微囊化新生猪甲状旁腺细胞异种移植的实验研究

目的 探讨微囊化新生猪甲状旁腺细胞异种移植治疗大鼠甲状旁腺功能低下症的效果。方法 应用微囊化技术，制备微囊化（海藻酸钠－聚赖氨酸－海藻酸钠生物微胶囊）新生猪甲状旁腺细胞，32只去甲状旁腺的Wistar大鼠随机分成微囊组、非微囊组、空囊组和对照组，分别移植微囊化新生猪甲状旁腺细胞、甲状旁腺细胞、空微囊及生理盐水。移植后监测血钙及甲状旁腺素水平40周，40周后回收移植物，透射电镜检查。结果 移植后，微囊组大鼠血钙及甲状旁腺素水平恢复到正常范围内，直至观察结束时（40周），透射电镜检查显示移植物存活良好；非微囊组、空囊组和对照组大鼠的血钙及甲状旁腺素水平无改善。结论 微囊化新生猪甲状旁腺细胞异种移植在不用免疫抑制剂情况下，可以在大鼠体内存活，且有功能；海藻酸钠－聚赖氨酸－海藻酸钠生物微胶囊对免疫活性细胞及抗体具有屏蔽作用。     

微囊化异种甲状旁腺组织移植的研究

目的探讨微囊化异种甲状旁腺(PTG)组织移植对Wistar大鼠甲状旁腺功能低下的治疗作用及微囊的通透性。方法 40只去甲状旁腺Wistar大鼠随机分为微囊组、非微囊组、空囊组、空白对照组。用海藻酸-钡交联微囊包裹兔甲状旁腺组织,移植至Wistar大鼠肾包囊。移植后每隔2周取血测血钙,移植后第16周取移植物进行透射电镜检查及T淋巴细胞、大鼠IgG抗体的免疫组织化学染色。结果微囊组移植后第4周血清钙由(1．62±0．04)mmol／L恢复至正常水平 (2．2～2．6)mmol／L,9例维持至观察期结束(P<0．01),非微囊组、空囊组及空白对照组血清钙差异无统计学意义(P>0．05)。第16周取出移植物检测显示移植物活性良好,微囊周围可见较多T 淋巴细胞浸润,囊壁及囊内IgG抗体染色阳性。结论海藻酸-钡交联微囊可对甲状旁腺组织起到有效的保护作用,使甲状旁腺组织较长时间存活并发挥正常功能。但海藻酸-钡交联微囊并未减轻受体免疫排斥反应的激活且未有效的免疫隔离IgG抗体。     

Serum calcium and phosphate concentrations and parathyroid morphology in rats treated with vitamin D metabolites

Summary The serum concentrations of calcium and phosphate and parathyroid morphology were studied in rats treated with vitamin D metabolites. Twenty hours after a single injection of 1.25-dihydroxycholecalciferol (1.25-DHCC) or 25-hydroxycholecalciferol (25-HCC) the serum calcium and phosphate concentrations were not significantly altered in any group, but the 1.25-DHCC treated rates exhibited an increased number of dark chief cells and occurrence of a few atrophic chief cells. Four to eight weeks after daily injections of the vitamin D metabolites the 1.25-DHCC treated rats exhibited significantly increased serum calcium concentrations and parathyroid glands composed of atrophic and dark chief cells in solid and follicular arrangement, whereas the rats treated with 25-HCC showed unaffected serum calcium concentrations and parathyroid glands composed of solid sheets of light chief cells, often with vacuolated cytoplasm, a few dark chief cells, but no atrophic cells. The findings suggest a direct or indirect suppressive influence of 1.25-DHCC on parathyroid activity in rats.     

Microencapsulation of parathyroid tissue with photosensitive poly(L-lysine) and short chain alginate-co-MPEG

Human parathyroid glands were encapsulated using the alginate-PLL system in this study. In order to improve the mechanical strength and the biocompatibility, the microcapsules were fabricated with a three-layer structure that consisted of alginate/photosensitive poly(L-lysine)/short chain alginate-co-MPEG. These modified microcapsules were used for encapsulating human parathyroid tissue. In vitro experiments revealed that microencapsulated parathyroid glands maintained differentiative properties in culture, and the capsular membrane was freely permeable to the human parathyroid hormone. For in vivo experiments, these capsules were transplanted into parathyroidectomized SD-rats. After parathyroidectomy, serum calcium decreased from 2.25 to 1.68 mmol/L and remained in a constantly low concentration until transplantation. Parathyroidectomized SD-rats were normocalcemic after transplant of encapsulated parathyroid tissue. The microcapsules were then explanted at 12 weeks for examination. Histological evaluations of excised transplants revealed that the microcapsules remained intact structurally and were free of cell adhesions. The results demonstrated that human parathyroid tissue microencapsulated by this system retains stability and is functional both in vitro and in vivo. This encapsulating system will have valuable application for endocrine surgery in the future.     

