Adrenal insufficiency

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

Males

Adrenal insufficiency (or Addison’s disease) is seen often 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 patient group adrenal insufficiency accompanies the other (neurological) ALD symptoms. However, in some ALD patients, despite severe neurological involvement, adrenal insufficiency does not occur (even up to high age).
• In some patients, adrenal insufficiency may be the only symptom, this subgroup is subsequently dubbed the “Addison-only phenotype”.

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

Unrecognized adrenal insufficiency frequently can result in morbidity (which are the consequences or complications (other than death) that result from the disease) and even mortality. Careful periodic assessments can identify impaired adrenal reserve in an early stage and may facilitate initiation of therapy.

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

Presentation of an Addisonian crisis has been reported as the first presentation of ALD and may also require (short) medical interventions in patients known with 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 adrenal cortex are negative, or when signs of myelopathy are present.

Adrenal hormone therapy is mandatory to all ALD patients who have adrenal insufficiency, and it may be lifesaving. There is no evidence that adrenal hormone therapy alters the neurological progression due to ALD.

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

Females

Unlike the affected men clinical overt adrenal insufficiency is exceptionally rare in women with ALD. Studies in a large group of women with ALD demonstrated that adrenal insufficiency is present in about 1% of females with ALD.

Last modified | 2019-06-04