The Effect of Octreotide on Parathyroid Carcinoma

Amanda M. Denney and Nelson B. Watts

University of Cincinnati Medical Center, Division of Endocrinology/Metabolism, Cincinnati, Ohio 45267

Address correspondence to: Amanda M. Denney, M.D., University of Cincinnati Medical Center, Division of Endocrinology/Metabolism, P.O. Box 670547, Cincinnati, Ohio 45267-0547. E-mail: amandamdenney{at}yahoo.com or nelson.watts{at}uc.edu.

To the editor:

In her excellent review of parathyroid carcinoma, Shane (1) states, "The long-acting somatostatin analog, octreotide, has also been reported to inhibit PTH secretion in a woman with parathyroid carcinoma metastatic to bone ... ", citing a case report by Koyano et al. (2). This encouraged us to try octreotide treatment in a 46-yr-old woman with parathyroid carcinoma metastatic to the right jugular fossa, positive on octreotide scan, causing local discomfort and hypercalcemia. We ordered a low starting dose of octreotide, 50 µg sc every 12 h; however, due to a clerical error, she received 500 µg every 12 h. Despite the high dose of octreotide, her serum calcium increased from 10.0 mg/dl before treatment to 11.1 mg/dl the next day, with no significant change in serum PTH levels (1422 pg/ml before treatment, 1543 pg/ml after). Octreotide was held temporarily and restarted 4 d later at a dose of 25 µg every 8 h. The dose was gradually increased to 50 µg every 8 h, but nausea and vomiting precluded increasing it further. After 5 d of octreotide treatment, despite aggressive hydration, her serum calcium rose to 14.5 mg/dl, and octreotide was discontinued.

Because of our disappointing experience, we reviewed the report of Koyano et al. (2) that was cited by Shane (1). They described a patient with parathyroid carcinoma metastatic to the lumbar spine and right iliac bone in whom a 200-µg dose of octreotide resulted in serum PTH "falling" from 919 pg/ml before dosing to 812 pg/ml 2 h later and "returning" to approximately 960 pg/ml 6 h later. About 2 wk later, a 7-d course of octreotide, 100 µg every 8 h, caused PTH to "fall" from 1447 pg/ml to 1164 pg/ml, but then it "rose" to 1733 pg/ml (higher than pretreatment levels) within 5 d after discontinuation. Their report does not permit judging whether these changes in serum PTH concentration might be due to random fluctuations or a true effect of octreotide.

Although Miller and Edmonds (3) reported a patient with primary hyperparathyroidism who seemed to respond to octreotide (initially 50 µg and subsequently 100 µg every 12 h) with modest decreases in serum PTH concentration and near-normal levels of serum calcium, systematic investigation of patients with primary and secondary hyperparathyroidism has not shown any effect of octreotide on serum PTH concentrations or calcium levels. Lucarotti et al. (4) studied 21 patients with primary hyperparathyroidism who were given octreotide 100 µg every 12 h for 6 d with no effect on serum PTH or calcium. Zielke et al. (5) randomized 40 patients with primary hyperparathyroidism and 40 patients with secondary hyperparathyroidism to receive a single dose of 200 µg octreotide or placebo and found no effect on serum PTH concentration or calcium levels 4 h later. Additionally, no somatostatin receptors were found in any of the parathyroid tissue from the 80 patients of Zielke et al. (5).

Octreotide appears to be effective in treating hypercalcemia due to neuroendocrine malignancies that produce PTH-related protein (6). Ridefelt et al. (7) further suggest that octreotide may be helpful in treating hypercalcemia of neuroendocrine origin, but not of parathyroid origin. In mouse pancreatic B cells, octreotide and somatostatin reliably decreased glucose-stimulated elevations in cytoplasmic calcium, whereas in normal bovine parathyroid cells and adenomatous or hyperplastic human parathyroid cells, octreotide did not affect calcium or PTH release (7).

Side effects may limit treatment with octreotide. Zielke et al. (5) found that 45% of patients suffered adverse effects from a single 200-µg dose, including nausea, diarrhea, headaches, and dizziness.

Because there is no successful medical treatment of metastatic parathyroid carcinoma, a trial of octreotide therapy may be warranted. However, we see no evidence that octreotide is effective for treatment of hypercalcemia associated with parathyroid carcinoma, and it may be associated with side effects that preclude its long-term use.

Footnotes

A response to this letter was invited, but the authors of the original article chose not to provide one.

Received October 20, 2003.

References

  1. Shane E 2001 Parathyroid carcinoma. J Clin Endocrinol Metab 86:485–493[Free Full Text]
  2. Koyano H, Shishiba Y, Shimizu T, Suzuki N, Nakazawa H, Tachibana S, Murata H, Furui S 1994 Successful treatment by surgical removal of bone metastasis producing PTH: new approach to the management of metastatic parathyroid carcinoma. Intern Med 33:697–702[Medline]
  3. Miller D, Edmonds MW 1991 Hypercalcemia due to hyperparathyroidism treated with a somatostatin analogue. Can Med Assoc J 145:227–228[Medline]
  4. Lucarotti ME, Hamilton JA, Farndon JR 1994 Somatostatin and primary hyperparathyroidism. Br J Surg 81:1141–1143[Medline]
  5. Zielke A, Hasse C, Bruns C, Sitter H, Rothmund M 1997 Octreotide: effective treatment for hyperparathyroidism? A prospective, randomized, controlled clinical trial. Surgery 121:606–610[Medline]
  6. Macdonald JS 1991 Parathyroid neoplasia. Curr Opin Oncol 3:139–141[Medline]
  7. Ridefelt P, Rydinge J, Akerstrom G, Hellman P, Rastad J 1995 Somatostatin and octreotide interfere with calcium signalling in pancreatic B-cells but not in normal and pathological parathyroid cells. Horm Metab Res 28:588–591




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