Nocturnal Hypoglycemia Identified by a Continuous Glucose Monitoring System in Patients with Primary Adrenal Insufficiency (Addison's Disease)

Abstract

Background: Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Methods: Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3-5 days.Results: In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Conclusions: Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects.

Adrenal Crises in Children: Perspectives and Research Directions

“…Previous research has demonstrated that morning glucose levels are lower in adult AI patients [39, 74, 75], and that occult nocturnal hypoglycaemia can occur among adults with AI [76, 77]. As we have described previously [15], the underlying mechanism for this is likely to involve reduced nocturnal gluconeogenesis during an overnight fast, a process that is partially dependent on glucocorticoids.…”

MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia

“…One patient was detected to have nocturnal hypoglycemia with a blood glucose concentration of less than 50 mg/dL. When the patient's last hydrocortisone dosing was changed to late evening, there were no further episodes of hypoglycemia (112).…”

“…The study by Christiansen et al demonstrated that acute withdrawal of cortisol increased insulin sensitivity close to 70%, increased glucose oxidation by 50%, with decreased endogenous glucose production, implying that adrenocortical failure could result in hypoglycemia (111). Meyer et al studied 13 patients with primary adrenal insufficiency using continuous glucose monitoring for 3-5 days (112). One patient was detected to have nocturnal hypoglycemia with a blood glucose concentration of less than 50 mg/dL.…”

MANAGEMENT OF ENDOCRINE DISEASE: Epidemiology, quality of life and complications of primary adrenal insufficiency: a review

“…Studies in secondary adrenal insufficiency indicate that altered circadian cortisol patterns during replacement therapy affect both carbohydrate and lipid metabolism (82,83), but the effects of glucocorticoid and growth hormone failure and their replacement are hard to distinguish. It is, however, likely that lack of night-time cortisol in patients on regular glucocorticoid replacement therapy confers risk of nocturnal hypoglycaemia, which may be a problem particular to patients with concomitant diabetes mellitus (84). Use of once-daily modified release hydrocortisone tablet (Plenadren, Viropharma Inc, Exton, PA, USA) resulted in decreased body mass index (BMI) and HbA1c compared with conventional hydrocortisone treatment (43,85).…”