The nervous and endocrine systems act together to coordinate functions of all body systems.
- Nervous system acts through nerve impulses (action potentials) conducted along axons of neurons. At synapses, nerve impulses trigger the release of mediator (messenger) molecules called neurotransmitter.
- The endocrine system also controls body activities by releasing mediators, called hormones, but the means of control of the two systems are very different.
A hormone (hormon to excite or get moving) is a mediator molecule that is released in one part of the body but regulates the activity of cells in other parts of the body.
Most hormones enter interstitial fluid and then the bloodstream. The circulating blood delivers hormones to cells throughout the body.
Both neurotransmitters and hormones exert their effects by binding to receptors on or in their “target” cells.
Responses of the endocrine system often are slower than responses of the nervous system; although some hormones act within seconds, most take several minutes or more to cause a response.
The effects of nervous system activation are generally briefer than those of the endocrine system. The nervous system acts on specific muscles and glands. The influence of the endocrine system is much
broader; it helps regulate virtually all types of body cells.
The body contains two kinds of glands:
- Exocrine glands
- Endocrine glands.
Exocrine glands secrete their products into ducts that carry the secretions into body cavities, into the lumen of an organ, or to the outer surface of the body, including:
- sebaceous (oil)
- and digestive glands
Endocrine glands secrete their products (hormones) into the interstitial fluid surrounding the secretory cells rather than into ducts.
From the interstitial fluid, hormones diffuse into blood capillaries and blood carries them to target cells throughout the body. Considering that most hormones are required in very small amounts, circulating levels typically are low.
The endocrine glands include the:
- pineal glands
In addition, several organs and tissues are not exclusively classified as endocrine glands but contain cells that secrete hormones. These include the:
- small intestine
- adipose tissue
- and placenta.
Taken together, all endocrine glands and hormone-secreting cells constitute the endocrine system.
The Role of Hormone Receptors
Although a given hormone travels throughout the body in the blood, it affects only specific target cells.
Hormones, like neuro-transmitters, influence their target cells by chemically binding to specific protein receptors. Only the target cells for a given hormone have receptors that bind and recognize that hormone.
Receptors, like other cellular proteins, are constantly being synthesized and broken down.
If a hormone is present in excess, the number of target-cell receptors may decrease— an effect called down-regulation making a target cell less sensitive to a hormone.
In contrast, when a hormone is deficient, the number of receptors may increase. This phenomenon, known as up-regulation, makes a target cell more sensitive to a hormone.
Circulating and Local Hormones
Most endocrine hormones are circulating hormones
- they pass from the secretory cells that make them into interstitial fluid and then into the blood.
Other hormones, termed local hormones
- act locally on neighboring cells or on the same cell that secreted them without first entering the bloodstream.
Local hormones that act on neighboring cells are called paracrines (PAR-a-krins; para- beside or near), and those that act on the same cell that secreted them are called autocrines (AW-to¯ -krins; auto-self).
- Local hormones usually are inactivated quickly
- Circulating hormones may linger in the blood and exert their effects for a few minutes or occasionally for a few hours. In time, circulating hormones are inactivated by the liver and excreted by the kidneys.
Chemical Classes of Hormones
Chemically, hormones can be divided into two broad classes:
- Those that are soluble in lipids
- Those that are soluble in water
The lipid-soluble hormones include:
- Steroid hormones
- Thyroid hormones
- Nitric oxide
- Steroid hormones are derived from cholesterol. Each steroid
hormone is unique. Small differences allow for a large diversity
- Two thyroid hormones (T3 and T4) are synthesized by attaching
iodine to the amino acid tyrosine.
- The gas nitric oxide (NO) is both a hormone and a neurotransmitter.
The water-soluble hormones include:
- Amine hormones
- Peptide and protein hormones
- Eicosanoid hormones
- Amine hormones (a-ME¯ N) are synthesized by removing a molecule of CO2 and otherwise modifying certain amino acids. They are called amines because they retain an amino group
- Peptide hormones and protein hormones are amino acid polymers.
- Eicosanoid hormones (ı¯-KO¯ -sa-noyd) are derived from arachidonic acid, a 20-carbon fatty acid.
Hormone Transport in the Blood
Most water-soluble hormone molecules circulate in the watery blood plasma in a “free” form (not attached to other molecules), but most lipid-soluble hormone molecules are bound to transport proteins.
The transport proteins, which are synthesized by cells in the liver, have three functions:
- They make lipid-soluble hormones temporarily water-soluble, thus increasing their solubility in blood.
- They retard passage of small hormone molecules through the filtering mechanism in the kidneys, thus slowing the rate of hormone loss in the urine.
- They provide a ready reserve of hormone, already present in the bloodstream.
In general, 0.1–10% of the molecules of a lipid-soluble hormone are not bound to a transport protein. This free fraction diffuses out of capillaries, binds to receptors, and triggers responses.
As free hormone molecules leave the blood and bind to their receptors, transport proteins release new ones to replenish the free fraction.
MECHANISMS OF HORMONE ACTION
The response to a hormone depends on both the hormone and the target cell. Various target cells respond differently to the same hormone such as:
- The synthesis of new molecules.
- Changing the permeability of the plasma membrane
- Stimulating transport of a substance into or out of the target cells
- Altering the rate of specific metabolic reactions
- Causing contraction of smooth muscle or cardiac muscle
In part, these varied effects of hormones are possible because a single hormone can set in motion several different cellular responses.
However, a hormone must first “announce its arrival” to a target cell by binding to its receptors.
The receptors for lipid-soluble hormones are located inside target cells. The receptors for water-soluble hormones are part of the plasma membrane of target cells.
Action of Lipid-Soluble Hormones
Lipid-soluble hormones, including steroid hormones and thyroid hormones, bind to receptors within target cells.
Their mechanism of action is as follows:
- A free lipid-soluble hormone molecule diffuses from the blood, through interstitial fluid, and through the lipid bilayer of the plasma membrane into a cell.
- If the cell is a target cell, the hormone binds to and activates receptors located within the cytosol or nucleus. The activated receptor–hormone complex then alters gene expression: It turns specific genes of the nuclear DNA on or off.
- As the DNA is transcribed, new messenger RNA (mRNA) forms, leaves the nucleus, and enters the cytosol. There, it directs synthesis of a new protein, often an enzyme, on the ribosomes.
- The new proteins alter the cell’s activity and cause the responses typical of that hormone.
Action of Water-Soluble Hormones
Because amine, peptide, protein, and eicosanoid hormones are not lipid-soluble, they cannot diffuse through the lipid bilayer of the plasma membrane and bind to receptors inside target cells.
Instead, water-soluble hormones bind to receptors that protrude from the target-cell surface. The receptors are integral trans-membrane proteins in the plasma membrane.
When a water-soluble hormone binds to its receptor at the outer surface of the plasma membrane, it acts as the first messenger. The first messenger (the hormone) then causes production of a second messenger inside the cell, where specific hormone-stimulated responses take place. One common second messenger is cyclic AMP (cAMP).
The action of a typical water-soluble hormone occurs as follows:
- A water-soluble hormone (the first messenger) diffuses from the blood through interstitial fluid and then binds to its receptor at the exterior surface of a target cell’s plasma membrane activating a membrane protein called a G protein. The activated G protein in turn activates adenylate cyclase (a-DEN-i-la¯t SI¯ -kla¯s).
