Three hundred and forty–six patients with acute pulmonary tuberculosis were allocated at random to treatment with chemotherapy alone (streptomycin 1 g., sodium PAS 16g. and isoniazid 300 mg. daily — the Control series, 119 patients), or the same chemotherapy with three months corticotrophin 30 i.u. daily (the A.C.T.H. series, 111 patients) or the same chemotherapy with three months prednisone 30 mg. daily (the Prednisone series, 116 patients). The chemotherapy was prescribed for six months and the patients were treated in bed in hospital during this time; chemotherapy was continued without hormones in all three series, and observations were made for a further six months.
For patients allocated to the A.C.T.H. series, the purified preparation ‘Cortrophin ZN’ was at first used; subsequently a cruder preparation ‘Cortrophin Z’ (not now available) was prescribed. The efficacies of the two products were similar, but ‘Cortrophin Z’ produced considerably more side-effects than ‘Cortrophin ZN’. It is possible that the dosage of the corticotrophin used was too low in some patients, but it would be necessary to adjust the dosage for each patient's adreno-corticol activity in order to avoid undesirable side-effects.
In the A.C.T.H. and Prednisone series there was rapid improvement in clinical condition in the first three months, as observed by the clinician and as shown by the increase in weight, and falls in the erythrocyte sedimentation rate and average temperature; the improvement was maintained after stopping the hormones. The progress of the Control patients was slower but by twelve months the improvement was similar to that of the two hormone series.
The A.C.T.H. and Prednisone series had significantly less residual radiographic shadowing at three months, and the Prednisone series at six and twelve months, than the Control series. Transient radiographic deterioration between three and four months was observed in 47 patients (5 Control, 12 A.C.T.H. and 30 Prednisone). Clinical ‘rebound’ phenomena occurred in 6 A.C.T.H. and 34 Prednisone patients.
There was little difference between the three series in terms of cavitation changes and sputum conversion at any time. Almost all the patients in the three series had negative cultures at six months, and all but 1 Control patient at nine and 1 at twelve months.
Severe hypersensitive reactions to streptomycin, PAS or isoniazid, streptomycin toxicity or PAS intolerance, which necessitated a change of the chemotherapy, occurred in 31 patients (16 Control, 7 A.C.T.H. and 9 Prednisone); in 13 of these (8 Control, 3 A.C.T.H. and 2 Prednisone) the reactions occurred during the first three months. A further 7 patients (5 Control and 2 A.C.T.H.) had prednisone added to their chemotherapy because of lack of progress.
In 22 patients (15 A.C.T.H. and 7 Prednisone) side-effects caused the hormone therapy to be changed or stopped before the end of the prescribed three months. Of these, 6 A.C.T.H. patients (given ‘Cortrophin Z’) developed psychotic manifestations but all recovered on stopping the hormone. A further 18 patients (9 A.C.T.H. and 9 Prednisone) had transient reactions but only a brief interruption of the hormone.
It is concluded that prednisone has a place, with chemotherapy, in the treatment of selected cases of acute, extensive pulmonary tuberculosis, but that corticotrophin, in the dosage used in the present trial, was less effective.
