What are endocrine disorders? |

Process and Effects

Endocrine disorders include disturbances in the production of hormones that result from either insufficient or excessive activity and tissues unable to respond to hormones. To understand endocrine disorders, it is necessary to review briefly the location of the principal endocrine glands, the hormones secreted, and the normal functions of the hormones. The hormones are released into the bloodstream and are carried throughout the body, where they affect target cells or organs that have receptors for the given hormone.

The
pituitary gland, or hypophysis, is sometimes called the master gland because of its widespread influences on many other endocrine glands and the body as a whole. It is located in the midline on the lower part of the brain just above the posterior part of the roof of the mouth. The pituitary has three lobes: the posterior lobe, the intermediate lobe, and the anterior lobe.

The posterior lobe does not synthesize hormones, but it does have nerve fibers coming into it from the hypothalamus of the brain. The ends of these axons release two hormones that are synthesized in the hypothalamus, oxytocin and antidiuretic hormone (ADH). Oxytocin causes the contraction of the smooth muscles of the uterus during childbirth and the contraction of tissues in the mammary glands to release milk during nursing. ADH causes the kidneys to reabsorb water and thereby reduce the volume of urine to normal levels when necessary.

The intermediate lobe of the pituitary secretes melanocyte-stimulating hormone (MSH), a hormone with an uncertain role in humans but known to cause the darkening of melanocytes in animals. Sometimes, the intermediate lobe is considered to be a part of the anterior lobe.

The anterior lobe of the pituitary is under the control of releasing hormones produced by the hypothalamus and carried to the anterior lobe by special blood vessels. In response to these releasing hormones, some stimulatory and some inhibitory, the anterior lobe produces thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and somatotropin or growth hormone (GH). TSH stimulates the thyroid to produce thyroxine, ACTH stimulates the adrenal cortex to produce some of its hormones, FSH stimulates the growth of the cells surrounding eggs in the ovary and causes the ovary to produce estrogen, LH induces ovulation (the release of an egg from the ovary) and stimulates the secretion of progesterone by the ovary, prolactin is essential for milk production and various metabolic functions, and GH is needed for normal growth.

The
pineal gland, or epiphysis, is a neuroendocrine gland attached to the roof of the diencephalon in the brain. It produces
melatonin, which is released into the bloodstream during the night and has important functions related to an individual’s biological clock.

The
thyroid gland is located below the larynx in the front of the throat. It produces the hormones triiodothyronine (T3) and thyroxine (T4), which are essential for maintaining a normal level of metabolism and heat production, as well as enabling normal development of the brain in young children. Specialized cells called C cells are scattered throughout the thyroid, parathyroid, and thymus glands. These cells secrete the hormone calcitonin, which is involved in maintaining the correct blood levels of calcium. The thymus, located under the breast bone or sternum, produces the hormone thymosin that stimulates the immune system. Even the heart is an endocrine gland: It produces atrial natriuretic factor, which stimulates sodium excretion by the kidneys. The
pancreas, located near the stomach and small intestine,
produces digestive enzymes that pass to the duodenum, but also it produces insulin and glucagon in special cells called pancreatic islets. Insulin causes blood sugar (glucose) to be taken up from the blood into the tissues of the body, and glucagon causes stored glycogen to be broken down in the liver and thereby increases blood glucose levels.

The pair of
adrenal glands, located on the kidneys, are made up of two components: first, a cortex that produces glucocorticoids, mineralocorticoids, and sex steroids or androgens; and second, a medulla, or inner part, that secretes adrenaline and noradrenaline. The gonads, testes or ovaries, are located in the pelvic region and produce several hormones, including the estrogen and progesterone that are essential for reproduction in females and the testosterone that is essential for reproduction in males. The kidneys and digestive tract also produce hormones that regulate red blood cell formation and the functioning of the digestive tract, respectively.

Complications and Disorders

A wide variety of endocrine disorders can be treated successfully. In fact, the ability to restore normal endocrine function with replacement therapy has long been one of the techniques for showing the existence of hypothesized hormones.

The posterior pituitary releases both oxytocin and ADH. Chemicals similar to oxytocin are sometimes given to induce contractions in pregnant women so that birth will occur at a predetermined time. The other hormone released from the posterior pituitary, ADH, normally causes the reabsorption of water within the tubules of the kidney. A deficiency of ADH leads to diabetes insipidus, a condition in which many liters of water a day are excreted by the urinary system; the patient must drink huge quantities of water simply to stay alive. A synthetic form of ADH, desmopressin acetate, can be given in the form of a nasal spray that diffuses into the bloodstream and thus restores the reabsorption of water by the kidneys.

The anterior lobe of the pituitary produces six known hormones. The production of these hormones is stimulated and/or inhibited by special releasing hormones secreted by the hypothalamus and carried to the anterior lobe by the hypothalamohypophysial portal system of blood vessels. Thus, the source of some anterior pituitary disorders can reside in the hypothalamus. Tumors of anterior pituitary cells can result in the overproduction of a hormone, or if the tumor is destructive, the underproduction of a hormone. Radiation or surgery can be used to destroy tumors and thereby restore normal pituitary functioning.

Anterior pituitary hormones can be the basis of a variety of disorders. As with other hormones, there may be below-normal production of the hormone (hyposecretion) or overproduction of the hormone (hypersecretion). Because the pituitary hormones are often supportive of hormone secretion by the target organ or tissue, hyposecretion or hypersecretion of the tropic or supportive hormone leads to a similar change in the production of hormones by the target organ or tissue.