- Adenylate cyclase converts ATP into cyclic AMP (cAMP).
Because the enzyme’s active site is on the inner surface of the plasma membrane, this reaction occurs in the cytosol of the cell.
- Cyclic AMP (the second messenger) activates one or more protein kinases.
- Activated protein kinases phosphorylate(adds a phosphate group to) one or more cellular proteins. Phosphorylation activates some of these proteins and inactivates others, rather like turning a switch on or off.
- Phosphorylated proteins in turn cause reactions that produce physiological responses. Different protein kinases exist within different target cells and within different organelles of the same target cell.
- After a brief period, an enzyme called phosphodiesterase (fos-fo¯-dı¯-ES-ter-a¯s) inactivates cAMP. Thus, the cell’s response is turned off unless new hormone molecules continue to bind to their receptors in the plasma membrane.
The binding of a hormone to its receptor activates many G protein molecules, which in turn activate molecules of adenylate cyclase. Unless they are further stimulated by the binding of more hormone molecules to receptors, G proteins slowly inactivate, thus decreasing the activity of adenylate cyclase and helping to stop the hormone response. G proteins are a common feature of most second- messenger systems.
“Hormones that bind to plasma membrane receptors can induce their effects at very low concentrations because they initiate a cascade or chain reaction, each step of which multiplies or amplifies the initial effect.”
The responsiveness of a target cell to a hormone depends on:
- The hormone’s concentration in the blood
- The abundance of the target cell’s hormone receptors
- Influences exerted by other hormones
A target cell responds more vigorously when the level of a hormone rises or when it has more receptors (upregulation).
In addition, the actions of some hormones on target cells require a simultaneous or recent exposure to a second hormone. In such cases, the second hormone is said to have a permissive effect.
Sometimes the permissive hormone increases the number of receptors for the other hormone, and sometimes it promotes the synthesis of an enzyme required for the expression of the other hormone’s effects.
When the effect of two hormones acting together is greater or more extensive than the effect of each hormone acting alone, the two hormones are said to have a synergistic effect.
When one hormone opposes the actions of another hormone, the two hormones are said to have antagonistic effects.
CONTROL OF HORMONE SECRETION
The release of most hormones occurs in short bursts, with little or no secretion between bursts. When stimulated, an endocrine gland will release its hormone in more frequent bursts, increasing the concentration of the hormone in the blood. In the absence of stimulation, the blood level of the hormone decreases.
Regulation of secretion normally prevents overproduction or underproduction of any given hormone. Hormone secretion is regulated by:
- Signals from the nervous system
- Chemical changes in the blood
- Other hormones
Nerve impulses to the adrenal medullae regulate the release of epinephrine
Blood Ca2 level regulates the secretion of parathyroid hormone
A hormone from the anterior pituitary (adrenocorticotropic hormone) stimulates the release of cortisol by the adrenal cortex.
Most hormonal regulatory systems work via negative feedback, but a few operate via positive feedback.
Now that you have a general understanding of the roles of hormones in the endocrine system, we turn to discussions of the various endocrine glands and the hormones they secrete.
HYPOTHALAMUS AND PITUITARY GLAND
For many years, the pituitary gland was called the “master” endocrine gland because it secretes several hormones that control other endocrine glands.
We now know that the pituitary gland itself has a master— the hypothalamus. This small region of the brain below the thalamus is the major link between the nervous and endocrine systems.
Cells in the hypothalamus synthesize at least nine different hormones, and the pituitary gland secretes seven. Together, these hormones play important roles in the regulation of virtually all aspects of growth, development, metabolism, and homeostasis.
The pituitary gland
- pea-shaped &1–1.5 cm (0.5 in.) in diameter
- lies in the hypophyseal fossa of the sella turcica of the sphenoid bone.
It attaches to the hypothalamus by a stalk:
- The infundibulum (in-fun-DIB-u¯-lum a funnel)
and has two anatomically and functionally separate portions:
- the anterior pituitary
- the posterior pituitary
The anterior pituitary is composed of epithelial tissue & consists of two parts:
- The pars distalis is the larger portion
- The pars tuberalis forms a sheath around the infundibulum.
The posterior pituitary (posterior lobe),is composed of neural tissue. It also consists of two parts:
- the pars nervosa (ner-VO¯ -sa), the larger bulbar portion
- and the infundibulum.
The anterior pituitary secretes hormones that regulate a wide range of bodily activities, from growth to reproduction.
Release of anterior pituitary hormones is stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus. Thus, the hypothalamic hormones are an important link between the nervous and endocrine systems.
Hypophyseal Portal System
Hypothalamic hormones that release or inhibit anterior pituitary hormones reach the anterior pituitary through a portal system.
Usually, blood passes from the heart through an artery to a capillary to a vein and back to the heart.
In a portal system, blood flows from one capillary network into a portal vein, and then into a second capillary network before returning to the heart.
The name of the portal system indicates the location of the second capillary network.
In the hypophyseal portal system, blood flows from capillaries in the hypothalamus into portal veins that carry blood to capillaries of the anterior pituitary.
- Superior hypophyseal arteries bring blood into the hypothalamus
- At the junction of the median eminence of the hypothalamus and the infundibulum, these arteries divide into a capillary network called the primary plexus of the hypophyseal portal system.
- Blood drains into the hypophyseal portal veins that pass down the outside of the infundibulum
- In the anterior pituitary, the hypophyseal portal veins divide again and form another capillary network called the secondary plexus of the hypophyseal portal system.
- Neurosecretory cells synthesize the hypothalamic releasing and inhibiting hormones into
- Primary plexus of the hypophyseal portal system
- through the portal veins
- into the secondary plexus.
This direct route permits hypothalamic hormones to act immediately on anterior pituitary cells, before the hormones are diluted or destroyed in the general circulation.
Hormones secreted by anterior pituitary cells pass into the secondary plexus capillaries, which drain into the anterior hypophyseal veins and out into the general circulation. Anterior pituitary hormones then travel to target tissues throughout the body.
Those anterior pituitary hormones that act on other endocrine glands are called tropic hormones (TRO¯ -pik) or tropins
Cell Types & Hormones in the Anterior Pituitary Lobe
- Human Growth Hormone(HGH)
- Promotes protein synthesis i.e. tissue growth & lipolysis (ATP)
- Growth hormone–releasing hormone (GHRH) promotes secretion of human growth hormone
- Growth hormone–inhibiting hormone (GHIH) suppresses it.
- Thyroid Stimulating Hormone(TSH)
- Stimulates production of thyroxine (T4) & triiodothyronine (T3)
- Thyrotropin releasing hormone (TRH) from the hypothalamus controls secretion
- There is no thyrotropin-inhibiting hormone
- Follicle Stimulating Hormone (FSH)
- M – stimulates sperm production.
- F -stimulates growth of follicles and production of oestrogen
- Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates FSH release.
- Release of GnRH and FSH is suppressed by estrogens in females and by testosterone in males.
- There is no gonadotropin-inhibiting hormone.
- Luteinizing Hormone(LH)
- Male – stimulates production of testosterone
- Females – triggers ovulation
- Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates FSH release.
