Metabolism of intact parathyroid hormone in isolated perfused rat liver and kidney

1988 ◽  
Vol 254 (6) ◽  
pp. E740-E748 ◽  
Author(s):  
H. Daugaard ◽  
M. Egfjord ◽  
K. Olgaard
Keyword(s):  
Parathyroid Hormone ◽  
High Performance ◽  
Hepatic Clearance ◽  
Isolated Perfused Rat Liver ◽  
Intact Parathyroid Hormone ◽  
Human Parathyroid Hormone ◽  
Intact Pth ◽  
Glandular Secretion ◽  
Liver And Kidney ◽  
Rat Livers

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.

Aldosterone metabolism in combined isolated perfused rat liver and kidney

1991 ◽  
Vol 260 (4) ◽  
pp. F536-F548
Author(s):  
M. Egfjord ◽  
H. Daugaard ◽  
K. Olgaard
Keyword(s):  
High Performance ◽  
Hepatic Clearance ◽  
Fractional Excretion ◽  
Isolated Perfused Rat Liver ◽  
Metabolic Clearance ◽  
Perfused Liver ◽  
Isolated Perfused Liver ◽  
Polar Metabolites ◽  
Liver And Kidney ◽  
Intact Rats

The metabolism of aldosterone (Aldo) at 4 nM was studied by radioimmunoassay and by high-performance liquid chromatography in isolated perfused liver (IPL), isolated perfused kidney (IPK), and combined isolated perfused liver and kidney (CIPLK) of male Wistar rats. Effect of D[4-(14)C]aldosterone (D [4-(14)C]Aldo) on the function of IPK of intact and adrenalectomized (ADX) rats was also studied. Aldo clearance in the liver was most important, 16.3 +/- 1.7 ml/min. In IPK, the total clearance of Aldo was 0.27 +/- 0.36 ml/min (39% of the glomerular filtration rate) (GFR). Fractional excretion (FE) of Aldo was 16 +/- 8%. Metabolic clearance of Aldo was (0.21 +/- 0.23 ml/min), 78% of total renal clearance. In CIPLK, the kidney inhibited hepatic clearance of Aldo by 23% when compared with IPL (P less than 0.05). Hepatic Aldo metabolites were predominantly eliminated by biliary excretion of polar metabolites. Several hepatic polar metabolites and tetrahydroaldosterone (THA) accumulated in perfusate and were excreted in the urine in a similar pattern. After hydrolysis of the polar metabolites, some coeluated with THA and dihydroaldosterone (DHA), whereas other metabolites remained more polar than Aldo. Without addition of Aldo, in IPK of ADX rats FENa was higher (P less than 0.01), and FEK was lower (P less than 0.01), resulting in three- to fourfold higher urinary Na-K ratio (P less than 0.01) when compared with IPK and CIPLK of intact rats. In IPK of ADX rats with Aldo in perfusate, only FEK was restored. Addition of Aldo to IPK of intact rats had no effect. However, only in CIPLK, addition of Aldo resulted in an increasing kaliuresis in three subsequent periods of 30 min (0.56-0.95, P less than 0.01). Thus the hepatic metabolites of Aldo could in part mediate the kaliuretic effect of Aldo.

scholarly journals Pre-operative Localisation of the Parathyroid Glands in Secondary Hyperparathyroidism: A Retrospective Cohort Study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Takahisa Hiramitsu ◽  
Toshihide Tomosugi ◽  
Manabu Okada ◽  
Kenta Futamura ◽  
Makoto Tsujita ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cohort Study ◽  
Parathyroid Hormone ◽  
Secondary Hyperparathyroidism ◽  
Retrospective Cohort ◽  
Parathyroid Glands ◽  
Imaging Modalities ◽  
Intact Parathyroid Hormone ◽  
Intact Pth ◽  
Persistent Hyperparathyroidism

