Parathyroid Hormone-Related Protein Induced Coupled Increases in Bone Formation and Resorption Markers for 7 Years in a Patient With Malignant Islet Cell Tumors

Takeuchi, Yasuhiro; Fukumoto, Seiji; Nakayama, Konosuke; Tamura, Yasuhiro; Yanagisawa, Akio; Fujita, Toshiro

doi:10.1359/jbmr.2002.17.5.753

Cited by 7 publications

(4 citation statements)

References 17 publications

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“…Across the four models (Figure A), PTH suppression was greatest and identical in healthy and FBH models (78%) and the least suppression is observed in HHM (∼23%) because baseline PTH levels are already near the minimum . For PHPT no.…”

Section: Results and Discussionmentioning

confidence: 95%

“…Across the four models (Figure 4A), PTH suppression was greatest and identical in healthy and FBH models (78%) and the least suppression is observed in HHM (∼23%) because baseline PTH levels are already near the minimum. 26 For PHPT no. 1, the first hour PTH response profile was identical with the FBH and healthy groups, but the eventual PTH suppression was 7% lower at 71% (Figure 4A).…”

Section: Pth Suppressionmentioning

confidence: 99%

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A Model-Based Approach to Diagnosing Hypercalcemia

Christie

Achenie

Ayeni

2023

Ind. Eng. Chem. Res.

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The more common hypercalcemia-causing pathologies, primary hyperparathyroidism (PHPT), humoral hypercalcemia of malignancy (HHM), and familial benign hypercalcemia (FBH), have similar pathophysiologies. Currently, there are no standardized tests to differentiate among them. Using our previously developed computational models of physiological calcium regulation in healthy, FBH, PHPT, and HHM, this follow-up paper presents a model-based approach for differentially diagnosing these three pathologies. Additionally, for PHPT, our approach allows for predicting the size of PTG adenomatous growth and for inferring the stage of PHPT (early-to-mid stage or mid-to-late stage). Each model was subjected to 2-h calcium infusion while the intra- and postinfusion calciotropic response profiles of plasma Ca, PTH, calcitriol (CTL), and urinary Ca (Ca u) were analyzed using control engineering concepts. Our research showed that two model parametersminimum PTH secretory rate (A Ca(s),r) and hypercalcemic slope (m Ca(s) A)and the four metrics of Ca settling time, PTH and CTL suppression, and maximum urinary Ca ratio were sufficient to provide distinct differentiating characteristics across the three pathologies. Furthermore, in the case of PHPT, estimates of minimum PTH secretory rate and the level of PTH suppression observed were found to correlate with postsurgical PTG adenoma mass. The minimum PTH secretory rate increases from healthy to FBH to PHPT and is inconsequential in HHM. Also, for PHPT, the minimum PTH secretory rate increases with PTG adenomatous growth. Likewise, the hypercalcemic slope is similar in healthy and FBH; decreases with increasing PTG mass in PHPT; and is inconsequential in HHM. Both PTH and CTL suppression were highest in healthy and FBH, lower in PHPT (with decreasing levels as PTG adenoma increases), and lowest in HHM. Finally, the Ca settling time and maximum urinary Ca ratio were the lowest for healthy and FBH, increased with increasing stage of PHPT, and were highest in HHM. For PHPT, a series of three relationships is derived between PTH suppression, minimum PTH secretory rate, and PTG mass such that the PTG mass can be inferred from the observed PTH suppression. The method and results herein have aided in the development of a set of observations (seven in total) that can serve as a guide to the research clinician for making a quick preliminary diagnosis across the three pathologies.

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Section: Results and Discussionmentioning

confidence: 95%

Section: Pth Suppressionmentioning

confidence: 99%

A Model-Based Approach to Diagnosing Hypercalcemia

Christie

Achenie

Ayeni

2023

Ind. Eng. Chem. Res.

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“…Classical HPT (Bilezikian provides a detailed review (2) ) is characterized by (1) increases in circulating parathyroid hormone (PTH) secreted by abnormal parathyroid tissue; (2) increased osteoclastic resorption of bone; (3) increased osteoblastic bone formation; (4) increased renal calcium reabsorption; (5) increased renal tubular production of 1,25-dihydroxyvitamin D [1,25(OH) 2 D] with resultant increased absorption of calcium from the gastrointestinal (GI) tract; and (6) as a result of these combined effects, hypercalcemia. Primary HPT is characterized also by hypophosphatemia.…”

Section: The Clinical Biochemistry and Bone Histomorphometry Of Primamentioning

confidence: 99%

“…I N THIS issue of JBMR, Takeuchi et al (1) describe a patient with humoral hypercalcemia of malignancy (HHM) lasting for 7 years resulting from a neuroendocrine islet cell tumor. The case is unusual in several ways, but the primary focus of this case report is on increased bone formation in a patient with otherwise typical HHM, creating a clinical and biochemical profile more similar to classical primary hyperparathyroidism (HPT) than to classical HHM.…”

Section: Introductionmentioning

confidence: 99%