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.     

Effects of transforming growth factor-α on parathyroid hormone- and parathyroid hormone-related protein- mediated bone resorption and adenylate cyclase stimulation in vitro

The effects of transforming growth factor-alpha (TGF alpha) were determined on the ability of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) to stimulate bone resorption and adenylate cyclase in vitro. Bovine PTH-(1-34) and human PTHrP-(1-34) were equipotent in their ability to stimulate bone resorption in neonatal mouse calvaria with maximal stimulation (2.9 and 2.8-fold increases in 45Ca release, respectively) at a concentration of 10 nM. Combinations of TGF alpha with bPTH-(1-34) or hPTHrP-(1-34) had additive effects on their ability to stimulate bone resorption when submaximal concentrations of the agonists were used. There was no evidence of synergism between TGF alpha bPTH-(1-34) or hPTHrP-(1-34) in their ability to stimulate bone resorption in vitro, nor was TGF alpha able to increase bone resorption induced by maximal concentrations of bPTH-(1-34) or hPTHrP-(1-34). TGF alpha potentiated the effects of either bPTH-(1-34) or hPTHrP-(1-34) on the stimulation of adenylate cyclase in osteoblast-like ROS 17/2.8 cells. These data indicate that TGF alpha has additive effects with submaximal concentrations of PTH or PTHrP on their ability to stimulate bone resorption which may be important in the pathogenesis of humoral hypercalcemia of malignancy.     

Pathologically and serologically different avian nephritis virus isolates implicated in etiology of baby chick nephropathy.

Three virus isolates (WG-3, -4, and -5) from chicks affected by baby chick nephropathy were orally inoculated into 1-day-old specific-pathogen-free chicks of lines PDL-1 and 15I. Additional chicks were orally inoculated with avian nephritis virus (ANV) strain G-4260. Chicks inoculated with isolates WG-3, -4, and -5 died between 2 and 6 days postinoculation (PI), with mortality ranging from 0% to 53.3%. Pathological findings in the dead chicks included nephrosis in chicks inoculated with WG-3, -4, and -5, and nephritis and visceral urate deposition in chicks inoculated with G-4260. The stability of the WG-5 isolate, as well as the size of the particles and the nucleic acid type, were also similar to those of the G-4260 strain. All of the examined chicks inoculated with WG-3, -4, and -5 had interstitial nephritis at 14 days PI. Therefore, the three virus isolates were considered to be ANV. However, there was no serological relationship between the isolates and ANV (G-4260 and M-8 strains).     

Calcitonin mrna expression and plasma calciotropic hormones in fetal lambs

The object of this study was to measure basal levels of calciotropic hormones during gestation in the ovine fetus. Thyroid glands and plasma samples were collected from 49 Ile de France x (Limousine x Romanov) fetuses (range, 80 to 145 d). Total thyroidal RNA was extracted for calcitonin (CT) mRNA analysis. Plasma immunoreactive concentrations of CT, parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrP), and 1,25-dihydroxy-vitamin D [1,25(OH)ZD] were assayed. Plasma Ca and P concentrations were measured by atomic absorption spectrophotometry and colorimetry, respectively.The ratio of thyroidal weight/body weight decreased twice between Days 80 and 145 of gestation. Simultaneously, the CT mRNA rate increased but did not significantly vary after 89 d of gestation. Plasma CT concentration increased between 80 and 89 d and then did not significantly vary until Day 145. We could not detect PTH in ovine fetuses plasma; PTHrP concentration did not vary significantly between Days 80 and 145. The concentration of 1,25-(OH)₂D decreased in plasma essentially between Days 110 and 145. In conclusion, between Days 80 and 145 of gestation, CT, PTHrP, and 1,25-(OH)₂D concentrations can be easily measured in plasma from ovine fetuses, but plasma PTH was undetectable. In basal conditions, no relationship could be demonstrated between any hormonal concentrations in the fetal plasma and that of Ca or P.     

