From the Guidelines
Elevated parathyroid hormone (PTH) levels are typically caused by primary hyperparathyroidism, secondary hyperparathyroidism, or tertiary hyperparathyroidism, with the most common cause being primary hyperparathyroidism, which is best treated with parathyroidectomy if the patient is symptomatic or meets surgical criteria, as supported by the most recent study 1. The causes of PTH elevation can be categorized into three main types: primary, secondary, and tertiary hyperparathyroidism.
- Primary hyperparathyroidism is usually caused by a single parathyroid adenoma, and treatment involves parathyroidectomy, as recommended by the American College of Radiology 1.
- Secondary hyperparathyroidism is often seen in kidney disease, and requires addressing the underlying condition with treatments like vitamin D supplements, phosphate binders, or calcimimetics, as suggested by the K/DOQI clinical practice guidelines 1.
- Tertiary hyperparathyroidism can occur in patients with long-standing secondary hyperparathyroidism, and is characterized by a lack of PTH suppression despite rising serum calcium levels, as described in the ACR Appropriateness Criteria 1. Initial evaluation should include measuring serum calcium, phosphorus, vitamin D, and kidney function, and if calcium levels are normal with elevated PTH, vitamin D deficiency should be considered and treated with vitamin D supplementation, as recommended by the K/DOQI clinical practice guidelines 1. It is essential to investigate the underlying cause of PTH elevation before treatment, as the treatment approach varies depending on the type of hyperparathyroidism, and the most effective treatment for primary hyperparathyroidism is parathyroidectomy, as supported by the most recent study 1.
From the FDA Drug Label
The endogenous VDR activator, calcitriol [1,25(OH)2D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells VDR activation is essential for the proper formation and maintenance of normal bone. In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis. Decreased levels of 1,25(OH)2D3 have been observed in early stages of chronic kidney disease The decreased levels of 1,25(OH)2D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy.
The causes of Parathyroid hormone (PTH) elevation are:
- Diminished activation of vitamin D in the diseased kidney
- Decreased levels of 1,25(OH)2D3, often observed in early stages of chronic kidney disease 2 This leads to secondary hyperparathyroidism and disturbances in calcium and phosphorus homeostasis.
From the Research
Causes of Parathyroid Hormone (PTH) Elevation
The causes of PTH elevation can be categorized into primary, secondary, and tertiary hyperparathyroidism.
- Primary hyperparathyroidism is due to an intrinsic abnormal change in the parathyroid glands, altering the excretion of parathyroid hormone 3.
- Secondary hyperparathyroidism is caused by an extrinsic abnormal change affecting calcium homeostasis, stimulating the production of parathyroid hormone 3.
- Tertiary hyperparathyroidism is a consequence of long-standing secondary hyperparathyroidism, leading to hyperplasia of the parathyroid glands and autonomous secretion of parathyroid hormone.
Specific Causes of PTH Elevation
Some specific causes of PTH elevation include:
- Vitamin D deficiency, which is a common cause of secondary hyperparathyroidism, particularly in elderly people 3.
- Chronic kidney disease (CKD), which leads to defects in the activation of vitamin D, resulting in hypocalcemia and hyperphosphatemia, and subsequently causing secondary hyperparathyroidism 4, 5, 6.
- Low calcium intake, impaired renal function, malabsorptions, and drugs interfering with calcium/bone metabolism, such as lithium salts and antiresorptive osteoporosis therapies 7.
- Hypercalciuria due to a renal calcium leak 7.
Diagnostic Approach
When diagnosing the cause of an isolated elevated PTH, it is essential to rule out secondary hyperparathyroidism first, considering factors such as vitamin D deficiency, low calcium intake, and impaired renal function 7. If no cause of secondary hyperparathyroidism is found, the diagnosis of normocalcemic primary hyperparathyroidism should be considered, using tools such as a calcium load test or a thiazide challenge test 7.