Abstract Complete parathyroidectomy (PTx) is essential during total PTx for secondary hyperparathyroidism (SHPT) to prevent recurrent and persistent hyperparathyroidism. Pre-operative imaging evaluations, including computed tomography (CT), ultrasonography (US), and Tc-99m sestamibi (MIBI) scans, are commonly performed. Between June 2009 and January 2016, 291 patients underwent PTx for SHPT after pre-operative evaluations involving CT, US, and MIBI scans, and the diagnostic accuracies of these imaging modalities for identifying the parathyroid glands were evaluated in 177 patients whose intact parathyroid hormone (PTH) levels were <9 pg/mL after the initial PTx. Additional PTx procedures were performed on 7 of 114 patients whose intact PTH levels were >9 ng/mL after PTx, and the diagnostic validities of the imaging modalities for the remnant parathyroid glands were evaluated. A combination of CT, US, and MIBI scans achieved the highest diagnostic accuracy (75%) for locating bilateral upper and lower parathyroid glands before initial PTx. The accuracies of CT, US, and MIBI scans with respect to locating remnant parathyroid glands before additional PTx were 100%, 28.6%, and 100%, respectively. A combination of CT, US, and MIBI scans is useful for initial PTx for SHPT, and CT and MIBI scans are useful imaging modalities for additional PTx procedures.

Measurement of intact parathyroid hormone in the diagnosis of hyperparathyroidism

1991 ◽  
Vol 125 (6) ◽  
pp. 668-674 ◽  
Author(s):  
Anders Bergenfelz ◽  
Stig Valdermarsson ◽  
Bo Ahrén
Keyword(s):  
Parathyroid Hormone ◽  
Plasma Level ◽  
Primary Hyperparathyroidism ◽  
Plasma Levels ◽  
Diagnostic Information ◽  
Intact Parathyroid Hormone ◽  
Infusion Test ◽  
Intact Pth ◽  
Baseline Plasma Level ◽  
Edta Infusion

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.

A non-(1–84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples

1998 ◽  
Vol 44 (4) ◽  
pp. 805-809 ◽  
Author(s):  
Raymond Lepage ◽  
Louise Roy ◽  
Jean-Hugues Brossard ◽  
Louise Rousseau ◽  
Claude Dorais ◽  
...  
Keyword(s):  
Renal Failure ◽  
Parathyroid Hormone ◽  
Molecular Form ◽  
Diagnostic System ◽  
Intact Parathyroid Hormone ◽  
Intact Pth ◽  
Hplc Profiles ◽  
Uremic Patients ◽  
Commercial Kits ◽  
Carboxy Terminal

Abstract We have previously shown that the Nichols assay for intact parathyroid hormone (I-PTH) reacts with a non-(1–84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates in renal failure, accounting for 40–60% of the measured immunoreactivity. We wanted to see whether this was a common event with other commercial two-site I-PTH assays. We thus compared the ability of three commercial kits [Nichols (NL), Incstar (IT), and Diagnostic System Laboratories (DSL)] to measure I-PTH in 112 renal failure patients and to detect hPTH(1–84) and non-(1–84)PTH on HPLC profiles of serum pools from uremic patients with I-PTH concentrations of 10–100 pmol/L. The behavior of synthetic hPTH(7–84), a fragment possibly related to non-(1–84)PTH was also compared with hPTH(1–84) in the three assays. The I-PTH concentrations measured with the three assays in the 112 uremic samples were highly related (r2 ≥ 0.89, P &lt;0.0001), and the values measured with NL were, on average, 23% higher than IT. Values measured with DSL were 23% and 56% higher than IT for values less than and more than 40 pmol/L, respectively. The three assays detected two HPLC peaks on four different profiles corresponding to hPTH(1–84) and non-(1–84)PTH. This last peak represented 36 ± 8.4% of the immunoreactivity with NL, 24 ± 5.5% with IT, and 25 ± 2.8% with DSL (NL vs IT or DSL: P &lt;0.05). These differences were confirmed by a 50% lower immunoreactivity to hPTH(7–84) compared with hPTH(1–84) for IT and DSL but not for NL. These results suggest that most of the two-site I-PTH assays would cross-react with non-(1–84)PTH material, thus explaining about one-half of the 2–2.5 × higher I-PTH concentrations reported in uremic patients without bone involvement than in subjects without uremia.

