Hypothyroidism and resistance to human recombinant erythropoietin

Sir,

Many possible causes of resistance to human recombinant erythropoietin (rh-EPO) have been reported in patients with renal failure [1]. However, some factors remain controversial. We report a haemodialysis patient with a diminished response to rh-EPO in association with hypothyroidism.

The patient was a 62-year-old female who was treated with regular haemodialysis since 1993. She had a past medical history of primary hypertension and pulmonary tuberculosis. During 5 years, haemoglobin level ranged between 10.2 and 11.7 g/dl with rh-EPO alpha treatment of 9000 IU/week. In 1998, the patient developed secondary hyperparathyroidism (iPTH 1845 pg/ml) and worsened anaemia (Hb 9 g/dl) despite increasing doses of rh-EPO up to 15 000 IU/week. Successful subtotal parathyroidectomy was performed in October 1998 together with subtotal thyroidectomy because of nodular goiter. Haemoglobin level remained unchanged with normochromic, normocytic erythrocytes and normal leukocytes and platelets. All usual causes of epoietin resistance were ruled out, such as infection, malignancy, iron or vitamin deficiency states, aluminum overload and underdialysis. A few months later, hypercholesterolaemia appeared and subclinical hypothyroidism was diagnosed. Thyroid-stimulating hormone was >50 mIU/l, free triiodothyronine 4.4 pmol/l and free thyroxine 9 pmol/l. Thyroxine replacement therapy was started in April 1999 and the dose was progressively increased to 225 µg/day. Normalization of serum thyroid hormone levels was accompanied by improved response to epoetin (Figure 1). Haemoglobin level increased to 11.5 g/dl with a parallel reduction of rh-EPO dose to 6000 IU/week.



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Fig. 1. Evolution of haemoglobin level and thyroid stimulating hormone.

 
These findings, as in two previous reports [2,3], strongly support the hypothesis that hypothyroidism may contribute to epoietin resistance in chronic haemodialysis patients.

Conflict of interest statement. None declared.

Malik Touam1, Bruno Guéry1, Christophe Goupy1, Victorio Menoyo2 and Tilman Drüeke1

1Service de Néphrologie and Inserm U507 Hôpital Necker Paris 2Centre Henri Küntziger AURA Paris France Email: malikpablo{at}wanadoo.fr

References

  1. Richardson D. Clinical factors influencing sensitivity and response to epoetin. Nephrol Dial Transplant 2002; 17 [Suppl 1]: 53–59[Medline]
  2. Dilek M, Akpolat T, Cengiz K. Hypothyrodism as a cause of resistance to erythropoietin. Nephron 2002; 92: 248[CrossRef][ISI][Medline]
  3. Sungur C, Erbas T, Akpolat T et al. Resistance to human recombinant erythropoietin in hypothyroidism. Acta Haematol 1992; 88: 162[ISI][Medline]




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