Stay Away from Adrenal Cortical Extract (ACE)

Stephen Barrett, M.D.

Adrenal cortical extract (ACE) has no legitimate medical use. Although banned from the American marketplace in 1978, it is still prescribed by a few hundred fringe practitioners. This article describes what happened and why you should stay away from anyone who recommends it.

ACE is obtained from the adrenal glands of cattle and other domestic food animals. The major active component is the hormone hydrocortisone. Beginning in the 1920s, ACE was recommended for treating Addison's disease (adrenocortical insufficiency) , a condition in which gradual destruction of the cortex (outer portions) of the adrenal glands leads to a potentially fatal hormonal deficiency. However, as more effective synthetic and purified products became available, use of the crude extract became pointless. The 1971 edition of American Medical Association's Drug Evaluations called ACE an "obsolete preparation." [1]

As the scientific community developed its potent treatment for adrenal insufficiency, the quack community proposed other uses for ACE. In 1949, John W. Tintera, M.D. (1911-1969), of Yonkers, New York, began claiming that the symptoms of "hypoadrenal syndrome" were often similar to those of hypoglycemia (low blood sugar) and included excessive fatigue, nervousness, irritability, depression, excessive weakness, lightheadedness, faintness, insomnia, headache, and inability to concentrate [2,3]. Not long afterward, he greatly expanded this list and proclaimed that hypoglycemia was caused by "tired" or "worn out" adrenal glands. The long list of symptoms and conditions enabled him and a few hundred other maverick physicians to diagnose and prescribe ACE for "hypoglycemia" in patients who had neither Addison's disease nor actual hypoglycemia. In 1958, he presented his views in a series of articles in Woman's Day magazine, which led the New York Medical Society to censure him [4]. In 1967, the Westchester Medical Society advised him to abandon his "hypoglycemia" treatment [4].

Tintera's ideas were aggressively promoted by the Hypoglycemia Foundation, which he founded in the 1950s. The foundation's goal was to "put recognition and treatment of hypoglycemia on a par with diabetes" and to alert physicians to that condition "and indoctrinate them in its proper treatment." [4] Its publications claimed that hypoglycemia was an elusive diagnosis that could cause or contribute to:

chronic anxiety; rheumatoid arthritis; migraine headaches; nervousness and irritability; high-IQ youngsters called underachievers, asthmatic conditions; vasomotor rhinitis; Meniere's disease; miscarriages and premature births; backaches; eczema; allergies; epilepsy; homosexuality; disobedient, recalcitrant or delinquent children; gout; neuropsychiatric disorders; post duodenal bulb syndrome; susceptibility to respiratory infections [5].

In 1968, the Journal of the American Medical Association advised physicians that there was no scientific basis for the claims made by the foundation and that its literature contained "many errors" and some "bizarre statements." [4] In 1972, The Medical Letter concluded:

Many persons believe that hypoglycemia can cause disorders such as arthritis, alcoholism, drug addiction, insomnia, chronic fatigue, loss of libido, and schizophrenia. . . . The treatment usually recommended is avoidance of coffee and sweets and injections of adrenocortical extract. . . .

If physicians lack enthusiasm for such therapy, it is with good reason; hypoglycemia has not been a common finding, and when it does occur, it demands quite different treatment. Many of the symptoms and disorders listed by the Foundation respond to placebo therapy (particularly injections, as of adrenocortical extract, an obsolete preparation), and favorable results in trials that are not well controlled cannot be accepted as convincing evidence for the claims. . . .

Contrary to the belief of those who attribute many common ailments to hypoglycemia, it is an uncommon disorder. . . . When adrenal insufficiency is the cause of hypoglycemia, treatment calls for administration of sodium chloride, fluids, and either hydrocortisone or other glucocorticoids. In the treatment of hypoglycemia, there is no useful place for estrogens, testosterone or other anabolic agents, or adrenal cortical extract, an obsolete preparation once used for the treatment of Addison's disease [6].

