Winslow E Dixon-
CEO of Adrenal Alternatives Foundation.
Published Author of Townsend: The EverVigilant Series, Adrenal Insufficiency 101: A Patient’s Guide to Managing Adrenal Insufficiency, The Shivering Sunbeam, Arsenal of Arrows Devotional Journal Challenge Series, Peace by Peace Inspirational Health Journal and Chronically Stoned: The Guide to Winning the Battle Against Kidney Stones and UTIs.
*This information is for educational use only and is not to be used to treat or manage any condition*
During a surgical procedure, a cortisol deficient patient’s body will require an increase in steroid dosing to replace cortisol. Researchers have reported that in non cortisol deficient patients, HPA axis function during and after surgical procedures causes plasma cortisol levels to increase significantly. In patients without the presence of adrenal insufficiency, cortisol production rates have been shown to increase to 75–150 mg/day after major surgery.
In cortisol deficient patients, the recommendations differ depending on the length and severity of the procedure being performed. Cortisol deficiency patients will always require additional glucocorticoid supplementation during surgical procedures, but there is no uniform standard accepted regimen for glucocorticoid replacement therapy.
It is the best clinical practice to treat the patient instead of following a textbook response. If a patient with cortisol deficiency is declining, the administration of more cortisol should be a first line treatment protocol.
Anytime a cortisol deficient person is going under anesthesia, intravenous cortisol replacement medication must be administered.
If you have cortisol deficiency, be sure you alert your surgical team that you are cortisol dependent before your procedure and have a clear plan for your steroid dosing pre, during and post procedure. Any surgical team who refuses to administer steroids should be reported to medical authorities. Adequate steroid coverage is essential to the well being of cortisol deficient patients.
*DISCLAIMER* There is no universally agreed upon standard dose or duration of exogenous steroids used to treat adrenal insufficiency. Clinicians must be observant of a patient’s vital signs, empirical evidence and quality of life. It is also imperative clinicians be aware of the symptoms of adrenal crisis, which can widely vary in patients. In the event these symptoms should arise, an immediate dose of glucocorticoids should be administered until patient stabilizes.
For Minor Surgery: Double or triple the usual daily dose of glucocorticoid until recovery. Intravenous hydrocortisone 25 mg or equivalent at start of procedure. Usual replacement dose after procedure.
For Dental Procedures: Under local anesthesia, double the daily dose of glucocorticoid on day of procedure. Inject 100mg emergency cortisol injection if patient presents with adrenal crisis symptoms.
For Moderate Surgery: Intravenous hydrocortisone 75 mg/day on day of procedure (25 mg 8-hourly). Intravenous hydrocortisone 25 mg 8-hourly until recovery. Taper over next 1–2 days to usual replacement dose in uncomplicated cases.
For Major Surgery: Intravenous hydrocortisone 150 mg/day (50 mg 8-hourly) Taper over next 2–3 days only once clinical condition stabilizes.
For critical illness/intensive care/major trauma or life-threatening complications: 200 mg/day intravenous hydrocortisone (50 mg 6-hourly, or by continuous infusion)
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.
 COLLARD MD, C. D., SAATEE, M.D, S., REIDY, M.D, A. B. AND LIU, M.D, M. M. Perioperative Steroid Management: Approaches Based on Current Evidence: Collard MD, C., Saatee, M.D, S., Reidy, M.D, A. and Liu, M.D, M. (2017). Perioperative Steroid Management: Approaches Based on Current Evidence. [online] Anesthesiology: Trusted Evidence Discovery in Practice. Available at: https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2626031
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.
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, adrenal adenomas are found in 1 in every 10 people who have an imaging tests of the adrenal gland.
Adrenocortical carcinoma- It is estimated  that diagnosed 600 people are diagnosed in the United States each year.
Addison’s disease– Prevalence estimated to be between 40 and 60 cases per 1 million in the general population.
Antley-Bixler syndrome- (ABS) has been described in more than 100 patients.
Adrenoleukodystrophy– According the Stop ALD Foundation, this condition affects 1 in 18,000 people.
Cortisol Dysregulation– 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. Research also highlights the fact that cortisol dysregulation is present in up to 40% of stroke patients.
Cushing’s disease – An estimated 10-15 per million people are diagnosed with this condition in the United States every year.