Modified cryopreservation and xenotransplantation of human parathyroid tissue

Introduction: A modified cryopreservation technique for human parathyroid tissue was compared with the standard method using a programmed freezer. Methods: Total parathyroidectomy was performed in three groups of 6-week-old Rowett nude rats. Group I (control) underwent no transplantation of parathyroid tissue (n=9). After 10 days, the rats of groups II (n=15) and III (n=15) underwent xenotransplantation of 20 mg cryopreserved human parathyroid tissue, which had been stored in liquid nitrogen at –196°C for 1–22 months prior to xenotransplantation. The parathyroid tissue was derived from 15 parathyroidectomized patients with renal hyperparathyroidism. Two tissue samples were obtained from every patient. One sample from every patient was cryopreserved by means of the technique of programmed cryopreservation: programmed freezing of human parathyroid tissue at a controlled rate of –1°C/min to –80°C prior to transfer to liquid nitrogen (group II). The second sample from every patient was cryopreserved by means of a modified cryopreservation technique: immediate placement of human parathyroid tissue in a freezer at –20°C and transfer to liquid nitrogen after 2 h (group III). Calcium and intact parathyroid hormone concentrations in serum were determined over a period of 60 days. Furthermore, individual differences in the calcium concentrations were assessed for each rat on the basis of the calcium levels recorded preoperatively and at day 60. Results: All animals in the control group developed hypocalcemia. Serum calcium concentrations returned to normal levels 60 days after xenotransplantation of parathyroid tissue, which had been cryopreserved using the modified technique (group III) in 12 of 15 rats (80%). At day 60, serum calcium had normalized in 10 of 15 rats (67%) after xenotransplantation of parathyroid tissue cryopreserved using programmed freezing (group II). After modified cryopreservation (group III), the median individual difference in the calcium concentrations was –0.16 mmol/l after programmed freezing (group II). At the end of the study, a median level of human intact parathyroid hormone of 3.5 pg/ml and 2.4 pg/ml was estimated for groups II and III, respectively. There was no statistical significant difference of the individual differences in the calcium concentrations or of the levels of human intact parathyroid hormone between groups II and III. Conclusion: Human parathyroid tissue was successfully xenografted in the present experimental study. The results obtained after cryopreservation using the described modified technique were equivalent to those recorded after controlled freezing in a programmed freezer. The simplified cryopreservation technique therefore appears to be suitable for human parathyroid tissue. Received: 8 July 1998 Accepted: 11 February 1999     

人胚甲状旁腺细胞移植治疗甲状旁腺功能低下症

目的　探讨人胚甲状旁腺细胞移植治疗甲状旁腺功能减退症的临床意义。　方法　将培养的人胚甲状旁腺细胞在B超引导下移植到 6例甲状旁腺功能减退症患者的肾周围脂脂囊中。应用放射免疫方法测定患者术前、术后血中甲状旁腺激素 (PTH)及钙水平 ,并进行自身对照 ,对疗效进行评价。　结果　 6例患者在接受人胚甲状旁腺细胞移植前 ,血钙及PTH平均水平分别为 (1 6 3±0 12 )mmol/L及 (1 36± 0 2 1)ng/L ;接受移植 3d后分别为 (1 77± 0 2 2 )mmol/L及 (9 5 3± 2 2 1)ng/L ,两者差异有显著性意义 (P <0 0 1) ;6d后达正常水平 ,临床症状逐渐减轻至消失 ;术后观察 9～ 12个月病情保持稳定。　结论　培养的人胚甲状旁腺细胞肾周围脂肪囊内移植是治疗甲状旁腺功能减退症的一种较理想的新方法     

Effect of aluminium load on parathyroid hormone synthesis.

