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1.  Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism 
Journal of Clinical Investigation  1974;54(1):175-181.
The immunoreactive forms of parathyroid hormone (iPTH) in the plasma of six patients with primary, adenomatous hyperparathyroidism and six patients with ectopic hyperparathyroidism due to non-parathyroid cancer were compared by using gel filtration on columns of Bio-Gel P-150 and radioimmunoassay of iPTH in eluted fractions after concentration. We found much less (p<0.001) small (mol wt<9,500) COOH-terminal fragments of iPTH in plasma samples from ectopic hyperparathyroid patients (0.52±0.13 ng eq/ml) than in samples from primary hyperparathyroid patients (3.70±1.15 ng eq/ml). The quantity of iPTH eluting with or before native bovine PTH [1-84] was the same in both syndromes (ectopic hyperparathyroidism, 0.82±0.22 ng eq/ml; primary hyperparathyroidism, 0.73±0.09 ng eq/ml), and these values correlated positively with plasma calcium concentration (ectopic hyperparathyroidism, r=0.908; primary hyperparathyroidism, r=0.919). In both syndromes, plasma samples had an iPTH component that eluted well before PTH [1-84] (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al. 1971. J. Clin. Invest. 50: 2079); (b) there appears to be sufficient iPTH with presumed biologic activity to account for the hypercalcemia in both syndromes; (c) a large PTH component, not previously recognized in plasma, is present in both ectopic and primary hyperparathyroidism and may exist as the predominant immunoreactive form of the hormone in some patients with ectopic hyperparathyroidism.
Images
PMCID: PMC301537  PMID: 4834887
2.  Radioimmunoassay of human parathyroid hormone in serum 
A new radioimmunoassay for human parathyroid hormone (PTH) in serum, which can measure the hormone present in 94% of the normal sera tested, is described. It is based on the ability of human PTH to compete with 131I-labeled bovine PTH for binding to an antiserum directed against porcine PTH. This antiserum distinguishes between human PTH extracted from parathyroid adenomata and that present in hyperparathyroid sera. Evidence is given to suggest that this is due to immunochemical changes in the hormone extracted from adenomata and not to immunochemical heterogeneity of the hormone present in serum.
Physiologic data supporting the validity and specificity of the assay are presented. Induced episodes of hypercalcemia and hypocalcemia resulted in appropriate responses in serum immunoreactive PTH (IPTH) in normal subjects and in patients with Paget's disease of bone. In normals, there was a progressive increase in serum IPTH in the late afternoon and evening, suggesting a diurnal secretory rhythm. A negative correlation was found between the serum calcium and serum IPTH over the normal range of serum calcium values; a positive correlation was found between these variables in patients with primary hyperparathyroidism. There was apparent overlap between serum IPTH values in normal subjects and patients with primary hyperparathyroidism, but formal discriminate analysis of values for serum calcium and IPTH demonstrated separation of these two groups, without overlap.
PMCID: PMC291890  PMID: 5543877
3.  Immunoheterogeneity of Parathyroid Hormone in Venous Effluent Serum from Hyperfunctioning Parathyroid Glands 
Journal of Clinical Investigation  1977;60(6):1367-1375.
The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo.
To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH2)-terminal region of the molecule, the other toward the COOH-terminal region.
In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH2-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH2-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84).
We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.
PMCID: PMC372494  PMID: 915003
4.  Parathyroid Function in Primary Osteoporosis 
Journal of Clinical Investigation  1973;52(1):181-184.
Two major species of serum immunoreactive parathyroid hormone (iPTH) were measured in 47 untreated patients with primary osteoporosis by using two highly specific radioimmunoassays. Mean iPTH was normal with one antiserum but was lower than normal (P < 0.001) with the other, iPTH values did not correlate with biochemical parameters or with the proportion of bone-resorbing surfaces in iliac crest bone biopsy specimens. These data suggest that the increased bone resorption is not due to increased parathyroid function in most osteoporotic patients. However, seven of our patients (15%) appear to represent a separate population because they had increased values with one or the other of the antisera.