Congenital adrenal hyperplasia (CAH)– 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– 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– 17a hydroxylase deficiency has an estimated prevalence of 1 in 50,000 to 100,000.
3-Beta-hydroxysteroid dehydrogenase deficiency– 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– 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) – Estimated annual incidence of 1/100,000-200,000.
Hypopituitarism– 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– Estimated annual prevalence of 45.5 cases per 100,000 people.
Pheochromocytoma– The prevalence is estimated at 1:2,500 to 1:6,500 patients annually.
Pituitary Adenoma– 9.3 cases per 100,000 population yearly.
Secondary Adrenal Insufficiency– Yearly estimated prevalence is 150–280 per million.
Sheehan’s syndrome– Incidence of Sheehan syndrome is estimated to be 5 patients out of 100,000 births.
Lymphocytic Lypophysitis– 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
Cortisol testing in emergency room situations is not a current standard of care.
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.
Patient’s cortisol levels are tested initially at diagnosis but typically are not tested after diagnosis to evaluate effectiveness of their steroid replacement.
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.
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.
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.
There is currently no way to check blood serum cortisol levels outside of a laboratory setting.
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.
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:
Early detection and diagnosis prior to experiencing adrenal crisis.
Access to and awareness of all steroid options, which includes oral medications, subcutaneous cortisol injections and the cortisol pumping method.
Access to and awareness of testing that can evaluate cortisol deficient conditions and provide clinicians with insight on better cortisol regimens and replacement methods.
Education on the importance of medication compliance and the need to increase dosing in times of stress, sickness or injury.
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.
 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]
 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/
 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:
 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/
 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.
The Circadian rhythm refers to the biological processes that are 24-hour cycles in the body to modulate temperature, hormones, sleep, wakefulness, metabolism, cognitive performance and countless other physiological functions. Circadian rhythm cycles are the physical, mental, and behavioral changes that follow a 24-hour cycle.
Cortisol plays a major role in the regulation of a functional circadian rhythm. The body naturally produces cortisol at different intervals throughout the day, the highest being in the morning to generate the natural waking response and the lowest in the evening to induce sleep. Cortisol levels will also rise in accordance to stressors such as exercise, pain or emotional situations. All these factors must be considered when artificially managing cortisol via steroid replacement medications.
Cortisol regulates the body’s internal processes that regulate the sleep-wake cycle. Circadian rhythm refers to the physical, mental, and behavioral patterns that follow a daily cycle in human life. Cortisol is deeply crucial to circadian rhythm modulation. Because of this, circadian rhythm dosing is essential to effective cortisol replacement.
Cortisol replication needs to be administered according to circadian rhythm protocols; the highest cortisol would be produced by the body in the morning and levels slowly decrease throughout the day to allow for sleep at night. The body requires cortisol 24/7, however it needs higher levels in the early morning to induce the body’s cortisol waking response.
To induce a natural waking response, cortisol levels rise in the early morning hours and they will peak around mid-morning, begin to drop in the afternoon and continue to fall until evening. Cortisol levels decrease at night to allow for the release of melatonin. With adrenal insufficiency, the adrenal glands have failed so all cortisol production must be managed artificially. This is why the concept of the RIGHT DOSE, RIGHT TIME is essential for quality of life with cortisol deficiency. Cortisol deficient patients need the correct dose of cortisol replacement medications but also need these medications in their bodies at the correct time as well.
Adrenal patients need to work with their physicians to determine an optimal dosing schedule for their cortisol replacement medications to calculate the best possible care plan for quality of life. Cortisol replacement needs to be calculated according to circadian rhythm percentages, empirical patient symptoms, activity/stress level, and a patient’s personal cortisol metabolism. It is vital to keep track of blood pressure, heart rate, overall feeling of wellness, low cortisol symptoms, stress tolerance, energy levels and physical stamina.
Every adrenal patient is different and steroid replacement needs to be tailored to each patient depending on their health status and lifestyle. Steroids can cause side effects and the right dosing at the right time is imperative to achieve quality of life. Steroid dosing may differ from day to day depending on the body’s physical cortisol needs, which can change in times of stressors such as injury, surgery, pain, emotional situations or grief. Replacement needs may differ from day to day depending on the stressors the body may be exposed to. It is important to work with your overseeing physician to establish a baseline daily cortisol dose and stress dosing plan.