BACKGROUND: Aluminium overload leads to parathyroid hormone (PTH) suppression. However, it is unclear whether a decrease in synthesis or release of the hormone is mainly involved. The aim of this study was to assess the effect of an acute administration of aluminium on PTH synthesis and release in rats with chronic renal failure and secondary hyperparathyroidism. METHODS: The study was performed using 100 adult male Wistar rats (body weight 443+/-54 g). 7/8 nephrectomy was performed and the rats were maintained on a high dietary phosphorous intake. Five weeks after surgery, the rats were randomly divided into two groups, one loaded with aluminium (AlCl3) and the other given placebo. Aluminium or placebo were administered i.p. for two consecutive days. The placebo group received saline at the same pH as the aluminium solution. After 2 weeks, serum calcium, phosphorous, creatinine, PTH, and aluminium were measured. The parathyroid glands were removed and PTH messenger RNA (mRNA) was measured by northern blot. Intact PTH was measured by IRMA (Rat PTH, Nichols Institute). RESULTS: No differences in serum PTH levels were found between the two groups after 5 weeks of renal failure. At the end of the study the rats given aluminium had higher aluminium levels than the placebo group and lower PTH levels. No significant differences were found for calcium, phosphorous, renal function, or body weight. PTH mRNA expression was lower in the aluminium group than in the placebo group. CONCLUSION: The administration of aluminium in rats with chronic renal failure resulted in reductions in serum PTH and PTH mRNA. Thus far, previous studies had demonstrated that aluminium suppressed PTH release. The present findings suggest that PTH synthesis is also reduced.     

Compensatory parathyroid hypertrophy after hemiparathyroidectomy in rats feeding a low calcium diet

Summary The functional and anatomic compensatory response of the parathyroid gland was examined in hemiparathyroidectomized (HPTx) rats whose parathyroid hormone (PTH) secretion was stimulated by a low calcium diet. These responses were compared with those observed in the thyroid gland of hemithyroidectomized (HTx) rats. Rats kept on a low calcium diet for 10 days were subjected to HPTx, HTx, or sham operations. Throughout the experiment (up to 28 days after surgery), serum calcium levels of HPTx rats were lower than the basal, with Δ values (mg/dl, mean±SEM) of −0.66±0.17 and −0.84±0.17, (P<0.05) 3 and 28 days after surgery, respectively. Serum PTH decreased significantly from 7 to 21 days after HPTx, reaching normality at day 28 after surgery. In HTx rats, serum thyroxine (T4) levels diminished significantly 7 days after surgery, and attained normality thereafter. The mitotic index (number of metaphases/1,000 cells) in parathyroid glands of colchicine-treated HPTx rats increased significantly in comparison to sham-operated controls, when examined 2 or 40 days after surgery. The mitotic index of thyroid follicular cells was significantly higher than that of their respective controls, 2 but not 40 days after HTx. These results indicate that after HPTx, a delayed compensatory response is found when the animals are kept under a low calcium diet. Parathyroid response is both delayed and of a minor degree compared to that found in the thyroid gland after HTx.     

Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model

Introduction

Implantation of TheraCyte 4?×?10⁶ live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model.

Materials and methods

Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N?=?20); Group 2 rats were implanted with TheraCyte-encapsulated 4?×?10⁶ live parathyroid cells into the subcutis of their necks (TheraCyte; N?=?20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH).

Results

Based on manual palpation, the control group had a fusion rate of 33?% (6/18) and the TheraCyte group had a fusion rate of 72?% (13/18) (P?=?0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P?<?0.05); neither serum calcium nor phosphorus levels were significantly different between the two groups.

Discussion

This pilot animal study revealed that there were more fusions in rats that received TheraCyte-encapsulated 4?×?10⁶ live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.     

同种异体甲状旁腺组织移植治疗甲状旁腺功能低下的实验研究

目的 探讨甲状旁腺经不同预处理并移植于腹直肌内后甲状旁腺移植物的功能和生存情况.方法 成年雄性Wistar大鼠70只作为供体,成年雄性SD大鼠35只作为受体,建立去甲状旁腺模型受体后采用随机数字表法随机分为直接移植组、高氧培养移植组、环孢素A组、60Co照射移植组及综合处理组5组,每只受体接受2只供体的4个甲状旁腺组织块,甲状旁腺移植于大鼠的腹直肌内.观察各组大鼠在甲状旁腺移植前后不同时相血清钙和甲状旁腺激素(PTH)的变化.结果 各组在甲状旁腺组织移植后,1周内血清钙和PTH均能达到或接近正常水平,与移植前相比差异均有统计学意义(P＜0.01).各组移植物的存活时间不同,直接移植组的存活时间最短,血清钙和PTH维持正常水平的时间分别为3周和4周.高氧培养移植组、环孢素A组、60Co照射移植组以及综合处理组血清钙及PTH维持在正常或接近正常水平的时间分别为5周和8周、6周和8周、5周和7周以及5周和9周;除高氧培养移植组移植术后9周(血清钙)及60Co照射移植组移植术后8周(PTH)差异无统计学意义外,其余4组的血清钙和PTH水平在移植术后4～9周与直接移植组比较其差异均具有统计学意义(P＜0.05),直接移植组较低;高氧培养移植组、CsA组和60Co照射移植组的血清钙和PTH水平在移植术后7～9周低于综合处理组(P＜0.05),综合处理组的血清钙和PTH的维持时间较长.结论 腹直肌内甲状旁腺移植能维持血钙于正常水平;甲状旁腺移植物或受体经预处理后能延长其存活时间.甲状旁腺组织经培养后再移植是治疗甲状旁腺功能减退症的一条有效途径.     

