Role of the Pituitary Gland

BASIC CONCEPTS

ENDOCRINE SYSTEM :-
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone into the bloodstream to regulate the body. It derives from the Greek words endo meaning inside, within, and crinis for secrete. The endocrine system is an information signal system like the nervous system. Hormones are substances (chemical mediators) released from endocrine tissue into the bloodstream that attach to target tissue and allow communication among cells. Hormones regulate many functions of an organism, including mood, growth and development, tissue function, and metabolism. The field of study that deals with disorders of endocrine glands is endocrinology, a branch of internal medicine.
The endocrine system is made up of a series of glands that produce chemicals called hormones. A number of glands that signal each other in sequence is usually referred to as an axis, for example, the hypothalamic-pituitary-adrenal axis. Typical endocrine glands are the pituitary, thyroid, and adrenal glands. Features of endocrine glands are, in general, their ductless nature, their vascularity, and usually the presence of intracellular vacuoles or granules storing their hormones. In contrast, exocrine glands, such as salivary glands, sweat glands, and glands within the gastrointestinal tract, tend to be much less vascular and have ducts or a hollow lumen.
In addition to the specialized endocrine organs mentioned above, many other organs that are part of other body systems, such as the kidney, liver, heart and gonads, have secondary endocrine functions. For example the kidney secretes endocrine hormones such as erythropoietin and renin.

HORMONES :-
A Hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one cell to another. All multicellular organisms produce hormones; plant hormones are also called phytohormones. Hormones in animals are often transported in the blood. Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor protein, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses.
Endocrine hormone molecules are secreted (released) directly into the bloodstream, whereas exocrine hormones (or ectohormones) are secreted directly into a duct, and, from the duct, they flow either into the bloodstream or from cell to cell by diffusion in a process known as paracrine signalling.
Recently it has been found that a variety of exogenous modern chemical compounds have hormone-like effects on both humans and wildlife. Their interference with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body are responsible of homeostasis, reproduction, development, and/or behavioural changes sameway as the endogenous produced hormones.

THEIR FUNCTIONS

Hormones have the following effects on the body:

Mood swings

Induction or suppression of apoptosis (programmed cell death)

Activation or inhibition of the immune system

Regulation of metabolism

Preparation of the body for mating, fighting, fleeing, and other activity

Preparation of the body for a new phase of life, such as puberty, parenting, and menopause

Stimulation or inhibition of growthControl of the reproductive cycle

WHAT IS THE PITUITARY GLAND ?

INTRODUCTION

In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g (0.02 oz.), in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold . The pituitary is functionally connected to the hypothalamus by the median eminence via a small tube called the infundibular stem (Pituitary Stalk). The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa at the base of the brain. The pituitary gland secretes nine hormones that regulate homeostasis. It is an important link between the nervous system and the endocrine system and releases many hormones which affect growth, sexual development, metabolism and the system of reproduction. The "hypothalamus" is a tiny cluster of brain cells just above the pituitary gland, which transmits messages from the body to the brain. Hypophyseal veins are veins which receive hormones from the pituitary gland. Hypophyseal arteries supply blood to the pituitary gland. The pituitary gland has two distinct parts, the anterior and the posterior lobes, each of which releases different hormones which affect bone growth and regulate activity in other glands. This gland was once believed to be the main controlling gland of the body, but we now know that, important as it is, it is subservient to a master gland called the hypothalamus, which is the needed link between the pituitary gland and the brain. This "master gland" is really a way station between the body and the brain and sorts out messages going to and from the brain. It responds to the body through the pituitary gland, which is suspended just below it. It sometimes replies by nerve impulses and sometimes with needed hormones. The pituitary gland then makes hormones of its own in answer to the body's needs. These are then circulated in the blood to a variety of the body's tissues.
SECTIONS OF THE PITUITARY GLAND

The pituitary gland consists of two components: the anterior pituitary (or adenohypophysis) and the posterior pituitary (or neurohypophysis), and is functionally linked to the hypothalamus by the pituitary stalk (also named the "infundibular stem", or simply the "infundibulum"). It is from the hypothalamus that hypothalamic tropic factors are released to descend down the pituitary stalk to the pituitary gland where they stimulate the release of pituitary hormones. While the pituitary gland is known as the 'master' endocrine gland, both of the lobes are under the control of the hypothalamus; the anterior pituitary receives its signals from the parvocellular neurons and the posterior pituitary receives its signals from magnocellular neurons .

