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Basal and stimulated calcitonin secretion in primary hyperparathyroidism before and after parathyroidectomy.

To investigate calcitonin secretion in primary hyperparathyroidism, basal and stimulated (3 mg Ca++/kg body weight/10 min) immunoreactive calcitonin plasma levels were studied before parathyroidectomy. Plasma calcitonin levels were raised in 50% of patients regardless of sex, but a significant correlation between basal plasma calcium and calcitonin was found only in males. A reduced calcitonin response to calcium infusion was observed in all patients. Parathyroidectomy invariably induced a normalization of calcitonin basal levels. Our findings confirm the existence of a decreased parafollicular cell reserve probably as a consequence of the persistent hypercalcemic state in hyperparathyroid patients and suggest that it is more frequent in females.

Adult↗

Feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) 99mTc-sestamibi protocol.

Aim of the present study was to investigate the feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) 99mTc-sestamibi dose protocol compared to conventional "high 740 MBq (20 mCi) 99mTc-sestamibi dose protocol" in patients with primary hyperparathyroidism (PHPT). The data of focused radioguided surgery obtained in a group of 320 consecutive PHPT patients with high probability of the presence of a solitary parathyroid adenoma (PA) were studied. All patients underwent preoperative imaging work-up of double-tracer 99mTc-pertechnetate/99mTc-sestamibi subtraction parathyroid scintigraphy (Sestamibi scintigraphy) and high resolution neck ultrasound (US). In 301/320 patients (96.6%) focused minimally invasive radioguided surgery was successfully performed by administering a "low" 37 MBq (1 mCi) 99mTc-sestamibi dose in the operating room 10 minutes before operation. No major intraoperative complications were recorded. Focused radioguided surgery required a mean time of 32 min and a mean hospital stay of 1.2 days. Local anesthesia was applied in 75 patients, 66 of whom (88%) were patients older than 65 years with comorbidities contraindicating general anesthesia. No case of persistent or recurrent PHPT was observed during post-surgical follow-up (range = 18-70 months; mean +/- SD = 15.3 +/- 9.1 months). Radiation exposure dose to the operating surgeon was 1.2 microSi/hour with the "low 37 MBq (1 mCi) 99mTc-sestamibi dose", and less than 1.0 microSi/hour for the other operating-room personnel. Focused low dose radioguided parathyroidectomy is a safe and effective means to localize parathyroid adenomas in patients affected by solitary PA thus reducing by 20 fold the radiation exposure dose to the patients and operating room personnel.

Journal Article↗

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↗

Growth hormone, prolactin and insulin following arginine infusion in primary hyperparathyroidism before and after parathyroidectomy.

The secretion of growth hormone, prolactin and insulin following arginine infusion was studied in 9 patients with primary hyperparathyroidism before and after parathyroidectomy. Growth hormone, insulin and glucose levels after arginine administration were significantly higher before parathyroidectomy compared with the corresponding data obtained in the post-operative state, whereas plasma prolactin concentrations did not differ before and after operation.

Adult↗

Cortical bone mineral content in primary hyperparathyroidism. Changes after parathyroidectomy.

The bone mineral content (BMC) of 35 patients with primary hyperparathyroidism (PHPT) was measured at the mid radius (95% cortical bone) by photon absorptiometry of a 241Am source. The majority of the patients had an overt disease of moderate to severe degree. Average serum calcium of the group was 12.3 mg/100 ml (range 10.6 to 18.0 mg/100 ml). The percentage of normality of the BMC was (Av +/- 1 SD) 75.1 +/- 13.0% for the whole group. The average increment of BMC in 14 patients 9 to 26 months after parathyroidectomy was 9.9%, with a wide dispersion. However a highly significant negative correlation (r: 0.83; P less than 0.01) was found between the initial bone mass and the percentage increment per month after surgery. No further gain was observed 2 years after parathyroidectomy except in one patient with an extremely severe bone loss. In spite of the gain obtained after surgery the bone mass remained markedly diminished in most patients showing that the cortical bone loss caused by PHPT is mainly irreversible.

Adolescent↗

Selective intraarterial DSA of the parathyroid glands in patients with hyperparathyroidism after parathyroidectomy.

Eighteen patients with recurrent hyperparathyroidism after parathyroidectomy were prospectively examined with selective intraarterial digital subtraction angiography (DSA) of the brachiocephalic arteries. The results were compared with findings at reoperation. Seventeen of the 21 remaining abnormal parathyroid glands were correctly detected by selective DSA (sensitivity = 81%). In the neck and mediastinum, sensitivities were 73% (8/11) and 90% (9/10), respectively. All patients with histopathologic confirmation of primary hyperparathyroidism (17/18) became normocalcemic postoperatively. We conclude that selective intraarterial DSA is indicated in patients with recurrent hypercalcemia after parathyroidectomy when the results of noninvasive imaging techniques are uncertain.

