Metabolism of synthetic human parathyroid hormone (PTH) 2 X 10(-10) to 5 X 10(-9) M was studied in 16 isolated perfused rat kidneys and 12 isolated perfused rat livers. Organ clearances were measured by assays specific for intact PTH. Production of fragments was analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassays specific for NH2-terminal, midmolecule, and COOH-terminal PTH. The livers cleared intact PTH and NH2-terminal immunoreactive PTH (iPTH) at the same rate. Midmolecule iPTH was cleared significantly (P less than 0.001) slower, as was COOH-terminal iPTH (P less than 0.005), and HPLC studies demonstrated production of midmolecule/COOH-terminal PTH fragments, while no NH2-terminal fragments were found. Clearance in the kidneys of intact PTH and of NH2-terminal, midmolecule, and COOH-terminal iPTH was not significantly different from clearance of inulin. No clearance of intact PTH was found in nonfiltering kidneys. HPLC studies did not demonstrate release of any PTH fragments from the kidneys. In conclusion, the liver was not selective for intact PTH, and differential hepatic clearance, possibly together with direct glandular secretion, may contribute to the predominance of COOH-terminal PTH fragments in plasma.

The endocrine abnormality that causes slipped capital femoral epiphysis (SCFE) has not been revealed. Recent studies have shown that parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] are involved in growth-plate chondrogenesis and matrix mineralization. Thus we examined in 13 patients with SCFE the serum levels of three immunoreactive forms of PTH (iPTH): the whole peptide [(1-84)PTH], the fragment containing the COOH-terminal portion (C-PTH), and the midportion (M-PTH). Additionally, serum levels of 25-hydroxyvitamin D [25-(OH)D] and 1,25-(OH)2D were measured. We found that the levels of M-PTH were significantly lower than those of controls, whereas levels of C-PTH and (1-84)PTH were not significantly different from those of controls. Similarly, levels of 1,25-(OH)2D were also significantly lower than control levels. In patients with initially low levels of M-PTH and 1,25-(OH)2D in whom the levels were monitored over a period, all levels returned to normal within a year after the onset of disease. The deficiency of M-PTH or 1,25-(OH)2D during the growth spurt could result in SCFE, although in this study, we cannot deny the possibility that the slippage may cause the deficiency.

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue.

OBJECTIVE

To investigate the deficiencey and insufficiency of 25-hydroxyvitamin D3 [25 (OH) D3], 1,25- dihydroxyvitamin D3 [1,25 (OH)2 D3] in patients with diabetic nephropathy (DN), an their association with carotid artery intima-media thickness (IMT) and coronary artery calicfication.

METHODS

The concentrations of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH) were determined by radioimmunoassay in 151 DN patients. Based on the level of 25-hydroxyvitamin D3, the patients were divided into Vitamin D deficiency group (Vit-D-D group, <15 ng/mL), insufficiency group (Vit-D-I group, 15-30 ng/mL), and normal group (Vit-D-N group, >30 ng/mL). The association of Vitamin D with IMT and coronary artery calcification was examined through group comparisons, logistic regression analysis and multiple linear regression analysis.

RESULTS

The mean level of 25-hydroxyvitamin D3 was (28 +/- 18.1) ng/mL, with an interquartile range of 16.92 - 35.45 ng/mL. The incidence of 25-hydroxyvitamin D3 insufficiency and deficiency was 47.01% (71/151) and 18.574% (28/151) respectively. The mean level of 1,25-dihydroxyvitamin D3 was (28.93 +/- 33.13) pg/mL, with an interquartile rang of 10.36 - 31.08 pg/mL. The incidence of 1,25-dihydroxyvitamin D3 insufficiency was 77.5% (117/151). Compared with the normal controls, the BMI, 24 h urine protein, CHO and LDL of those with Vitamin D deficiency increased significantly (P < 0.05). IMT ws associated with age, sex, and serum phosphorous. Coronary clcification was negative correlated with 1,25-dihydroxyvitamin D3.

CONCLUSIONS

The incidence of vitamin D deficiency and insufficiency in DN patients is high. The patients with vitamin D deficiency have higher urinary protein, CHO and LDL. Corornary artery calcification is reversely correlated with 1,25(OH)2D3.

BACKGROUND

Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests.