- There is no gonadotropin-inhibiting hormone.
- Promotes breast growth & milk production post partum
- Prolactin-releasing hormone (PRH) from the hypothalamus stimulates prolactin release
- In females, prolactin inhibiting hormone (PIH) inhibits the release of prolactin
- Adrenocorticotropic Hormone(ACTH)
- Stimulates production of hormones by the adrenal cortex mainly cortisol
- Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates secretion of ACTH.
- Stress-related stimuli, such as low blood glucose or physical trauma, and interleukin-1, a substance produced by macrophages, also stimulate release of ACTH. Glucocorticoids inhibit CRH and ACTH release via negative feedback.
Control of Secretion by the Anterior Pituitary
Secretion of anterior pituitary hormones is regulated in two ways.
First, neurosecretory cells in the hypothalamus secrete:
- five releasing hormones, which stimulate secretion of anterior pituitary hormones,
- and two inhibiting hormones, which suppress secretion of anterior pituitary hormones.
Second, negative feedback in the form of hormones released by target glands decreases secretions of three types of anterior pituitary cells.
In such negative feedback loops, the secretory activity of:
decreases when blood levels of their target gland hormones rise.
For example, ACTH stimulates the cortex of the adrenal gland to secrete cortisol. In turn, an elevated blood level of cortisol decreases secretion of both corticotropin and corticotropin-releasing hormone (CRH) by suppressing the activity of the anterior pituitary corticotrophs and hypothalamic neurosecretory cells.
Human Growth Hormone and Insulin like Growth Factors
Somatotrophs are the most numerous cells in the anterior pituitary, and human growth hormone (hGH) is the most plentiful anterior pituitary hormone.
The main function of hGH is to:
- Promote synthesis and secretion of small protein hormones called insulin like growth factors (IGFs). In response to human growth hormone, cells in the:
- skeletal muscles
- and other tissues secrete IGFs,
which may either enter the bloodstream from the liver or act locally in other tissues as autocrines or paracrines.
The functions of IGFs include the following:
- IGFs cause cells to grow and multiply.
- IGFs also decrease the breakdown of proteins and the use of amino acids for ATP production.
- Due to these effects of the IGFs, human growth hormone increases the growth rate of the skeleton and skeletal muscles during childhood and the teenage years.
- In adults, human growth hormone and IGFs help maintain the mass of muscles and bones and promote healing of injuries and tissue repair.
Somatotrophs in the anterior pituitary release bursts of human growth hormone every few hours, especially during sleep.
Their secretory activity is controlled mainly by two hypothalamic hormones:
- Growth hormone–releasing hormone (GHRH) promotes secretion of human growth hormone
- Growth hormone–inhibiting hormone (GHIH) suppresses it.
A major regulator of GHRH and GHIH secretion is the blood glucose level
Thyroid-stimulating hormone (TSH) stimulates the synthesis and secretion of the two thyroid hormones:
- triiodothyronine (T3)
- thyroxine (T4)
both produced by the thyroid gland.
Thyrotropin releasing hormone (TRH) from the hypothalamus controls TSH secretion.
- Release of TRH in turn depends on blood levels of T3 and T4
- high levels of T3 and T4 inhibit secretion of TRH via negative feedback.
- There is no thyrotropin-inhibiting hormone.
In females, the ovaries are the targets for follicle-stimulating hormone (FSH).
- Each month FSH initiates the development of several ovarian follicles, saclike arrangements of secretory cells that surround a developing oocyte.
- FSH also stimulates follicular cells to secrete estrogens (female sex hormones).
In males, FSH stimulates sperm production in the testes.
- Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates FSH release.
- Release of GnRH and FSH is suppressed by estrogens in females and by testosterone (the principal male sex hormone) in males through negative feedback systems.
- There is no gonadotropin-inhibiting hormone.
In females, luteinizing hormone (LH) triggers ovulation, the release of a secondary oocyte (future ovum) by an ovary.
- LH stimulates formation of the corpus luteum (structure formed after ovulation) in the ovary and the secretion of progesterone (another female sex hormone) by the corpus luteum.
- Together, FSH and LH also stimulate secretion of estrogens by ovarian cells. Estrogens and progesterone prepare the uterus for implantation of a fertilized ovum and help prepare the mammary glands for milk secretion.
In males, LH stimulates cells in the testes to secrete testosterone.
Secretion of LH, like that of FSH, is controlled by gonadotropin-releasing hormone (GnRH).
Prolactin (PRL), together with other hormones, initiates and maintains milk production by the mammary glands.
- By itself, prolactin has only a weak effect.
- Only after the mammary glands have been primed by estrogens, progesterone, glucocorticoids, human growth hormone, thyroxine, and insulin, which exert permissive effects, does PRL bring about milk production.
- Ejection of milk from the mammary glands depends on the hormone oxytocin, which is released from the posterior pituitary.
- Together, milk production and ejection constitute lactation.
The hypothalamus secretes both inhibitory and excitatory hormones that regulate prolactin secretion.
In females, prolactin inhibiting hormone (PIH), which is dopamine, inhibits the release of prolactin from the anterior pituitary most of the time.
Each month, just before menstruation begins, the secretion of PIH diminishes and the blood level of prolactin rises, but not enough to stimulate milk production. Breast tenderness just before menstruation may be caused by elevated prolactin. As the menstrual cycle begins anew, PIH is again secreted and the prolactin level drops. During pregnancy, the prolactin level rises, stimulated by prolactin-releasing hormone (PRH) from the hypothalamus. The sucking action of a nursing infant causes a reduction in hypothalamic secretion of PIH.
Corticotrophs secrete mainly adrenocorticotropic hormone (ACTH).
ACTH controls the production and secretion of cortisol and other glucocorticoids by the cortex (outer portion) of the adrenal glands.
Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates secretion of ACTH by corticotrophs.
Stress-related stimuli, such as low blood glucose or physical trauma, and interleukin-1, a substance produced by macrophages, also stimulate release of ACTH. Glucocorticoids inhibit CRH and ACTH release via negative feedback.
Although the posterior pituitary does not synthesize hormones, it does store and release two hormones.
It consists of axons and axon terminals of ,hypothalamic neurosecretory cells. The neuronal cell bodies synthesize the hormone oxytocin and produce antidiuretic hormone (ADH), also called vasopressin.
After their production in the cell bodies of neurosecretory cells, oxytocin and antidiuretic hormone are packaged into secretory vesicles, which move by fast axonal transport to the axon terminals in the posterior pituitary, where they are stored until nerve impulses trigger exocytosis and release of the hormone.
- Blood is supplied to the posterior pituitary by the inferior hypophyseal arteries, which branch from the internal carotid arteries.
- They drain into the capillary plexus of the infundibular process, a capillary network that receives secreted oxytocin and antidiuretic hormone.
- From this plexus, hormones pass into the posterior hypophyseal veins for distribution to target cells in other tissues.
Control of Secretion by the posterior pituitary
During and after delivery of a baby, oxytocin affects two target tissues:
- the mother’s uterus
- and breasts.
During delivery, stretching of the cervix of the uterus stimulates the release of oxytocin which, in turn, enhances contraction of smooth muscle cells in the wall of the uterus
After delivery, it stimulates milk ejection (“letdown”) from the mammary glands in response to the mechanical stimulus provided by a suckling infant.
