What are the causes of secondary Hyperparathyroidism (HPT)?

From the Guidelines

Secondary hyperparathyroidism is most commonly caused by chronic kidney disease (CKD), where decreased kidney function leads to phosphate retention, decreased vitamin D activation, and subsequent hypocalcemia, as supported by 1. The condition occurs when the parathyroid glands produce excess parathyroid hormone (PTH) in response to low calcium levels caused by an underlying condition. Key causes of secondary hyperparathyroidism include:

• Chronic kidney disease (CKD)
• Vitamin D deficiency
• Malabsorption syndromes like celiac disease, inflammatory bowel disease, and bariatric surgery
• Certain medications, including phenytoin, phenobarbital, rifampin, and bisphosphonates
• Severe magnesium deficiency
• Pseudohypoparathyroidism, a genetic disorder characterized by end-organ resistance to PTH
• Chronic hypercalciuria (excessive urinary calcium excretion) According to the most recent study 1, treatment focuses on addressing the underlying cause while maintaining normal calcium, phosphate, and vitamin D levels, and parathyroidectomy may be considered in cases of persistent hyperparathyroidism after kidney transplantation. It is essential to note that the optimal therapeutic approach may vary depending on the individual case and the underlying condition, as highlighted by 1. In terms of management, parathyroidectomy is associated with lower mortality than the use of calcimimetics, as indicated by 1, and may be a more effective option for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. However, the choice of treatment should be based on the individual patient's needs and medical history, and calcimimetics may be used in the first year after kidney transplantation, as suggested by 1.

From the Research

Causes of Secondary Hyperparathyroidism

• Secondary hyperparathyroidism commonly develops in patients with chronic kidney disease (CKD) in response to:
  • High phosphate levels 2, 3
  • Low calcium levels 2, 3
  • Low 1alpha,25-dihydroxyvitamin D(3) (calcitriol) levels 2, 3
• Defect in the activation of vitamin D in the kidneys due to CKD leads to hypocalcemia and hyperphosphatemia, resulting in a compensatory increase in parathyroid gland cellularity and parathyroid hormone production 3
• Vitamin D deficiency is an established trigger of secondary hyperparathyroidism (SHPT) in patients with CKD 4

Pathophysiology

• Serum calcium concentration is the main determinant of parathyroid hormone (PTH) release 3
• Abnormalities in serum calcium and phosphate profile, along with a decline in calcitriol synthesis, contribute to parathyroid hyperplasia and abnormal parathyroid hormone synthesis and secretion 5
• A reduced density of specific receptors for vitamin D and calcium in several tissues and organs are also present, thus contributing to parathyroid hyperplasia and abnormal parathyroid hormone synthesis and secretion 5

Clinical Presentation and Management

• Correction and maintenance of normal serum calcium and phosphate are essential to preventing SHP, hungry bone disease, cardiovascular events, and anemia development 3
• Medical interventions to control serum calcium, phosphate, and PTH such as vitamin D analogs, calcium receptor blockers, and parathyroidectomy are needed in some CKD patients 3, 4, 5