METHODS

ARBD was considered to be present when>> 15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 microns 2/mm2/day. Patients in which the Aluminon staining was positive >> 0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was>> 15 micrograms/g wet weight and/or the Aluminon staining was positive >> 0%).

RESULTS

Using the proposed criteria 15 patients were found to have ARBD; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (delta sA1) above 50 micrograms/l (5 mg/kg) or 70 micrograms/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH>> 650 ng/l had a positive staining >> 0%) even when the bone aluminium level was elevated >> 15 micrograms/g wet weight). In the detection of patients at risk for aluminium toxicity delta sA1 thresholds of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold delta sA1 levels of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively.

CONCLUSIONS

The low-dose DFO test is a reliable test for the detection of aluminium overload; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1992.

AMG 416 is a novel peptide agonist of the calcium-sensing receptor. In support of the clinical development program, a pharmacokinetic (PK)/pharmacodynamic (PD) model was developed to describe the relationship between plasma AMG 416 levels and serum intact parathyroid hormone (iPTH) concentrations in healthy male subjects. AMG 416 plasma concentrations were characterized by a three-compartment linear PK model, while serum iPTH levels were described by an indirect response model with drug effect on the production of iPTH characterized with an inhibitory Emax model. The production of iPTH was modeled by a circadian rhythm function. The systemic clearance of plasma AMG 416 was estimated to be 6.94 L/h. Two sine functions best described iPTH circadian rhythm with an amplitude estimated to be 0.15 and 0.08, respectively. The maximum response Emax and the potency parameter EC50 were estimated to be 0.69 and 21.0 ng/mL, respectively. This work improved our understanding of the interaction between AMG 416 PK and iPTH concentrations in healthy adult male subjects. Data suggest additional PK/PD studies with AMG 416 are warranted in the hemodialysis population.

To evaluate the features of primary hyperparathyroidism (HPT) with normal serum intact parathyroid hormone (iPTH) levels, we studied 271 consecutive patients undergoing surgery for primary HPT. In 20 patients, serum iPTH levels were within the normal range (10-65 ng/l). In their records, the most common clinical features were fatigue (n=13), polyuria (n=6), renal stone (n=5), and hypertension (n=5). Mean serum calcium and phosphorus were 2.78 and 0.85 mmol/l, respectively: 14 had serum phosphorus within the normal range. Mean serum iPTH was 48.5 ng/l, and was <45 ng/l in nine patients. Cervical ultrasound demonstrated a parathyroid adenoma in nine, and was normal in four. Tc sestamibi parathyroid scintigraphy always demonstrated an adenoma (9/9). In eight patients, normal iPTH values delayed diagnosis. Physicians should be aware of the possibility of HPT in patients with hypercalcaemia, even when serum phosphorus and iPTH levels are within the normal limits. Particularly, HPT cannot be excluded when serum iPTH levels are below the upper part of the normal range. In such cases, cervical imaging, which has the same sensitivity as in other HPT, should be undertaken. These explorations are useful, because many patients are symptomatic and can take advantage of surgery.

The mechanism accounting for normal calcemia in certain cases of primary hyperparathyroidism (HPT) remains unclear and more generally the relative importance of each determinant of calcemia has not been systematically studied so far. 52 primary HPT patients with stable calcemias, ranging from 95 to 137 mg/l, were investigated. They all exhibited identical ionized to total plasma calcium ratios. Values of serum iPTH and nephrogenous cyclic AMP were similarly elevated in all patients, and all displayed similar high values for net bone resorption and intestinal absorption of calcium. Tubular reabsorption of calcium was normal or slightly subnormal in the normocalcemic subgroup, and rose in proportion to the increase in serum calcium in the hypercalcemic subgroup. No correlation was found between tubular reabsorption of calcium on the one hand and serum immunoreactive calcitonin, degree of phosphate depletion, sodium urinary excretion or magnesemia on the other. Plasma acid base equilibrium was normal in all patients. Finally, after surgical removal of adenomas, fasting calciuria and intestinal absorption of calcium returned to normal. It is concluded that (1) the main determinant of plasma calcium value in stable calcemia primary HPT is tubular reabsorption of calcium and (2) the absence of correlation between the tubular reabsorption of calcium and the degree of PTH hypersecretion suggests that as yet undetermined factors interfere with the tubular action of PTH.