As its name implies, an antidiuretic is a substance that decreases urine production. ADH causes the kidneys to return more water to the blood, thus decreasing urine volume.
In the absence of ADH, urine output increases more than tenfold, from the normal 1 to 2 liters to about 20 liters a day. Drinking alcohol often causes frequent and copious urination because alcohol inhibits secretion of ADH.
ADH also decreases the water lost through sweating and causes constriction of arterioles, which increases blood pressure. This hormone’s other name, vasopressin reflects this effect on blood pressure. The amount of ADH secreted varies with blood osmotic pressure and blood volume.
The butterfly-shaped thyroid gland is located just inferior to the larynx (voice box). It is composed of right and left lateral lobes, one on either side of the trachea, that are connected by an isthmus (IS-mus a narrow passage) anterior to the trachea.
About 50% of thyroid glands have a small third lobe, called the pyramidal lobe. It extends superiorly from the isthmus. The normal mass of the thyroid is about 30 g (1 oz).
Microscopic spherical sacs called thyroid follicles make up most of the thyroid gland. The wall of each follicle consists primarily of cells called follicular cells, most of which extend to the lumen (internal space) of the follicle. A basement membrane surrounds each follicle.
The follicular cells produce two hormones:
- Thyroxine (thı¯-ROK-se¯n), which is also called T4 because it contains four atoms of iodine
- Triiodothyronine (trı¯-ı¯-o¯-do¯-THI¯-ro¯-ne¯n) or T3, which contains three atoms of iodine.
T3 and T4 together are also known as thyroid hormones.
A few cells called parafollicular cells (par-a-fo-LIK-u-lar) or C cells lie between follicles. They produce the hormone calcitonin (kal-si-TO¯ -nin), which helps regulate calcium homeostasis.
Formation, Storage, and Release of Thyroid Hormones
The thyroid gland is the only endocrine gland that stores its secretory product in large quantities—normally about a 100-day supply.
Synthesis and secretion of T3 and T4 occurs as follows:
- Iodide trapping. Thyroid follicular cells trap iodide ions (I)
- Synthesis of thyroglobulin(TGB). Thyroid follicular cells synthesize thyroglobulin (TGB) which is then released into the lumen of the
- Oxidation of iodide. As the iodide ions are being oxidized(removal of electrons), they pass through the membrane into the lumen of the follicle.
- Iodination of tyrosine. Iodine molecules form & react with tyrosines. Binding of one iodine atom yields T1, and a second produces T2. The TGB with attached iodine atoms is stored in the lumen of the thyroid follicle, and is termed colloid.
- Coupling of T1 and T2. Two T2 molecules join to form T4, or one T1 and one T2 join to form T3.
- Pinocytosis and digestion of colloid. Colloid reenter follicular cells and merge with lysosomes. Digestive enzymes in the lysosomes break down TGB, cleaving off molecules of T3 and T4.
- Secretion of thyroid hormones. Because T3 and T4 are lipid soluble, they diffuse through the plasma membrane into interstitial fluid and then into the blood. T4 normally is secreted in greater quantity than T3, but T3 is several times more potent. Moreover, after T4 enters a body cell, most of it is converted to T3 by removal of one iodine.
- Transport in the blood. More than 99% of both the T3 and the T4 combine with transport proteins in the blood, mainly thyroxine-binding globulin (TBG).
Actions of Thyroid Hormones
Because most body cells have receptors for thyroid hormones, T3 and T4 exert their effects throughout the body.
- Thyroid hormones increase basal metabolic rate (BMR), the rate of oxygen consumption under standard or basal conditions (awake, at rest, and fasting), by stimulating the use of cellular oxygen to produce ATP. When the basal metabolic rate increases, cellular metabolism of carbohydrates, lipids, and proteins increases.
- A second major effect of thyroid hormones is to stimulate synthesis of additional sodium–potassium pumps (Na/K ATPase), which use large amounts of ATP to continually:
- Eject sodium ions (Na) from the cytosol into the extracellular fluid
- Eject potassium ions (K) from the extracellular fluid into the cytosol.
As cells produce and use more ATP, more heat is given off, and body temperature rises. This phenomenon is called the calorigenic effect. In this way, thyroid hormones play an important role in the maintenance of normal body temperature.
- Thyroid hormones stimulate protein synthesis and increase the use of glucose and fatty acids for ATP production. They also increase lipolysis and enhance cholesterol excretion, thus reducing blood cholesterol level.
- The thyroid hormones enhance some actions of the catecholamines:
because they up-regulate beta receptors. For this reason, symptoms of hyperthyroidism include:
- Increased heart rate
- more forceful heartbeats
- and increased blood pressure
- Together with human growth hormone and insulin, thyroid hormones accelerate body growth, particularly the growth of the nervous and skeletal systems. Deficiency of thyroid hormones during fetal development, infancy, or childhood causes severe mental retardation and stunted bone growth.
Control of Thyroid Hormone Secretion
- Thyrotropin-releasing hormone (TRH) from the hypothalamus
- and thyroid-stimulating hormone (TSH) from the anterior pituitary
stimulate synthesis and release of thyroid hormones:
- Low blood levels of T3 and T4 or low metabolic rate stimulates the hypothalamus to secrete TRH
- TRH enters the hypophyseal portal veins and flows to the anterior pituitary, where it stimulates thyrotrophs to secrete TSH
- TSH stimulates virtually all aspects of thyroid follicular cell activity
- The thyroid follicular cells release T3 and T4 into the blood until the metabolic rate returns to normal
- An elevated level of T3 inhibits release of TRH and TSH (negative feedback inhibition).
Conditions that increase ATP demand:
- a cold environment
- high altitude
also increase the secretion of the thyroid hormones.
Produced by the parafollicular cells of the thyroid gland, calcitonin (CT) can decrease the level of calcium in the blood. Calcitonin inhibits the activity of osteoclasts.
The secretion of CT is controlled by a negative feedback system.
When its blood level is high, calcitonin lowers the amount of blood calcium and phosphates by inhibiting bone resorption.
Partially embedded in the posterior surface of the lateral lobes of the thyroid gland are several small, round masses of tissue called the parathyroid glands (para- beside).
Each has a mass of about 40 mg (0.04 g). Usually, one superior and one inferior parathyroid gland are attached to each lateral thyroid lobe, for a total of four.
Microscopically, the parathyroid glands contain two kinds of epithelial cells.
- The more numerous cells, called chief (principal) cells, produce parathyroid hormone (PTH).
- The function of the other kind of cell, called an oxyphil cell, is not known in a normal parathyroid gland. However, its presence clearly helps to identify the parathyroid gland histologically due to its unique staining characteristics.
Parathyroid hormone is the major regulator of the levels of:
- calcium (Ca2)
- magnesium (Mg2)
- and phosphate (HPO4 2)
ions in the blood.
The specific action of PTH is to increase the number and activity of osteoclasts. The result is elevated bone resorption, which releases ionic calcium and phosphates into the blood.
PTH also acts on the kidneys.
- First, it slows the rate at which calcium and magnesium are lost from blood into the urine.