ANTERIOR PITUITARY

A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland. The anterior pituitary regulates several physiological processes including stress, growth, and reproduction.
Its regulatory functions are achieved through the secretion of various peptide hormones that act on target organs including the adrenal gland, liver, bone, thyroid gland, and gonads. The anterior pituitary itself is regulated by the hypothalamus and by negative feedback from these target organs.
Disorders of the anterior pituitary are generally classified by the presence of over- or underproduction of pituitary hormones. For example, a prolactinoma is a pituitary adenoma that overproduces prolactin. In Sheehan's syndrome of postpartum hypopituitarism, the anterior pituitary uniformly malfunctions and underproduces all hormones. Proper function of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

HORMONES PRODUCED

The posterior pituitary as a down growth of the brain, is a neurosecretory organ (Wheater, Burkitt & Daniels, 1987). The secretion of hormones from the posterior pituitary is controlled directly by neurons in the hypothalamus (Marieb, 2004). The connecting stalk between the hypothalamus and the lobes of the pituitary gland, the infundibulum, carries the hormones of the posterior pituitary from nuclei in the hypothalamus. The hypothalmic supraoptic nuclei manufacture anti-diruetic hormone and the hypothalmic paraventricular nuclei manufacture oxytocin. These hormones are then stored in pituitary axons until their release is triggered (Marieb, 2004).
The anterior pituitary is a glandular secretory organ (Wheater, Burkitt & Daniels, 1987). The secretion of hormones from the anterior pituitary is controlled by inhibiting and releasing factors secreted by neurons in the hypothalamus. These inhibiting and releasing factors are released into a primary capillary plexus where they travel, via portal veins, to a secondary capillary plexus where they stimulate the glandular tissue of the anterior pituitary to release its hormones.

Anterior Pituitary Hormones Adrenocorticotrophic Hormone (ACTH) Thyroid-Stimulating Hormone (TSH) or thyrotropin Luteinising Hormone (LH) Follicle-Stimulating Hormone (FSH) Prolactin (PRL) Growth Hormone (GH) Melanocyte-Stimulating Hormone (MSH)

HORMONES PRODUCED BY THE HYPOTHALAMUS

The secretion of hormones from the anterior pituitary is controlled by the production of hormones by the hypothalamus. Although there are a number of different hormones they can be split into two main types:

Hormones that tell the pituitary to switch on production of a hormone (a releasing hormone); and

Hormones that tell the pituitary to switch off production of a hormone (an inhibiting hormone).

Thyrotropin
Thyrotropin is also called thyroid-stimulating hormone (TSH). Thyrotropin-producing cells (thyrotrophs) make up about 10 percent of the anterior pituitary and are located mainly in the center of the gland. Thyrotropin becomes attached firmly to receptors on the surface of the thyroid cells, forming thyroid follicles in the thyroid gland. Following binding, a complex train of events occurs so that preformed thyroid hormones are secreted and steps are set in motion for the synthesis of additional thyroid hormones. Thyrotropin exerts other pervasive effects. It stimulates the growth of thyroid cells and leads to increased blood flow through the gland. It also enhances the breakdown of thyroglobulin, a large thyroid-hormone-containing glycoprotein that is stored within the follicles of the thyroid gland.

The levels of thyrotropin in circulating fluids become elevated during thyroid hormone deficiency because there is no negative feedback inhibition of pituitary thyrotropin release by thyroid hormone. Elevated thyrotropin levels are found in other pathological states, including the presence of a thyrotropin-producing pituitary tumor. Low serum thyrotropin levels occur following damage to cells in the hypothalamus that produce thyrotropin-releasing hormone (TRH), following damage to the pituitary stalk, or, finally, following damage to the thyrotrophs themselves. Tests of increased sensitivity have made the measurement of thyrotropin in blood valuable in detecting subtle changes of both thyroid hyperfunction and hypofunction.

