The PPH Epidemic Related to Anorexic Drug Use


Guerry R. Thornton, Jr.
Copyright © - Guerry R. Thornton, Jr. 1997


Primary pulmonary hypertension is a rare, and often fatal malady. It took the international medical community over 100 years of study before PPH became a formal disease category. The progress which lead to the discovery of PPH began in 19th century Europe and lead to the conclusion by Swiss medical experts that the 1967 PPH outbreak in Central Europe was caused by appetite-suppressant drugs. This is the landmark diagnosis that may have eventually contributted to the PPH warnings on weight loss drugs. The history and adequacy of the warnings is at issue in liability suits related to Fen-Phen.

The complexity of PPH as a disease makes it essential that Fen-Phen lawyers and medical experts understand the early history of primary pulmonary hypertension and the European PPH outbreak in the 1960s. To assist our research related to fenfluramine and Redux product claims, I travelled to France and Switzerland in May, 1998, to research the European experience hoping to advance legal efforts in the United States.

The contacts I made in Montreux and Bern brought me a new understanding how PPH is linked to diet drugs. I am indebted to Dr. Claude Rossel, Director of the Biotonus Clinic in Montreux and Regulia Wittmer, Spa Director at Le Mirador in Vevey, for their valuable guidance. It was through them that I discovered the work of Dr. Hans Peter Gurtner in Bern, whose research laid the foundation for the linkage between appetite-suppressant drugs and primary pulmonary hypertension.

Based on interviews, library reviews, medical studies and internet research, I will provide an overview of the European PPH experience and attempt to relate it to the progress of Fen-Phen litigation in our courts.


The great 19th Century physician Dr. William Osler admonished his colleagues to "listen to your patient. He is telling you the diagnosis." This lesson became the tool that cracked the medical mysteries of PPH, the final diagnosis after all other cause of pulmonary hypertension are eliminated. The treating doctor is Hans Peter Gurtner at Bern University. His patient is given the name "Frau Z" to protect her privacy.

Frau Z presented at Dr. Gurtner's cardiology clinic in February, 1967. Dr. Gurtner carefully listened to her complaints and followed Dr. Osler's advice as he questioned his patient about predisposing conditions that may have contributed to her breathing problems. At that time, the accepted causes of pulmonary hypertension were heart failure, abnormalities of the heart, and pulmonary embolus, or blood clots that break loose and lodge in the fine arteries of the lung. Frau Z had none of these conditions at the onset of her symptoms.

Dr. Gurtner's review of Frau Z's cardio-pulmonary systems revealed that she indeed had pulmonary hypertension, but his investigation of the known causes were not supported by her history. She had no heart disease, no destruction of lung tissue and no congenital defect. Her lungs were resisting the flow of blood and her right ventricle was decomposing from being over-worked, leaving her body oxygen starved. Frau Z's condition was a "primary" disease, meaning that it could not be linked to the known causes. Gurtner HP, Journal Suisse de Medicine 1968; 41:1579-1589 & 1968; 43:1695-1707.

PPH is a rare disease and Dr. Gurtner's last patient had been seen in 1965. It had been a decade since heart catheters were first used to diagnose pulmonary malfunctions, and this new tool helped his clinic uncover about one case per year. The advent of cardiac catheterization helped prove that pulmonary arteriosclerosis was a late stage consequence of pulmonary hypertension and not the cause. These developments gave Dr. Gurtner the insight to deal with a stream of PPH patients which lead to the suspicion that some "outside" agent might be the culprit in this deadly disease.

The Bern team had an enhanced awareness that a new suspect might solve the PPH mystery and the next few months revealed the initial stages of a PPH epidemic in a pool of patients, mostly women. By early 1968, the Bern clinic had diagnosed 14 cases of PPH, and 2 had died within a few months. This increase compelled Gurtner to ask why and to delve deeper into the habits of each patient. They were questioned about contacts with chemicals, travels, fabrics, cosmetics, pets, parasites, allergens, hobbies and every possible link. Gurtner HP, Pulmonale Hypertonie, Medizinishe Welt 1972; 23:1036-1041.

The nature of the cases required an exhaustive search and new techniques. Although the clinical picture of the patients were the same as they had been in prior cases, the 1967 epidemic was different in these respects: PPH progressed faster, pulmonary embolism was less common, more than half were only a little overweight and "around 80% reported having taken an appetite suppressant" before any symptoms. Before 1967, most PPH patients were under-weight, with a mean 8 percent below Swiss norms. In 1967, the average patient was 12 percent over, and many were morbidly obese. The ones who were not, had just lost significant weight.

After an detailed analysis of each PPH victim's history, Dr. Gertsch, part of Gurtner's team, concluded: "There was only one overriding, common factor. Among the 23 patients we investi-gated . . . 13 reported they had undergone a weight reduction program using aminorex fumarate (Menocil)." Based on this obser-vation, the Bern team inquired of other health care providers, pharmacists and agencies to discover PPH victims who had denied Menocil consumption. They also looked at the relation between the first symptom, usually shortness of breath, and the first use of an appetite-suppressant. The intervals supported a link between the drugs and the onset of PPH.

