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From the Townsend Letter
February / March 2018

Cortisol Deficiency: Frequent, Life-Impairing, and How to Give Patients Their Lives Back by Correcting It Part 2
by Thierry Hertoghe, MD
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Daily Cortisol Production
How much cortisol do humans produce? Researchers have found that the cortisol production rate in sedentary adults assessed in an in-hospital resting unit is on average more in men (22.5 mg per 24 hours) than in women (9.2 mg per 24 hours)448 due to the bigger body surface area and adrenal glands of men. The average body surface area is 1.9 m² in men and 1.6 m² in women.449 Other investigators have found lower cortisol levels in men, an average of 9.1-10.9 mg/m² of the body,450-451 which equals about 17.3- 20.7 mg/day of cortisol for men with average body surface area.

However, these productions are valid only for sedentary resting conditions in laboratory units. In real life, the multiple mental and physical activities and higher stress conditions require and stimulate the adrenal glands to produce more cortisol. An average day in "real life" conditions requires at least 30–50% more cortisol production so that the real daily average cortisol production is probably 30 mg/day in men and 20 mg/day in women.

In people with heavy physical activity, daily cortisol production may even triple. Urinary cortisol excretion in female long-distance runners, for example, is threefold higher than that in sedentary persons.452
How much cortisol do cortisol-deficient patients need? My personal experience is that doses of less than 15 mg/day in female and less than 20 mg/day in male cortisol-deficient adults, respectively, do not work well. At too-low doses, patients feel – after an initial modest and short improvement in cortisol activity two-to-four hours after intake – a noticeable drop in energy, due to a fall in cortisol activity. Low doses of 5–10 mg/day of cortisol are just not sufficient to keep the baseline cortisol levels high enough for a satisfying quality of life.

How much cortisol is absorbed after intestinal intake? Does this mean that we need a maximum of 20 to 30 mg per day cortisol intake to correct a near total deficiency? No, because, on average, less than half – only 43% – of oral hydrocortisone (cortisol) is absorbed.453 This means that a patient who does not have any cortisol production, needs to take a dose equivalent to double the normal endogenous cortisol production – 40 to 60 mg per day of oral hydrocortisone – to compensate for the absence of endogenous cortisol production.

In fact, cortisol absorption in the intestines might even be lower because the 43% of hydrocortisone absorption was measured in optimal conditions in which hydrocortisone was perfused with water in the intestinal lumen. The more water is added, the more hydrocortisone is absorbed. Thus, water intake may improve hydrocortisone absorption.

Food ingestion before hydrocortisone intake, on the other hand, delays hydrocortisone absorption.454
Divided doses of hydrocortisone usually, but not always, work better. For most patients, hydrocortisone should be taken in divided doses, at least twice a day,455-456 for example, a higher dose in the morning after waking and the remaining dose during lunch. I recommend taking doses 5-20 minutes before breakfast and lunch, but some people experience stomach irritation because of the acetate that is bound to the hydrocortisone; it is pharmaceutically delivered as hydrocortisone acetate, which is an acid, and not as hydrocortisone alone. To avoid acidity, the hydrocortisone can be taken after meals or, if problems persist, prescribe the hydrocortisone pills with a protective (enteric coated) layer for the stomach.

Some people need to divide the doses further into three to four smaller portions taken at regular intervals throughout the day.454,456-458 In these cases, they can take a supplementary dose of 5 mg of hydrocortisone at 4 p.m. and before bedtime. The 5 mg of hydrocortisone at bedtime is too small to keep the patient awake at night, but it does provide better energy upon waking the next morning.

What if a patient forgets the second dose of hydrocortisone or cortisone at lunch? He or she should take it later (4 p.m., for example), but not too late (after evening meal). Patients who tend to forget to take the second dose can try taking the full daily dose after waking. Some people do fine and stay energized until bedtime; others do not and need two or even three bioidentical hydrocortisone or cortisone doses to feel well throughout the day.

Treatment with Synthetic Glucocorticoid Derivatives
In inflammatory diseases, such as the flu and rheumatoid arthritis, the synthetic cortisol derivative prednisone and its active metabolite, prednisolone, provide more efficient relief and the ability to avoid permanent adverse consequences, such as joint deformations, thanks to their prolonged duration of action.51,459-460

In overweight people and individuals with a tendency to foot edema and arterial hypertension, permanent use of methylprednisolone is generally a better option because, at equivalent doses, it retains less water and weight and increases blood pressure less than other glucocorticoids, particularly much less than the bioidentical hydrocortisone. When I prescribe it, I start with a period of two to six months and may continue administering it if the patient remains prone to the aforementioned disorders.

Table 3 (adapted from Chrousos et al., 2011)51 shows the absence at physiological dose of the water-retaining and blood pressure-increasing effect of methylprednisolone compared to cortisol and prednisone.

Table 3. Glucocorticoid Hypertensive Potencies .pdf

Dexamethasone is a potent synthetic derivative of cortisol. A dose of 0.25 mg of dexamethasone equals the activity of 20 mg of hydrocortisone. Because of its longer 48-hour duration of action, dexamethasone may considerably reduce adrenal hormone secretion, including the production of androgens (male hormones). Dexamethasone's capacity to drastically reduce adrenal androgens is useful in reducing excessive body hair growth in women resulting from an excessive production of adrenal androgens. A once-daily morning intake of dexamethasone is usually sufficient to considerably suppress adrenal androgen production for more than 24 hours. I do not find its intake every two days efficient, as patients do not usually feel well on the second day, perhaps due to recurrence of adrenal deficiency.

