iPTH Measurement Research Articles

Predictive value of intact parathyroid hormone measurement during surgery for renal hyperparathyroidism

In contrast to that in patients with primary hyperparathyroidism, the value of intraoperative intact parathyroid hormone (iPTH) measurement is still unclear in patients with renal hyperparathyroidism and was, therefore, evaluated in a large cohort of patients. Intraoperative iPTH measurement was performed in 153 patients with renal hyperparathyroidism (129 with terminal renal failure and 24 with functioning kidney graft). Subtotal and total parathyroidectomy were performed in 123 and 13 patients, respectively, during initial surgery. In patients with recurrent disease (17), the respective hyperfunctioning tissue was removed. Intraoperative blood samples were obtained by puncture of the internal jugular vein before preparation of the parathyroids (PTH0) and 15 min after parathyroidectomy (PTH15). iPTH was measured with the Elecsys 2010 system. Postoperative iPTH levels (PTH(post)) were determined at postoperative days 1 to 3 and at week 2. Patients were arbitrarily divided in four groups according to the postoperative iPTH values: 0-25 pg/ml (group 1), 26-65 pg/ml (group 2), 66-150 pg/ml (group 3) and more than 150 pg/ml (group 4). The mean PTH0 value was 869+/-57 pg/ml, which decreased to 167+/-15 pg/ml at PTH15. The mean relative PTH15 value was 21.6+/-1.7%. Postoperatively, iPTH decreased to 42+/-9 pg/ml. The postoperative iPTH value of the 129 patients with terminal renal failure was 25 pg/ml or less in 99 patients, 26-65 pg/ml in 11 patients, 66-150 pg/ml in eight patients and higher than 150 pg/ml in 11 patients. Two successive criteria of iPTH decrease were used: first, a PTH15 of < or =150 pg/ml or, second, a relative PTH15 of < or =30% less was used. Fifteen patients did not fulfil both criteria. In 13 of them (86.7%) iPTH(post) was higher than 65 pg (true failure to decline). Of 114 patients who fulfilled the criteria, 108 (94.7%) had normal postoperative iPTH values (true decline). Absolute PTH15 values of less than 150 pg/ml predicted normal postoperative iPTH levels in 77 of 78 patients. A PTH15 value of 150 pg/ml or less predicts operative success in patients with renal failure in 98.7% of cases, independently of the relative decay. In contrast, if the relative PTH15 is higher than 30%, high postoperative PTH values are predicted with a probability of 86.7%. Although there remain some borderline cases, intraoperative iPTH measurement is accurate and also can be useful in patients with renal hyperparathyroidism.

Intraoperative Intact Parathyroid Hormone Level Monitoring as a Guide to Parathyroid Reimplantation after Thyroidectomy

The goal of this study was to determine whether intraoperative intact parathyroid hormone (IOiPTH) levels can predict the functional status of remaining parathyroids at the end of total thyroidectomy and thereby be a guide for parathyroid autotransplantation when glands are deemed not functional. Prospective study involving 23 patients undergoing either total thyroidectomy or completion thyroidectomy During surgery, an attempt was made to identify all four parathyroid glands. Normal size vascular glands were preserved, whereas avascular glands were microdissected and reimplanted. Serial IOiPTH was measured preoperatively after each parathyroid was identified, manipulated, or removed and serum iPTH measurements were done postoperatively up to 56 days. The sensitivity of low IOiPTH in identifying a devascularized gland was 88.9%, and specificity was 92.9%. A normal IOiPTH level indicates at least two functioning glands. IOiPTH levels between 1.5 and 10 pg/mL indicate only one functional gland. Undetectable IOiPTH levels indicate no residual functioning gland. For patients undergoing total or completion thyroidectomy, IOiPTH should be routinely measured at the end of the procedure, and a level less than 10 pg/mL requires reassessment of remaining parathyroid glands. Vascularized glands should be preserved regardless of IOiPTH levels. Devascularized glands or glands of questionable vascularity should be considered for autotransplantation.

