Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism

1991 ◽  
Vol 37 (2) ◽  
pp. 162-168 ◽  
Author(s):  
David B Endres ◽  
Rocheile Villanueva ◽  
Charles F Sharp ◽  
FrederIck R Singer

Abstract Parathyrin (parathyroid hormone; PTH) was measured with three immunoassays: a two-site immunochemiluminometric (ICMA) and a two-site immunoradiometric (IRMA) method for intact PTH, and a sensitive radioimmunoassay for mid-region or "total" PTH, measuring both intact hormone and inactive fragments. Single specimens from normal subjects and from individuals with primary hyperparathyroidism, hypercalcemia associated with malignancy, and hypoparathyroidism were analyzed with all three methods. All individuals with primary hyperparathyroidism showed absolutely above-normal concentrations with the mid-region RIA, 28 of 29 did with the ICMA, and 21 of 29 did with the IRMA. PTH concentrations in primary hyperparathyroidism were most increased relative to normal subjects with the mid-region assay (10.4 times), less so with the intact assays (ICMA 5.5 times; IRMA 5.3 times). Concentrations of intact PTH were suppressed below normal in nearly all patients with hypercalcemia associated with malignancy, as measured with the ICMA (26 of 30) and the IRMA (28 of 30) assays. In marked contrast, results for mid-region PTH were normal or slightly above normal, consistent with studies suggesting that the parathyroids secrete both intact hormone and inactive fragments, the former being more sensitive to suppression by hypercalcemia. In hypoparathyroidism PTH concentrations were detectable but below normal in all patients by the intact assays and in all but one patient by the mid-region assay. These low concentrations are probably due to a nonspecific serum effect that could be resolved with selection of a more appropriate standard matrix. Although all three assays are useful in the differential diagnosis of hypercalcemia, two-site intact assays are more convenient and more specific in patients with compromised renal function.

1979 ◽  
Vol 57 (5) ◽  
pp. 435-443 ◽  
Author(s):  
M. A. Dambacher ◽  
J. A. Fischer ◽  
W. H. Hunziker ◽  
W. Born ◽  
J. Moran ◽  
...  

1. The distribution of intact parathyroid hormone-(1–84) [PTH-(1–84)] and of its COOH-terminal fragments was determined in human serum by column chromatography. In addition to PTH-(1–84) (peak I), COOH-terminal fragments having molecular weights of approximately 4000–7000 (peak II) and immunoreactive components co-eluting with human PTH-(1–12) (peak III) were observed. 2. Mean concentrations of intact PTH-(1–84) and of its COOH-terminal fragments were significantly raised in chronic renal failure as compared with those of normal subjects. Mean amounts of peak II were higher in patients with chronic renal insufficiency than in nutritional vitamin D deficiency, in pseudohypoparathyroidism and in primary hyperparathyroidism, despite comparable amounts of PTH-(1–84). 3. In chronic renal failure as well as in a group of patients with vitamin D deficiency, pseudohypoparathyroidism and primary hyperparathyroidism and in controls, significant linear relations were found between the serum concentrations of calcium and log (peak II/peak I). Our findings suggest that the conversion of intact PTH-(1–84) into COOH-terminal fragments by the parathyroid glands (resulting in a raised secretion of fragments) and/or in peripheral organs may be directly related to the serum concentration of calcium. However, the degradation of the fragments may also be suppressed in a calcium-dependent manner.


2021 ◽  
Vol 12 ◽  
pp. 204062232110159
Author(s):  
Ana Kashfia Islam

The parathyroid glands, one of the last organs to be discovered, are responsible for maintaining calcium homeostasis, and they continue to present the clinician with diagnostic and management challenges that are reviewed herein. Primary hyperparathyroidism (PHPT) comprises the vast majority of pathology of the parathyroid glands. The classic variant, presenting with elevated calcium and parathyroid hormone levels, has been studied extensively, but the current body of literature has added to our understanding of normocalcemic and normohormonal variants of PHPT, as well as syndromic forms of PHPT. All variants can lead to bone loss, kidney stones, declining renal function, and a variety of neurocognitive, gastrointestinal, and musculoskeletal complaints, although the majority of PHPT today is asymptomatic. Surgery remains the definitive treatment for PHPT, and advances in screening, evolving indications for surgery, new imaging modalities, and improvements in intra-operative methods have greatly changed the landscape. Surgery continues to produce excellent results in the hands of an experienced parathyroid surgeon. For those patients who are not candidates for surgery, therapeutic advances in medical management allow for improved control of the hypercalcemic state. Parathyroid cancer is extremely rare; the diagnosis is often made intra-operatively or on final pathology, and recurrence is common. The mainstay of treatment is normalization of serum calcium via surgery and medical adjuncts.


