The endocrine system is a control system of ductless endocrine glands that secrete chemical messengers called hormones that circulate within the body via the bloodstream to affect distant organs. It does not include exocrine glands such as salivary glands, sweat glands and glands within the gastrointestinal tract. The field of medicine that deals with disorders of endocrine glands is endocrinology, a branch of the wider field of internal medicine.

Physiology

The endocrine system consists of a number of ductless glands located in different parts of body, which produce chemical substances called hormones (from Greek word mean-ing 'to excite') directly into the bloodstream, which affect various body functions and activities. Each hormone has a specific role and a target tissue or a target organ to act upon. These target organs respond to the effects of hormones. The hormones are re-leased in very minute concentrations at a time, depending upon the body's require-ment. The hormones are poured directly into the bloodstream, from where they go to their target organs or tissues regulating their activity without affecting any other metabolic activities. The production and release of hormones is controlled by a regulating mechanism called feedback mechanism, which inhibits or accelerates the production of hormones so that overproduction or underproduction does not take place. Over-production (hypersecretion) and underproduction (hyposecretion) of the hormones occurs when this regulating mechanism is not operating well and can lead to many disorders in the body.

List of all endocrine glands and their hormones secreted in both sexes starting from the head and going downwards

Hypothalamus

· Thyrotropin-releasing hormone (TRH)

· Gonadotropin-releasing hormone (GnRH)

· Growth hormone-releasing hormone (GHRH)

· Corticotropin-releasing hormone (CRH)

· Somatostatin

· Dopamine

Pituitary gland

Anterior lobe (adenohypophysis)

· GH (human growth hormone)

· PRL (prolactin)

· ACTH (adrenocorticotropic hormone)

· TSH (thyroid-stimulating hormone)

· FSH (follicle-stimulating hormone)

· LH (luteinizing hormone)

Posterior lobe (neurohypophysis)

· Oxytocin

· ADH (antidiuretic hormone)

Pineal gland

· Melatonin

Thyroid gland

· Thyroxine (T4)

· Triiodothyronine (T3)

· Calcitonin

Parathyroid glands

· Parathyroid hormone (PTH)

Heart

· Atrial-natriuretic peptide (ANP)

Stomach and intestines

· Gastrin

· Secretin

· Cholecystokinin (CCK)

· Somatostatin

· Neuropeptide Y

Liver

· Insulin-like growth factor

· Angiotensinogen

· Thrombopoietin

Islets of Langerhans in the pancreas

· Insulin

· Glucagon

· Somatostatin

Adrenal glands

Adrenal cortex

· Glucocorticoids - cortisol

· Mineralocorticoids - aldosterone

· Androgens (including testosterone)

Adrenal medulla

· Adrenaline (epinephrine)

· Noradrenaline (norepinephrine)

Kidney

· Renin

· Erythropoietin (EPO)

· Calcitriol

Skin

· Calciferol (vitamin D3)

Adipose tissue

· Leptin

In males only

Testes

· Androgens (testosterone)

In females only

Ovarian follicle

1. Estrogens

2. Testosterone

Corpus luteum

· Progesterone

Placenta (when pregnant)

· Progesterone

· Human chorionic gonadotrophin (HCG)

· Human placental lactogen (HPL)

However, endocrine glands of major significance in the human body and also transcription are the pituitary gland, thyroid gland, parathyroid gland, adrenal gland, pancreas, thymus gland, testes (in males) and ovaries (in females).

Pituitary Gland

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea that sits in the small, bony cavity (sella turcica) at the base of the brain. Its posterior lobe is connected to a part of the brain called the hypothalamus via the infundibulum (or stalk), giving rise to the tuberoinfundibular pathway. The posterior lobe is thus derived from neural ectoderm while the anterior lobe is derived from oral ectoderm. The anterior pituitary lobe receives releasing hormones from the hypothalamus via a portal vein system. The pituitary gland secretes hormones regulating a wide variety of bodily activities, including trophic hormones that stimulate other endocrine glands. For a while, this led scientists to call it the master gland, but now we know that it is in fact regulated by releasing hormones from the hypothalamus. It is physically attached to the brain by the pituitary, or hypophyseal stalk connected with the median eminence.

The pituitary gland is divided into two sections: the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The posterior pituitary is, in effect, a projection of the hypothalamus. It does not produce its own hormones, but only stores and releases the hormones oxytocin and antidiuretic hormone (ADH - also known as vasopressin).

The anterior lobe of pituitary produces six hormones, which are instrumental in controlling the activities of various other endocrine organs. These are:

1. Growth hormone: It regulates general body growth, growth of bones, cartilages, and also muscle growth.

2. Adrenocorticotrophic hormone (ACTH): ACTH controls activity of adrenal cortex to release glucocorticosteroid, especially cortisol.

3. Thyroid-stimulating hormone (TSH) or thyrotropin: TSH controls the activity of thyroid gland and helps in the secretion of hormones.

4. Follicle-stimulating hormone: In women, the follicle-stimulating hormone stimulates the development of ova in the Graafian follicles of ovary and also stimulates the secretion of estrogen by follicle cells. In male, it stimulates formation of spermatozoa in testes.

