Clinical Medicine I Clinical Medicine I EndocrinologyEndocrinology

Jimmy Santana, MBA, P.A. - CJimmy Santana, MBA, P.A. - C

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Welcome BackWelcome Back

Hope you had a good Hope you had a good breakbreak

Get ready for a busy Get ready for a busy but fun semesterbut fun semester

QUESTION #1QUESTION #1

How is it that humans and animals How is it that humans and animals maintain quite constant blood maintain quite constant blood concentrations of glucose throughout concentrations of glucose throughout their lives despite wildly varying their lives despite wildly varying frequencies of meals?frequencies of meals?

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DID YOU KNOW?DID YOU KNOW?

If your blood glucose concentration drops If your blood glucose concentration drops much below 1 mg per ml, your neurons will much below 1 mg per ml, your neurons will begin to misbehave, leading ultimately to begin to misbehave, leading ultimately to coma and death. Yet skipping breakfast is coma and death. Yet skipping breakfast is rarely life-threatening. rarely life-threatening.

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ANSWER # 1ANSWER # 1

A battery of chemical messengers - A battery of chemical messengers - hormoneshormones - are secreted into blood in - are secreted into blood in response to rises and falls in blood response to rises and falls in blood glucose concentration and stimulate glucose concentration and stimulate metabolic pathways that pull glucose metabolic pathways that pull glucose concentrations back into the normal concentrations back into the normal range.range.

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Two systems control all physiologic Two systems control all physiologic processes:processes:

The nervous systemThe nervous system

The endocrine systemThe endocrine system

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The nervous systemThe nervous system exerts exerts point-to-point control through point-to-point control through nerves, similar to sending nerves, similar to sending messages by conventional messages by conventional telephone. Nervous control is telephone. Nervous control is electrical in nature and fast.electrical in nature and fast.

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The endocrine systemThe endocrine system – broadcasts its hormonal broadcasts its hormonal

messages to essentially all messages to essentially all cells by secretion into blood cells by secretion into blood and extracellular fluid. and extracellular fluid.

– Like a radio broadcast, it Like a radio broadcast, it requires a receiver to get the requires a receiver to get the message - in the case of message - in the case of endocrine messages, cells endocrine messages, cells must bear a must bear a receptorreceptor for the for the hormone being broadcast in hormone being broadcast in order to respond. order to respond.

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Endocrinology is the study of Endocrinology is the study of hormones, their receptors and the hormones, their receptors and the intracellular signaling pathways they intracellular signaling pathways they invoke.invoke. Distinct endocrine organs are scattered Distinct endocrine organs are scattered throughout the body. throughout the body. These are organs that are largely or at These are organs that are largely or at least famously devoted to secretion of least famously devoted to secretion of hormones hormones

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DefinitionsDefinitions

Endocrinology- Endocrinology- the study of hormone and the study of hormone and glandular abnormalities- diabetes, thyroid glandular abnormalities- diabetes, thyroid problems, and circus performersproblems, and circus performersHormones-Hormones-biologically active substances biologically active substances secreted by glands.secreted by glands. – Endocrine-Endocrine- hormones that have a biological hormones that have a biological

effect far away. effect far away. – ParacrineParacrine- hormones that have a biological - hormones that have a biological

effect nearby. effect nearby. – AutocrineAutocrine- hormones that have a local effect- hormones that have a local effect

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Hormone FunctionsHormone Functions

Growth and development: Growth and development: Thyroid, GH, Thyroid, GH, Sex Steroids, CortisolSex Steroids, CortisolReproduction: Reproduction: Estrogen, Testosterone, Estrogen, Testosterone, FSH, LH, ThyroidFSH, LH, ThyroidHomeostasis: Homeostasis: Thyroid, CortisolThyroid, CortisolChanges in environment: Changes in environment: Cortisol, Thyroid Cortisol, Thyroid AldosteroneAldosterone

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Endocrine Organ MappingEndocrine Organ MappingHypothalamusHypothalamus– TRHTRH– GnRHGnRH

