Can hypocortisolism (low cortisol) cause hypoglycemia (low blood sugar)?

From the Guidelines

Low cortisol levels can indeed cause hypoglycemia, as evidenced by the association between hypoglycemia and primary adrenal insufficiency (PAI) in patients with low cortisol levels 1.

Key Points to Consider

• Cortisol plays a crucial role in regulating blood glucose levels by promoting gluconeogenesis in the liver and reducing insulin sensitivity in peripheral tissues.
• In conditions like adrenal insufficiency or Addison's disease, low cortisol levels can compromise the body's ability to maintain normal blood glucose levels, leading to hypoglycemia.
• The diagnosis of PAI should consider symptoms like unexplained collapse, hypotension, vomiting, diarrhea, hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia, as outlined in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1.
• Treatment of adrenal insufficiency typically involves cortisol replacement therapy, usually with hydrocortisone at doses of 15-25 mg daily divided into 2-3 doses, to mimic the body's natural cortisol rhythm, as recommended in the guideline 1.
• During acute illness or stress, patients with adrenal insufficiency need to increase their cortisol replacement dose to prevent adrenal crisis, which can include severe hypoglycemia as a component, highlighting the importance of prompt treatment and monitoring 1.

Clinical Implications

• Patients with low cortisol levels should be closely monitored for signs of hypoglycemia, particularly during fasting or stress.
• Cortisol replacement therapy should be tailored to individual patient needs, taking into account the severity of adrenal insufficiency and the presence of other underlying medical conditions.
• Education on self-management of daily medications and situations of minor to moderate concurrent illnesses is crucial for patients with adrenal insufficiency, as emphasized in the guideline 1.

From the Research

Relationship Between Cortisol and Hypoglycemia

• Low cortisol levels can contribute to hypoglycemia, as cortisol plays a role in glucose metabolism and regulation 2.
• A study found that patients with growth hormone and cortisol deficiencies had lower plasma glucose concentrations and were more susceptible to hypoglycemia 2.
• Another study found that children with classical congenital adrenal hyperplasia, who have lower cortisol levels, experienced disrupted daily glucose patterns and were at risk of hypoglycemia, particularly at night 3.
• The study also found that a greater percentage of time in hypoglycemia was associated with lower cortisol concentrations 3.

Cortisol Replacement Therapy and Hypoglycemia

• Cortisol replacement therapy is used to treat patients with primary adrenocortical insufficiency, and the goal is to mimic the normal physiological secretion of cortisol 4, 5.
• However, the therapy can be challenging, and there is a risk of over-replacement, which can lead to adverse effects 4, 5.
• A study found that fasting serum glucose did not correlate with hydrocortisone dose, but did present a positive correlation with body mass and age 4.

Diagnostic Criteria for Central Adrenal Insufficiency

• Morning serum cortisol level can be used to predict central adrenal insufficiency, with a cutoff value of ≤126.4 nmol/L having a high specificity for deficient response to insulin tolerance test 6.
• The study also found that a morning serum cortisol concentration >444.7 nmol/L can predict a normal response to insulin tolerance test 6.