Major endocrine glands. ( Male left, female on the right.) 1. Pineal gland 2. Pituitary gland

Physiologic anatomical peculiarities of endocrine system in children. Methodics of endocrine glands investigation. Semiotics of hypo- and hyperfunction of some endocrine glands and diseases of the endocrine system.By Nykytyuk S  

Major endocrine glands. (Male left, female on the right.)

1. Pineal gland 2. Pituitary gland 3. Thyroid gland 4. Thymus 5. Adrenal gland 6. Pancreas 7. Ovary 8. Testis

The endocrine system provides a chemical connection from the hypothalamus of the brain to all the organs that control body metabolism, growth and development, and reproduction.

There are two types of hormones secreted in the endocrine system: (1) steroidal and (2) nonsteroidal, or protein based, hormones. The endocrine system regulates its hormones through negative feedback control. Increases in hormone activity decreases the production of that hormone. The immune system and other factors contribute as control factors also, maintaining constant levels of hormones.

Endocrine glands and the hormones secreted Hypothalamus produces 1. Thyrotropin-releasing hormone

(TRH) 2. Gonadotropin-releasing hormone

(GnRH) 3. Growth hormone-releasing

hormone (GHRH) 4. Corticotropin-releasing hormone

(CRH) 5. Somatostatin (SS; also GHIH,

growth factor-inhibiting hormone) 6. Dopamine (DA)

Pineal Gland produces 1. Melatonin

Endocrine glands and the hormones secreted Pituitary gland (hypophysis)

produces Anterior pituitary lobe

(adenohypophysis) Growth hormone (GH) Prolactin (PRL) Adrenocorticotropic hormone (ACTH, corticotropin) Thyroid-stimulating hormone (TSH, thyrotropin) Follicle-stimulating hormone (FSH, a gonadotropin) Luteinizing hormone (LH, a gonadotropin)

Posterior pituitary lobe (neurohypophysis)

1. Oxytocin (ocytocin) 2. Arginine vasopressin (AVP; also

ADH, antidiuretic hormone) 3. Lipotropin

Endocrine glands and the hormones secreted Thyroid gland produces

Triiodothyronine (T3), the potent form of thyroid hormone Thyroxine (T4), a less active form of thyroid hormone Calcitonin

Parathyroid gland produces Parathyroid hormone (PTH)

Heart produces Atrial-natriuretic peptide (ANP)

Stomach and intestines produce

Cholecystokinin (CCK) Gastrin Ghrelin Neuropeptide Y (NPY) Secretin Somatostatin

Endocrine glands and the hormones secreted Liver produces

Insulin-like growth factor (IGF) Angiotensinogen Thrombopoietin

Islets of Langerhans in the pancreas produce

Insulin Glucagon Somatostatin

Adrenal glands produce Adrenal cortex

Glucocorticoids (chiefly cortisol) Mineralocorticoids (chiefly aldosterone) Androgens (including DHEA and testosterone)

Adrenal medulla Adrenaline (epinephrine) Noradrenaline (norepinephrine)

Testosterone

Endocrine glands and the hormones secreted Kidney produces

Renin Erythropoietin (EPO) Calcitriol (the active form of vitamin D3)

Skin produces Vitamin D3 (calciferol)

Adipose tissue Leptin Estrogens (mainly estrone

Endocrine glands and the hormones secreted In males only Testes

Androgens (chiefly testosterone)

In females only Ovarian follicle

Estrogens (mainly estradiol) Corpus luteum

Progesterone Estrogens (mainly estradiol)

Placenta (when pregnant) Progesterone Estrogens (mainly estriol) Human chorionic gonadotropin (HCG) Human placental lactogen (HPL)

Pineal gland

The pineal gland is a reddish-gray body about the size of a pea (8 mm in humans), located just rostro-dorsal to the superior colliculus and behind and beneath the stria medullaris, between the laterally positioned thalamic bodies. It is part of the epithalamus.