For example, hyperthyroidism, or Graves’ disease, can be caused by excessive secretion of TSH by the pituitary, leading to hypersecretion of thyroxine, or by nodules within the thyroid that produce excessive thyroxine. In the diagnosis process, blood levels of both TSH and thyroxine are usually measured to determine the specific cause of the disorder. Similarly,
hypothyroidism can be induced by deficits at several levels. The lack of iodine in the diet can prevent the production of thyroxine, which requires iodide as part of its molecular composition. The production of thyroxine usually has a negative feedback effect on the hypothalamus and pituitary, reducing TSH production. The failure to produce thyroxine causes high blood levels of TSH and an abnormal growth of the thyroid that results in a greatly enlarged thyroid, called a
goiter. The addition of iodine to salt has eliminated the incidence of goiter in developed countries. Even with an adequate supply of iodine in the diet, however, hypothyroidism can still develop from other sources. The usual treatment is to ingest a dose of thyroxine daily.

Other examples of anterior pituitary disorders include those involving changes in GH secretion. Undersecretion of GH can lead to short stature or even a type of dwarfism called pituitary dwarfism, in which an individual has normal body proportions but is smaller than normal. Now it is possible to obtain human GH from bacteria genetically engineered to produce it. Replacement GH can be given during the normal growth years to enhance growth. A tumor sometimes develops in the pituitary cells that produce GH, and this can cause abnormally increased growth or gigantism. If the tumor develops during the adult years, only a few areas of abnormal growth can occur, such as in the facial bones and the bones of the hands and feet. This condition is called acromegaly. Abraham Lincoln is thought to have had abnormal levels of GH that caused gigantism in his youth and then acromegaly in his later years. Acromegaly can be treated by radiation or surgery of the anterior pituitary.

Pineal gland tumors have been associated with precocious puberty, in which children become sexually developed in early childhood. It is thought that
melatonin normally inhibits sexual development during this period. The pineal gland is influenced by changes in the daily photo-period, so that the highest levels of melatonin appear in the blood during the night, especially during the long nights of winter.
Seasonal affective disorder (SAD), a mental depression that occurs during the late fall and winter, has been linked to seasonally high melatonin levels. Daily exposure to bright lights to mimic summer has been used to treat SAD. The pineal gland and melatonin are also being studied with regard to jet lag and disorders associated with shift work. The pineal gland thus seems to be involved in the functioning of the body’s biological clock.

The pancreatic islets, also called the islets of Langerhans, produce insulin and glucagon.
Diabetes mellitus is caused by insufficient insulin production (type 1 or juvenile-onset diabetes) or by the lack of functional insulin receptors on body cells (type 2 diabetes). Type 1 diabetes can be treated with insulin injections, an implanted insulin pump, or even a transplant of fetal pancreatic tissue. Type 2 diabetes is treated with diet and weight loss. Weight loss induces an increase in insulin receptors. Long-term complications resulting from high blood-sugar levels include damage to the kidneys, to the blood vessels in the retina (diabetic retinopathy), to the legs and feet, and to the nerves (diabetic neuropathy).

Changes in the levels of steroid hormones (glucocorticoids, mineralocorticoids, or androgens) secreted by the adrenal cortex can lead to disease. For example, hypersecretion of the glucocorticoid cortisol results in Cushing’s syndrome
and hyposecretion of cortisol results in Addison disease. Similar to the thyroid, the hormones produced by the adrenal cortex participate in a feedback loop mechanism with the pituitary and hypothalamus. Thus, when levels of hormones released by the adrenal glands are low, the pituitary and hypothalamus try to compensate by secreting higher levels of their own hormones. In Addison disease, low levels of adrenal glucocorticoids causes increased ACTH release from the pituitary. Addison disease is characterized by low blood pressure and a poor physiological response to stress: It can be treated by the administration of exogenous glucocorticoids. Extreme cases of adrenal insufficiency can bring about an “adrenal crisis.” In this situation, an immediate injection of glucocorticoid hormone is given to prevent death.

In addition to treating Addison disease, glucocorticoids, particularly cortisone, are used to treat inflammation; however, overuse can lead to adrenal cortex suppression by the negative feedback mechanism. When athletes abuse the androgen sex hormones for the purpose of increasing muscle mass, adrenal suppression can develop along with sterility and damage to the heart. Masculinization is observed in women who have tumors of the androgen-producing cells of the adrenal glands. These women display several changes associated with increased male sex hormones, changes that include beard growth and increased muscle development.

Perspective and Prospects

The early history of endocrinology noted that boys who were castrated failed to undergo the changes associated with puberty. A. A. Berthold in 1849 described the effects of castration in cockerels. The birds failed to develop large combs and wattles and failed to show male behavior. He noted that these effects could be reversed if testes were transplanted back into the cockerels. W. M. Bayliss and E. H. Starling in 1902 first introduced the term “hormone” to refer to secretin. They found that secretin is produced by the small intestine in response to acid in the chyme and that secretin causes the pancreas to release digestive enzymes into the small intestine. Most important, F. G. Banting and G. H. Best in 1922 reported their extraction of insulin from the pancreas of dogs and their success in alleviating diabetes in dogs by means of injections of the insulin. Frederick Sanger in 1953 established the amino acid sequence for insulin and later won a Nobel Prize for this achievement.

Another Nobel Prize was awarded to Earl W. Sutherland, Jr., in 1971, for his demonstration in 1962 of the role of cyclic AMP as a second messenger in the sequence involved in the stimulation of cells by many hormones. Andrew V. Schally and Roger C. L. Guillemin in 1977 received a Nobel Prize for their work in isolating and determining the structures of hypothalamic regulatory peptides.

More recent achievements in endocrinological research have centered on the identification of receptors that bind with the hormone when the hormone stimulates a cell and on the genetic engineering of bacteria to produce hormones such as human growth hormone. The use of fetal tissues in endocrinological research and therapy—the host usually does not reject fetal implants—continues to be an area for future research.

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