In January 1978, the FDA sent regulatory letters to 78 drug firms in which it said that ACE products represented a substantial risk of undertreatment because of the drug's low potency and therefore posed a significant potential hazard to patients with adrenal insufficiency. The FDA medical officer responsible for the initial actions against ACE also noted that no studies had demonstrated that ACE was safe or effective for the treatment of hypoglycemia [7]. After Rep. Barry M. Goldwater, Jr. (R-CA), questioned whether the FDA's decision was justified, the General Accounting Office concluded that it was [7].

Most companies responded to the FDA's letter by stopping the sale of ACE. But a few companies here and abroad continued to market it to maverick physicians who overdiagnosed and treated "hypoglycemia." In 1989, the FDA issued an import alert barring importation of ACE from other countries [8].

In 1996, after receiving reports that patients had developed serious infections at the site of ACE injections, the FDA issued a public warning and initiated a recall of injectable ACE manufactured by Hallmark Labs and distributed by Phyne Pharmaceuticals of Scottsdale, Arizona [9,10]. Public health investigators eventually located 87 people from 16 states who had developed abscesses, some of which persisted for several months. The investigators also found that the practitioners included 19 medical doctors, 17 osteopaths, 9 naturopaths, 6 chiropractors, and 11 whose credentials were not determined [11]. The FDA also initiated a recall of ACE manufactured by a Texas firm after FDA inspectors found improper manufacturing practices and units that lacked the active ingredient [12].

According to an Associated Press news report: (a) a woman who injected ACE developed boils all over her hands, feet, arms, legs and buttocks and required three months of hospital care and intravenous antibiotic treatment over a 2-year period; (b) the woman won a $500,000 suit against Phyne Pharmaceuticals and the compounding pharmacy that had sold her the drug; and (c) Phyne and its president (James R. Critchlow Sr.) pleaded guilty to three federal felonies. The judge fined Phyne more than $11,000 and ordered the company never to sell ACE or any other unapproved drug [13]. In 2002, the judge ruled that Critchlow had violated probation and barred him from any further involvement in the pharmaceutical business. The compounder, Wellness Health & Pharmaceuticals of Birmingham, Alabama is now called Wellness Pharmacy.

In 1999, the FDA expressed concern that if ACE is extracted from the glands of cows infected with bovine spongiform encephalopathy, a user could develop new variant Creutzfeldt-Jacob disease. Although regulatory measures have reduced the chances of getting this disease from ACE are low, the FDA says that the risk should be taken seriously because the disease appears to always be fatal [14].

References

  1. Drug Evaluations, First Edition. Chicago: American Medical Association, Jan 1971.
  2. Tintera JW. The hypoadrenocortical state and its management. New York State Journal of Medicine 55(13):1-14, 1955.
  3. Tintera JW. The hypoadrenal state. Presented at the annual seminar of the Adrenal Metabolic Research Society of the Hypoglycemia Foundation, Inc. Jan 16-19, 1969.
  4. Low blood sugar: Fact and fiction. Consumer Reports, July 1971, pp 44-46.
  5. Hypoglycemia and me? You can bet your sweet life! (pamphlet) Scarsdale, NY: Hypoglycemia Foundation, 1966.
  6. The Medical Letter, Jan 21, 1972.
  7. Adrenal Cortical Extracts Taken Off market. GAO Report HRD-81-61, April 20, 1981.
  8. Unapproved new drugs promoted in the United States. Import Alert #66-41, March 2 1989.
  9. Nationwide alert on Hallmark Labs injectable adrenal cortex extract. FDA news release P96-13, Aug 30, 1996.
  10. Infection with Mycobacterium abscesses associated with intramuscular injection of adrenal cortex extract—Colorado and Wyoming, 1995-1996. MMWR 45:713-715, 1996.
  11. Galil K and others. Abscesses due to Mycobacterium abscesses linked to injection of unapproved alternative medication. Emerging Infectious Diseases 5:681-687, 1999.
  12. List of drug products that have been withdrawn or removed from the market for reasons of safety or effectiveness. Federal Register 64:10944-10947 1999.
  13. FDA oversight of drugs fails to protect many patients. Intelihealth Web site, accessed July 23, 2003.
  14. FDA Enforcement Report, Oct 9, 1996.
This article was revised on February 6, 2008.

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