Pituitary GlandPituitary Gland– GHGH– ACTHACTH– TSHTSH– FSHFSH– LHLH– ProlactinProlactin– ADHADH– OxytocinOxytocin

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Thyroid glandThyroid gland– ThyroxineThyroxine– TriiodothyronineTriiodothyronine

Parathyroid glandParathyroid gland– Parathyroid hormoneParathyroid hormone

PancreasPancreas– InsulinInsulin– GlucagonGlucagon

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Adrendal glandAdrendal gland– CortisolCortisol– AldosteroneAldosterone– NorepinephrineNorepinephrineTestesTestes– TestosteroneTestosterone– Estrogen for sensitivityEstrogen for sensitivityOvariesOvaries– EstrogenEstrogen– ProgestroneProgestrone– Testosterone Testosterone

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Pursuit of an understanding of endocrinology is Pursuit of an understanding of endocrinology is complicated by several of its principles: complicated by several of its principles: – All pathophysiologic events are influenced by the All pathophysiologic events are influenced by the

endocrine milieu:endocrine milieu: There are no cell types, organs or processes that are not influenced There are no cell types, organs or processes that are not influenced - often profoundly - by hormone signaling. - often profoundly - by hormone signaling.

– All "large" physiologic effects are mediated by multiple All "large" physiologic effects are mediated by multiple hormones acting in concert:hormones acting in concert:

Normal growth from birth to adulthood, for example, is surely Normal growth from birth to adulthood, for example, is surely dependent on growth hormone, but thyroid hormones, insulin-like dependent on growth hormone, but thyroid hormones, insulin-like growth factor-1, glucocorticoids and several other hormones are growth factor-1, glucocorticoids and several other hormones are also critically involved in this process. also critically involved in this process.

– There are many hormones known and little doubt that There are many hormones known and little doubt that others remain to be discovered.others remain to be discovered.

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Most commonly, hormones are categorized Most commonly, hormones are categorized into four structural groups, with members of into four structural groups, with members of each group having many properties in each group having many properties in common:common:

1.1. Peptides and proteins Peptides and proteins 2.2. Steroids Steroids 3.3. Amino acid derivatives Amino acid derivatives

4.4. Fatty acid derivativesFatty acid derivatives

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Peptide and protein hormonesPeptide and protein hormones

Vary considerably in size, ranging from Vary considerably in size, ranging from peptides as short as three amino acids to peptides as short as three amino acids to large, multi-subunit glycoproteins. large, multi-subunit glycoproteins.

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Many protein hormones are synthesized Many protein hormones are synthesized as prohormones, then proteolytically as prohormones, then proteolytically clipped to generate their mature form. clipped to generate their mature form. In other cases, the hormone is originally In other cases, the hormone is originally embedded within the sequence of a larger embedded within the sequence of a larger precursor, then released by multiple precursor, then released by multiple proteolytic cleavages. proteolytic cleavages.

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Most peptide hormones circulate unbound Most peptide hormones circulate unbound to other proteins, but exceptions exist; for to other proteins, but exceptions exist; for example, insulin-like growth factor-1 binds example, insulin-like growth factor-1 binds to one of several binding proteins. to one of several binding proteins. In general, the half-life of circulating In general, the half-life of circulating peptide hormones is only a few minutes. peptide hormones is only a few minutes.

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SteroidsSteroidsSteroids are lipids and, more specifically, derivatives Steroids are lipids and, more specifically, derivatives of cholesterol.of cholesterol. – Examples include the sex steroids such as testosterone and Examples include the sex steroids such as testosterone and

adrenal steroids such as cortisol. adrenal steroids such as cortisol.