The pineal gland is large in children, but shrinks at puberty. It appears to play a major role in sexual development, hibernation in animals, metabolism, and seasonal breeding. The abundant melatonin levels in children is believed to inhibit sexual development, and pineal tumors have been linked with precocious puberty. When puberty arrives, melatonin production is reduced. Calcification of the pineal gland is typical in adults.

Pituitary gland The pituitary gland, or

hypophysis, is an endocrine gland about the size of a pea that sits in a small, bony cavity (sella turcica) at the base of the brain.

The pituitary gland secretes hormones regulating homeostasis, including trophic hormones that stimulate other endocrine glands. It is functionally connected to the hypothalamus by the median eminence.

Posterior pituitary (neurohypophysis)

The posterior lobe is connected to a part of the brain called the hypothalamus via the infundibulum (or stalk), giving rise to the tuberoinfundibular pathway. Hormones are made in nerve cell bodies positioned in the hypothalamus, and these hormones are then transported down the nerve cell's axons to the posterior pituitary. Hypothalamic neurons fire such hormones, releasing them into the capillaries of the pituitary gland.

The hormones secreted by the posterior pituitary are Oxytocin comes from the paraventricular nucleus in the

Hypothalamus Antidiuretic hormone (ADH - also known as vasopressin), comes

from the supraoptic nucleus in the Hypothalamus

Anterior pituitary (Adenohypophysis)

The anterior pituitary produces and secretes:

1. growth hormone 2. prolactin 3. follicle-stimulating hormone 4. luteinizing hormone 5. thyroid-stimulating hormone 6. adrenocorticotropic hormone endorphins and other hormones

It does this in response to releasing hormones produced by the hypothalamus. These travel to the anterior lobe by way of a special capillary system, called the hypothalamic-hypophyseal portal system. These hypothalamic signalling hormones include:

TRH (thyrotropin-releasing hormone) CRH (corticotropin-releasing hormone) DA (dopamine, "prolactin inhibiting

factor"/PIF) GnRH (gonadotropin-releasing

hormone) GHRH (growth hormone releasing

hormone)

Intermediate lobe

In adult humans it is just a thin layer of cells between the anterior and posterior pituitary, nearly indistinguishable from the anterior lobe. The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary.

FunctionsThe pituitary gland helps control the following body processes:1. Growth 2. Blood pressure 3. Some aspects of pregnancy and childbirth 4. Breast milk production 5. Sex organ functions in both women and men 6. Thyroid gland function 7. The conversion of food into energy (metabolism) 8. Water and osmolarity regulation in the body

Adrenocorticotropic hormone

ACTH acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells. ACTH stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids, mainly glucocorticoids but also mineralcorticoids and sex steroids (androgens). Together with ACTH the hormones lipotropin, melanocyte-stimulating hormone (MSH), β-endorphin and met-enkephalin are also released. ACTH is also related to the circadian rhythm in many organisms.

Growth hormone Growth hormone (GH

or somatotropin) is a polypeptide hormone synthesised and secreted by the anterior pituitary gland which stimulates growth and cell reproduction in humans

Functions of GH

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other protein hormones GH acts by interacting with a specific receptor on the surface of cells.

Height growth in childhood is the best known effect of GH action, and appears to be stimulated by at least two mechanisms.

1. GH directly stimulates division and multiplication of chondrocytes of cartilage. These are the primary cells in the growing ends (epiphyses) of children's long bones (arms, legs, digits).

2. GH also stimulates production of insulin-like growth factor 1 (IGF1, formerly known as somatomedin C), a hormone homologous to proinsulin.

Growth hormone excess: (acromegaly and pituitary gigantism) The most common disease of GH excess is a pituitary tumor

comprised of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. Prolonged GH excess thickens the bones of the jaw, fingers and toes. Resulting heaviness of the jaw and increased thickness of digits is referred to as acromegaly. GH-secreting tumors are typically recognized in the 5th decade of life. It is extremely rare for such a tumor to occur in childhood, but when it does the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism.