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PMCID: PMC302240  PMID: 4734167
5.  Limited role for intraoperative intact PTH measurement in parathyroid surgery. 
Primary hyperparathyroidism may be cured surgically by complete excision of abnormal parathyroid tissue. Reoperation for persistent hypercalcaemia due to residual abnormal parathyroid tissue may be associated with a high complication rate. It is possible to assay intact parathormone (iPTH) intraoperatively and as iPTH has a relatively short half-life, its measurement intraoperatively may be used to predict successful parathyroidectomy. We have studied intraoperative iPTH levels in a consecutive series of 33 patients undergoing surgery for primary hyperparathyroidism. We found that iPTH levels fell significantly (P < 0.05) from a median pre-excision level of 122 pg/ml to a median level of 36 pg/ml 20 min after excision. However, in 3/31 successful parathyroidectomies, the intraoperative iPTH levels either remained unchanged or had risen. Reliance on intraoperative iPTH levels in these patients may have resulted in unnecessary re-exploration. We conclude that intraoperative iPTH measurement has limited usefulness as a predictor of successful parathyroidectomy for primary hyperparathyroidism.
PMCID: PMC2502514  PMID: 7717640
6.  Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test 
Journal of Clinical Investigation  1977;60(4):771-783.
Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1°HPT), and 10 patients with chronic hypoparathyroidism.
In the group with 1° HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium ≤10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%).
The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1° HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1° HPT, avoided entirely the inadequacies of alternative expressions.
Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed.
PMCID: PMC372425  PMID: 197123
7.  Rapid Decrease of Intact Parathyroid Hormone Could Be a Predictor of Better Response to Cinacalcet in Hemodialysis Patients 
Yonsei Medical Journal  2013;54(2):453-463.
Purpose
Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response.
Materials and Methods
A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month.
Results
Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target.
Conclusion
Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.
doi:10.3349/ymj.2013.54.2.453
PMCID: PMC3575968  PMID: 23364981
Cinacalcet; end-stage renal disease; hemodialysis; parathyroid hormone; secondary hyperparathyroidism
8.  Reversal of Secondary Hyperparathyroidism by Cimetidine in Chronically Uremic Dogs 
Journal of Clinical Investigation  1981;67(6):1753-1760.
Chronic cimetidine therapy has been shown to suppress circulating concentrations of immunoreactive parathyroid hormone (iPTH) in hemodialysis patients. To evaluate the long-term metabolic effects of cimetidine treatment, we studied seven chronically uremic dogs for 20 wk. The dogs were studied under metabolic conditions before, during, and after cimetidine therapy. iPTH fell progressively in the five treated dogs from 536±70 μleq/ml (mean±SE) (nl < 100 μleq/ml) before treatment to 291±25 μleq/ml at 12 wk (P < 0.001) and 157±32 μleq/ml at 20 wk (P < 0.001). The control dogs showed no consistent change in iPTH. The fall in iPTH was not associated with a change in serum ionized calcium. However, serum phosphorus decreased from 5.7±0.9 mg/dl to 3.4±0.2 mg/dl by the 20th wk (P < 0.05). By contrast, the serum concentration of 1,25-dihydroxycholecalciferol increased in all treated dogs from 33.4±4.3 pg/ml to 51.8±2.4 pg/ml during treatment (P < 0.01). Calcium balance was negative in all seven dogs before cimetidine (−347±84 mg/72 h) and remained so in the control dogs; it became positive in the five treated dogs after 12 wk (1,141±409 mg/72 h) (P < 0.05). Phosphorus balance, 24-h fractional phosphate excretion, and creatinine clearance remained unchanged. Pooled samples of serum obtained during the control and 20th wk of therapy were fractionated by gel filtration and the eluates assayed for immunoreactivity. The decrease in iPTH was associated with a decrease in all the immunoreactive species, indicating suppression of parathyroid gland secretion.
These observations indicate that cimetidine suppressed circulating concentration of biologically active parathyroid hormone. A probable net decrease in the loss of phosphorus from bone to blood ensued, resulting in a fall in serum phosphorus. This may have stimulated synthesis of 1,25-dihydroxycholecalciferol and led to a positive calcium balance, thereby maintaining the serum ionized calcium concentration. The maintenance of phosphate balance, despite suppression of iPTH by cimetidine, indicates that factors other than hyperparathyroidism relate to phosphate homeostasis in chronically uremic dogs.
PMCID: PMC370753  PMID: 7240419
9.  Perioperative Management Difficulties in Parathyroidectomy for Primary Versus Secondary and Tertiary Hyperparathyroidism 
Mædica  2012;7(2):117-124.
ABSTRACT
Background: In patients with hyperparathyroidism, parathyroidectomy is the only curative therapy. Anaesthetic management differs function of etiology (primary vs. secondary or tertiary hyperparathyroidism) and surgical technique (minimally invasive or classic parathyroidectomy).