Newly synthesized steroid hormones are rapidly Newly synthesized steroid hormones are rapidly secreted from the cell, with little if any storagesecreted from the cell, with little if any storage. . – Increases in secretion reflect accelerated rates of synthesis. Increases in secretion reflect accelerated rates of synthesis. – Following secretion, all steroids bind to some extent to plasma Following secretion, all steroids bind to some extent to plasma

proteins. proteins. – This binding is often low affinity and non-specific (e.g. to This binding is often low affinity and non-specific (e.g. to

albumin), but some steroids are transported by specific binding albumin), but some steroids are transported by specific binding proteins, which clearly affects their half-life and rate of proteins, which clearly affects their half-life and rate of elimination. elimination.

– Steroid hormones are typically eliminated by inactivating Steroid hormones are typically eliminated by inactivating metabolic transformations and excretion in urine or bile. Steroid metabolic transformations and excretion in urine or bile. Steroid hormones are typically eliminated by inactivating metabolic hormones are typically eliminated by inactivating metabolic transformations and excretion in urine or bile. transformations and excretion in urine or bile.

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Amino Acid Derivatives Amino Acid Derivatives There are two groups of hormones derived There are two groups of hormones derived from the amino acid tyrosine:from the amino acid tyrosine: Thyroid hormonesThyroid hormones are basically a "double" are basically a "double" tyrosine with the critical incorporation of 3 or 4 tyrosine with the critical incorporation of 3 or 4 iodine atoms.iodine atoms.

CatecholaminesCatecholamines include epinephrine and include epinephrine and norepinephrine, which are used as both norepinephrine, which are used as both hormones and neurotransmitters. hormones and neurotransmitters.

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The circulating half-life of thyroid The circulating half-life of thyroid hormones is on the order of a few days. hormones is on the order of a few days. They are inactivated primarily by They are inactivated primarily by intracellular de-iodinases. intracellular de-iodinases. Catecholamines, on the other hand, are Catecholamines, on the other hand, are rapidly degraded, with circulating half-lives rapidly degraded, with circulating half-lives of only a few minutes. of only a few minutes.

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Two other amino acids are used for Two other amino acids are used for synthesis of hormones:synthesis of hormones: TryptophanTryptophan is the precursor to serotonin is the precursor to serotonin and the pineal hormone melatonin and the pineal hormone melatonin Glutamic acidGlutamic acid is converted to histamine is converted to histamine

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Fatty Acid Derivatives - Fatty Acid Derivatives - Eicosanoids Eicosanoids

EicosanoidsEicosanoids are a large group of are a large group of molecules derived from polyunsaturated molecules derived from polyunsaturated fatty acids. fatty acids. The principal groups of hormones of The principal groups of hormones of this class are prostaglandins, this class are prostaglandins, prostacyclins, leukotrienes and prostacyclins, leukotrienes and thromboxanesthromboxanes

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Arachadonic acid is the most abundant Arachadonic acid is the most abundant precursor for these hormones.precursor for these hormones. Stores of arachadonic acid are present in Stores of arachadonic acid are present in membrane lipids and released through the membrane lipids and released through the action of various lipases. action of various lipases. The specific eicosanoids synthesized by a cell The specific eicosanoids synthesized by a cell are dictated by the battery of processing are dictated by the battery of processing enzymes expressed in that cell. enzymes expressed in that cell. These hormones are rapidly inactivated by being These hormones are rapidly inactivated by being metabolized, and are typically active for only a metabolized, and are typically active for only a few secondsfew seconds

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Control of Endocrine ActivityControl of Endocrine Activity

The physiologic effects of hormones The physiologic effects of hormones depend largely on their concentration depend largely on their concentration in blood and extracellular fluid.in blood and extracellular fluid. Almost inevitably, disease results when Almost inevitably, disease results when hormone concentrations are either too hormone concentrations are either too high or too low, and precise control over high or too low, and precise control over circulating concentrations of hormones is circulating concentrations of hormones is therefore crucial. therefore crucial.

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The concentration of hormone as seen by target cells is The concentration of hormone as seen by target cells is determined by three factors:determined by three factors:

Rate of production:Rate of production: – Synthesis and secretion of hormones are the most highly regulated Synthesis and secretion of hormones are the most highly regulated

aspect of endocrine control. Such control is mediated by positive and aspect of endocrine control. Such control is mediated by positive and negative feedback circuits, as described below in more detail.negative feedback circuits, as described below in more detail.

