Correspondence

Correction

Octreotide for Tumor-Induced Osteomalacia

N Engl J Med 2002; 346:1748-1749May 30, 2002

Article

To the Editor:

Seufert et al. (Dec. 27 issue)1 describe a man with tumor-induced (oncogenic) osteomalacia, in which the subcutaneous administration of octreotide abolished renal tubular phosphate wasting. The authors suggest that in patients who cannot undergo surgery, phosphate wasting may be relieved by treatment with somatostatin analogues, provided that the tumor expresses somatostatin receptors. We believe that this statement is a misleading generalization. We observed a case of oncogenic osteomalacia in which total-body octreotide scintigraphy detected the tumor. We therefore intravenously administered octreotide at a dose of 600 μg per day for six days — a dose in the same order of magnitude as the dose administered subcutaneously by Seufert et al. We did not observe any effect on the biochemical variables (Figure 1Figure 1Serum Phosphorus Level and Threshold for Renal Tubular Reabsorption of Phosphate during Intravenous Octreotide Therapy in a Patient with Tumor-Induced Osteomalacia.).

The lack of response in our patient could be attributed either to the heterogeneous distribution of somatostatin receptors among tumor cells2,3 or to the prevalence of cells lacking somatostatin receptors, as has been documented in some neuroendocrine tumors.3 In the latter case, it is possible that treatment with the analogues of somatostatin affects only some areas of the tumor. In fact, octreotide binds with high affinity to somatostatin receptor subtypes 2 and 5 and with moderate affinity to subtype 3 but does not bind to subtypes 1 and 4. Finally, it is unclear whether the secretion of phosphaturic factors by the tumor cells is modulated by somatostatin receptors. In any case, we do not support the widespread use of somatostatin analogues, especially considering their cost.

Federica Paglia, M.D.
Simona Dionisi, M.D.
Salvatore Minisola, M.D.
Università degli Studi di Roma La Sapienza, 00193 Rome, Italy
salvatore.minisola@uniroma1.it

3 References

1. 1

   Seufert J, Ebert K, Muller J, et al. Octreotide therapy for tumor-induced osteomalacia. N Engl J Med 2001;345:1883-1888
   Full Text | Web of Science | Medline

2. 2

   Wynick D, Anderson JV, Williams SJ, Bloom SR. Resistance to metastatic pancreatic endocrine tumours after long-term treatment with the somatostatin analogue octreotide (SMS 201-995). Clin Endocrinol (Oxf) 1989;30:385-388
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   Lamberts SWJ, van der Lely A-J, de Herrder WW, Hofland LJ. Octreotide. N Engl J Med 1996;334:246-254
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Paglia et al. point out that octreotide therapy does not affect phosphate wasting in all patients with tumor-induced osteomalacia. We have become aware of similar cases characterized by the obvious contradiction of positive results on octreotide scintigraphy and little therapeutic effect of the compound. By reporting our single case, we certainly did not mean to imply that the findings could be generalized to all tumors. The two findings we wanted to stress are that tumors can be diagnosed with the use of octreotide scans if conventional localization procedures fail and that a therapeutic trial of octreotide may be worthwhile in individual patients. Furthermore, this case might be considered as a paradigm for the novel concept of secretory control of phosphaturic substances in humans. We notice differences between the two patients such as the route of octreotide administration and the basal phosphate reabsorption threshold — differences that can be evaluated only if one has the opportunity to analyze more patients. However, fibroblast growth factor 23 was recently reported to suppress 25-hydroxyvitamin D₃ 1α-hydroxylase activity in the kidney,1 which may, in part, explain the low levels of 1,25-dihydroxyvitamin D₃ in patients with tumor-induced osteomalacia.2 This finding could contribute to the low renal tubular threshold of phosphate reabsorption. Concomitant 1,25-dihydroxyvitamin D₃ treatment in our patient may have had a permissive effect on normalization of phosphaturia. The relative heterogeneity of underlying histologic entities3,4 may serve as an alternative explanation for the lack of an effect of octreotide in octreotide-positive tumors. Although tumor-induced osteomalacia is a rare disorder, we propose that systematic analysis of somatostatin-receptor expression has relevance to tumor-derived phosphatonin secretion.

In Table 1 of our article, the threshold for renal tubular reabsorption of phosphate before octreotide therapy should have been 0.2 mmol per liter, not 0.6 mmol per liter.

Jochen Seufert, M.D.
Franz Jakob, M.D.
University of Würzburg, 97070 Würzburg, Germany
j.seufert@mail.uni-wuerzburg.de

4 References

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   Strewler GJ. FGF23, hypophosphatemia, and rickets: has phosphatonin been found? Proc Natl Acad Sci U S A 2001;98:5945-5946
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   Crouzet J, Mimoune H, Beraneck L, Juan LH. Hypophosphatemic osteomalacia with plantar neurilemoma: a review of the literature (100 cases). Rev Rhum Engl Ed 1995;62:463-466
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   Park YK, Unni KK, Beabout JW, Hodgson SF. Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions. J Korean Med Sci 1994;9:289-298
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   M Odette Gore, Brian J Welch, Weidong Geng, Wareef Kabbani, Naim M Maalouf, Joseph E Zerwekh, Orson W Moe, Khashayar Sakhaee. (2009) Renal phosphate wasting due to tumor-induced osteomalacia: a frequently delayed diagnosis. Kidney International 76:3, 342-347
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   Michèle Duet, Samar Kerkeni, Raja Sfar, Cécile Bazille, Frédéric Lioté, Philippe Orcel. (2008) Clinical Impact of Somatostatin Receptor Scintigraphy in the Management of Tumor-induced Osteomalacia. Clinical Nuclear Medicine 33:11, 752-756
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   S. Harish, E. Jurriaans, E. Jan, M. Sur, N. Colterjohn. (2008) Giant cell tumour of soft tissue causing oncogenic osteomalacia: report demonstrating the use of octreotide scintigraphy in tumour localization. Clinical Radiology 63:1, 101-107
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   Florencia Halperin, Ronald J Anderson, Jean E Mulder. (2007) Tumor-induced osteomalacia: the importance of measuring serum phosphorus levels. Nature Clinical Practice Endocrinology & Metabolism 3:10, 721-725
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   Marianne S. Elston, Inge J. Stewart, Roderick Clifton-Bligh, John V. Conaglen. (2007) A case of oncogenic osteomalacia with preoperative secondary hyperparathyroidism: Description of the biochemical response of FGF23 to octreotide therapy and surgery. Bone 40:1, 236-241
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