Addisons Disease (Adrenal Crisis)

This condition is part one of the three major catergories of Adrenoleukodystrophy (ALD) which refers to several different inherited conditions that affect the nervous system and adrenal glands.

The other two are categories of ALD are:

• Childhood cerebral ALD
• Adrenomyelopathy (ALD) – (X-linked adrenoleukodystrophy)
  • Primarily affects adult men.
  • It’s milder than childhood cerebral ALD, it also progresses slowly by comparison.

Both will be discussed in this chapter (the main focus on this chapter is Addison’s disease).

Causes and risk factors

• The adrenoleukodystrophy protein (ALDP) helps your body break down very long chain fatty acids (VLCFAs). If the protein doesn’t do its job, the fatty acids build up inside your body. This can harm the outer layer of cells in your:
  • Spinal cord
  • Brain
  • Adrenal glands (Addison’s disease)
  • Testes
• People with ALD have mutations in the gene that makes ALDP. Their bodies don’t make enough ALDP.
• Men are typically affected by ALD at an earlier age than women and usually have more severe symptoms.

Inherited factors:

• ALD affects males more than females because it is inherited in an X-linked pattern. This means that the responsible gene mutation is on the X chromosome.
• Men only have one X chromosome, while women have two. Because women have two X chromosomes, they can have one normal gene and one copy with the gene mutation.
• Women who have only one copy of the mutation have much milder symptoms than men.
• In some cases, women who carry the gene don’t have symptoms at all.
• Their normal copy of the gene makes enough ALDP to help mask their symptoms.
• Most women with ALD have adrenomyelopathy. Addison’s disease and childhood cerebral ALD are less common.

Diagnosing adrenoleukodystrophy

ALD symptoms can mimic those of other illnesses. Tests are needed to distinguish ALD from other neurological conditions. Your doctor may order a blood test to:

• Look for abnormally high levels of VLCFAs (very long chain fatty acids)
• Check your adrenal glands
• Find the genetic mutation that causes ALD

Your doctor may also look for:

• Damage to your brain using an MRI scan.
• Skin samples or a biopsy and fibroblast cell culture can also be used to test for VLCFAs.
• Children with suspected ALD may need additional testing, including vision screens.

Healthline

(Primary adrenal insufficiency or hypoadrenalism, Addison’s disease)

A rare condition where the two adrenal glands (located above kidneys) don’t produce enough  steroid (cortisol), mineralocorticoids (especially aldosterone- needed in blood pressure control) and sex hormones (testosterone).

Cortisol functions:

• Hormone that gives feeling of ‘fight/aggression feeling’ and control stress.
• It helps in high blood pressure and heart to work properly.
• Control blood sugar levels (glucose in the blood to avoid diabetes).
• Control food to turn to energy (metabolism).
• Control salt and water in the body by retaining salt in blood and removing potassium in the kidney, this is important to avoid low blood pressure.
• It makes our immune system (our defence system) weaker.

Diagnosis Tests

Once suspected, adrenal insufficiency can be confirmed by assaying morning cortisol levels between the hours of 08:00 and 09:00.

(these values are a guide as results can vary depending on testing equipment/assays used)

• Below 150nmol/L : The patient may have adrenal insufficiency. Consider starting treatment and refer to endocrinology
• Between 150 and 300nmol/L: The diagnosis of adrenal insufficiency is uncertain. Consider repeating the test and referring to endocrinology
• Above 300nmol/L: Adrenal insufficiency is very unlikely

National Institute for Health and Care Excellence (NICE). Adrenal insufficiency: identification and management [NG243]

The Pharmaceutical Journal, PJ, November 2024,
Vol 313, No 7991;313(7991)::
DOI:10.1211/PJ.2024.1.338894

• A patient is considered to have demonstrated a normal adrenal response if they achieve a stimulated plasma cortisol of 450nmol/L

Endocrine bible. Imperial Centre for Endocrinology. 2023. Accessed November 2024.
https://imperialendo.co.uk/Bible2023.pdf

Other Tests

• Short Synacthen test
• Insulin tolerance and glucagon stimulation tests (done by a specialist)