1991 ◽  
Vol 125 (6) ◽  
pp. 668-674 ◽  
Author(s):  
Anders Bergenfelz ◽  
Stig Valdermarsson ◽  
Bo Ahrén

Abstract. Plasma levels of parathyroid hormone were determined pre-operatively in 27 consecutive patients with clinical and biochemical signs of primary hyperparathyroidism, by the use of one assay recognizing the intact PTH molecule and one assay recognizing the mid-portion of PTH. Plasma levels of mid-molecule PTH were normal in 5 of the patients with primary hyperparathyroidism. In 4 of these patients, plasma levels of intact PTH were raised. Conversely, in 6 patients with primary hyperparathyroidism, intact PTH were normal pre-operatively. In 5 of these cases, plasma levels of mid-molecule PTH were raised. The EDTA infusion test was performed in 6 patients with normal baseline plasma level of intact PTH pre-operatively. The test correctly predicted all the patients in this group who were found to have primary hyperparathyroidism, as well as a patient with normal parathyroid glands found at operation. We conclude that some patients with primary hyperparathyroidism have normal baseline plasma levels of intact PTH. In these patients, plasma levels of mid-molecule PTH and an EDTA infusion test provide further diagnostic information.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Sophy Mo

Hypercalcemia is a presentation commonly encountered in the clinical setting. Due to its vast differential diagnosis, a systematic approach is necessary when approaching patients with hypercalcemia. This article presents a simple, yet thorough approach to help clinicians determine the etiology of their patient's hypercalcemia. The main components of history taking, physical examination, and laboratory investigations for patients with hypercalcemia are highlighted. Emphasis is put on the importance of determining whether the hypercalcemia is associated with elevated or inappropriately normal parathyroid hormone (PTH) or not. The main etiologies of PTH-dependent hypercalcemia and PTH-independent hypercalcemia are explored. Primary hyperparathyroidism and hypercalcemia secondary to malignancy are highlighted as together, they make up 90% of hypercalcemia cases. A presentation of the management principles of hypercalcemia is also provided.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Rym Belaid ◽  
Ibtissem Oueslati ◽  
Melika Chihaoui ◽  
Meriem Yazidi ◽  
Wafa Grira ◽  
...  

Von Hippel–Lindau disease is an autosomal dominant inherited syndrome predisposing to a variety of highly vascularised tumors in different organs. Although bilateral pheochromocytoma was reported in patients with von Hippel–Lindau disease, the coexistence of primary hyperparathyroidism is not a common condition. We report an observation of a primary hyperparathyroidism secondary to an ectopic secretion of intact parathyroid hormone in a 17-year-old girl with von Hippel–Lindau disease and bilateral pheochromocytoma. She presented with a newly diagnosed diabetes mellitus and a severe arterial hypertension. Blood tests disclosed hypercalcemia with increased intact PTH level. Cervical ultrasound and sestamibi scintigraphy were normal. Twenty-four-hour urinary normetanephrine level was highly elevated pointing to a catecholamine-secreting tumor. The abdominal computed tomography showed bilateral adrenal masses. MIBG scintigraphy exhibited a high accumulation of the tracer in both adrenal tumors. Genetic testing revealed a mutation of the VHL gene. The patient underwent a bilateral adrenalectomy. The postoperative outcome was marked by normalization of blood pressure, blood glucose, calcium, and PTH levels. In our case, the elevation of intact PTH and its spontaneous normalization after surgical treatment of pheochromocytomas confirms its ectopic secretion.


2005 ◽  
Vol 51 (2) ◽  
pp. 395-400 ◽  
Author(s):  
Jean-Claude Souberbielle ◽  
Véronique Fayol ◽  
Corinne Sault ◽  
Ethel Lawson-Body ◽  
André Kahan ◽  
...  

