Definition of Tertiary Hyperparathyroidism
Tertiary hyperparathyroidism is characterized by a lack of PTH suppression despite rising serum calcium levels, manifesting as hypercalcemic hyperparathyroidism that occurs in patients with long-standing secondary hyperparathyroidism. 1
Key Characteristics
Tertiary hyperparathyroidism (THPT) develops when parathyroid glands continue to oversecrete parathyroid hormone (PTH) autonomously after longstanding secondary hyperparathyroidism, despite normalization or elevation of serum calcium levels 2
It is most commonly encountered following kidney transplantation in patients with long-standing chronic kidney disease 1, 3
The condition represents a transition from an appropriate compensatory mechanism (secondary hyperparathyroidism) to autonomous parathyroid function that persists despite resolution of the original stimulus 4
Pathophysiology
Long-standing chronic kidney disease (CKD) causes metabolic disturbances including hyperphosphatemia, calcitriol deficiency, and hypocalcemia that lead to increased PTH secretion 2
Prolonged hypocalcemia and hyperphosphatemia cause parathyroid chief cell hyperplasia and excess PTH production 2
After correction of the primary disorder (typically through kidney transplantation), the hypertrophied parathyroid tissue fails to resolve and continues to oversecrete PTH despite normal or elevated calcium levels 2, 3
Pathologic Features
Marked parathyroid hyperplasia is the predominant morphologic feature (95% of cases), with 10-40 fold increases in parathyroid mass 5
Histologically, there is a predominance of chief cells and an abundance of oxyphil cells 5
True parathyroid adenomas are rare in tertiary hyperparathyroidism, occurring in only about 5% of cases 5
Diffuse, moderately enlarged hyperplastic glands are found predominantly in transplant patients, while nodular, markedly enlarged hyperplastic parathyroids are observed more frequently in patients treated by dialysis 5
Clinical Significance
The main indication for treatment is persistent hypercalcemia and/or increased PTH levels 2
Surgical excision (parathyroidectomy) is recommended for medically refractory cases 1
As tertiary hyperparathyroidism typically involves multigland disease (parathyroid hyperplasia), preoperative imaging aims to identify all eutopic and potential ectopic or supernumerary glands to guide the surgical approach 1
Treatment Options
Three surgical procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy 2
It is important to remove superior parts of the thymus during surgery as well 2
The optimal surgical approach remains controversial, with limited data available from only a few small trials with short follow-up 3