5. Luteinizing hormone (LH) or interstitial cell-stimulating hormone (ICSH): In females, it stimulates ovulation, formation and maintenance of corpus luteum, secretion of progesterone in the ovary, and prepares the uterus for implantation. In men, it stimulates development and activity of interstitial cells to produce testosterone and semen. (Note: Both LH and FSH are together called pituitary gonadotrophic hormones as they control the growth and activity of the gonads and the functions associated with them.

6. Prolactin: Prolactin initiates and maintains milk secretion by the mammary glands after childbirth.

Posterior lobe of pituitary secretes

I. Antidiuretic hormone (ADH) or vasopressin: ADH regulates the amount of water passed by the kidneys. It also increases t he reabsorption of water by the kidneys and raises the blood pressure by constricting the peripheral blood vessels.

2. Oxytocin: Oxytocin stimulates contraction of a pregnant uterus during labor and childbirth. It also stimulates the milk expulsion from the mammary glands.

There is also an interaction between the hormones from the hypothalamus, i.e. TRH induces the release of prolactin. The control of release of hormones from the pituitary is in a negative feedback loop. Their release is inhibited by increasing levels of hormones from the target gland on which they act.

Thyroid

The thyroid is one of the larger endocrine glands in the body. It is located in the neck and produces hormones, principally thyroxine and triiodothyronine, that regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body.

Gross anatomy

The thyroid is situated on the front side of the neck at the level of C5 to T1 vertebral bodies, just below the laryngeal prominence (Adam's apple), near the thyroid cartilage over the trachea but covered by layers of skin and muscle. The thyroid is one of the larger endocrine glands - 10-20 grams in adults- and butterfly-shaped: the wings correspond to the lobes and the body to the isthmus of the thyroid. It may enlarge substantially during pregnancy and when affected by a variety of diseases.

Blood supply

The thyroid gland is supplied by two pairs of arteries: the superior and inferior thyroid arteries of each side. The superior thyroid artery is the first branch of the external carotid, and supplies mostly the upper half of the thyroid gland, while the inferior thyroid artery is the major branch of the thyrocervical trunk, which comes off of the subclavian artery.

Histology of the thyroid

The thyroid is composed of spherical follicles that selectively absorb iodine (as iodide ions, I-) from the blood and for production of thyroid hormones. Twenty-five percent of all the body I- is in the thyroid gland. The follicles are made of a single layer of thyroid epithelial cells, which secrete T3 and T4. Inside the follicles is a colloid, which is rich in a protein called thyroglobulin. The colloidal material serves as a reservoir of materials for thyroid hormone production and, to a lesser extent, a reservoir of the hormones themselves. Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells or C cells, which secrete calcitonin.

Physiology

The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. Up to 40% of the T4 is converted to T3 by peripheral organs such as the liver and spleen.

T3 & T4

Thyroxine is synthesized by the follicular cells from the tyrosine residues of the protein called thyroglobulin (TG). In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. Only the free fraction (not bound to these proteins) has hormonal activity. The production of thyroxine is regulated by thyroid-stimulating hormone (TSH), released by the pituitary. The thyroid and thyrotropes form a negative feedback loop: TSH production is suppressed when the T4 levels are high, and vice versa. The TSH production itself is modulated by thyrotropin-releasing hormone, which is produced by the hypothalamus and secreted at an increased rate in situations such as cold (in which an accelerated metabolism would generate more heat). TSH production is blunted by somatostatin (SRIH).

Calcitonin

Parafollicular cells produce calcitonin in response to hypercalcemia (not TSH, which stimulates thyroxine production). Calcitonin plays a role in the calcium metabolism; it is the functional opposite of parathyroid hormone, but exerts its influence mainly on bone. Its relatively small role is signified by the fact that after removal of the thyroid, calcium levels typically remain stable.

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. Iodized salt is a cheap and easy way of adding iodine to the diet. This has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour mandatory.

Diseases of the thyroid gland

Hyper- and hypofunction:

Hypothyroidism

· Hashimoto's thyroiditis / thyroiditis

· Ord's thyroiditis

· Postoperative hypothyroidism

· Postpartum thyroiditis

· Silent thyroiditis

· Acute thyroiditis

· Iatrogenic hypothyroidism

Hyperthyroidism

· Thyroid storm

· Graves-Basedow disease

· Toxic thyroid nodule

· Toxic nodular struma (Plummer's disease)

· Hashitoxicosis

· Iatrogenic hyperthyroidism

Anatomical problems:

· Goitre

· Endemic goitre

· Diffuse goitre

· Multinodular goitre

· Lingual thyroid

· Thyroglossal duct cyst

Tumors:

· Thyroid adenoma

· Thyroid cancer

· Papillary

· Follicular

· Medullary

· Anaplastic

· Lymphomas and metastasis from elsewhere (rare)

Hypothyroidism

Hypothyroidism is the disease state caused by insufficient production of thyroid hormone by the thyroid gland. There are several distinct causes for chronic hypothyroidism, the most common being Hashimoto's thyroiditis and hypothyroidism following radioiodine therapy for hyperthyroidism.

The severity of hypothyroidism varies widely. Patients are classified as "subclinical hypothyroid" if diagnostic findings show thyroid hormone abnormalities, but they do not exhibit any symptoms.

