Autoimmune Addison Disease

English physician Thomas Addison was the first to describe primary adrenal insufficiency in 1855, according to NCBI, an incidence of 0.6 per 100,000 of the population annually. The total number of people affected by this condition at a given time ranges from 4 to 11 per 100,000 of the population. In adults, 30 to 50 years is the common age group. In contrast to adults, where women constitute the majority (70%) of patients, boys make up around 75% of patients in children. The destruction of the cortex of the adrenal glands is the underlying disease. Reduced or absent cortisol secretion may or may not be accompanied by a corresponding decrease in or lack of aldosterone. The level of the hormone adrenocorticotrophic hormone (ACTH) is increased.

Addison's disease is a potentially life-threatening emergency condition but a rare disease. Reduced adrenocortical hormones, such as cortisol, aldosterone, and androgens, result from bilateral adrenal cortex destruction. The insidious course of Addison's disease often begins with glucocorticoid deficiencies and progresses to mineralocorticoid shortage. The degree and rate of involvement of adrenal function determine autoimmune adrenalitis and how adrenal insufficiency develops. Primary adrenal insufficiency is mostly caused by, also known as Addison disease, which is linked to elevated levels of 21-hydroxylase antibodies.

This results from the adrenal cortex's failure to create enough adrenocortical hormones. Adrenal insufficiency is of two types: Primary and Secondary.

Primary Adrenal Insufficiency autoimmune-mediated intrinsic adrenal gland dysfunction (both cortisol and aldosterone deficiency).

Any disease process that causes direct injury to the adrenal cortex results in primary adrenal insufficiency (Addison disease).

Autoimmune: The most common cause of Addison's disease is autoimmune destruction of the adrenal glands. Autoimmune polyglandular endocrinopathies (types 1 and 2) and isolated cases of immunological damage are both possible. Polyglandular autoimmune syndromes are more prevalent in patients with autoimmune adrenal disease.

Secondary Adrenal Insufficiency- chronic glucocorticoid administration resulting in hypothalamic-pituitary dysfunction (only cortisol deficiency).

The most frequent cause of secondary insufficiency is exogenous steroid treatment, which suppresses ACTH production. The synthesis of glucocorticoids is decreased because of a pituitary-dependent loss of ACTH secretion. Aldosterone secretion, however, continues to be at an essentially normal level. Compared to primary insufficiency, it is more frequent. Symptoms often appear after stopping the steroid.

Risk factors for the autoimmune (most common) type of Addison's disease include other autoimmune diseases like - Type I diabetes, Hypoparathyroidism, Hypopituitarism, Pernicious anemia, Graves' disease, Chronic thyroiditis, Dermatitis herpetiformis, Vitiligo, Myasthenia gravis.

Addison's disease is a serious disease that must be correctly identified and treated right away. Delay in diagnosis carries a serious risk of morbidity and death. A multidisciplinary group of healthcare professionals, including an endocrinologist, an intensivist, an infectious disease expert, and a pharmacist, is therefore well-suited to address the medical condition. For patients with chronic diseases, patient education is essential. This duty is split among doctors, nurses, and pharmacists. Treatment administration, patient monitoring, and team communication are all responsibilities of nurses. The results are determined by the underlying reason once the diagnosis has been made. Any delay in starting the therapy might have negative effects. It is essential to encourage everyone with Addison's disease to wear a medical alert bracelet. Patients should be informed about the symptoms and indicators. If there are any warning symptoms, they should be reminded to call their primary care doctor. Finally, patients should be advised to increase the number of steroids and visit their primary care physician during stressful periods, such as a fever.

Diagnosis of Autoimmune Addison Disease

Low cortisol and aldosterone levels, blunt cortisol response to ACTH stimulation, and a high renin level all support the diagnosis. The evaluation's methodology is as follows:

• An inappropriately low cortisol level.
• Evaluating the functional ability of the adrenal cortex to produce cortisol and figuring out if the lack of cortisol is connected to a lack of corticotropin (ACTH). This will assist in determining whether the insufficiency of the adrenal glands is primary or secondary.
• Identifying the presence of a curable cause. The goal of additional analysis should be to identify the root cause of the problem.

Cortisol Level

A low random cortisol level is typically observed. Since cortisol has a diurnal pattern and rises in the early morning, it is best to measure it in the early morning. However, taking a cortisol level at the emergency department (ED) in the morning is difficult. Also, at the time of the ED presentation, these results were not readily available. To evaluate adrenal function, a serum cortisol level measurement alone is insufficient. A morning cortisol level above 18 micrograms/dL, however, is normal and rules out the diagnosis. All that is needed to identify adrenal insufficiency is a low cortisol level (< 3 mcg/dL).

18 microgram/dL = Normal

<3 microgram/dL = Adrenal insufficiency

 3-19 microgram/dL /dL = Equivocal and further evaluation is suggested.