Gonadotropins

Gonadotrophs, which amount to about 7 percent of all pituitary cells, secrete two hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but not in equal amount. The rate of secretion varies widely at different ages and at different times in the menstrual cycle of the female. Secretion of LH and FSH is low before puberty in both sexes. After puberty, about five times more LH than FSH is secreted. During menstrual cycles there is a dramatic rise in both hormones at the time of ovulation (see the ovary), and secretion increases as much as 15-fold following {menopause} menopause.

In men FSH stimulates the development of spermatozoa, in large part by acting on special cells in the testes called Sertoli cells. In women FSH stimulates the synthesis of estrogens as well as the maturation of cells lining the spherical, egg-containing structures known as the Graafian follicles. In menstruating women, there is a preovulatory surge in FSH levels in the blood. Inhibin, a hormone secreted by the Graafian follicles of the ovary and the Sertoli cells of the testis, inhibits the secretion of FSH from the pituitary gonadotroph.

In men androgens (male hormones) are secreted by specialized cells called Leydig cells, a process stimulated by LH. In women a preovulatory surge of LH is essential for rupture of the Graafian follicle so that the egg can be discharged on its journey to the uterus. The empty follicle becomes filled with other, progesterone-producing cells, transforming it into a corpus luteum.

When a disease process leads to encroachment on the cells of the pituitary gland, usually the first evidence of cell failure is in the gonadotroph. Thus, disappearance of menstrual periods may be the first sign of a pituitary tumor in the female. In the male the most common symptom of gonadotropin deficiency is impotence. Isolated deficiencies of both LH and FSH do occur, but only rarely. In a male, LH deficiency alone leads to the appearance of what has been described as a “fertile eunuch”; there is sufficient FSH present to permit the maturation of spermatozoa, but because of the LH deficiency the man has, nonetheless, many of the characteristics of a castrate. Tumors also can produce an excess of LH or FSH, and pituitary tumors that secrete only the nonspecific, hormonally inactive alpha unit of glycoprotein hormones are not rare.

Corticotropin or ACTH

Corticotropin, also called adrenocorticotropin hormone (ACTH), is a segment of a much larger prohormone glycoprotein molecule called pro-opiomelanocortin, which is synthesized by pituitary corticotrophs. This prohormone is split into a number of biologically active polypeptide fragments when the secretory granule is discharged from the cell. Among these hormones are corticotropin, whose major action is to stimulate growth and secretion of the cells of the adrenal cortex; alpha- and beta-melanotropin (melanocyte-stimulating hormone, MSH), which increases pigmentation of the skin; beta-lipotropin (LPH), which stimulates the release of fatty acids from adipose tissue; a small fragment of ACTH thought to improve memory; and beta-endorphin, a polypeptide that has excited a good deal of popular as well as scientific interest (see the adrenal cortex).

Beta-endorphins (along with the enkephalins, which are neuromodulators) were discovered when investigators postulated that, since opiates such as morphine bind firmly to cell-surface receptors, there must exist natural substances that do likewise and have a narcotic action. The endorphins and enkephalins are known, therefore, as endogenous (self-generated) opiates or opioids. They have powerful painkilling properties. Beta-endorphins instilled in the spinal fluid are capable of alleviating otherwise intractable pain in cancer patients. It has often been observed that severely traumatized individuals, those in battle, for example, appear to be free of pain. This phenomenon is due to the simultaneous release of beta-endorphin along with corticotropin in response to the stressful stimulus of the injury. There have also been reports of children with endorphin-producing pituitary tumors who are highly insensitive to pain. In addition, the release of endorphin or enkephalin may account for the euphoria (“high”) experienced by long-distance runners. Finally, there is evidence, not fully accepted, that endogenous opioids stimulate appetite. This is seen in rats and obese persons who have a rare disease called Prader-Labhart-Willi syndrome. In these instances, the appetite is diminished after the administration of a narcotic antagonist, such as naloxone.