Signs and Symptoms

· Slowed speech and a hoarse, breaking voice

· Impaired memory

· Increased sensitivity to heat and cold

· A slow heart rate and sluggish reflexes

· Dry puffy skin, especially on the face, and hair loss, especially thinning of the outer 1/3 of the eyebrows

· Depression (especially in the elderly)

· Weight gain and obesity

· Anemia

· Slowed metabolism

· Constipation

· Fatigue

· Choking sensation or difficulty swallowing

· Shortness of breath

· Increased need for sleep

· Muscle cramps and joint pain

· Decreased sex drive

· Brittle fingernails

· Paleness

· Irritability

· Abnormal menstrual cycles

· Thin, fragile or absent cuticles

· Infertility or difficulty becoming pregnant

· Elevated serum cholesterol

Treatment

1. Substitution of thyroid hormones by taking thyroxine (T4) tablets, usually in the form of levothyroxine. Doses are started with smaller amounts of thyroxine and then slowly titrated under control of TSH levels. Usually the maintenance dose is about 1 to 2 micrograms (µg) per kilogram of body weight.

2. Deficiencies of some dietary minerals and iodine can lead to hypothyroidism. Supplementation can be an effective treatment, but only if iodine deficiency has been documented.

3. Synthetic T3.

Hashimoto's thyroiditis

Hashimoto's thyroiditis, the most common form of thyroiditis, is an autoimmune disease where the body's own antibodies fight the cells of the thyroid. It is four times more common among women than men, and runs in families, with the HLADR5 gene most strongly implicated (conferring a relative risk of 3) in the UK. The genes implicated vary in different ethnic groups.

In many cases, Hashimoto's thyroiditis usually results in hypothyroidism, although in its acute phase, it can cause a transient hyperthyroid state. Treatment is by daily thyroxine, with the sodium salt of thyroxine liothyronine given when the need to raise levels of circulating thyroxine is urgent. Symptoms of Hashimoto's thyroiditis include symptoms of hypothyroidism and a goitre.

Hyperthyroidism

Hyperthyroidism (or "overactive thyroid gland") is the clinical syndrome caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both.

Major causes are:

· Graves' disease (the most common etiology with 70-80%)

· Toxic thyroid adenoma

· Toxic multinodular goitre

· Other causes of hyperthyroxinemia (high blood levels of thyroid hormones) are not to be confused with true hyperthyroidism and include subacute and other forms of thyroiditis (inflammation). Thyrotoxicosis (symptoms caused by hyperthyroxinemia) can occur in both hyperthyroidism and thyroiditis. When it causes acutely increased metabolism, it is sometimes called "thyroid storm".

Signs and symptoms

Major clinical features in humans are weight loss (often accompanied by a ravenous appetite), fatigue, weakness, hyperactivity, irritability, apathy, depression, polyuria, and sweating. Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), dyspnea, infertility, loss of libido, nausea, vomiting, and diarrhea.

Diagnosis

A diagnosis is suspected through blood tests, by measuring the level of TSH (thyroid stimulating hormone) in the blood. If TSH is low, there is likely to be increased production of T4 and/or T3. Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves' disease, may contribute to the diagnosis. In all patients with hyperthyroxinemia, scintigraphy is required in order to distinguish true hyperthyroidism from thyroiditis.

Treatment

Surgery-Surgery (to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method.

Radioiodine-In Radioiodine (treatment) therapy, radioactive iodine is given orally (either by pill or liquid) on a one-time basis to ablate a hyperactive gland. The iodine given for ablative treatment is different from the iodine used in a scan. Radioactive iodine is given after a routine iodine scan, and uptake of the iodine is determined to confirm hyperthyroidism. The radioactive iodine is picked up by the active cells in the thyroid and destroys them. Since iodine is only picked up by thyroid cells, the destruction is local and there are no widespread side effects with this therapy.

Thyrostatics-are drugs that inhibit the production of thyroid hormones, such as methimazole (Tapazole®) or PTU (propylthiouracil).

Graves-Basedow disease or Graves’ disease

Graves-Basedow disease is a form of thyroiditis, an autoimmune disorder that stimulates the thyroid gland, being the most common cause of hyperthyroidism (overactivity of the thyroid). Also known in the English-speaking world simply as Graves' disease, it occurs most frequently in women (8:1 compared to men) of middle age. Symptoms include fatigue, weight loss and rapid heart beat. Because similar antibodies to those stimulating the thyroid also affect the eye, eye symptoms are also commonly reported. Treatment is with medication that reduces the production of thyroid hormone (thyroxin), surgery thyroidectomy or with radioactive iodine if refractory.

Goitre

A goitre is a swelling in the neck (just below Adam's apple or larynx) due to an enlarged thyroid gland. They are classified in different ways:

A "diffuse goitre" is a goitre that has spread through all of the thyroid (and is contrasted with a "simple goitre", "single thyroid nodule" and "multinodular goitre".

"Toxic goitre" refers to goitre deriving from inflammation, neoplasm, or malfunction of the thyroid, while "nontoxic goitre" refers to all other types (such as that caused by lithium or an autoimmune reaction.)