The effect of parenteral administration of magnesium was studied in five patients with hypomagnesaemic hypocalcaemia. The initial metabolic state was characterized by a normal level of serum immunoreactive parathyroid hormone (iPTH), and by low or undetectable serum 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH)2D). A parathyroid response was elicited by the acute intravenous injection of magnesium chloride. In contrast, 1,25(OH)2D did not change up to 24 h after the injection. Intramuscular magnesium sulphate restored serum magnesium and calcium to normal, whereas iPTH was transiently increased. 25OHD remained low and unchanged. 1,25(OH)2D rose very slowly, but the correction of hypocalcemia began before any change in 1,25(OH)2D levels could be demonstrated. Thus, the early correction of hypocalcemia mainly depended on the restoration of an adequate parathyroid function independently of the secretion of 1,25(OH)2D.

The effect of calcium (Ca) infusions on serum prolactin (Prl) was studied in normal controls and children with disorders of Ca metabolism: Three patients with secondary hyperparathyroidism (vitamin D deficiency rickets), 2 children with idiopathic hypoparathyroidism, 13 epileptic patients with anticonvulsant drug induced inhibition of calcitonin (CT) secretion and 1 patient with vitamin D resistant rickets with normal CP and low PTH secretion. Ca induced a significant decline of serum Prl in most subjects which could not be explained by the associated increase of CT or decrease of iPTH. The important role of Ca for the in vitro secretion of dopamine has been established for a long time. It is speculated that the inhibitory effect of Ca infusion or serum Prl may be due to dopamine release from nerve tracts in the hypothalamus.

Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal 47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P less than 0.05); 24-h urinary calcium excretion rose by 98% (P less than 0.001), and forearm bone mass increased by 5.6% (P less than 0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.

BACKGROUND

There is currently no consensus regarding the utilization of intact parathyroid hormone (iPTH) for predicting postthyroid surgery hypocalcemia. The objective of this study was to determine a threshold value for the 1-hour postoperative iPTH level that can identify those patients at significantly increased risk for the development of symptomatic hypocalcemia.

METHODS

A prospective study of 21 individuals undergoing either total or completion thyroid operations was performed. One-hour postoperative iPTH levels were drawn along with ionized calcium at 6 hours postoperatively and at 7 am the following morning. Symptoms of hypocalcemia were recorded.

RESULTS

Of the 21 patients recruited into the study cohort, there were 18 individuals that developed hypocalcemia (4 symptomatic and 14 asymptomatic) and 3 that remained normocalcemic. The mean <em>iPTH</em> level 1 hour postoperatively was significantly different when comparing the normocalcemic, asymptomatic hypocalcemic, and symptomatic hypocalcemic patient groups (6.50 pmol/L versus 3.76 pmol/L versus 0.7 pmol/L, respectively; P = .007). An <em>iPTH</em> level <or=2.5 pmol/L was 100% sensitive for predicting which individuals would go on to develop symptomatic hypocalcemia.

CONCLUSIONS

This study suggests that a 1-hour postoperative <em>iPTH</em> level <or=2.5 pmol/L can identify those individuals at risk for developing symptomatic hypocalcemia. Therefore, we recommend early calcium supplementation for these patients to decrease their postoperative morbidity from symptomatic hypocalcemia.

The acute effect of 25 and 50 g of alcohol on the variation in serum osteocalcin, a specific and sensitive marker of bone formation, and on serum cortisol and serum parathyroid hormone (PTH)(1-84) was calculated in 6 normal young adults. They were studied during three periods, each lasting from 4 p.m.-7:30 a.m. Alcohol was ingested between 4:15 and 5 p.m. during period two and three. Blood was taken at 4 p.m. and every 15 minutes from 4:30 til 6 p.m., followed by hourly sampling until 12 p.m. The last blood sample was taken after an overnight fast at 7:30 a.m. Initial and end values before and after alcohol ingestion did not differ significantly from control values. Repeated measures analysis of variance showed that 50 g of ethanol decreased serum osteocalcin significantly (P less than 0.02) and increased serum cortisol (P less than 0.05) during the 4-12 p.m. interval. The interaction of 50 g of ethanol on the variation in serum osteocalcin was already significant during the first 2 hours (P less than 0.02), where no significant effect on serum cortisol could be detected. Although insignificant, the same pattern was observed after 25 g of alcohol. There was no significant change in the variation of serum iPTH(1-84) during the 4-6 p.m. after alcohol intake. We conclude that 3-4 drinks of alcohol taken over 45 minutes decreases serum osteocalcin in a dose-dependent way. The time lag between changes in serum osteocalcin and cortisol indicates that the decrease in serum osteocalcin is not related to the increase in serum cortisol.