Early prediction of postthyroidectomy hypocalcemia by one single iPTH measurement

We prospectively evaluated the possibility to make an early prediction of postthyroidectomy hypocalcemia by postoperative intact parathyroid hormone (iPTH) measurements. Fifty-three consecutive patients who underwent bilateral thyroid resection were included; iPTH was measured preoperatively, at the end of the surgical procedure, and at 2, 4, 6, 24, and 48 hours after the operation. Patients who had hypocalcemia (serum total calcium, <8.0 mg/dL) were compared with normocalcemic patients. Sixteen patients experienced hypocalcemia. Six patients experienced symptoms. No significant difference was found between hypocalcemic and normocalcemic patients concerning demographic, pathologic, and preoperative laboratory data, surgical procedure, and intraoperative findings. Postoperative iPTH levels were reduced in hypocalcemic patients at the end of the procedure and at 2, 4, 6, 24, and 48 hours after the operation ( P < .001). IPTH levels below the normal range (<10 pg/mL) at 4 and 6 hours after the operation correctly predicted postoperative hypocalcemia and symptoms in all but 1 patient with a self-limiting, asymptomatic hypocalcemia (serum calcium concentration, 7.8 mg/dL) (specificity, 100%; sensitivity, 94%; overall accuracy, 98%). One single iPTH measurement reliably can predict, early after thyroidectomy, which patients are prone to clinically relevant postoperative hypocalcemia and necessitate supplementation treatment and which patients are eligible for a safe early discharge.

Fine Needle Aspiration and Intraparathyroid Intact Parathyroid Hormone Measurement for Reoperative Parathyroid Surgery

Some authors have praised the value of fine needle aspiration (FNA) with measurement of intraparathyroid intact parathyroid hormone (iPTH) for localization of the hypersecreting gland(s) in recurrent or persistent primary hyperparathyroidism (HPT). The aim of the present study was to determinate whether FNA for iPTH assay is an effective procedure to distinguish between normal and hypersecreting parathyroid glands. We performed a prospective study of 170 patients who underwent cervicotomy. They were divided into three groups: group A, 50 patients with thyroid diseases; group B, 100 patients with primary HPT; group C, 20 patients with secondary HPT. We performed intraoperative FNA for iPTH measurement from the thyroid, and from the normal and enlarged parathyroid glands, and we compared the different intraglandular iPTH assays. In group A, the intraparathyroid iPTH level was < 1000 pg/ml in 68% of the patients. In group B, in the pathological parathyroid gland iPTH was > 1000 in 88%; conversely, in the normal adjacent parathyroid glands it was < 1000 in 79%. In group C, intraparathyroid iPTH of enlarged glands was > 1000 in 80%. Intrathyroid iPTH was < 100 pg/ml in 96% for the three groups. We conclude that FNA for intraglandular iPTH measurement is an effective tool for distinguishing between normal and pathological parathyroid glands in the setting of primary HPT (p < 0.05), and between thyroid and parathyroid glands in groups A and B. But the procedure should be carried out in conjunction with the sestamibi scan and ultrasonography before surgical reintervention.

Intact PTH assay overestimates true 1-84 PTH levels after maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

Although the so-called intact parathyroid hormone (iPTH) assay detects not only true 1-84 PTH (1-84PTH) but also large C-terminal PTH fragments, it remains inconclusive whether the 1-84PTH assay is more useful in clinical practice. Previous studies have shown that the results of these two PTH assays in dialysis patients are closely correlated. Chronic dialysis patients whose plasma iPTH levels were >400 pg/ml were selected for inclusion in the present study. Following a 4 week wash-out time during which all vitamin D administration was halted, maxacalcitol was intravenously injected at the end of dialysis sessions three times per week for 24 weeks, at an initial dosage of 10 micro g. Ninety-seven patients with secondary hyperparathyroidism were included in our analysis. Their serum calcium levels were elevated from the start levels while phosphate levels remained unchanged. The plasma 1-84PTH levels constantly declined throughout the 24 weeks. Although the patients' plasma 1-84PTH and iPTH levels were closely correlated with each other both at the beginning of the study and after 24 weeks of maxacalcitol therapy, the ratio of 1-84PTH/iPTH consistently decreased throughout the study period (P<0.01). The changes in the ratio were significantly correlated with changes in serum calcium levels. Twenty-four weeks of intravenous maxacalcitol injection therapy significantly reduced the 1-84PTH/iPTH ratio. Estimated 1-84PTH levels from iPTH levels using a conversion formula obtained before the treatment were 21.0+/-20.4% higher than measured 1-84PTH levels after the therapy. Thus, iPTH measurement has a potential risk to overestimate 1-84PTH levels when evaluating the efficacy of maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

