Adrenal insufficiency

Authors: Gabor Linthorst, M.D., Ph.D. and Stephan Kemp, Ph.D.

Males

Adrenal insufficiency (or Addison’s disease) is common in ALD:

• The vast majority (80% or more) of patients with childhood cerebral ALD and adrenomyeloneuropathy (AMN) have clinical and biochemical evidence of adrenal insufficiency. In this group of patients, adrenal insufficiency accompanies the other (neurological) symptoms of ALD. However, in some ALD patients, despite severe neurological involvement, adrenal insufficiency does not occur (even into old age).
• In some patients, adrenal insufficiency may be the only symptom; this subgroup is referred to as the “Addison-only phenotype”.

While adrenal insufficiency often precedes the onset of neurological symptoms, there are no disease characteristics (e.g., ALD genotype or VLCFA concentrations) that can accurately predict the occurrence of adrenal insufficiency in a given ALD patient.

Unrecognized adrenal insufficiency can often lead to morbidity (i.e., the consequences or complications (other than death) that result from the disease) and even mortality. Careful periodic assessment can detect impaired adrenal reserve early and facilitate initiation of therapy.

Adrenal insufficiency results in decreased production of the stress hormone cortisol by the adrenal gland. A gradual decrease in cortisol levels often goes unnoticed, and symptoms may include fatigue, orthostatic hypotension (low blood pressure when standing up), weight loss, and browning of the skin and gums. However, an increase in cortisol levels is required when the body is exposed to physical stress, such as a viral infection (common cold) or worse. In such cases, a lack of cortisol can lead to dangerously low blood pressure (also known as an Addisonian crisis).

The occurrence of an Addisonian crisis has been reported as a first presentation of ALD and may also require (brief) medical intervention in patients with known ALD and adrenal insufficiency.

A prospective evaluation of adrenal function in a cohort of 49 neurologically presymptomatic boys (mean age 4 years) with ALD showed that 80% already had impaired adrenal function (Dubey et al. 2005). Therefore, endocrinologists should test for VLCFA in boys and men with adrenal insufficiency when tests for autoantibodies to the adrenal cortex are negative or when signs of myelopathy are present.

Adrenal hormone therapy is mandatory for all ALD patients with adrenal insufficiency and it can be lifesaving. There is no evidence that adrenal hormone therapy alters the neurological course of ALD.

Because adrenal insufficiency due to ALD is caused by direct toxic effects of VLCFA on the adrenal gland, plasma ACTH (adrenocorticotropic hormone, a hormone needed for the adrenal glands to work properly and help the body respond to stress) can be used as a laboratory marker of adrenal dysfunction in children, adolescents, and adults. Short Synthetix ACTH tests (Synacthen test) can be used to study adrenal reserve in detail.

Females

In contrast to affected men, clinical overt adrenal insufficiency is extremely rare in women with ALD. Studies in a large group of women with ALD have shown that adrenal insufficiency is present in approximately 1% of women with ALD.

Last modified | 2024-06-24