OBJECTIVE

To assess the value of 24-hour intact parathyroid hormone (iPTH), serum calcium, and decreases in both were evaluated against preoperative values (iPTH and serum calcium decline) and used to determine the existence of permanent hypoparathyroidism (pHPP) after total thyroidectomy (TT).

METHODS

The clinical data of patients who underwent total thyroidectomy in our hospital between September 2014 and July 2015 were retrospectively analyzed.

RESULTS

There were 42 cases with normal parathyroid function, 58 cases with temporary HPP, and 10 cases with pHPP. When iPTH and serum calcium were administered at 24 h after surgery, iPTH decline and calcium decline differed significantly among the three groups above (P < .01). The accuracy and positive predictive value of 24 h iPTH for pHPP were higher than any one of the others. The sensitivity, specificity, false positive rate, and accuracy were 100%, 95%, 33.33%, and 94.45%, respectively. The AUC was 0.982 when 24-hour iPTH was equal to or <3.15 pg/mL. The use of blood calcium equal to or <2.03 mmol/L (8.12 mg/dL) pointed to a diagnosis of pHPP, with a sensitivity of 100%, specificity of 63%, false positive rate of 78.72%, and accuracy of 66.36%.

CONCLUSIONS

Measurement of the postoperative 24-h intact parathyroid hormone and serum calcium concentration can predict the occurrence of permanent hypoparathyroidism and the former is more advantageous. Postoperative 24-h intact parathyroid hormone equal to or <3.15 pg/mL is a reliable index, and it is suitable for the prediction of postoperative permanent hypoparathyroidism.

BACKGROUND

There is a well established relationship between primary hyperparathyroidism and recurrent calcium-containing calculi. Traditionally, the diagnosis is confirmed by the presence of elevated intact parathyroid hormone (iPTH) and serum ionised calcium levels. The prevalence and role of elevated iPTH in the presence of normocalcemia in patients with renal stone disease is poorly understood. The aim of the present study was to describe the findings in patients who had renal stone disease, an elevated iPTH level and normocalcemia.

METHODS

During the last decade, 414 patients, who had normal renal function, were investigated and treated for renal calculi in the Renal Stone Clinic of the Toronto Western Hospital. Of these 414 patients, 40 (9.6%) had an elevated intact iPTH level and normal serum calcium (total and ionised) on repeated measurements. In all these patients we performed detailed clinical and laboratory investigations to determine risk factors for stone formation. Correlation analysis was done using Pearson test and the weights of factors influencing iPTH level were compared using multiple regression analysis.

RESULTS

The average duration of a history of stone disease was 12.0 +/- 10.5 years. Most of these patients had passed their stones spontaneously, 15 underwent lithotripsy, in six the stones were removed by basket catheters and one patient each had partial nephrectomy, nepholithotomy or uretero-lithotomy. Twelve had a positive family history, two had history of intestinal malabsorption and one patients had a history of immobilisation. All of these patients had elevated serum parathyroid hormone in the range of 3% to 134% (median 20.5%) above upper limit of normal (F = M); all had normal serum total and ionised calcium and normal urine excretion of calcium (except in one). Additional risk factor for stone formation included: low level of 25-hydroxyvitamin D in four patients, low output and high urine osmolality in four patients, high urine sodium in nine and high oxalate excretion in eight patients. Citrate excretion was low in seven, magnesium excretion in six patients and tubular reabsorption of phosphate in 22 patients. Urine hydroxyprolin was increased in two and decreased in four patients. Combined abnormalities were found in 14 while 17 patients did not have any abnormality apart from elevated iPTH level. Multiple regression analysis did not suggest that any of the selected predictors had a significant influence on PTH release.

