Case Report

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A 42-year-old man who had had splenectomy for spontaneous splenic hematoma in 1976 was first referred to the department of hematology in 1988 for evaluation of polycythemia. His hematologic variables were the following: hemoglobin level, 187 g/L; hematocrit, 0.58; total blood volume, 88 mL/kg body weight (normal value less than 80 mL/kg body weight); erythrocyte mass, 41 mL/kg body weight; and plasma volume, 46 mL/kg body weight. Serum erythropoietin levels (measured by immunoenzyme assay) were barely detectable at 2 U/L (Table 1). The bone marrow aspirate was hypercellular, with a predominance of erythroid and megakaryocytic progenitors. Marrow samples were then tested by using an in vitro colony-forming unit erythroid assay. Under serum and serum-free conditions, marrow cultures showed spontaneous growth of erythroid progenitors in the absence of exogenous erythropoietin. Several features excluded the diagnosis of secondary polycythemia: normal oxygen saturation, no cardiac or hemoglobin abnormalities, no tumor lesions, and no history of smoking. Leukocyte and platelet counts were normal, and polycythemia vera was diagnosed on the basis of spontaneous in vitro growth of erythroid progenitors [7, 8]. The patient then had therapeutic phlebotomies.

In 1990, the patient was referred to the department of endocrinology for evaluation of acromegaly. His serum growth hormone (throughout a diurnal hourly profile), serum IGF-1, and urinary growth hormone levels were increased (Table 1). Results of assays for other pituitary hormones were normal. An 8-mm intrasellar pituitary growth hormone-secreting adenoma was surgically removed.

Six months after surgery, serum growth hormone levels, IGF-1 levels, and other pituitary functions were normal, and the hematologic abnormalities had resolved (Table 1). Results of in vitro colony assays no longer showed spontaneous colony growth. After a 4-year follow-up, we have seen no evidence of acromegaly or polycythemia.

Discussion

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This patient presented with diagnostic features of polycythemia vera, including an increased hematocrit, erythrocyte mass, and total blood volume; marrow hypercellularity; low serum erythropoietin levels; and spontaneous growth of erythroid progenitors. Spontaneous erythroid progenitor growth, a well-accepted hallmark of myeloproliferative diseases, is known to persist regardless of the course or treatment of the disease [7, 8]. In our patient, the curative effect on hematologic variables of removing the growth hormone or IGF-1 stimulus strongly suggests that hypersensitivity of an abnormal progenitor clone to IGF-1 contributed, at least in part, to the development of polycythemia.

In retrospect, some of the hematologic abnormalities could have been caused by underlying acromegaly. In patients with acromegaly, the hemoglobin level and hematocrit are usually normal and the bone marrow is usually normocellular. We did not observe spontaneous growth of colony-forming unit erythroids in marrow cultures from two patients with active acromegaly (unpublished observations). Although most untreated patients with acromegaly have a normal hematocrit, they also have substantially higher plasma volume, erythrocyte mass, and total blood volume than normal persons; these indices return to normal after treatment [9, 10]. In our patient, the return of these variables to normal may simply reflect the correction of growth hormone levels. After therapy, the hematocrit, erythropoietin level, and in vitro growth of erythroid progenitors also returned to normal, suggesting that growth hormone, IGF-1, or both also induced these abnormalities.

Spontaneous erythroid progenitor growth in vitro is specifically observed with polycythemia vera [7, 8] and is caused, at least in part, by low IGF-1 levels in serum or nondelipidated albumins [11]. Polycythemia vera erythroid progenitors are hypersensitive to low IGF-1 levels compared with normal progenitors [2].

In our patient, the findings suggest that high serum levels of growth hormone, IGF-1, or both may have enhanced the proliferation of an abnormal, hypersensitive progenitor clone to IGF-1. The patient will be followed to determine whether a quiescent, abnormal clone has the potential to recur in the absence of excess hormonal stimulation.

Acknowledgments: The authors thank Drs. Lorian and Helal, who referred the patient to the Department of Endocrinology at the Hopital Bicetre.

Dr. Casadevall: Service d'Hematologie, Hopital Raymond Poincare, 104 Boulevard R. Poincare, F-92380, Garches, France. Dr. Abboud: Department of Medicine/Nephrology, University of Texas Health Science Center, 77 Floyd Curl Drive, San Antonio, TX 78248.