Growth hormone deficiency (GHD) Deficiency of GH produces significantly different

problems at various ages. In children, growth failure and short stature are the major manifestations of GH deficiency. In adults the effects of deficiency are more subtle, and may include deficiencies of strength, energy, and bone mass, as well as increased cardiovascular risk.

Other GH uses and treatment indications

Many other conditions besides GH deficiency cause poor growth, but growth benefits (height gains) are often poorer than when GH deficiency is treated. Examples of other causes of shortness often treated with growth hormone are Turner syndrome, chronic renal failure, Prader-Willi syndrome, intrauterine growth retardation, and severe idiopathic short stature. Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above physiologic.

Thyroid-stimulating hormone Thyroid-stimulating hormone (also known as TSH or

thyrotropin) is a hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland. TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3). TSH production is controlled by a Thyrotropin Releasing Hormone, (TRH), which is manufactured in the hypothalamus and transported to the pituitary gland, where it increases TSH production and release. Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release.

Primarily Abnormal Pituitary Function Higher than normal levels of TSH combined with high

levels of thyroid hormone (T3 and T4) may indicate dysfunction of the hypothalamus and pituitary gland. In these case, a high TSH is often produced by a benign tumor of the pituitary (adenoma). Conversely, low levels of TSH, while blood levels of T3 and T4 are also low, indicates abnormally low function of the pituitary, known as hypopituitarism.

Primarily Abnormal Thyroid function On the other hand, due to the negative feedback

described above, abnormally high levels of Thyroid hormone, due to overproduction in the thyroid, results in low TSH levels. This occurs in diseases such as hyperthyroidism or Grave's disease. Conversely, an underproduction of T3 and T4 caused by diseases such as congenital hypothyroidism (cretinism), hypothyroidism or thyroid hormone resistance, gives rise to an increase in the measured TSH.

Clearly both TSH and T3 and T4 should be measured to ascertain where a specific thyroid disfunction is caused by primary pituitary or by a primary thyroid disease. If both are up (or down) then the problem is probably in the pituitary. If the one component (TSH) is up, and the other (T3 and T4) is down, then the disease is probably in the thyroid itself. The same holds for a low TSH, high T3 and T4 finding.

Prolactin

Prolactin is a peptide hormone synthesised and secreted by lactotrope cells in the adenohypophysis (anterior pituitary gland). It is also produced in other tissues including the breast and the decidua. Pituitary prolactin secretion is regulated by neuroendocrine neurons in the hypothalamus, most importantly by neurosecretory dopamine neurons of the arcuate nucleus, which inhibit prolactin secretion.

Prolactin has many effects, the most important of which is to stimulate the mammary glands to produce milk (lactation).

Increased serum concentrations of prolactin during pregnancy cause enlargement of the mammary glands of the breasts and increases the production of milk. However, the high levels of progesterone during pregnancy act directly on the breasts to stop ejection of milk. It is only when the levels of this hormone fall after childbirth that milk ejection is possible.

Follicle-stimulating hormone

Follicle stimulating hormone (FSH) is a hormone synthesised and secreted by gonadotropes in the anterior pituitary gland. In the ovary FSH stimulates the growth of immature Graafian follicles to maturation. As the follicle grows it releases inhibin, which shuts off the FSH production. In men, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes and is critical for spermatogenesis. FSH and LH act synergistically in reproduction.

High FSH levels

High FSH levels are indicative of situations where the normal restricting feedback from the gonad is absent, leading to an unrestriced pituitary FSH production. While this is typical in the menopause, it is abnormal in the reproductive years. There it may be a sign of:

1. Premature menopause 2. Gonadal dysgenesis, Turner syndrome 3. Castration 4. Swyer syndrome 5. Certain forms of CAH 6. Testicular failure

Deficient FSH activity

Diminished secretion of FSH can result in failure of gonadal function (hypogonadism). This condition is typically manifest in males as failure in production of normal numbers of sperm. In females, cessation of reproductive cycles is commonly observed. Conditions with very low FSH secretions are:

