Risk-factors for nodular hyperplasia of parathyroid glands in sHPT patients

<div><p>Introduction</p><p>Nodular hyperplasia of parathyroid glands (PG) is the most probable cause of medical treatment failure in secondary hyperparathyroidism (sHPT). This prospective cohort study is located at the interface of medical and surgical consideration of sHPT treatment options and identifies risk-factors for nodular hyperplasia of PG.</p><p>Material and methods</p><p>One-hundred-eight resected PG of 27 patients with a broad spectrum of sHPT severity were classified according to the degree of hyperplasia by histopathology. Twenty routinely gathered parameters from medical history, ultrasound findings of PG and laboratory results were analyzed for their influence on nodular hyperplasia of PG by risk-adjusted multivariable binary regression. A prognostic model for non-invasive assessment of PG was developed and used to weight the individual impact of identified risk-factors on the probability of nodular hyperplasia of single PG.</p><p>Results</p><p>Independent risk-factors for nodular hyperplasia of single PG were duration of dialysis in years, PG volume in mm³ determined by ultrasound and serum level of parathyroid hormone in pg/mL. Multivariable analyses computed a model with an Area Under the Receiver Operative Curve of 0.857 (95%-CI:0.773–0.941) when predicting nodular hyperplasia of PG. Theoretical assessment of risk-factor interaction revealed that the duration of dialysis had the strongest influence on the probability of nodular hyperplasia of single PG.</p><p>Conclusions</p><p>The three identified risk-factors (duration of dialysis, PG volume determined by ultrasound and serum level of parathyroid hormone) can be easily gathered in daily routine and could be used to non-invasively assess the probability of nodular hyperplasia of PG. This assessment would benefit from periodically collected data sets of PG changes during the course of sHPT, so that the choice of medical or surgical sHPT treatment could be adjusted more to the naturally changing type of histological PG lesion on an individually adopted basis in the future.</p></div

Probability of nodular hyperplasia of PG depending on values of individual risk-factors.

<p>Values of the duration of dialysis (−∙−∙−), PG volume measured by US (---) and serum levels of PTH (−−−) were categorized and standard units for a 10-step alteration were defined. The duration of dialysis was prolonged from 1 to 10 years by steps of 1 year. The PG volume determined by US was increased from 100 to 1.000 mm³ by steps of 100 mm³. The units of the 10-step alteration are given at the x-axis. The serum level of PTH was decreased from 1.000 to 100 pg/mL by steps of 100 pg/mL. While altering each parameter separately, the others were set to a default reference level with duration of dialysis = 2 years, PG volume determined by US = 400 mm³, and PTH serum level = 600 pg/mL. The calculated probability for nodular hyperplasia of PG is given in percent at the y-axis.</p

Internal validation of the developed prognostic score using randomized bootstrapping.

<p>Internal validation of the developed prognostic score using randomized bootstrapping.</p

Topography and size of parathyroid glands at parathyroidectomy and ultrasound.

<p>Topography of the right-sided superior and inferior PG after luxation of the thyroid gland (A). Topography and measurement of corresponding PG by US: superior (B+C) and inferior (D+E). Volumes of PG were 479mm³ (PG superior) and 99mm³ (PG inferior) when calculated with US measurements. Documentation of PG size during surgery: superior (F+G) and inferior (H+I). Volumes of PG were 858mm³ (PG superior) and 293mm³ (PG inferior) when calculated with intra-operative measurements. PGs, superior parathyroid gland; PGi, inferior parathyroid gland.</p

Receiver operating characteristic—curve for the prediction of nodular hyperplasia in individual parathyroid glands by the use of the prognostic model.

<p>The AUROC is 0.857 with a binominal exact 95% confidence interval: 0.773–0.941. The best Youden index determined a predicted probability of 52.9% as the cut-off value with best sensitivity and specificity for prediction of nodular hyperplasia in individual (specificity 86.1%, sensitivity 70.6%, overall correctness 78.3%). Good model fit was demonstrated by use of Pearson (0.75), Deviance (0.49), and Hosmer-Lemeshow tests (0.16).</p

Characteristics of parathyroid glands.

<p>Characteristics of parathyroid glands.</p

Independent risk factors for nodular hyperplasia of individual parathyroid glands (multivariable binary logistic regression analysis).

<p>Independent risk factors for nodular hyperplasia of individual parathyroid glands (multivariable binary logistic regression analysis).</p