Analysis of immunoreactive and biologically active human parathyroid hormone-peptides by high-performance-liquid-chromatography

1984 ◽  
Vol 107 (1) ◽  
pp. 60-69 ◽  
Author(s):  
T. Schettler ◽  
B. Aufm' Kolk ◽  
M.J. Atkinson ◽  
H. Radeke ◽  
C. Enters ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Parathyroid Adenoma ◽  
High Performance ◽  
Biologically Active ◽  
Peptide Sequence ◽  
Human Parathyroid Hormone ◽  
Healthy Individuals ◽  
In Vitro Bioassay

Abstract. A combination of high-performance-liquidchromatography (HPLC), sensitive radioimmunoassays and a homologous in vitro bioassay was used to characterise human parathyroid hormone (hPTH)-peptides in human parathyroid adenoma and plasma. Chromatography of several synthetic hPTH-peptides allows the calibration of the HPLC column. On the basis of sequence hydrophobicity the elution position of peptides can be predicted. A model for the determination of the minimal peptide sequence of each peptide has been developed which based on immunological and physicochemical properties allows the characterisation of unknown hPTH-peptides. Using this technique the heterogeneity of circulating hPTH-peptides in human plasma has been examined. Plasma extracts from healthy individuals, osteoporotic, hyperparathyroid and pseudohyperparathyroid patients were investigated. A uniform pattern in the heterogeneity of hPTH-peptides was detected. Using parathyroid adenoma as reference disease specific changes were characterised.

scholarly journals A Case of Von Hippel–Lindau Disease with Bilateral Pheochromocytoma and Ectopic Hypersecretion of Intact Parathyroid Hormone in an Adolescent Girl

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Rym Belaid ◽  
Ibtissem Oueslati ◽  
Melika Chihaoui ◽  
Meriem Yazidi ◽  
Wafa Grira ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Adrenal Tumors ◽  
Intact Parathyroid Hormone ◽  
Intact Pth ◽  
High Accumulation ◽  
Von Hippel Lindau ◽  
Ectopic Secretion ◽  
Bilateral Pheochromocytoma ◽  
Von Hippel Lindau Disease

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.

scholarly journals A Survey of Diagnoses in Patients with a Low Intact Parathyroid Hormone Concentration

1993 ◽  
Vol 30 (3) ◽  
pp. 252-255 ◽  
Author(s):  
E M C Manning ◽  
W D Fraser
Keyword(s):  
Renal Failure ◽  
Parathyroid Hormone ◽  
Chronic Renal Failure ◽  
Paget’S Disease ◽  
Blood Sampling ◽  
Intact Parathyroid Hormone ◽  
Hormone Concentration ◽  
Intact Pth ◽  
Common Diagnosis ◽  
Wide Range

Intact parathyroid hormone (PTH) was analysed in 1107 samples over a 13 month period. Of these, 181 samples (16%) gave results of ≤ 1 pmol/L and the case notes of 169 of these 181 patients were examined. Eighty-two patients (48%) were hypercalcaemic at the time of the PTH assay. As expected, the most common diagnosis in this group was hypercalcaemia of malignancy but surprisingly this accounted for only 42 of the hypercalcaemic patients; an unexpectedly high proportion (20 patients) had chronic renal failure with hypercalcaemia due to excessive treatment with 1α-hydroxycholecalciferol; eight patients had transient unexplained hypercalcaemia and the remaining 12 patients were hypercalcaemic for a variety of causes including immobilization, bendrofluazide treatment and Paget's disease. Fifty-nine patients (35%) were normocalcaemic: 26 had osteoporosis, 10 had chronic renal failure and the remainder had a wide range of diagnoses. It is possible that the low intact PTH result in a proportion of the normocalcaemic group was caused by ingestion of calcium tablets prior to blood sampling for PTH. Twenty-eight patients (17%) were hypocalcaemic: 24 of these had hypoparathyroidism, two had chronic renal failure and two had transient unexplained hypocalcaemia.

scholarly journals Parathyroid hormone: what are we measuring and does it matter?

2002 ◽  
Vol 39 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Aubrey Blumsohn ◽  
Amna Al Hadari
Keyword(s):  
Vitamin D ◽  
Renal Failure ◽  
Parathyroid Hormone ◽  
Chronic Renal Failure ◽  
Primary Hyperparathyroidism ◽  
Intact Parathyroid Hormone ◽  
Intact Pth ◽  
Improve Outcome ◽  
Shed Light ◽  
Improved Outcome

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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