Parathyroid hormone: Data mining for age‐related reference intervals in adults

Farrell, Christopher-John L; Nguyễn, Lan; Carter, Andrew Christopher

doi:10.1111/cen.13486

Cited by 22 publications

(13 citation statements)

References 34 publications

(84 reference statements)

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“…As reported in previous studies (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), the PTH values did not follow a normal distribution. Thus, the normality range was defined as corresponding to 95% of the results and the 2.5 th and 97.5 th percentiles as corresponding to the lower and upper limit, respectively (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). PTH levels were compared between men and women (preand postmenopausal) and between subjects < 60 and > 60 years (2)…”

Section: Discussionsupporting

confidence: 59%

“…Any observed differences in PTH concentrations might be due to differences in vitamin D concentrations, eGFR, comorbidities and medication use, which was not the case in the present study in which the subgroups were uniform in terms of the selection criteria (vitamin D > 30 ng/dL, eGFR > 60 mL/ min/1.73m 2 , no comorbidities or use of interfering medications). However, we recognize that any difference may not have been detected because of the size of the subgroups (18).…”

Section: Discussionmentioning

confidence: 83%

“…A reasonable number of subjects were evaluated. Rigorous selection was performed, following not only the traditionally required criteria [normocalcemia (in this study, total and ionized calcium); vitamin D sufficiency (defined as concentrations > 30 ng/dL); absence of chronic kidney disease, and no use of interfering drugs (2)], but also excluding other factors that can alter PTH in apparently healthy individuals (e.g., hypercalciuria, conditions of malabsorption, hyperphosphatemia, hypomagnesemia), which were not considered in previous studies (2,18,19). In addition to the selection criteria of the subjects, for the measurement of PTH, the guidelines on blood collection and processing were followed (2).…”

Section: Discussionmentioning

confidence: 99%

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Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

Rosário¹,

Calsolari²

2019

Archives of Endocrinology and Metabolism

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Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper-or hypophosphatemia, hypo-or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m 2 , urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5 th and 97.5 th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

Rosário¹,

Calsolari²

2019

Archives of Endocrinology and Metabolism

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“…HPT, and especially nHPT, is an increasing clinical problem since it is highly uncertain if, or how, we should treat nHPT, and whether a scheduled and systematic follow-up of nHPT is required [20,21]. It remains unclear whether this laboratory finding is pathological, and therefore a target for treatment, or just a part of the aging process [22]. S-PTH levels may rise due to low levels of circulating S-25(OH)D levels and/or low calcium intake.…”

Section: Discussionmentioning

confidence: 99%

Hyperparathyroidism in men – morbidity and mortality during 21 years’ follow-up

Kontogeorgos

Welin

et al. 2019

Scandinavian Journal of Clinical and Laboratory Investigation

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Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D ! 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up. A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age. Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.

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“…For instance, an investigation into PTH reference intervals which excluded subjects with abnormal albumin-adjusted serum calcium, estimated glomerular filtration rate below 60 mL/min/1.73m 2 and 25-hydroxyvitamin D less than 75 nmol/L found that the observed 2.5 th and 97.5 th percentiles for the entire cohort (1.4-12.3 pmol/L), matched the reference interval derived using the more sophisticated statistical approach of Bhattacharya analysis (1.8-12.2 pmol/L). 27 Rather than use expert opinion, some investigators have instead looked for statistical associations between test results. For instance, the REALAB collaboration used a multivariate algorithm to identify correlations between results of numerous tests.…”

Section: Subjects With Disease Excluded From the Extracted Datamentioning

confidence: 99%

Indirect Reference Intervals: Harnessing the Power of Stored Laboratory Data

2019

CBR

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Reference intervals are relied upon by clinicians when interpreting their patients’ test results. Therefore, laboratorians directly contribute to patient care when they report accurate reference intervals. The traditional approach to establishing reference intervals is to perform a study on healthy volunteers. However, the practical aspects of the staff time and cost required to perform these studies make this approach difficult for clinical laboratories to routinely use. Indirect methods for deriving reference intervals, which utilise patient results stored in the laboratory’s database, provide an alternative approach that is quick and inexpensive to perform. Additionally, because large amounts of patient data can be used, the approach can provide more detailed reference interval information when multiple partitions are required, such as with different age-groups. However, if the indirect approach is to be used to derive accurate reference intervals, several considerations need to be addressed. The laboratorian must assess whether the assay and patient population were stable over the study period, whether data ‘clean-up’ steps should be used prior to data analysis and, often, how the distribution of values from healthy individuals should be modelled. The assumptions and potential pitfalls of the particular indirect technique chosen for data analysis also need to be considered. A comprehensive understanding of all aspects of the indirect approach to establishing reference intervals allows the laboratorian to harness the power of the data stored in their laboratory database and ensure the reference intervals they report are accurate.

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Parathyroid hormone: Data mining for age‐related reference intervals in adults

Abstract: Data mining was demonstrated to be a useful tool for establishing age-related PTH reference intervals. The technique demonstrated that increasing age is associated with higher PTH concentrations and that age-related reference intervals are important for accurate result interpretation.

Cited by 22 publications

References 34 publications

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

Hyperparathyroidism in men – morbidity and mortality during 21 years’ follow-up

Indirect Reference Intervals: Harnessing the Power of Stored Laboratory Data

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