Disorders of the parathyroid glands

The three calcitropic hormones, parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol and calcitonin are together responsible for calcium homeostasis in the mammal. Feline PTH is an 84 amino acid, single chain polypeptide with a molecular weight of 9449, which is secreted by the parathyroid glands. The principle secretagogue for PTH is a low plasma ionised calcium concentration, although both 1,25-dihydroxycholecalciferol and phosphate have significant roles in regulating PTH secretion. The ability to accurately measure circulating PTH in the cat has simplified the evaluation of disorders of calcium metabolism in this species. In primary parathyroid disorders the lesion is located within the parathyroid gland, with parathyroid secretion being inappropriate to the prevailing mineral balance. By contrast, in secondary conditions a pathological state out with the parathyroid gland alters mineral homeostasis and the parathyroid gland responds in an appropriate manner. The measurement of circulating PTH may then be used to determine if PTH secretion is appropriate to the prevailing calcium concentrations to differentiate primary from secondary disorders. Although primary hyper and hypoparathyroidism are generally considered rare endocrine conditions of the cat, the ability to measure PTH has led to their increasing recognition.     

成纤维细胞生长因子23在骨矿物质代谢中的作用及其调控机理

骨源性激素成纤维细胞生长因子23(FGF23)介导由甲状旁腺、肾脏、骨骼和维生素D组成的负反馈回路,建立"骨骼-肾脏-甲状旁腺"内分泌轴,参与骨矿物质代谢并发挥重要作用。钙、磷、铁、维生素D、甲状旁腺素(PTH)、成纤维细胞生长因子受体(FGFR)/FGF以及蛋白质翻译后修饰调控FGF23的分泌、活性和胞内过程。随着深入的研究,探索出了一些以FGF23为靶点治疗骨矿物质代谢障碍疾病的新疗法。本文综述了FGF23在骨矿物质代谢中的作用及其调控机理的研究进展,以期为相关研究提供参考依据。     

Effects of vitamin or mineral deficiency on the morphology of medullary bone in laying hens.

Adult laying hens were fed diets deficient in phosphorus, calcium, calcium and phosphorus, and vitamin D3 to determine their effects on bone histology and parathyroid gland size. The phosphorus deficient diet caused an insignificant decrease in parathyroid size while the other diets caused significant increases. A considerable amount of individual variation in medullary bone volume and osteoid seam width was observed in all groups but, despite this, the calcium, calcium and phosphorus and vitamin D3 deficient diets clearly resulted in increased osteoid. Birds receiving diets deficient in calcium and phosphorus, and in vitamin D3 for longer periods were observed to have partially or completely resorbed medullary bone. Osteodystrophia fibrosa was noted in vitamin D3 deficient birds which had no follicular activity.     

Short-term prednisolone therapy has minimal impact on calcium metabolism in dogs with atopic dermatitis

Glucocorticoids (GCs) are a large group of drugs used to treat a range of inflammatory, autoimmune and neoplastic diseases in dogs. Glucocorticoids have been linked to disturbances in calcium metabolism and skeletal disorders in humans, yet their effects at therapeutically effective dosages in dogs with spontaneous diseases are poorly understood. Serum concentrations of calcium, phosphate, vitamin D metabolites and plasma concentrations of parathyroid hormone and ionised calcium together with urinary fractional excretion of calcium and phosphate, were measured in 16 dogs with atopic dermatitis before and 6weeks after standard dosage prednisolone treatment (0.93-1.06mg/kg) every other day after 7days of treatment with the same dosage once daily. The severity of their physical signs, as assessed by the canine atopic dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh Pruritus Scale (EPS), decreased in all dogs following prednisolone treatment. There was no significant difference in any of the biochemical parameters measured following prednisolone treatment. This study indicates that prednisolone, used at a therapeutically effective dose, has minimal impact on calcium metabolism in dogs with atopic dermatitis.     

