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The role of parathyroidectomy in the treatment of secondary hyperparathyroidism before and after renal transplantation.

In a series of 335 renal transplant recipients, 28 patients underwent parathyroidectomy due to secondary hyperparathyroidism. Twenty patients were operated on prior to renal transplantation, 8 subsequent to it. Solitary adenomas were found in 6 cases, diffuse hyperplasia in 22. Fifteen of the patients with diffuse hyperplasia underwent total parathyroidectomy with autotransplantation of parathyroid fragments into the sternocleidomastoid muscle, subtotal parathyroidectomy was performed in 7. Four hypercalcaemic patients underwent parathyroid surgery because of deteriorating transplant function but without improvement. Following parathyroidectomy, 21 patients became hypocalcaemic. 15 of these patients had undergone total parathyroidectomy and autotransplantation. Dihydrotachysterol substitution was accompanied by toxic symptoms in three patients on dialysis and by deteriorating renal function in two transplanted patients. Therefore, subtotal parathyroidectomy is recommended as the surgical procedure of choice in the treatment of secondary hyperparathyroidism before, as well as after renal transplantation.

Adolescent

The effect of parathyroidectomy and large doses of cholecalciferol on the ability of rats to adapt to changes in dietary intake of calcium.

1. Adaptation to different dietary levels of calcium was produced by feeding a low (0-2%) calcium diet or one of two high (1-6 or 0-8%) calcium diets for 4 or 6 weeks. Adaptive changes in true and apparent absorption of calcium, apparent absorption of phosphate and urinary excretion of calcium, were observed. 2. Parathyroidectomy performed prior to adaptation did not greatly impair the ability of rats to adapt to different levels of calcium in the diet. The response of the rats to parathyroidectomy was affected by their subsequent dietary history. 3. Six weeks after parathyroidectomy the plasma calcium was significantly higher than it had been immediately post-operatively. This rise in plasma calcium was seen in the rats adapted to the 1-6% calcium diet but not in those adapted to the 0-2% calcium diet. 4. Parathyroidectomy performed after adaptation had taken place did not abolish the adaptive changes. The response of rats to parathyroidectomy was affected by their previous dietary history. 5. Large doses of cholecalciferol given for 8 days after adaptation had taken place increased the absorption of calcium in rats adapted to the 0-8% calcium diet thereby abolishing or reducing the adaptive differences in absorption between these rats and rats adapted to the 0-2% calcium diet. The cholecalciferol increased urinary calcium excretion but did not abolish adaptive differences in urinary excretion of calcium between rats adapted to diets with different calcium levels. 6. It is concluded that parathyroid hormone does not play a major role in mediating adaptation to different dietary intakes of calcium. The possible role of 1-25 dihydroxycholecalciferol is discussed.

Adaptation, Physiological

Effect of parathyroidectomy on crystallization of calcium salts in urine of patients with primary hyperparathyroidism.

The effect of parathyroidectomy on the crystallization of calcium salts in urine was examined in seven stone-forming patients with primary hyperparathyroidism. After parathyroidectomy, urinary calcium decreased significantly from 205 +/- 30 to 67 +/- 11 mg per day (P less than 0.01); there were no significant changes in urinary phosphorus, oxalate, magnesium, sodium, potassium, uric acid, pH, or total volume. The urinary activity product ratio (state of saturation) of brushite (CaHPO4.2H2O) and calcium oxalate decreased significantly from 1.34 +/- 0.14 to 0.75 +/- 0.18 and from 3.20 +/- 0.56 to 1.53 +/- 0.21 respectively (P less than 0.05), owing principally to the decline in urinary calcium. Moreover, the urinary formation product ratio of calcium oxalate, which reflects the minimum supersaturation required for spontaneous nucleation, increased significantly after parathyroidectomy, from 7.19 +/- 1.19 to 12.99 +/- 1.69 (P less than 0.001). The results indicate that parathyroidectomy restores the normal urinary environment with respect to saturation and inhibitor and/or promoter activity.

Calcium

Results of subtotal parathyroidectomy for primary chief cell hyperplasia.