Hyperplasia or adenoma of corticotrophs gives rise to the constellation of symptoms called Cushing's syndrome (discussed in more detail on the next page). A deficiency of corticotropin also occurs both as part of the multiple deficiencies of panhypopituitarism and as an isolated defect. The diagnosis of corticotropin deficiency is important because afflicted persons who are also subjected to stress can succumb to severe shock. Once frequently administered in the treatment of disorders including allergic states, collagen disorders, and autoimmune diseases, corticotropin has been largely displaced by a number of synthetic variants of adrenal steroids.

Melanocyte-Stimulating Hormone (MSH)

Melanocyte-stimulating hormone gets its name because of its effect on melanocytes: skin cells that contain the black pigment, melanin. In humans, melanocytes are responsible for moles, freckles, and suntan (and, if they turn cancerous, melanoma).

In most vertebrates, MSH is produced by an intermediate lobe of the pituitary gland. Its secretion causes a dramatic darkening of the skin of fishes, amphibians, and reptiles. The darkening occurs as granules of melanin spread through the branches of specialized melanocytes called melanophores.

Prolactin

Prolactin is a hormone produced by the anterior pituitary gland in both men and women. It is known as a gonadotrophic hormone as it affects the gonads (testes and ovaries). It also has an effect on other organs in the body, however, only the effects on the reproductive organs will be discussed here.

In males, prolactin influences the production of testosterone and affects sperm production. In conditions where prolactin secretion is increased (hyperprolactinaemia), testosterone levels drop and sperm production is reduced or absent, resulting in male infertility.

On the evolutionary scale, prolactin is an ancient hormone serving multiple roles in mediating the care of progeny (it has been called the “parenting” hormone). Prolactin is a large protein molecule synthesized and secreted from cells, the lactotrophs, which compose 20 percent of the anterior pituitary gland and are located largely in the two lateral portions. Unlike other anterior pituitary cells whose activities are stimulated by hypothalamic-releasing hormones, the major modulating influence on lactotroph secretion is the inhibitory effect of the neurotransmitter dopamine, which, in the case of prolactin, functions as a hypothalamic neurohormone.

The main action of prolactin in females is the induction and maintenance of lactation (breastfeeding). Prolactin levels build up during pregnancy but milk secretion does not begin until after birth. As an infant suckles, prolactin is released into the mother's blood stream, causing the milk glands to produce more milk. Prolactin and other hormones are responsible for the development of mammary glands during pregnancy. Prolactin also affects the ovaries. The main target area is the corpus luteum, the secretory organ formed from the ruptured ovarian follicle after ovulation. High prolactin levels lead to reduced progesterone function. The result of hyperprolactinaemia can be the non-appearance of menarche (beginning of menstruation at puberty), amenorrhoea (absence of menstruation in a woman after puberty) and anovulatory menstrual cycles (absence of ovulation i.e. no mature eggs produced). These effects can be the basis of female infertility.

Growth Hormone

Somatotrophs are plentiful in the pituitary, constituting 40 percent of the gland. They are located predominantly in the lateral lobes and secrete between one and two milligrams of growth hormone (GH; also called somatotropin) per day. Growth hormone stimulates growth, not only of bone but of essentially all the tissues of the body. In biochemical terms, growth hormone simultaneously stimulates protein synthesis in tissues and enhances the breakdown of fat to provide the energy for the stimulated growth. Growth hormone is also an insulin antagonist and, in susceptible individuals, can lead to elevated sugar levels in the blood and diabetes mellitus.

While GH may act on tissues directly, much of its effect is mediated by way of stimulating the liver and other tissues to manufacture and release secondary hormones, called somatomedins, which partly mimic the action of insulin. During childhood, somatomedin levels in the serum rise progressively with age, with an accelerated increase occurring at the time of the growth spurt of puberty, followed by a reduction to adult levels.