1. Kallmann syndrome 2. Hypothalamic suppression 3. Hypopituitarism 4. Hyperprolactinemia 5. Gonadotropin deficiency 6. Gonadal suppression therapy

GnRH antagonist GnRH agonist (downregulation)

Luteinizing hormone

Luteinizing hormone (LH) is a hormone synthesized and secreted by gonadotropes in the anterior lobe of the pituitary gland. In concert with the other pituitary gonadotropin follicle stimulating hormone (FSH) it is necessary for proper reproductive function. In the female, an acute rise of LH – the LH surge – triggers ovulation. In the male, where LH had also been called Interstitial Cell Stimulating Hormone (ICSH), it stimulates Leydig cell production of testosterone.

LH levels are normally low during childhood and, in women, high after menopause. During the reproductive years typical levels are seen between 5-20 mIU/ml. Physiologic high LH levels are seen during the LH surge (v.s.), typically they last 48 hours.

Disease States

Relative elevations In children with precocious puberty of

pituitary or central origin, LH and FSH levels may be in the reproductive range and not at the low levels typically for their age.

High LH levels Persistently high LH levels are

indicative of situations where the normal restricting feedback from the gonad is absent, leading to an unrestricted pituitary production of both, LH and FSH. While this is typical in the menopause, it is abnormal in the reproductive years. There it may be a sign of:

1. Premature menopause 2. Gonadal dysgenesis, Turner syndrome 3. Castration 4. Swyer syndrome 5. Certain forms of CAH 6. Testicular failure

Deficient LH activity Diminished secretion of LH can result in failure of gonadal

function (hypogonadism). This condition is typically manifest in males as failure in production of normal numbers of sperm. In females, amenorrhea is commonly observed. Conditions with very low FSH secretions are:

1. Kallmann syndrome 2. Hypothalamic suppression 3. Hypopituitarism 4. Eating disorder 5. Hyperprolactinemia 6. Gonadotropin deficiency

Thymus

The thymus plays an important role in the development of the immune system in early life, and its cells form a part of the body's normal immune system. It is most active before puberty.

In the two thymic lobes, lymphocyte precursors mature into T cells (where T stands for “thymus”). The thymus is critically required for the production of the vast majority of T cells. Once made, T cells leave the thymus and patrol the body.

They protect against foreign invaders by making immune responses, that are initiated via T cell receptors expressed by these T cells. Each T cell has a different T cell receptor, allowing the immune system to recognize many distinct foreign invaders by generating many T cells.

The thymus of a full-time fetus, exposed in situ.

Immature thymocytes undergo a process of selection, based on the specificity of their T cell receptors. This involves selection of T cells that are functional (positive selection), and elimination of T cells that are autoreactive (negative selection).

Cells that pass both levels of selection are released into the bloodstream to perform vital immune functions.

Thymus continues to grow until the time of puberty and then begins to atrophy.

The thymus is most active before puberty, after which it shrinks in size and activity in most individuals and is replaced with fat (a phenomenon known as "involution").

1. birth-about 15 grams;2. Puberty-about 35 grams3. twenty-five years-25 grams4. sixty years-less than 15 grams5. seventy years-about 6 grams

Pancreas

The pancreas is an organ in the digestive and endocrine system that serves two major functions: exocrine (producing pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin).

1: Head of pancreas2: Uncinate process of pancreas3: Pancreatic notch4: Body of pancreas5: Anterior surface of pancreas6: Inferior surface of pancreas7: Superior margin of pancreas8: Anterior margin of pancreas9: Inferior margin of pancreas10: Omental tuber11: Tail of pancreas12: Duodenum

There are four main types of cells in the islets of Langerhans. beta cells-Insulin and

Amylin alpha cells-Glucagon Deltacells-Somatostatin

PP cells-Pancreatic polypeptide

50-80% lower blood sugar

15-20%raise blood sugar 3-10%inhibit endocrine

pancreas 1%inhibit exocrine

pancreas

Insulin

The structure of insulin. The left-hand side is a space-filling model of the insulin monomer, believed to be biologically active. Carbon is green, hydrogen white, oxygen red, and nitrogen blue. On the right-hand side is a cartoon of the hexamer, believed to be the stored form. A monomer unit is highlighted with the A chain in blue and the B chain in cyan. Yellow denotes disulfide bonds, and magenta spheres are zinc ions.