As another factor in the Bern clinical picture, amphetamines or "speed", played a role in some cases. In the PPH group, 3 used amphetamine derivatives prior to Menocil and 1 had only used amphetamines a few years prior to any problems associated with pulmonary hypertension. Before the end of the epidemic, of 67 patients seen from 1967 until mid-February of 1970, 60 were women, 50 of whom had used aminorex, and 7 were men, 3 of whom used the drug. The disease progressed faster than normal, and 11 died within a few years.

The reports show that Dr. Gurtner presented the Bern inves-tigation to the Swiss Society for Internal Medicine in Chur on May 10, 1968. While they reported a 20-fold increase in PPH cases, the report concentrated on clinical evaluation and treat-ment and gave etiology, or causation, secondary consideration. However, the PPH study did lead the Bern group to press for early regulatory action. One month after the Chur report, Gurtner and his colleagues communicated their findings to the Swiss Inter-cantonal Pharmacetical Control Agency, which recommended that the drug be taken off the market. Gurtner HP "Aminorex & Pulmonary Hypertension", Cor Vasa 1985;27:160.

Based on concerns about safety raised by the Gurtner report, McNeil Laboratories, the U.S. manufacturer of aminorex, notified the FDA that it would suspend its research. Later, the British authorities declined permission for the drug to be used in clinical trials. In October of 1968, the European distributor of Menocil, Cilag Chemie, suspended sales as a precaution while noting a clear "lack of clear scientific evidence incriminating Menocil." Drug regulators in Austria and Germany took similar action. Cahal DA, "Appetite Suppressants & Pulmonary Hyper-tension" (Letter) Lancet 1969;i:947; Greiser, Lung Hypertension, Die Zeit (Hamburg) 12/15/68, P. 30.

As a postscript to Gurtner's research, five years later 23 cardiology center in Switzerland, Germany and Austria collected their patient data to more fully evaluate the epidemic. This cases included 582 patients with PPH from 1960 through 1972. The incidence of diagnosis had not varied through 1966. The number of cases with PPH suddenly doubled in 1967, doubled again the next year and stayed elevated in 1969. The reported cases then fell as sharply as they had risen in 1970 and 1971. By 1072, the disease was almost as rare as it had been before the epidemic. Experts who review the data attributed the changes to patients who said they had used Menocil. In countries where Menocil was not on the market, experts saw no increase in PPH cases. Greiser & Gahl, "Aminorex & Incidence of PPH", German Internal Medicine Journal, 1972;78:1073-1076.

The disease pattern in other studies was equally incrimi-nating for Menocil. PPH was most common in middle age women, and the incidence of the disease was tied to the duration of use of the drug. Greiser estimated a risk of one in one thousand for those who took one or two of the 40 tablet packs, and the risk rose rapidly with higher consumption. In women who had taken 5 to 6 packs, the rate was one per one hundred; and it rose to one in ten for those who used 8 packs or more. The issue of dose- response and incidence rates between Menocil and PPH is a vital concern when medical-legal experts compare Menocil to anorexigens in pending diet pill liability suits.

Aminorex fumarate was first discovered in the United States by McNeil in 1960. Peters & Gourzis, Pharmacology & Aminorex in the United States, Hans Huber Publishers, Bern, 1970. It was found to suppress appetites in rats and had a similar effect on humans. It is chemically related to the natural stimulant ephedrine. It is related to epinephrine, the chemical mammals produce in response to danger. It may induce a mild euphoria, as it is closely related to amphetamine derivatives. Studies of early use of the drug do not reveal firm evidence linking them to PPH or other serious cardio-pulmonary diseases. This lack of early detection may be due to linking pulmonary hypertension to the traditional causes.

Reports of the PPH epidemic in English language journals appeared in 1971. A British Medical Journal account mentioned a Basel cases among long-term users of Menocil with an elevated risk of disease. This supported Greiser's view that the incident rate rose with the dosage. BMJ, 1971;1:265-266. The most important questions for medical-legal experts in the diet pill controversy is the acutal magnitude of the disease rate that can be associated with Menocil, and the extent to which the incidence rate may attach to other, similar appetite-suppressant drugs. As Greiser's prediction of risks approached almost 10 percent for prolonged use. However, these high elevations may not withstand scientific scrutiny because his results were not recorded under currently accepted reporting rules.

THE AUTHOR: Guerry R. Thornton, Jr., a lawyer in Atlanta, handles Phen/Fen claims & is counsel in the Sankey action; he has prosecuted claims in the $2.5 billion Dalkon Shield plan & the $230 million Dupont Plaza Hotel disaster; he is a member of The Association of Trial Lawyers of America & has published articles on mass tort litigation in Trial Magazine & The National Law Journal; his Internet site is:

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