Adrenal insufficiency is a disease of the endocrine system in which the adrenal glands, located on top of each kidney, do not make enough hormones. There are two types of adrenal insufficiency: primary and secondary. Primary adrenal insufficiency is referred to as Addison's disease, where the glands are damaged and do not synthesize enough cortisol and aldosterone. These hormones are important for regulating blood pressure and metabolism and are also key responders to stress. Secondary adrenal insufficiency is the most common kind, and it begins in the pea-sized pituitary gland located in the brainstem. With this type, the pituitary gland does not make adrenocorticotropin (ACTH), which is necessary for the adrenal glands to produce cortisol.
Hyperpigmentation occurs only with Addison's disease, which, as mentioned, is the primary form of adrenal insufficiency. Since Addison's disease involves damaged adrenal glands that do not make enough hormones, the pituitary gland responds by making more of the adrenal-stimulating hormone ACTH. ACTH is directly involved in making melanin, the hormone responsible for darkening the skin. As melanin increases in the body, it causes darkening of the skin. It is often seen around joints, scar tissue, and mucous membranes. It can also cause the lips, rectum, and lining of the mouth to turn a bluish-black. Black freckles are usually found on the face, neck, and shoulders. Areas of the body not normally in the sunlight will still darken, but parts of the body in the sunlight will become even darker.
Hypoglycemia is the condition in which the body's blood sugar level plummets. An affected individual can feel shaky, dizzy, nauseated, fatigued, or have tunnel vision. Feeling like one is about to faint is a common symptom of low blood sugar. Cortisol, in part, is responsible for helping the liver change its stored sugars into blood sugars to provide energy. In adrenal insufficiency, low levels of cortisol make the liver unable to convert these sugars and blood sugar levels drop. This condition is exacerbated during stress because the body has an increased need to use those stored sugars. Cortisol is normally released during stressful scenarios, and without it, the body is unable to generate energy.
Nausea And Vomiting
Nausea, which is feeling the impending need to vomit, can be felt in the upper abdomen, chest, and throat. Vomiting is the involuntary action of the stomach to force its contents out of the body through the mouth. Nausea and vomiting, present in about fifty percent of those with adrenal insufficiency, accompany one another as nausea often precedes vomiting. Some medicines can ease the discomfort of nausea and sometimes stop vomiting. Vomiting is usually a sign that the disease has progressed. The body's gag reflex and couching protect it from aspirating vomit, but these protections can fail in cases of unconsciousness. It is important to roll an unconscious vomiting individual on their side to lessen this possibility.
With lowered production of homeostasis-regulating hormones, extreme fatigue is common with both types of adrenal insufficiency. It is characterized by weakness, sleepiness, and general malaise. Affected individuals might wake up every morning with the feeling of not having slept at all. It might be difficult for a patient to get out of bed, go to work, and complete simple daily activities. Fatigue is a continuous feeling, and it does not come and go with activity level. There is usually no obvious reason an individual would feel fatigued such as extreme exercising or not sleeping. Without being able to participate in regular activities, fatigue can lead to anxiety and depression.
Low Blood Pressure
Low blood pressure is more common in Addison's disease rather than type 2 adrenal insufficiency. Low blood pressure means anything under 90/60 and is caused by low levels of aldosterone in the blood. Aldosterone helps to moderate blood pressure by controlling sodium and potassium in the body. If sodium is too low, aldosterone signals to the kidneys to add more to the blood. If potassium is too high, it signals to the kidneys to release it in urine. Symptoms of this condition include lightheadedness, dizziness, blurred vision, fainting, and nausea. In some cases, there may be no symptoms at all.
Muscle And Joint Pain
Adrenal insufficiency can manifest as muscle and joint pain as a symptom of the disorder. The adrenal cortex is responsible for releasing glucocorticoids including cortisol when the hypothalamus and pituitary trigger it. Cortisol is responsible for helping the body synthesize protein, carbohydrates, and fats into cellular energy properly so the muscles can use it. Without enough cortisone due to adrenal insufficiency, proteins are synthesized into non-functional carbohydrates that cannot be stored in the muscles and liver. Glycogen is a form of carbohydrate released from the liver when the muscles require glucose to function. Cortisol deficiency causes the depletion of glycogen in the liver, rendering it unable to supply energy to the muscles. As a result, the muscles become weak and unable to function properly, leading to soreness and joint pain.
Additionally, cortisol acts as a potent anti-inflammatory agent in the body through its inhibition of leukocytic responses, lysosome stabilization, and stopping cytokine production. The smallest muscular or skeletal injury during a state of deficiency in cortisol can cause an inflammatory response that is persistent and handicaps healthy healing processes. Pain sensitivity increases as a result of prolonged cytokine elevation, while nerve damage is associated with widespread tissue inflammation. A combination of one or more of these malfunctions that occur in the absence of cortisol can cause muscle and joint pain.