Hyperparathyroidism in dogs with hyperadrenocorticism

OBJECTIVES: To assess the effect of canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), phosphate and calcium concentrations. METHODS: PTH concentrations and routine biochemical parameters were measured in 68 dogs with HAC. Ionised calcium was measured in 28 of these dogs. The results obtained were compared with an age- and weight-matched group of 20 hospital patients that did not show signs of HAC. RESULTS: There were significant differences between the PTH, phosphate, alkaline phosphatase, creatinine and albumin concentrations between the two groups. Total and ionised calcium concentrations were not significantly different. Most of the dogs (92 per cent) with HAC had PTH concentrations that were greater than the reference range (10 to 60 pg/ml), and in 23 dogs they were greater than 180 pg/ml. There were significant positive correlations between the PTH and basal cortisol, post-adrenocorticotropic hormone (ACTH) cortisol and alkaline phosphatase concentrations, and also the phosphate and post-ACTH cortisol concentrations. CLINICAL SIGNIFICANCE: Adrenal secondary hyperparathyroidism is a cause of increased PTH concentrations and may be associated with abnormalities in calcium and phosphate metabolism in dogs with HAC. The findings of this study could explain why canine HAC may cause clinical signs such as calcinosis cutis that are associated with altered calcium metabolism.     

Some acute metabolic effects of parathyroid hormone in sheep

PERSSON, J. and J. LUTHMAN: Some acute metabolic effects of parathyroid hormone in sheep. Acta vet. scand. 1974, 15, 381–397. — It is now well established that calcium ions play a key role in the activation of many different cell systems. Parathyroid hormone (PTH) causes a shift of calcium into bone cells, and lipolytic hormones have little or no effect in calcium-free media. In the present investigation sheep were used to study the acute effects of intravenous injection of bovine PTH on mineral and lipid metabolism. A significant initial hypocalcaemia was found in all groups of animals. The subsequent rise in plasma calcium was most pronounced in rams. Thyroid-ectomized animals showed a greater calcium response than did intacts. PTH was found to have a strong lipolytic effect, comparable to that of catecholamines, and a slight hyperglycaemic effect. The rise in plasma NEFA was blocked by nicotinic acid, while the hyper-glycaemia was potentiated. Hypophosphataemia was obtained in young rams but not in young ewes, and in elder ewes a slight increase in the plasma phosphate level was found. Plasma magnesium decreased in all groups after PTH injection, while PTH + nicotinic acid caused a rise in magnesium concentration. The results are discussed in the view of current knowledge of mineral and lipid metabolism.parathyroid hormone; hypocalcaemia; lipolysis; sheep.     

轻度缺钙对笼养蛋鸡内分泌及骨代谢的影响

选用58周龄新扬州鸡产蛋母鸡300只,随机设计分为2组(对照组、低钙组),每组5个重复,分别饲喂钙水平为3.5%、2.5%的玉米-豆粕型日粮,研究轻度缺钙对老龄蛋鸡骨钙素(BGP)、甲状旁腺素(PTH)、降钙素(CT)、雌二醇(E2)及骨密度(BMD)的影响。结果表明,轻度钙供应不足情况下,骨质疏松逐渐明显,BGP升高,E2、BMD均下降,BGP、E2、BMD变化显著。PTH、CT均呈升高趋势,但变化不显著。结论:轻度缺钙时,老龄蛋鸡骨代谢和雌激素发生了显著变化,但对钙调节激素的影响不显著。     

Functional analysis of ectopic parathyroid activity in cats

The ability of ectopic parathyroid tissue to support calcium homeostasis was evaluated by measuring serum concentrations of calcium, phosphorus, albumin, magnesium, and parathyroid hormone before and for 12 weeks after bilateral thyroparathyroidectomy in 14 cats. During the immediate postoperative period, significant decrease was observed in serum calcium, magnesium, and parathyroid hormone (PTH) concentrations. Serum PTH concentration remained subnormal and did not significantly increase during the 12-week observation period. Despite persistent hypoparathyroidism, serum calcium and magnesium concentrations gradually increased. Ectopic parathyroid tissue is not capable of maintaining normal serum calcium concentration immediately after thyroparathyroidectomy. Serum calcium concentration gradually normalizes after thyroparathyroidectomy, apparently by means of a PTH-independent mechanism.     

