Parathyroidectomy in the treatment of secondary renal hyperparathyroidism

Abstract

Although the association between chronic renal failure and bone disease was first recognized 90 years ago [1], its nature and origin are still the subject of active enquiry. Initially, enthusiasm for this was tempered by the fact that the renal failure usually dominated the clinical picture and prognosis. However, the last decade has seen enormous advances in the care of patients with renal failure, and it has become apparent that bone disease is an important factor which frequently limits rehabilitation. The complexity of the pathological picture is probably explained by the simultaneous occurrence of two processes which interfere with the mobilization and formation of bone. These two processes, hyperparathyroidism and vitamin D resistance, are probably initially independent; but with the advancement of renal failure, they may interact, possibly explaining the third major component of uremic osteodystrophy, osteosclerosis. Occasionally, each of these components appears in an almost pure form, but more usually they appear in varying combinations in different patients. MacCallum [2] was the first to record the occurrence of enlarged parathyroid glands in patients dying with chronic renal failure. Later work amply confirmed this observation [3-5] and, more recently, Berson and Yalow [6] have shown that these glands produce excessive amounts of parathyroid hormone. Slatopolsky et al [7] have provided evidence suggesting that phosphate retention may be the initial stimulus to hyperparathyroidism and have suggested that the occurrence of hyperparathyroidism in a patient with progressive renal disease may be prevented or delayed by reduction of the dietary phosphate intake in proportion to the fall in glomerular filtration rate. This recommendation is based on the hypothesis that the development of hyperparathyroidism represents an attempt on the part of the organism faced with advancing renal failure to maintain a normal plasma phosphate (and thus a normal plasma calcium) by increasing the amount of phosphate excreted by each nephron. Clearly the development of vitamin D resistance renders the situation much more complicated since this also serves to lower the plasma calcium concentration and prevents the calcium mobilizing effect of parathyroid hormone on the bone [8]. Thus, hyperparathyroidism may be seen initially as a compensatory phenomenon, acting to maintain the composition of the extracellular fluid within the normal range. It should be expected, therefore, that the plasma calcium concentration of patients with advancing renal failure should be maintained below or within the normal range and that hypercalcemia should not normally occur. In 1966 Stanbury and Lumb [9] analyzed the plasma calcium concentration of patients with renal failure and bone disease and showed that if the patients were separated, on the basis of skeletal X-rays, into a group in which hyperparathyroidism predominated and a group in which osteomalacia predominated, the former showed plasma calcium concentrations which were usually in the range 9 to 11.5mg/100 ml while the latter showed concentrations in the range 6 to 9 mg/100 ml. This again confirmed the physiological effectiveness of parathyroid hormone.