Computer-generated image of insulin hexamers highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues involved in zinc binding.

Insulin (from Latin insula, "island", as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. Apart from being the primary effector in carbohydrate homeostasis, it has effects on fat metabolism and it can change the liver's ability to release fat stores. Insulin's concentration has extremely widespread effects throughout the body.

Nobel Prizes

Macleod and Banting were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Banting, insulted that Best was not mentioned, shared his prize with Best, and MacLeod immediately shared his with Collip. The patent for insulin was sold to the University of Toronto for one dollar.

The exact sequence of amino acids comprising the insulin molecule, the so-called primary structure, was determined by British molecular biologist Frederick Sanger. It was the first protein to have its structure be completely determined. He was awarded the Nobel Prize in Chemistry in 1958.

In 1967, after decades of work, Dorothy Crowfoot Hodgkin determined the spatial conformation of the molecule, by means of X-ray diffraction studies. She had been awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography.

Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin.

Glucose test

Diabetes mellitus

Diabetes mellitus is a metabolic disorder, specifically affecting carbohydrate metabolism. It is a disease characterized by persistent hyperglycemia (high glucose blood sugar). It is a metabolic disease that requires medical diagnosis, treatment and lifestyle changes. The World Health Organization recognizes three main forms of diabetes: type 1, type 2 and gestational diabetes (or type 3, occurring during pregnancy)[1], although these three "types" of diabetes are more accurately considered patterns of pancreatic failure rather than single diseases.

Type 1 diabetes mellitus

Type 1 diabetes mellitus - formerly known as insulin-dependent diabetes (IDDM), childhood diabetes, or juvenile-onset diabetes - is characterized by loss of the insulin-producing beta cells of the islets of Langerhans of the pancreas leading to a deficiency of insulin. It should be noted that there is no known preventative measure which can be taken to avoid type 1 diabetes.

In type 1 diabetes, the beta cells of the pancreas produce little or no insulin, the hormone that allows glucose to enter body cells. Once glucose enters a cell, it is used as fuel.

Without adequate insulin, glucose builds up in the bloodstream instead of going into the cells. The body is unable to use this glucose for energy despite high levels in the bloodstream, leading to increased hunger.

In addition, the high levels of glucose in the blood causes the patient to urinate more, which in turn causes excessive thirst. Within 5 to 10 years after diagnosis, the insulin-producing beta cells of the pancreas are completely destroyed, and no more insulin is produced.

Symptoms 1. Increased thirst 2. Increased urination 3. Weight loss despite increased appetite 4. Nausea 5. Vomiting 6. Abdominal pain Fatigue Absence of menstruation

Signs and tests The following tests can be used to diagnose diabetes:

1. Urinalysis shows glucose and ketone bodies in the urine, but a blood test is required for diagnosis

2. Fasting blood glucose is 126 mg/dL or higher 3. Random (nonfasting) blood glucose exceeds 200 mg/dL (this

must be confirmed with a fasting test) 4. Insulin test (low or undetectable level of insulin) 5. C-peptide test (low or undetectable level of the protein C-

peptide, a by-product of insulin production)

The long-term goals of treatment are to prolong life, reduce symptoms, and prevent diabetes-related complications such as blindness, kidney failure, and amputation of limbs.

These goals are accomplished through education, insulin use, meal planning and weight control, exercise, foot care, and careful self-testing of blood glucose levels.

Ovary

Ovaries are egg-producing reproductive organs found in female organisms. They are part of the vertebrate female reproductive system. Ovaries in females are homologous to testes in males. The term gonads refers to the ovaries in females and testes in males.