Rate of delivery:Rate of delivery: – An example of this effect is blood flow to a target organ or group of An example of this effect is blood flow to a target organ or group of

target cells - high blood flow delivers more hormone than low blood flow.target cells - high blood flow delivers more hormone than low blood flow.

Rate of degradation and elimination:Rate of degradation and elimination: – Hormones, like all biomolecules, have characteristic rates of decay, and Hormones, like all biomolecules, have characteristic rates of decay, and

are metabolized and excreted from the body through several routes. are metabolized and excreted from the body through several routes. – Shutting off secretion of a hormone that has a very short half-life causes Shutting off secretion of a hormone that has a very short half-life causes

circulating hormone concentration to plummet, circulating hormone concentration to plummet, – but if a hormone's biological half-life is long, effective concentrations but if a hormone's biological half-life is long, effective concentrations

persist for some time after secretion ceases. persist for some time after secretion ceases.

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Feedback Control of Hormone ProductionFeedback Control of Hormone Production

Feedback circuits are at the root of most Feedback circuits are at the root of most control mechanisms in physiology, and are control mechanisms in physiology, and are particularly prominent in the endocrine particularly prominent in the endocrine system. system. Instances of positive feedback certainly Instances of positive feedback certainly occur, but negative feedback is much occur, but negative feedback is much more common. more common.

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Negative feedback is seen when the output of a Negative feedback is seen when the output of a pathway inhibits inputs to the pathway. pathway inhibits inputs to the pathway.

The heating system in your home is a simple The heating system in your home is a simple negative feedback circuit. When the furnace negative feedback circuit. When the furnace produces enough heat to elevate temperature produces enough heat to elevate temperature above the set point of the thermostat, the above the set point of the thermostat, the thermostat is triggered and shuts off the furnace thermostat is triggered and shuts off the furnace (heat is feeding back negatively on the source of (heat is feeding back negatively on the source of heat). heat).

When temperature drops back below the set When temperature drops back below the set point, negative feedback is gone, and the point, negative feedback is gone, and the furnace comes back on. furnace comes back on.

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An important example of a negative An important example of a negative feedback loop is seen in control of thyroid feedback loop is seen in control of thyroid hormone secretion. hormone secretion. The thyroid hormones thyroxine and The thyroid hormones thyroxine and triiodothyronine ("T4 and T3") are triiodothyronine ("T4 and T3") are synthesized and secreted by thyroid glands synthesized and secreted by thyroid glands and affect metabolism throughout the body. and affect metabolism throughout the body.

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Neurons in the hypothalamus secrete Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), thyroid releasing hormone (TRH), which stimulates cells in the anterior which stimulates cells in the anterior pituitary to secrete thyroid-stimulating pituitary to secrete thyroid-stimulating hormone (TSH).hormone (TSH).

TSH binds to receptors on epithelial TSH binds to receptors on epithelial cells in the thyroid gland, stimulating cells in the thyroid gland, stimulating synthesis and secretion of thyroid synthesis and secretion of thyroid hormones, which affect probably all hormones, which affect probably all cells in the body.cells in the body.

When blood concentrations of thyroid When blood concentrations of thyroid hormones increase above a certain hormones increase above a certain threshold, TRH-secreting neurons in threshold, TRH-secreting neurons in the hypothalamus are inhibited and the hypothalamus are inhibited and stop secreting TRH. stop secreting TRH.