Histomorphometric study of the parathyroid glands of the spontaneously hypercholesterolemic (SHC) rats with chronic renal failure

Light and electron microscopic morphometry was performed on the parathyroid (PT) glands of the SHC rats with naturally occurring chronic renal failure. Macroscopically, the PT glands were distinctively hypertrophied in 24-week-old male SHC rats when compared with the corresponding controls, Sprague Dawley (SD) rats. Light microscopic morphometry on consecutive sections of the PT glands showed that the volume was about 3 times greater in the SHC rats, whereas there was no difference in the size of the chief cells. Mitoses were often found in the PT glands of the SHC rats. The total number of mitoses was about 8.5 times greater in the SHC rats, and was closely related to the volume of the PT glands. Ultrastructural morphometry of the chief cells revealed an increase in the cell surface area by the interdigitation of the plasma membrane and increases in the volume of mitochondria and Golgi complex. Secretory granules sometimes existed close to the cell surface in the SHC rats, but not in the SD rats. These results suggest that the PT glands of the SHC rats are hyperplastic mainly because of the proliferation of the chief cells. Concurrently, an increase in volume of the cell organelles suggests enhanced secretion activity in the chief cells.     

Serum parathyroid hormone and calcitonin levels in racehorses with fracture

Serum parathyroid hormone (PTH) and calcitonin (CT) levels in fractured racehorses were measured by radioimmunoassay. Racehorses with fracture of large bone such as the radius, third metacarpus, third carpus, digital bone or tibia, showed normal PTH level and elevated CT level in the serum. Serum PTH level was slightly higher in racehorses with sesamoid bone fracture compared to that of healthy racehorses, but not statistically significant. Moreover, serum CT level of racehorses with sesamoid bone fracture was significantly higher than that of healthy racehorses. Racehorses with sesamoid bone fracture and large bone fracture might be in different conditions of calcium regulation.     

Primary Hyperparathyroidism in a Quarter Horse Mare Associated With a Chief Cell Adenoma

Primary hyperparathyroidism is rare in large animal species, and little is known regarding its pathophysiology, endocrine and electrolyte derangements, diagnosis, medical management, and prognosis. This report describes the clinicopathologic diagnosis of a parathyroid (PT) gland chief cell adenoma in a 12-year-old Quarter Horse mare, including PT hormone (PTH) and electrolyte disarrangements associated with the neoplasia, the surgical removal of the adenoma, and medical management of the case. This report also describes for the first time the use PTH immunohistochemistry to confirm the nature of this neoplasia in a horse.     

Alterations in calcium, phosphorus and C-terminal parathyroid hormone levels in equine acute renal disease

The changes in serum and urinary levels of calcium and phosphorus and serum parathyroid hormone (PTH) were studied during controlled, chemically induced, acute renal disease in 4 ponies. There was an initial rise in daily urinary calcium and hydroxyproline excretion in 2 ponies which may have indicated increased bone resorption. Mild hypercalcemia, hypophosphatemia and elevated C-terminal PTH levels were associated with oliguria. Total daily urinary excretion of calcium and phosphorus decreased as oliguria developed. The levels of C-terminal PTH were increased in all four animals. This appears to have been related to their diminished renal function in that C-terminal fragments of intact PTH (which require functioning kidneys in order to be cleared) were probably being accumulated. Although there was no evidence with regard to an actual increase in PTH secretion, prolongation of intact PTH half-life due to renal tubular damage may have contributed to the development of hypercalcemia.     