Objectives: To evaluate peri-operative management (focusing on hemodynamic changes, cardiac arrhythmias and patients’ awakening quality) in parathyroidectomy for hyperparathyroidism of various etiologies, in a tertiary center.
Material and methods: 292 patients who underwent surgery for hyperparathyroidism between 2000-2011 were retrospectively reviewed; 96 patients (19M/77F) presented with primary hyperparathyroidism (group A) and 196 (80M/116F) with secondary and tertiary hyperparathyroidism due to renal failure (group B). Biochemical parameters (serum calcium, phosphate, creatinine) were determined by automated standard laboratory methods. Serum intact PTH was measured by ELISA (iPTH - normal range: 15-65 pg/mL).
Outcomes: Median surgery duration was 30 minutes in group A (minimally invasive or classic parathyroidectomy) and 75 minutes in group B (total parathyroidectomy and re implantation of a small parathyroid fragment into the sternocleidomastoid muscle). During anaesthesia induction, arterial hypotension developed significantly more frequent in group B (57 out of 196 pts, 29.1%) than in group A (8 out of 96 pts, 8.34%), p<0.0001, especially in patients receiving Fentanyl-Propofol. During surgery and anaesthesia maintenance, bradycardia was significantly more frequent in group A (67 out of 96 pts, 69.8%) than in group B (26 out of 196 pts, 13.3%), p<0.0001, especially during searching of parathyroid glands. By contrary, ventricular premature beats were less frequent in group A (25 out of 96 pts, 25.25%) than in group B (84 out of 196 pts, 42.85%), p=0.003. There were no statistically significant differences between the studied group regarding frequency of arterial hypertension and hypotension, paroxysmal atrial fibrillation.
Conclusions: anaesthetic management in parathyroid surgery may be difficult because of cardiac arrhythmias (bradycardia in primary hyperparathyroidism and ventricular premature beats in secondary and tertiary hyperparathyroidism, respectively) and arterial hypotension during anaesthesia induction in patients with secondary and tertiary hyperparathyroidism.
PMCID: PMC3557418  PMID: 23399537
hyperparathyroidism; parathyroidectomy; anaesthesia; arrhythmias; arterial hypotension
10.  The Relationship Between Technetium-99m-Methoxyisobutyl Isonitrile Parathyroid Scintigraphy and Hormonal and Biochemical Markers in Suspicion of Primary Hyperparathyroidism 
Objective: Technetium-99m-methoxyisobutyl isonitrile (Tc-99m MIBI) has been widely used to evaluate hyperfunctioning autonomous parathyroid glands in patients with elevated intact parathyroid hormone (iPTH) and/or calcium (Ca) level. The aim of this study was to evaluate the relationship between Tc-99m MIBI parathyroid scintigraphy and hormonal and biochemical markers in suspicion of primary hyperparathyroidism (PHPT).
Material and Methods: Dual-phase Tc-99m MIBI parathyroid scintigraphy and total serum iPTH, Ca, phosphorus (P) and albumin measurements were performed in 60 patients (52 females, 8 males; mean age, 59.38±12.51 years; range, 34 to 86 years) with suspicion of PHPT.
Results: The iPTH median level was 160.3 pg/mL (47.8 to 782.6). Thirty-five of the patients had surgical resection of hyperfunctioning parathyroid glands. Of the 35 patients, parathyroid gland pathology was detected in 30 patients using scintigraphic examination. Tc-99m MIBI parathyroid scintigraphy was negative in 30 patients. The iPTH, Ca and P levels were significantly different between in the Tc-99m MIBI positive group and the negative group, respectively: For iPTH, 202.1 (47.8-782.6) pg/mL versus 111.6 (80.1-373) pg/mL; p<0.001. For Ca, 11.7±1.15 mg/dL versus 10.3±1.05 mg/dL; p<0.001 and for P levels, 2.46±0.62 mg/dL versus 3.40±0.70 mg/dL; p<0.001). There was no significant difference in serum albumin levels between the MIBI positive and MIBI negative groups (4.25±0.27 g/dL versus 4.25±0.41 g/dL; p>0.05). Tc-99m MIBI parathyroid scintigraphy showed good correlation with iPTH level and histopathological diagnosis. Sensitivity and specificity was found 83.3% and 76.7%, respectively at the level of iPTH>147.7pg/mL.
Conclusion: Tc-99m MIBI parathyroid scintigraphy is most likely to produce identification and localization of a parathyroid adenoma when both iPTH and Ca are elevated as well as decreased P levels.
