Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency

Riccardo Pofi; Alessandro Prete; Vivien Thornton-Jones; Jillian Bryce; Salma R Ali; S Faisal  Ahmed; Antonio Balsamo; Federico Baronio; Amalia Cannuccia; Ayla Guven; Tülay Güran; Feyza Darendeliler; Claire Higham; Walter Bonfig; Liat de Vries; Tania A S S Bachega; Mirela C Miranda; Berenice B Mendonca; Violeta Iotova; Marta Korbonits; Nils P Krone; Ruth Krone; Andrea Lenzi; Wiebke Arlt; Richard J Ross; Andrea M Isidori; Jeremy W Tomlinson

doi:10.1210/clinem/dgz055

Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency

Riccardo Pofi, Alessandro Prete, Vivien Thornton-Jones, Jillian Bryce, Salma R Ali, S Faisal Ahmed, Antonio Balsamo, Federico Baronio, Amalia Cannuccia, Ayla Guven, Tülay Güran, Feyza Darendeliler, Claire Higham, Walter Bonfig, Liat de Vries, Tania A S S Bachega, Mirela C Miranda, Berenice B Mendonca, Violeta Iotova, Marta KorbonitsNils P Krone, Ruth Krone, Andrea Lenzi, Wiebke Arlt, Richard J Ross, Andrea M Isidori, Jeremy W Tomlinson^*

^*Corresponding author for this work

Metabolism and Systems Science

Research output: Contribution to journal › Article › peer-review

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Abstract

Context: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.

Objective: To explore the relationship between mineralocorticoid replacement dose, plasma renin concentration (PRC) and clinically important variables to determine which are most helpful in guiding mineralocorticoid dose titration in primary adrenal insufficiency.

Design: Observational, retrospective, longitudinal analysis.
Patients: 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (SW-CAH) (149 adults and 55 children) and 39 adult patients with Addison’s disease (AD) were analysed.

Main outcome measures: PRC, electrolytes, blood pressure (BP) and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.

Results: PRC was low, normal or high in 19%, 36% and 44% of patients, respectively, with wide variability in mineralocorticoid dose and PRC. Univariate analysis demonstrated a direct positive relationship between mineralocorticoid dose and PRC in adults and children. There was no relationship between mineralocorticoid dose and BP in adults, while BP increased with increasing mineralocorticoid dose in children. Using multiple regression modelling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in mineralocorticoid dose was able to predict potassium, but not BP or PRC.

Conclusions: The relationship between mineralocorticoid dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last mineralocorticoid dose, adherence and concomitant medications. Our data suggests that mineralocorticoid titration should not primarily be based only on PRC normalization, but also on clinical parameters as BP and electrolyte concentration.

Original language	English
Pages (from-to)	314–326
Number of pages	13
Journal	Journal of Clinical Endocrinology and Metabolism
Early online date	16 Oct 2019
DOIs	https://doi.org/10.1210/clinem/dgz055
Publication status	Published - Jan 2020

Keywords

congenital adrenal hyperplasia
salt-wasting CAH
primary adrenal insufficiency
mineralocorticoid replacement
plasma renin concentration
fludrocortisone

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Pofi_et_al_Plasma_renin_measurements_are_unrelated_to_mineralocorticoid_dose_in_patients_with_primary_adrenal_insufficiency_Journal_of_Clinical_Endocrinology_and_Metabolism_2019
This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Clinical Endocrinology & Metabolism following peer review. The version of record Riccardo Pofi, Alessandro Prete, Vivien Thornton-Jones, Jillian Bryce, Salma R Ali, S Faisal Ahmed, Antonio Balsamo, Federico Baronio, Amalia Cannuccia, Ayla Guven, Tulay Guran, Feyza Darendeliler, Claire Higham, Walter Bonfig, Liat de Vries, Tania A S S Bachega, Mirela C Miranda, Berenice B Mendonca, Violeta Iotova, Màrta Korbonits, Nils P Krone, Ruth Krone, Andrea Lenzi, Wiebke Arlt, Richard J Ross, Andrea M Isidori, Jeremy W Tomlinson, Plasma renin measurements are unrelated to mineralocorticoid replacement dose in patients with primary adrenal insufficiency, The Journal of Clinical Endocrinology & Metabolism, , dgz055, https://doi.org/10.1210/clinem/dgz055 is available online at: https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgz055/5588075
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https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgz055/5588075Licence: None: All rights reserved

