What is the primary cause of secondary hyperparathyroidism?

The primary cause of secondary hyperparathyroidism is hypocalcemia, particularly in the context of chronic kidney disease (CKD). In CKD, the kidneys are unable to excrete phosphate effectively, leading to hyperphosphatemia. The elevated phosphate levels can bind to calcium, lowering serum calcium levels and causing hypocalcemia.

To compensate for the decreased calcium levels, the parathyroid glands are stimulated to produce more parathyroid hormone (PTH), resulting in secondary hyperparathyroidism. This is an adaptive mechanism; the body attempts to restore calcium homeostasis by increasing PTH levels, which normally works to increase serum calcium through actions on the kidney, bone, and intestine.

While vitamin D deficiency can also lead to secondary hyperparathyroidism due to its role in calcium absorption, the context of chronic kidney disease makes hypocalcemia the more primary underlying cause that directly stimulates the parathyroid glands. Other conditions, such as primary hyperparathyroidism and malignancy, lead to different forms of parathyroid dysfunction and are not part of the secondary response seen in conditions like CKD.