Conflict of interest:None declared.
doi:10.4274/Mirt.21931
PMCID: PMC3629790  PMID: 23610725
Technetium-99m sestamibi; primary hyperparathyroidism; parathyroid hormone; calcium; phosphorus
11.  Serum calcitonin-lowering effect of magnesium in patients with medullary carcinoma of the thyroid. 
Journal of Clinical Investigation  1975;56(6):1615-1621.
The effect of magnesium chloride or magnesium sulfate infusion on circulating levels of immunoreactive calcitonin (iCT) was evaluated on nine occasions in three patients with metastatic medullary carcinoma of the thyroid. One patient was normocalcemic and had normal circulating levels of immunoreactive parathyroid hormone (iPTH), one patient was hypocalcemic and had surgical hypoparathyroidism, and one patient had mild to moderate hypercalcemia associated with bone metastases. The basal serum iPTH levels were undetectable in the latter two patients. In every instance magnesium administration produced a rapid and striking fall in circulating iCT and usually a detectable fall in serum calcium. During the hypermagnesemic state, serum iPTH fell from normal to undetectable in the patient with normal parathyroid function, while serum iPTH levels remained undetectable in the hypoparathyroid patient and in the patient with hypercalcemia associated with bone metastases. The results of these studies indicate that: (a) contrary to what has been reported in normal experimental animals, magnesium administration lowers circulating iCT in human subjects with thyroid medullary carcinoma and (b) the calcium-lowering effect produced by magnesium in patients with medullary carcinoma may, in part at least, be due to a redistribution of body calcium that is not mediated by the actions of either parathyroid hormone or clacitonin.
PMCID: PMC333141  PMID: 1202087
12.  Hypertension and hyperparathyroidism are associated with left ventricular hypertrophy in patients on hemodialysis 
Indian Journal of Nephrology  2009;19(4):153-157.
Conflicting data for association between left ventricular hypertrophy (LVH) and secondary hyperparathyroidism has been reported previously among dialysis patients. The present study was conducted to evaluate the association of hyperparathyroidism and hypertension with LVH. Charts of 130 patients on hemodialysis for at least six months were reviewed. All were subjected to M-mode echocardiography. Left ventricular mass (LVM) was calculated by Devereux's formula. LVM Index (LVMI) was calculated by dividing LVM by body surface area. Sera were analyzed for intact parathyroid hormone (iPTH). iPTH of > 32 pmol/l and a mean blood pressure (MAP) of > 107 mmHg were considered high. Patients were stratified into groups according to their MAP and iPTH. A total of (47.7%) patients were males and 68 (52.3%) were females. Their median age was 57 years. The median duration on dialysis was 26 months. Forty eight (36.9%) patients had high BP and 54 (41.5%) had high iPTH. Both high BP and high iPTH were present in 38 (29.2%) patients. Analysis of the relationship between LVM, LVMI, MAP and iPTH showed that LVM and LVMI were significantly (P < 0.001) higher in patients with concomitant high BP and high iPTH. LVMI was significantly higher in patients with high iPTH alone. Concomitant high iPTH and high MAP increase the risk of LVH in hemodialysis patients. High iPTH alone might contribute in escalating LVH. Adequate control of hypertension and hyperparathyroidism might reduce the risk of developing LVH.
doi:10.4103/0971-4065.59337
PMCID: PMC2875705  PMID: 20535251
Hemodialysis; hypertension; hyperparathyroidism; left ventricular hypertrophy
13.  Water-clear cell adenoma: A rare form of hyperparathyroidism☆ 
INTRODUCTION
Primary hyperparathyroidism is a common endocrine disorder, with an incidence of 21.6 per 100,000 person-years. Asymptomatic elevated serum calcium levels on routine biochemical investigations accounts for 80% of newly diagnosed primary hyperparathyroidism. Solitary adenoma is the commonest cause of primary hyperparathyroidism and can be treated by excision of a single gland.
PRESENTATION OF CASE
We present a case of primary hyperparathyroidism in a 74-year-old female was referred to our surgery endocrine outpatients for assessment of a persistently elevated calcium level, lower abdominal pain and constipation. Biochemical analysis revealed corrected serum calcium of 3.13 mmol/L (reference range 2.17–2.51 mmol/L) and an intact parathyroid hormone level (iPTH) of 488.9 ng/L (reference range 15–65 ng/L). Sestamibi scan localised a persistent increased area of activity inferior to the lower pole of the left lobe of thyroid gland.