Growth hormone secretion is stimulated by growth hormone-releasing hormone (GHRH; also known as somatocrinin) and is inhibited by somatostatin. There are prominent daily fluctuations in growth hormone secretion in normal individuals, with the largest increase occurring shortly after the onset of sleep. Again, this increase is most pronounced at the time of puberty. Growth hormone levels in the serum are elevated in individuals with tumors that produce growth hormone, and its levels are unresponsive to stimulation in states of malnutrition.

The term acromegaly refers to the enlargement of the distal parts of the body; there is, in fact, progressive enlargement of the hands, feet, chin, and nose. Most other organs also become enlarged. The presence of a pituitary tumor causes severe headaches, and the pressure of the tumor on the optic chiasm causes visual defects.

The acromegalic patient has overgrown supraorbital ridges, enlarged nasal sinuses that give a sonorous quality to the voice, an overgrown jaw, spaces between the teeth, and an enlarged tongue. The skin thickens, producing a permanently furrowed brow. The enlarged fingers are no longer tapered and become spatulated.

Because the metabolic actions of growth hormone are antagonistic to those of insulin, some acromegalic patients develop diabetes mellitus and are subject to all of its complications. Other problems include elevated blood pressure, heart disease, and progressive arthritis. Finally, because some of these tumors produce prolactin as well as growth hormone, males may have enlarged breasts, and both sexes may show abnormal lactation (milk secretion). Acromegaly can be treated with a considerable degree of success with surgery, with X-ray therapy, and with drugs such as bromocriptine or a synthetic, long-acting somatostatin.

TABLE 1

Hormone
Other names
Symbol(s)
Target
Effect
Adrenocorticotropic hormone
Corticotropin
ACTH
Adrenal gland
Secretion of glucocorticoids
Thyroid-stimulating hormone
Thyrotropin
TSH
Thyroid gland
Secretion of thyroid hormones
Follicle-stimulating hormone
-
FSH
Gonads
Growth of reproductive system
Luteinizing hormone
Lutropin
LH
Basophil
Gonads
Growth hormone
Somatotropin
GH
Acidophil
Liver
Prolactin
Lactogenic hormone
PRL
Ovaries mammary glands

POSTERIOR PITUITARY
The posterior pituitary lobe consists largely of extensions of processes (axons) from large clusters of cell bodies called nuclei. One pair, known as the superoptic nuclei, lies immediately above the optic tract, while the other pair, the paraventricular nuclei, lies on each side of the third ventricle of the brain. This anatomical complex forms the neurohypophyseal unit. There are neural connections upward to other centers of the brain, including a centre that modulates thirst. The two major neurohypophyseal hormones, vasopressin (also called antidiuretic hormone [ADH]) and oxytocin, synthesized in the cell body of the nuclei, descend through the long axons to be stored in secretory granules in the posterior lobe of the pituitary. Functionally, therefore, the posterior lobe is a storage and secretion site only.

HORMONES PRODUCED BY POSTERIOR PITUITARY

Anti-Diuretic Hormone (ADH)

Oxytocin

Oxytocin

Oxytocin is responsible for uterine contractions, both before and after delivery. The muscle layers of the uterus (myometrium) become more sensitive to oxytocin near term. Towards the end of a term pregnancy, levels of progesterone decline, and contractions that were previously suppressed by progesterone begin to be more frequent and stronger. This change in the oxytocin/progesterone ratio is believed to be one of the initiators of labor.

Oxytocin is responsible for the contractions that bring about delivery, by thinning and dilating the cervix, and applying pressure that helps the baby descend in the pelvis. It is also important after delivery, as it continues to cause the myometrium to contract. These contractions help constrict the blood vessels that are sending blood to the uterus at the time of childbirth at the rate of a liter a minute!

Oxytocin is also responsible for milk ejection during breastfeeding, by contraction of the myoepithelial cells in the lactating mammary gland. The uterine "cramping" that often occurs with breastfeeding is a signal that oxytocin is still causing the uterus to contract after delivery. These contractions help the uterine muscle to continue to constrict the uterine blood vessels, and bring about a decrease in the amount of vaginal bleeding after delivery.

