At a Glance

Secondary hyperparathyroidism is an overproduction of parathyroid hormone (PTH) production secondary to a chronic abnormal stimulus for PTH production. The most common causes are chronic renal failure and vitamin D deficiency. Secondary hyperparathyroidism often develops early in chronic kidney disease, even before dialysis or transplantation is considered. Most patients with end-stage renal disease have elevated PTH. Hypocalcemia and hyperphosphatemia are particular powerful stimuli for PTH secretion. Chronic overproduction of PTH contributes to osteitis fibrosa cystica and mixed uremic osteodystrophy, which can manifest as soft-tissue calcifications, endocrine disturbances, compromised immune function, and psychiatric changes. Secondary hyperparathyroidism may also be suspected when hypocalcemia is noted incidentally during routine laboratory testing.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The initial biochemical work-up consists of serum calcium, magnesium, phosphorus, PTH, albumin, thyroid function tests (e.g., thyroid-stimulating hormone (TSH), free thyroxine, and measures of kidney function (e.g., blood urea nitrogen, creatinine). In secondary hyperparathyroidism, low to normal serum calcium and elevated serum PTH are usually seen. 25-Hydroxyvitamin D should also be ordered as a follow-up to elevated PTH. Both creatinine and phosphorus help distinguish secondary hyperparathyroidism caused by renal failure versus vitamin D deficiency. Serum phosphorus is usually high in patients with renal failure and low in patients with vitamin D deficiency.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Low serum albumin can complicate interpretation of serum calcium. In patients with hypoalbuminemia, corrected calcium should be calculated or, alternatively, an ionized calcium should be . Thiazide diuretics and lithium can complicate the interpretation of laboratory studies. Ideally, these drugs should be discontinued prior to laboratory work-up.

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What Lab Results Are Absolutely Confirmatory?

There are no definitive laboratory tests. The biochemical work-up is aimed at uncovering the cause of the secondary hyperparathyroidism, which is typically renal failure or vitamin D deficiency.

Additional Issues of Clinical Importance

Untreated secondary hyperparathyroidism can lead to serious complications, such as skeletal deformities, bone pain, fractures, and renal stones. Also, given that renal failure and vitamin D deficiency are both common problems throughout the world, patients may present with both renal failure and vitamin D deficiency.

Errors in Test Selection and Interpretation

A common error is to misdiagnose primary hyperparathyroidism when, in fact, a secondary cause, such as vitamin D deficiency, is driving the hyperparathyroidism.

Some of the biochemical features of secondary hyperparathyroidism (e.g., hypocalcemia, elevated serum PTH) can also be seen in pseudohypoparathyroidism, a syndrome of resistance to the biochemical actions of PTH. Although pseudohypoparathyroidism is a rare disorder, it should be considered if renal failure or vitamin D deficiency does not seem to be the cause of hypocalcemia and elevated serum PTH.