Q. Can you explain why patients with renal failure have hyperparathyroidism?
A. Yes – but first, a quick note about the parathyroid. Unlike other endocrine organs, the parathyroid gland is not controlled by the pituitary. It secretes parathyroid hormone in response to serum calcium levels. That’s it. No pituitary/hypothalamic input. The function of parathyroid hormone is to raise serum calcium; so when the calcium level drops below normal, that’s the signal for the parathyroid to start secreting parathyroid hormone.
Hyperparathyroidism can be caused by a number of different things. Primary hyperparathyroidism occurs when the parathyroids are over-functioning because of some intrinsic parathyroid gland problem (for example, a parathyroid adenoma that’s busy secreting parathyroid hormone). Secondary hyperparathyroidism occurs when the parathyroids are overfunctioning because something is causing chronic hypocalcemia (the “something” is usually chronic renal failure). Tertiary hyperparathyroidism occurs when the parathyroids are autonomously over-functioning (this happens in a few patients with secondary hyperparathyroidism). There’s also something called pseudohyperparathyroidism, which occurs when a carcinoma (usually squamous cell lung carcinoma) secretes a protein that acts so much like parathyroid hormone that it actually raises serum calcium. This type of situation is called a paraneoplastic syndrome, and it occurs with other malignancies and hormones too (for example, small cell lung carcinoma can secrete proteins that acts like ADH or ACTH).
Getting back to the kidney: in chronic renal failure, phosphate is not excreted well, and vitamin D is not converted to its active form very readily. Calcium phosphate forms in the circulation, leading to a decrease in free serum calcium. The hypocalcemia then stimulates the parathyroids to grow and secrete parathyroid hormone, and voila, you have hyperparathyroidism.
The signs and symptoms of primary hyperparathyroidism have been referred to as “stone, bone, moan and groan:”
Stone: kidney stones, nephrocalcinosis (calcification of renal interstitium and tubules), calciphylaxis (calcification of vessels leading to ischemia in skin, other organs).
Bone: bone pain. Stimulated osteoclasts erode bone (leading to thin, delicate, fragile trabeculae). If hyperparathyroidism goes on long enough, patients can get osteitis fibrosa cystica (thinned cortex and fibrotic marrow with hemorrhage and cysts) and brown tumors (big masses of osteoclasts and hemorrhagic (brown) debris that can be mistaken for neoplasms – check out the radiograph, above).