Excerpts from “Mild Adrenocortical Deficiency, Chronic Allergies, Autoimmune Disorders and the Chronic Fatigue Syndrome: A Continuation of the Cortisone Story

Jefferies,W.McK., Med Hypoth 1994; 42: 183-189

The links below will redirect you the personal web pages of Dr. William McK. Jefferies. The copyright of the contents on these pages are owned by Dr. Jefferies and his heirs.

1. Homepage of Dr. William McK. Jefferies
2. Research Focus: “Cortisone: A Problem in Pharmaceutical Marketing
3. Safe Uses of Cortisol
4. A Continuation of the Cortisone Story: “Mild Adrenocortical Deficiency, Chronic Allergies, Autoimmune Disorders and the Chronic Fatigue Syndrome”
5. Low Dosage Glucocorticoid Therapy (Excerpts)
6. Reproduction of Dr. Jefferies Hydrocortisone Handout
7. Dr. Jefferies’ Reference Ranges for Serum Cortisol


“When patents expired on cortisone and cortisol, the more potent derivatives, whose patents persisted, were promoted more vigorously and the natural hormone tended to be forgotten. Package inserts no longer differentiated between physiologic and pharmacologic dosages of cortisol and it was implied that all of the grim side effects might develop at any dosage level.”

“Most physicians practicing today are therefore under the impression that any dosage of cortisol can produce any of the serious side-effects that occur only with administration of large, pharmacologic dosages of this normal hormone.”

“Reports documenting the safety and effectiveness of physiologic dosages of cortisol were published in reputable medical journals over 25 years ago, but computerized reviews of the medical literature, such as Medline, do not yet cover publications that remote, so few physicians today are aware of the existence of these reports.”

“One of the most alarming effects of pharmacologic dosages was impairment of immunity, causing patients to become susceptible to infections…. It has even been suggested that the increased production of cortisol that occurs at the onset of infection may serve to limit the reaction from overshooting and hence would be consistent with the anti-immune effects of pharmacologic dosages, but a more likely explanation of this increased production is that of Ingle, which states: “The increased secretion of adrenal hormones serves to meet an increased need during stress and tends to maintain homeostasis rather than to disturb it. The increased secretion does not cause a state of hypercorticism such as develops when the titer of these hormones is increased artificially in the absence of need.”

“Evidence that cortisol impairs immunity only in large, pharmacologic dosages and that in physiologic amounts this hormone is essential for the development and maintenance of normal immunity has been reported by investigators over the past 40 years, but largely overlooked,…”

“Before patients are given other hormones, tests of the function of the glands that produce those hormones are usually performed, but tests of adrenocortical function are seldom made on patients before the administration of glucocorticoids.”

“Normal ranges for blood cortisol levels and other tests of adrenal function have been determined on subjects who did not have obvious adrenocortical excess (Cushing’s syndrome), or deficiency (Addison’s disease), or panhypopituitarism,or any other apparent illness, and are rather broad. Hence they may include patients with mild deficiency or excess of cortisol. Also it must be remembered that resistance to cortisol may occur because of a defect in receptor function,so blood cortisol levels in the normal or even supranormal range do not exclude the possibility of symptoms associated with deficiency of cortisol effects.”

“If cortisol is administered to patients with mild primary adrenal deficiency in an amount less than a full replacement dosage, there appears to be no summation effect beyond the reaching of an optimum level since patients receiving such dosages have not developed hypercortisolism. If they receive a full replacement dosage for a prolonged period, however,their adrenals might be suppressed sufficiently to impair further their resistance to stress.”

“As with patients with severe adrenal deficiency, if a patient with mild adrenal deficiency has evidence of an active inflammatory processor infection, a larger dosage of cortisol, up to 20 mg 4 times daily, in conjunction with a suitable antibiotic or other type of therapy, is advisable,but when this condition is under control, the dosage of cortisol should be tapered to the maintenance level (between 2.5-7.5 mg four times daily)over 2 to 4 days.”

“During exacerbations, patients with allergies or autoimmune disorders need to take larger dosages of cortisol (20 mg four times daily is usually adequate), but as soon as symptoms are under control, the dosage should be tapered to a physiologic maintenance dosage. If this is not possible without a return of symptoms, a careful search should be made for obscure infection or other persistent source of stress that is preventing the return to a safe maintenance dosage.”

“Since subreplacement dosages of cortisol do not produce an excess of glucocorticoid, they have not tended to promote the development of osteoporosis or any other undesirable side-effects that can result from administration of large, pharmacologic dosages.”

“Patients have been treated with this schedule of cortisol or cortisone acetate for as long as 40 years without significant problems. Because some of these patients had ovarian dysfunction and infertility, and because continuation of small, physiologic dosages helped to protect against miscarriages,over 200 babies have been born to women who continued these physiologic dosages through their pregnancies and sometimes during their postpartum(including nursing) periods with no evidence of harm to either mothers or babies.”