Association Between Nighttime/Early Morning Cough and Decreased Cortisol Levels
There is no established direct association between nighttime or early morning cough (2am-4am) and decreased cortisol levels in the general population, but in patients with adrenal insufficiency or those on chronic corticosteroid therapy, low cortisol levels can contribute to nocturnal airway symptoms through reduced suppression of airway inflammation.
Understanding the Cortisol-Cough Relationship
In Asthmatic Patients
Lower endogenous cortisol levels, particularly at midnight, are associated with worse nocturnal airflow limitation in children with asthma, with subjects experiencing nocturnal asthma having significantly lower cortisol at 0000,0800, and 1200 hours compared to controls 1.
Higher mean 24-hour cortisol levels correlate with significantly higher FEV1 values at 0400,0800, and 2000 hours in asthmatic patients, suggesting that lower cortisol contributes to overall lower lung function, especially at night, likely due to inadequate suppression of airway inflammation 1.
Greater 24-hour cortisol variation (the normal diurnal rhythm) is associated with lower FEV1 at all time points, indicating that the physiologic drop in cortisol during nighttime hours may contribute to nocturnal respiratory symptoms 1.
In Patients with Adrenal Insufficiency
Patients with adrenal insufficiency experience multiple symptoms that can include respiratory manifestations, though cough is not specifically listed as a cardinal feature of the condition 2.
Nausea occurs in 20-62% of patients with adrenal insufficiency, frequently accompanied by morning symptoms that represent under-replacement of glucocorticoids, and adjusting the timing of hydrocortisone dosing (such as taking the first dose earlier in the morning) can relieve these morning symptoms 2.
Adrenal insufficiency must be excluded in patients presenting with hyponatremia and unexplained symptoms, as it is present in 90% of newly diagnosed cases and can present with a clinical picture nearly identical to other conditions 2.
Impact of Corticosteroid Therapy on Cough
Inhaled Corticosteroids and Adrenal Suppression
Chronic use of medium-high dose inhaled corticosteroids can cause secondary adrenal insufficiency through hypothalamic-pituitary-adrenal axis suppression, which may manifest with various symptoms including potential worsening of respiratory control 3, 4.
Screening for adrenal insufficiency should be considered in select patient groups using inhaled corticosteroids, particularly those on high doses or with suggestive symptoms, starting with an early morning serum cortisol followed by low-dose corticotropin stimulation testing if abnormal 4.
Cough Response to Corticosteroids
Heightened cough reflex sensitivity is an independent factor contributing to daytime asthmatic cough that remains refractory to inhaled corticosteroids, while airway hyperreactivity and less atopic status contribute to nighttime cough that doesn't respond to ICS 5.
The presence or absence of nighttime cough should not be used to diagnose or exclude psychogenic cough in adults with chronic cough, as cough characteristics alone are not diagnostic 6.
Clinical Implications for Patients on Cortisol Replacement
Timing of Glucocorticoid Dosing
Standard maintenance dosing for hydrocortisone is 15-25 mg daily in divided doses, typically given as 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM to approximate physiological cortisol secretion 2.
Patients experiencing morning symptoms may benefit from waking earlier to take the first hydrocortisone dose and then returning to sleep, which can relieve morning nausea and potentially other early morning symptoms 2.
Monitoring and Adjustment
Under-replacement of glucocorticoids is characterized by lethargy, nausea, poor appetite, and weight loss, and adjusting the timing of glucocorticoid dosing based on when symptoms occur during the day is recommended 2.
Medications that increase hydrocortisone requirements include anti-epileptics, antituberculosis drugs, antifungal medications, etomidate, and topiramate, which could theoretically worsen early morning symptoms if replacement is inadequate 2.
Critical Pitfalls to Avoid
Do not assume that nighttime or early morning cough is directly caused by low cortisol levels without considering other common causes such as asthma, gastroesophageal reflux disease, upper airway cough syndrome, or medication effects 6.
In patients with known adrenal insufficiency experiencing new or worsening respiratory symptoms, ensure adequate glucocorticoid replacement before attributing symptoms to other causes, as under-replacement can contribute to multiple systemic symptoms 2.
Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures if a patient presents with unexplained collapse, hypotension, or severe symptoms—immediate IV hydrocortisone 100 mg and saline infusion are required 2.