Cloning and sequence analysis of the complementary DNA for feline preproparathyroid hormone

OBJECTIVES: To clone and sequence the cDNA for feline preproparathyroid hormone (preproPTH) and to compare that sequence with other known parathyroid hormone (PTH) sequences. SAMPLE POPULATION: Parathyroid glands from 1 healthy cat. PROCEDURES: A cDNA library was constructed in lambda phage from feline parathyroid gland mRNA and screened with a radiolabeled canine PTH probe. Positive clones were sequenced, and nucleic acid and deduced amino acid sequences were analyzed and compared with known preproPTH and PTH sequences. RESULTS: Screening of approximately 2 X 10(5) recombinant plaques revealed 3 that hybridized with the canine PTH probe; 2 clones comprised the complete sequence for feline preproPTH. Feline preproPTH cDNA consisted of a 63-base pair (bp) 5'-untranslated region (UTR), a 348-bp coding region, and a 326-bp 3'-UTR. The coding region encoded a 115-amino acid peptide. Mature feline PTH consisted of 84 amino acids. Amino acid sequence analysis revealed that feline PTH was > 83% identical to canine, bovine, swine, equine, human, and macaque PTH and 69, 71, and 44% identical to mouse, rat, and chicken PTH, respectively. Within the region responsible for hormonal activity (amino acids 1 to 34), feline PTH was > 79% identical to other mammalian PTH sequences and 64% identical to the chicken sequence. CONCLUSIONS AND CLINICAL RELEVANCE: The amino acid sequence of PTH is conserved among mammalian species. Knowledge of the cDNA sequence for feline PTH may be useful to investigate disturbances of calcium metabolism and alterations in PTH expression in cats.     

Influence of dietary conjugated linoleic acid isomers on early inflammatory responses in male broiler chickens

1. The influence of dietary conjugated linoleic acid isomer (CLA, 0 and 10 g/kg) on the metabolic and physiological responses to immune stimulation induced by a single injection of Salmonella enteritidis lipopolysaccharide (LPS) or repeated injections of LPS and Sephadex G-50 was determined in male broiler chicks. 2. In experiment 1, 10-d-old chicks were fed on experimental diets for 14 d and half of the birds fed on each diet were injected intraperitoneally with LPS (1.5 mg/kg body weight). In experiment 2,7-d-old chicks were fed on experimental diets for 18 d. Immune stimulation was started at 19 d old and continued for 5 d. Half of the birds fed on each diet were injected intraperitoneally with 0.25 mg/kg body weight of LPS at 19, 21 and 23 d of age, and with 250 mg/kg body weight of Sephadex at 20 and 22 d of age to stimulate the immune system. 3. In experiment 1, giving CLA prevented an increase in blood heterophil to lymphocyte ratio 7 h after a single injection of LPS, and increases in plasma ceruloplasmin and alpha 1 acid glycoprotein (AGP) 24 h after the injection, but not 7 h after the injection. CLA also prevented a decrease in food intake for 24 h after LPS injection. 4. In experiment 2, the CLA diet partially prevented reductions in body weight gain and weight gain to feed intake ratio caused by repeated injections of LPS and Sephadex. Feeding CLA prevented increases in plasma ceruloplasmin and AGP at 24 d of age caused by repeated injections of LPS and Sephadex, but not at 20 d of age. 5. These results suggest that feeding CLA alleviates some undesirable metabolic and physiological changes induced by immunological stimulation in male broiler chicks.     

Distribution and ontogeny of gastrin- and serotonin-immunoreactive cells in the proventriculus of developing chick, Gallus gallus domestica

The ontogeny and distribution of gastrin- and serotonin-immunoreactive (IR) cell in the proventriculus of chicks (Gallus gallus domestica, n = 60) in different growth periods was examined immunohistochemically using antisera specific to gastrin and serotonin. Gastrin and serotonin-IR cells were detected in chick proventriculus. Gastrin-IR cells were first evident after 12 days of incubation in lamina epithelialis and compound glands, while serotonin-IR cells were observed only in compound glands at that same time. Gastrin-IR and serotonin-IR cells increased in frequency on incubation day 14 and 16, respectively. Towards the end of incubation, gastrin- and serotonin-IR cell numbers decreased. In adult chicken, both IR cells were present but not lower numbers. The observations demonstrate the presence of gastrin- and serotonin-IR cells in the proventriculus of developing chicks in temporally changing frequencies.     

Selective parathyroidectomy of the dog.