- Second, it increases loss of phosphate from blood into the urine. Because more phosphate is lost in the urine than is gained from the bones, PTH decreases blood phosphate level and increases blood calcium and magnesium levels.
- A third effect of PTH on the kidneys is to promote formation of the hormone calcitriol (kal-si-TRI¯-ol), the active form of vitamin D. Calcitriol increases the rate of calcium, phosphate, and magnesium absorption from the gastrointestinal tract into the blood.
The blood calcium level directly controls the secretion of both calcitonin and parathyroid hormone via negative feedback loops that do not involve the pituitary gland:
- A higher than normal level of calcium ions (Ca2) in the blood stimulates parafollicular cells of the thyroid gland to release more calcitonin. Calcitonin inhibits the activity of osteoclasts, thereby decreasing the blood calcium level.
- A lower than normal level of calcium in the blood stimulates chief cells of the parathyroid gland to release more PTH. PTH promotes resorption of bone extracellular matrix, which releases calcium into the blood and slows loss of calcium in the urine, raising the blood level of calcium.
- PTH also stimulates the kidneys to synthesize calcitriol, the active form of vitamin D.
- Calcitriol stimulates increased absorption of calcium from foods in the gastrointestinal tract, which helps increase the blood level of calcium.
The paired adrenal (suprarenal) glands, one of which lies superior to each kidney in the retroperitoneal space, have a flattened pyramidal shape. In an adult, each adrenal gland is 3–5 cm in height, 2–3 cm in width, and a little less than 1 cm thick, with a mass of 3.5–5 g, only half its size at birth.
During embryonic development, the adrenal glands differentiate into two structurally and functionally distinct regions:
- a large, peripherally located adrenal cortex comprising 80–90% of the gland
- and a small, centrally located adrenal medulla.
A connective tissue capsule covers the gland. The adrenal glands, like the thyroid gland, are highly vascularized.
The adrenal cortex produces steroid hormones that are essential for life. Complete loss of adrenocortical hormones leads to death due to dehydration and electrolyte imbalances in a few days to a week, unless hormone replacement therapy begins promptly.
The adrenal medulla produces three catecholamine hormones:
- and a small amount of dopamine
The adrenal cortex is subdivided into three zones, each of which secretes different hormones:
- The outer zone, just deep to the connective tissue capsule, is the zona glomerulosa (glo-mer-u¯-LO¯ -sa). Its cells secrete hormones called mineralocorticoids because they affect mineral homeostasis.
- The middle zone, or zona fasciculata (fa-sik-u¯-LA-ta), is the widest of the three zones. The cells secrete mainly glucocorticoids (gloo-ko¯-KORti- koyds), primarily cortisol, so named because they affect glucose homeostasis.
- The cells of the inner zone, the zona reticularis (re-tik-u¯-LAR-is), synthesize small amounts of weak androgens, steroid hormones that have masculinizing effects.
Aldosterone (al-DOS-ter-o¯n) is the major mineralocorticoid.
It regulates homeostasis of two mineral ions—namely:
- Sodium ions (Na)
- and potassium ions (K)
and helps adjust blood pressure and blood volume.
Aldosterone also promotes excretion of H in the urine; this removal of acids from the body can help prevent acidosis (blood pH below 7.35).
The renin–angiotensin–aldosterone or RAA pathway controls secretion of aldosterone:
- Stimuli that initiate the renin–angiotensin–aldosterone pathway include dehydration, Na deficiency, or hemorrhage.
- These conditions cause a decrease in blood volume.
- Decreased blood volume leads to decreased blood pressure.
- Lowered blood pressure stimulates certain cells of the kidneys, to secrete the enzyme renin
- The level of renin in the blood increases.
- Renin converts angiotensinogen (an-je¯-o¯-ten-SIN-o¯ -jen), a plasma protein produced by the liver, into angiotensin I.
- Blood containing increased levels of angiotensin I circulates in the body.
- As blood flows through capillaries, particularly those of the lungs, the enzyme angiotensin-converting enzyme (ACE) converts angiotensin I into the hormone angiotensin II.
- Blood level of angiotensin II increases.
- Angiotensin II stimulates the adrenal cortex to secrete aldosterone.
- Blood containing increased levels of aldosterone circulates to the kidneys.
- In the kidneys, aldosterone increases reabsorption of Na, which in turn causes reabsorption of water by osmosis. As a result, less water is lost in the urine. Aldosterone also stimulates the kidneys to increase secretion of K and H into the urine.
- With increased water reabsorption by the kidneys, blood volume increases.
- As blood volume increases, blood pressure increases to normal.
- Angiotensin II also stimulates contraction of smooth muscle in the walls of arterioles. The resulting vasoconstriction of the arterioles increases blood pressure and thus helps raise blood pressure to normal.
- Besides angiotensin II, a second stimulator of aldosterone secretion is an increase in the K concentration of blood (or interstitial fluid). A decrease in the blood K level has the opposite effect.
The glucocorticoids, which regulate:
- Resistance to stress
- cortisol (KOR-ti-sol; also called hydrocortisone)
- corticosterone (kor-ti-KOS-ter-o¯n)
- cortisone (KOR-tiso ¯n).
Of these three hormones secreted by the zona fasciculata, cortisol is the most abundant, accounting for about 95% of glucocorticoid activity.
Control of glucocorticoid secretion occurs via a typical negative feedback system.
Low blood levels of glucocorticoids, mainly cortisol, stimulate:
- Neurosecretory cells in the hypothalamus to secrete corticotropin–releasing hormone (CRH)
- CRH (together with a low level of cortisol) promotes the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary.
- ACTH flows in the blood to the adrenal cortex, where it stimulates glucocorticoid secretion
Glucocorticoids have the following effects:
- Protein breakdown, mainly in muscle fibers increasing amino acids in the bloodstream which may be used by body cells for synthesis of new proteins or for ATP production.
- Glucose formation. Liver cells may convert certain amino acids to glucose,which can be used for ATP production.
- Lipolysis. The release of fatty acids from adipose tissue into the blood.
- Resistance to stress. The additional glucose supplied by the liver cells provides tissues with a ready source of ATP to combat a range of stresses such as fright. Because glucocorticoids make blood vessels more sensitive to other hormones that cause vasoconstriction, they raise blood pressure.
- Anti-inflammatory effects. White blood cells that participate in inflammatory responses are inhibited. Glucocorticoids also retard tissue repair, and as a result, they slow wound healing.
- Depression of immune responses. For this reason, they are prescribed for organ transplant recipients to retard tissue rejection by the immune system.
In both males and females, the adrenal cortex secretes small amounts of weak androgens.
The major androgen secreted by the adrenal gland is:
- Dehydroepiandrosterone(DHEA)de¯-hı¯-dro¯- ep-e¯-an-DROS-ter-o¯ n
After puberty in males, the androgen testosterone is also released in much greater quantity by the testes. Thus, the amount of androgens secreted by the adrenal gland in males is usually so low that their effects are insignificant.
In females, however, adrenal androgens play important roles.
- They promote libido (sex drive) and are converted into estrogens (feminizing sex steroids) by other body tissues.
- After menopause, when ovarian secretion of estrogens ceases, all female estrogens come from conversion of adrenal androgens.