Estrogen and progesterone are the most important in mammals. These hormones serve many functions:1. They induce and maintain the physical changes of puberty and

the secondary sex characteristics. 2. They support maturation of the uterine endometrium in

preparation of implantation of a fertilized egg. 3. They provide signals to the hypothalamus and pituitary that help

maintain the menstrual cycle. 4. Estrogen plays an important role in maintaining subcutaneous

fat, bone strength, and some aspects of brain function.

Testicle

The testicles, or testes (singular testis), are the male generative glands. Male mammals have two testicles, which are often contained within an extension of the abdomen called the scrotum.

Like the ovaries (to which they are homologous), testicles are components of both the reproductive system (being gonads) and the endocrine system (being endocrine glands). The respective functions of the testicles are:

1. producing sperm (spermatozoa) 2. producing male sex hormones, of which testosterone is the

best-known Both functions of the testicle, sperm-forming and endocrine, are

under control of gonadotropic hormones produced by the anterior pituitary:

1. luteinizing hormone (LH) 2. follicle-stimulating hormone (FSH)

Cryptorchidism Cryptorchidism is a medical term referring to absence

from the scrotum of one or both testes. This usually represents failure of the testis to move, to "descend," during fetal development from an abdominal position, through the inguinal canal, into the ipsilateral scrotum. About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis, making cryptorchidism the most common birth defect of male genitalia. However, most testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall.

A testis absent from the normal scrotal position can be:1. found anywhere along the "path of descent" from high in the posterior

(retroperitoneal) abdomen, just below the kidney, to the inguinal ring; 2. found in the inguinal canal; 3. ectopic, that is, found to have "wandered" from that path, usually outside the

inguinal canal and sometimes even under the skin of the thigh, the perineum, the opposite scrotum, and femoral canal;

4. found to be undeveloped (hypoplastic) or severely abnormal (dysgenetic); 5. found to have vanished (also see Anorchia). About two thirds of cases without other abnormalities are unilateral; 1/3

involve both testes. In 90% of cases an undescended testis can be palpated (felt) in the inguinal canal; in a minority the testis or testes are in the abdomen or nonexistent (truly "hidden").

Thyroid

The thyroid (from the Greek word for "shield", after its shape) is one of the larger endocrine glands in the body. It is a double-lobed structure located in the neck and produces hormones, principally thyroxine (T4) and triiodothyronine (T3), that regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. The hormone calcitonin is also produced and controls calcium blood levels. Iodine is necessary for the production of both hormones. Hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid) are the most common problems of the thyroid gland.

Physiologic effects of thyroid hormone Regulates metabolic rate of all cells; protein, fat, and

carbohydrate catabolism; and nitrogen excretion Regulates body heat production and heat-dissipating

mechanisms Regulates protein synthesis and catabolism, ammo acid

incorporation into protein, and transcription of messenger RNA

Increases gluconeogenesis and peripheral utilization of glucose

Physiologic effects of thyroid hormone Maintains appetite and secretion of gastrointestinal

substances Maintains calcium mobilization Stimulates cholesterol synthesis and hepatic

mechanisms that re move cholesterol from the circulation; stimulates lipid turn over and free fatty acid release

Regulates hepatic conversion of carotene to vitamin A Maintains growth hormone secretion, skeletal

maturation, and tissue differentiation

Physiologic effects of thyroid hormone Is necessary for muscle tone and vigor and normal skin

constituents Maintains cardiac rate, force, and output Affects respiratory rate, depth of oxygen utilization, and

carbon dioxide formation Affects central nervous system development and

cerebration during first 2 to 3 years Affects milk production during lactation and menstrual

cycle fertility Maintains sensitivity to insulin and insulin degradation

Physiologic effects of thyroid hormone Affects red cell production Affects cortisol secretion, probably caused by

direct effect on adrenal glands and by increasing ACTH secretion

T3 and T4 production and action

Thyroxine is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (TG). Iodine, captured with the "iodine trap" by the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO) and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on TG, and on free tyrosine. Upon stimulation by TSH (see below), the follicular cells reabsorb TG and proteolytically cleave the iodinated tyrosines from TG, forming T4 and T3 (in T3, one iodine is absent compared to T4), and releasing them into the blood. Deiodinase enzymes convert T4 to T3. Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3.