Selective parathyroidectomy (PTX) is preferred to thyroparathyroidectomy (TPTX) when specific effects of parathyroid hormone depletion are being studied. However, because of the anatomic proximity of thyroid and parathyroid glands, TPTX often is performed, leaving animals depleted of thyroxine (T4) and calcitonin as well as parathyroid hormone (PTH). In the present study, six normal dogs had parathyroid tissue and about seven-eighths of thyroid tissue removed. This quantity of thyroid tissue was inadequate to maintain normal serum T4 concentrations, despite allowance of 168 days for thyroid recovery. Five of six dogs with reduced renal mass had successful selective PTX and normal serum T4 concentrations at 28 days, when one-half or more of thyroid tissue was spared. We conclude that with attention to the surgical technique, selective PTX can be achieved in a high percentage of dogs and sufficient thyroid tissue spared to maintain euthyroidism.     

Characterisation of hepatic microsomal glucose-6-phosphatase from broiler chickens

1. The hepatic glucose-6-phosphatase (G-6-Pase) kinetic variables from chickens were studied in intact and disrupted microsomes using two substrates: glucose-6-phosphate (G-6-P) and pyrophosphate (PPi). They were studied from embryonic life to 51 d of age. 2. The phosphohydrolase activity studied in the broiler chicken liver microsomes corresponds to a true glucose-6-phosphatase. 3. The enzyme VMAX with both substrates in intact and disrupted microsomes showed 2 maxima: one in 19-d-old embryos and the other in 9-d-old chickens. Pyrophosphatase (PPase) VMAX in intact microsomes was higher than that of the G-6-Pase at all ages studied, except in 12 d embryos and 3-d-old chicks. In disrupted microsomes the VMAX of both enzymatic activities were similar. The G-6-Pase latency was high in the 19-d-old embryos and 51-d-old chickens. 4. The KM for PPi and G-6-Pase decreased when microsomes were disrupted. In intact microsomes the G-6-P KM was low in embryos and 3-d-old chicks and later increased. On the other hand, the PPi KM in intact microsomes showed little change during the animal's life and was lower than that of G-6-P. In disrupted microsomes the KM for both substrates were similar. 5. These results suggest a sequential incorporation of the G-6-Pase system components in the endoplasmic reticulum.     

Parathyroid gland function in the uremic rabbit

Rabbits with renal failure have been reported to be hypercalcemic and to have decreased parathyroid hormone (PTH) concentrations. Thus, it would seem that uremic rabbits are resistant to secondary hyperparathyroidism (HPT). The work reported here was designed to investigate parathyroid gland function in uremic rabbits and the effect of diets with different calcium (Ca) and phosphorus (P) content. The relationship between PTH and ionized calcium (Ca2+), parathyroid gland size and parathyroid cell cycle were studied in three groups of rabbits: Group I, rabbits with normal renal function on a standard diet (Ca = 1.2%, P = 0.6%); Group II, partially nephrectomized rabbits on a standard diet; and Group III, partially nephrectomized rabbits on a low Ca (0.6%)-high P (1.2%) diet. Group I rabbits had baseline Ca2+ = 1.71 +/- 0.05 mmol/l and PTH = 26.9 +/- 3.2 pg/ml. During hypo- and hypercalcemic stimulation PTH reached maximal values (PTHmax) of 94.4 +/- 5.5 pg/ml and minimal concentrations (PTHmin) of 3.2 +/- 0.2 pg/ml. Rabbits from Group II were hypercalcemic (baseline Ca2+ = 2.03 +/- 0.06 mmol/l) and had very low PTH levels (1.7 +/- 0.5 pg/ml); however, they reached a PTHmax that was similar to Group I, 92 +/- 8.7 pg/ml. Group III rabbits were hypocalcemic (baseline Ca2+ = 1.22 +/- 0.08 mmol/l) and had very high basal PTH levels (739 +/- 155 pg/ml). Their PTHmax and PTHmin were 801 +/- 169.4 pg/ml and 102.2 +/- 22.2 pg/ml, respectively. Both parathyroid gland size and parathyroid cell proliferation were increased in Group III. In conclusion, our results show that the Ca and P content of the diet markedly influence PTH secretion in the uremic rabbit and that when placed on a low Ca-high P diet uremic rabbits develop secondary HPT.     

