When most people are diagnosed with adrenal disease, they are told it is a rare disease. Even though over approximately 1,000,000 people in the US and Europe have been diagnosed with cortisol related conditions.

Though it may be true that specific adrenal diseases are rare in occurrence, the incidence of diseases that impact cortisol and require the need for cortisol replacement medications are not as rare as endocrinologist believe. There are many forms of adrenal disease, but the treatment for all cortisol deficient conditions requires steroid replacement medications, leading us to believe that the cortisol deficient population is a large demographic.

Cortisol Deficient Conditions[1]

The following statistics indicate the prevalence of all cortisol related conditions that require cortisol replacement. All statistics are based on an annual scale in the United States unless otherwise noted. Research references are located in footnotes.

Over 1,000,000 people in the US and Europe have been diagnosed with cortisol related conditions such as:
Adrenal adenoma- According to the American Cancer Society[2], adrenal adenomas are found in 1 in every 10 people who have an imaging tests of the adrenal gland.
Adrenocortical carcinoma- It is estimated [3] that diagnosed 600 people are diagnosed in the United States each year.
Addison’s disease[4]– Prevalence estimated to be between 40 and 60 cases per 1 million in the general population.
Antley-Bixler syndrome- (ABS) has been described[5] in more than 100 patients.
Adrenoleukodystrophy[6]– According the Stop ALD Foundation, this condition affects 1 in 18,000 people.
Cortisol Dysregulation[7]– The WHO states that conditions where in which cortisol dysregulation is indicated, form a part of a group of illnesses termed as “noncommunicable diseases” (NCDs) accounts for the majority of deaths with 17.9 million people dying annually. Noncommunicable diseases (NCDs) kill 41 million people each year worldwide, equivalent to 71% of all deaths globally[8]. In the Americas, 5.5 million deaths are by NCDs. Research[9] also highlights the fact that cortisol dysregulation is present in up to 40% of stroke patients.  
Cushing’s disease – An estimated [10]10-15 per million people are diagnosed with this condition in the United States every year.
Congenital adrenal hyperplasia (CAH)[11]– The most common form of CAH, 21 hydroxylase deficiency, affects approximately 1:10,000 to 1:15,000 people in the United States and Europe. Among the Yupik Eskimos, the occurrence of the salt-wasting form of this disorder may be as high as 1 in 282 individuals.
11-Beta hydroxylase deficiency[12]– It is estimated that 11-beta-hydroxylase deficiency occurs in 1 in 100,000 to 200,000 newborns. This condition is prevalent in Moroccan Jews living in Israel and occurs in approximately 1 in 5,000 to 7,000 births.
17a-hydroxylase deficiency[13]– 17a hydroxylase deficiency has an estimated prevalence of 1 in 50,000 to 100,000.
3-Beta-hydroxysteroid dehydrogenase deficiency[14]– Human 3 beta-hydroxysteroid dehydrogenase deficiency (3b-HSD) resulting from HSD3B2 gene mutations has an estimated diagnosis of less than 1/1,000,000.
Congenital lipoid adrenal hyperplasia[15]– Exact statistics for Americans diagnosed with this condition are unknown, however recent studies estimate the rate for this mutation seen in Asian populations to be between 1 in 200 and 1 in 300 people yearly.
PORD (P450 oxidoreductase deficiency)[16] – Estimated annual incidence of 1/100,000-200,000.
Hypopituitarism[17]– Globally, the prevalence is estimated to be 4.2 cases per 100,000 per year, and the prevalence is approximately 45.5 cases per 100 000 people.
Panhypopituitarism[18]– Estimated annual prevalence of 45.5 cases per 100,000 people.
Pheochromocytoma[19]– The prevalence is estimated at 1:2,500 to 1:6,500 patients annually.
Pituitary Adenoma[20]– 9.3 cases per 100,000 population yearly.
Secondary Adrenal Insufficiency[21]– Yearly estimated prevalence is 150–280 per million.
Sheehan’s syndrome[22]– Incidence of Sheehan syndrome is estimated to be 5 patients out of 100,000 births.
Lymphocytic Lypophysitis[23]– The prevalence is approximately 1 in 9 million.

The WHO states that conditions where in which cortisol dysregulation is indicated, form a part of a group of illnesses termed as “noncommunicable diseases” (NCDs) accounts for the majority of deaths with 17.9 million people dying annually. Noncommunicable diseases (NCDs) kill 41 million people each year worldwide, equivalent to 71% of all deaths globally. In the Americas, 5.5 million deaths are by NCDs. Current Research also highlights the fact that cortisol dysregulation is present in up to 40% of stroke patients.

Though cortisol testing is inexpensive and easily performed, in emergency room situations it is not a current standard of care.

This information begs the question, how many unknown causes of death are truly caused by cortisol deficiency?