CORTISOL REPLACEMENT THERAPY NEEDS TO BE A PERSONALIZED, CALCULATED PROCESS WHERE THE FOLLOWING FACTORS ARE CONSIDERED.
1– Cortisol metabolism. Blood cortisol testing can be done to determine how quickly your body metabolizes cortisol. Saliva tests cannot be used to determine the same data as blood serum cortisol testing. Saliva cortisol testing only measures free cortisol and will not evaluate total cortisol levels.
Multi Specimen Cortisol Blood Lab Tests available in the U.S:
Labcorp- Cortisol, Six specimens (Test code: 024091. CPT Code: 82533(x6)
2– Daily baseline dose needs. Every adrenal patient is different. Your dose will depend on your specific body’s needs according to your health status, comorbidities, pain levels, weight, and cortisol metabolism.
3–Dosing times. Cortisol replacement needs to be administered as closely to the circadian rhythm as possible. Dosing schedules need to attempt to match the body’s natural cortisol production.
4- Stress dosing needs. Stress dosing is imperative to preventing a life-threatening adrenal crisis. It is important to note that anything that stresses the body can require more cortisol. This includes physical, emotional or environmental stressors.
Your prescribing physician should “over” write your prescription for days you may need extra cortisol. For example, if your dose is 15 mg, your doctor can write the prescription for 25 mg daily in case you need extra cortisol in case of illness, fever, trauma, or excess stress.
If you are updosing frequently, you may need to adjust your daily dose baseline.
It is also important to understand what steroid works best for your body. Finding the right steroid is dependent on each adrenal insufficient patient. Different steroids have different pharmacokinetics, and some are metabolized faster than others. For example, hydrocortisone has the shortest half-life of 90 minutes, verses dexamethasone, which is the longest acting steroid. It is important to work with a physician who is proficient in managing adrenal disease to determine the most optimal steroid replacement medication. Additional options for patients who have not responded well to any oral steroids are alternative cortisol delivery methods such as the cortisol pump.
ORAL STEROID OPTIONS FOR ADRENAL INSUFFICIENCY
The following list are the oral medications commonly prescribed for Adrenal Insufficiency. This is not an all-inclusive list and is not to be used to diagnose or replace medical care.
Cortisone Acetate- The acetate salt form of cortisone, a synthetic or semisynthetic analog of the naturally occurring cortisone hormone. Cortisone itself is inactive; it is converted in the liver to the active metabolite hydrocortisone.
Dexamethasone (Decadron)- Medication is used in the treatment of cancers such as leukemias, and lymphomas and to treat diseases involving destruction by the body’s own immune system. Also used to treat adrenal insufficiency. Dexamethasone is a long-acting steroid and remains in blood circulation for approximately 16 hours after administration, with a half-life of about 4 hours.
Fludrocortisone (Florinef) – Synthetic medication used to treat salt wasting diseases such as primary Addison’s disease. Fludrocortisone cannot be converted to another corticosteroid on the basis of anti-inflammatory potency. It is not a replacement for cortisol but is used in addition to cortisol replacement in some forms of adrenal disease.
Hydrocortisone (Cortef) – Medication is the most bio-identical form of cortisol. It is a short acting steroid used to treat autoimmune diseases, allergic reactions and also adrenal insufficiency. The pharmaceutical properties of the dosage of hydrocortisone are determined by intestinal absorption rate and the plasma concentration-time profile of hydrocortisone (cortisol) in a specific patient’s body. There are many factors that cause or result in pharmacokinetic variability; therefore, the short elimination half-life of hydrocortisone is approximately 1.5 hours when given in traditional immediate-release dosage forms.
Methylprednisolone (Medrol)- Medication which is a synthetic corticosteroid and is mainly used to achieve prompt suppression of inflammation but can also be used to treat adrenal insufficiency.
Prednisolone (Prelone)- Synthetic glucocorticoid replacement medication used to treat adrenal insufficiency and also used to treat autoimmune diseases and allergic reactions.