DISCUSSION
The patient underwent a minimally invasive parathyroidectomy using a 3 cm incision with intra-op radionucliotide localisation. At surgery a single large parathyroid gland measuring 5.5 cm was excised without complication. Grossly the parathyroid gland was an encapsulated tan mass measuring 5.5 cm × 2.5 cm × 2 cm and weight 13 g and histological assessment revealed a water-clear cell (WCC) adenoma. She made an uneventful post op recovery with normalisation of her serum calcium.
CONCLUSION
WCC adenomas have a “low endocrinological activity” in which serum calcium levels do not elevate until the adenoma has reached considerable size. Our case supports this hypothesis and aids to the understanding of these rare tumours.
doi:10.1016/j.ijscr.2013.07.016
PMCID: PMC3785846  PMID: 23995477
Water clear cell adenoma; Parathyroid adenoma; Hypercalcaemia
14.  Could the eZ-SCOPE AN Gamma Camera Replace Intraoperative Measurement of iPTH for PHPT? 
International Surgery  2012;97(2):99-103.
Intraoperative intact parathyroid hormone (iPTH) measurements have been proposed as an effective assay in surgery for primary hyperparathyroidism (PHPT). We have demonstrated the efficiency of the use of a hand-held gamma camera, eZ-SCOPE AN, with technetium-99m sestamibi (Tc-MIBI) scintigraphy for navigation surgery for PHPT. The aim of this preliminary study was to assess the possibility that the eZ-SCOPE AN can replace the measurement of intraoperative iPTH in surgery for PHPT. Sixteen consecutive patients with documented primary hyperparathyroidism underwent surgery using this compact camera. iPTH was routinely measured preoperatively and 10 minutes after the complete removal of adenoma. All patients had a well-defined parathyroid lesion identified on preoperative Tc-MIBI. The eZ-SCOPE revealed hyperfunctioning parathyroid glands in all cases. iPTH levels were decreased in all cases after the removal of adenomas. Our results suggest that this gamma camera is useful for confirming complete resection of endocrinologically active tissue in surgery for PHPT. In selective patients with scan-positive cases identified by preoperative Tc-MIBI, the eZ-SCOPE may replace the intraoperative iPTH assay in surgery for PHPT.
doi:10.9738/CC138.1
PMCID: PMC3723210  PMID: 23102074
Primary hyperparathyroidism; Navigation surgery; Gamma camera; Sestamibi scintigraphy; Intact PTH
15.  Etiology of Hyperparathyroidism and Bone Disease during Chronic Hemodialysis. III. EVALUATION OF PARATHYROID SUPPRESSIBILITY 
Journal of Clinical Investigation  1973;52(1):173-180.
Parathyroid function was assessed by calcium infusions (4-8 h) in 16 patients with chronic renal insufficiency being treated by long-term hemodialysis. The concentrations of two immunoreactive species of parathyroid hormone in plasma (iPTH-9, mol wt 9500; iPTH-7, mol wt 7000) were estimated by radioimmunoassays utilizing two relatively specific antisera. Control values of the smaller species, iPTH-7, were uniformly high, whereas values of iPTH-9 were normal in 12 of 19 studies. Response of iPTH-7 to calcium infusions was variable, with significant decreases occurring only five times in 27 infusions. Concentrations of iPTH-9, however, decreased during every calcium infusion. In contrast to these acute responses, five of six patients studied during periods of dialysis against both low (< 6 mg/100 ml) and high (7-8 mg/100 ml) calcium concentrations in the dialyzate showed a decrease in values of iPTH-7 during the period of dialysis against the higher calcium concentration. It is concluded that plasma concentrations of iPTH-9 reflect primarily the moment-to-moment secretory status of the parathyroid glands, while concentrations of iPTH-7 reflect more closely chronic parathyroid functional status. It is further concluded that the failure of iPTH-7 to decrease during induced hypercalcemia should not be equated with autonomy of parathyroid gland function.
PMCID: PMC302239  PMID: 4734166
16.  High-intensity focussed ultrasound (HIFU) treatment in uraemic secondary hyperparathyroidism 
Background.
The recently developed non-invasive high-intensity focussed ultrasound (HIFU) technique for the destruction of parathyroid adenomas could also be of interest for the treatment of secondary hyperparathyroidism (SHP) in patients with chronic kidney disease (CKD). We conducted a pilot study using this method.
Methods.
Five chronic haemodialysis patients with severe SHP underwent one to three HIFU treatments, respectively. They had at least one or two enlarged parathyroid glands, which were accessible to this technique.
