Inhaled corticosteroids (ICS) improve lung function and quality of life for chronic respiratory disorders. However, their ability to suppress the Hypothalamopituitary adrenal (HPA) axis is under-recognised in adults (1). We report a case of secondary adrenal insufficiency (AI) related to chronic inhaled fluticasone presenting as euvolemic hyponatraemia.
A 76 year old woman presented with an infective exacerbation of bronchiectasis. Her usual ICS was Fluticasone 1000mcg daily, with previous Prednisolone 18 months ago. She developed fatigue, nausea and postural presyncope with euvolaemic hyponatraemic (123mmol/L). These symptoms persisted despite improvement in her respiratory infection. Investigations revealed elevated urinary sodium, hypocortisolaemia (41nmol/L) and inappropriately low ACTH (11ng/L)(see Table 1). A short synacthen test (SST) confirmed subnormal response, reflecting AI. Stress-dose intravenous hydrocortisone rapidly normalised her hyponatraemia and resolved symptoms.
Secondary AI describes the suppression of ACTH, and thus cortisol, by exogenous corticosteroids. Since the clinical features can be vague-nausea, malaise, and hypotension, it may go unrecognised. Although oral corticosteroids are the most common cause, ICS are an increasingly recognised cause of AI. A 5 year retrospective analysis of 228 adult patients on inhaled, intra-nasal and topical glucocorticoids showed 24.6% failed SST (2). Of ICS, fluticasone is most likely to suppress the HPA axis due to its long half-life and lipophilia (3).
Hyponatraemia in hospital inpatients is most commonly caused by the Syndrome of Inappropriate ADH Secretion while ACTH deficiency is a rare but important cause (4).
In our patient, SIADH was unlikely as hyponatraemia persisted despite improvement of respiratory infection. The rapid improvement in hyponatraemia with glucocorticoid therapy and SST confirmed ACTH deficiency due to ICS.
Table 1:
|
Test |
Result |
Normal range |
|
Sodium |
123mmol/L |
135-145mmol/L |
|
Osmolality |
257mmol/L |
275-295mmol/L |
|
Urine Sodium |
110mmol/L |
|
|
Urine Osmolality |
431mmol/Kg |
|
|
ACTH |
11ng/L |
10-50ng/L |
|
Cortisol |
41nmol/L |
140-640nmol/L |
|
SST |
41 (0min)-148 (30min)-178 (60min) |
140-640nmol/L (0mins)->200nmol/L (30mins)->500nmol/L (60mins) |