Calcium homeostasis and intact plasma parathyroid hormone during exercise and training in young Standardbred horses

Physical exercise is known to affect calcium homeostasis in horses, but there is little information on the hormonal regulation of calcium metabolism during exercise. In order to evaluate the effects of exercise and training on calcium homeostasis and intact plasma parathyroid hormone, 7 untrained Standardbred horses were studied in a 6 week training programme. These horses were accustomed to running on the treadmill 3 weeks before onset of training and were exercised on a high-speed treadmill with an initial incremental standardised exercise test (SET 1: 6 incremental steps of 5 min duration each; first step 5 m/s, increase 1 m/s). SET 1 was followed by a lactate-guided training programme (6 weeks in total) with 2 types of exercise in alternating order with a day of rest after each work day: high-speed exercise (HSE) of 15 min duration, starting at VLa4, continuous increase in speed every 60 s by 0.3 m/s (14 incremental steps); and low-speed exercise (LSE) at a constant velocity at VLa2.5, duration approximately 60-90 min. The whole training programme consisted of 8 HSE and 8 LSE sessions. HSE and LSE were calculated to require the same energy expenditure. A final SET (SET 2) finished the training programme. Blood samples for lactate, plasma total calcium [Ca], blood ionised calcium [Ca2+], blood pH, plasma inorganic phosphorus [P(i)] and plasma intact parathyroid hormone [PTH] were collected before, during and after SETs 1 and 2, before and after the first and eighth HSE and LSE. During SETs 1 and 2, HSEs 1 and 8 there was a decrease in ionised Ca2+ and pH and a rise in lactate, intact PTH and P(i). LSEs 1 and 8 resulted in an increase in pH, whereas lactate, ionised Ca2+, total Ca, P(i) and intact PTH were not affected. No changes in calcium metabolism were detected during training. Results of this study suggest that intact PTH is a mediator in counter-regulation of exercise-induced hypocalcaemia.     

Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism

The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid hormone and parathyroid hormone-related protein (PTHrp) were measured in 25 dogs with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium, ionised calcium, albumin and parathyroid hormone-related protein were measured in 18 clinically normal control dogs. The concentration of PTHrp was high in 12 of the 14 dogs that were hypercalcaemic because of an underlying malignancy but was within the reference range in all the control dogs, in the 17 normocalcaemic dogs with lymphoma and in the seven dogs which were hypercalcaemic because of a parathyroid adenoma.     

骨代谢相关血液生化指标的研究进展

骨代谢包括骨合成和骨吸收两个过程。受到很多因素的影响,遗传、营养、环境、性别及内分泌等都是关键调节因素。当骨吸收过程大于骨合成过程,导致骨量流失,骨密度降低,进一步发展为骨质疏松症。骨代谢过程受到内分泌的影响,很多骨代谢血液生化指标对骨病的研究起到重要作用。近年来,国内外大量的研究报道了与骨代谢相关的血液生化指标。作者着重对血钙与血磷、甲状旁腺激素、1,25-二羟维生素D₃、白细胞介素、血清总碱磷酶和骨碱磷酶等骨代谢血液生化指标对骨形成和分解的影响进行了综述。     

Intact Parathyroid Hormone Assay and Total Calcium Concentration in the Diagnosis of Disorders of Calcium Metabolism in Dogs

Serum samples from eight dogs with primary hyperparathyroidism, seven dogs with hypercalcemic lymphosarcoma (hypercalcemia of malignancy), and four dogs with primary hypoparathyroidism were submitted to the Animal Health Diagnostic Laboratory at Michigan State University for intact parathyroid hormone (PTH) assay. When compared with the adjusted total serum calcium concentration, the intact PTH concentration was consistent with the correct diagnosis in all cases. Two dogs with hypercalcemic lymphosarcoma were mildly azotemic. In both of these cases the intact PTH concentration was consistent with hypercalcemia of malignancy despite the presence of azotemia. These data support a significant role for intact serum PTH assay in the differential diagnosis of disorders of calcium metabolism.     

