Addison’s disease and Type 1 diabetes

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In 1855, English physician, Thomas Addison, described bronze skin disease as being caused by the destruction of the adrenal glands. This resulted in a deficiency of the hormones produced by the adrenals.

The adrenal gland

Image by hopkinsmedicine.org

Addison’s work showed that the adrenal gland is essential for life. The gland is divided into two sections (cortex and medulla) and produces three main hormones:

• Glucocorticoid – cortisol
• Mineralcorticoid – aldosterone
• Adrenalin

These hormones are critical for, among other things, the regulation of blood pressure, fluid balance, immune function, and carbohydrate metabolism. Any damage to the glands will result in a decrease in the hormones produced and thus, cause a range of clinical problems.

Decreased function of the adrenal glands may be described as primary or secondary.

Primary – Direct damage to the adrenal glands.

Secondary – Damage is to the pituitary gland and affects the secretion of ACTH, the hormone that control glucocorticoid release. The most common cause of this is the use of cortisone-based medications (e.g. prednisone).

Primary Addison’s disease (adrenocorticoid deficiency)

Causes

1. Autoimmune – This is the most common cause and can occur in combination with other autoimmune conditions and this is known as polyglandular endocrinopathies:
   1. Type 1 Autoimmune polyglandular syndrome – This has a classic triad of Addison’s disease, hypoparathyroidism and mucocutaneous candidiasis (a skin disorder).
   2. Type 2 Autoimmune polyglandular syndrome – Combines several conditions such as Addison’s disease, Type 1 diabetes, thyroiditis, pernicious anaemia (vitamin B12 deficiency), vitiligo or alopecia.
2. Infections – In South Africa HIV and tuberculosis are more common ones.
3. Adrenal haemorrhage – This can be caused by trauma or severe illness.
4. Infiltrations – Unusual conditions such as haemochromatosis (iron overload) and, rarely, cancer that has spread.
5. Congenital disorders occur rarely.
6. Medications – Ketoconazole (an antifungal) and etomidate (a sedative).

Clinical presentation

Addison’s disease can develop insidiously and be missed for a long time. Patients may complain of general feelings of fatigue, general body weakness, loss of weight, nausea and vomiting with abdominal pain, and dizziness.

On examining the patient, it’s important to test blood pressure lying and standing as a drop in blood pressure on standing confirms postural hypotension which is a feature of Addison’s disease.

Almost all patients will have areas of their skin that are dark in colour (hyperpigmented), especially in sun-exposed skin. This is due to the high levels of ACTH binding to melanocyte receptors which are responsible for pigmentation.

There really does need to be a high level of suspicion to diagnose Addison’s disease early due to non-specific presentation. Patients at increased risk of Addison’s disease are those with other autoimmune diseases as listed above.

Addison’s crisis

Some patients develop adrenal insufficiency rapidly, often after trauma or severe infection. They present critically ill with dehydration, severely low blood pressure, confusion and can go into shock. Areas of skin hyperpigmentation may be present.

Diagnosis

Adrenal hormone secretion is controlled by the hypothalamus and pituitary gland. The hypothalamus secretes corticotropin releasing hormone (CRH) which stimulates the release of adrenocorticotrophic hormone (ACTH) in the pituitary gland. ACTH then stimulates the release of cortisol from the adrenal gland. This is all controlled by a precise feedback loop.

Image by courses.washington.edu

If an Addison’s crisis is suspected, the blood tests should be taken immediately in casualty, so that empirical treatment can be started, and the diagnosis reviewed later.

Imaging studies may help with the cause of Addison’s disease, e.g. an ultrasound or CT scan of the adrenals can show haemorrhage or infiltration. Autoimmune destruction of the adrenals will reveal small glands.

Treatment

The mainstay of treatment is to replace the hormones that aren’t being produced:

• Glucocorticoid (cortisol) – hydrocortisone or prednisone given in divided doses.
• Mineralocorticoid (aldosterone)– fludrocortisone usually daily.

In Addison’s crisis fluid replacement is critical and large doses of glucocorticoids will be given intravenously.

Maintenance

It’s important for patients with Addison’s to be aware of the impact any stress to their body will have on their chronic management of their condition. When the human body is stressed (due to illness, trauma), the adrenal glands produce more hormones to compensate.

A person with Addison’s disease must increase their medication dose during these periods to provide the same protection and avoid a crisis. They should also wear a medical alert bracelet so that if in an accident the emergency personnel will know to give life-saving cortisone.

The person living with Addison’s disease and Type 1 diabetes

Although the risk is there, this is an unusual combination. It’s not recommended to routinely screen people living with Type 1 diabetes for Addison’s disease. There are some factors that would increase the risk of the combination and indicate to the doctor that tests should be done. These risks factors are:

1. Recurrent, unexplained hypoglycaemia – This would naturally mean the person is constantly decreasing their insulin dose.
2. Repeat requests for a glucagon hypo kit prescription – Again the increased use of glucagon would indicate frequent and significant hypoglycaemia.
3. Presence of diabetic retinopathy.
4. Concomitant diagnosis of autoimmune thyroid disease.

The daily burden of care will still be directed at Type 1 diabetes. Studies have shown that overall people living with both Type 1 diabetes and Addison’s disease have a lower basal insulin requirement and increased mealtime insulin needs. This is related to the change in the insulin sensitivity due to cortisone replacement. There are further challenges when there is an intercurrent illness or other stress as this will affect both the corticosteroid requirement and the glucose levels. Similarly, if diabetes control is not good this will cause ongoing stress to the body and higher doses of glucocorticoid replacement may be required.

A specialist and latest technology are a must

For this reason, people living with both conditions should be given access to flash or continuous glucose monitoring, and the option of insulin pump therapy. Access to this technology will allow more regular and accurate adjustments to the insulin regimen.

A patient with the combination of Addison’s disease and Type 1 diabetes must be looked after by a specialist. They must have access to 24/7 advice and have a home protocol of what to do if unwell. In this way the complications of hypoglycaemia, diabetic ketoacidosis and adrenal crisis can be avoided.

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