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Another type of feedback is seen in endocrine Another type of feedback is seen in endocrine systems that regulate concentrations of blood systems that regulate concentrations of blood components such as glucose.components such as glucose. Drink a glass of milk or Drink a glass of milk or eat a candy bar and the following series of events will eat a candy bar and the following series of events will occur: occur:

Glucose from the ingested lactose or sucrose is Glucose from the ingested lactose or sucrose is absorbed in the intestine and the level of glucose in absorbed in the intestine and the level of glucose in blood rises. blood rises. Elevation of blood glucose concentration stimulates Elevation of blood glucose concentration stimulates endocrine cells in the pancreas to release insulin. endocrine cells in the pancreas to release insulin. Insulin has the major effect of facilitating entry of glucose Insulin has the major effect of facilitating entry of glucose into many cells of the body - as a result, blood glucose into many cells of the body - as a result, blood glucose levels fall. levels fall. When the level of blood glucose falls sufficiently, the When the level of blood glucose falls sufficiently, the stimulus for insulin release disappears and insulin is no stimulus for insulin release disappears and insulin is no longer secreted. longer secreted.

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Hypothalamus and Pituitary Gland Hypothalamus and Pituitary Gland

The pituitary gland, also The pituitary gland, also known as the known as the hypophysishypophysisIt is a roundish organ that It is a roundish organ that lies immediately beneath lies immediately beneath the hypothalamus,the hypothalamus,Rests in a depression of Rests in a depression of the base of the skull the base of the skull called the sella turcica called the sella turcica ("Turkish saddle"). ("Turkish saddle"). In an adult human or In an adult human or sheep, the pituitary is sheep, the pituitary is roughly the size and roughly the size and shape of a garbonzo shape of a garbonzo bean. bean.

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A key to understanding the endocrine A key to understanding the endocrine relationship between hypothalamus and anterior relationship between hypothalamus and anterior pituitary is to appreciate the vascular pituitary is to appreciate the vascular connections between these organs. connections between these organs. Secretion of hormones from the anterior pituitary Secretion of hormones from the anterior pituitary is under strict control by hypothalamic hormones is under strict control by hypothalamic hormones

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These hypothalamic hormones reach the anterior These hypothalamic hormones reach the anterior pituitary through the following route: pituitary through the following route:

– A branch of the hypophyseal artery branches into a capillary bed A branch of the hypophyseal artery branches into a capillary bed in the lower hypothalamus, and hypothalmic hormones destined in the lower hypothalamus, and hypothalmic hormones destined for the anterior pituitary are secreted into that capillary blood.for the anterior pituitary are secreted into that capillary blood.

– Blood from those capillaries drains into Blood from those capillaries drains into hypothalamic-hypothalamic-hypophyseal portal veinshypophyseal portal veins. Portal veins are defined as veins . Portal veins are defined as veins between two capillary beds; the hypothalamic-hypophyseal between two capillary beds; the hypothalamic-hypophyseal portal veins branch again into another series of capillaries within portal veins branch again into another series of capillaries within the anterior pituitary.the anterior pituitary.

– Capillaries within the anterior pituitary, which carry hormones Capillaries within the anterior pituitary, which carry hormones secreted by that gland, coalesce into veins that drain into the secreted by that gland, coalesce into veins that drain into the systemic venous blood. Those veins also collect capillary blood systemic venous blood. Those veins also collect capillary blood from the posterior pituitary gland. from the posterior pituitary gland.

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Pituitary Hormones Pituitary Hormones The pituitary gland is The pituitary gland is often portrayed as the often portrayed as the "master gland" of the "master gland" of the body.body. Such praise is justified in Such praise is justified in the sense that the the sense that the anterior and posterior anterior and posterior pituitary secrete a battery pituitary secrete a battery of hormones that of hormones that collectively influence all collectively influence all cells and affect virtually cells and affect virtually all physiologic processes. all physiologic processes.

