Hi Dr. Boone, Can hyperparathyroidism cause MGUS? If so, are you aware of any patients whose MGUS healed after parathyroidectomy? Thank you.
This is a very good question, and somewhat difficult to answer.
Here is the short answer: We do not have definitive evidence that parathyroid disease causes MGUS or that MGUS will resolve after parathyroidectomy.
Long answer: Monoclonal gammopathy of undetermined significance (MGUS) is a condition characterized by abnormal proteins in the blood. In most cases, this condition is benign and does not need to be treated. A small number of patients can develop cancer (multiple myeloma). MGUS occurs in about 3% of adults over age 50 and the incidence increases with age, so it is uncommon but not rare in older adults.
In the 1970s, several researchers published case reports of small numbers of patients with hyperparathyroidism who also had MGUS. It was suggested that the two diagnoses were related, and that parathyroid disease may have caused MGUS. There were even some plausible explanations given as to how this might be the case. We did not really have any evidence that they were linked, but it seemed like they could be. Personally, I have treated many patients with parathyroid disease who also had MGUS, and it seemed like they might be related.
But further research questioned the relationship between MGUS and hyperparathyroidism. These were larger studies, looking at the overall rate of MGUS in the population. The rationale is like this: if hyperparathyroidism is linked to MGUS, then we would expect to see much higher rates of MGUS in parathyroid patients than we do in patients without parathyroid disease. There should be a noticeable correlation between people with parathyroid disease and those with MGUS. But when we do this analysis in large groups of people, it turns out that MGUS occurs at the same rate in parathyroid patients as it does in everyone else (1). In the early case studies, it was likely a coincidence that the patients had both hyperparathyroidism and MGUS. If I looked hard enough, I would be able to find a small subset of parathyroid patients who also had injuries to their right thumbs as children, but these two conditions would be unrelated.
Very few studies have looked at what happens to MGUS after parathyroid surgery. In my review of published studies, I found only one incidence in which MGUS resolved after parathyroid surgery (2). Another study included 9 patients with MGUS - none of them had any improvement after parathyroid surgery (3). I have not personally had a patient who no longer had MGUS after parathyroid surgery.
Overall, I would say that the link between MGUS and parathyroid disease is uncertain. In most cases, patients who have both MGUS and parathryoid disease just happen to have both of them. Hyperparathyroidism and MGUS are both uncommon, but not rare, conditions, and so there will always be some patients who happen to get both of them. In very rare cases, they may be related, and parathyroid surgery might help. This is likely extremely rare. For patients with MGUS and parathyroid disease, parathyroid surgery is not likely to help their MGUS.
Bida JP, Kyle RA, Therneau TM, et al. Disease associations with monoclonal gammopathy of undetermined significance: a population-based study of 17,398 patients. Mayo Clin Proc. 2009;84(8):685-693. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719521/
Cañas CA, Echeverri AF, Anaya JM. Total recovery from monoclonal gammopathy and autoimmune phenomena after parathyroidectomy. Open Rheumatol J. 2012;6:180-182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412230/
Mundis RJ, Kyle RA. Primary hyperparathyroidism and monoclonal gammopathy of undetermined significance. Am J Clin Pathol. 1982;77(5):619-621. https://pubmed.ncbi.nlm.nih.gov/7081154/