Correspondence

Pleuropulmonary Disease in a Man with Diabetes Who Was Treated with Troglitazone

N Engl J Med 1998; 339:1400November 5, 1998

Article

To the Editor:

Troglitazone is an antidiabetic drug that decreases hyperglycemia by increasing the sensitivity of peripheral tissue to insulin.1 Its most serious adverse effect is hepatic dysfunction, which occurs in a small percentage of patients.2 We describe a case of pleuritis in a patient who was treated with troglitazone.

The patient was a 47-year-old man who had been treated for hypertension and type 2 diabetes mellitus with slow-release nifedipine and glyburide, respectively. He had smoked 1 1/2 packs of cigarettes daily for 18 years but had stopped 10 years earlier. He had no history of drug allergy or occupational exposure to substances that cause lung disease, and he had had a normal chest film two months earlier. Because his glycosylated hemoglobin concentration was 7.0 percent (normal, 4.0 to 5.8 percent), the glyburide was discontinued and twice-daily treatment with 200 mg of troglitazone was begun.

One week later, a productive cough, dyspnea, and night sweats developed without arthralgia, rash, edema, or fever. Treatment with antibiotics and antitussive drugs did not ameliorate the symptoms. A chest film obtained two weeks later revealed blunting of the costophrenic angle, with slightly blurred vascular markings in both lower lung fields, suggesting the presence of pleuritis and possible interstitial pneumonitis (Figure 1Figure 1Chest Film Obtained in a Patient with Type 2 Diabetes Treated with Troglitazone, Showing Bilateral Pleuritis and Possible Interstitial Pneumonitis in the Lower Lobes.). The leukocyte count was 7000 per cubic millimeter, with a normal differential count, and the erythrocyte sedimentation rate was 14 mm per hour. Serum aminotransferase concentrations were normal. Cultures of sputum for bacteria and Mycobacterium tuberculosis were negative, and no eosinophils were found in a sputum sample. The troglitazone was discontinued, and the patient became asymptomatic within 24 hours. A chest film obtained six days later was normal.

The temporal association between the initiation of troglitazone therapy and the occurrence of pleuropulmonary disease and between the cessation of therapy and the resolution of the pleuropulmonary disease suggests a causal relation.3

Hideo Koshida, M.D.
Kazuhiko Shibata, M.D.
Tomio Kametani, M.D.
Kohseiren Takaoka Hospital, Toyama 933-8555, Japan

3 References

1. 1

   Imura H. A novel antidiabetic drug, troglitazone -- reason for hope and concern. N Engl J Med 1998;338:908-909
   Full Text | Web of Science | Medline

2. 2

   Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998;338:916-917
   Full Text | Web of Science | Medline

3. 3

   Rosenow EC III. Drug-induced pulmonary disease. In: Murray JF, Nadel JA, eds. Textbook of respiratory medicine. 2nd ed. Vol. 2. Philadelphia: W.B. Saunders, 1994:2117-44.
   

Author/Editor Response

A spokesperson for Parke-Davis Pharmaceutical Research, the manufacturer of troglitazone, replies:

To the Editor: We appreciate the opportunity to comment on the report by Koshida et al. of a patient in whom possible interstitial pneumonitis developed after one week of troglitazone therapy. We have reviewed our controlled-clinical-trial data base, which includes data on more than 2700 patients who were treated with troglitazone, and can identify no similar cases. A further review of post-marketing reports of adverse events in the United States, where more than 1.3 million patients have been treated with troglitazone, also failed to reveal any similar cases. Given the onset of this event relative to the initiation of troglitazone therapy, one would have to postulate a hypersensitivity or allergic reaction, which is not substantiated by the presence of eosinophilia in either the patient's peripheral-blood smear or the sputum sample. In the absence of other, similar reports and given the unusual nature of this case, it is difficult to conclude that there was a direct cause-and-effect relation.

Randall W. Whitcomb, M.D.
Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105

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