Analysis of the long-term results of subtotal parathyroidectomy in patients with primary chief cell hyperplasia provides evidence that refutes the recent assertion that such treatment is often ineffective. With the use of rigid criteria, 55 patients with unequivocal chief cell hyperplasia were culled from 1,576 patients who had been operated on for primary hyperparathyroidism at the Mayo Clinic between July, 1959, and July, 1976. Follow-up information, including serum levels of calcium, was obtained for all patients up to at least July, 1977. Follow-up for surviving patients ranged from 1 year to 17 years (average, 3.9 years). Seven patients (13%) were not cured by subtotal parathyroidectomy and were left with persistent hyperparathyroidism after operation, presumably because a supernumerary gland was overlooked. However, not a single patient experienced recurrent hyperparathyroidism during the 213 patient-years of follow-up. In only three patients (5%) did permanent hypoparathyroidism develop following operation. These results reaffirm the efficacy of subtotal parathyroidectomy for primary chief cell hyperplasia and call into serious question the recent advocacy of total parathyroidectomy and autotransplantation of parathyroid tissue in these cases.

Female

Metabolic effects of parathyroidectomy in asymptomatic primary hyperparathyroidism.

Effects of parathyroidectomy on parathyroid function and calcium (Ca) metabolism were carefully evaluated in 6 patients with primary hyperparathyroidism without symptoms normally attributed to the disease and in 7 with bone disease or nephrolithiasis. Before parathyroidectomy, both groups of patients demonstrated evidence of the sequelae of parathyroid hormone (PTH) excess, since they presented one or more of the following features: low bone density by 125I-photon absorption, hypercalciuria (urinary Ca greater than 200 mg/day on an intake of 400 mg/day), negative Ca balance (absorbed Ca less than urinary Ca), elevated fasting urinary Ca greater than 0.2 mg/mg creatinine for a night-time sample after a 6-hour fast), and decreased renal function (creatinine clearance of less than 65 ml/min). Following parathyroidectomy, most of these deleterious effects were reversed commensurate with the return of immunoreactive serum PTH, serum Ca, and urinary cyclic AMP toward normal. These quantitative non-invasive techniques may be useful for the initial evaluation and follow-up of patients with asymptomatic primary hyperparathyroidism.

Adult

Parathyroidectomy after renal transplantation.

Among 569 patients treated with renal transplantation during a 12-year period in Gothenburg, eleven patients were subjected to subtotal parathyroidectomy after successful transplantation. All patients had comparatively long histories of advanced renal failure and/or long-lasting haemodialysis treatment before transplantation. Signs of hyperfunctioning parathyroid glands (elevated total serum calcium with or without clinical symptoms) appeared within the first few months after transplantation in eight cases, and after 1-3 years in three cases. Four patients had symptoms of bone disease and/or soft tissue calcium deposits whereas renal functional impairment was not noted in any patient. The remaining seven patients were operated upon because of persistently elevated serum calcium levels only, in order to prevent such complications. In spite of our extremely restrictive policy concerning parathyroidectomy in patients awaiting renal transplantation and, conversely, a liberal attitude to this operation after transplantation, parathyroidectomy was a rare event among our patients. The rationale for surgical treatment of mild hyperparathyroidism following renal transplantation is questioned, as is the need for sophisticated diagnostic procedures to detect more cases of asymptomatic hyperparathyroidism.

Adult

Explorative parathyroidectomy before and after kidney transplantation.

Twentytwo parathyroidectomies were performed in a series of about 200 patients. Surgical exploration was performed in less than 5% of patients with slowly progressive uremia, and of patients on maintenance haemodialysis, whereas as many as 15% of patients returning to dialysis after graft failure were operated on. After successful transplantation appoximately 10% of a patients with an initially functioning graft ultimately had a neck exploration. On three occasions this parathyroidectomy was acutely performed. In about one third of the surgically explored cases the parathyroid glands displayed marked assymetry and/or histological features possibly indicative of adenoma formation or "autonomous nodules". The incidence of surgical complications was low and beneficial clinical effect were often encountered. It thus seems possible to defend a liberal attitude towards the performance of parathyroidectomy in patients accepted into a transplantation programme.

Adult

Changes of urinary cyclic AMP excretion and plasma parathyroid hormone levels before and after parathyroidectomy in patients with primary hyperparathyroidism.

Urinary cyclic AMP excretion and plasma parathyroid hormone(PTH) levels were examined in three patients with primary hyperparathyroidism before and after parathyroidectomy. Plasma PTH and urinary cyclic AMP in the individual patients decreased in parallel following parathyroidectomy. During surgery there was a statistically significant correlation between PTH levels and cyclic AMP excretion in individual patients. These findings support the claim that the rate of urinary cyclic AMP excretion reflects endogenous PTH activity in patients with primary hyperparathyroidism.

Adult

The influence of parathyroidectomy upon calcium and phosphate homeostasis in adult sheep.