Adolescent↗

Vertebral mineralization after parathyroidectomy: measurement by quantitative CT.

Quantitative CT has been used to document abnormally low levels of vertebral bone mineral in hyperparathyroid states. No one has yet reported an improvement in vertebral bone mineral concentration after parathyroidectomy. Quantitative CT was used to measure mineralization of lumbar vertebral bodies in five women with primary hyperparathyroidism, at the time of surgical resection of a parathyroid adenoma and again 4 months after surgery. Four of the patients had increased vertebral mineralization after 4 months; the increase for the entire group (13%) was statistically significant. In one patient, examined for a third time 8 months after surgery, a continuing increase in vertebral bone mineral concentration was seen. A final examination, obtained 20-33 months after surgery, revealed that in every patient the bone mineral concentration was lower than on the first postoperative study and in some cases was less than the original preoperative measurement. We conclude that a temporary increase in vertebral trabecular mineralization occurs after parathyroidectomy for primary hyperparathyroidism. During the following 3 years, however, this increase is not sustained.

Adult↗

The aortic content of glycosaminoglycans, hydroxyproline and calcium in experimental uraemia with special reference to parathyroidectomy and vitamin-D treatment.

The contents of the various glycosaminoglycan (GAG) fractions, hydroxyproline and calcium in the thoracic aorta from the rat were studied. The effect on these contents of induced uraemia (3/4 kidney resection) combined with parathyroidectomy and/or 1-alpha-hydroxycholecalciferol (1-alpha-OH-D3) treatment was evaluated. Confirming earlier results increased levels of GAGs (predominately of chondroitin and dermatan sulphate) were found in the aortae of uraemic rats. The present study showed that parathyroidectomy or treatment with 1-alpha-OH-D3 did not significantly further alter the aortic content of GAGs in uraemic rats. Arteriosclerotic changes (calcifying medial necrosis) were only found in non-parathyroidectomized uraemic rats given 1-alpha-OH-D3. The aorta from these rats had a lower total content of GAGs, mainly due to a decrease in hyaluronic acid, than that from uraemic rats without calcifications. The aortic content of calcium was lowest in uraemic parathyroidectomized rats. Treatment with 1-alpha-OH-D3 increased this content, which was augmented 100-200-fold when calcifications were present. No correlation between the aortic contents of calcium and GAGs was found. There was a statistically significant correlation between the aortic content of calcium and the serum calcium X phosphate product. A significantly lower content of hydroxyproline was found in uraemic non-parathyroidectomized rats given 1-alpha-OH-D3, especially in those with arteriosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Osteomalacia after parathyroidectomy in patients with uremia.

Five patients on maintenance dialysis had symptoms of osteomalacia, proven by biopsy, after parathyroidectomy. In all five patients clinical and radiographic manifestations of secondary hyperparathyroidism were present before surgery, and in two patients preoperative biopsy of bone confirmed the existence of osteitis fibrosa. Like previously described patients with osteomalacia all five had multiple fractures and normal or high serum calcium concentrations that rose to abnormally high values on treatment with vitamin D or dihydrotachysterol. Quantitative histomorphometry of biopsy after parathyroidectomy showed no residual parathyroid hormone effect and nearly complete cessation of mineralization. Four patients had forearm autografts of parathyroid tissue that appeared to be functioning at very low rates according to paired venous sampling, and all five patients had relatively low circulating concentrations of parathyroid hormone. This and earlier experiences reported by others suggest that secondary hyperparathyroidism may have an important facilitative role in the mineralization of bone in uremic patients.

Adult↗

Radioguided parathyroidectomy for reexploration of primary hyperparathyroidism-- a case report.

BACKGROUND: We report a case of radioguided parathyroidectomy using a hand-held gamma probe for the reexploration of primary hyperparathyroidism. CASE REPORT: The patient was a 66-year-old Japanese woman. She had previously undergone surgical exploration for primary hyperparathyroidism due to a left inferior parathyroid tumor detected by 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy. However, the pathological diagnosis of the resected tumor was adenomatous goiter. 99mTc-MIBI scintigraphy was performed again and revealed an abnormal uptake close to the right lower lobe of the thyroid. However, venous sampling for PTH measurements did not support this finding. Sestamibi was injected and the radioactivity was measured pre- and intraoperatively with a hand-held gamma probe. With the patient under general anesthesia, the tumor, which was adjacent to the right recurrent laryngeal nerve, was resected, but it contained only a low level of radioactivity ex vivo, indicating that it was not a parathyroid tumor. A hand-held gamma probe accurately located the radioactive parathyroid tumor in the right lower neck. The resected tumor measured 15 x 6 mm and weighed 331 mg. The pathological diagnosis was parathyroid adenoma. CONCLUSIONS: Radioguided parathyroidectomy is useful to localize parathyroid tumors not only in primary hyperparathyroidism at the initial neck exploration but also for reexploration.