Nicotinamide suppresses hyperphosphatemia in hemodialysis patients

The use of calcium- or aluminum-based phosphate binders against hyperphosphatemia is limited by the adverse effects of hypercalcemia or aluminum toxicity in long-term hemodialysis. Because nicotinamide is an inhibitor of sodium-dependent phosphate cotransport in rat renal tubule and small intestine, we examined whether nicotinamide reduces serum levels of phosphorus and intact parathyroid hormone (iPTH) in patients undergoing hemodialysis. Sixty-five hemodialysis patients with a serum phosphorus level of more than 6.0 mg/dL after a 2-week washout of calcium carbonate were enrolled in this study. Nicotinamide was administered for 12 weeks. The starting dose was 500 mg/day, and the dose was increased by 250 mg/day every 2 weeks until serum phosphorus levels were well controlled at less than 6.0 mg/dL. A 2-week posttreatment washout period followed the cessation of nicotinamide. Blood samples were collected every week for measurement of serum calcium, phosphorus, lipids, iPTH, and blood nicotinamide adenine dinucleotide (NAD). The mean dose of nicotinamide was 1080 mg/day. The mean blood NAD concentration increased from 9.3 +/- 1.9 nmol/105 erythrocytes before treatment to 13.2 +/- 5.3 nmol/105 erythrocytes after treatment (P < 0.01). The serum phosphorus concentration increased from 5.4 +/- 1.5 mg/dL to 6.9 +/- 1.5 mg/dL with the pretreatment washout, then decreased to 5.4 +/- 1.3 mg/dL after the 12-week nicotinamide treatment (P < 0.0001), and rose again to 6.7 +/- 1.6 mg/dL after the posttreatment washout. Serum calcium levels decreased during the pretreatment washout from 9.1 +/- 0.8 mg/dL to 8.7 +/- 0.7 mg/dL with the cessation of calcium carbonate. No significant changes in serum calcium levels were observed during nicotinamide treatment. Median serum iPTH levels increased with pretreatment washout from 130.0 (32.8 to 394.0) pg/mL to 200.0 (92.5 to 535.0) pg/mL and then decreased from the maximum 230.0 (90.8 to 582.0) pg/mL to 150.0 (57.6 to 518.0) pg/mL after the 12-week nicotinamide treatment (P < 0.05). With nicotinamide, serum high-density lipoprotein (HDL) cholesterol concentrations increased from 47.4 +/- 14.9 mg/dL to 67.2 +/- 22.3 mg/dL (P < 0.0001) and serum low-density lipoprotein (LDL) cholesterol concentrations decreased from 78.9 +/- 18.8 mg/dL to 70.1 +/- 25.3 mg/dL (P < 0.01); serum triglyceride levels did not change significantly. Nicotinamide may provide an alternative for controlling hyperphosphatemia and hyperparathyroidism without inducing hypercalcemia in hemodialysis patients.

Osteodystrophy in Indonesian haemodialysis patients.

A preliminary study of the intact-parathyroid hormone (i-PTH) measurements from haemodialysis patients was conducted to determine the prevalence of renal bone diseases at the Dr Soetomo Hospital. The objective of this study is to evaluate the osteodystrophy renal pattern in haemodialysis patients using i-PTH and radiological parameters. The selected populations of 48 (32 males and 16 females), the mean age 48 +/- 10.3 years, was evaluated to conduct a cross-sectional study. The calorimetric method was applied to measure serum P and Ca, while a radioimmunoassay was used to assay the i-PTH level. Of those 48 patients receiving haemodialysis, with a duration ranging from 4 to 432 weeks, 61% had hypocalcaemia and 10% had hypercalcaemia. The i-PTH levels below 100 pg/mL (normal, 10-65 pg/mL) suggested 'aplastic' bone, and values of 100-200 pg/mL most commonly indicated 'normal' bone turnover. The i-PTH levels over 200 pg/mL suggested hyperparathyroidism. The results of this study demonstrated that 42% of those patients had <100 pg/mL (low turnover bone presumed, no biopsy), 23% had 100 - <200 pg/mL ('normal' bone turnover) and 35% of them had >200 pg/mL ('hyperparathyroidism'). In addition, the radiological study showed that 10% of those patients were positive for renal bone diseases. In conclusion, this study shows that the common type of renal osteodystrophy was of a low turnover type, which was different from the findings in other previous studies. It is postulated that this difference is likely to be caused by some factors such as the general health condition of the population those patients belong to and, in particular, the nutritional status of those patients.

Preanalytical Factors in the Measurement of Intact Parathyroid Hormone with the DPC IMMULITE Assay

Intact parathyroid hormone (iPTH) is commonly measured with two-site immunometric assays. The DPC IMMULITE 2000 assay (Diagnostics Products Corporation) measures iPTH by a chemiluminescence reaction with a monoclonal murine capture antibody and a polyclonal caprine signal antibody conjugated to alkaline phosphatase. Accurate and precise iPTH measurements are needed for the correct triage of individuals with hyper- or hypocalcemia and for the evaluation of PTH function in bone and mineral disorders (1)(2). In end-stage renal failure, iPTH measurements are commonly used to determine medical management (administration of vitamin D) and surgical therapeutic options (subtotal parathyroidectomy for extreme hyperparathyroidism) (3)(4). Collection of whole blood into EDTA-containing sample tubes offers increased iPTH stability at room temperature (5) compared to serum samples (6) and is recommended by the manufacturer of the DPC IMMULITE 2000 iPTH assay. However, insufficient sample volume can lead to increased final EDTA concentration in the sample-reagent mixture, causing chelation of metallic cations, and this can affect the activity of the alkaline phosphatase label used …

Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.