Adrenal androgens also:
- stimulate growth of axillary and pubic hair in boys and girls
- and contribute to the prepubertal growth spurt.
Although control of adrenal androgen secretion is not fully understood, the main hormone that stimulates its secretion is ACTH.
The inner region of the adrenal gland, the adrenal medulla, is a modified sympathetic ganglion of the autonomic nervous system (ANS). Rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones.
Because the ANS exerts direct control, hormone release can occur very quickly.
The two major hormones are:
- Epinephrine (ep-i-NEF-rin) – (adrenaline) 80%
- Norepinephrine (NE),- (noradrenaline) 20%
The hormones of the adrenal medulla intensify sympathetic responses that occur in other parts of the body.
In stressful situations and during exercise, impulses from the hypothalamus stimulate sympathetic neurons, which in turn stimulate the chromaffin cells to secrete epinephrine and norepinephrine.
These two hormones greatly augment the fight-or-flight response.
By increasing heart rate and force of contraction, epinephrine and norepinephrine increase the output of the heart, which increases blood pressure. They also increase blood flow to the heart, liver, skeletal muscles, and adipose tissue; dilate airways to the lungs; and increase blood levels of glucose and fatty acids.
The pancreas is both an endocrine gland and an exocrine gland.
A flattened organ that measures about 12.5–15 cm (5–6 in.) in length, the pancreas is located in the curve of the duodenum, the first part of the small intestine, and consists of a head, a body, and a tail.
- 99% of the exocrine cells of the pancreas are arranged in clusters called acini (AS-i-nı¯).
- The acini produce digestive enzymes, which flow into the gastrointestinal tract through a network of ducts.
- Scattered among the exocrine acini are 1–2 million tiny clusters of endocrine tissue called pancreatic islets.
- Abundant capillaries serve both the exocrine and endocrine portions of the pancreas.
Cell Types in the Pancreatic Islets
Each pancreatic islet includes four types of hormone-secreting cells:
- 1. Alpha or A cells constitute about 17% of pancreatic islet cells and secrete glucagon (GLOO-ka-gon).
- 2. Beta or B cells constitute about 70% of pancreatic islet cells and secrete insulin (IN-soo-lin).
- 3. Delta or D cells constitute about 7% of pancreatic islet cells and secrete somatostatin (so¯-ma-to-STAT-in).
- 4. F cells constitute the remainder of pancreatic islet cells and secrete pancreatic polypeptide.
The interactions of the four pancreatic hormones are complex and not completely understood. We do know that glucagon raises blood glucose level, and insulin lowers it.
Regulation of Glucagon and Insulin Secretion
- The principal action of glucagon is to increase blood glucose level when it falls below normal.
- Insulin, on the other hand, helps lower blood glucose level when it is too high.
The level of blood glucose controls secretion of glucagon and insulin via negative feedback:
Low blood glucose level (hypoglycemia)
Stimulates secretion of glucagon from alpha cells of the pancreatic islets.
Glucagon acts on hepatocytes (liver cells) to:
- Accelerate the conversion of glycogen into glucose
- Promote formation of glucose from lactic acid and certain amino acids
- As a result, hepatocytes release glucose into the blood more rapidly
and blood glucose level rises.
If blood glucose continues to rise, high blood glucose level (hyperglycemia) inhibits release of glucagon (negative feedback).
High blood glucose (hyperglycemia)
Stimulates secretion of insulin by beta cells of the pancreatic islets. Insulin acts on various cells in the body to:
- Accelerate facilitated diffusion of glucose into cells to:
- Speed conversion of glucose into glycogen
- Increase uptake of amino acids by cells and to increase protein synthesis
- To speed synthesis of fatty acids
- To slow the conversion of glycogen to glucose
- To slow the formation of glucose from lactic acid and amino acids
As a result, blood glucose level falls.
If blood glucose level drops below normal, low blood glucose inhibits release of insulin (negative feedback) and stimulates release of glucagon.
OVARIES AND TESTES
Gonads are the organs that produce gametes:
- Sperm in males
- Oocytes in females
In addition to their reproductive function, the gonads secrete hormones.
The ovaries, paired oval bodies located in the female pelvic cavity, produce several steroid hormones including:
- Two estrogens (estradiol and estrone)
- and progesterone.
These female sex hormones, along with FSH and LH from the anterior pituitary:
- Regulate the menstrual cycle
- Maintain pregnancy
- Prepare the mammary glands for lactation
- They also promote enlargement of the breasts and widening of the hips at puberty, and help maintain these female secondary sex characteristics.
The ovaries also produce inhibin, a protein hormone that inhibits secretion of follicle-stimulating hormone (FSH).
During pregnancy, the ovaries and placenta produce a peptide hormone called relaxin (RLX), which increases the flexibility of the pubic symphysis during pregnancy and helps dilate the uterine cervix during labor and delivery. These actions help ease the baby’s passage by enlarging the birth canal.
The male gonads, the testes, are oval glands that lie in the scrotum.
The main hormone produced and secreted by the testes is:
- Testosterone, an androgen or male sex hormone.
- Testosterone stimulates descent of the testes before birth
- Regulates production of sperm
- and stimulates the development and maintenance of male secondary sex characteristics, such as beard growth and deepening of the voice.
The testes also produce inhibin, which inhibits secretion of FSH.
PINEAL GLAND AND THYMUS
The pineal gland is a small endocrine gland attached to the roof of the third ventricle of the brain at the midline.
The pineal gland secretes melatonin, an amine hormone derived from serotonin. Melatonin appears to contribute to the setting of the body’s biological clock, which is controlled by the nucleus of the hypothalamus.
As more melatonin is liberated during darkness than in light, this hormone is thought to promote sleepiness.
In response to visual input from the eyes (retina), the nucleus stimulates sympathetic neurons , which in turn stimulate the pineal gland to secrete melatonin in a rhythmic pattern, with low levels of melatonin secreted during the day and significantly higher levels secreted at night.
The thymus is located behind the sternum between the lungs.
The hormones produced by the thymus:
- thymic humoral factor (THF)
- thymic factor (TF)
- and thymopoietin promote the maturation of T cells
Homeostasis is the condition of equilibrium (balance) in the body’s internal environment due to the constant interaction of the body’s many regulatory processes.
Homeostasis is a dynamic condition. In response to changing conditions, the body’s equilibrium can shift among points in a narrow range that is compatible with maintaining life.
Homeostasis and Body Fluids
An important aspect of homeostasis is maintaining the volume and composition of body fluids, dilute, watery solutions containing dissolved chemicals that are found inside cells as well as surrounding them.
The fluid within cells is intracellular fluid (ICF). The fluid outside body cells is extracellular fluid (ECF). The ECF that fills the narrow spaces between cells of tissues is known as interstitial fluid.
- ECF within blood vessels is termed blood plasma
- Within lymphatic vessels it is called lymph
- In and around the brain and spinal cord it is known as cerebrospinal fluid
- In joints it is referred to as synovial fluid
- and the ECF of the eyes is called aqueous humor and vitreous body.
The proper functioning of body cells depends on precise regulation of the composition of the interstitial fluid surrounding them. Because of this, interstitial fluid is often called the body’s internal environment.
The composition of interstitial fluid changes as substances move back and forth between it and blood plasma. Such exchange of materials occurs across the thin walls of the smallest blood vessels in the body, the blood capillaries.
