Excerpts from “Low Dosage Glucocorticoid Therapy: An appraisal of its safety and mode of action in clinical disorders, including rheumatoid arthritis”

Jefferies,W. McK., Arch Intern Med 1967, 119:265-78.
Read in part before the annual meeting of The American College of Physicians in New York City on April 18, 1966.

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.


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


“By extrapolation it is apparent that total suppression of endogenous adrenocortical activity [by the normal hormone, cortisol, in tablet form] should occur with approximately 35 mg/day ( 10 mg before each meal and 5 mg at bedtime), a dose similar to the 40 mg ( 10 mg 4 times daily, ac & hs) that has proven to be a satisfactory replacement dose.”

“These observations, therefore, support the concept that low dosages cause compensatory decreases in adrenocorticotropic hormone just sufficient to result in the maintenance of a normal total effective quantity of cortisol in the body and they provide evidence against the occurrence of a summation effect.”

“…in the 371 patients treated for periods of six months to nine years with dosages not exceeding 20 mg of cortisone acetate or hydrocortisone daily….no signs of hypercorticism occurred in any patient, ….nor was there impairment of resistance to stress”.

“Resistance to minor infections such as common respiratory diseases also was not impaired; on the contrary, many patients commented that they seemed to have a greater resistance to respiratory infections while receiving the low dosage glucocorticoid therapy.”

“The corticotropin response indicated a more normal state of adrenocortical activity while the patient was taking cortisone than had been present prior to its administration.”

“These observations, therefore, provide further evidence that low dosage glucocorticoid therapy only partially suppresses endogenous adrenocortical activity, that it does not produce hypercorticism or a summation effect,…and that it does not lower resistance to stress.”

“These observations suggest that an abnormality of steroid metabolism may exist in rheumatoid arthritis.”

“It is conceivable that at least some patients with collagen disorders or chronic allergic conditions might benefit from low dosage glucocorticoid therapy indefinitely.”

“Two cases of rheumatoid arthritis achieved symptomatic remissions without evidence of summation effect.”

“Five women with untreated rheumatoid arthritis had similar abnormalities in urinary excretion of 11-desoxy-17-ketosteroid fractions before and after a standard adrenocorticotropic hormone stimulus.”

“The administration of low doses of natural glucocorticoids is, therefore, not attended by the hazards characteristic of larger dosages; antirheumatic effects do not necessarily depend upon the presence of an excess of glucocorticoid, and patients with rheumatoid arthritis may have an obscure disorder of steroid metabolism.”