CONCLUSIONS

9.6% of patients with recurrent kidney stones had normocalcemia and elevated iPTH level in the presence of normal renal function. The study did not show any distinct pattern of abnormalities that would suggest a mechanism of stone disease in these patients. Further investigations are necessary to determine the significance of elevated iPTH in normocalcemic patients with renal stone disease and establish whether we should consider neck exploration for parathyroidectomy in these patients.

A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.

The epidemiology and presentation of primary hyperparathyroidism (PHPT) is changing. Full-blown disease in its tertiary stage is rarely seen. Instead, asymptomatic hypercalcemia draws more attention because of the widespread use of screening laboratory tests. In recent years, clinicians have started ordering intact parathyroid hormone (iPTH) assays for a variety of reasons (eg, during the evaluation of fractures, nephrolithiasis, osteomalacia and low bone mass), even in individuals who have no evidence of hypercalcemia. The increased levels of iPTH without an underlying etiology may represent an early phase, or a distinct subtype, of PHPT, termed as normocalcemic primary hyperparathyroidism (NPH). The prevalence and clinical significance of NPH are unknown and are a matter of great debate. No guidelines regarding management of this entity exist. The authors describe a patient who had increased levels of iPTH, osteopenia and normal calcium and vitamin D. There was no discernible secondary cause for hyperparathyroidism (renal insufficiency, osteomalacia, vitamin D deficiency, lithium use, etc), and no intervention was offered aside from periodic monitoring of laboratory values and bone density. Analysis of data in patients with NPH should include elucidation of its natural history, temporal patterns in calcium level and prevalence of low bone mass, nephrolithiaisis and fragility fractures and could assist in devising evidence-based guidelines for management of the condition. Further characterization of NPH will be of benefit in defining its clinical impact and associated complications, to clarify the rationale behind the use of the iPTH assay as a screening test, and to assist in management of this entity.

To assess the role of peripheral sympathetic nerves in the regulation of parathyroid hormone (PTH) release rats subjected to bilateral superior cervical ganglionectomy (SCGx) 8-24 h earlier were used. SCGx did not result in significant changes of basal serum calcium (Ca) or immunoreactive PTH (iPTH) levels. The i.p. administration of EDTA every 30 min for up to 3 h brought about an impending decrease of serum Ca levels in both sham-operated and SCGx rats when assessed 23 h after surgery. The extent of hypocalcemia was significantly larger in the SCGx group. In sham-operated controls serum iPTH increased by 32-145%, 1-3 h after beginning EDTA treatment whereas such increases were considerably lower or absent in SCGx rats. In 3 out of 7 SCGx animals that survived to a double EDTA dose, iPTH increased to levels indistinguishable from controls. When SCGx rats subjected to surgery 23 h earlier and receiving d-1-propranolol (5 mg/kg) or phentolamine (10 mg/kg) 4 h and 30 min earlier were submitted to iterative EDTA injection serum iPTH increased, whereas no changes were detected in SCGx rats treated with vehicle and subjected to the same EDTA treatment. These data indicate that (1) SCGx does not affect basal release of iPTH or serum Ca concentration; (2) 23-26 h after SCGx there is a significant impairment of homeostatic iPTH responses to low Ca levels which can be overcome by suitable Ca stimulus; (3) circulating catecholamines may affect denervated parathyroid cells, as revealed by the changes in serum iPTH and Ca elicited by alpha- and beta-adrenoceptor-blocker treatment of SCGx rats.

BACKGROUND

Minimally invasive radio-guided parathyroidectomy (MIRP) has been embraced as an acceptable therapeutic approach to primary hyperparathyroidism. Preoperative sestamibi scanning has facilitated this technique. Here we evaluate the addition of a rapid intraoperative parathyroid hormone (iPTH) assay for patients undergoing MIRP.

METHODS

A series of 51 patients underwent sestamibi localization of parathyroid glands followed by MIRP for primary hyperparathyroidism. Using peripheral venous samples, iPTH levels were measured prior to gland excision, as well as post-excision at 5, 10, and 15 minutes, taking a 50% reduction in iPTH level as indicative of complete excision. Next, changes in serum iPTH were compared with preoperative and postoperative changes in serum calcium, as well as levels of intraoperative ex-vivo radiation counts taken by hand-held gamma probe.