Cells of the brain are a major target for thyroid hormone. Thyroid hormones play a particularly crucial role in brain development during pregnancy]. A transport protein (OATP1C1) has been identified that seems to be important for T4 transport across the blood brain barrier. A second transport protein (MCT8) is important for T3 transport across brain cell membranes.

In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity. As with the steroid hormones and retinoic acid, thyroid hormones cross the cell membrane and bind to intracellular receptors (α1, α2, β1 and β2), which act alone, in pairs or together with the retinoid X-receptor as transcription factors to modulate DNA transcription.

Calcitonin

An additional hormone produced by the thyroid contributes to the regulation of blood calcium levels. Parafollicular cells produce calcitonin in response to hypercalcemia. Calcitonin stimulates movement of calcium into bone, in opposition to the effects of parathyroid hormone. However calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid, but not the parathyroids.

The significance of iodine

In areas of the world where iodine (essential for the production of thyroxine, which contains four iodine atoms) is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre.

In humans, children born with thyroid hormone deficiency will have physical growth and development problems, and brain development can also be severely impaired, in the condition referred to as cretinism. Newborn children in many developed countries are now routinely tested for thyroid hormone deficiency as part of newborn screening by analysis of a drop of blood. Children with thyroid hormone deficiency are treated by supplementation with synthetic thyroxine, which enables them to grow and develop normally.

Endemic cretinizm

Diseases of the thyroid glandHyper- and hypofunction (affects about 2% of the population):

Hypothyroidism (underactivity)

Hashimoto's thyroiditis / thyroiditis Ord's thyroiditis Postoperative hypothyroidism Postpartum thyroiditis Silent thyroiditis Acute thyroiditis Iatrogenic hypothyroidism

Hyperthyroidism (overactivity)

Thyroid storm Graves-Basedow disease Toxic thyroid nodule Toxic nodular struma (Plummer's disease) Hashitoxicosis Iatrogenic hyperthyroidism De Quervain thyroiditis (inflammation starting as hyperthyroidism, can end as hypothyroidism)

Hypotyrosis congenital

Hypotyrosis congenital

Thyroid hormone deficiency. Thyroid hormone deficiency is always associated with

poor growth and delayed bone maturation. Hypothyroidism that is present from birth causes severe stunting of linear growth, which is evident early in life. When the deficiency begins before the skeletal age of 9 or 10 years, the child maintains infantile proportions with short legs compared to the length of the spine; he tends to be pale, sluggish, inactive, and obese; and intellectual achievement at school deteriorates.

Acquired hypothyroidism varies with the degree and duration of the deficiency, but skeletal age is delayed if the condition has been present more than 12 months .

Parathyroid Glands 1. Parathyroid glands are embedded in the thyroid

glands. 2. Parathyroid hormone (PTH) increases blood calcium

levels. -PTH stimulates osteoclasts and inhibts osteoblasts. -PTH promotes calcium reabsorption by the kidneys and

the formation of active vitamin D by the kidneys.Active vitamin D increases calcium absorption by the

intestine. 3. A decrease in blood calcium levels stimulates PTH

secretion.

Growth hormone deficiency. Growth hormone deficiency, associated with

hypopituitarism, inhibits somatic growth in all cells of the body. Although children with hypopituitarism are normal at birth, they show growth patterns that progressively deviate from the normal growth rate, of ten beginning in infancy. The chief complaint in most instances is short stature. Of those who seek help, boys out number girls three to one. Skeletal proportions are normal for the age, but these children appear younger than their chronologic age, tend to be

relatively inactive, and are less apt to participate in aggressive, sporting-type activities. Bone age is nearly always retarded but is closely related to height age; the degree of retardation depends on the duration and extent of the hormonal deficiency. Diminished function of recent onset may show little retardation in skeletal age, whereas children with a long-standing deficiency may evidence a skeletal age only 40% to 50% of their chronologic age.

