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.
Cortisol Secretion Percentages over a 24-hour period: (Source: Hindmarsh. CAHISUS)
6:00am to noon 35% of cortisol is produced.
Noon to 6:00pm 20% of cortisol is produced.
6:00pm to Midnight 15% of cortisol is produced.
Midnight to 6:00am 30% of cortisol is produced.
RIGHT DOSE AT THE RIGHT TIME
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:
Quest Lab- Cortisol, Six specimens (Test Code 6734. CPT Code 82533 (x6)
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.
More information on managing adrenal disease can be found in the book A patient’s guide to managing adrenal insufficiency.
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.
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- 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
- Hindmarsh, P., & CAHISUS (n.d.). Circadian Rhythm Dosing. Retrieved from: http://www.cahisus.co.uk/pdf/CIRCADIAN%20RHYTHM%20DOSING.pdf
- Endocrine Reviews, Volume 38, Issue 1, 1 February 2017, Pages 3–45, https://doi.org/10.1210/er.2015-1080