Prednisone- Synthetic corticosteroid which mimics the action of cortisol produced in the body by the adrenal glands. Most often used for its potent anti-inflammatory effects, particularly in autoimmune and inflammatory diseases and conditions. Also used to treat adrenal insufficiency. Prednisone is inactive in the body and in order to be effective first must be converted to prednisolone by enzymes in the liver. Prednisone may not work as effectively in people with liver disease whose ability to convert prednisone to prednisolone is impaired.
Rayos- Long-acting corticosteroid medication in the form of delayed-release prednisone. This medication releases the action of prednisone about 4 hours after tablets are ingested. Used the treatment of such rheumatoid arthritis polymyalgia rheumatica and also adrenal insufficiency.
Cortisol deficient patients need the right steroid, at the right dose, at the right time.
Proper cortisol replacement is deeply crucial to circadian rhythm modulation and quality of life. Standard oral hydrocortisone replacement done incorrectly can render adrenal insufficient patients under or over replaced within the same 24-hour dosing period. Inaccurate dosing is why a majority of patients diagnosed with adrenal insufficiency suffer from a poor quality of life, with increased mortality rates, sleep disturbances, impaired psychological wellness. Cortisol replication needs to be administered according to circadian rhythm protocols; the highest cortisol would be produced by the body in the morning and levels slowly decrease throughout the day to allow for sleep at night. The body requires cortisol 24/7, however it needs higher levels in the early morning to induce the body’s cortisol waking response.
Speak with your overseeing physician about cortisol circadian dosing.
Chan, Sharon, and Miguel Debono. “Replication of Cortisol Circadian Rhythm: New Advances in Hydrocortisone Replacement Therapy.” Therapeutic Advances in Endocrinology and Metabolism. SAGE Publications, June 2010. Web. www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279
Type 1 Diabetes is the disease where the pancreas fails to produce the correct amount of insulin, thus rendering someone insulin dependent.
Adrenal insufficiency is a disease where the adrenal glands fail to produce the proper amounts of steroid hormones and requires lifelong steroid medication for cortisol replacement.
Unlike diabetic patients who have glucometers, adrenal disease sufferers have no meter to check their cortisol levels. They must be constantly vigilant of their own low cortisol symptoms. The excitement from a happy event, the sadness from a death of a loved one or the strain from exercising are examples of things that would cause the body to release more cortisol. In an adrenal insufficient person, this does not happen. They must artificially manage their cortisol, which can differ from day to day. They require an emergency cortisol injection if their levels drop to a critical point.
Hydrocortisone is the standard cortisol replacement medication, which only has a blood serum half-life of 90 minutes and must be taken multiple times a day. This medication must be processed through the stomach and the liver before reaching the blood stream. This causes an abnormal rise and fall of cortisol levels, which results in subpar function, increases mortality rate and decreases quality of life.
However, advances in research have found a solution for adrenal patients. The concept of Cortisol Pumping is the use of solu-cortef (inject-able version of cortisol when mixed with saline) used in an insulin pump programmed to disperse cortisol according to the natural circadian rhythm. This method bypasses the gastric passage and delivers cortisol in a more natural way. With this method, an adrenal insufficient patient can receive cortisol constantly. Side effects due to malabsorption are decreased and patients have been reported to have improved sleep, weight management and experience an overall improvement in their quality of life. This method has also been proven to lessen the prevalence of adrenal crises and lessen hospitalizations due to low cortisol.
Despite the vast amount of research showing the efficacy of this treatment, infusion pumps are not offered to adrenal insufficient patients. Unlike diabetics, they do not have easy access to infusion pumps and supplies.
The Right to Try Act which was passed in 2018, mandated that patients now have legal rights to access life-saving treatments which are not yet FDA approved. Adrenal Alternatives Foundation is a 501c3 organization dedicated to providing adrenal insufficient patients with the resources to safely and legally begin the cortisol pumping method. The nonprofit works to educate physicians on how to manage this protocol. They also assist patients in obtaining insurance approval and their “Pumps for Purpose Program” helps provide pumps and supplies to adrenal patients, with or without insurance coverage. They have also created the resources: Cortisol Pump Guide Book and the Cortisol Pumping website to help guide patients in their pumping journey. Their hope is that one day, there will be disease equality and both adrenal patients and diabetics will both have easy access to infusion pumps.
This information was brought to you by the Adrenal Alternatives Foundation for educational use only and is not meant to provide medical care or legal advice.