What is the Endocrine System?
by Judy Luborsky, Ph.D.
Endocrine autoimmunity deals with autoimmune disorders that affect specific endocrine glands. Hashimoto’s thyroiditis (low thyroid function) and Graves’ disease (overactive thyroid function), are among the most commonly occurring endocrine autoimmune diseases.
What is the Endocrine System?
The endocrine system co-ordinates the body’s physiology and assists in responses to internal or external stimuli. Endocrine cells produce hormones that are secreted into the bloodstream, and act at distant sites throughout the body. Endocrine cells may be grouped into glands (e.g., pituitary, thyroid, pancreas, adrenal, ovary, etc) or reside within other organs (e.g., gastric cells in the stomach). Many endocrine organs are regulated by the hypothalamus, an area in the brain that synthesizes “releasing hormones”. The “releasing hormones” in turn stimulate hormone release from the pituitary gland (situated at the base of the brain). The pituitary gland secretes a variety of hormones that regulate different target endocrine glands. An example of a hormone is estrogen, produced by the ovary. Cyclic secretion of pituitary FSH (follicle stimulating hormone) and LH (luteinizing hormone) regulates the ovary. During each cycle, growing follicles produce estrogen. Estrogen modifies the metabolism of many tissues such as muscle, bone, nerve cells, etc. Thus at menopause, as the function of the ovary declines and estrogen decreases, there are multiple effects on the cardiovascular system, skeletal and nervous system.
The action of hormones on cells is specific. Although hormones circulate through the body, only specific cells respond. The cells that respond have specific receptors that recognize the correct hormone. The receptors perform two functions, they recognize and bind the appropriate hormone, and then translate the recognition event into a cellular signal that alters the cell function.
This article from a recent InFocus Newsletter provides information about Endocrine autoimmunity, the Endocrine System, Graves’ disease, Addison’s disease, Hashimoto’s disease and the risk factors associated with endocrine autoimmunity. Also discussed are the advances made in treating this disorder. InFocus Newsletter has many articles dealing with autoimmunity and autoimmune related diseases.
The general features of endocrine autoimmune disorders are similar to those for all autoimmunity. The disorders develop gradually, and may take several years to show clinically recognizable symptoms. Autoimmunity seems to arise from multiple factors that includes a genetic predisposition combined with specific triggers. The diagnosis of endocrine autoimmunity by a physician involves assessing symptoms and measurement of a relevant hormone to determine if it is within normal levels. Antibody tests to specific cellular components often are performed to confirm autoimmunity. Treatment for endocrine autoimmunity usually consists of hormone replacement or agents to suppress overactive glands.
Family history and genetics: Autoimmunity tends to run in families. However, different family members can have any type of autoimmune disease, not necessarily just endocrine autoimmunity.
Age: Although autoimmune diseases can occur at any age, there is a general tendency for autoimmune disease to increase with age.
Sex: Women are more likely to develop many of the autoimmune disorders, with different probabilities for different disorders. Overall, autoimmune disease is 5 times more common in women. Diabetes (IDDM) is one exception and occurs at similar rates in men and women.
Ethnicity: The incidence of autoimmune diseases is different in different ethnic groups. The specific differences depend on the disease. For example, (IDDM) is higher in Caucasians while non-autoimmune diabetes (NIDDM) is more frequent in African Americans, Hispanic and Native Americans.
Life events: Although the exact mechanisms that trigger an autoimmune disease in susceptible individuals are not well understood, there is an association with some life events. For example, childhood neck irradiation is associated with later development of thyroid disease. Pregnancy may trigger thyroid autoimmunity (postpartum thyroiditis) in susceptible individuals.
Environmental and dietary influence: The incidence of some autoimmune diseases varies by geographic location. Dietary components may be another factor in development of autoimmune diseases. An example of a dietary and environmental factor is the relationship of iodine and thyroid autoimmunity. Iodine was introduced into the diet (iodized salt) in the US to reduce goiter. In western Europe, which has not added iodine to food, there is a lower prevalence of Hashimoto’s disease, but a higher prevalence of nodular goiter and thyroid cancer. Although these observations are intriguing, the exact mechanism of how dietary and environmental factors influence autoimmune diseases remains to be determined.