Sevelamer hydrochloride reverses parathyroid gland enlargement via regression of cell hypertrophy but not apoptosis in rats with chronic renal insufficiency.

BACKGROUND: Dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion, synthesis, and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI), independently of serum calcium and 1,25(OH)2D3 levels. This study was conducted to examine whether sevelamer hydrochloride (sevelamer), a metal-free phosphate binder, could regress an advanced parathyroid gland (PTG) hyperplasia and enlargement in rats with CRI. METHODS: Male Sprague-Dawley rats were fed a diet containing adenine for 6 weeks to establish CRI. Normal rats and adenine-treated rats were sacrificed to obtain the PTG (baseline group). The adenine diet was changed to a normal diet or diet containing 1 or 3% sevelamer for another 4 weeks. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of the study, the PTG was weighed and examined histologically. RESULTS: Adenine-treated rats developed severe CRI with marked elevation of serum phosphorus and PTH. The PTG weight markedly increased with enlarged cell volume (i.e. cell hypertrophy) at baseline. Sevelamer treatment rapidly lowered serum phosphorus and PTH levels within 6 days, and after 4 weeks, reduced the PTG weight by 38% compared to adenine-treated rats at baseline. The reduction in PTG weight was due to regression of cell hypertrophy, but not to decreased cell number by apoptosis. Decreased expression of calcium receptor in the PTG at baseline was partially recovered by the sevelamer treatment. CONCLUSIONS: The sevelamer treatment can reduce the PTG weight with a reduction in serum PTH levels via regression of cell hypertrophy but not apoptosis in rats with CRI. Reduced PTG function might contribute to the regression of cell hypertrophy.     

Routine parathyroid autotransplantation during total thyroidectomy: the influence of technique.

OBJECTIVE: To find out whether injecting a suspension of finely minced parathyroid tissue into the muscle bed had any adverse outcomes as it is simpler and potentially safer than implanting parathyroid tissue into muscle pockets. DESIGN: Prospective, randomised, controlled clinical trial. SETTING: University hospital, Australia. PATIENTS: 50 patients who were to have total thyroidectomy and routine parathyroid autotransplantation. INTERVENTIONS: Patients were randomised to either the injection technique or the implantation technique. MAIN OUTCOME MEASURES: Clinical assessment; corrected serum calcium and intact parathyroid hormone concentrations (PTH) measured immediately before, and at 1 day, 2 weeks, and 3 months after operation. RESULTS: Calcium was reduced significantly in both groups immediately after thyroidectomy. Although mean PTH concentrations decreased immediately after thyroidectomy and parathyroid autotransplantation in both groups, these changes were significant only in the implantation group. By 2 weeks and again by 3 months, calcium and intact parathyroid hormone concentrations had returned to baseline in both groups. At 3 months, 2 patients in each group still required some form of calcium supplement. At 6 months, no patients in the injection group required supplement. CONCLUSIONS: Injection of a suspension of parathyroid tissue is a simple, safe, and rapid technique for parathyroid autotransplantation during total thyroidectomy and is not associated with any more adverse outcome than is the standard technique.     

A portal factor influences serum calcium homeostasis.