不同来源高钙日粮对青年蛋鸡血清和肾脏线粒体自由基代谢的影响

以海蓝褐蛋鸡为试验对象,通过检测蛋鸡血清和肾脏线粒体自由基代谢的变化,研究不同来源高钙日粮对青年蛋鸡血清和肾脏线粒体自由基代谢的影响。选40日龄海蓝褐蛋鸡120羽,随机分成3组,每组40羽,分别饲喂正常钙日粮（以磷酸氢钙形式含钙0.9%,对照组）、石粉高钙日粮（含钙3.78%,试验组1）、磷酸氢钙高钙日粮（含钙3.78%,试验组2）,试验期65d。于试验65d,每组随机选取蛋鸡12羽,观察其病理学变化,并分离血清和肾脏线粒体,检测自由基代谢变化。结果显示：试验期间,高钙日粮组均出现青年蛋鸡的异常死亡。试验65d时,与正常对照组相比,石粉高钙组和磷酸氢钙高钙组的左肾重、右肾重、两侧肾总重及肾/体质量比均升高显著或极显著（P〈0.05或P〈0.01）,并导致肾脏出现不同程度的病理学损伤;高钙日粮组可导致蛋鸡血清及肾线粒体MDA、NO含量及XOD活性升高（P〈0.05或P〈0.01）,T-AOC、GSH-PX及SOD活性下降（P〈0.05或P〈0.01）;高钙组组间比较,石粉高钙组表现更严重的组织损伤,血清T-AOC活性降低,与磷酸氢钙高钙组比较差异显著（P〈0.05）。结果提示：高钙日粮可导致青年蛋鸡生长发育的缓慢,肾脏肿大,血清及肾线粒体的自由基生成增多及抗氧化功能的下降。     

Hypercalcemia following renal transplantation in a cat

An 11-year-old 3.0-kg (6.6-lb) neutered male Persian was referred for renal transplantation. Serum total calcium concentration was slightly high prior to surgery, but the week after surgery, total and ionized calcium concentrations were extremely high, and a small mass was palpable on the right side of the trachea at the level of the thyroid and parathyroid glands. Exploratory surgery of the ventral aspect of the neck was performed, and a right external parathyroid mass was removed. One hour after surgery, the serum ionized calcium concentration was within reference limits, and the serum calcium concentration remained normal for the next 14 months without any specific treatment. The gross and histologic appearance of the mass, combined with the rapid decrease in serum calcium concentration following its removal, confirmed that the mass was a functional parathyroid adenoma. Although a common postoperative complication in people, hypercalcemia following renal transplantation appears to be a rare complication in cats. Surgery should be considered if the condition is a result of a parathyroid adenoma.     

Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice.

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein-infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia.     

Ciclosporin therapy is associated with minimal changes in calcium metabolism in dogs with atopic dermatitis

Background – Ciclosporin is widely used in the management of canine atopic dermatitis. In humans, ciclosporin therapy has been linked to disturbances in calcium metabolism and resultant skeletal disorders. Objectives – The objective of this study was to assess calcium homeostasis in dogs before and after a 6 week course of once daily oral ciclosporin at the licensed dose (5 mg/kg). Animals – Sixteen client‐owned dogs with spontaneous atopic dermatitis. Methods – Serum concentrations of calcium, phosphate, creatinine, 25‐hydroxyvitamin D, 1,25‐dihyroxyvitamin D and plasma concentrations of ionized calcium and parathyroid hormone (PTH) were measured, together with the urinary fractional excretion of calcium and phosphate. The extent of skin lesions was scored using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)‐03 and the degree of pruritus by the Edinburgh Pruritus Scale prior to and at the end of the study. Results – The CADESI‐03 and the Edinburgh Pruritus Scale scores decreased satisfactorily in all dogs by the end of the study. Plasma PTH concentrations were significantly increased (P = 0.02) following ciclosporin treatment, whereas all other biochemical parameters were not significantly different from their starting values. The increase in PTH was mild in most cases and the proportion of dogs that had a PTH concentration above the reference range was not significantly different following treatment. Conclusions and clinical importance – This study indicates that ciclosporin has minimal impact on calcium metabolism in dogs with atopic dermatitis when used at the licensed and clinically effective dosage for 6 weeks.     

In vitro and in vivo characterization of avian reoviruses. II. Clinical evaluation of chickens infected with two avian reovirus pathotypes

The effect of two avian reovirus isolates (2408 and 1733) on digestion and nutrient metabolism in infected chickens was assessed by an in vitro absorption assay and clinical blood chemistry analysis. Birds of various ages were inoculated orally and intratracheally with reovirus and sampled periodically for the respective assays. Transitory malabsorption was observed in the duodenum of birds infected with reovirus 2408. Conversely, increased absorption was detected in the ileum of these same birds. Clinical blood chemistry analyses of birds infected with both isolates revealed that severely affected birds had abnormally elevated plasma total protein, plasma albumin, and calcium levels. Decreases were found in percent bone ash and, due to abnormally high globulin levels, in albumin:globulin (A:G) ratios. A significant (P less than 0.05) correlation between body weights and total protein, albumin, A:G ratio, and bone ash was found in infected birds. The most pronounced metabolic and physiologic changes occurred in the severely affected birds, and, in general, pathogenicity of the isolates was reflected by the degree of metabolic change.     

