Glucocorticoid Deficiency (Cortisol Deficiency)

What glucocorticoids do

Glucocorticoids are steroid hormones made in the outer layer (cortex) of the adrenal glands, which sit on top of the kidneys. The main one is cortisol. Its production is controlled by ACTH, a hormone from the pituitary gland in the brain. Cortisol:

• keeps blood pressure up by helping blood vessels respond to adrenaline
• raises blood sugar between meals and overnight
• dampens inflammation
• helps the body survive physical stress such as infection, surgery or injury, when needs can rise severalfold

When cortisol is low, these functions fail, and the effect is most dangerous during illness.

Causes and types

Steroid-induced deficiency is by far the most common type. Taking glucocorticoid medicines for more than about 3 to 4 weeks switches off the body's own production. If the medicine is stopped suddenly, the adrenal glands may take months to recover.

Familial glucocorticoid deficiency

This is a rare inherited condition in which the adrenal glands do not respond to ACTH, most often because of changes in the MC2R or MRAP genes. Cortisol is low but aldosterone is normal, so salt balance is usually preserved. It typically shows up in infancy or early childhood with low blood sugar (sometimes causing seizures), repeated or severe infections, failure to thrive and very dark skin from high ACTH levels. Some children are unusually tall. It is treated with hydrocortisone.

Other causes

Congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune polyendocrine syndromes, some medicines (such as ketoconazole and etomidate), and surgical removal of both adrenal glands.

Glucocorticoid deficiency symptoms

Symptoms usually build up slowly over months and are easy to mistake for other things:

• tiredness and muscle weakness
• loss of appetite and weight loss
• nausea, vomiting and abdominal pain
• dizziness or fainting when you stand up, from low blood pressure
• low mood, irritability and poor concentration
• muscle and joint aches
• low blood sugar, especially in children: shakiness, sweating, confusion

In primary adrenal insufficiency, you may also notice:

• darkening of the skin, especially in palm creases, knuckles, scars, lips and gums, caused by high ACTH
• salt craving and dehydration from aldosterone loss

Adrenal crisis

An adrenal crisis is a sudden, severe shortage of cortisol, usually triggered by an infection, vomiting illness, injury or surgery, or by missing doses. Signs include severe vomiting and diarrhea, intense abdominal or leg pain, very low blood pressure, confusion and collapse. Without urgent hydrocortisone and fluids it can be fatal.

How to tell if you have glucocorticoid deficiency

You cannot diagnose it from symptoms alone. Doctors use blood tests:

1. Early morning cortisol (around 8 a.m.): a very low level strongly suggests deficiency. A clearly normal level makes it unlikely.
2. ACTH level: high in primary (adrenal) disease, low or normal in secondary (pituitary) disease.
3. ACTH stimulation (synacthen) test: synthetic ACTH is injected and cortisol is measured 30 to 60 minutes later. A poor rise confirms adrenal insufficiency.
4. Other blood tests: sodium and potassium, blood sugar, renin and aldosterone, and adrenal antibodies.
5. Imaging: a CT scan of the adrenals or MRI of the pituitary, depending on the type.

Tell your doctor about any steroid medicine you have used in the past year, including inhalers, joint injections and skin creams, as these can affect results.

Glucocorticoid deficiency treatment

Daily replacement

Hydrocortisone tablets are the usual replacement, taken two or three times a day in a pattern that mimics the body's natural rhythm, with the largest dose on waking. Prednisolone once daily is an alternative for some adults. People with primary adrenal insufficiency usually also take fludrocortisone to replace aldosterone. The aim is the lowest dose that keeps you well, because too much causes weight gain, bone thinning and high blood sugar.

Sick-day rules

During illness the body needs more cortisol. Your endocrinology team will give you written rules, typically:

• double your usual daily dose during a fever, an infection needing antibiotics, or when bedbound
• use your emergency hydrocortisone injection if you are vomiting, cannot keep tablets down, or collapse, then go to the ER
• extra steroid cover is needed for surgery, dental procedures under anesthesia and childbirth

Other essentials

• Carry a steroid emergency card and wear medical ID.
• Never stop steroid tablets suddenly.
• After long-term steroid treatment for another illness, doses are tapered slowly so the adrenal glands can recover. Your doctor may check a morning cortisol level during the taper.

Outlook

With correct replacement and sick-day rules, most people lead a full, active life, including work, sport and pregnancy. Fatigue can persist for some, and doses may need fine-tuning. The main risk is adrenal crisis, which is largely preventable through education, an emergency kit and prompt treatment of illness.

Frequently asked questions

What are the symptoms of glucocorticoid deficiency?

Common symptoms are tiredness, weakness, weight loss, poor appetite, nausea, abdominal pain, dizziness on standing and low blood sugar. In primary adrenal disease, skin darkening and salt craving are typical. Symptoms often develop slowly, but illness can trigger a sudden adrenal crisis.

How can I tell if I have glucocorticoid deficiency?

Only blood tests can confirm it. An early morning cortisol level is the first test. If it is low or borderline, an ACTH stimulation (synacthen) test shows whether the adrenal glands respond properly. An ACTH level shows whether the problem is in the adrenals or the pituitary.

What is the treatment for glucocorticoid deficiency?

Treatment is lifelong replacement with hydrocortisone or a similar steroid, plus fludrocortisone if aldosterone is also low. You increase the dose during illness following sick-day rules, carry an emergency hydrocortisone injection, and wear medical ID.

Is glucocorticoid deficiency the same as Addison's disease?

Not exactly. Addison's disease is one cause, where the adrenal glands themselves are damaged, usually by autoimmunity. Glucocorticoid deficiency also includes pituitary causes, deficiency after stopping steroid medicines, and rare inherited forms such as familial glucocorticoid deficiency.

Can stopping prednisone cause glucocorticoid deficiency?

Yes. Taking prednisone or similar steroids for more than a few weeks suppresses your own cortisol production. Stopping suddenly can cause fatigue, nausea, dizziness and, rarely, adrenal crisis. Doses should be tapered gradually under medical advice.