Adrenal insufficiency (AI) occurs when the adrenal glands, located atop the kidneys, do not produce sufficient hormones, primarily cortisol. Diabetes mellitus is characterized by the body’s inability to regulate blood glucose levels effectively due to insufficient insulin or resistance to its effects. While distinct, these two endocrine disorders share a significant connection. This relationship involves two factors: the physiological role of adrenal hormones in blood sugar regulation and a shared autoimmune origin. The presence of one condition profoundly impacts the control and treatment of the other.
The Role of Adrenal Hormones in Glucose Control
Cortisol, a glucocorticoid produced by the adrenal glands, functions as a counter-regulatory hormone to insulin. Its primary role in glucose metabolism is to raise blood sugar, which is particularly important during periods of stress, illness, or fasting. Cortisol achieves this by stimulating a process in the liver called gluconeogenesis, which is the creation of new glucose from non-carbohydrate sources like amino acids and fats.
This hormone also actively opposes the action of insulin in peripheral tissues, such as muscle and fat cells, reducing their uptake and utilization of glucose. This combined effect ensures the brain has a continuous supply of glucose, preserving energy for survival during stressful events. Cortisol also plays a permissive role, meaning it allows other glucose-raising hormones, like glucagon and epinephrine, to work at their optimal capacity.
In a person with adrenal insufficiency, the lack of cortisol severely compromises the body’s ability to execute this counter-regulatory response. The body cannot effectively raise blood sugar when levels drop, nor can it sufficiently counteract the effects of insulin. This physiological deficit leads to a heightened and constant risk of hypoglycemia, or dangerously low blood sugar, especially when fasting or experiencing minor stress.
The risk of severe hypoglycemia is amplified in people with AI, even without diabetes, because their primary defense mechanism against low blood glucose is impaired. For individuals with diabetes using insulin or other glucose-lowering medications, the absence of cortisol makes blood glucose control highly precarious.
Autoimmune Syndromes Linking Both Conditions
The most common causal link between adrenal insufficiency and diabetes is a shared autoimmune etiology, where the immune system mistakenly attacks the body’s own tissues. Primary adrenal insufficiency, often called Addison’s disease, is overwhelmingly caused by an autoimmune attack on the adrenal glands. Similarly, Type 1 Diabetes (T1D) results from the immune system destroying the insulin-producing beta cells in the pancreas.
When multiple autoimmune endocrine conditions occur in the same person, they are often classified under the umbrella of Autoimmune Polyglandular Syndromes (APS). Specifically, APS Type 2, also known as Schmidt’s Syndrome, is the most common presentation linking the two conditions. The diagnosis of APS Type 2 requires the presence of autoimmune Addison’s disease along with either autoimmune thyroid disease or Type 1 Diabetes.
The co-occurrence of these conditions is not coincidental; it is rooted in a genetic predisposition that makes a person susceptible to developing multiple organ-specific autoimmune diseases. While the combination of Addison’s disease and Type 1 Diabetes is rare in the general population, the risk of developing Addison’s disease is significantly higher—estimated to be about 10 times greater—in individuals already diagnosed with Type 1 Diabetes.
Due to this strong association, a diagnosis of one autoimmune endocrine disorder prompts healthcare providers to screen for others. For example, a person with new-onset Type 1 Diabetes may be monitored for the development of Addison’s disease, which typically presents later, often in adulthood around the age of 30. Proactive monitoring and early diagnosis can prevent life-threatening complications like an adrenal crisis.
Navigating Treatment When Both Conditions Are Present
Managing diabetes becomes significantly more complex when adrenal insufficiency is also present, primarily due to the dual-edged nature of cortisol replacement therapy. People with AI require daily glucocorticoid medication, such as hydrocortisone, to replace the hormone their body no longer produces. However, this replacement medication, while life-sustaining, mimics the effects of natural cortisol by raising blood glucose levels and promoting insulin resistance.
This means the treatment for adrenal insufficiency can make diabetes management more challenging by requiring higher doses of insulin or other diabetes medications to counteract the steroid’s hyperglycemic effect. The goal is to find the lowest effective dose of steroid replacement that prevents AI symptoms without causing unnecessary high blood sugar, requiring close monitoring and frequent adjustments.
A second major complexity arises with the need for “stress dosing” of glucocorticoids during times of physical stress, such as illness, injury, or surgery. In these scenarios, the body requires a temporary increase in cortisol to cope, and patients with AI must increase their hydrocortisone dose, often doubling or tripling it. This necessary increase in steroid dosage, while protecting against an adrenal crisis, simultaneously causes a sharp spike in blood glucose levels, potentially leading to diabetic ketoacidosis.
Sick-day protocols are essential, requiring patients to manage two opposing risks simultaneously: adrenal crisis from under-dosing the steroid and severe hyperglycemia from the stress dose. Continuous communication between the patient and their endocrinology team is necessary to coordinate insulin adjustments with steroid dose changes. For some patients, alternative steroids like prednisolone may be used to achieve a more stable blood sugar profile, avoiding the peaks and troughs associated with hydrocortisone replacement.