Pathologist On Call: Fluctuating Parathyroid Hormone with Normal Calcium in an Elderly Man

Case:

A 75 year old Alzheimer’s dementia patient.  Parathyroid hormone (PTH) levels were ordered.

Why order PTH? 

PTH is ordered to assess for hyperparathyroidism.  There are two forms of hyperparathyroidism: primary and secondary.  Primary hyperparathyroidism can be caused by a parathyroid (PT) adenoma,  PT hyperplasia, or a non-PT malignancy such as squamous cell cancer or multiple myeloma.  Secondary hyperparathyroidism occurs in response to hypocalcemia which can arise from insufficient intake of vitamin D or chronic renal failure (which results in insufficient vitamin D).   There is weak evidence suggesting a positive correlation between PTH and cognitive decline.(1, 2)  Progression of cognitive decline is slowed when PTH and vit D levels are normalized.

Action of PTH: PTH is a peptide hormone that controls calcium levels in the blood. It is secreted as a prohormone and is cleaved in the blood.  The 34 residue N-terminal fragment is active and has a half-life of about 5 minutes.  The C-terminal end has a half-life or 2 hours and is diagnostically insignificant because it is physiologically inactive.  PTH activates receptors on osteoclasts which causes them to release bone calcium.  PTH also increases renal synthesis of 1,25 OH₂ vitamin D which, in turn, increases intestinal absorption of calcium.

What would make the PTH level fluctuate so much?

This is most likely a case of incipient normocalcemic primary hyperparathyroidism (NPH).(3-5)  PTH levels are higher than normal but calcium levels are normal.  PTH levels tend to fluctuate. Calcium can also be sometimes elevated as well.   The disease is thought to be a mild or early form of hyperparathyroidism and 20 percent of patients go on to develop worsening hyperparathyroidism. How should NPH be managed?  Parathyroidectomy or monitoring are the primary alternatives; however, the best way to manage this disease is unknown.

References

1. Lourida I, Thompson-Coon J, Dickens CM, et al. Parathyroid hormone, cognitive function and dementia: A systematic review. PLoS ONE 2015;10.

2. Björkman MP, Sorva AJ, Tilvis RS. Does elevated parathyroid hormone concentration predict cognitive decline in older people? Aging Clinical and Experimental Research 2010;22:164-9.

3. Shlapack MA, Rizvi AA. Normocalcemic primary hyperparathyroidism-characteristics and clinical significance of an emerging entity. Am J Med Sci 2012;343:163-6.

4. Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism: Further characterization of a new clinical phenotype. Journal of Clinical Endocrinology and Metabolism 2007;92:3001-5.

5. Crowley RK, Gittoes NJ. Elevated PTH with normal serum calcium level: A structured approach. Clinical Endocrinology 2016;84:809-13.

-Robert Schmidt, MD, PhD, MBA, MS is currently an Associate Professor at the University of Utah where he is Medical Director of the clinical laboratory at the Huntsman Cancer Institute and Director of the Center for Effective Medical Testing at ARUP Laboratories.