Evidence That Patients With Addison's Disease Are Undertreated With Fludrocortisone

Smith, S J; Markandu, Nirmala D.; Banks, RichardA.; Dorrington-Ward, P; MacGregor, G. A.; Bayliss, J; Prentice, MalcolmG.; Wise, P. H.

doi:10.1016/s0140-6736(84)90181-8

Cited by 39 publications

(18 citation statements)

References 7 publications

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“…Admittedly, the use of plasma electrolyte concentrations and clinical signs as markers of clinical control may not reflect adequate plasma volume. In humans with PH, PRA is negatively correlated with plasma volume . The utilization of PRA as a marker for DOCP treatment would have been ideal, but the complexity of blood sampling and sparse availability of this test make it impractical for most practitioners to use in management of dogs with PH .…”

Section: Discussionmentioning

confidence: 99%

Desoxycorticosterone Pivalate Duration of Action and Individualized Dosing Intervals in Dogs with Primary Hypoadrenocorticism

Jaffey¹,

Nurre²,

Cannon

et al. 2017

Veterinary Internal Medicne

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BackgroundClinicians alter dosing for desoxycorticosterone pivalate (DOCP) to mitigate costs, but this practice has not been critically evaluated in a prospective clinical trial.Hypothesis/ObjectivesThe duration of action of DOCP is longer than 30 days in dogs with primary hypoadrenocorticism (PH).AnimalsA total of 53 client‐owned dogs with PH. Twenty‐four dogs with newly diagnosed PH (Group 1) and 29 dogs with treated PH (Group 2).MethodsProspective, multicenter, clinical trial. For phase I, DOCP was administered and plasma sodium and potassium concentrations were measured until the dog developed hyponatremia or hyperkalemia at a planned evaluation, or displayed clinical signs with plasma electrolyte concentrations outside of the reference interval independent of a planned evaluation, thus defining DOCP duration of action. Plasma electrolyte concentrations then were assessed at the end of the individualized dosing interval (IDI; i.e., DOCP duration of action minus 7 days, phase II and at least 3 months after concluding phase II, phase III).ResultsThe duration of action of DOCP in dogs in phase I with naïve PH (n = 24) ranged from 32 to 94 days (median, 62 days; 95% confidence interval [CI], 57, 65) and previously treated PH (n = 29) from 41 to 124 days (median, 67 days; CI, 56, 72). Overall, the final DOCP dosing interval for all dogs that completed phase II (n = 36) ranged from 38 days to 90 days (median, 58 days; CI, 53, 61). No dog that completed phase III (n = 15) required reduction in the IDI. The DOCP duration of action, independent of group, was not significantly associated with several baseline variables. The median drug cost reduction using IDI was approximately 57.5% per year.Conclusion and Clinical ImportanceThe duration of action of DOCP in dogs with PH is >30 days, and plasma sodium and potassium concentrations can be maintained with an IDI >30 days long term.

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Section: Discussionmentioning

confidence: 99%

Desoxycorticosterone Pivalate Duration of Action and Individualized Dosing Intervals in Dogs with Primary Hypoadrenocorticism

Jaffey¹,

Nurre²,

Cannon

et al. 2017

Veterinary Internal Medicne

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“…The 2 patients reported appeared inactive for tuberculosis, when hyperreninemia developed. Patient 1 was treated with fludrocortisone, but the dose that he received was less than the standard dose (0.1 mg/day) [10], and no fludrocortisone treatment was given to patient 2. Thus, the insufficient mineralocorticoid substitution treatment could contribute to the persistence of the hyperreninemic state [7,11] in both patients.…”

Section: Discussionmentioning

confidence: 99%

Focal Segmental Glomerular Sclerosis in Two Patients with Addison’s Disease: Any More than Fortuitous Development of Glomerular Disease?

Arrizabalaga

Bergadá

Solé³

et al. 2002

Am J Nephrol

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Adjustment of the mineralocorticoid activity under substitution therapy is of primary importance in Addison’s disease. We report the clinical and biological conditions of 2 patients with Addison’s disease who developed nephrotic proteinuria during their deficient mineralocorticoid state. Renal biopsy was performed and the specimens processed using conventional histochemistry, Congo red staining, and indirect immunofluorescence. The renal biopsy specimens showed focal segmental glomerular sclerosis and nodular deposits of IgM and C3. Negative for Congo red staining. Serum complement, circulating immune complexes, and anti-DNA and hepatitis B and C and human immunodeficiency virus antibodies were all normal or negative. Absence of vesicoureteral reflux was assessed by X-ray studies. Our observations suggest that deficiency in mineralocorticoid substitution therapy inducing a status of hyperreninemia could play a role in the development of focal segmental glomerulosclerosis in patients with Addison’s disease.

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“…In contrast, other glucocorticoids have only a weak mineralocorticoid action, for example prednisolone; or no MC action, for example dexamethasone. The use of these latter two compounds thus requires addition of mineralocorticoid replacement [59].…”

Section: Justificationmentioning

confidence: 99%

“…Measurement of plasma renin constitutes the most precise marker of sodium balance and effective plasma volume [63], where there is an inverse relationship between plasma renin activity and plasma volume [59,64]. Measurement of renin activity or direct assay of plasma renin can be performed at any time, independent of the time of fludrocortisone administration [64].…”

Section: Parameters For Surveillancementioning

confidence: 99%

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Group 4: Replacement therapy for adrenal insufficiency

Castinetti

Guignat

Bouvattier

et al. 2017

Annales d'Endocrinologie

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Evidence That Patients With Addison's Disease Are Undertreated With Fludrocortisone

Cited by 39 publications

References 7 publications

Desoxycorticosterone Pivalate Duration of Action and Individualized Dosing Intervals in Dogs with Primary Hypoadrenocorticism

Desoxycorticosterone Pivalate Duration of Action and Individualized Dosing Intervals in Dogs with Primary Hypoadrenocorticism

Focal Segmental Glomerular Sclerosis in Two Patients with Addison’s Disease: Any More than Fortuitous Development of Glomerular Disease?

Group 4: Replacement therapy for adrenal insufficiency

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