Results.
In Patients 1-I and 5-V, serum intact parathyroid hormone (iPTH) could be successfully reduced in the long run. In Patient 3-N, serum iPTH decreased dramatically down to the normal range but increased again subsequently. In Patients 2-E and 4-D, transient reductions in serum iPTH were also obtained but HIFU failed to correct SHP during follow-up. Serum total calcium and phosphorus decreased in four among the five patients, either transiently or permanently. Serum total alkaline phosphatases were reduced in four of five patients. Side effects included local oedema, transient impairment of vocal cord mobility and bitonal voice.
Conclusions.
HIFU treatment may be of help in controlling SHP in selected patients with CKD. Further experience is clearly needed.
doi:10.1093/ndt/gfr590
PMCID: PMC3276310  PMID: 22015443
chronic kidney disease; high-intensity focussed ultrasound; parathyroid ablation; secondary hyperparathyroidism
17.  The pattern of the descent of PTH measured by intraoperative monitoring of intact-PTH in surgery for renal hyperparathyroidism 
The Indian Journal of Surgery  2008;70(2):62-67.
Background
In the setting of total parathyroidectomy and autotransplantation surgery (TPTxAS) treatment for secondary hyperparathyroidism (SHPT) we evaluated whether intraoperative parathyroid hormone (iPTH) monitoring is an useful tool as a reference for total parathyroid removal.
Design
Prospective open single value measurement efficacy study of one intraoperative (i.o.) diagnostic monitoring method (iPTH) on a cohort of surgical patients.
Patients
All patients (n = 35) undergoing TP and SCTx at the Department of Surgery, Donostia Hospital from January 2002 to December 2006.
Main outcome measures
Serum levels of iPTH during surgery and prediction time of the of descent of PTH levels (measured in the clinic, at admission day and intra-operatively during induction of anesthesia, and every 5 and 10 minutes after removal of adenoma and 24 hours thereafter) were analyzed.
Results
iPTH levels dropped clearly at ten minutes in all 35 patients and were non-measurable at 24 hours. iPTH decreased from pathological (1302.24 + 424.9 pg/ml) to half (50%) the values at the third intra-operative determination — minute 10 − (614.8 ± 196.62) and was undetectable at 24 hours.
Conclusions
Intra-operative measurement of iPTH is useful in the prediction of complete removal of all parathyroid tissue prior to autotransplantation thus avoiding persistence because of incomplete surgery.
doi:10.1007/s12262-008-0017-9
PMCID: PMC3452396  PMID: 23133023
Total parathyroidectomy; Autotransplantation surgery; Secondary hyperthyroidism; Parathyroid hormone
18.  Intrathyroidal parathyroid hyperplasia in tertiary hyperparathyroidism 
Journal of Surgical Case Reports  2013;2013(5):rjt034.
We report herein a case of intrathyroidal parathyroid hyperplasia in a patient with tertiary hyperparathyroidism. The patient was recommended for parathyroidectomy due to sustained hypercalcemia after kidney transplantation. Preoperative radiologic evaluations showed a benign-looking thyroid mass and three enlarged parathyroid glands. Intraoperative intact parathyroid hormone (iPTH) level and frozen biopsy results indicated a missed parathyroid gland after immediate subtotal parathyroidectomy. Then, a secondary partial resection of thyroid including the thyroid nodule was performed. An excised intrathyroid nodule was diagnosed to be parathyroid hyperplasia by frozen biopsy, and intraoperative iPTH level abruptly decreased. A benign-looking thyroidal mass in patients with secondary or tertiary hyperparathyroidism should be carefully evaluated considering the possibility of an intrathyroidal parathyroid hyperplasia.
doi:10.1093/jscr/rjt034
PMCID: PMC3813706
19.  Validation study of intraoperative fine-needle aspiration of parathyroid tissue with measurement of parathyroid hormone levels using the rapid intraoperative assay 
Background
Surgical treatment of hyperparathyroidism relies on the ability to accurately identify parathyroid tissue. The use of intraoperative fine-needle aspiration (FNA) with measurement of intact parathyroid hormone level (iPTH-FNA) has been suggested as a useful adjunct and is evaluated in this pilot study.
Methods
An institutional review board–approved retrospective review was performed on patients undergoing parathyroid exploration for primary hyperparathyroidism who also underwent selective FNA at the end of the procedure. FNA was performed on excised parathyroid tissue, ipsilateral thyroid tissue, and muscle.