Adenoma↗

The role of the parathyroids for the adaptation to a low calcium intake. 3. The long-term effect of parathyroidectomy on the adaptation to a low calcium intake in adult rats with special reference to plasma calcium, bone tissue and adrenal glands.

One-year-old selectively parathyroidectomized rats responded with a plasma calcium reduction to below 4.1 mEq./1 in 86 per cent at a normal and in 100 per cent at a low dietary calcium intake. Among the former, 17 per cent normalized their plasma calcium level within 8 weeks and another 40 per cent between the 8th ana 27th week of observation. Among the latter, only 10 per cent showed a normalization and first after the long-term period of observation. On the normal level of dietary calcium the parathyroidectomized animals with persistently reduced plasma calcium showed a significantly increased bone mass which was paradoxical in view of their inability of adaptation. On the low level of dietary calcium a normal bone resorptive activity was maintained despite parathyroidectomy possibly through the action of increased levels of 1,25-dihydroxycholecalciferol provoked by the profoundly reduced plasma calcium. This was, however, insufficient for adaptation and no osteoporosis developed. For the adaptation to a reduced calcium intake skeletal calcium reserves had to become mobilized through the action of the parathyroids with resulting osteoporosis. This was brought about by increased mobilization of skeletal calcium with resulting osteoporosis, a phenomenon which could be seen also among the parathyroidectomized animals on a low dietary calcium and with a normalized plasma calcium level. This osteoporosis was similar to that found in the calcium deficient intact animals. The described bone changes were progressing in character and there was no major influence by any eventual effect on bone growth. At histological and morphometric analyses of the adrenal cortex no apparent changes were found after parathyroidectomy.

Adaptation, Physiological↗

[Novel approach to parathyroid adenoma: minimally invasive, focused, scan guided parathyroidectomy--experience from the first 100 cases].

BACKGROUND: Traditionally, the surgical approach to parathyroid adenoma included formal bilateral neck exploration, inspection and evaluation of all four glands. Recently, following progress in the precision of pre-operative localization by sonography and scintigraphy and the availability of a real time PTH assay, focused, minimally invasive approaches to the removal of a single adenoma were proposed. We review our experience in the first 100 cases. METHOD: After localization of the suspected adenoma by TC-99m-MIBI scintigraphy and neck sonography, a second scan was performed just before surgery and the presumed site was marked on the patients skin. Under general anesthesia, via a limited incision, the suspected adenoma was excised and examined by a frozen section. RESULTS: Between July 1999 and August 2001, 97 patients (64 females and 33 males, mean age; 56 +/- 14, range 19-88) underwent 100 focused, minimally invasive, MIBI guided parathyroidectomies (3 patients were operated on twice due to a residual second adenoma). Pre-operative blood levels of calcium and PTH were 11.5 +/- 0.8 mg/dl and 140 +/- 90 pg/ml, respectively. In 93 cases, an adenoma was identified and excised (mean weight, 600 mg, range, 100-4900). Mean operative time, including frozen section was 66 +/- 39 minutes. The patients were discharged on the same day or on POD 1 (mean calcium level 9 +/- 0.9 mg/dl) and had normal calcium levels at the follow-up tests. In 2 cases, the scan was falsely negative for adenoma (positive for other thyroid pathology), but the adenoma was successfully excised according to the sonographic localization (overall success rate in the primary procedure, 95%). In 3 cases, pathologically proven enlarged parathyroid was excised, as localized by the scan, but hypercalcemia relapsed. The patients were re-operated in a focused fashion and a residual second adenoma was found (N = 2), or underwent formal exploration for hyperplasia of the remaining 3 glands (N = 1). In 2 more cases, no parathyroid tissue was found in the specimen. However, consequently, calcium levels normalized after surgery (N = 1) and a successful focused re-operation was performed after relocalization (N = 1). There were no significant post-operative complications. CONCLUSIONS: Focused MIBI guided parathyroidectomy is safe and efficient in most patients. Failures, which may be the results of erroneous diagnosis (hyperplasia vs. adenoma, 1%), residual additional adenoma (2%) or a false positive scan due to pathology in the thyroid gland (2%), can be treated safely and effectively in a second focused procedure.