Insulin-like growth factor binding proteins and mitogenic activity of partially fractionated sheep amniotic fluid

Amniotic fluid collected from ewes on various days of gestation was examined for the presence of insulin-like growth factor (IGF) binding proteins. IGF-binding proteins with a molecular mass of 40-45 kDa appeared at day 41 of gestation. The level of these major IGF-binding proteins increased during pregnancy and reached a maximum at day 106. Smaller IGF-binding molecules with an approximate molecular mass of 35 kDa and 25 kDa appeared at day 90, also reaching a concentration peak at day 106. The mitogenic activity of sheep amniotic fluid after chromatography on Sephadex G-50 was separated into two peaks. The peak having lower molecular mass corresponded to an elution profile of 125I-IGF-I. The first peak, having higher molecular mass, was eluted immediately after the void volume of column. Electrophoresis and ligand blotting showed that proteins in the first peak had similar properties as IGF-binding proteins.     

Polytetrafluoroethylene gas intoxication in broiler chickens

A poultry research facility that housed 2400 Peterson x Hubbard cross broilers (48 pens of 50 chicks each) experienced 4% mortality within 24 hr of chick placement. Mortality started within 4 hr of placement, and within 72 hr, cumulative mortality had reached 52%. Mild dyspnea was the only clinical sign noted in some chicks prior to death. The primary gross lesion noted in the chicks submitted was moderate to severe pulmonary congestion. The lungs of four of these chicks sank in formalin, and blood-tinged fluid was noted in the mouth and nares of two chicks. The microscopic lesions noted in the affected chicks were moderate to severe pulmonary edema and congestion. The diagnosis indicated to the submitter was that pulmonary edema caused by exposure to an unidentified noxious gas caused the death of the chicks. The poultry house environment was tested for sulfur dioxide, oxides of nitrogen, carbon monoxide, carbon dioxide, and volatile organic compounds (as produced by combustion engines); all tests were negative for significant levels of these compounds. A second broiler flock was placed in the same facility and the mortality at 6 wk was 11%, which was greater than the 2.5%-4.7% mortality seen in the previous four flocks on the farm. Further investigation revealed that the only change in management practice in this facility prior to the onset of the severe mortality problem was the replacement of 48 heat lamp bulbs (one for each pen). The new heat lamp bulbs were polytetrafluoroethylene (PTFE) coated. PTFE gas intoxication has been reported in several exotic avian species, but this intoxication has not been previously reported in a poultry flock.     

Validation of a Rapid Parathyroid Hormone Assay and Intraoperative Measurement of Parathyroid Hormone in Dogs with Benign Naturally Occurring Primary Hyperparathyroidism

Objectives— To (1) validate a rapid chemiluminescent parathyroid hormone (PTH) assay, (2) determine it's usefulness locating a parathyroid nodule(s), and (3) determine if >50% decrease in PTH corresponds with excision of autonomously functioning parathyroid tissue. Study Design— Prospective cohort study. Animals— Dogs (n=12) with naturally occurring primary hyperparathyroidism and 25 healthy dogs. Methods— The assay was validated with linearity, precision, and intermethod comparison. Preoperative and postoperative systemic plasma PTH concentrations, measured from saphenous venous blood, were compared. Intraoperative local PTH concentrations were measured in right and left jugular venous blood before and after surgical excision of the grossly abnormal parathyroid gland(s). Results— Within run and day‐to‐day precisions were acceptable (coefficient of variation <15%). Dilutional parallelism was used to demonstrate high correlation between measured and calculated PTH concentrations (R²=0.99). The assay methods had good correlation but numerical results of the rapid assay were usually lower than the immunoradiometric assay. Seven of 12 dogs had uniglandular disease and five had multiglandular disease. Systemic and local PTH concentrations decreased >50% in all the dogs after excision of the parathyroid gland(s). Mean preoperative systemic plasma PTH concentrations were significantly higher than mean postoperative systemic concentrations. Local PTH concentrations could not be used reliably to differentiate the side of the autonomously functioning gland(s). Hypercalcemia resolved postoperatively in all the dogs. Conclusion— This assay measures PTH in dogs. Rapid PTH measurement provided documentation of decreased PTH concentration after removal of autonomously functioning parathyroid tissue. Clinical Relevance— Use of this assay allows documentation of a significant decrease in PTH concentration after excision of autonomously functioning parathyroid tissue.     