To reduce skin rashes or to avoid keloid (voluminous scar) formation, a cream of 1-3% hydrocortisone may prove efficient. A concentration of 3% equals 30 mg of hydrocortisone per gram of cream. If this does not suffice, a lotion with a synthetic glucocorticoid derivative may help, but only if the area of skin application is small (several square centimeters), otherwise too much of the more potent synthetic derivative will penetrate through the skin into the body and cause side effects.

In emergencies, injections with high doses (50 to 250 mg) of cortisol or synthetic derivatives may be helpful, but this should be limited to exceptional cases as overdoses produce side effects. Table 4 summarizes the various cortisol treatments.

Table 4. Typical Glucocorticoid Treatment Schedules .pdf

Dealing with Inflammation, Infections, Allergies, or Stresses
In nature, vigorous adrenal glands react to stress by increasing their secretion of cortisol and other adrenal hormones. People with adrenal deficiency have lost a great part of their ability to produce additional amounts of cortisol in cases of extra need. Their inability to increase their secretion of cortisol explains why they suffer from stress much more than people with healthy adrenal glands. Their excessive stress sensitivity can progress into a real hate of any kind of stress.

The solution for these patients is to mimic nature by taking additional cortisol in conditions where more cortisol is needed. Taking a dose of 5 mg of hydrocortisone, 1.25 mg of prednisolone or prednisone, or 1 mg of methylprednisolone every 30 minutes until mild or moderately important infections or stressful feelings disappear may do the job.91,461 In cases of severe inflammation or infection, this small dosage may have to be doubled. In most cases, stressful feelings and infections disappear within two hours. Continuously increasing every 30 minutes for more than three hours is not recommended. The total amount of cortisol that may be needed the day of an infection or heavy stress may be the double or triple of the regular daily dose without any side effects other than the disappearance of inflammation or stress.

Transiently increasing cortisol is really efficient when the increase is applied in the minutes that the patient feels the first signs of infection or stress. The longer patients wait to increase their doses, the less efficient this method becomes. When I start to get a sore throat, or feel my body aching because of the flu, even if it is in the middle of the night, I take an extra dose of hydrocortisone or, even better, switch to 1 to 2.5 mg prednisolone or prednisone every 30 minutes. These synthetic glucocorticoids are more efficient in alleviating flu symptoms thanks to their greater anti-inflammatory effects and prolonged 24-hour action. In general, one, two, or three additional intakes every 30 minutes are necessary to alleviate flu symptoms or a sore throat.

When patients wait too long after the start of an infection – two days for example – to increase their cortisol treatment, they often do better by limiting the increase in cortisol intake to an average of 50% more than their usual daily dose and must often continue this higher dose for three to ten days to rid themselves of the persisting infection, inflammation, or allergy. Such a prolonged intake of a higher dose of cortisol is generally unnecessary when the patient intervenes quickly and increases the dose in the minutes after noticing the first signs of an infection or allergy symptoms.

In stressful conditions, such as speaking at a meeting or participating in a radio or TV show, people with adrenal deficiency greatly benefit from taking 5–10 mg, 30 minutes to two hours before speaking. They experience more punch and perform better.

Can people not on glucocorticoid treatment occasionally take cortisol? Each time a person has a flu or another type of viral infection or has to face a stressful event, occasional intake of cortisol (preferable with an equal amount of protective DHEA) may stimulate the immune system without harm so that the infection is overcome in a matter of hours if the patient reacts quickly. A dose of 5-10 mg of hydrocortisone before a stressful event or 20-30 mg in one intake at the occasion of an infection may be sufficient to alleviate acute viral infections.

Side Effects and Risks of Cortisol Treatment
Three types of side effects of cortisol treatment can occur:

  • Overdose effects due to excessive cortisol levels.
  • Imbalance effects due to an absence or deficiency in anabolic hormones, whose roles are to block any unwanted catabolic effects from cortisol.
  • Adrenal gland suppression is when secretion of hormones by adrenal glands is partially or totally blocked by treatment through negative feedback to the pituitary gland's secretion of ACTH.

Total suppression of the hormone secretions of the adrenal glands usually occurs only with very high glucocorticoid doses that are considerably higher than those proposed in Table 4. Total adrenal suppression may endanger life in cases in which cortisol secretion stops suddenly, as life is not sustainable without cortisol.

In general, at 20 to 30 mg per day of hydrocortisone, adrenal suppression is only partial (20–35%) and transient. After stopping these physiological doses, patients recover their initial cortisol secretion within two to six weeks. However, when very high doses are given for four to six months, as with some patients with severe rheumatoid disorders, the decrease in adrenal secretion of cortisol may persist for eight months before returning to the initial state.

Neglecting to correct other hormone deficits and a high-carb diet may increase the need for higher cortisol doses. In my experience, patients whose rheumatism does not sufficiently respond to physiological doses of cortisol, in fact, have other hormone deficiencies (testosterone, estrogen, thyroid, DHEA, etc.) that contribute to their rheumatoid disorder. Their diets (sweets, artificial sweeteners, grains) trigger inflammation and block cortisol action. These patients need to correct their diets and other hormone deficits, not to take pharmacological glucocorticoid doses.

How to Stop a Treatment
Patients on long-term high glucocorticoid doses should never abruptly stop their treatments. Rather, they should slowly decrease the dose over a period of two to four months, lowering their dose by 5 mg/day of cortisol or 1-1.25 mg/day of synthetic glucocorticoid every 10-14 days. If this slow and gradual decrease in cortisol supplementation does not gradually revive adrenal glands, regular stimulation of adrenal production with intramuscular injections of 1–2 mg of long-acting ACTH twice a week may restore cortisol production in two to four months.

Table 5 presents an overview of the most frequent complaints and physical signs of glucocorticoid treatment excess.

Table 5. Glucocorticoid Excess .pdf

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Consult your doctor before using any of the treatments found within this site.

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