The most common cause for goitre in the world is iodine deficiency. Iodine is necessary for the synthesis of the thyroid hormones, triiodothyronine and thyroxine (T3 and T4). When iodine is not available, these hormones cannot be made. In response to low thyroid hormones, the pituitary gland releases thyroid stimulating hormone (TSH). Thyroid stimulating hormone acts to try and increase synthesis of T3 and T4, but it also causes the thyroid gland to grow in size as a type of compensation.

Goitre is more common among women. Treatment may not be necessary if the goitre is not caused by disease and is small. Removal of the goitre may be necessary if it causes difficulty with breathing or swallowing.

Thyroid cancer

Thyroid cancer is cancer of the thyroid gland. There are four forms: papillary, follicular, medullary and anaplastic. The most common forms (papillary and follicular) are fairly benign, and the medullary form also has a good prognosis; the anaplastic form is fast-growing and poorly responsive to therapy.

Masses of the thyroid are diagnosed by fine needle aspiration (FNA) or frequently by thyroidectomy (surgical removal and subsequent pathological examination). As the thyroid concentrates iodine, radioactive iodine is a commonly used modality in thyroid carcinomas.

Thyroid cancers can be classified according to their pathological characteristics. The following variants can be distinguished:

· Papillary thyroid cancer (75%, incl. mixed papillary/follicular)

· Follicular thyroid cancer (16%)

· Medullary thyroid cancer (5%)

· Anaplastic thyroid cancer (3%)

· Lymphoma (1%)

· Squamous cell carcinoma, sarcoma (0.5 - 2%)

Parathyroid Gland

The parathyroid glands are small endocrine glands in the neck, usually located within the thyroid gland, which produce parathyroid hormone. Most often there are four parathyroid glands but have been known to number six or eight.

Parathyroid hormone is a small protein that takes part in the control of calcium and phosphorus homeostasis, as well as bone physiology. When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated to release hormone into the blood. It then stimulates osteoclasts to break down bone and release calcium into the blood. The sole purpose of the parathyroid glands is to regulate the calcium level in our bodies within a very narrow range so that the nervous and muscular systems can function properly.

The single major disease of parathyroid glands is overactivity of one or more of the parathyroid lobes, which make too much parathyroid hormone causing a potentially serious calcium imbalance. This is called hyperparathyroidism; it leads to hypercalcemia and osteitis fibrosa cystica.

Adrenal Gland

The adrenal glands (also known as suprarenal glands or colloquially as kidney hats) are the triangle-shaped endocrine glands that sit atop the kidneys. They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines, including cortisol and adrenaline.

Anatomically, the adrenal glands are located in the abdomen, situated on the anterosuperior aspect of the kidneys. In humans, the adrenal glands are found at the level of the 12th thoracic vertebra and receive their blood supply from the adrenal arteries.

It is separated into two distinct structures, the adrenal medulla and the adrenal cortex, both of which receive regulatory input from the nervous system. As its name suggests, the adrenal medulla is at the center of the adrenal gland surrounded by the adrenal cortex.

The adrenal medulla is the body's main source of the catecholamine hormones epinephrine and norepinephrine.

The cortex produces a group of steroid hormones. These are glucocorticoids, mineralocorticoids, and gonadocorticoids.

1. Glucocorticoids: Glucocorticoids regulate the metabolism of carbohydrates, proteins, and fats. Various glucocorticoids include cortisol, cortisone, and corticosterone. Of these, cortisol has the greatest activity. Secretion of the glucocorticoid hormones is regulated by the adrenocorticotrophic hormone (ACTH) secreted from the anterior pituitary Glucocorticoids also regulate the concentration of glucose in the blood.

2. Mineralocorticoids: Aldosterone is one of the major mineralocorticosteroids in human beings. It regulates the electrolyte and water balance of the body. It maintains the homeostasis of sodium and potassium in the body It promotes reabsorption of sodium by the kidneys into the blood and excretion of potassium by the kidneys. It also promotes water conservation by reducing the urine output.

3. Gonadocorticoids: Gonadocorticoids are considered to stimulate the development of male secondary sexual characteristics like hoarseness of voice, presence of body and pubic hair, etc. Androstenedione and androstenolone (dehydro-3-epiandrosterone) are gonadocorticoids produced from the adrenal cortex.

Pathology

Adrenal cortex:

· Hypoadrenalism (e.g. due to Addison's disease)

· Cushing's syndrome

· Congenital adrenal hyperplasia

· Conn's syndrome

Adrenal medulla:

· Pheochromocytoma is a catecholamine-secreting tumor of the adrenal medulla.

Cushing's Syndrome

Cushing's syndrome or hypercortisolism is an endocrine disorder caused by excessive levels of the endogenous corticosteroid hormone cortisol. It may also be induced iatrogenically by treatment with exogenous corticosteroids for other medical conditions. When Cushing's is suspected, a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH levels) and 24-hour urinary measurement for cortisol have equal detection rates. A novel approach is sampling cortisol in saliva over 24 hours, which may be equally sensitive.

Cortisol is secreted by the adrenal glands under regulation by the pituitary gland and hypothalamus. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. Cushing's disease refers only to hypercortisolism secondary to excess production of adrenocorticotropin (ACTH) from a pituitary gland adenoma.