Specific Disorders: symptoms, diagnosis and treatment
Thyroid: Pituitary TSH (thyroid stimulating hormone) stimulates the thyroid to produce T4 (thyroxine) and T3. Synthesis of thyroid hormones is accompanied by the uptake of iodine from the blood and its incorporation into thyroglobulin, the precursor of T4 and T3. T4 and T3 regulate metabolic functions by co-operating with other factors throughout the body. Low thyroid function (Hashimoto’s disease) is associated with elevated TSH and decreased T3 and T4 compared to normal, and antibodies to thyroid cell components [TPO (thyroid peroxidase) and/or TG (thyroglobulin)]. Hypothyroidism affects about 5 million Americans, and affects women about 10 times more often than men. Symptoms commonly associated with Hashimoto’s are fatigue, depression, weight gain (fluid retention), cold intolerance, hair loss, altered menstrual cycles, infertility, constipation, dry skin, etc. Hormone replacement in the form of thyroxine is usually given for hypothyroidism. Graves’ disease, or overactive thyroid, is associated with decreased pituitary secretion of TSH, but increased T3 and T4. The overstimulation of the thyroid is related to auto-antibodies that bind to the TSH receptor and act like hormone, but with more prolonged effects. Graves’ disease occurs 5-10 times more often in women (or about 2% of women in the United States). Symptoms of Graves’ include nervousness, heart palpitations, weight loss, insomnia, increased sweating, premature graying of hair, muscle weakness, heat intolerance, altered menstrual cycles, and in some cases goiter (enlarged thyroid) and exophthalmos. Exophthalmos is an independent autoimmune disease that results in protrusion of the eyes. Graves’ disease is diagnosed by measurement of TSH, T4 and T3 and TSH receptor antibody. TPO and TG antibodies may also be present. There are several treatments for Graves’, all directed at reducing thyroid function: radioactive iodine to shrink the thyroid or anti-thyroid drugs such as propylthiouracil or methimazole. Graves’ disease may switch to Hashimoto’s over time, since treatments directed at suppressing an over-active thyroid may eventually reduce thyroid function below normal. These individuals may then be treated with thyroxine replacement. Individuals with other autoimmune diseases such as lupus, rheumatoid arthritis, vitiligo, myasthenia gravis, IDDM, etc. are more likely to also develop thyroid autoimmunity.
Adrenal: The adrenal secretes cortisol in response to pituitary ACTH (adrenocorticotropic hormone). Cortisol has many functions, but the most significant are to control immune inflammatory reactions, balance insulin effects, assist in the maintenance of blood pressure and cardiovascular function, and modification of general metabolism. The adrenal also produces aldosterone, which helps maintain blood pressure and acts on the kidney to promote water and salt balance. Addison’s disease is characterized by inadequate levels of cortisol and sometimes aldosterone (adrenal insufficiency or hypocortisolism). Addison’s disease is relatively rare, affects about 1/20,000 individuals, and occurs in men and women at about equal rates. Symptoms may include weight loss, salt craving, fatigue, muscle weakness, hyperpigmentation and low blood pressure. When Addison’s is suspected, it may be confirmed by a poor cortisol (measured in blood or urine) response to ACTH stimulation. Treatment is usually by oral cortisol replacement.
Pancreas: The autoimmune target of IDDM (insulin dependent diabetes mellitus) is the pancreas. IDDM (type 1 diabetes) represents about 5-10% of all diabetes (overall diabetes affects about 8% of women and 8% of men). IDDM often, but not always, develops in children and young adults. Symptoms include increased thirst and urination, blurred vision, constant hunger, weight loss and tiredness. IDDM is diagnosed by measurement of abnormally elevated fasting glucose. Tests for antibody to pancreatic beta cells are not well correlated with disease progression and thus are not standardly used in diagnosis. IDDM is treated with insulin replacement and glucose monitoring.
Ovary: As mentioned above, ovarian production of estrogen is controlled by cyclic secretion of the pituitary hormones, FSH and LH. In turn, estrogen controls the pituitary production of FSH and LH. Thus as the ovary fails, and estrogen declines, FSH increases dramatically. Premature menopause (i.e. ovarian failure before age 40) occurs in about 1% of women. There is no similar disorder documented for the testes. Recent evidence has shown that a majority of premature menopause is autoimmune. FSH becomes elevated, and estrogen declines, similar to natural menopause. The usual treatment is estrogen replacement to protect cardiovascular, skeletal and nervous systems.
Polyglandular: There is a tendency for some disorders to occur together. For descriptive purposes these are termed polyendocrine type I and type II and type III (see “InFocus” vol 4, #5, Dec 1997). Type I tends to begin in early childhood with skin infection (Candidiasis) and is commonly associated with hypoparathyroidism as well as Addison’s and is often associated with gonadal failure. Type II usually involves diabetes or thyroid disease and Addison’s disease and sometimes ovarian failure and non-endocrine autoimmune diseases. Type III involves thyroid autoimmune disease and at least two other autoimmune diseases, but not Addison’s disease.
The current advances related to endocrine autoimmunity involve improved hormone preparations for therapy, and greater awareness leading to earlier detection and treatment. The advances related to autoimmunity in general include understanding the genetics, triggering influences, and the relationship of stress (and the hypothalamic-adrenal axis) to development of autoimmunity.
Judy Luborsky, Ph.D. is an associate professor of Obstetrics and Gynecology and Director, Endocrine Immunology at Rush Medical College (of Rush- Presbyterian-St. Luke’s Medical Center) in Chicago, Illinois
Copyright 1998 American Autoimmune Related Diseases Association, Inc.
Where to find it: http://www.aarda.org/endocrine_art2.html