RESULTS

In this series, a drop of greater than 50% in iPTH levels was observed in 94% of patients (n=48). Moreover, a significant drop in iPTH occurred within 10 minutes of excision in the majority (n=42) of cases (P<0.004). Changes in iPTH were comparable with the therapeutic reduction in calcium levels, as well as with the change in intraoperative ex-vivo gamma counts.

CONCLUSIONS

This study demonstrates that the addition of an iPTH assay to MIRP provides a quick and reliable intraoperative diagnostic modality in confirming correct adenoma removal. Moreover, it precludes the requirement of frozen section.

The levels of vitamin D metabolites were measured in three children with a decreased dietary intake of calcium and vitamin D and sun exposure. All three children had hypocalcemia, hypophosphatemia, and elevated alkaline phosphatase activities. Two children had rickets, aminoaciduria, and elevated immunoreactive parathyroid hormone (iPTH) concentrations. The concentrations of vitamins D2 and D3, 25-hydroxyvitamins D2 and D3 (25-OH-D2 and 25-OH-D3), and 24,25-dihydroxyvitamin D (24,25-[OH]2D) were reduced. Nonetheless, the levels of calcitriol (1,25-[OH]2D) were normal. The combination of hypocalcemia, hypophosphatemia, and increased iPTH concentrations should result in supranormal calcitriol concentrations. Moreover, the ratio of PTH to calcitriol is significantly higher than in normal subjects. Accordingly, in patients with vitamin D deficiency and "normal" calcitriol values, the synthesis of this compound may be reduced. The evaluation of vitamin D deficiency should include the measurement of all metabolites.

Fluorosis is a major public health problem in the world, including India. The present study was undertaken to investigate the role of molybdenum (Mo) in the deposition of fluoride (F) in bone and whether copper (Cu) supplementation has any alleviating role when F and Mo are ingested together. For this purpose, four groups of rabbits were used [control (C), fluoride (F), fluoride + molybdenum (F + Mo), and fluoride + molybdenum + copper (F + Mo + Cu)] to find out the effect of these treatments on various bone-related parameters like intact parathyroid hormone (iPTH), alkaline phosphatase and Cu in serum, hydroxyproline and calcium (Ca) in urine, and minerals (F, Cu, manganese, and zinc) in femur bone ash. Bone mineral content (BMC), bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)], and strength of femur bones were also assessed. F content in the femur was significantly higher (P < 0.01) in all experimental groups compared to control group. Mo supplementation increased F deposition in femur bone in the F + Mo group, whereas supplementation of Cu reduced F deposition in the F + Mo + Cu group compared to the F + Mo and F groups. Levels of Cu in femurs of the F + Mo and F + Mo + Cu groups were significantly higher (P < 0.05, P < 0.01, respectively) than in the C group, although serum Cu was significantly lower in the F and F + Mo than the C and F + Mo + Cu groups. Magnesium levels in the F + Mo group were significantly higher (P < 0.05) than in the F and F + Mo + Cu groups. Cu supplementation in the F + Mo + Cu group increased deposition of zinc significantly (P < 0.05) compared to the F and F + Mo groups. Serum iPTH, alkaline phosphatase, and urinary hydroxyproline and Ca were significantly higher (P < 0.01) in the F and F + Mo than in the C and F + Mo + Cu groups. However, serum iPTH and urinary hydroxyproline were higher in the F + Mo group than the F group. Alkaline phosphatase was significantly higher in the F + Mo group than the F and F + Mo + Cu groups. Levels of serum Cu in the F and F + Mo groups were lower than in the C group, though serum Cu was significantly higher in the F + Mo + Cu than in all other groups. DXA analysis of femur bone indicated that BMD in the F + Mo group was significantly higher than in the F (P < 0.05), C (P < 0.01), and F + Mo + Cu (P < 0.05) groups. However, there was no significant difference in BMC among the groups. Bone strength was significantly higher (P < 0.05) in the F + Mo group than in the C group. Results of the present study show that ingestion of Mo with F does not create secondary Cu deficiency (due to increased excretion of Cu through urine). However, Cu concentration was decreased in serum in this group (F + Mo) compared to the C and F + Mo + Cu groups. Deposition of F in femur bone was more (22%) when it was given along with Mo compared to F alone, while F deposition in femur bone was less in the F + Mo + Cu group by 80% compared to the F group. Also, deposition of F in the F + Mo + Cu group was 120% less compared to the F + Mo group. The increase in F level due to Mo addition appears to be offset by supplementation with Cu. Supplementation with Cu showed a beneficial effect on bone resorption as well as bone formation.