Results
Ten patients underwent FNA. Mean iPTH-FNA values were 1559.6 pg/mL (range, 675–1775) for parathyroid, 51.4 pg/mL(range, 10–248) for thyroid, and 34.1 pg/mL (range, 14–128) for muscle. All iPTH-FNA assay results were significantly higher for parathyroid tissue than for either thyroid tissue (P < 0.05) or muscle (P < 0.05). There were no significant iPTH-FNA assay differences between thyroid and muscle (P = 0.09).
Conclusions
Intraoperative FNA of parathyroid tissue with the rapid iPTH assay can correctly identify parathyroid tissue. It may prove to be a useful surgical adjunct in the treatment of hyperparathyroidism.
PMCID: PMC1200727  PMID: 16200175
20.  Calcium Metabolism in Newborn Infants THE INTERRELATIONSHIP OF PARATHYROID FUNCTION AND CALCIUM, MAGNESIUM, AND PHOSPHORUS METABOLISM IN NORMAL, “SICK,” AND HYPOCALCEMIC NEWBORNS 
Journal of Clinical Investigation  1974;54(2):287-296.
Serum immunoreactive parathyroid hormone (iPTH) and plasma total calcium, ionized calcium, magnesium, and phosphorus levels were determined during the first 9 days of life in 137 normal term infants, 55 “sick” infants, and 43 hypocalcemic (Ca <7.5 mg/100 ml; Ca++<4.0 mg/100 ml) infants.
In the cord blood, elevated levels of plasma Ca++ and Ca were observed, while levels of serum iPTH were either undetectable or low. In normal newborns during the first 48 h of life there was a decrease in plasma Ca and Ca++, while the serum iPTH level in most samples remained undetectable or low; after 48 h there were parallel increases in plasma Ca and Ca++ and serum iPTH levels. Plasma Mg and P levels increased progressively after birth in normal infants.
In the sick infants, plasma Ca, Ca++ and P levels were significantly lower than in the normal newborns, while no significant differences were found in the plasma Mg levels. The general pattern of serum iPTH levels in the sick infants was similar to that observed in the normal group, though there was a tendency for the increase in serum iPTH to occur earlier and for the iPTH levels to be higher in the sick infants.
In the hypocalcemic infants, plasma Mg levels were consistently lower than in the normal infants after 24 h of age, while no significant differences were found in the plasma P levels. Hyperphosphatemia was uncommon and did not appear to be a contributing factor in the pathogenesis of hypocalcemia in most infants. Most of the hypocalcemic infants, including those older than 48 h, had inappropriately low serum iPTH levels.
Evidence obtained from these studies indicates that parathyroid secretion is normally low in the early new born period and impaired parathyroid function, characterized by undetectable or low serum iPTH, is present in most infants with neonatal hypocalcemia. Additional unknown factors appear to contribute to the lowering of plasma Ca in the neonatal period. The net effect of unknown plasma hypocalcemic factor(s) on the one hand and parathyroid activity on the other may account for differences in plasma Ca levels observed between normal, sick, and hypocalcemic infants. Depressed plasma Mg is frequently present in hypocalcemic infants. To what degree the hypomagnesemia reflects parathyroid insufficiency or the converse, to what degree parathyroid insufficiency and hypocalcemia are secondary to hypomagnesemia, is uncertain.
PMCID: PMC301556  PMID: 4858778
21.  Spontaneous Resolution of Primary Hyperparathyroidism in Parathyroid Adenoma 
Case Reports in Endocrinology  2012;2012:793753.
A 71 yo woman with primary hyperparathyroidism awaiting surgery because of significant hypercalcemia and hypercalciuria presented to the local emergency department with the chief complaints of discomfort in her neck, sore throat, and difficulty swallowing. She was found to be hypocalcemic with a calcium level of 8.1 mg/dL. She was seen by her endocrinologist three days later at which time serum calcium, iPTH, and serum phosphate levels were all within normal limits. Based on history and a series of ultrasounds the patient was diagnosed with spontaneous infarction of her parathyroid adenoma, which resulted in resolution of her primary hyperparathyroidism.
doi:10.1155/2012/793753
PMCID: PMC3502788  PMID: 23198183
22.  Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level 
Background
Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and intact-parathyroid hormone levels are the most useful diagnostic parameters that allow differentiating primary hyperparathyroidism from non-parathyroid-dependent hypercalcemia. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. Approximately 5% of patients who underwent parathyroidectomy present with persistent or recurrent hyperparathyroidism due to ectopic localization of the adenoma. Functioning oxyphil parathyroid adenoma is an uncommon histological form, seldom causing primary hyperparathyroidism. Parathyroid adenoma with hypercalcemia exhibiting normal parathyroid hormone level is rare. An incidence of 5% to 33% has been documented in the literature; no etiologic explanation has been given. In 1987, parathyroid-hormone-related peptide was isolated as a causative factor of humeral hypercalcemia of malignancy. The presence of parathyroid-hormone-related peptide in parathyroid tissue under normal and pathological conditions has been described in the literature; however, its role in causing hyperparathyroidism has not yet been defined.