ACTH Level and Corticotropin Stimulation Test 

A considerably increased ACTH level defines primary adrenal insufficiency. However, the level is neither high nor within the standard range for people with central adrenal insufficiency. An ACTH (cosyntropin) stimulation test is used to confirm the diagnosis when it is unclear. Cortisol and aldosterone production are quickly stimulated. This is a primary diagnostic test for determining whether an individual has adrenal insufficiency. After administering ACTH, plasma cortisol levels should be checked at 0, 30, and 60 minutes. The pituitary releases ACTH when CRH is present. A high ACTH level, which increases further following CRH stimulation but is insufficient to promote blood cortisol release, is seen in primary adrenal insufficiency. However, a low ACTH level is present in secondary adrenal insufficiency and does not respond to CRH.

Aldosterone and Renin Level

To determine whether a mineralocorticoid shortage is present, serum renin and aldosterone levels should be measured. With primary adrenal insufficiency, there is a lack of both cortisol and aldosterone. Despite significantly elevated plasma renin activity, there is a low aldosterone concentration. Aldosterone levels in secondary adrenal insufficiency will be normal.  It is possible to find elevated plasma renin activity, which denotes adrenal cortex dysfunction. A high level occurs when the serum aldosterone level is low.

TSH Level

Adrenal insufficiency causes a small increase in TSH levels. This happens because of a drop in cortisol levels and an irregular TSH circadian cycle. The risk of hypothyroidism should be considered if TSH increases.

Imaging Studies

A small heart appears on a chest radiograph; this might be the result of a reduction in the cardiac workload. An abdominal CT scan helps identify the source of suspected adrenal hemorrhage situations. For instance, an adrenal hemorrhage results in bilateral enlargement of the adrenal glands.

Diagnostic Market Players

Treatment of Autoimmune Addison Disease

Addison's disease is treated with medications. Hormone replacement treatment restores the body's inadequate production of steroid hormones. Oral corticosteroids are also used in some therapies.

Cortisol and aldosterone, which are low in Addison's disease, are replaced by synthetic versions of the hormones. Aldosterone and cortisol are both substituted by the medication’s fludrocortisone and hydrocortisone respectively. Due to the chronic nature of Addison's disease, the patient always needs to take medicine. Each person requires a different amount of these drugs, and to avoid an acute adrenal crisis when the patient is dealing with an illness, trauma, surgery, or other stressful events, the doctor raises the dosage. The doctor advises the patient to consume more salt if the patient takes fludrocortisone, particularly in hot and humid conditions and after intense workouts.

Treatment Market Players         

Market Trends Analysis

In June 2023 TGA approved DEXAMETHASONE ANS, sponsored by Southern XP IP Pty Ltd in which the active ingredient is dexamethasone sodium phosphate. It is used in Replacement therapy for adrenocortical insufficiency.

Due to its mostly glucocorticoid action, Dexamethasone cannot serve as a full replacement treatment for adrenocortical insufficiency. Deoxycorticosterone, a mineralocorticoid, and salt should be added to dexamethasone. Dexamethasone should be used when supplemented in:

• Acute adrenocortical insufficiency - Addison's disease, bilateral adrenalectomy
• Primary and secondary adrenocortical insufficiency

Dexamethasone is prescribed to treat the following conditions:

Collagen diseases, pulmonary disorders, Blood disorders, Rheumatic diseases, Skin diseases, Gastrointestinal disorders, Oedema, Eye disorders, Neoplastic states, Endocrine disorders, Preoperative and postoperative support.

When there is a question about the adrenocortical reserve, dexamethasone is given in any surgical operation. This covers the management of surgical shock brought on by significant blood loss.

Clinical Trial Analysis-

The importance of clinical trials in the field of evidence-based medicine and healthcare transition has been highlighted by the government's growing emphasis on comparative effectiveness studies. One of the main goals of the healthcare revolution is achieved with the assistance of clinical data, which allows market participants to accurately compare medical therapy.

The table below highlights the study titles of the ongoing clinical trials as well as the stages in which they are taking place.

Conclusion-

For healthcare organizations looking to effectively manage Autoimmune Addison Disease, DiseaseLandscape Insights (DLI) a healthcare consulting firm is ready to offer a wide range of strategic services to all our stakeholders. Services with a wide range that includes conducting market research and analysis to identify trends and opportunities.

Additionally, DLI also provides advice to clients to ensure regulatory compliance on utilizing clinical expertise for evidence-based approaches, developing creative product development strategies, facilitating collaboration with important stakeholders, and more.

DLI services are equipped to navigate clients on the complex landscape of Autoimmune Addison Disease management and help them make well-informed choices that improve patient outcomes by providing customized recommendations.

Services offered by DLI help the market players to carry out clinical trials for novel medications and therapies easily. Also, it supports patient recruitment, regulatory compliance, and other activities. DLI also provides detailed information about market competitors, growth of the market, and new regulations and rules across the globe to industry players. DLI services assist all market participants in gaining a stronger foothold in the Autoimmune Addison Disease sector.