This movement in both directions across capillary walls provides needed materials, such as: glucose, oxygen, ions, and so on, to tissue cells.
It also removes wastes, such as carbon dioxide, from interstitial fluid.
Control of Homeostasis
Homeostasis in the human body is continually being disturbed.
Some disruptions come from the external environment in the form of physical insults such as the intense heat of a hot summer day or a lack of enough oxygen for that two-mile run. Other disruptions originate in the internal environment, such as a blood glucose level that falls too low when you skip breakfast.
Homeostatic imbalances may also occur due to psychological stresses in our social environment— the demands of work and school, for example.
In most cases the disruption of homeostasis is mild and temporary, and the responses of body cells quickly restore balance in the internal environment. However, in some cases the disruption of homeostasis may be intense and prolonged, as in:
- overexposure to temperature extremes,
- severe infection,
- or major surgery.
Fortunately, the body has many regulating systems that can usually bring the internal environment back into balance. Most often, the nervous system and the endocrine system, working together or independently, provide the needed corrective measures.
The nervous system regulates homeostasis by sending electrical signals known as nerve impulses (action potentials) to organs that can counteract changes from the balanced state.
The endocrine system includes many glands that secrete messenger molecules called hormones into the blood.
Nerve impulses typically cause rapid changes, but hormones usually work more slowly. Both means of regulation, however, work toward the same end, usually through negative feedback systems.
What is the difference between positive and negative feedback?
NEGATIVE FEEDBACK SYSTEMS
A negative feedback system reverses a change in a controlled condition.
Consider the regulation of blood pressure. Blood pressure (BP) is the force exerted by blood as it presses against the walls of blood vessels.
When the heart beats faster or harder, BP increases. If some internal or external stimulus causes blood pressure (controlled condition) to rise, the following sequence of events occurs:
- Baroreceptors(the receptors), pressure-sensitive nerve cells located in the walls of certain blood vessels, detect the higher pressure.
- The baroreceptors send nerve impulses (input) to the brain (control center), which interprets the impulses and responds by sending nerve impulses (output) to the heart and blood vessels (the effectors).
- Heart rate decreases and blood vessels dilate (widen), which cause BP to decrease (response).
This sequence of events quickly returns the controlled condition—blood pressure—to normal, and homeostasis is restored.
Notice that the activity of the effector causes BP to drop, a result that negates the original stimulus (an increase in BP). This is why it is called a negative feedback system.
POSITIVE FEEDBACK SYSTEMS
Unlike a negative feedback system, a positive feedback system tends to strengthen or reinforce a change in one of the body’s controlled conditions.
In a positive feedback system, the response affects the controlled condition differently than in a negative feedback system.
The control center still provides commands to an effector, but this time the effector produces a physiological response that adds to or reinforces the initial change in the controlled condition. The action of a positive feedback system continues until it is interrupted by some mechanism.
Normal childbirth provides a good example of a positive feedback system.
- The first contractions of labor (stimulus) push part of the fetus into the cervix, the lowest part of the uterus, which opens into the vagina.
- Stretch-sensitive nerve cells (receptors) monitor the amount of stretching of the cervix (controlled condition).
- As stretching increases, they send more nerve impulses (input) to the brain (control center), which in turn releases the hormone oxytocin (output) into the blood.
- Oxytocin causes muscles in the wall of the uterus (effector) to contract even more forcefully.
- The contractions push the fetus farther down the uterus, which stretches the cervix even more.
- The cycle of stretching, hormone release, and ever-stronger contractions is interrupted only by the birth of the baby.
- Then, stretching of the cervix ceases and oxytocin is no longer released.
Another example of positive feedback is what happens to your body when you lose a great deal of blood. Under normal conditions, the heart pumps blood under sufficient pressure to body cells to provide them with oxygen and nutrients to maintain homeostasis.
Upon severe blood loss:
- blood pressure drops
- and blood cells (including heart cells) receive less oxygen and function less efficiently.
If the blood loss continues:
- heart cells become weaker
- the pumping action of the heart decreases further
- and blood pressure continues to fall.
This is an example of a positive feedback cycle that has serious consequences and may even lead to death if there is no medical intervention.
These examples suggest some important differences between positive and negative feedback systems.
Because a positive feedback system continually reinforces a change in a controlled condition, some event outside the system must shut it off. If the action of a positive feedback system is not stopped, it can “run away” and may even produce life-threatening conditions in the body.
The action of a negative feedback system, by contrast, slows and then stops as the controlled condition returns to its normal state.
Usually, positive feedback systems reinforce conditions that do not happen very often, and negative feedback systems regulate conditions in the body that remain fairly stable over long periods.
Disorders: Homeostatic Imbalances
Disorders of the endocrine system often involve either:
- Hyposecretion (hypo- too little or under), inadequate release of a hormone, or
- Hypersecretion (hyper- too much or above), excessive release of a hormone.
In other cases, the problem is:
- Faulty hormone receptors,
- An inadequate number of receptors,
- Or defects in second-messenger systems.
Because hormones are distributed in the blood to target tissues throughout the body, problems associated with endocrine dysfunction may also be widespread.
Pituitary Gland Disorders
Several disorders of the anterior pituitary involve:
Human growth hormone (hGH)
Hyposecretion of hGH during the growth years slows bone growth, and the epiphyseal plates close before normal height is reached. This condition is called pituitary dwarfism. Other organs of the body also fail to grow, and the body proportions are childlike.
Treatment requires administration of hGH during childhood, before the epiphyseal plates close.
Hypersecretion of hGH during childhood causes giantism, an abnormal increase in the length of long bones. The person grows to be very tall, but body proportions are about normal.
Hypersecretion of hGH during adulthood is called acromegaly (ak-ro¯ -MEG-a-le¯). Although hGH cannot produce further lengthening of the long bones because the epiphyseal plates are already closed,
the bones of the hands,feet,cheeks,and jaws thicken and other tissues enlarge.
In addition, the eyelids, lips, tongue, and nose enlarge, and the skin thickens and develops furrows, especially on the forehead and soles.
Thyroid Gland Disorders
Thyroid gland disorders affect all major body systems and are among the most common endocrine disorders.
Congenital hypothyroidism, hyposecretion of thyroid hormones that is present at birth causes severe mental retardation and stunted bone growth. At birth, the baby typically is normal because lipid–soluble maternal thyroid hormones crossed the placenta during pregnancy and allowed normal development. If congenital hypothyroidism exists, oral thyroid hormone treatment must be started soon after birth and continued for life.
Hypothyroidism during the adult years produces myxedema (mixe-DE¯-ma), which occurs about five times more often in females than in males. A hallmark of this disorder is edema (accumulation of interstitial fluid) that causes the facial tissues to swell and look puffy.
A person with myxedema has:
- a slow heart rate,
- low body temperature,
- sensitivity to cold,
- dry hair and skin,
- muscular weakness,
- general lethargy,
- and a tendency to gain weight easily.
Because the brain has already reached maturity, mental retardation does not occur, but the person may be less alert.
Oral thyroid hormones reduce the symptoms.
