Clinical Manifestation of Hypercalcemia Caused by Adrenal Insufficiency in Hemodialysis Patients: A Case-series Study

Abstract

Objective The goal of this study was to clarify the clinical manifestation of hypercalcemia due to hypoadrenalism in hemodialysis (HD) patients. Methods We retrospectively analyzed the clinical characteristics of five HD patients who had presented with hypercalcemia due to adrenal insufficiency (age: 69±7 [58-75] years old, time on HD: 13±11 [2-32] years). We conducted corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) stimulation tests. We also examined serum bone turnover markers before and after glucocorticoid replacement. Results All patients had critical illnesses at the onset of hypercalcemia. They had at least one symptom, such as eosinophilia, hypoglycemia, or fever. The prevalence of hypercalcemia due to adrenal insufficiency was 1.3% in maintenance HD patients on admission. The causes of adrenal insufficiency were isolated ACTH deficiency, pituitary apoplexy, pituitary atrophy, glucocorticoid withdrawal syndrome, and unilateral adrenalectomy. Serum calcium (Ca) levels corrected by serum albumin were maximally increased to 12.9 to 14.3 mg/dL in four anuric HD patients and mildly elevated to 10.4 mg/dL in a patient with residual diuresis. Their basal serum cortisol levels ranged from <1.0 to 15.4 μg/dL. Single CRH injections failed to increase serum cortisol in any of the patients. Glucocorticoid replacement acutely normalized serum Ca and decreased levels of carboxy-terminal telopeptide of type I collagen, a marker of bone resorption. Conclusion Adrenal insufficiency could therefore be an occult cause of hypercalcemia in anuric HD patients who are critically ill.

Adrenal function testing in dialysis patients – a review of the literature

“…Whereas most studies had the aim of investigating the responsiveness of the hypothalamo-pituitary-adrenal axis in asymptomatic patients on HD, three studies tested for adrenal insufficiency due to clinical suspicion. The case series of Sakao et al reported AI as a secondary cause for hypercalcemia [ 24 ]. Arregger et al and Koh et al performed adrenal function testing due to hypotension in HD patients [ 9 , 25 ].…”

“…ACTH testing was performed in seven of the retrieved 16 studies, but in none of these during ongoing HD [ 6 , 20 , 22 , 24 , 26 , 32 , 33 ].…”

“…In their cohort of patients on HD not treated with prednisolone, only 3% of cases (1/30) had hypoadrenalism. In the case series of Sakao et al, all five participants (100%) obviously had an AI, of which four had secondary AI and one had primary AI due to unilateral adrenalectomy [ 24 ]. In the other five studies which performed an ACTH test, there were no HD patients diagnosed with AI.…”

“…Four other studies also conducted a CRH stimulation test with different results [ 24 , 27 , 29 , 30 ]. Siamopoulos et al, Ramirez et al and Vigna et al all reported increased stimulated plasma cortisol in controls and cases [ 22 , 27 , 29 ].…”

Eosinophilia With Special Reference to Helminthiasis

“…Clinical suspicion of adrenal insufficiency was high in 8/10 patients, and treatment with hydrocortisone resulted in hemodynamic improvement in seven. Sakao et al (2014) in Japan analyzed retrospectively the clinical characteristics of five HD patients who were presented with hypercalcemia due to adrenal insufficiency (age: 69±7), time on HD: 13±11years old. All patients had critical illnesses at hypercalcemia onset, with at least one symptom, such as eosinophilia, hypoglycemia, or fever.…”