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Hormone Major target organ(s) Major Physiologic Effects

AnteriorAnteriorPituitaryPituitary

Growth hormone Liver, adipose tissue Promotes growth (indirectly), control of protein, lipid and carbohydrate metabolism

Thyroid-stimulating hormone

Thyroid gland Stimulates secretion of thyroid hormones

Adrenocorticotropic hormone

Adrenal gland (cortex)

Stimulates secretion of glucocorticoids

Prolactin Mammary gland Milk production

Luteinizing hormone Ovary and testis Control of reproductive function

Follicle-stimulating hormone

Ovary and testis Control of reproductive function

PosteriorPosteriorPituitaryPituitary

Antidiuretic hormone Kidney Conservation of body water

Oxytocin Ovary and testis Stimulates milk ejection and uterine contractions 3838

Growth HormoneGrowth Hormone

Growth hormone, also known as Growth hormone, also known as somatotropinsomatotropin, , is a protein hormone of about 190 amino acids is a protein hormone of about 190 amino acids that is synthesized and secreted by the anterior that is synthesized and secreted by the anterior pituitary. pituitary. It is a major participant in control of several It is a major participant in control of several complex physiologic processes, including growth complex physiologic processes, including growth and metabolism. and metabolism. Growth hormone is also of considerable interest Growth hormone is also of considerable interest as a drug used in both humans and animals. as a drug used in both humans and animals.

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Effects on GrowthEffects on Growth

Growth is a very complex process, and requires the Growth is a very complex process, and requires the coordinated action of several hormones. coordinated action of several hormones. The major role of growth hormone in stimulating The major role of growth hormone in stimulating body growth is to stimulate the liver and other body growth is to stimulate the liver and other tissues to secrete IGF-I.tissues to secrete IGF-I. IGF-I stimulates proliferation of chondrocytes (cartilage IGF-I stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. cells), resulting in bone growth. Growth hormone does seem to have a direct effect on Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of bone growth in stimulating differentiation of chondrocytes. chondrocytes. IGF-I also appears to be the key player in muscle IGF-I also appears to be the key player in muscle growth.growth. It stimulates both the differentiation and proliferation of It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. protein synthesis in muscle and other tissues.

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Metabolic EffectsMetabolic Effects

Protein metabolism:Protein metabolism: – This effect reflects increased amino acid uptake, increased protein This effect reflects increased amino acid uptake, increased protein

synthesis and decreased oxidation of proteins.synthesis and decreased oxidation of proteins.

Fat metabolism:Fat metabolism: – Growth hormone enhances the utilization of fat by stimulating Growth hormone enhances the utilization of fat by stimulating

triglyceride breakdown and oxidation in adipocytes.triglyceride breakdown and oxidation in adipocytes.

Carbohydrate metabolism:Carbohydrate metabolism: – Growth hormone is one of a battery of hormones that serves to maintain Growth hormone is one of a battery of hormones that serves to maintain

blood glucose within a normal range. blood glucose within a normal range. – Growth hormone is often said to have anti-insulin activity, because it Growth hormone is often said to have anti-insulin activity, because it

supresses the abilities of insulin to stimulate uptake of glucose in supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver. peripheral tissues and enhance glucose synthesis in the liver.

– Somewhat paradoxically, administration of growth hormone stimulates Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia. insulin secretion, leading to hyperinsulinemia.

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Disease States Disease States States of both growth hormone deficiency and excess provide very visible testaments to the role of this hormone in normal physiology. – Such disorders can reflect lesions in either the

hypothalamus, the pituitary or in target cells.– A deficiency state can result not only from a

deficiency in production of the hormone, but in the target cell's response to the hormone.

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Clinically, deficiency in growth Clinically, deficiency in growth hormone or receptor defects are as hormone or receptor defects are as growth retardation or dwarfism.growth retardation or dwarfism. The manifestation of growth hormone The manifestation of growth hormone deficiency depends upon the age of onset deficiency depends upon the age of onset of the disorder and can result from either of the disorder and can result from either heritable or acquired disease. heritable or acquired disease.

