The Safe Use of Cortisol by William McK Jefferies MD is a medical classic, and along with its companion classic by Broda Barnes, Hypothyroidism, the Unsuspected Illness, both books should be required reading by every medical student and MD and deserve a prominent place in every medical library. I have read both numerous times, and plan to re-read both again.This book contains a condensation of clinical knowledge from the career of a medical giant, and a wealth of knowledge not found anywhere else, and is complete with references to the medical literature, case histories, laboratory studies and dosages.In this slim volume, Safe Use of Cortisol, Dr. McK Jefferies points out an important distinction which is not widely known by mainstream doctors or the public. This is the distinction between the lower and completely safe, physiologic doses of cortisol, and the dangerous higher pharmacologic dosage levels commonly used by mainstream doctors to treat rheumatoid arthritis and other auto-immune diseases.While the lower cortisol doses below 40 mg per day are safe, above this dosage level is increased risk of adrenal suppression, and increased risk of adverse side effects including moon face, osteoporosis with spontaneous fractures, thinning of skin with easy bruising, striae, subcutaneous hemorrhages, fluid retention with edema, and cataracts.Cortisol is widely available as inexpensive Cortef from the corner drug store, and is the bio-identical hormone secreted by the adrenal gland. Since it is a natural hormone, it cannot be patented, explaining the lack of funding for research by the pharmaceutical companies.Chapter 4 of the book discusses generally accepted uses of Cortisol, starting with the most logical use which is adrenal insufficiency, also called Addison's disease. However, McK Jefferies also discusses mild adrenal insufficiency, which is not usually recognized by mainstream doctors, and should be. Other uses of low dose cortisol include ovarian dysfunction with infertility, chronic fatigue, allergies and auto-immune diseases.McK Jefferies relies on the Cortrosyn ACTH stimulation test to evaluate adrenal function, as well as urinary cortisol metabolites and serum cortisol tests. He also addresses thyroid function as part of the overall clinical picture; hence the connection with Broda Barnes and the continued advocacy of McK Jefferies' work by the Broda Barnes Institute.I found Chapter 5, Gonadal Dysfunction and Infertility, to be the most fascinating and clinically useful chapter. McK Jefferies used low dose cortisol to successfully treat thousands of young women suffering from irregular menstrual cycles, ovarian dysfunction, hirsutism (facial hair, and acne, both signs of elevated testosterone).Nowadays, teenagers with irregular menstrual bleeding are routinely given birth control pills with synthetic hormones to regulate their cycles. The synthetic hormones in BCPs are associated adverse side effects and do not address the underlying fertility issues.Unknown to the mainstream medical system, the real treatment for irregular menstrual bleeding is found in this medical classic book, namely low dose cortisol and thyroid which successfully normalizes menstrual cycles and restores fertility. Dr. McK Jefferies suggests that the cause of the infertility and irregular periods in these patients is usually excess adrenal production of either androgen (PCOS) or estrogen, and the low dose cortisol serves to suppress this excess hormone production by the adrenals and allow normal ovarian function.Now recognized as the most common genetic disorder in the population, (CYP21A2) non-classical 21-hydroxylase deficiency is associated with menstrual irregularities, hirsutism and acne from elevated testosterone. Rather than low dose cortisol, current practice is to use similar low dose dexamethasone (See the 2006 review in J Clin Endo & Metab Vol. 91, No. 11 4205-4214, by Maria I New). Perhaps non-classical 21-OH should be renamed McJefferies Syndrome to give proper credit to this great clinician.McJefferies stresses that normalization of thyroid function is also required for menstrual regularity and fertility. Broda Barnes agrees with McK Jefferies on the importance of thyroid for normalizing menstrual cycles, and both treat with thyroid medication even though the thyroid blood tests may be completely normal. They have found the blood tests to be unreliable. This is at variance with mainstream medical practice which clings dogmatically to the thyroid blood tests. Most mainstream doctors would refuse to offer thyroid medication unless there is a documented "out of range" lab value.Chapter 9 deals with using low dose cortisol for viral infections such as influenza. Although there was some initial concern that low dose cortisol would reduce immunity in some way, Dr. Mc Jefferies was surprised to find in clinical practice that his patients maintained on low dose cortisol typically reported fewer common colds and other viral illnesses than their family members, suggesting an enhancement of immunity. Another practice he used was to increase the cortisol dosage when patients felt a common cold or viral influenza coming on. He found that this enabled the patient to ward off or recover from the illness more quickly. Of course, he also points out that excess doses of cortisol would have the opposite effect and impair resistance to infection.The final chapters of the book discuss the use of low dose physiologic cortisol for rheumatoid arthritis, allergies, auto-immune disease, chronic fatigue.In addition to the ACTH stimulation tests still in use today, we now have the newer, salivary cortisol testing which I am sure Mc Jefferies would have found useful in his day. What he would have written about the use of salivary cortisol testing ? Unfortunately we will never know. Perhaps a future medical author will build on McK Jefferies work and incorporate salivary testing and other new developments in a future book.I reviewed the third edition which was published in 2004. The first edition was published in 1983. Other books recommended along side this one are, Adrenal Fatigue by James Wilson, Hypothyroidism, the Unsuspected Illness by Broda Barnes, From Fatigued to Fantastic: by Jacob Teitelbaum, Your Thyroid and How to Keep it Healthy by Barry Durrant Peatfield.Jeffrey Dach MD