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Consensus # 3 Cortisol Replacement Therapy in Milder Forms of Adrenal Deficiency in Adults

December 09, 2005

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After a literature review and discussions with physicians from all over the world who are well versed in treating patients with endocrine abnormalities, we, the members of the Consensus Group of Experts of the International Hormone Society, think the time is ripe to reconsider current concepts on glucocorticoid treatment of adrenal deficiency, and in particular to consider treating cortisol deficiency in adults, not only those affected by severe deficiencies, but also those that suffer from milder forms.

We acknowledge and approve the worldwide consensus that has been reached on glucocorticoid treatment of adults suffering from severe cortisol deficiency.Generally, in such conditions there is a total or near total cortisol deficiency due to a total or near total removal or inactivation of the adrenal glands, the endocrine glands that secrete cortisol.

We think that the amount of supporting data on cortisol's beneficial effects and the data on eventual side-effects are now sufficient to extend the recommendation of cortisol treatment to patients with milder forms of cortisol deficiency. Among the milder deficiencies, those forms that may appear in adults during the aging process, due to a progressive deterioration of the pituitary-adrenal axis, are included.

The evidence is that cortisol is not only essential for survival of severely cortisol depleted patients, but also essential for the mental and physical health of all adults, including the elderly. An adequate amount of cortisol is essential for multiple organ systems: the brain, skin, joints, muscles, the digestive tract, the immune system, and the cardiovascular system. Cortisol deficiency is often associated with fatigue, poor stress tolerance, confusion and malaise, summarized as a diminished quality of life with severe impairment in patients who are more sensitive to the deficiency. Glucocorticoid treatment has, on the other hand, been reported to improve the quality of life, the mind and mood of patients. Adverse physical consequences of cortisol deficiency range from feeling weak to the often debilitating effects of inflammatory diseases (rheumatoid disorders, gastro-enteritis, colitis, immune disorders, allergies, etc.) and even to the increase in mortality of high-risk conditions uch as septic shock. The milder forms of a cortisol deficiency can still be harmful and can pose more serious health issues than previously thought.
As cortisol and other glucocorticoids have been associated with serious side effects, we do, however, recommend that physicians treat patients for cortisol deficiency by observing safety guidelines. Immune system suppression, osteoporosis, an increase in bruising, weight gain, skin atrophy, high blood pressure, excessive adrenal suppression, and a Cushingoid physical appearance, are some of the possible adverse consequences. We estimate that in general the adverse consequences attributed to glucocorticoids are due to excessive doses and treatments that are not well-balanced with other hormones, in particular the anabolic ones. Anabolic hormones can block the disproportionate tissue breakdown caused by excessive amounts of corticoids. In some cases of cortisol deficiency, in particular for the patients with an extreme deficit such as Addison's disease, the use of synthetic derivatives of cortisol may be less effective (and associated with side effects) than the use of cortisol that is identical chemically to our endogenous cortisol (hydrocortisone).

Diagnosis of cortisol deficiency

1. Laboratory Testing:
At least two of the below-mentioned tests should be ordered based on the type of adrenal deficiency suspected.
Blood tests:
  • Serum total cortisol and (calculated) free cortisol, and transcortin (CBG) in the morning and late afternoon.
  • Serum ACTH
  • ACTH stimulation test with a dilute formulation of 1.0 micrograms rather than 250 micrograms.
24-hour Urine Test:

  • Urinary cortisol and its metabolites, 17-hydroxysteroids using gas chromatography.
It is helpful to test for levels of anabolic hormones such as
  • DHEA sulphate
Other blood tests:
  • Serum Estradiol, SHBG, androstanediol glucoronide, IGF-1, IGF-BP-3, freeT3, freeT4 (as cortisol may lower the conversion of T4 to T3, and cortisol deficiency does exactly the opposite); urinary 17-ketosteroids (gas chromatography), aldosterone, 6-sulfatoxy-melatonin, growth hormone,
  • Sodium and potassium (checking the mineral corticoid effects of cortisol)
2. Interpretation of laboratory tests:
A certain number of patients may show clinical signs and symptoms of cortisol deficiency, and test values that are in one or more tests borderline low for cortisol, close to the lower reference value (2 standard deviations from the mean of a laboratory designated population). In such borderline patients, a therapeutic test may be warranted. The patient can be given cortisol in a combination with a safe anabolic hormone, at least DHEA (Dehydroepiandrosterone) to assure a correct catabolic-anabolic balance. The same balance is also needed in the patients with a more severe cortisol deficiency.

Traitement - Daily Doses:
1. Milder cortisol deficiencies: should be treated with
  • 15 to 30 mg of hydrocortisone (or 2.5 to 7. mg of prednisolone, or 2 to 6 mg of methylprednisolone) per day in women
  • 20 to 40 mg of hydrocortisone (or 2.5 to 7. mg of prednisolone, or 2 to 6 mg of methylprednisolone) per day in men

2. More severe cases : need generally 30 % higher doses than the maximum useful for milder deficiencies.

Tips: Men need higher doses because their adrenal glands secrete approximately 50 % more cortisol than those of women. Only about half of the doses are absorbed through the intestinal tract. For stress related conditions, such as infections, surgery, severe emotional distress, etc., the doses should be temporarily increased.
Precautions: as glucocorticoid treatment may further aggravate any existing deficiency in thyroid hormones, aldosterone, and adrenal androgens (such as DHEA), we recommend that the physician correct any of these deficiencies.

In conclusion, no convincing data have been found against the use of cortisol or other glucocorticoids in adults suffering from mild cortisol deficiency. On the contrary, reports of maintaining cortisol deficiency in patients results in adverse effects on their health that can be avoided by treating with physiologic doses of cortisol.
Therefore we recommend treating patients with low cortisol level and/or low 17-hydroxysteroid levels. Cortisol or other glucocorticoid treatments should be restricted to physiological amounts and in most cases balanced with anabolic hormone supplements (if these levels are low), and be monitored carefully by regular check-ups.


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286 signatures for this petition
1 to 10

Karin Esztermann
(no comment)
Beverly Ferguson
United States
(no comment)
Mia Dravers
(no comment)
Alexander Weber
(no comment)
Clacina Tanner
United States
(no comment)
Monsie Pickles
Your information is invaluable. We do not get help from doctors.
monsie pickles
Mary Rickey
United States
(no comment)
Deborah Eckardt
United States
(no comment)
Catherine Docous
United States
Replacement can be life changing; this is criminal this treatment is not recognized.
Shelley Asper
United States
(no comment)



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