Sternal marrow studies in thyrotoxicosis treated with thiouracil and review of literature regarding thiouracil effects on blood.

A review of the available literature to date shows 1914 casest of thyrotoxicosis in which thiouracil was employed. This does not include the use of thiourea or other related compounds nor the use of thiouracil in any condition but thyrotoxicosis. Forty-four cases (1.3 per cent) had resulting agranulocytosis, and of these, i per cent) died because of the agranulocytosis. Ninety-three patients per cent) developed significant leukopenia. There are obvious disadvantages in this method of estimating the occurrence of these complications. However, two recent articles have presented data on the same subject and the results are similar (see table i). There are unavoidable duplications in these two series and in our review of the literature. Table 2. shows a brief summary of the 44 reported cases of agranulocytosis due to thiouracil. Eight were male and 2.6 female (io unspecified). This ratio probably approximates that of thyrotoxicosis itself. The ages ranged from i6 to 70, the average being 45 years. Marrow findings were described in i cases, but in many cases we do not know how long the agranulocytosis had existed when the marrow studies were done. In most cases the marrow was described as hypoplastic, or with “maturation arrest” in the granulocyte series, a concept first presented by Fitz-Hugh and Krumbhaar in I932.. ’ In only i case had a control marrow study been done before thiouracil was given.” Dameshek35 states that in agranulocytosis the bone marrow goes through the following stages: immediate reaction with reduced numbers of granulocyte precursors; shortly thereafter a loss of mature, then immature granulocytes takes place. if the patient survives, the granulocyte precursors reappear, and this is the stage which has frequently and perhaps erroneously been termed “maturation arrest”; the mature granulocytes then reappear. Dameshek quotes the work of Plum,35b who performed serial sternal punctures in many of his 114 cases of agranulocytosis, most of them following aminopyrine. Braun36 reports serial