Another factor in current endocrine diagnostics is that early detection is key to quality of life for those with cortisol deficient diseases. Research shows that cortisol deficient patients diagnosed post adrenal crisis suffer from lowered quality of life and most are declared disabled. Diagnosis prior to adrenal crisis is essential to preventing impairments.

Despite research supported, legal, medical advances, cortisol deficiency patients remain a poorly served demographic with high mortality rates and low quality of life.

Barriers In current cortisol care

  1. Cortisol testing in emergency room situations is not a current standard of care.
  2. There is currently no center in the United States soley dedicated to managing cortisol care. Vital testing to manage cortisol deficiency such as 24-hour cortisol day curve testing is not available. This test evaluates the effectiveness of a patient’s cortisol replacement medication by drawing a cortisol blood lab once an hour for 24 hours and provides insight on a patient’s cortisol metabolism and absorption.
  3. Patient’s cortisol levels are tested initially at diagnosis but typically are not tested after diagnosis to evaluate effectiveness of their steroid replacement.
  4. Comparative assays of blood, urine and saliva testing to help establish a correct steroid dosing milligram and regiment are not offered in standard endocrinology clinics.
  5. Cortisol deficiency patients are not typically given multiple options to manage their care. The lack of cortisol replacement options is likely due to poor clinician awareness on the latest research showing standard administration of hydrocortisone 2-3x daily is inadequate to replicate the body’s natural cortisol production.
  6. Advances in cortisol replacement medications are available in the United States, but awareness of options such as all steroid medications and alternative cortisol delivery methods such as subcutaneous injections and the cortisol pumping method are not prominent.
  7. There is currently no way to check blood serum cortisol levels outside of a laboratory setting.
  8. Education on the proper management of cortisol deficiency is scarce within the endocrine community, who are mainly educated on diabetes and thyroid conditions. Advances such as circadian rhythm dosing can make massive improvements in quality of life for adrenal patients, yet many endocrinologists are unaware of this advancement.
  9. All EMS personnel are not authorized to administer the life saving cortisol injection in the event of an adrenal crisis.

Solutions to CUrrent Barriers in Cortisol Care:

  1. Early detection and diagnosis prior to experiencing adrenal crisis.
  2. Access to and awareness of all steroid options, which includes oral medications, subcutaneous cortisol injections and the cortisol pumping method. 
  3. Access to and awareness of testing that can evaluate cortisol deficient conditions and provide clinicians with insight on better cortisol regimens and replacement methods.
  4. Education on the importance of medication compliance and the need to increase dosing in times of stress, sickness or injury.
  5. Advancements in research to create biotechnology such as a cortisol meter.

How ADrenal Alternatives Foundation intends to solve these problems

Adrenal alternatives foundation is in the process of obtaining the funding to open a cortisol care center to provide appropriate cortisol testing and all possible care options to manage conditions that result in cortisol deficiency or dysregulation. Advances in cortisol care are available, but awareness and access to these options are limited and not widely offered.

Adrenal Alternative’s Cortisol Care Center will be a centralized location for all conditions that result in cortisol deficiency and cortisol dysregulation to have access to all steroid options, which includes oral medications, subcutaneous cortisol injections and the cortisol pumping method. Our center will provide diagnostic testing to screen for cortisol deficiency and dysregulation and also provide comparative lab assays of blood, urine and saliva cortisol levels, testing protocols such as the Cortisol Day Curve and the testing of all adrenal hormones to help patients find better quality of life.  

Our goal is to save and improve lives.

We appreciate all contributions which allow us to further our mission, Education, Advocacy and Awareness for all adrenal disease and will help us get closer to our goal of making the cortisol care center a reality.

Donate to Adrenal Alternatives Foundation

This information was brought to you by the Adrenal Alternatives Foundation for educational use only and is not meant to provide medical care or advice.

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Sources:

[1] Types of Adrenal Gland Disorders

https://www.nichd.nih.gov/. (2020). Types of adrenal gland disorders. [online] Available at: https://www.nichd.nih.gov/health/topics/adrenalgland/conditioninfo/types

[2] American Cancer Society. https://www.cancer.org/cancer/adrenal-cancer/about/key-statistics.html#:~:text=Adrenal%20tumors%20(most%20of%20which,any%20age%2C%20even%20in%20children.

[3] Adrenal Gland Tumor: Statistics. American Society of Clinical Oncology (ASCO) Cancer.Net Editorial Board, 01/2021

[4] Addison’s Disease Rare Disease Database. National Organization for Rare Disease (NORD)  https://rarediseases.org/rare-diseases/addisons-disease/

[5] Antley-Bixler syndrome Orphanet Clinical genetics review (2017) https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83

[6] Stop ALD Foundation.  Available at: http://www.stopald.org/what-is-ald

[7] Cortisol level dysregulation and its prevalence—Is it nature’s alarm clock? Physiol Rep. 2021 Jan; 8(24): e14644.