Pheochromocytoma

A pheochromocytoma is a tumor of the medulla of the adrenal glands originating in the chromaffin cells, which secretes excessive amounts of catecholamines, usually epinephrine and norepinephrine. The diagnosis can be established by measuring catecholamine and metanephrines in plasma or urine. One diagnostic test used in the past for a pheochromocytoma is to administer clonidine (Catapres®), a centrally-acting alpha-2 agonist used to treat high blood pressure.

Pancreas

The pancreas is an organ that serves two functions:

Exocrine - it produces pancreatic juice containing digestive enzymes.

Endocrine - it produces several important hormones, including insulin.

The pancreas is an organ located posterior to the stomach and in close association with the duodenum. The pancreas is a small, elongated organ in the abdomen. It is described as having a head, body and tail. The pancreatic head abuts the second part of the duodenum while the tail extends towards the spleen. The pancreatic duct runs the length of the pancreas and empties into the second part of the duodenum at the ampulla of Vater. The common bile duct commonly joins the pancreatic duct at or near this point.

The pancreas produces enzymes that break down all categories of digestible foods (exocrine pancreas) and secretes hormones that affect carbohydrate metabolism (endocrine pancreas).

Exocrine

The pancreas is covered in a tissue capsule that partitions the gland into lobules. The bulk of the pancreas is composed of pancreatic exocrine cells, whose ducts are arranged in clusters called acini (singular acinus). The cells are filled with secretory granules containing the pre-cursor digestive enzymes (mainly trypsinogen, chymotrypsinogen, pancreatic lipase, and amylase) that are secreted into the lumen of the acinus. These granules are termed zymogen granules (zymogen referring to the inactive precursor enzymes). Zymogen granules are localized to the subapical area of pancreatic acinar cells.

The pancreas is the main source of enzymes for digesting fats (lipids) and proteins - the intestinal walls have enzymes that will digest polysaccharides. The two major proteases the pancreas secretes are trypsinogen and chymotrypsinogen. Pancreatic secretions accumulate in intralobular ducts that drain to the main pancreatic duct, which drains directly into the duodenum.

Due to the potency of its enzyme contents, it is a very dangerous organ to injure and a puncture of the pancreas tends to require careful medical intervention.

Endocrine

Embedded throughout the exocrine tissue are small clusters of cells called the Islets of Langerhans, which are the endocrine cells of the pancreas and secrete insulin, glucagon, and several other hormones. The islets contain three major types of cells — alpha cells, beta cells, and delta cells. The largest number of cells are, by far, the beta cells which produce insulin. The alpha cells produce glucagon and the delta cells produce somatostatin, which lead to both decreased glucagon and insulin levels. There are also the PP cells and the D1 cells, about which little is known.

Diseases of the pancreas

· Benign tumors

· Carcinoma of pancreas

· Cystic fibrosis-Cystic fibrosis (CF), also called mucoviscidosis is an autosomal recessive hereditary disease of the exocrine glands. It affects the lungs, sweat glands and the digestive system. It causes chronic respiratory and digestive problems. About one in five babies with CF are diagnosed at birth, when their gut becomes blocked by extra thick meconium (the black tar-like bowel contents that all babies pass soon after birth). This condition may need surgery. Just over half of people with CF are diagnosed as babies because they are not growing or putting on weight as they should. This is because the pancreas is not producing chemicals (enzymes) which pass into the gut as food leaves the stomach. Without these enzymes, the fat in food cannot be properly digested. In children who are affected, the fat passes straight through the gut. The child does not benefit from the energy from the fat. Since the stools contain an excess of fat, they are oily and very smelly.

· Diabetes

· Acute pancreatitis

· Chronic pancreatitis

· Pancreatic pseudocyst-A pancreatic pseudocyst is a circumscribed collection of pancreatic fluid typically located in the lesser omentum.

Pancreatic Cancer

Pancreatic cancer (also called cancer of the pancreas) is represented by the growth of a malignant tumour within the small pancreas organ.

Types

1. The most common form of this disease is known as adenocarcinoma of the pancreas. It is one of the most lethal forms of cancer with few victims still alive 5 years after diagnosis, and complete remission still extremely rare.

2. A less common, and typically far less aggressive form of pancreatic cancer, is called islet-cell tumor (and is sometimes also known by the term neuroendocrine tumor).

Risk factors for pancreatic cancer include

Male gender

African-American ethnicity

Smoking

Diets high in meat

Obesity

Diabetes

Chronic pancreatitis

Occupational exposure to certain pesticides, dyes, and chemicals related to gasoline

Family history

Helicobacter pylori infection

Diagnosis

Early diagnosis of pancreatic cancer is difficult because the symptoms are so non-specific and varied. Common symptoms include abdominal pain, loss of appetite, significant weight loss, jaundice, digestive problems, and depression. Patients diagnosed with pancreatic cancer typically have a poor prognosis because the cancer usually causes no symptoms early on, leading to metastatic disease at time of diagnosis.