Minimal-invasive Parathyreoidektomie in Lokalanaesthesie in Verbindung mit Ultrasonographie, Sestamibi-Szintigraphie und intraoperativer Parathormonmessung

The standard procedure in patients with primary hyperparathyroidism (pHPT) includes cervical exploration and identification of all four enlarged parathyroid glands. New localization techniques, i.e., ultrasonography associated with color duplex sonography, 99mTc-sestamibi scintigraphy and the possibility of intraoperative parathormone (iPTH) measurement permit minimally invasive parathyroidectomy (MIP). Three different methods have been established: minimally invasive open parathyroidectomy, endoscopic parathyroidectomy and video-assisted parathyroidectomy. We present our experience with open MIP with the patient under local anesthesia (LA). In 25 patients with pHPT the operation was started under local anesthesia. Preoperatively, ultrasonography and sestamibi scintigraphy were performed in each patient. iPTH measurement was carried out intraoperatively. In 23 patients (92%) the operation was done successfully in LA. There were no postoperative complications. During follow-up none of the patients developed hypercalcemia again. MIP in connection with ultrasonography, sestamibi scintigraphy and intraoperative PTH measurement offers a promising treatment for patients with pHPT.

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels

Background. Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. Methods. Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. Results. Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 ± 0.9 mg/dL (± SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 ± 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 ± 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = −.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 ± 0.9 pg/mL) with a mean iPTH level of 74.8 ± 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. Conclusions. Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels. (Surgery 2000;128:930-6.)

Intraoperative parathyroid hormone monitoring as an adjunct to parathyroidectomy

Parathyroidectomy has a success rate of greater than 95% in the hands of experienced surgeons. To maintain this result in a more cost-effective way, intraoperative monitoring of intact parathyroid hormone (iPTH) has been used to decrease operative times. This technique signals when all hyperfunctioning tissue has been excised or when further dissection is necessary. Eighty-nine consecutive patients with hyperparathyroidism had plasma samples measured for iPTH levels during parathyroidectomy. Nine patients had previous neck explorations. Perioperative iPTH measurements using immunochemiluminescent assays with a turnaround time of 10 minutes were done after excision of each suspected abnormal parathyroid gland. All patients except one returned to and maintained normal calcium levels during the follow-up period of 8 months (range, 1 to 25 months). Prediction of postoperative calcium levels by means of quick immunochemiluminescent assay has a sensitivity of 97%, specificity of 100%, and an overall accuracy of 97%. Specific influence on surgical judgment was noted in four patients with multiglandular disease, in seven with difficult localization problems, and in one patient in whom the hyperfunctioning parathyroid tissue was not recognized. Monitoring the plasma iPTH levels during parathyroidectomy directly aided the surgeon's operative approach in these 12 patients. Intraoperative iPTH assay is useful with predictive accuracy of 97%. It influenced or changed the operative approach in 13% of patients.

Diagnosis and treatment of aluminium bone disease.

Aluminium accumulation in serum and tissues is a well-known complication in patients with chronic renal failure, and retention of the element in bone has been implicated in the pathogenesis of the so-called aluminium-related bone disease (ARBD). Regular serum aluminium monitoring remains mandatory to detect patients and centres at risk for aluminium intoxication. Early recognition of ARBD however requires a desferrioxamine (DFO) test in combination with a serum iPTH measurement. Definite diagnosis of ARBD is made by histological examination of a bone biopsy. Once ARBD has been identified DFO treatment should be initiated and all potential sources of aluminium exposure eliminated. In order to minimize the risk for DFO-related cerebral, auditory and visual side-effects, and siderophore-mediated opportunistic infections the chelator should be used at low doses (5 mg/kg) and administered widely spaced (once weekly) following well-defined strategies of administration.

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload

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. 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%). 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. 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.

The effect of cimetidine on parathyroid function and histopathology in primary hyperparathyroidism.