The absorption and secretion of Ca and PO4 were measured with the use of radioactive isotopes in 4 adult sheep before and after parathyroidectomy. Secretion of Ca and PO4 into the stomach and intestines was measured separately. Parathyroidectomy resulted in a negative balance for Ca and PO4 and an accompanying fall in plasma Ca and PO4 concentrations. In the case of PO4 this response was attributed primarily to a reduced intestinal absorption, but for Ca increases in urinary excretion and intestinal secretion also contributed significantly. Secretion of PO4 to the stomach was reduced but endogenous PO4 excretion in the faeces was unchanged which indicated a reduced reabsorption of secreted PO4 by the intestines.

Animals

Urinary cAMP excretion during surgery: an index of successful parathyroidectomy in patients with primary hyperparathyroidism.

Urinary phosphate (Up) and urinary cAMP (UcAMP) excretion were determine in patients undergoing neck exploration for primary hyperparathyroidism in order to evaluate these parameters as indices of successful surgery. UcAMP fell below 1.5 micro mol/g creatinine in all 12 patients in whom single gland removal corrected hypercalcemia and in 0 of 3 patients in whom no parathyroid tissue was found. The mean time to drop below 1.5 was 2.0 +/- 0.8 h (mean /+- SD) from the time of parathyroidectomy. UcAMP fell below 1.5 in only 1 of 6 patients who had multiple enlarged parathyroid glands removed, irrespective of the outcome of surgery. Changes in Up excretion lagged behind UcAMP changes, so that within the time period studied Up fell to varying degrees in only 10 of 15 patients in whom hypercalcemia was corrected. A spurt in UcAMP excretion, possibly reflecting parathyroid hormone release due to manipulation of a parathyroid gland, occurred in 3 patients. The results suggest that an intraoperative fall in UcAMP below 1.5 predicts successful parathyroidectomy and that an intraoperative spurt in UcAMP may provide a clue to the location of abnormal parathyroid tissue.

Calcium

Effect of parathyroidectomy on serum 1 alpha,25-dihydroxyvitamin D and intestinal calcium absorption in primary hyperparathyroidism.

Serum concentration of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] and intestinal absorption were measured before and after parathyroidectomy in 11 patients with primary hyperparathyroidism. Serum 1,25(OH)2D was high preoperatively (P less than 0.001) and normal postoperatively. Ca absorption was elevated preoperatively (P less than 0.001) and decreased significantly after parathyroidectomy (P less than 0.001). However, 5 of 11 patients had a persistent hyperabsorption of Ca postoperatively, despite normal serum 1,25(OH)2D. The results suggest that factors other than 1,25(OH)2D contribute to the maintenance of high intestinal Ca absorption in hyperparathyroid patients in the postoperative state.

Adult

Parathyroidectomy in chronic renal failure.

During the period 1971-1976, subtotal parathyroidectomy was performed on 34 patients with chronic renal failure, representing 8% of all uraemic patients treated on the Renal Ward. Preoperative treatment of renal failure was conservative therapy in 6, haemodialysis in 20 and renal transplantation in 8 patients. The operation was indicated by grave clinical symptoms (pruritus, bone pains and mental disturbances), gastric ulcer and radiological abnormalities (osteoporosis, fractures, subperiosteal resorption and metastatic calcifications). The serum immunoreactive parathyroid hormone was determined in 13 cases, and the value was elevated in all. The serum calcium level was elevated in 8 out of 34 cases. Less than 500 mg of parathyroid tissue was removed in 12 cases, between 500 and 6000 mg in 19 and over 6000 mg in 3. Nodular hyperplasia was present in 11 patients, diffuse hyperplasia in 23. Postoperatively marked falls in serum parathyroid hormone and serum calcium values were observed. The bone pains, pruritus and mental disturbances were alleviated, and the general condition was favourably influenced. The operation had a lesser and more retarded effect on the radiological changes. Complete recovery was only achieved with successful renal transplant. Parathyroidectomy often had a favourable effect on the grave symptoms and may, therefore, be considered in some cases of severe hyperparathyroidism secondary to chronic renal failure.

Adolescent

Post-parathyroidectomy psychosis: clinical and research implications.

The case of a 52-year-old female who suffered a post-parathyroidectomy pyschosis is presented and similar cases from the literature are reviewed. Studies of calcium and mangnesium metabolism in mental illness are reviewed, as fluctuations of these ions are felt to be involved in the pathogenesis of this condition. A definable syndrome of post-parathyroidectomy psychosis may exist and the implications of such a syndrome are discussed.