Antidiuretic Hormone (ADH)

The function of ADH is to inhibit or prevent the formation of urine. Osmoreceptors monitor the solute concentrations in the blood. During pregnancy the osmoreceptors are "reset" to deal with the increased blood volume of pregnancy. If the osmoreceptors send excitatory messages to the "ADH secreting neurones," less urine is produced, leaving more volume in the circulating blood.

The actions of the hormones of the posterior pituitary are especially important to consider in the pregnant woman who is at risk for preterm labor. Maternal dehydration may trigger the secretion of ADH by the posterior pituitary. It is thought that oxytocin may also be released at the same time, bringing about uterine contraction before the optimum time. These uterine contractions, or uterine "irritability" (low intensity, high frequency contractions) of preterm labor are often treated with maternal hydration. Women at risk for preterm labor are encouraged to drink copious amounts of water throughout the day. And, if hospitalized for contractions, hydration with a bolus of IV fluid is often effective to "quiet" the uterus.

Secretion of ADH is also stimulated by pain, low blood pressure and drugs such as nicotine, morphine and barbiturates. In trauma situations, a great deal of ADH is released, to counteract blood loss. The result is constriction of smooth muscles of the blood vessels, in order to raise the arterial blood pressure. (As a result, of this "pressor" effect, ADH is sometimes referred to as vasopressin.) Very little blood is getting to the baby through the constricted blood vessels.

DISORDERS OF THE PITUITARY GLAND

Acromegaly Adult Growth Hormone Deficiency Dwarfism Craniopharyngioma Cushing's Disease Diabetes Insipidus Hypopituitarism

ACROMEGALY
Acromegaly is caused when a tumor on the pituitary gland produces too much growth hormone (GH). These tumors are almost always benign (i.e. not cancerous) and therefore do not spread to other areas of the body.

Acromegaly is a very rare condition and usually develops between the ages of 30 and 50. If the condition develops before a person has stopped growing (which usually occurs between the ages of 15 to 17 years of age), it causes gigantism because growth hormone promotes growth of bones in the body.

Typical symptoms

coarsening of facial features enlarged hands and feet thickening of the soft tissue in the palms and soles of the feet carpal tunnel syndrome (tingling feeling or pains in the hands) excessive sweating and oily skin headaches vision disturbances sleep apnea general tiredness irregular periods (oligomenorrhoea) or loss of normal menstrual function (amenorrhoea) -
All these symptoms tend to develop gradually and the changes may not be noticed for some time.

ADULT GROWTH HORMONE DEFICIENCY (AGHD)

Growth Hormone (GH) is a protein made in the pituitary gland and passed from there into the blood stream. GH has effects on virtually all the organs of the body, but its primary use during childhood is making children grow.

GH deficiency is usually caused by damage to the pituitary gland or the part of the brain which controls this gland (the hypothalamus). The damage may be due to a tumor or to the effects of treatment for the tumor (surgery or radiotherapy) or to problems with the blood supply to the pituitary gland.

Typical symptoms

increase in adipose (fatty) tissue (especially around the waist) decrease in lean body mass (muscle) decrease in strength and stamina, reduction in exercise capacity decrease in bone density, increase in rate of fracture in middle age and beyond changes in blood cholesterol concentrations (increase in LDL and decrease in HDL) excessive tiredness anxiety and depression feelings of social isolation reduction in 'quality of life' increased sensitivity to cold or heaT

DWARFISM

There are many causes of short stature or dwarfism other than deficient growth hormone secretion; for example, chromosomal abnormalities, malnutrition (including poorly controlled diabetes mellitus), thyroid deficiency, and disorders of bone formation are all examples of dwarfism with normal GH secretion. Nonetheless, growth hormone deficiency is a fairly common cause of short stature. Perhaps most frequent is GH deficiency resulting from damage to the hypothalamus and pituitary during fetal development or at birth because of trauma, lack of oxygen, or any of a number of other causes. When damage to the hypothalamus or pituitary is mild, growth hormone deficiency may be the only detectable manifestation of a disease state because the somatotrophs are the most sensitive of the pituitary cells to injury. When all of the cells of the pituitary are severely damaged or destroyed the patient is said to have panhypopituitarism (leading to diminished function of the gonads, the thyroid, and the adrenal glands).