In order to evaluate the importance of a portal factor in serum calcium homeostasis, end-to-side portacaval shunts were performed in groups of adult, male Lewis rats either before or after parathyroidectomy. Subsequent changes in serum calcium values were followed. When parathyroidectomy was performed one day or 28 days after a portacaval shunt, hypocalcemic changes occurred soon after. However, in these shunted, parathyroidectomized animals which were maintained on a normal calcium diet the serum calcium concentrations soon began to rise and by three weeks after operationthe rats became normocalcemic. In animals which had a portacaval shunt performed three days after parathyroidectomy, the serum calcium levels again rose and became normal in approximately three weeks. In the shunted, parathyroidectomized animals, both the serum calcium and phosphorus concentrations remained normal as long as the rats were maintained ona normal calcium diet. When a low calcium diet was introduced, marked hypocalcemia occurred and serum parathyroid hormone values were barely detectable, both of which attest to the completeness of parathyroidectomy. These data support the hypothesis that following portacaval shunt, a calcium elevating factor, which is similar in action to parathyroid hormone but is not PTH itself, bypasses the liver and becomes effective in the systemic circulation. It acts to correct the hypocalcemia and hyperphosphatemia of parathyroidectomized rats. The possible role of various known gastrointestinal factors in this process is discussed.     

Sevelamer hydrochloride (Renagel), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency.

BACKGROUND: It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI. METHODS: Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser. RESULTS: Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area. CONCLUSIONS: Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.     

Treatment of osteoporosis with TheraCyte-encapsulated parathyroid cells: a study in a rat model

Introduction The purpose of this study was to evaluate parathyroid function at monthly intervals following the implantation of TheraCyte-encapsulated live human parathyroid cells into ovariectomized rats and to determine the effect on bone mineral density (BMD) 4 months after ovariectomy ( 3 months after implantation). Methods Parathyroid tissues were obtained from patients undergoing surgery for secondary hyperparathyroidism. In total, 21 Sprague-Dawley rats divided randomly into three groups were subjected to one of three treatments: (1) implanted with TheraCyte A-encapsulated 4×10⁶ live parathyroid cells; (2) implanted with TheraCyte B-encapsulated 4×10⁵ live parathyroid cells; (3) a sham operation; the control group. Rats were ovariectomized 1 month prior to the implantation of the TheraCyte. Blood was drawn at the time of implantation and at monthly intervals thereafter for 3 months to check the levels of calcium, phosphorus and intact parathyroid hormone (iPTH). The BMD of the lumbar spine (L1–L5) and of the left femoral bone was measured with dual-energy-X-ray absorptiometry (DEXA) 1 month after ovariectomy and 3 months after implantation of the TheraCyte (4 months after ovariectomy). Results We found that the viability ratio of cryopreserved tissues was between 55 and 79% after thawing. In the control group, the BMD of the lumbar spine (L1–L5) had not decreased significantly (p=0.237) nor had the BMD of the left femoral bone increased significantly (p=0.063) 3 months after implantation. In the TheraCyte A group, the BMD of both the lumbar spine (p=0.018) and left femoral bone (p=0.018) had increased significantly 3 months after implantation. In the TheraCyte B group, the BMD of both the lumbar spine (p=0.017) and the left femoral bone (p=0.025) had also increased significantly 3 months after implantation. Serum iPTH levels were higher in the TheraCyte A group than in the TheraCyte B group (p=0.006), and higher in the TheraCyte B group than in the control group (p=0.040). Serum calcium levels were not significantly higher in the TheraCyte group A than in the TheraCyte B group or in the control group. Serum phosphorus levels were not significantly different between the TheraCyte A and TheraCyte B groups. Conclusions Implantation of TheraCyte A-encapsulated 4×10⁵ live parathyroid cells and TheraCyte B-encapsulated 4×10⁶ cells can increase the BMD of ovariectomized rats within 3 months of implantation. Neither cause high serum calcium and low phosphorus concentrations.     

Sensitivity of the thyroid and parathyroid glands to radiation

Iodine-125 seeds selectively inhibited thyroid compared with parathyroid function. Stimulation of thyroid tissue by TSH and suppression of thyroid tissue by thyroxine did not alter the sensitivity of thyroid tissue to radiation, since serum TSH concentrations were not different in the thyroxine-suppressed, control, or TSH-stimulated animals 9 weeks after discontinuing the radiation. TSH stimulation by the low iodine diet and TSH suppression by exogenous thyroxine did alter the function of the parafollicular C cells of the thyroid, since serum calcitonin concentrations were increased in the former and decreased in the latter. Serum calcium concentrations were also increased in the rats receiving the low iodine diet, but the reason for this increase is not known.     

