Disorders of the Endocrine System

Addison’s Disease (Primary Adrenal Insufficiency)

Addison's disease (also called primary adrenal insufficiency) is a disorder that occurs when the adrenal glands do not produce enough cortisol hormone. In many cases, they also do not produce enough aldosterone hormone. This disorder is commonly caused by an autoimmune disease. In fact, people with Addison’s disease are more likely to also have another type of autoimmune disease. Symptoms of Addison’s disease can start slowly and often include extreme tiredness, salt cravings, and weight loss. Without treatment, adrenal insufficiency can be life-threatening. Treatment involves hormone treatment to replace those that are missing.^[1]

Cushing’s Disease

Cushing’s disease is caused by elevated levels of the cortisol hormone produced by the adrenal glands, which results in a wide variety of symptoms. Cushing’s disease affects 10 to 15 per one million people worldwide, and females are at higher risk than males. This condition usually occurs in adults between the ages of 20 and 50, but children may also be affected. The first symptom of Cushing’s disease is typically weight gain around the trunk and in the face. Affected individuals may get stretch marks (striae) on their thighs and abdomen, and they may bruise easily. They may also develop a hump on their upper back caused by abnormal deposits of fat. Additional symptoms include muscle weakness, severe tiredness, and progressively thin and brittle bones that are prone to fracture. People with Cushing’s disease have a weakened immune system and are at an increased risk of infections. They are also at increased risk of developing high blood pressure and diabetes. Cushing’s disease can cause mood disorders such as anxiety, irritability, and depression and can also affect a person’s concentration and memory. Women with Cushing’s disease may experience irregular menstruation and have excessive hair growth (hirsutism) on their face, abdomen, and legs. Men with Cushing’s disease may have erectile dysfunction. Children with Cushing’s disease typically experience slow growth. The primary treatment for Cushing’s disease involves surgical removal of a tumor in the pituitary gland, which is often the cause of excess cortisol production. Other options include radiation therapy, medications to inhibit cortisol production, or bilateral adrenalectomy (removal of both adrenal glands).^[2]

Diabetes Insipidus^[3]

Diabetes insipidus is a condition marked by increased thirst and urination. It is not to be confused with the more common type of diabetes, diabetes mellitus.

Central diabetes insipidus is the most common type and is caused by destruction of part of the pituitary gland that produces ADH (vasopressin), which regulates water balance and urine output from the kidneys. In infants and children, this is often an inherited condition. Other causes include tumors, infections and head injury.

Nephrogenic diabetes Insipidus occurs when the pituitary produces enough ADH, but the kidneys fail to recognize it because of an inherited or acquired kidney disease.

Maintaining proper water balance by drinking enough fluids is critical for children with diabetes insipidus, as they tend to lose a lot of water with frequent urination, which can lead to life-threatening dehydration. However, drinking too much water is also dangerous, as it may lead to a rare condition called water intoxication.

Symptoms of diabetes insipidus include increased thirst, frequent urination, increased urine volume, pale or colorless watery urine, nocturia and fatigue due to frequent nighttime urination and interrupted sleep.

Medications that deliver synthetic ADH are the therapy for central diabetes insipidus. For nephrogenic Diabetes insipidus, diuretics are used.

Diabetes Mellitus

Diabetes mellitus is a disorder of the endocrine system where the body has trouble making insulin or using it properly, which affects how cells take in and use glucose (sugar) from the blood. Over 18 million adults and over 200,000 children in the United States have diabetes mellitus, and as many as 7 million adults are estimated to have the condition but have not yet been diagnosed. In addition, approximately 79 million people in the US have prediabetes, a condition in which blood glucose levels are abnormally high, but not yet high enough to be classified as diabetes.

There are two main forms of diabetes mellitus called type 1 and type 2 diabetes. Type 1 diabetes mellitus causes less than 5 percent of all diabetes cases. It is an autoimmune disease that destroys the beta cells of the pancreas, so they no longer produce insulin. There is no cure for type 1 diabetes, but it is treated with daily synthetic insulin doses that are administered by injection or infusion pump.

Type 2 diabetes mellitus accounts for approximately 95 percent of all diabetes cases. Around 80 to 90 percent of people with type 2 diabetes are overweight or obese and have contributing lifestyle factors such as poor diet and low physical activity that greatly increase a person’s risk. In type 2 diabetes, cells become resistant to insulin. In response, the pancreas increases its insulin secretion, but over time, the beta cells become exhausted. Diabetes is diagnosed when lab tests reveal that blood glucose levels are higher than normal, a condition called hyperglycemia. In many cases, type 2 diabetes can be reversed by moderate weight loss, regular physical activity, and a healthy diet. Oral medications are typically prescribed to individuals with type 2 diabetes to stimulate the production of insulin and make body cells more sensitive to insulin. However, if blood glucose levels cannot be controlled with these treatments, the individual will eventually require insulin.

Early symptoms of diabetes mellitus are excessive urination, excessive thirst, and hunger. These symptoms are caused by elevated blood glucose levels that pull water into the blood and, ultimately, result in an abnormally large amount of sugary urine and excessive thirst. The individual may also experience persistent hunger and weight loss because the body’s cells are unable to access the glucose in the bloodstream.