Effects of Broiler Strain,Dietary Nonphytate Phosphorus,and Phytase Supplementation on Chick Performance and Tibia Ash

Three experiments were conducted to study the effects of broiler strain and phytase supplementation on chick nonphytate P (NPP) requirements for growth, feed intake, and tibia ash. The first experiment compared the NPP requirements for 8- to 22-d-old chicks from 2 broiler strains, Ross 308 and 708, that have been selected for differences in early weight gain and performance. The second experiment utilized similar 8- to 22-d-old Ross 308 and 708 chicks but also compared the effects of dietary fungal phytase supplementation (600 U/kg) on broiler NPP requirements. The third experiment utilized a younger starting age, 5 to 23 d old, for Ross 308 and 708 chicks with and without phytase supplementation. Minor differences in chick growth did not affect chick NPP requirements in Experiments 1 and 3, but a substantial and unexplained reduction of growth of the Ross 708 chicks in Experiment 2 resulted in a lower NPP requirement for chick growth and feed intake but not for tibia ash. As expected, supplementation of diets with fungal phytase did result in decreased NPP requirements for growth, feed intake, and tibia ash in both strains used in Experiment 3.     

Pathology of experimental vitamin D deficiency in chickens and effects of treatment with vitamin D metabolites

Structural changes in bone, parathyroid, and ultimobranchial body were examined in three groups of chicks fed a vitamin D-deficient diet; one group was treated with vitamin D3 and another with 1,25(OH)2D3. Diets were fed from day of hatching until 5 weeks old, when deficient chicks were near death due to hypocalcemic tetany, loss of fat and muscle, and marked bone deformities. In deficient chicks, parathyroid mass increased linearly to 7.5 times normal at 5 weeks. Parathyroid cells were irregular and vacuolated, with few granules. 1,25(OH)2D3 had normal parathyroids until the fifth week, when parathyroid mass increased greatly. There were few differences in length of growth cartilage, but marked changes in length of metaphyses. Deficient chicks had metaphyses nearly five times longer than vitamin D3-treated chicks. Metaphyses in chicks given 1,25(OH)2D3 were twice as long as those of vitamin D-treated chicks at 5 weeks. Both osteoblasts and osteoclasts were more numerous in deficient chicks. These studies suggest that vitamin D3 is more effective than 1,25(OH)2D3 in preventing parathyroid and bone lesions of vitamin D deficiency.     

Effect of the gut microflora on chick growth and utilisation of protein and energy at different concentrations of dietary protein

The effect of the gut flora on chick growth and protein and energy utilisation at a marginal dietary energy level (calculated metabolisable energy value 11.7 MJ/kg) was determined with diets containing 227 or 293 g protein/kg. Germ-free (GF) and conventional (CV) chicks were reared for 10 d on the diets, and excreta were collected during the last 4 d. The chicks were killed and carcases and droppings were analysed for N and fat. The GF chicks grew significantly faster than the CV controls on both diets. The growth of CV chicks given the high protein diet was similar to that of GF chicks given the adequate protein diet. Protein and energy utilisation were significantly less for CV than for GF chicks on both diets. It was concluded that the energy requirement of CV chicks was greater than that of their GF counterparts, and that their poorer growth was due to utilisation of some dietary protein as an energy source.