Midgets usually suffer from one of two forms of hereditary (familial) isolated growth hormone deficiency. In some families the deficiency is the result of underproduction of GHRH, in which case growth hormone secretion may be stimulated by infusion of GHRH. In others, the problem lies in the somatotrophs themselves when they become incapable of manufacturing growth hormone. Growth hormone levels also tend to fall in some aged persons who otherwise appear to be normal.

In other forms of dwarfism, the hypothalamus and pituitary function adequately, and the abnormality lies rather in the lack of response of body tissues. A well-studied example is that of the Laron dwarf. These children suffer from a hereditary disorder characterized by the inability of growth hormone to bind to specific receptors in the body's tissues; circulating GH levels are elevated but somatomedin levels remain low because GH, unable to bind to receptors, cannot stimulate somatomedin secretion. Another example is the African Pygmy, in whom there is a resistance to the administration of GH. This is caused by an unresponsiveness to somatomedin, which suggests that there is a defect in the somatomedin receptors.

Growth hormone alone cannot generate growth without an adequate supply of food, so that in states of malnutrition dwarfism occurs in the face of a mild elevation in growth hormone concentrations in the blood.

Finally, an example of the effect of emotional and environmental factors on growth is found in the condition known as psychosocial dwarfism. Such children suffer emotional deprivation from uncaring or abusive parents. Growth hormone levels are low but return to normal along with an increased rate of growth when the children are removed to a more supportive environment, only to have the cycle repeated when the child is returned to the custody of the parents. These victims tend to be withdrawn and apathetic. They have disrupted sleep and bizarre eating and drinking habits. All of these symptoms are dramatically reversed when the child is removed to compassionate care in a hospital or foster home.

An adult GH-deficient dwarf has the body proportions of a young child. Radiographs (X-ray pictures) of growing ends of bone also show growth retardation in relation to the patient's chronological age. These changes are not apparent at birth but appear some time within the first two years of life. Puberty is often delayed, but untreated individuals may be fertile and give birth to normal children. When it appears in adults, GH deficiency produces only subtle changes, with minor decreases in strength and in the density of bones.

Growth hormone-deficient dwarfs respond dramatically to injections of human growth hormone. Supplies of GH were greatly limited in the past because the only source was GH extracted from human pituitary glands obtained at autopsies. With the availability of human GH manufactured by recombinant DNA technology using bacteria, the supply is potentially unlimited. Most treated patients achieve normal height, but in some, particularly those with the hereditary inability to synthesize growth hormone, antibodies to the injected growth hormone may block the therapeutic action. There is evidence that children with “constitutional short stature,” that is, children from otherwise normal families in whom short stature is the rule in the absence of disease, may also respond to GH treatment.

Excess levels of growth hormone are most often caused by a benign tumor (adenoma) of somatotrophs of the pituitary gland. Rarely, a tumor of the lung or the pancreatic islets produces GHRH, which stimulates normal pituitary somatotrophs to excess secretion when released into the circulation. Even more rarely is there excessive, ectopic production of GH by tumor cells that do not ordinarily synthesize GH. If hypersecretion of growth hormone occurs during childhood, growth progresses at an inordinately rapid rate to extremes, 8 feet, 11 inches in the case of the “Alton Giant.” Giantism is rare because such individuals usually have all of the infirmities described below for acromegaly.

CRANIOPHARYNGIOMA

Craniopharyngiomas are very rare benign (non-cancerous) tumors, with 50% occurring in children under 16 years, and the remainder at any time in adult life.

The tumors can be solid, cystic (full of fluid), calcified, or full of debris. They are slow-growing tumors that can take 2-3 years (or longer) to manifest themselves before a diagnosis is made.