Abstract Background: The recent development of nonradioactive automated assays for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) has made measurement of these two hormones possible in many laboratories. In this study, we compared two new assays for PTH and 25OHD adapted on an automated analyzer, the LIAISON®, with two manual immunoassays used worldwide. Methods: We studied 228 osteoporotic patients, 927 healthy individuals, 38 patients with primary hyperparathyroidism, and 167 hemodialyzed patients. Serum PTH was measured with the Allegro® and the LIAISON assays, and 25OHD was measured with DiaSorin RIA and the LIAISON assay. Regression analysis was used to calculate decision thresholds for the LIAISON assays that were equivalent to those of the Allegro PTH and DiaSorin 25OHD assays. Results: The 25OHD concentrations obtained with the LIAISON assay and the RIA in osteoporotic patients were well correlated (r = 0.83; P <0.001). Regression and Bland–Altman analyses suggested that the LIAISON 25OHD assay reads lower than the DiaSorin RIA at low concentrations but higher at high concentrations. However, the cutoff (50 nmol/L) used in our laboratories to define vitamin D insufficiency with the DiaSorin RIA is applicable to the LIAISON 25OHD assay. In 927 healthy individuals, the 3rd–97th percentile intervals were 3–80 ng/L and 13–151 nmol/L for the LIAISON PTH and 25OHD concentrations, respectively. However, 506 individuals (54.6%) were vitamin D-insufficient; we therefore considered only the 421 individuals with a LIAISON 25OHD >50 nmol/L as eligible for the reference population for the LIAISON PTH assay. In this group, the 3rd–97th percentile interval for LIAISON PTH was 3–51 ng/L. Considering upper reference limits of 46 and 51 ng/L for the Allegro and LIAISON assays, respectively, the frequency of above-normal PTH concentrations in patients with primary hyperparathyroidism was similar in both assays. Regression analysis between serum PTH measured by the Allegro and LIAISON assays in 167 hemodialyzed patients and the corresponding Bland–Altman analysis of these data suggest that the LIAISON PTH assay tends to read higher than the Allegro assay at low concentrations but lower at high concentrations (>300 ng/L). Conclusions: Because clinical decision limits for both PTH and 25OHD should be assay specific, we propose equivalences between these assays and two manual assays used worldwide. These assay-specific decision limits should help potential users of the LIAISON PTH and 25OHD assays.


1987 ◽  
Vol 115 (1) ◽  
pp. 183-186 ◽  
Author(s):  
G. M. Almahroos ◽  
K. Docherty ◽  
J. A. Fletcher ◽  
T. Webb ◽  
D. A. Heath

ABSTRACT Familial benign hypercalcaemia (FBH) closely resembles primary hyperparathyroidism (PHPT) both clinically and biochemically. Using a cDNA probe for the parathyroid hormone (PTH) gene we have studied restriction fragment length polymorphisms in normal British subjects and have shown them to be similar to those found in previous studies in a German population. The pattern of inheritance of these restriction fragment length polymorphisms in a family with FBH shows that the PTH gene is not involved in the pathogenesis of the condition. Limited studies in PHPT indicate that it is unlikely that a major structural defect or rearrangement is responsible for the sporadic form of the disease. J. Endocr. (1987) 115, 183–186


Author(s):  
Aubrey Blumsohn ◽  
Amna Al Hadari

Immunometric assays claiming to determine intact parathyroid hormone (PTH) generally cross-react with N-truncated forms such as PTH(7-84). Laboratories need to examine the relevance of new assays with probable PTH(1-84) specificity. It is logical that assays should measure what they state they do. However, it seems unlikely that use of older 'intact' PTH assays will affect the clinical interpretation of results in primary hyperparathyroidism or vitamin D deficiency. It is plausible that appropriate application of new PTH assays could improve outcome in chronic renal failure. However, it has never been suggested that straightforward replacement of existing assays with new PTH(1-84) assays will lead to this improved outcome. A better understanding of PTH fragments and their interaction with PTH receptors may shed light on the relevance of different PTH assays. In the meantime, older technologies will continue to work well for the vast majority of patients.


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