Steroids may have a less than perfect reputation in the media, but some steroids naturally occur in the body and function as a vital part of our endocrine system. For example, estrogens and testosterone serve important roles in human reproduction, while cortisol and aldosterone are integral in helping the body maintain equilibrium, especially in times of stress. 

Addison’s disease is defined as the condition in which the steroid hormones produced by the adrenal cortex are either low or absent. It’s known by other names, too: chronic adrenal insufficiency, hypocortisolism, and hypoadrenalism, to name just a few.

Cortisol has many functions, including maintaining a consistent blood glucose level, reducing inflammation, and regulating water balance. Aldosterone primarily maintains sodium and water balance, which are necessary for keeping a consistent blood volume and pressure. 

Both cortisol and aldosterone are produced by the adrenal glands, small endocrine glands that rest on top of both kidneys. The adrenal glands have two layers: the medulla, or inner, layer, and the cortex, the outer layer. In most cases of Addison’s disease, the cells that make up the adrenal cortex are destroyed. The destruction of these cells results in primary adrenal insufficiency, because cortisol and aldosterone are simply not produced. This is different from secondary insufficiency, in which either one or both hormones are made, but the body is unable to use them properly.

So, how does this fit into those other names for Addison’s disease? Since hypo means ‘low’ and the primary glucocorticoid is cortisol, a low amount of cortisol is ‘hypocortisolism.’ As you might guess, Addison’s is also characterized by hypoaldosteronism, low amounts of aldosterone. You’ll want to remember the roots hypo and its opposite hyper, which means high.

CAUSES

Let’s take a look at what happens to destroy the cells of the adrenal cortex. In about 80% of patients that have Addison’s, primary adrenal insufficiency is caused by an autoimmune response in which the body’s immune system mistakes its own cells or biochemicals for pathogens. Specifically, the body sees some part of a pathway used by the body for synthesis or use of cortisol and aldosterone as a threat and targets it for destruction. 

Other things that cause primary adrenal insufficiency are: 

• Adrenal dysgenesis, a genetic disorder in which the adrenal glands aren’t formed properly 
• Difficulties in converting cholesterol to steroid hormones 
• Infection from HIV or tuberculosis 
• Other diseases that impair the adrenal cortex, like adrenoleukodystrophy and cancer 

CLINCAL FEATURES

• Symptoms of Addison’s can also occur after a patient stops steroid use, especially if the medication taken has been taken for a long period of time or in high doses.
• Sustained use of medications like hydrocortisone and prednisone can desensitize the adrenal gland to the chemical that normally stimulates cortisol production, cause its cells to shrink, and impair its ability to make natural steroid hormones. This is called a iatrogenic response, an instance where treatment causes a disorder. 

The symptoms of Addison’s disease are caused by the absence of aldosterone and cortisol. If you think about the functions of these two hormones, then it’s less difficult to determine the symptoms that arise when they’re not present. Here’s where ‘hyper’ and ‘hypo’ start to come into play. 

Cortisol

• Keeps blood sugar levels in balance by stimulating the creation of glucose in the liver. Its absence means a drop in blood glucose, which, in turn, leads to fatigue and lethargy.
• Cortisol and aldosterone work together to maintain salt and water balance, so their loss leads to orthostatic hypotension, a sudden low blood pressure that occurs on standing.

Aldosterone

• Its absence also causes a drastic upset in electrolyte balance, leading to nausea, diarrhea, and vomiting. Together, these pose a real danger of causing dehydration, and, eventually, hypovolemia or low blood volume.
• Because electrolytes like sodium and potassium ions are crucial for nerve and muscle function, symptoms like heart arrhythmia and nervous system changes (especially in the form of mood disorders) are common, as is a craving for salt in an effort to replace the sodium being over-excreted in the urine.