Calcium

Results of parathyroidectomy for autonomous hyperparathyroidism.

Autonomous hyperparathyroidism occurred in 15% of 152 patients maintained by long-term home dialysis during the past nine years. Twenty-two patients with elevated serum parathormone levels and progressive bone disease in the presence of normal serum phosphate and calcium levels were treated by subtotal parathyroidectomy. All had parathyroid hyperplasia. Eighteen of the 22 patients are presently alive and undergo dialysis. Symptoms of bone pain, pruritus, and muscle cramps had improved in three fourths of the patients. The serum parathormone level decreased from a preoperative average of 576 muLEq/mL to an average of 188 muLEq/mL postoperatively. All 18 patients, observed for six to 77 months, showed improvement in x-ray films of their bone disease. The autonomous hyperparathyroidism of end-stage renal disease is corrected by subtotal parathyroidectomy, and the effect is sustained.

Adult

Proximal and distal intestinal calcium transport in vitro as influenced by low calcium diet, uremia, parathyroidectomy and 1,25-dihydroxycholecalciferol treatment in rats.

Duodenal and ileal in vitro calcium transport was studied in 5/6 nephrectomized rats. Low calcium diet resulted in an increase of the duodenal calcium transport in kidney intact control animals but not in uremic rats; the ileal transport however increased in controls as well as in uremic rats. Parathyroidectomy decreased this adaptive transport at both gut sites in intact and uremic rats. Supplementation with low doses of 1,25-dihydroxycholecalciferol (1,25-DHCC) restored the duodenal transport in nephrectomized rats to the level of controls; nephrectomized plus parathyroidectomized animals increased the duodenal but not the ileal calcium transport. A close correlation between calcium transport and serum phosphorus concentrations of all groups of rats studied points towards a possible role of phosphate for intestinal calcium transport. It is concluded that duodenal calcium transport is regulated by the parathyroid-1,25-DHCC axis with 1,25-DHCC as effector; ileal calcium transport in contrast is regulated by combined direct effects of 1,25-DHCC and parathyroid hormone, the latter being essential for active transport.

Animals

Uraemic arterial disease. An experimental study with special reference to the effect of parathyroidectomy.

A histophatologic study of uraemic arterial lesions was performed in rats. They were made uraemic by 5/6 kidney resection, and the aorta and peripheral arteries were examined after intervals of up to 36 weeks. The characteristics of the arterial lesions were necrosis of medial smooth muscle cells and, in some cases, calcification of the media. The changes appeared first in the aorta, but after long uraemic periods also in peripheral arteries. The incidence and severity of necrosis and of calcification were assessed separately. Parathyroidectomy largely prevented the development of calcification, and to a lesser degree also smooth muscle cell necrosis. The results suggest that secondary hyperparathyroidism plays an important part in the development of uraemic arterial disease.

Adrenal Glands

Anti-beta adrenoreceptor blockade activity of plasma ultrafiltrate in two uraemic patients: effect of parathyroidectomy.

A possible interaction between d-1 propranolol and hyperparathyroid plasma ultrafiltrate on guinea pig auricles has been studied in "in vitro" experiments. Plasma ultrafiltrates have been samples in two patients on chronci haemodialysis before (pre-PTx) and after (post-PTx) parathyroidectomy. A significant inhibition of propranolol depressant activity on cardiac contractile strength has been observed in the presence of pre-PTx plasma ultrafiltrates. On the contrary, no such inhibition was noted in the presence of post-PTx plasma ultrafiltrates.

Animals

Secondary hyperparathyroidism and parathyroidectomy in terminal chronic renal failure.

Subtotal parathyroidectomy was performed on 34 patients with severe renal insufficiency. The indications were grave clinical symptoms (pruritus, bone pains and mental disturbances), gastric ulcer and radiological abnormalities (metastatic calcifications, osteoporosis, fractures and subperiostal resorption). The serum calcium level was elevated in eight cases. The serum parathormone value was determined in 13 cases, it was elevated in all cases. Less than 500 mg tissue was removed in 12, between 500 and 6000 mg in 19 and over 6000 mg in 3 cases. Nodular hyperplasia was demonstrated in 11 and diffuse hyperplasia in 23 patients. The serum calcium and parathormone levels fell markedly after the operation, and pruritus, bone pains and mental disturbances were markedly alleviated. Complete recovery was achieved only by a successful renal transplantation, but the operation had often a favourable effect on the grave symptoms.

Adolescent