Over time, elevated levels of blood glucose injure tissues throughout the body, especially those in the blood vessels and nerves. Inflammation and injury of the lining of arteries can lead to atherosclerosis, resulting in an increased risk of heart attack and stroke. Damage to the microscopic blood vessels of the kidney impairs kidney function and can lead to kidney failure. Damage to blood vessels in the eyes can lead to blindness. Blood vessel damage also reduces circulation to the limbs, where nerve damage leads to a loss of sensation, called neuropathy, particularly in the hands and feet. These changes increase the risk of injury, infection, and tissue death (necrosis), contributing to a high rate of toe, foot, and lower leg amputations in people with diabetes. Together, these complications make diabetes the seventh leading cause of death in the United States.

Uncontrolled diabetes can also lead to a specific type of metabolic acidosis called ketoacidosis. Without glucose, cells increasingly rely on fat stores for fuel. With no glucose, the liver is forced to use lipids, which result in the increased production of ketones that are acidic. The build-up of ketones in the blood causes ketoacidosis, that, if left untreated, can cause a life-threatening “diabetic coma.”

Hyperparathyroidism

Abnormally high activity of the parathyroid glands can cause hyperparathyroidism, a disorder caused by an overproduction of PTH that results in excessive calcium reabsorption from bone. Hyperparathyroidism can significantly decrease bone density, leading to spontaneous fractures or deformities. As blood calcium levels rise, cell membrane permeability to sodium is decreased, and the responsiveness of the nervous system is reduced. At the same time, calcium deposits may collect in the body’s tissues and organs, impairing their function. Hyperparathyroidism is often surgically treated by removing the abnormal parathyroid gland.

Hypoparathyroidism

Abnormally low blood calcium levels may be caused by parathyroid hormone deficiency, called hypoparathyroidism. Hypoparathyroidism may develop after inadvertent removal of the parathyroid glands during surgery involving the thyroid gland. Low blood calcium increases membrane permeability to sodium, resulting in muscle twitching, cramping, spasms, or convulsions. Severe deficits can paralyze muscles, including those involved in breathing, and can be fatal. Treatment includes calcium replacement therapy.

Hyperthyroidism

Hyperthyroidism is an abnormal, elevated level of thyroid hormone in the blood. It is characterized by an increased metabolic rate, excess production of body heat, sweating, diarrhea, weight loss, and increased heart rate. Hyperthyroidism is often caused by a pituitary or thyroid tumor and is more common in females. Hyperthyroidism is also caused by Graves’ disease, an autoimmune disease in which antibodies overstimulate the thyroid gland. In addition to the hyperthyroidism symptoms previously described, the eyes of an individual with Grave’s disease may bulge (called exophthalmos) as antibodies produce inflammation in the soft tissues of the orbits. The person may also develop a goiter or enlarged thyroid gland.

Hyperthyroidism can be treated with a combination of approaches, including medication, radioiodine therapy, or surgery. Antithyroid medications are used to control thyroid hormone production, and radioiodine therapy can shrink the thyroid gland. Surgical removal of part of the thyroid may be necessary in certain cases, such as large goiters or when medications are ineffective.

Hypothyroidism

Hypothyroidism is a clinically abnormal, low level of thyroid hormone in the blood. It is characterized by low metabolic rate, weight gain, cold extremities, constipation, and reduced mental activity and is more common in females. Hypothyroidism is treated by taking daily hormone replacement medication called levothyroxine. Hypothyroidism can be congenital, meaning it is present from birth, and caused by iodine deficiency, or a result of treatment for hyperthyroidism.

Congenital Hypothyroidism

Congenital hypothyroidism is a type of hypothyroidism that is present from birth. Congenital hypothyroidism occurs in about 1 out of every 3,000 to 4,000 newborns, and females are twice as likely to have the condition. Congenital hypothyroidism occurs when a newborn’s thyroid gland doesn’t develop properly or work like it should, resulting in thyroid hormone deficiency. Left untreated, congenital hypothyroidism can cause developmental delays. In fact, congenital hypothyroidism is one of the most common preventable risk factors for intellectual disability. For this reason, health care providers screen newborns shortly after birth to check their thyroid function with a simple blood test. Most babies with congenital hypothyroidism will need lifelong thyroid hormone replacement, but some babies have temporary hypothyroidism that resolves within a few weeks or months.^[4]

Iodine Deficiency

Consumption of dietary iodine is required for the production of thyroid hormones T3 and T4. In many parts of the world, foods don’t provide enough iodine because its content depends on the soil, water, and fertilizers used in farming. Therefore, the primary source of dietary iodine in many countries is in the form of iodized salt. Fortification of salt with iodine to prevent hypothyroidism began in the United States in 1924, and international efforts to iodize salt in the world’s poorest nations continue today. Iodine deficiency is the main cause of preventable intellectual disabilities worldwide. Neonatal hypothyroidism is characterized by cognitive deficits, short stature, and sometimes deafness and muteness in children born to mothers who were iodine-deficient during pregnancy.

Deficiency of dietary iodine can result in the inability to produce T3 and T4, leading to a variety of severe disorders. When T3 and T4 cannot be produced, TSH is secreted in increasing amounts. As a result of this hyperstimulation, the thyroid gland increases its overall size, a condition called a goiter. See Figure 9.17 for an illustration of a goiter.

Figure 9.17. Goiter (https://openstax.org/books/anatomy-and-physiology-2e/pages/17-4-the-thyroid-gland#fig-ch18_04_03)

A: “Goitre” by Almazi is in the Public Domain