Management of Recurrent Oncogenic Osteomalacia


Question

I would be most grateful for help with a very difficult problem of oncogenic osteomalacia. The patient is a 62-year-woman who presented to me in 2001 with multiple rib fractures resulting in severe pain. Her serum phosphate was low at 0.56 mmol/L, and she had an undetectable 1,25 Dihydroxy Vitamin D and a low 25 Hydroxy Vitamin D at 29.8 nmol/L. She had an ovoid tumor between the metacarpals in her right hand, and this was removed in March 2002 (unfortunately incompletely removed). This was read at the Armed Forces Institute of Pathology as an atypical fibrochondo-osseous neoplasm of uncertain malignant potential with features suggestive of a phosphaturic mesenchymal tumor (mixed connective tissue variant).

After this first operation on March 1, 2002, there was remarkable improvement, and by March 27, 2002, the serum phosphate was 1.30 mmol/L and her 1,25 Dihydroxy Vitamin D was normal. At this time she was asymptomatic, and her fractures appear to have healed. Her serum phosphate gradually fell after that, and during 2002 and 2003, it was approximately 0.89 mmol/L – at the lower end of the normal range, but by February 2005, it was low at 0.42 mmo/L. She was being treated, at this time, with Rocaltrol 0.5 µg t.i.d., Calcium Citrate 500 mg t.i.d., and Phosphate Novartis 500 mg q.i.d.

She had a second operation on August 12, 2004, for the removal of residual tumor, but after this, there was little improvement in the phosphate level. She also had a course of radiation to her hand consisting of 6200 rads in 26 fractions in 2004 and early 2005, but this did not help. Her serum phosphate remained low. In addition, we had been able to send off her FGF-23 to the reference lab in Indiana, and it was high at the beginning and fell back to normal after the first operation. Unfortunately, we have not been able to get it assayed since.On April 5, 2005, she started Octreotide 100 µg t.i.d. subcutaneously, and by June of that year, she was 50% improved in symptoms. Because of expense, this was changed to the long-acting form of Sandostatin LAR 20 mg IM every four weeks. In March 2006, this was increased to Sandostatin LAR 30 mg.

The phosphate did not normalize after starting the Octreotide; although, her symptoms were somewhat better. At the beginning the tumor was visualized on a Somatostatin scan, and this was true also of the situation before the second operation but since then a Somatostatin scan after being off Sandostatin LAR for a month was negative. Recently her serum phosphate has become very low again, and her symptoms of pain have recurred, and she has multiple fractures again. We are restarting Octreotide 100 mg t.i.d. subcutaneously. I presume that we have either residual tumor in the arm or metastatic tumor, which so far has not been located by imaging investigations. D . W. Ingram, MB, FRCPC, FACP

Response

Your case is very convincing for a diagnosis of oncogenic osteomalacia. The biochemistry, location, and response to initial therapy are all very typical. The case also presents the difficult management challenges in the disorder. I think you have to assume that there is either residual/recurrent tumor or metastases. I would suggest you try alternate imaging techniques to try and localize this. In addition to octreotide scans, sestamibi and MRI have been used. Most recently the PET scan using CT coregistration has been fruitful and I would suggest this approach. You may also wish to attempt regional venous sampling for FGF23 levels to try and focus the area of concentration of CT scanning, if possible. In addition to the standard therapeutic maneuvers you have tried, another potential therapy could be used (radiofrequency ablation) if the tumor is in a difficult location (see Hesse E et al, NEJM 357: 422, 2007). Thomas Carpenter, MD

Is Growth Hormone Therapy Safe with Residual Pituitary Tumor?


Question

I have a 60 year old patient who is post transsphenoidal resection of a large macroadenoma. He has growth hormone deficiency and hypogonadism and I am weaning him off of steroids. He is much better symptomatically on growth hormone, but a post-op MRI reveals

some residual tumor. Is growth hormone contraindicated here because of the residual tumor? Thank you very much. Ann Ward>

Response

This is an interesting question. There are two parts to this: firstly, the value of replacing GH in an older age group, and secondly, its safety when there is residual tumour. The answer to both is positive. There is published evidence that GH replacement should be considered regardless of age, although of course the normal range in which one would like to get circulating IGF-1 falls with age; we try and place the IGF-1 in the normal age- and sex-adjusted range but above the median. In terms of safety, there have now been numerous reports which can reference if you are interested in which GH has been shown not to be a risk factor for tumour regrowth or recurrence. However, you should bear in mind that when there is residual tumour postoperativey, the 10-year recurrence rate is pretty high in the absence of external beam radiotherapy regardless as to wh e ther GH is admi n istered. Regards, Ashley Grossman, MD