Published online 2020 Dec 19. doi: 10.14814/phy2.14644 PMCID: PMC7749606 PMID: 33340273. Available at:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749606/

[8] Chronic noncommunicable diseases (NCDs) Americas of the World Health Organization. Pan American Health Organization. Available at: https://www.paho.org/en/topics/noncommunicable-diseases

[9] Olsson, T. , Marklund, N. , Gustafson, Y. , & Nasman, B. (1992). Abnormalities at different levels of the hypothalamic‐pituitary‐adrenocortical axis early after stroke. American Heart Association Journal: Stroke, 23(11), 1573–1576. [PubMed] [Google Scholar]

[10] Cushing’s Syndrome/Disease. 2021 American Association of Neurological Surgeons. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Cushings-Disease

[11] Congenital Adrenal Hyperplasia. Rare Disease Database. National Organization for Rare Disease (NORD) Available at: https://rarediseases.org/rare-diseases/congenital-adrenal-hyperplasia/#:~:text=The%20most%20common%20form%20of,as%201%20in%20282%20individuals.

[12] Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Genetics Home Reference. Available at: https://medlineplus.gov/genetics/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency/#references

[13] A case of 17 alpha-hydroxylase deficiency. Clin Exp Reprod Med. 2015 Jun; 42(2): 72–76. Published online 2015 Jun 30. doi: 10.5653/cerm.2015.42.2.72 PMCID: PMC4496435. PMID: 26161337 Sung Mee Kim1 and Jeong Ho. Saint Mary’s Women’s Hospital, Daegu, Korea. Department of Obstetrics and Gynecology, Keimyung University College of Medicine, Daegu, Korea. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496435/

[14] Human 3 beta-hydroxysteroid dehydrogenase deficiency associated with normal spermatic numeration despite a severe enzyme deficit. Endocr Connect. 2018 Mar; 7(3): 395–402. Published online 2018 Feb 2. doi: 10.1530/EC-17-0306. PMCID: PMC5827574. Available at:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827574/#__ffn_sectitle

[15] Lipoid Congenital Adrenal Hyperplasia: Genetic Steroid Disorders, 2014. ScienceDirect ® Elsevier B.V. Available at: https://www.sciencedirect.com/topics/neuroscience/lipoid-congenital-adrenal-hyperplasia

[16] Cytochrome P450 Oxidoreductase Deficiency. Jan Idkowiak, MD, PhD, Deborah Cragun, MS, CGC, Robert J Hopkin, MD, and Wiebke Arlt, MD, DSc. GeneReviews® Adam MP, Ardinger HH, Pagon RA, Seattle (WA): University of Washington, Seattle; Initial Posting: September 8, 2005; Last Update: August 3, 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1419/

[17]  Hypopituitarism Epidemiology. Yolanda Smith, B.Pharm, Dr. Liji Thomas, MD. Medical News Life Sciences. News-Medical.net. Available at: https://www.news-medical.net/health/Hypopituitarism-Epidemiology.aspx#:~:text=Hypopituitarism%20is%20considered%20to%20be,cases%20per%20100%20000%20people.

[18] Panhypopituitarism. Bernard Corenblum, MD, FRCPC Professor of Medicine, Director, Endocrine-Metabolic Testing and Treatment Unit, Ovulation Induction Program, Department of Internal Medicine, Division of Endocrinology, University of Calgary Faculty of Medicine, Canada. Medscape.

Available at: https://emedicine.medscape.com/article/122287-overview#:~:text=Internationally%2C%20hypopituitarism%20has%20an%20estimated,per%20100%2C000%20without%20gender%20difference.

[19] Pheochromocytoma In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

2013 Jun 10. PMID: 25905204 Bookshelf ID: NBK278970 Available at: https://pubmed.ncbi.nlm.nih.gov/25905204/

[20] The Journal of Clinical Endocrinology & Metabolism, Volume 91, Issue 12, 1 December 2006, Pages 4769–4775, https://doi.org/10.1210/jc.2006-1668

[21] Adrenal Insufficiency. National Center for Biotechnology Information, U.S. National Library of Medicine

Nicolas C Nicolaides, M.D., George P Chrousos, MD, MACE, MACP, FRCP, and Evangelia Charmandari, M.D. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279083/#:~:text=Secondary%20adrenal%20insufficiency%20occurs%20more,life%20(18%2C%2019).

[22] Sheehan Syndrome. Mark P. Schury; Rotimi Adigun. StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK459166/

[23] Hypophysitis: Evaluation and Management. Clin Diabetes Endocrinol. 2016; 2: 15. Published online 2016 Sep 6. doi: 10.1186/s40842-016-0034-8 PMCID: PMC5471685.PMID: 28702249, Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471685/#__ffn_sectitle

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