Primary adrenal insufficiency

Primary adrenal insufficiency, is a rare endocrine disorder that happens when the adrenal gland isn’t able to produce enough of the hormones that the body needs, particularly aldosterone and cortisol. The reason it’s called “primary” is that the underlying problem is localized to the adrenal gland itself, rather than a problem of a hormone that acts on the adrenal gland or elsewhere in the body. Primary adrenal insufficiency can develop acutely or chronically, and a really famous example of someone having this condition is John F. Kennedy, who was diagnosed at age 30.

Now, there are two adrenal glands, one above each kidney, and each one has an inner layer called the medulla and an outer layer called the cortex which is subdivided into three more layers, the zona glomerulosa, zona fasciculata, and the zona reticularis. The outermost layer is the zona glomerulosa, and it’s full of cells that make the hormone aldosterone.

Aldosterone is part of a hormone family or axis which work together and are called the renin-angiotensin-aldosterone system. Together these hormones decrease potassium levels, increase sodium levels, and increase blood volume and blood pressure.

Aldosterone is secreted in response to elevated levels of renin, and its role is to bind to receptors on two types of cells along the distal convoluted tubule of the nephron.

First it stimulates the sodium/potassium ion pumps of the principal cells to work even harder. These pumps drive potassium from the blood into the cells and from there it flows down its concentration gradient into the tubule to be excreted as urine. At the same time, the pumps drive sodium in the opposite direction from the cell into the blood, which allows more sodium to flow from the tubule into the cell down its concentration gradient.

Since water often flows with sodium through a process of osmosis, water also moves into the blood, which increases blood volume and therefore blood pressure.

The other function of aldosterone is to stimulate the proton ATPase pumps in alpha-intercalated cells which causes more protons to get excreted into the urine. Meanwhile, ion exchangers on the basal surface of the cell move the negatively charged bicarbonate into the extracellular space, causing an increase in pH.

The middle layer of the adrenal gland is the zona fasciculata, and the cells there make the hormone cortisol as well as other glucocorticoids. Cortisol is also needed in times of emotional and physical stress like arguing with a friend or fleeing from a pack of raccoons. In those situations, the hypothalamus—which is an almond-size structure which sits at the base of the brain, releases corticotropin-releasing hormone, which is then received by the pituitary gland, the pea-sized structure sitting just underneath the hypothalamus. In response, the pituitary gland sends out adrenocorticotropic hormone, or ACTH, which travels through the blood to the zona fasciculata of the adrenal glands and signals cells there to release cortisol.