BACKGROUND

The metabolic effects of oral calcium (Ca) supplementation during plateletpheresis were evaluated in a randomized, placebo-controlled trial.

METHODS

Twenty-three donors underwent four plateletpheresis procedures each, receiving in random order, elemental Ca (Ca) 1 or 2 g orally, or a corresponding placebo, 30 minutes before donation. Ten of these donors underwent a fifth procedure using a 4-g Ca dose. All procedures were performed at a fixed citrate infusion rate of 1.5 mg per kg per minute.

RESULTS

Oral Ca induced dose-sensitive changes in parathyroid hormone (iPTH), total (tCa), and ionized (iCa) calcium levels. Compared to placebo, the greatest improvement in tCa and iCa levels occurred after the 2-g Ca dose (tCa of 73, 89, and 25% above placebo levels at 60 min, using 1, 2, and 4 g of oral Ca, respectively). Twenty-four hours after apheresis, serum tCa and iCa levels were higher, and iPTH levels lower, in donors who received oral Ca rather than placebo. Marked increases in urinary Ca and magnesium (Mg) excretion occurred at the completion of apheresis, were unaffected by Ca dose, and returned to baseline within 24 hours. Plateletpheresis also induced significant changes in serum alkaline phosphatase, 1,25-dihydroxyvitamin D, and osteocalcin levels immediately and at 24 hours after apheresis.

CONCLUSIONS

Plateletpheresis induces marked acute metabolic effects, with sustained changes evident up to 24 hours after the completion of apheresis. Oral Ca supplementation exerts a significant but clinically modest impact on selected laboratory variables associated with these effects. Further studies are indicated to examine the long-term impact of plateletpheresis, with or without Ca supplementation, on donor Ca balance and bone density.

BACKGROUND

Osteomalacia (OSM) and rickets are widely prevalent in developing countries especially in females. The factors associated with such predisposition are not known.

OBJECTIVE

To identify nutritional, endocrine and genetic factors related to calcium and vitamin D metabolism that are associated with OSM/rickets in females.

METHODS

We studied 98 patients with OSM or rickets and their relatives including male and female sibs and parents (n = 221) for the presence of biochemical OSM {low serum 25-hydroxyvitamin D [25(OH)D], raised intact PTH (iPTH) and raised alkaline phosphatase} and associated nutritional and genetic factors. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping vitamin D receptor (VDR) (BsmI and FokI) and PTH gene (BstBI and DraII) single nucleotide polymorphisms (SNPs) in 74 families. The differences in the factors associated with calcium and vitamin D among the different groups were analysed by analysis of variance (ANOVA). Logistic regression analysis and the transmission disequilibrium test (TDT) were carried out to assess association between nutritional and genetic factors, and the disease, respectively.

RESULTS

Most of the patients were female (91.8%). The mean serum 25(OH)D level of the female patients was comparable to that of the female sibs (14.4 +/- 5.7 vs. 18.3 +/- 9.7 nmol/l). The frequency of biochemical OSM was fivefold higher in female than in male sibs (24.4%vs. 4.9%). Female sibs also had significantly lower 25(OH)D, dietary calcium intake and sunshine exposure than male sibs. The frequency of biochemical OSM was comparable between mothers and fathers. The odds of biochemical OSM in the family members was reduced by 11% per 15-min daily sunshine exposure [odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.81-0.98, P = 0.02] and decreased by 20% per 100 mg dietary calcium intake (OR = 0.80, 95% CI = 0.67-0.96, P = 0.02). VDR/PTH gene SNPs showed no association with OSM/rickets on TDT analysis.

CONCLUSIONS

Among the immediate family members of patients with OSM/rickets, female sibs have features of biochemical OSM in up to 24.4%. Female sibs, unlike male sibs, share with patients features of markedly low serum 25(OH)D levels, poor dietary calcium intake and poor exposure to sunshine. Genetic factors such as VDR and PTH gene SNPs were not associated with OSM/rickets.