the patient’s clinical condition. 
• Monitoring: Observation of the cardiac and renal functions and electrolyte balance about their possible alterations. 

Education and Self-Management 

• Patient Education: General information about the condition, knowing signs and the signs of an adrenal crisis, and knowledge on how to manage the dosage of medication during stress (illness or surgery). 
• Emergency Injection Kit: Have an emergency hydrocortisone injection kit available. 

Regular Monitoring and Adjustments 

• Follow-up Visits: Periodic check-ups with the endocrinologist to review the hormone status and finalize the treatment. 
• Blood Tests: Electrolyte level check, blood pressure, and general health. 
• Dosage Adjustments: Changing dosages during illness, stress or surgery and such instances. 

Lifestyle Modifications 

• Balanced Diet: In some cases, specifically, patients on fludrocortisone it is important to supplement the intake of sodium. 

Additional Considerations 

• Secondary Adrenal Insufficiency: The treatment mainly takes the form of glucocorticoids without requiring mineralocorticoids. 
• Pregnancy: Closely managed and titrating of the use of hormone replacement therapy. 

Endocrinology, Metabolism

Nutrition 

• Balanced Diet: Maintain a balanced diet including whole foods mainly fruits, vegetables, lean meats and whole grain products. 
• Salt Intake: Pay attention to the intake of salt particularly on cases where one is on fludrocortisone as it interferes with the balance of sodium. 
• Hydration: keep hydrated, especially during hot weather / during physical activity. 

Regular Monitoring 

• Routine Check-ups: From time to time consult your doctor so that your dosages may be checked and if needed it should be changed accordingly. 
• Self-Monitoring: Since you have the condition resulting from hormonal imbalance, you should recognize symptoms of changes in your hormone levels including fatigue, muscle weakness, weight loss, and low blood pressure among others. 

Illness Management 

• Infection Control: Initiate measures to prevent getting diseases because they lead to adrenal crisis. 
• Increased Medication: If you are under corticosteroid therapy you should consult your physician when your dose should be increased significantly when you are undergoing surgery, or under severe stress. 

Endocrinology, Reproductive/Infertility

• Hydrocortisone
  Usually in a range of 15-25 mg per day in divided doses for the adults, depending on the client’s requirements.
  Hydrocortisone is a synthetic form of cortisol, a hormone that is naturally produced in the body. 
• Prednisone
  Tolerance is 5-10 mg per day; however, specific patient may require higher dosage.
  Prednisone is classified as a pro-drug, which is metabolized in the liver into an active substance called prednisolone. It is longer acting than hydrocortisone. 
• Dexamethasone
  Typically, 0. 25-0.75mg per day, or more, depending on the response to the treatment.
  Dexamethasone is the most potent Glucocorticoid, and its action is comparatively long-lasting. It is mainly prescribed when higher potency is required. 
• Prednisolone
  Generally, it is given in doses of 3-5 mg daily.
  Prednisolone is the active metabolite of prednisone and does not require hepatic conversion, this being beneficial in patients with liver disease. 
• Plenadren
  Plenadren (Takeda) gained approval for treating AI in the adult population in the same year, 2011. The main pharmacological principle is a dual-release system resulting from an outer layer providing immediate release and an inner retard formulation. 

Endocrinology, Reproductive/Infertility

Acute Phase: 

• Immediate Treatment: Hydrocortisone as IV fluids controlling for an adrenal crisis. 
• Fluid and Electrolyte Replacement: IV fluids for replenishing depleted intracellular and extracellular fluids, electrolytes and glucose. 

Maintenance Phase: 

• Long-term Hormone Replacement: Steroids include oral glucocorticoids such as hydrocortisone and prednisone and mineralocorticoids such as fludrocortisone which are used to replace the body’s deficient hormones. 
• Regular Monitoring: Adequate periodical checks with physicians to discuss modifications of dosages because of symptoms worsening, stress, or illness. 

Patient Education and Lifestyle Adjustments:  

• Education: Education of patient for their condition, follow up on the use of their medications, and methods to cope with stress and ailments. 
• Emergency Preparedness: Explain to the patient factors for identifying an adrenal crisis and have them use the emergency hydrocortisone injection kits. 
• Lifestyle Modifications: Advising on maintaining a balanced diet, managing stress, and ensuring adequate salt intake.