Pancreatitis

Pancreatitis describes the condition of inflammation of the pancreas that causes mild to severe pain in the abdomen. The most common causes of pancreatitis are gallstones and frequent and excessive consumption of alcohol (80% of cases), and less common causes are drugs or medication. The onset of pain in the abdomen region usually occurs within a day of binge drinking or eating a large meal. Sufferers often feel better in 2 to 3 days if they abstain from food and liquids.

There are two forms of pancreatitis, which are different in causes and symptoms, and require different treatment:

Acute pancreatitis: Acute pancreatitis is a rapidly-onset inflammation of the pancreas. Depending on its severity, it can have severe complications and high mortality despite treatment. While mild cases settle with conservative measures or endoscopy, severe cases require surgery (often more than one intervention) to contain the disease process.

Chronic pancreatitis: Chronic pancreatitis can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. Patients with chronic pancreatitis can present with persistent abdominal pain or steatorrhea (diarrhea resulting from malabsorption of the fats in food, typically very bad-smelling and equally hard on the patient), as well as severe nausea. Some patients with chronic pancreatitis often look very sick, while others don't appear to be unhealthy at all. Serum amylase and lipase may well not be elevated in cases of advanced chronic pancreatitis, but are often used as markers for detecting pancreatic inflammation in undiagnosed patients. Common tests used to determine chronic pancreatitis are serum amylase and serum lipase blood tests, triglyceride blood tests, X-rays, Ultrasounds, CT-scans, MRIs and MRCPs. A more invasive test called an ERCP, (Endoscopic Retrograde Cholangiopancreatography), is considered the gold standard procedure for diagnosing chronic pancreatitis. Pancreatic calcification can often be seen on X-rays, as well as CT-scans.

Whipple procedure

The Whipple procedure is a technique of pancreaticoduodenectomy, or surgical removal of pancreatic cancer. It was named for American surgeon Dr. Allen Whipple who devised the procedure in 1935 and subsequently came up with multiple refinements to his technique. The Whipple procedure today is very similar to Whipple's original procedure. It consists of removal of the distal half of the stomach (antrectomy), the gall bladder (cholecystectomy), the distal portion of the common bile duct (choledochectomy), the head of the pancreas, duodenum, proximal jejunum, and regional lymph nodes. Reconstruction consists of attaching the pancreas to the jejunum (pancreaticojejunostomy) and attaching the common bile duct to the jejunum (choledochojejunostomy) to allow digestive juices and bile to flow into the gastrointestinal tract and attaching the stomach to the jejunum (gastrojejunostomy) to allow food to pass through.

Originally performed in a two-step process, Whipple refined his technique in 1940 into a one-step operation.

Diabetes

Diabetes mellitus is a medical disorder characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Hyperglycemia itself can lead to dehydration and ketoacidosis. Longer-term complications include cardiovascular disease (doubled risk), chronic renal failure (it is the main cause for dialysis), retinal damage which can lead to blindness, nerve damage which can lead to erectile dysfunction (impotence), gangrene with risk of amputation of toes, feet, and even legs. The more serious complications are more common in people who have a difficult time controlling their blood sugars with medications (glycemic control).

The most important forms of diabetes are due to decreased or the complete absence of the production of insulin (type 1 diabetes), or decreased sensitivity of body tissues to insulin (type 2 diabetes, the more common form). The former requires insulin injections for survival; the latter is generally managed with diet, weight reduction and exercise in about 20% of cases, though the majority require these strategies plus oral medication (insulin is used if the tablets are ineffective).

Causes and types

Since insulin is the principal hormone that regulates uptake of glucose into cells (primarily muscle and fat cells) from the blood, deficiency of insulin or its action plays a central role in all forms of diabetes.

Type 1 diabetes

Type 1 diabetes (formerly known as insulin-dependent diabetes, childhood diabetes, or juvenile onset diabetes) is most commonly diagnosed in children and adolescents, but can occur in adults as well. It is characterized by β-cell destruction, which usually leads to an absolute deficiency of insulin. Most cases of type 1 diabetes are immune-mediated characterized by autoimmune destruction of the body's β-cells in the Islets of Langerhans of the pancreas, destroying them or damaging them sufficiently to reduce insulin production. Currently, type 1 diabetes is treated with insulin injections, lifestyle adjustments, and careful monitoring of blood glucose levels using blood test kits.

Type 2 diabetes

Type 2 diabetes is characterized by "insulin resistance" as body cells do not respond appropriately when insulin is present. This is a more complex problem than type 1, but is often easier to treat, since insulin is still produced, especially in the initial years. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. Type 2 is initially treated by changes in diet and through weight loss. The next step, if necessary, is treatment with oral antidiabetic drugs: the sulfonylureas, metformin, or (if these are insufficient) thiazolidinediones. If these fail, insulin therapy may be necessary to maintain normal glucose levels.

Gestational diabetes

Gestational diabetes mellitus appears in about 2-5% of all pregnancies. It is temporary and fully treatable, but if untreated it may cause problems with the pregnancy, including macrosomia (high birth weight) of the child. It requires careful medical supervision during the pregnancy. In addition, about 20-50% of these women go on to develop type 2 diabetes.

Genetics

Both type 1 and type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by infection, stress, or environmental factors (e.g. exposure to a causative agent). There is a genetic element in the susceptibility of individuals to some of these triggers which has been traced to particular HLA genotypes.