Typical symptoms

headaches (sometimes accompanied by nausea or vomiting) diabetes insipidus disturbed sleep patterns vision disturbance behavioural changes, including introversion and inability to concentrate slow growth increased sensitivity to cold or heat early or delayed puberty - children irregular periods or loss of normal menstrual function (amenorrhoea) - adult females impotence - adult males reduced fertility - adults decrease in sex drive - adults tiredness and susceptibility to infections appetite and weight variations

CUSHING'S DISEASE

Cushing's syndrome describes the condition resulting from too much exposure to steroid hormones.

The commonest cause of Cushing's syndrome (apart from the use of synthetic steroids to treat other conditions) is Cushing's disease. This is a problem arising in the pituitary gland caused by a tumor which overproduces a hormone called ACTH. This in turn stimulates the adrenal glands to overproduce the steroid hormone cortisol. Cushing's syndrome can also be caused by a small growth in one, or both, of the adrenal glands.

Cushing's is rare and is more often found in women than in men. It can affect all age groups, but the peak incidence is in middle age.

Typical symptoms

behavioral changes, depression and mood swings, occasionally psychological problems can be severe face tends to be rounder (moon face) and redder weight gain around the trunk (central obesity) muscle wasting and proximal myopathy (patients have difficulty standing from a seated position without use of arms) tendency to bruise easily appearance of red 'stretch marks' on the abdomen, similar to those which occur during pregnancy irregular periods (oligomenorrhoea) or loss of normal menstrual function (amenorrhoea) - females impotence - males reduced fertility decrease in sex drive increase in hair growth on the face and body (hirsutism) increase in blood pressure development of mild diabetes mellitus Because Cushing's progresses slowly and gradually in most cases, it can go unrecognized for some time.

DIABETES INSIPIDUS

Diabetes Insipidus (DI) is a disorder in which the kidneys are unable to retain water. This results in the production of large amounts of urine which in turn makes you feel dry and very thirsty.

Neurogenic Diabetes Insipidus
This condition is caused by the lack of a water-retaining hormone or chemical in the blood (called vasopressin or ADH). Neurogenic DI is sometimes referred to as Cranial, Central or Pituitary DI.

Nephrogenic Diabetes Insipidus
This condition is caused by an abnormality in the kidneys which prevents the kidneys from responding to the water-retaining hormone.

Diabetes insipidus is not related to the type of diabetes most people have heard of, diabetes mellitus.

Typical symptoms

frequent need to pass urine (polyuria) even during the night extreme thirst leading to excessive drinking (polydipsia) imbalance of electrolytes (relatively high levels of sodium and potassium) Top

HYPOPITUITARISM
The pituitary gland produces a number of hormones or chemicals which are released into the blood to control other glands in the body. If the pituitary is not producing one or more of these hormones, or not producing enough, then this condition is known as hypopituitarism. The term Multiple Pituitary Hormone Deficiency (MPHD) is sometimes used to describe the condition when the pituitary is not producing two or more of these hormones. If all the hormones produced by the pituitary are affected this condition is known as panhypopituitarism.

Hypopituitarism is most often caused by a benign (i.e. not cancerous) tumor of the pituitary gland, or of the brain in the region of the hypothalamus. Pituitary underactivity may be caused by the direct pressure of the tumor mass on the normal pituitary or by the effects of surgery or radiotherapy used to treat the tumor. Less frequently, hypopituitarism can be caused by infections (such as meningitus) in or around the brain or by severe blood loss, by head injury, or by various rare diseases such as sarcoidosis (an illness which resembles tuberculosis).

Typical symptoms

excessive tiredness and decreased energy muscle weakness reduced body hair irregular periods (oligomenorrhoea) or loss of normal menstrual function (amenorrhoea) - females impotence - males reduced fertility decrease in sex drive weight gain increased sensitivity to cold constipation dry skin pale appearance low blood pressure and dizziness on standing (postural hypotension) headaches vision disturbances diabetes insipidus