The most common form of hyperthyroidism is Graves’ disease, which also occurs seven to ten times more often in females than in males, usually before age 40. Graves’ disease is an autoimmune disorder in which the person produces antibodies that mimic the action of thyroid-stimulating hormone (TSH).
The antibodies continually stimulate the thyroid gland to grow and produce thyroid hormones.
A primary sign is an enlarged thyroid, which may be two to three times its normal size. Graves’ patients often have a peculiar edema behind the eyes, called exophthalmos (ek-sof-THAL-mos), which causes the eyes to protrude.
Treatment may include:
- Surgical removal of part or all of the thyroid gland (thyroidectomy),
- The use of radioactive iodine (131I) to selectively destroy thyroid tissue,
- The use of antithyroid drugs to block synthesis of thyroid hormones.
A goiter is simply an enlarged thyroid gland. It may be associated with:
- or euthyroidism (u¯-THI¯-royd-izm; eu good), which means normal secretion of thyroid hormone.
In some places in the world, dietary iodine intake is inadequate; the resultant low level of thyroid hormone in the blood stimulates secretion of TSH, which causes thyroid gland enlargement
Pancreatic Islet Disorders
The most common endocrine disorder is diabetes mellitus (MEL-itus), caused by an inability to produce or use insulin.
Diabetes mellitus is the fourth leading cause of death by disease in the United States, primarily because of its damage to the cardiovascular system.
Because insulin is unavailable to aid transport of glucose into body cells, blood glucose level is high and glucose “spills” into the urine (glucosuria).
Hallmarks of diabetes mellitus are the three “polys”:
- polyuria, excessive urine production due to an inability of the kidneys to reabsorb water;
- polydipsia, excessive thirst;
- and polyphagia, excessive eating.
Both genetic and environmental factors contribute to onset of the two types of diabetes mellitus—type 1 and type 2—but the exact mechanisms are still unknown.
Type 1 diabetes, previously known as insulin-dependent diabetes mellitus (IDDM), occurs because the person’s immune system destroys the pancreatic beta cells.
As a result, the pancreas produces little or no insulin.
Type 1 diabetes usually develops in people younger than age 20 and it persists throughout life. By the time symptoms of type 1 diabetes arise, 80–90% of the islet beta cells have been destroyed.
Because insulin is not present to aid the entry of glucose into body cells, most cells use fatty acids to produce ATP.
Stores of dietary fats in adipose tissue are broken down to yield fatty acids and glycerol. The by-products of fatty acid breakdown—organic acids called ketones accumulate. Buildup of ketones causes blood pH to fall, a condition known as ketoacidosis.
Unless treated quickly, ketoacidosis can cause death. The breakdown of stored triglycerides also causes weight loss.
As lipids are transported by the blood from storage depots to cells, lipid particles are deposited on the walls of blood vessels, leading to atherosclerosis and a multitude of cardiovascular problems, including:
- cerebrovascular insufficiency,
- ischemic heart disease,
- peripheral vascular disease,
- and gangrene.
A major complication of diabetes is loss of vision due either:
- to cataracts (excessive glucose attaches to lens proteins, causing cloudiness)
- or to damage to blood vessels of the retina.
Severe kidney problems also may result from damage to renal blood vessels.
Type 1 diabetes is treated through:
- self-monitoring of blood glucose levels daily,
- regular meals containing 45–50% carbohydrates and less than 30% fats,
- and periodic insulin injections. Several implantable pumps are available to provide insulin without the need for repeated injections.
Type 2 diabetes, formerly known as non-insulin-dependent diabetes mellitus (NIDDM), is much more common than type 1, representing more than 90% of all cases.
Type 2 diabetes most often occurs in obese people who are over age 35.
Clinical symptoms are mild, and the high glucose levels in the blood often can be controlled by:
- and weight loss.
Although some type 2 diabetics need insulin, many have a sufficient amount (or even a surplus) of insulin in the blood. For these people, diabetes arises not from a shortage of insulin but because target cells become less sensitive to it due to down-regulation of insulin receptors.
Parathyroid Gland Disorders
Hypoparathyroidism is too little parathyroid hormone.
It leads to a deficiency of blood Ca2, which causes:
- neurons and muscle fibers to depolarize and produce action potentials spontaneously.
- This leads to twitches, spasms, and tetany (maintained contraction) of skeletal muscle.
The leading cause of hypoparathyroidism is accidental damage to the parathyroid glands or to their blood supply during thyroidectomy surgery.
Hyperparathyroidism, an elevated level of parathyroid hormone, most often is due to a tumor of one of the parathyroid glands.
An elevated level of PTH causes:
- excessive resorption of bone matrix,
- raising the blood levels of calcium and phosphate ions
- and causing bones to become soft and easily fractured.
- High blood calcium level promotes formation of kidney stones.
- Fatigue, personality changes,and lethargy are also seen in patients with hyperparathyroidism.
Adrenal Gland Disorders
Hypersecretion of cortisol by the adrenal cortex produces Cushing’s syndrome.
- a tumor of the adrenal gland that secretes cortisol,
- or a tumor elsewhere that secretes adrenocorticotropic hormone (ACTH), which in turn stimulates excessive secretion of cortisol.
The condition is characterized by:
- breakdown of muscle proteins and redistribution of body fat, resulting in spindly arms and legs accompanied by a rounded “moonface,” “buffalo hump” on the back, and pendulous (hanging) abdomen.
- Facial skin is flushed, and the skin covering the abdomen develops stretch marks.
- The person also bruises easily, and wound healing is poor.
The elevated level of cortisol causes:
- increased susceptibility to infection,
- decreased resistance to stress,
- and mood swings.
Hyposecretion of glucocorticoids and aldosterone causes Addison’s disease (chronic adrenocortical insufficiency).
The majority of cases are autoimmune disorders in which antibodies cause adrenal cortex destruction or block binding of ACTH to its receptors.
Symptoms, which typically do not appear until 90% of the adrenal cortex has been destroyed, include:
- mental lethargy,
- nausea and vomiting,
- weight loss,
- and muscular weakness.
Loss of aldosterone leads to:
- elevated potassium and decreased sodium in the blood,
- low blood pressure,
- decreased cardiac output, arrhythmias, and even cardiac arrest.
- The skin may have a “bronzed” appearance that often is mistaken for a suntan.
Treatment consists of replacing glucocorticoids and mineralocorticoids and increasing sodium in the diet.
Kallmann syndrome is a rare genetic hormonal condition that is characterized by a failure to start or a failure to complete puberty.
The underlying cause of the failure of the of the hypothalamus to release the hormone GnRH which in normal circumstances induces the anterior pituitary to release the gonadotropin hormones known as luteinising hormone (LH) and follicle stimulating hormone (FSH).
The condition can occur in both males and females but is more commonly diagnosed in males. Left untreated, patients with Kallmann syndrome will almost invariably be infertile.
Role of conventional radiography
- Sometimes the pathology processes present themselves skeletally
- Avascular necrosis
- Essential to consider full patient history as the effects of hormones are profound.
- Derangement of hormones can be a precursor to other pathology e.g. renal stones
- Pattern of investigation helps to explain patient referral
- If junior doctors involved a good knowledge and understanding can help to reduce patient dose
Other Imaging Modalities
- CT/MRI/ U/S much better
- Positron Emission Tomography (PET)