Individuals who have adrenal insufficiency may present with symptoms of depression as a result of their disorder. Numerous factors that occur in this disorder can trigger depression. Cortisol in the body has a significant influence on an individual's healthy sleep-wake cycle, and sleep difficulties have proven to trigger depression. Reduced cardiovascular output and low blood pressure from lack of cortisol can cause a patient to feel frequently fatigued and contribute to depressive feelings. In healthy individuals, cortisol manages glucose levels and reallocates energy from nonvital organ systems to the neuromuscular system and actively functioning brain throughout the day. Without this energy distribution management mechanism due to lack of cortisol, depression can be triggered by decreased energy levels, weakness, and mental fatigue.
Low serotonin levels are associated with depression and can be caused by an increase of cytokine production, a process of which cortisol is responsible for mediating. Pro-inflammatory cytokines activate the TRYCAT pathway that steals a compound called tryptophan away from the brain's healthy production of serotonin. Furthermore, nociceptors become sensitized due to a long duration of elevated cytokine levels not managed due to a deficiency of cortisol. Sensitized nociceptors present as an increase in sensitivity to pain, and chronic pain often leads to depressive disorders.
Craving For Salt
An individual experiencing an excessive craving for salt may have adrenal insufficiency. This symptom is most often caused by the patient's immune system attacking their adrenal cortex. This autoimmune action impairs the adrenal cortex function of producing mineralocorticoids in response to signals sent from the kidneys. The kidneys send signals when the fluid levels in the body become too low or too high. Aldosterone is a mineralocorticoid produced by the adrenal gland that stimulates the kidney's action of reabsorbing sodium into the blood and releasing potassium into the urine, saliva, sweat, and gastrointestinal tract. This mechanism works well in healthy individuals to ensure they maintain a proper homeostatic balance of fluid.
However, adrenal insufficiency means the adrenal glands do not supply aldosterone, resulting in the opposite effect. The kidneys actually excrete too much salt and hold onto too much potassium. This malfunction is dangerous because salt takes fluids with it from the body when it is excreted, resulting in excessive fluid loss. When the body is losing more fluid than it is taking in, the individual is dehydrated. The brain will increase an individual's craving for salt when they are dehydrated to encourage fluid intake.
Body Hair Loss
Body hair loss can be an indicative symptom that manifests in an adrenal insufficiency patient. This symptom occurs most commonly in those who have adrenal insufficiency as a result of an autoimmune attack on their adrenal glands. The adrenal gland releases androgens, which function as weakened male hormones. Androgens are converted in a female's ovaries into estrogen hormones, and androgens in males are converted to more potent testosterone hormones in the testes. Androgens also influence the growth of hair in different regions of the body. Inside of the hair follicle, androgens change the interactions between mesenchyme and epithelial cells.
This mechanism changes the duration of hair growth, keratinocyte activity, dermal papilla size, and the activity of melanocytes. Androgen is essential for hair growth, and an overproduction of androgens causes the affected individual to experience excessive hair growth around the body. However, adrenal insufficiency patients have adrenal glands that do not produce enough androgens, causing body hair to fall out and excessive dryness of their skin. Androgen shortage can also delay puberty in preteens.
Adrenal insufficiency may present with weight loss as a manifestation of the disorder. This symptom is mainly caused by the adrenal glands failing to produce enough cortisol for the body. Cortisol functions in healthy individuals to move triglycerides from storage to the fat cells underneath the abdominal muscles or visceral fat cells. It is also a key factor in the maturation of adipocytes into matured fat cells. In addition, cortisol functions to remove glucose from liver storage and relocate it to the bloodstream when it's needed. Cortisol inhibits the production of insulin to keep glucose levels high in the blood to help accomplish this. This process causes cells to become deprived of glucose, reducing their production of energy. Cellular energy deprivation stimulates the transmission of hunger signals to the brain, enhancing appetite.
Adrenal insufficiency patients do not get cortisol from the adrenal glands, so these metabolic processes that stimulate appetite do not occur. Cortisol can also have a direct influence on appetite through binding with receptors in the hypothalamus. Cortisol decreases inflammatory immune system processes that can induce poor appetite. Furthermore, fifty percent of individuals with adrenal insufficiency caused by autoimmune action reported complications of nausea, vomiting, and diarrhea. The combination of one or more of these mechanisms can result in the affected individual burning off more calories than are being consumed, causing weight loss.