There is an even stronger inheritance pattern for Type 2 diabetes; those with type 2 ancestors or relatives have very much higher chances of developing Type 2. Concordance among monozygotic twins is close to 100%, and 25% of those with the disease have a family history of diabetes. It is also often connected to obesity, which is found in approximately 85% of (North American) patients diagnosed with that form of the disease, so some experts believe that inheriting a tendency toward obesity seems also to contribute.

Diagnosis

The diagnosis of type 1 diabetes and many cases of type 2 is usually prompted by recent-onset symptoms of excessive urination (polyuria) and excessive thirst (polydipsia), often accompanied by weight loss. These symptoms typically worsen over days to weeks; about 25% of people with new type 1 diabetes have developed a degree of diabetic ketoacidosis by the time the diabetes is recognized.

1. Diabetes screening is recommended for many types of people at various stages of life or with several different risk factors, like random glucose, a fasting glucose and insulin, a glucose 2 hours after 75 g of glucose, or a formal glucose tolerance test.

2. Many medical conditions are associated with a higher risk of various types of diabetes and warrant screening. A partial list includes: high blood pressure, elevated cholesterol levels, coronary artery disease, past gestational diabetes, polycystic ovary syndrome, chronic pancreatitis, hepatic steatosis (fatty liver), cystic fibrosis, several mitochondrial neuropathies and myopathies, myotonic dystrophy, Friedreich's ataxia, some of the inherited forms of neonatal hyperinsulinism and many others. Risk of diabetes is higher with chronic use of several medications, including high dose glucocorticoids, some chemotherapy agents (especially L-asparaginase), and some of the antipsychotics and mood stabilizers (especially phenothiazine and some atypical antipsychotics).

3. Diabetes is often detected when a person suffers a problem frequently caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.

Criteria for diagnosis

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of

· Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dl);

· Plasma glucose at or above 11.1 mmol/L (200 mg/dl) two hours after a 75 g glucose load; or

· Symptoms of diabetes and a random plasma glucose at or above 11.1 mmol/L (200 mg/dL).

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is an acute, dangerous complication and is always a medical emergency. Prompt proper treatment usually results in full recovery, though death can result from inadequate treatment or a variety of complications.

Hypoglycemia

Hypoglycemia in patients with diabetes almost always arises as a result of poor management of the disease either from too much or poorly timed insulin or oral hypoglycemics or too much exercise, not enough food, or poor timing of either. If blood glucose levels are low enough, the patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system - they may experience feelings similar to dread and immobilized panic. Consciousness can be altered, or even lost, in extreme cases, leading to coma and/or seizures or even death and brain damage.

Long-term complications

Among the major risks of the disorder are chronic problems affecting multiple organ systems, which will eventually arise in patients with poor glycemic control. Many of these arise are

Small vessel disease complications:

· Proliferative retinopathy and macular edema which can lead to severe vision loss or blindness;

· Peripheral neuropathy which, particularly when combined with damaged blood vessels, can lead to foot ulcers, and possibly progressing to necrosis, infection and gangrene, sometimes requiring limb amputation, see below

· Diabetic nephropathy (due to microangiopathy) which can lead to renal failure

Large vessel disease complications:

· Ischemic heart disease caused by both large and small vessel disease

· Stroke

· Peripheral vascular disease which contributes to foot ulcers and the risk of amputation

Management of the disease

Diabetes management includes proper planning of

· Insulin

· Meal plan

· Blood glucose monitoring

· Exercise

Type 1 Diabetes

Persons with type 1 diabetes require insulin every day. Insulin can either be injected, which involves the use of a needle and syringe, or it can be given by an external or internal insulin pump, insulin pen, jet injector, or insulin patch. Extra amounts of insulin may be taken before meals, depending on the blood glucose level and food to be eaten.

Insulin cannot be taken as a pill. Because it is a protein, it would be broken down during digestion just like the protein in food. It must be injected into the fat under the skin for insulin to get into the blood. The amount of insulin needed depends on height, weight, age, food intake, and activity level. Insulin doses must be balanced with meal times and activities, and dosage levels can be affected by illness, stress, or unexpected events.

Type 2 Diabetes

Persons with type 2 diabetes may continue to produce adequate insulin for sometime but their bodies can become incapable of using it, called as insulin resistance and may indicate the need for oral medications that can help stimulate the pancreas to release insulin or optimize the body's ability to use the insulin secreted.

Diet and exercise can often bring blood glucose levels down to normal. When these measures are no longer enough, the next step is the addition of medications that lower blood glucose levels.

Oral anti-diabetic medications

Diabetic pills that lower the blood sugar levels include the following types:

Biguanides-Biguanides decrease the amount of sugar produced in the liver and also lower the amount of insulin in the body.

Sulfonylureas-Sulfonylureas stimulate the production of insulin in the pancreas and help the body to use the insulin that is currently being produced.

Meglitinides-Meglitinides stimulate the production of insulin in the pancreas, but are shorter-acting than sulfonylureas.

Thiazolidinediones-Thiazolidinediones help make the cells in the body more sensitive to insulin.