Case presentation
We present a case of persistent hypercalcemia with a normal level of intact-parathyroid hormone due to a substernal parathyroid adenoma, treated with radioguided parathyroidectomy. The final histological diagnosis was oxyphil adenoma, positive for parathyroid-hormone-related peptide antigens.
Conclusion
In clinical practice, this atypical biochemical presentation of primary hyperparathyroidism should be considered in the differential diagnosis of hypercalcemia. The parathyroid-hormone-related peptide should be considered not only in the presence of malignancy.
doi:10.1186/1477-7819-6-24
PMCID: PMC2279131  PMID: 18291038
23.  Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism? 
BMC Nephrology  2012;13:76.
Background
Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P.
Methods
The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300–799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (≤4.5 and ≤5.5 mg/dL) in relation to achievement of iPTH ≤300 pg/mL during the efficacy assessment phase (EAP; weeks 17–23).
Results
Patients who achieved iPTH ≤ 300 pg/mL (or a reduction of ≥30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ≤ 300 pg/mL, 43% achieved P ≤4.5 mg/dL and 70% achieved P ≤5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ≤ 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ≤300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ≤4.5 mg/dL during EAP in patients above this threshold at baseline.
Conclusions
This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received.
Trial registration
Clinicaltrials.gov identifier NCT00110890
doi:10.1186/1471-2369-13-76
PMCID: PMC3473247  PMID: 22863242
24.  Association of Secondary Hyperparathyroidism with Hemoglobin Level in Patients with Chronic Kidney Disease 
Purpose:
Secondary hyperparathyroidism (SHPT) is one of the less recognized reasons of anemia in chronic kidney disease (CKD). In this study, we evaluated the role of SHPT as a cause of anemia and correlation of intact parathyroid hormone (iPTH) and hemoglobin (Hb) level in hemodialysis (HD) patients.
Methods:
This cross-sectional study was carried out in 63 individuals admitted in HD unit of the institute. Serum samples were collected and urea, creatinine, Hb, ferritin and iPTH levels were measured. Statistical analysis was carried out using the SPSS software (IBM, NY, USA).
Results:
Mean ± standard deviation for serum urea, creatinine, Hb, ferritin and intact PTH were 177 ± 15.52, 15.16 ± 2.28 mg/dl, 7.03 ± 2.26 g/dl, 654.7 ± 563.4 ng/ml, 539.18 ± 493.59 pg/ml respectively. A reverse correlation was found between intact PTH and Hb level.
Conclusions:
A variety of postulated pathophysiological mechanisms linking SHPT and anemia in CKD are discussed. An efficient control of parathyroid hormone hypersecretion may be required to achieve a better management of anemia in HD patients.
doi:10.4103/0974-2727.115935
PMCID: PMC3758707  PMID: 24014970
Anemia; chronic kidney disease; ferritin; hemoglobin; intact parathyroid hormone; secondary hyperparathyroidism
25.  The Effect of a Predialysis Calcitriol Administration Protocol on Postdialysis Parathyroid Hormone Levels 
The Permanente Journal  2006;10(3):21-25.
Patients with chronic kidney disease often develop secondary hyperparathyroidism because of decreases in 1,25(OH)2-vitamin D (calcitriol) levels. These changes may be ameliorated with appropriate administration of oral calcitriol during the predialysis period. A calcitriol administration protocol was used with patients beginning on June 1, 2001. Mean serum intact parathyroid hormone (iPTH), calcium, and phosphorous levels from the three months preceding and three months following initiation of dialysis were measured. A significant difference in iPTH levels between patients treated under the calcitriol protocol and patients in the control group was observed. In addition, patients treated under the protocol were more likely to receive calcitriol than those who were not. No significant difference in serum calcium or phosphorous levels was observed. Administration of calcitriol via a protocol in predialysis patients reduced iPTH levels among patients after the initiation of dialysis.
PMCID: PMC3078774  PMID: 21519465

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