Adenoma↗

[Parathyroidectomy for patients with renal osteodystrophy].

It has been proposed that we should focus our attention on prevention of cardiovascular complication rather than to prevent osteitis fibrosa as the purpose to control secondary hyperparathyroidism (2HPT) induced by chronic renal failure. Active vitamin D and these analogues influence the bone turnover in hemodialysis patients and recently we often encounter the patients whose bone turnover is not high in spite of high PTH level. The aim of parathyroidectomy is gradually changed from improvement of bone disease to reduce high PTH level to prevent cardiovascular complication and extraskeletal symptoms. When it is difficult to control high PTH level without increase of calcium phosphate product, parathyroidectomy should be chosen.

English Abstract↗

Total parathyroidectomy and autotransplantation in hyperplasia of the parathyroid gland.

Hyperparathyroidism caused by multiple-gland hyperplasia has traditionally been treated by subtotal parathyroidectomy. Excellent results have been reported by some, particularly in primary hyperparathyroidism, but other have reported a significant incidence of recurrent hyperparathyroidism. Since 1979, we have chosen to avoid the possibility of remedial exploration of the neck and its attendant risks by treating all patients with primary and secondary hyperplasia with total parathyroidectomy and heterotopic autotransplantation. A total of 20 patients were studied. There were no failures of grafts and no operative complications. We conclude that this procedure is a reliable and safe alternative in the treatment of primary or secondary hyperplasia of the parathyroid gland.

Adult↗

Surgical findings and results of subtotal and total parathyroidectomy in hypercalcemic patients with uremic hyperparathyroidism.

Surgical and histopathologic findings and results of subtotal resection and total parathyroidectomy with autotransplantation were evaluated in 82 hypercalcemic patients with uremic hyperparathyroidism. The mean preoperative serum calcium concentration was 2.89 mM, and the highest values were associated with more rapidly progressing hypercalcemia. Despite greatly increased total weight of the parathyroid tissue (mean 1,509 mg), 34 patients had one to five normal-sized parathyroid glands. The incidence of such glands decreased with total gland weight. Nodular hyperplasia was found in 74% of the patients, and was characterized by considerable intraindividual size difference, while diffuse hyperplasia was associated with more moderate and symmetric glandular enlargement. During follow-up averaging 4.5 years, the incidence of persistent or recurrent hypercalcemia was slightly higher after subtotal than after total parathyroidectomy (11 and 11%, vs. 9 and 7%). Biochemical and/or radiologic signs of parathyroid bone disease were present in 36 (44%) of the patients before neck exploration and normalized postoperatively in all but seven. The outcome of parathyroid surgery thus was favorable in uremic patients with hypercalcemic hyperparathyroidism.

Adolescent↗

Time-dependent changes in serum gastrin measurements after parathyroidectomy.

A prospective study involving 7 patients with primary hyperparathyroidism and hypergastrinaemia was conducted to assess the time-dependent change in serum gastrin value before and after parathyroidectomy and to determine at which postoperative stage persistent hypergastrinaemia may be indicative of an associated gastrinoma (Zollinger-Ellison syndrome). Five of the 7 patients had hypergastrinaemia in the early postoperative period. One patient had a strikingly high serum gastrin level pre-operatively (1,500 pg/ml). The mean serum gastrin value declined to within the normal range 6 weeks after parathyroidectomy, except in 1 patient who had a gastrinoma. It is concluded that hypergastrinaemia in patients with primary hyperparathyroidism should only be considered significant if pre-operative gastrin levels are strikingly supranormal and/or levels fail to normalise by the 6th postoperative week.

Adult↗

Total parathyroidectomy with autotransplantation in haemodialysed patients with secondary hyperparathyroidism--should it be abandoned?

The development of secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. Medical management frequently fails and in such circumstances parathyroidectomy becomes a necessity. Total parathyroidectomy with autotransplantation of parathyroid tissue into the patient's forearm has been advocated as the surgical procedure of choice. In a previous publication we reported our experience with this technique in six haemodialysed patients. We now extend our follow-up to 19 patients over an observation period ranging from 6 to 66 months. Five of these patients required graft removal because of recurrent secondary hyperparathyroidism. Despite total graft removal, two patients had clinical and laboratory evidence of persistent hyperparathyroidism. Histology of the removed graft tissue demonstrated severe hyperplasia as well as invasion of adjacent muscle, adipose tissue, and vascular channels by parathyroid cells. This raises the possibility of local and distant metastatic spread of parathyroid tissue resulting in hyperparathyroidism. We suggest that parathyroid autotransplantation is potentially hazardous and should in fact be abandoned.

Female↗