Why is the thyroid so prone to autoimmune disease?

The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients.

Circulating nucleic acids in type 1 diabetes may modulate the thymocyte turnover rate.

The autoimmunity of type 1 diabetes is associated with T-cell hyperactivity. Current study was designed to examine the effect of circulating ribonucleic acids (RNAs), isolated from type 1 diabetic patients on proliferative, apoptotic and inflammatory potential of rat thymocytes. Rat thymocytes were assayed for proliferating nuclear cell antigen (PCNA), Bcl-2, Bax and NF-κB level, using the flow cytometric and fluorometric assays. Cells were allocated into groups, treated with RNAs purified from plasma of juvenile diabetics, adult type 1 diabetic patients, control healthy children, healthy adult persons, nucleic acids and polynucleotide standards (RNA, polyC, PolyA, PolyIC, and CpG). The upregulation of PCNA and Bcl-2 protein and downregulation of Bax protein and NF-κB was shown when the thymocytes where incubated with RNA purified from plasma of juvenile type 1 diabetic patients. The dysregulation of inflammatory cascade and central tolerance may be a defect in autoimmune diseases related to innate immunity leading to corresponding alteration in adaptive immune response.

Hyperprolactinemia: different clinical expression in childhood.

BACKGROUND: Hyperprolactinemia is the most common disturbance in pituitary gland secretion. Functional diversity of prolactin action is responsible for different initial clinical expressions of hyperprolactinemia. PATIENTS AND METHODS: We investigated causes of hyperprolactinemia in 11 children and adolescents (6 females and 5 males), aged from 1.5 to 17.5 years. Children with primary hypothyroidism, iatrogenic hyperprolactinemia and adolescents with polycystic ovaries were excluded. RESULTS: Four patients had short stature or growth deceleration, the same number were clinically obese, 2 adolescent girls had secondary amenorrhea, 1 girl had premature thelarche and gynecomastia, and hypogonadism was the indication for the endocrinologic examination of two adolescent boys. Delayed pubertal development was present in both sexes. Hyperprolactinemia was also found in the youngest girl with multiple ovarian cysts. A very high prolactin (PRL) level was documented in the PRL profile of all patients (mean 2,553.00 +/- 1,020.97 mU/l). MRI of the pituitary was indicated and revealed 4 microprolactinomas, one congenital hypophyseal cyst and one tumor of the hypothalamus. Dopamine agonist treatment was efficacious in almost all the patients. CONCLUSION: Hyperprolactinemic children expressed a wide variety of initial clinical presentations. The most common were growth and puberty disorders and obesity. PRL determination should be included in investigation protocols of obese and short stature children.

Glucocorticoids and oxidative stress.

Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.