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Pofi, R., Prete, A., Thornton-Jones, V., Bryce, J., Ali, S. R., Ahmed, S. F., Balsamo, A., Baronio, F., Cannuccia, A., Guven, A., Güran, T., Darendeliler, F., Higham, C., Bonfig, W., de Vries, L., Bachega, T. A. S. S., Miranda, M. C., Mendonca, B. B., Iotova, V., ... Tomlinson, J. W. (2020). Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency. Journal of Clinical Endocrinology and Metabolism, 314–326. https://doi.org/10.1210/clinem/dgz055

@article{27d37006c1bd45da923f7d2014780e21,

title = "Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency",

abstract = "Context: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.Objective: To explore the relationship between mineralocorticoid replacement dose, plasma renin concentration (PRC) and clinically important variables to determine which are most helpful in guiding mineralocorticoid dose titration in primary adrenal insufficiency.Design: Observational, retrospective, longitudinal analysis.Patients: 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (SW-CAH) (149 adults and 55 children) and 39 adult patients with Addison{\textquoteright}s disease (AD) were analysed.Main outcome measures: PRC, electrolytes, blood pressure (BP) and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.Results: PRC was low, normal or high in 19%, 36% and 44% of patients, respectively, with wide variability in mineralocorticoid dose and PRC. Univariate analysis demonstrated a direct positive relationship between mineralocorticoid dose and PRC in adults and children. There was no relationship between mineralocorticoid dose and BP in adults, while BP increased with increasing mineralocorticoid dose in children. Using multiple regression modelling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in mineralocorticoid dose was able to predict potassium, but not BP or PRC.Conclusions: The relationship between mineralocorticoid dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last mineralocorticoid dose, adherence and concomitant medications. Our data suggests that mineralocorticoid titration should not primarily be based only on PRC normalization, but also on clinical parameters as BP and electrolyte concentration. ",

keywords = "congenital adrenal hyperplasia, salt-wasting CAH, primary adrenal insufficiency, mineralocorticoid replacement, plasma renin concentration, fludrocortisone",

author = "Riccardo Pofi and Alessandro Prete and Vivien Thornton-Jones and Jillian Bryce and Ali, {Salma R} and Ahmed, {S Faisal} and Antonio Balsamo and Federico Baronio and Amalia Cannuccia and Ayla Guven and T{\"u}lay G{\"u}ran and Feyza Darendeliler and Claire Higham and Walter Bonfig and {de Vries}, Liat and Bachega, {Tania A S S} and Miranda, {Mirela C} and Mendonca, {Berenice B} and Violeta Iotova and Marta Korbonits and Krone, {Nils P} and Ruth Krone and Andrea Lenzi and Wiebke Arlt and Ross, {Richard J} and Isidori, {Andrea M} and Tomlinson, {Jeremy W}",

year = "2020",

month = jan,

doi = "10.1210/clinem/dgz055",

language = "English",

pages = "314–326",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

}

Pofi, R, Prete, A, Thornton-Jones, V, Bryce, J, Ali, SR, Ahmed, SF, Balsamo, A, Baronio, F, Cannuccia, A, Guven, A, Güran, T, Darendeliler, F, Higham, C, Bonfig, W, de Vries, L, Bachega, TASS, Miranda, MC, Mendonca, BB, Iotova, V, Korbonits, M, Krone, NP, Krone, R, Lenzi, A, Arlt, W, Ross, RJ, Isidori, AM & Tomlinson, JW 2020, 'Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency', Journal of Clinical Endocrinology and Metabolism, pp. 314–326. https://doi.org/10.1210/clinem/dgz055

