Yeah, say that three times fast! (And wish me good luck with typing it a bazillion times in the following paragraphs.)
So we all know that elevated parathyroid hormone (PTH) levels are common in the chronic hypophosphatemia community. They can be high even before starting treatment, although most often, the elevation appears to be triggered by the old (terrible) treatment with phosphate/calcitriol, especially if the proportion between the two supplements is out of whack.
Which means that patients on the old treatment sometimes needed to then pursue an additional treatment for the side-effects of the phos/calcitriol. Sometimes, simply discontinuing the phos/calctriol could reverse the hyperparathyroidism, but other times (usually after it’s been ongoing for a long time), it becomes “tertiary” (third stage), and is irreversible.
You can read more about the basics in “Hyperparathyroidism in Patients With XLH,” published in the Journal of Bone and Mineral Research. When the hyperparathyroidism becomes tertiary, there are basically two options for treatment: pharmaceutical and surgical (partial or complete removal of the glands). Surgical intervention can be successful, although the article cites another study that showed the parathyroids can grow back if not removed completely. I suspect that the key to whether surgical intervention is successful is the experience of the surgeon. My understanding is that the glands, even when enlarged, are extremely small and difficult to locate correctly, leading to some less-experienced surgeons removing parts of the thyroid instead of the parathyroids (or vice-versa when thyroid surgery is intended)!
The article specifically mentions the lack of experienced parathyroid surgeons as a reason to pursue pharmaceutical intervention. Then, the basic options are cinacalcet (used to be extremely expensive in the US, so some insurers were resistant to paying for it beyond an initial trial period, but it appears to have come down in cost), or paricalcitol (appears to still be expensive, although nowhere near the cost of burosumab, and I don’t know how insurers have responded). Another possibility mentioned in the article is that patients with hyperparathyroidism who are not already on burosumab treatment when their PTH becomes over-active, may find that starting burosumab will lower their PTH levels, along with improving their phosphorus levels.
I have slightly elevated parathyroid levels, despite being on burosumab (no real idea why), but it’s easily managed with a low dose of calcitriol. Also, my PTH levels even without the calcitriol, are not what I call “scary high.” In the past, my levels were technically high, but not high enough to worry my endocrinologist. During the brief period when I was taking phos/calcitriol however, my PTH levels went even higher, and that was when the endocinologist became concerned and put me on cinacalcet. It lowered the PTH, but ultimately my doctor and I decided that it made more sense to just discontinue the phos/calcitriol that triggered the elevated PTH, since the phos/calcitriol treatment didn’t actually make me feel any better. Once I stopped the phos/calcitriol, my PTH went back to slightly-high-but-not-scary-high, and I no longer needed the cinacalcet.
From what I understand (not a doctor, rember!), the medical community has only fairly vague ideas about the interplay between PTH and FGF23 and phosphorus, as compared to the more detailed biochemical understanding they have about the interplay of FGF23 and phosphorus in the kidneys. And they have even less information about the pros and cons of surgical versus pharmaceutical intervention for tertiary hyperparathyroidism.
Some of the issues may become moot as patients start burosumab at a younger age and the parathyroids are never triggered by the old phos/calcitriol treatment. But for now, we have a lot of patients in our community who either have or are at risk of irreversible hyperparathyroidism, and we don’t have a lot of information about the pros and cons of treatment options. We don’t even have, as far as I know, any good natural-history data on the progression of parathyroid issues in our community. It’s definitely an area ripe for more research!
I’d love to hear from you if you’ve had issues with hyperparathyroidism and whether it pre-existed phos/caclitriol treatment. If you had pharmaceutical intervention, what was it, and how successful was it? If you had surgical intervention, was it partial or complete, how successful was it, and were there any adverse consequences?
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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