Effects of mithramycin on calcium metabolism and bone in dogs.

Mithramycin (0.1 mg/kg) was administered intravenously to eight Beagle dogs on days 0 and 7 to determine its effects on calcium and phosphorus metabolism, serum parathyroid hormone concentration, osteoclastic bone resorption, and serum biochemical and hematologic parameters. Ionized calcium concentration was paradoxically increased on day 1 and decreased on day 8 in association with an increased serum parathyroid hormone concentration. Serum phosphorus concentration was decreased on days 1 and 2. Osteoclastic bone resorption in iliac cancellous bone was significantly decreased on day 8. There were mild increases in serum alkaline phosphatase (days 1, 2, 4, 8, 9), aspartate aminotransferase (day 9), and gammaglutamyl transpeptidase (days 7, 9) activities. Platelet numbers were increased on days 7 through 13, and packed red blood cell volumes were mildly decreased. This investigation demonstrates that two doses of mithramycin can be administered safely to dogs and may inhibit bone resorption in diseases associated with increased osteoclastic bone resorption, such as humoral hypercalcemia of malignancy.     

Calcium metabolism in eight dogs with hypoadrenocorticism

Hypoadrenocorticism is a well-described endocrinopathy in dogs that results from deficient production and secretion of glucocorticoids and/or mineralocorticoids. Although hyperkalaemia, hyponatraemia and hypochloraemia are the most common electrolyte disturbances, hypercalcaemia also occurs in approximately 30 per cent of cases. The pathogenesis of hypercalcaemia in dogs with hypoadrenocorticism is unknown. This case series reports ionised calcium, parathyroid hormone, parathyroid hormone-related protein and vitamin D metabolite concentrations that were measured in eight dogs with concurrent hypercalcaemia and hypoadrenocorticism. Ionised calcium was increased in five of seven dogs with hypercalcaemia associated with hypoadrenocorticism. Parathyroid hormone, parathyroid hormone-related protein and 1,25 dihydroxyvitamin D concentrations were within their reference ranges in seven of eight dogs, six of seven cases and six of seven dogs, respectively. This case series highlights that hypercalcaemia associated with hypoadrenocorticism is rarely associated with increases in plasma parathyroid hormone, parathyroid hormone-related protein or serum 1,25 dihydroxyvitamin D concentrations.     

Subclinical hypocalcaemia in captive Asian elephants (Elephas maximus)

The hypothesis that hypocalcaemia may play a role in dystocia in captive Asian elephants (Elephas maximus) was investigated. The objectives of the study were to measure the total calcium concentration in elephant plasma; assess the changes in parameters of calcium metabolism during a feeding trial; investigate a possible relationship between calcium metabolism and dystocia; and assess bone mineralisation in captive Asian elephants in vivo. The following parameters were measured: total and ionised calcium, inorganic phosphorous and magnesium, the fractional excretions of these minerals, intact parathyroid hormone, 25-OH-D(3) and 1,25-OH-D(3). Radiographs were taken from tail vertebrae for assessment of bone mineralisation. The mean (sd) heparinised plasma total calcium concentration was 2.7 (0.33) mmol/l (n=43) ranging from 0.84 to 3.08 mmol/l in 11 Asian elephants. There was no significant correlation between plasma total calcium concentration and age. Following feeding of a calcium rich ration to four captive Asian elephant cows, plasma total and ionised calcium peaked at 3.6 (0.24) mmol/l (range 3.4 to 3.9 mmol/l) and 1.25 (0.07) mmol/l (range 1.17 to 1.32 mmol/l), respectively. Plasma ionised calcium concentrations around parturition in four Asian elephant cows ranged from 0.37 to 1.1 mmol/l only. The present study indicates that captive Asian elephants might be hypocalcaemic, and that, in captive Asian elephants, the normal plasma concentration of total calcium should actually be around 3.6 mmol/l and normal plasma concentration of ionised calcium around 1.25 mmol/l. Given the fact that elephants absorb dietary calcium mainly from the intestine, it could be concluded that elephants should be fed calcium-rich diets at all times, and particularly around parturition. In addition, normal values for ionised calcium in captive Asian elephants should be reassessed.