Assessment of parathyroid autotransplantation for preservation of parathyroid function after total thyroidectomy

BACKGROUND: Hypoparathyroidism with permanent hypocalcemia is a well-recognized complication after thyroid surgery. AIM: This study was conducted to assess the role of immediate parathyroid autotransplantation in the preservation of parathyroid function after total thyroidectomy. PATIENTS AND METHODS: Twenty-eight patients had autotransplantation of parathyroid glands resected or devascularized during total thyroidectomy. Data were collected prospectively regarding demographics, indication for surgery, operative procedure, pathologic diagnosis, number of glands transplanted, and subsequent course. Thyroid nodules were evaluated by ultrasonography, radionuclide scanning, and/or fine-needle aspiration cytology. All patients had serum ionized calcium, phosphorus, and intact parathyroid hormone (PTH) levels measured preoperatively and monitored regularly postoperatively for a period of 14 weeks and again at 6 months after operation. Patients were categorized into three groups according to the number of glands transplanted: one (group 1, n = 6), two (group 2, n = 14), or three glands (group 3, n = 8). In three other volunteers, one parathyroid gland was transplanted in the brachioradialis and subjected to electron microscopy 1, 2, and 4 weeks after transplantation. RESULTS: Total thyroidectomy was performed for malignant disease in 16 patients (57.1%) and for benign disease in 12 (42.9%) patients. All patients reverted to asymptomatic normocalcemia without the need for any medications within 4 to 14 weeks. Normal levels of serum markers were regained slower when one gland was transplanted compared with two or three glands (P <.01). Electron microscopic examination showed evidence of ischemic degeneration in the transplanted tissues 1 week postoperatively. Regeneration started by the second week and coincided with normalization of PTH levels. Optimum resting and nearly normal status of parathyroid tissue was achieved by the fourth week. CONCLUSIONS: This study showed that active PTH production coincides with regeneration of parathyroid cells and that autotransplantation of at least two resected or devascularized glands during total thyroidectomy nearly eliminates permanent postoperative hypoparathyroidism, thus improving the safety of total thyroidectomy performed for malignant or benign disease.     

The effect of chronic ammonium chloride ingestion on parathyroid hormone function.

The purpose of this study was to examine the effect of ammonium chloride ingestion on the hypercalcemic effect of parathyroid hormone in vivo. Thyroparathyroidectomized rats were given 1.5% ammonium chloride for 5-6 days. Ingestion of ammonium chloride increased serum calcium, but also significantly enhanced the calcium elevating effect of injected parathyroid extract. This result is compatible with a proposed hypothesis that the calcium mobilizing function of the parathyroid hormone may be enhanced by the hormone's own influence on systemic hydrogen ion concentration.     

Effect of fluoride on parathyroid activity of normal and calcium-deficient rats

Summary Forty 5-week-old rats were randomly divided into 1 control group given a normal diet and water low in fluoride (0.026 mM/1) and experimental group receiving the same basic diet and a fluoride supplement of 2.6 mMol/l in the drinking water. After 30 weeks, half of the fluoride-supplemented and half of the nonsupplemented animals were given a calcium-deficient diet for another 16 weeks. Parathyroid activity was estimated by determinations of serum levels of parathyroid hormone and by light microscopic, morphometric evaluation of randomized sections of the parathyroid glands. Serum iPTH and parathyroid nuclear size were significantly increased in the calcium-deficient animals without any fluoride supplement. Fluoride administration to animals on a normal diet did not cause any increase in the serum iPTH levels or in the morphometric parameters for nuclear size. Calcium-deficient animals given a fluoride supplement also showed normal serum iPTH levels and normal parathyroid nuclear size. It is therefore concluded that fluoride does not induce hyperparathyroidism and, further, that fluoride seems to inhibit increased parathyroid activity caused by calcium deficiency.     

Effect of fluoride on parathyroid activity of normal and calcium-deficient rats

Forty 5-week-old rats were randomly divided into 1 control group given a normal diet and water low in fluoride (0.026 mM/1) and experimental group receiving the same basic diet and a fluoride supplement of 2.6 mMol/l in the drinking water. After 30 weeks, half of the fluoride-supplemented and half of the nonsupplemented animals were given a calcium-deficient diet for another 16 weeks. Parathyroid activity was estimated by determinations of serum levels of parathyroid hormone and by light microscopic, morphometric evaluation of randomized sections of the parathyroid glands. Serum iPTH and parathyroid nuclear size were significantly increased in the calcium-deficient animals without any fluoride supplement. Fluoride administration to animals on a normal diet did not cause any increase in the serum iPTH levels or in the morphometric parameters for nuclear size. Calcium-deficient animals given a fluoride supplement also showed normal serum iPTH levels and normal parathyroid nuclear size. It is therefore concluded that fluoride does not induce hyperparathyroidism and, further, that fluoride seems to inhibit increased parathyroid activity caused by calcium deficiency.