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About 18% of adults in the United States have anxiety disorders, which include posttraumatic stress disorder, obsessive-compulsive disorder, and various phobias. About 7% of adults had at least one major depressive episode in the past year. Bipolar disorder affects about 2.5% of adults, and just over 1% of adults have schizophrenia. Serious mental-illness costs Americans more than $193 million in lost earnings annually. Thyroid dysfunction may be related to a variety of mental disorders. Depression is an example of a mental disorder that actually may be one of the first symptoms of thyroid dysfunction. Patients may be mislabeled as having a major mental disorder even though hypothyroidism or hyperthyroidism is causing their symptoms. When thyroid function is not normal, a variety of mental symptoms and conditions may develop. These include anxiety, bipolar disorder, depression, irritability, aggression, obsessive-compulsive disorder, panic attacks, phobia, and even schizophrenia. As many as 15% of patients treated for depression have elements of mild or overt hypothyroidism. Conditions commonly linked to mental disorders include cretinism, myxedema, and Graves’ disease with stress.

Obesity goes hand in hand with insulin resistance, which is a fundamental aspect of type 2 diabetes and is linked to hypertension, hyperlipidemia, atherosclerosis, polycystic ovarian disease, and metabolic syndrome. The human body maintains blood glucose within an extremely narrow range, utilizing the hormones insulin and glucagon, both of which are secreted by the pancreas. The production of these endocrine hormones ultimately determines if a person has disorders such as diabetes or hypoglycemia. Both hormones are secreted in response to blood glucose levels, but in opposing ways. Many mechanisms by which obesity causes systemic insulin resistance are still unknown. However, clinicians now understand the adipo-insulin axis that involves the adipocyte hormone called leptin. Its actions include the regulation of food intake and energy expenditure. Leptin also controls the insulin–glucose axis, peripheral glucose, and insulin responsiveness. This chapter focuses on the disorders of insulin regulation known as type 2 diabetes and metabolic syndrome.

The global impact of thyroid disorders, including hypothyroidism, hyperthyroidism, Graves’ disease, and thyroid cancer, is increasing by about 3.3% each year. The key determinant of thyroid disease risks is iodine nutrition. However, other factors that influence the epidemiology of thyroid disorders include aging, smoking, genetics, ethnicities, endocrine disruptors, and the use of various treatments. Hypothyroidism and hyperthyroidism, in all their forms, affect every population throughout the world. However, the prevalence and incidence of thyroid dysfunction is always changing because of differences in diagnostic thresholds, sensitivity of various tests, the populations being selected for study, and changes in the availability of dietary iodine. The burden of thyroid disorders reaches up to billions of dollars, globally, every year.

The thyroid gland is the largest purely endocrine gland in the body. It is located in the anterior neck and has a butterfly-like shape. It curves across the anterior surface of the trachea and is slightly inferior to the larynx. This gland regulates basal body metabolism via the various hormones that it releases. The thyroid is also involved in gluconeogenesis, protein synthesis, glycogenolysis, lipogenesis, and thermogenesis. The parathyroid glands are embedded in the posterior surface of the lateral lobes of the thyroid gland and aid in calcium homeostasis.

Many factors have been implicated in the pathogenesis of migraine headache, including activation of the trigeminovascular system, dysfunction of: cerebral blood vessels, circulating vasoactive substances, mitochondrial energy metabolism, brain oxygenation and metabolism, platelet disorder, alterations in serotonin levels, low levels of brain tissue magnesium, altered transport of ions across the cell membrane, and inheritance and dysfunction of the brainstem periaqueductal gray matter. The headache phase of migraine is associated with cerebral vasodilation and inflammation, presumably mediated by the release of vasoactive substances and neuropeptides including CGRP (calcitonin gene-related peptide). Increased serum CGRP levels have been detected during migraine and cluster headache. One strategy to treat migraine is to inhibit the release of neuropeptides or to block their receptors. This article briefly reviews some experimental and clinical investigations focused on neuropeptide involvement in migraine. Drug Dev Res 68:294–314, 2007. © 2007 Wiley-Liss, Inc.

In mouse models of later onset forms of human hereditary demyelinating neuropathies, the immune system plays a crucial pathogenic role. Here, we investigated the influence of immune cells on early onset dysmyelination in mice homozygously deficient of the myelin component P0. In peripheral nerves of P0 −/− mice, CD8+ T-lymphocytes increased with age. Macrophages peaked at 3 months followed by a substantial decline. They were mainly of hematogenous origin. To evaluate the functional role of immune cells, we cross-bred P0 −/− mutants with RAG-1-deficient mice. At 3 months, the number of endoneurial macrophages did not differ from the macrophage number of immunocompetent myelin mutants, but the later decline of macrophages was not observed. Quantitative electron microscopy revealed that in plantar nerves of 6-month-old double mutants, significantly more axons had degenerated than in immunocompetent littermates. These data suggest a neuroprotective net effect of T-lymphocytes on axon survival in inherited, early onset dysmyelination.