Alpha-glucosidase inhibitors-Alpha-glucosidase inhibitors block the enzymes that digest starches, resulting in a slower rise in the blood sugar.

Diagnostic Tests and Pharmacology

Important procedures in diagnoses of endocrinological disorders

CT Scan

Computerized tomography scan is used to obtain the anatomic information from the cross-sectional planes of the body by the synthesis of the x-ray transmission data. It is used to trace the pathology of the soft body tissues, especially the pancreas, thyroid, and adrenal glands. Generally, such CT scans make use of radiographic contrast mediums to detect any abnormality in the soft tissues.

Fasting blood sugar (FSS)

Fasting blood sugar measures the glucose level in the blood sugar after fasting for atleast 12 hours. A diagnosis of diabetes is made when the fasting blood sugar is consistently over 140. Similarly, if the random blood sugar is consistently above 180, the patient is diagnosed as having diabetes mellitus.

Glucose tolerance test (GTT)

Glucose tolerance test helps in the detection of diabetes mellitus and hypoglycemia. Glucose is administered orally or intravenously into the body of a fasting person. In a normal person, the blood sugar quickly rises and then falls to normal standards within 2 hours. In a patient of diabetes mellitus, the increase is too sharp and the fall back to normal a bit prolonged. In a hypoglycemic, depressed glucose level may be noticed in 3 to 5 hours.

Insulin tolerance test

Insulin tolerance test is conducted to determine the insulin level in the blood. Insulin is administered into the body and the glucose level is measured at timed intervals. Hypoglycemics will have a lower level of glucose and will take longer than in normal people to return to normal glucose levels.

Protein-bound iodine (PSI)

Protein-bound iodine or PBl test is a test used to monitor the thyroid function. This test measures the serum protein-bound iodine and provides an estimate of the hormone bound to protein in the peripheral blood.

Radioactive iodine uptake (RAIU)

Radioactive iodine uptake test is also known as ¹³¹I uptake test. This is a test of thyroid function in which iodine is administered orally. Then, after the expiry of 24 hours, the amount present in the thyroid gland is measured and compared with the normal values. This test is done to monitor the ability of the gland to take up or absorb the iodine from the blood. This helps in the detection of thyroid nodules and tumors.

Thyroid echogram

Thyroid echogram is the ultrasound examination of the thyroid. It detects the cysts from the solid nodules. In the first case, the liquid is aspirated from the fluid-filled cysts and surgery is avoided. The reflected sound waves help in the detection of the non-functioning thyroid nodules.

Thyroid function tests

Thyroid function tests are done to assess the functioning of the thyroid glands. It also includes the physical examination in addition to laboratory tests. The two thyroid hormones generally tested are triiodothyronine (T₃) and thyroxine (T₄), as well as the thyroid stimulating hormone (TSH). RAIU is also a part of the full thyroid function test.

Total calcium

Total calcium test measures the presence of calcium in the blood. The measurement of calcium, in turn, indicates the presence or absence of bone or parathyroid disorders. A calcium level of more than the normal indicates hyperparathyroidism, and a calcium level of less than the normal indicates hypoparathyroidism.

Pharmacology Associated With Endocrinology

Anabolic agents

Anabolic agents have the capacity to increase the muscle mass. They are the compounds with androgenic properties and are used in the cases of emaciation, and at times by the athletes to increase the muscle size, strength, and endurance. Some of the examples are Histerone, Depo- Testosterone, Malogen, etc.

Corticosteroids

Corticosteroid is a steroid produced by the adrenal cortex. Corticosteroids are used for adrenal insufficiency. They suppress the inflammation, allergy, reduce the chances of rejection in transplantation cases, and also treat some kinds of tumors. The two kinds of corticosteroids are mineralocorticoids and glucocorticoid. Aldosterone is a mineralocorticoid. The examples of glucocorticoids are hydrocortisone, prednisolone, triamcinolone, etc.

Antidiabetic and hypoglycemics

Antidiabetic agents are also known as hypoglycemics and they lower the blood sugar level. Drugs like chlorpropamide (Diabinese), glyburide, pioglitazone (Actos), glipizide (Glucotrol), metformin and phenformin are some examples of hypoglycemics. On the other hand, hyperglycemics increase the blood sugar level and are given in the cases of hypoglycemia. Glucagonis a popular hyperglycemic agent.

ACTH

Adrenocorticotropic hormone, secreted by pituitary gland,

ADH

Antidiuretic hormone, called also vasopressin.

BMR

Basal metabolic rate.

DI

Diabetes insipidus.

DM

Diabetes mellitus.

FBS

Fasting blood sugar.

FSH

Follicle stimulating hormone.

GH

Growth hormone (somatotropin).

GTT

Glucose tolerance test.

HGH

Human growth hormone.

IDDM

Insulin-dependent diabetes mellitus, type I.

K

Potassium.

LH

Luteotropic hormone.

Na

Sodium.

NIDDM

Non insulin-dependent diabetes mellitus, type II.

Prl

Prolactin.

PTH

Parathyroid hormone.

RIA

Radioimmunoassay.

SIADH

Syndrome of inappropriate antidiuretic hormone secretion.

TFT

Thyroid function test.

TSH

Thyroid stimulating hormone.