Hyperparathyroidism and Parathyroidectomy in Renal Failure

Among the many homeostatic responses to the loss of renal function, increased synthesis and secretion of parathyroid hormone (PTH) is uniformly present. As time passes the number and size of the parathyroid chief cells increase resulting in established secondary hyperparathyroidism (1-3). Although these facts have been known for over fifty years, the process that initiates these changes remains uncertain. In established chronic renal failure (glomerular filtration rates [GFR] <25 ml/minute) the reasons for the continued stimulus to the parathyroids are not difficult to find. Total and ionized calcium levels are often low, in part due to hyperphosphatemia but also to reduced gastro-intestinal absorption of calcium. This in turn is due to reduced synthesis of 1,25 dihydroxycholecalciferol (1,25 (OH)2D3) by the failing kidney (4-5). Compounding factors are end-organ (bone) resistance to parathyroid hormone (6), fewer parathyroid receptors for 1,25 (OHhD3 (7), and an alteration in the glandular response to the ambient ionized calcium level. This "set point" is shifted so that higher calcium levels are needed to inhibit hormone secretion (8). In early renal insufficiency (GFR 25-75 ml/minute), PTH levels may still be elevated but now the cause(s) is more obscure. Serum calcium and phosphorus levels are usually normal and 1,25(OHhD3 is normal or slightly reduced (9, 10). Nevertheless dietary phosphate restriction or, the administration of exogenous 1,25(OH)2D3 or its analogues will suppress PTH secretion to normal. Phosphate traffic, inappropriately high for the number of functioning nephrons, leads to a production rate for 1,25(OH)2D3 by the kidney that is insufficient to prevent parathormone hypersecretion. At this stage these changes appear to be readily reversible. The clinician is confronted with the dilemma of now being able to arrest the development of secondary hyperparathyroidism, yet knowing at the same time that most patients will suffer no effects from this abnormality and will die or be transplanted blissfully unaware of their PTH levels. (Distinction must be made between the undesirable effects of hyperphosphatemia and those of PTH excess. It is the latter to which the treatment dilemma refers). The dilemma exists because the management could be harmful while the condition being treated is rarely so and then only after many years. Harm can be caused by hypercalcemia if the dose of vitamin D analogues is excessive and not carefully monitored or from calcium salts used for phosphate binding. Use of aluminum salts is contraindicated because of the risk of eventual aluminum storage and toxicity. It is suggested that in most instances the use of 1,25(OHhD3 and its analogues be deferred until the start of dialysis, when control and monitoring will be more precise and possible undesirable effects on renal function from hypercalcemia will no longer be relevant. Exceptions would be patients with a protracted stable course of chronic renal failure, who are very compliant and are followed carefully. Irrespective of future advances, there are currently thousands of patients with end-stage renal disease, most of whom are hyperparathyroid. Among these a few will require glandular removal for hypercalcemia (>3 mmol/L) or severe osteitis fibrosa. Uncontrolled metastatic calcification and the calciphylaxis syndrome would also be indications for surgery. The best clinical response will be in the subjects with documented severe parathyroid bone disease. Three different operative procedures are available in these circumstances. For each the operative mortality and morbidity is very low and the patients usually leave hospital within a week. The immediate post-operative concern is hypocalcemia. This is due to the mass movement of calcium from extracellular