Recent evidence suggests that cimetidine given pre-operatively in primary hyperparathyroidism (1 degree HPT) might cause structural changes in parathyroid glands, while its suppressive effects on the disease are disputable. To determine these possible changes we studied 38 patients with 1 degree HPT who underwent parathyroidectomy. In 14 of these (group I) cimetidine was given pre-operatively (1000 mg orally daily for 4 weeks). The remaining 24 patients (group II) did not take any drug. Parathyroid function was estimated by nephrogenous cAMP (NcAMP) and serum immunoreactive parathyroid hormone (iPTH) measurements. Histological examination of the parathyroids was made by conventional techniques. In group I at the end of cimetidine treatment, the only change observed was a small but significant (p less than 0.05) decrease of plasma calcium (-0.77 mg/dl). Histologically, the glands of group I--compared with those of group II--showed the following findings: increased gland mass: mean increase 1050 mg (adenomas) and 700 mg (hyperplasias); central oedema in all the cases of group I only; increased (about 50 per cent) cellular size and intranuclear 'inclusions' in 10 out of 14 cases of group I only. It is concluded that treatment with cimetidine in 1 degree HPT is followed by histopathologic alterations leading to increased size of the diseased parathyroids.

Evaluation of Hypocalcemia with a Highly Sensitive, Homologous Radioimmunoassay for the Midregion of Parathyroid Hormone

The diagnosis of hypoparathyroidism by radioimmunoassay of serum parathyroid hormone (PTH) has been hampered by lack of an assay system sensitive enough to allow discrimination between low and normal values. A new assay for human PTH that has improved sensitivity has been developed. It uses an homologous antiserum (against the human hormone) and uses a carboxy-terminal fragment of bovine PTH as tracer to provide an assay monospecific for the midregion of PTH. Immunoreactive PTH (iPTH) was detectable in 25/27 normal children and borderline detectable in the other two. The pediatric normal range was slightly lower than that previously established in adults. Among patients with secondary hyperparathyroidism and normal renal function, iPTH was 3- to 8-fold elevated in those with rickets, and 1.3- to 2.0-fold above normal in those with more acute forms of hypocalcemia. Twelve patients with hypoparathyroidism were studied. iPTH was undetectable in seven with permanent total hypoparathyroidism, and was borderline detectable in five, including four neonates who proved to have transient hypoparathyroidism. In these four patients, iPTH became detectable as the requirements for supplemental calcium decreased. Measurement of iPTH with an adequately sensitive assay may be useful in the diagnosis and management of pediatric hypocalcemia.

Diagnosis of hyperparathyroidism in patients with urolithiasis using measurement of serum immunoreactive parathyroid hormone and serum calcium.

Serum immunoreactive PTH (iPTH) was measured in 74 patients with urolithiasis and correlated to the corresponding serum calcium values. Serum iPTH was measured using a rooster antibovine iPTH antiserum which crossreacted with the human hormone within the 44-68 amino acid residue region. Sixty-six of these patients had normal serum iPTH and calcium concentrations. Their calcium values varied from 2.2 mmol/l to 2.6 mmol/l and their serum iPTH concentrations were less than 0.6 micrograms/l. The remaining 8 patients with urolithiasis were judged to have primary hyperparathyroidism because of an abnormal iPTH/calcium relationship. These patients had serum calcium concentrations varying from 2.6 mmol/l to 3.4 mmol/l and iPTH concentrations between 0.35 micrograms/l and 3.03 micrograms/l. The diagnosis was verified histologically in 7 patients after operation. In the last patient iPTH was reduced from 1.01 micrograms/l to 0.21 micrograms/l after surgery, and serum calcium changed from 2.6 mmol/l to 2.2 mmol/l. The combined evaluation of serum iPTH and calcium may improve the diagnosis for hyperparathyroidism and was in our series helpful in making a correct diagnosis in 2 out of 7 patients who had histologically verified disease. In addition, iPTH measurements are valuable to rule out hyperparathyroidism as the cause of hypercalcaemia.

Parathyroid hormone in chronic renal failure: studies with two different parathyroid hormone radioimmunoassays.

Two assays for immunoreactive parathyroid hormone (iPTH) with different specificities were used to evaluate the role of iPTH measurement in patients with chronic renal failure (CRF). One measured largely C-terminal iPTH fragments, the other largely intact iPTH. In untreated CRF, the log iPRH for each assay was significantly correlated with the reciprocal of the creatinine clearance (CCr). C-terminal iPTH was elevated at relatively high CCr values, but intact iPTH was not elevated until later in the progression of CRF. In hemodialysis patients treated with 25-hydroxyvitamin D3, intct iPTH correlated better than C-terminal iPTH with clinical improvement. These two assays used together were more helpful in evaluation of CRF patients than either assay alone.