Graves' disease in a 3 year-old patient with agranulocytosis due to anti-thyroid drugs: Radioiodine ablation therapy as an effective alternative. / Enfermedad de Graves en un paciente de 3 años con agranulocitosis asociada a fármacos antitiroideos: terapia ablativa con radioyodo como una alternativa eficaz.

The case is presented of a 3 year-old girl with mitochondrial disease (subacute necrotizing encephalomyelopathy of Leigh syndrome), v-stage chronic kidney disease of a diffuse mesangial sclerosis, as well as developmental disorders, and diagnosed with hyperthyroidism Graves-Basedow disease. Six weeks after starting the treatment with neo-carbimazole, the patient reported a serious case of agranulocytosis. This led to stopping the anti-thyroid drugs, and was treated successfully with 131I ablation therapy. The relevance of the article is that Graves' disease is uncommon in the paediatric age range (especially in children younger than 6 years old), and developing complications due to a possible late diagnosis. Agranulocytosis as a potentially serious adverse effect following the use of anti-thyroid drugs, and the few reported cases of ablation therapy with 131I at this age, makes this case unique.

[An elderly case with pseudogout exacerbated by the administration of granulocyte-colony stimulating factor during drug-induced granulocytopenia].

A 82-year-old woman was admitted because of dehydration and chronic renal failure. Although her renal function was improved by hydration, granulocytopenia (granulocyte number 645/mm3) occurred. Treatment with a relatively high dose of H2 blocker for one month before admission may have caused the granulocytopenia. To prevent possible infection in the patient, we administered 75 g of granulocyte-colony stimulating factor (G-CSF) for 5 consecutive days but 4 days after commencement of administration of G-CSF, pain in both knee joints suddenly appeared. Synovial fluid aspiration revealed granulocytosis (10,400/mm3) and deposition of calcium pyrophosphate dihydrate in the knee joints. The level of G-CSF in the synovial fluid was increased in the joints (700 pg/ml), compared with the serum concentration (62 pg/ml). Furthermore, the concentrations of interleukin-6 and interleukin-8 were markedly increased in the synovial fluid. The results indicated that her pseudogout exacerbation by G-CSF was at least in part explained by the increased production of cytokines in the knee joints. Because the prevalence of pseudogout and gout is overwhelming in the elderly, the possibility of GCSF induced exacerbation of joint pain should be carefully considered in elderly patients.

[Granulocyte colony-stimulating factor (G-CSF) in the early stage of thyrostatic-induced agranulocytosis]. / Granulozytenkolonie-stimulierender Faktor (G-CSF) in der Frühphase der thyreostatika-induzierten Agranulozytose.

After coronary angiography a 66-year-old man developed manifest hyperthyroidism (fT3 8.7 pg/ml, fT4 3.7 ng/dl) marked by tremor, restlessness and sweating. The hyperthyroidism was controlled by high dosages of thiamazole (240 mg daily) and lithium (24-36 mmol daily). But the white cell count dropped from 8,000/microliters to 4,900/microliters on the eighth day. Although the thiamazole dose was reduced to 40 mg daily, the granulocytopenia became more severe and, on the 24th day of treatment, agranulocytosis occurred (neutrophilic granulocyte count 200/microliters), although the thiamazole had been discontinued. The patient was then isolated and treated prophylactically with ofloxacin. Simultaneously he received 5 micrograms/kg granulocyte-colony stimulating factor (G-CSF) subcutaneously daily for 7 days. On the sixth day of this treatment the granulocyte count was 520/microliters, next day 3,800/microliters, and after a further 2 days it overshot to 31,000/microliters, then gradually returning to normal values. -It is recommended that the use of G-CSF should be considered also for thyrostatic-induced agranulocytosis, because it may shorten this dangerous phase.

[Chronic idiopathic neutropenia improved by recombinant granulocyte colony stimulating factor].

A 55-year-old man was admitted to our hospital for the evaluation of neutropenia. On physical examination, he had apthae and splenomegaly. CBC showed 1,000/microliter WBC with 5% neutrophils, and microcytic anemia consistent with iron deficiency. Bone marrow examination revealed a marked decrease of mature neutrophils, but normal percentage of immature myeloid cells. There was no morphological abnormality in the hemopoietic cells. He had no drug or family history responsible for the neutropenia. Anti-neutrophil auto-antibody was negative. Hence, a diagnosis of chronic idiopathic neutropenia (CIN) was made. He developed frequent episodes of infection such as balanitis, peri-anal infection, gingivitis, and pharyngitis. He was treated with steroid pulse therapy, anabolic hormone, and high dose gamma-globulin infusion, but no significant improvement occurred. Then, recombinant granulocyte-colony stimulating factor (rG-CSF) was started. The neutrophil count was normalized by the 7th day of 5 micrograms/kg/day rG-CSF administration. The administration of G-CSF was discontinued after a 14-day course. Thereafter, the neutrophil count remained at near normal level (approximately 1,500/microliter) and there have been no episodes of infection in the last 5 months. However this cannot be explained simply by the direct effect of rG-CSF on the myeloid precursors; rather, it suggests some unknown effect of G-CSF on the bone marrow microenvironment regulating myeloid hemopoiesis. We consider this to be a rare case of CIN with frequent episodes of infection, which was successfully treated with G-CSF.

Use of blood and blood components.

The indications for transfusions are anemia compromising delivery of oxygen, acute blood loss, cardiopulmonary bypass, exchange transfusion, maintenance of hemostasis, and sepsis associated with granulocytopenia. When transfusion therapy is indicated, only that component of whole blood which is needed for correction of the problem should be given. The options for use each component have been discussed.