TY - JOUR

T1 - Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency

AU - Pofi, Riccardo

AU - Prete, Alessandro

AU - Thornton-Jones, Vivien

AU - Bryce, Jillian

AU - Ali, Salma R

AU - Ahmed, S Faisal

AU - Balsamo, Antonio

AU - Baronio, Federico

AU - Cannuccia, Amalia

AU - Guven, Ayla

AU - Güran, Tülay

AU - Darendeliler, Feyza

AU - Higham, Claire

AU - Bonfig, Walter

AU - de Vries, Liat

AU - Bachega, Tania A S S

AU - Miranda, Mirela C

AU - Mendonca, Berenice B

AU - Iotova, Violeta

AU - Korbonits, Marta

AU - Krone, Nils P

AU - Krone, Ruth

AU - Lenzi, Andrea

AU - Arlt, Wiebke

AU - Ross, Richard J

AU - Isidori, Andrea M

AU - Tomlinson, Jeremy W

PY - 2020/1

Y1 - 2020/1

N2 - Context: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.Objective: To explore the relationship between mineralocorticoid replacement dose, plasma renin concentration (PRC) and clinically important variables to determine which are most helpful in guiding mineralocorticoid dose titration in primary adrenal insufficiency.Design: Observational, retrospective, longitudinal analysis.Patients: 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (SW-CAH) (149 adults and 55 children) and 39 adult patients with Addison’s disease (AD) were analysed.Main outcome measures: PRC, electrolytes, blood pressure (BP) and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.Results: PRC was low, normal or high in 19%, 36% and 44% of patients, respectively, with wide variability in mineralocorticoid dose and PRC. Univariate analysis demonstrated a direct positive relationship between mineralocorticoid dose and PRC in adults and children. There was no relationship between mineralocorticoid dose and BP in adults, while BP increased with increasing mineralocorticoid dose in children. Using multiple regression modelling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in mineralocorticoid dose was able to predict potassium, but not BP or PRC.Conclusions: The relationship between mineralocorticoid dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last mineralocorticoid dose, adherence and concomitant medications. Our data suggests that mineralocorticoid titration should not primarily be based only on PRC normalization, but also on clinical parameters as BP and electrolyte concentration.

AB - Context: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.Objective: To explore the relationship between mineralocorticoid replacement dose, plasma renin concentration (PRC) and clinically important variables to determine which are most helpful in guiding mineralocorticoid dose titration in primary adrenal insufficiency.Design: Observational, retrospective, longitudinal analysis.Patients: 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (SW-CAH) (149 adults and 55 children) and 39 adult patients with Addison’s disease (AD) were analysed.Main outcome measures: PRC, electrolytes, blood pressure (BP) and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.Results: PRC was low, normal or high in 19%, 36% and 44% of patients, respectively, with wide variability in mineralocorticoid dose and PRC. Univariate analysis demonstrated a direct positive relationship between mineralocorticoid dose and PRC in adults and children. There was no relationship between mineralocorticoid dose and BP in adults, while BP increased with increasing mineralocorticoid dose in children. Using multiple regression modelling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in mineralocorticoid dose was able to predict potassium, but not BP or PRC.Conclusions: The relationship between mineralocorticoid dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last mineralocorticoid dose, adherence and concomitant medications. Our data suggests that mineralocorticoid titration should not primarily be based only on PRC normalization, but also on clinical parameters as BP and electrolyte concentration.

KW - congenital adrenal hyperplasia

KW - salt-wasting CAH

KW - primary adrenal insufficiency

KW - mineralocorticoid replacement

KW - plasma renin concentration

KW - fludrocortisone

U2 - 10.1210/clinem/dgz055

DO - 10.1210/clinem/dgz055

M3 - Article

SN - 0021-972X

SP - 314

EP - 326

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

ER -

Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency

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