In children with a partial growth hormone deficiency, the growth retardation is less marked than in children with a growth hormone deficiency.

Growth hormone deficiency may be attributed to an idiopathic or organic etiology. The extent of idiopathic growth hormone deficiency may be complete or partial, but the cause is unknown. It is frequently associated with other pituitary hormone deficiences, such as deficiences of thyroid-stimulating hormone and ACTH;

Thus it is theorized that the disorder is probably secondary to hypothalamic deficiency. It has also been observed that there is a higher than average frequency in some families, which indicates a possible genetic etiology in a number of instances.

Sex hormone deficiency. Sex hormone deficiency that causes delayed puberty

can occur as a result either of pituitary dysfunction or of hypogonadism. A hypofunctioning pituitary gland, as briefly discussed in the preceding segment on endocrine dysfunction, can produce a deficiency in either the gonadotropic hormones, which retards maturation of the gonads, or growth hormone, which will diminish total growth during childhood.

Cortisol excess. Cortisol excess as a result of organic causes or of

prolonged cortisone therapy also has an adverse effect on growth in children. This effect is produced by direct action on growing cartilage, interference with production of growth hormone, or interference with the response to or production of somatomedin. Because of the growth-suppressing effect of cortisone in excess of minimal requirements, therapy is limited to short-term administration when ever possible.

Syndromes of primary gonadal failure. The most frequently seen disorders associated with

primary gonadal failure are the sex chromosomal defects categorized collectively as gonadal dysgenesis, principally Turner's syndrome. Chromosomal impairment of male sexual function is most commonly caused by Klinefelter's syndrome. Derangements that become apparent at puberty are more common. Clinical presentation in the female may be masculinization, sexual infantilism or hypoplasia, primary absence of menstruation (amenorrhea),

or abnormally scanty or infrequent menstruation (oligomenorrhea or hypomenorrhea).

The child with an endocrine dysfunction

The major chemical regulators of the body are the internal secretions and their secreting cells,. The function of the endocrine system is to secrete intracellularly

synthesized hormones into the circulation where they are transported to nearby or distant sites to stimulate,

catalyze, or serve as pacemaker substances for metabolic processes. Together with the closely related but more rapidly reacting nervous

system, they serve to integrate the various physiologic functions of the organism in adjusting to external and internal environmental demands.

Endocrine substances even in extremely small concentrations are effective in modifying metabolism, behavior, and development.

What kind of training dopediatric endocrinologists have?Pediatric endocrinologists are medical doctors whohave had•Four years of medical school• Three years of pediatric residency• Three or more years of fellowship training inpediatric endocrinology

What types of treatment do pediatric endocrinologists provide?Pediatric endocrinologists diagnose, treat, and managehormonal disorders including the following:•Growth problems, such as short stature• Early or delayed puberty• Enlarged thyroid gland (goiter)•Underactive or overactive thyroid gland• Pituitary gland hypo/hyper function•Adrenal gland hypo/hyper function• Ambiguous genitals/intersex•Ovarian and testicular dysfunction

• Diabetes•Low blood sugar (hypoglycemia)• Obesity•Problems with Vitamin D (rickets, hypocalcemia)

Pediatric endocrinologists—the best care for childrenChildren are not just small adults. As growing individuals they have

special needs related to growth and development. In addition, their psychological needs are different from those of adults. Hormone problems affecting growth or sexual development can have significant effects on a child’s physical and emotional well-being. Pediatric endocrinologists are sensitive to these issues.

A pediatric endocrinologist cares for your child in a setting that is appropriate for children and teens. Support personnel, including nurses, psychologists, pediatric diabetes educators, and nutritionists, are all attuned to the needs of children and teens.