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The effect of excessive secretion of growth hormone is also very The effect of excessive secretion of growth hormone is also very dependent on the age of onset and is seen as two distinctive dependent on the age of onset and is seen as two distinctive disorders:disorders:

GiantismGiantism– is the result of excessive growth hormone secretion that begins in young is the result of excessive growth hormone secretion that begins in young

children or adolescents.children or adolescents.– It is a very rare disorder, usually resulting from a tumor of somatotropes. One of It is a very rare disorder, usually resulting from a tumor of somatotropes. One of

the most famous giants was a man named Robert Wadlow. He weighed 8.5 the most famous giants was a man named Robert Wadlow. He weighed 8.5 pounds at birth, but by 5 years of age was 105 pounds and 5 feet 4 inches tall. pounds at birth, but by 5 years of age was 105 pounds and 5 feet 4 inches tall. Robert reached an adult weight of 490 pounds and 8 feet 11 inches in height. He Robert reached an adult weight of 490 pounds and 8 feet 11 inches in height. He died at age 22.died at age 22.

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AcromegalyAcromegaly – results from excessive secretion of growth results from excessive secretion of growth

hormone in adults. hormone in adults. – The onset of this disorder is typically The onset of this disorder is typically

insideous. insideous. – Clinically, an overgrowth of bone and Clinically, an overgrowth of bone and

connective tissue leads to a change in connective tissue leads to a change in appearance that might be described as appearance that might be described as having "coarse features". having "coarse features".

– The excessive growth hormone and IGF-I also The excessive growth hormone and IGF-I also lead to metabolic derangements, including lead to metabolic derangements, including glucose intolerance. glucose intolerance.

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A Guy with Acromegaly:

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Pharmaceutical Uses of Growth Hormone Pharmaceutical Uses of Growth Hormone Human growth hormone is commonly used to treat Human growth hormone is commonly used to treat children of pathologically short stature.children of pathologically short stature. There is concern that this practice will be extended to There is concern that this practice will be extended to treatment of essentially normal children - so called treatment of essentially normal children - so called "enhancement therapy" or growth hormone on demand. "enhancement therapy" or growth hormone on demand. Similarly, growth hormone has been used by some to Similarly, growth hormone has been used by some to enhance athletic performance. enhance athletic performance. Although growth hormone therapy is generally safe, it is Although growth hormone therapy is generally safe, it is not as safe as no therapy and does entail unpredictable not as safe as no therapy and does entail unpredictable health risks. health risks.

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LET REVIEW SOME LET REVIEW SOME IMPORTANT FACTORSIMPORTANT FACTORS

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Hormone RegulationHormone Regulation

Feedback loopsFeedback loops

Circadian RhythmsCircadian Rhythms

Receptor specificityReceptor specificity

Receptor concentrationReceptor concentration

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Interaction of HormonesInteraction of Hormones

GHT-4

Proteinsynthesis

GluconeogensisHRmetabtemp

Skeletal

growth

Organ

growth

Sex steroids

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Hormone ClassificationHormone Classification

ProteinsProteins-thyroid stimulating hormone, -thyroid stimulating hormone, insulin, parathyroid hormoneinsulin, parathyroid hormone

Amino acidsAmino acids-thyroid hormone, -thyroid hormone, epinephrineepinephrine

SteroidsSteroids-cortisol, aldosterone, -cortisol, aldosterone, testosteronetestosterone

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How dynamic are these systems?How dynamic are these systems?

www.antiaging.com/images/ testosterone_decline.gif

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Endocrine Rhythms:

0800 2000 0800

ACTH

0800 2000 0800

Cortisol

0800 2000 0800

TSH

0800 2000 0800

GH

0800 2000 0800

Testosterone

0800 2000 0800

LH

"It don't mean a thing if it ain't got that swing!"

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Clinical EndocrinologyClinical Endocrinology

Hypofunction of a glandHypofunction of a gland

Hyperfunction of a glandHyperfunction of a gland

Receptor defectReceptor defect

Second messenger defectSecond messenger defect

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Endocrine HypofunctionEndocrine Hypofunction

Congenital defects in hormone Congenital defects in hormone biosynthesisbiosynthesisAutoimmune destruction of glandsAutoimmune destruction of glandsSurgery or trauma to glandsSurgery or trauma to glandsInfiltration by tumors, infectionInfiltration by tumors, infection

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Endocrine HyperfunctionEndocrine Hyperfunction

Hormone secreting Pituitary tumorHormone secreting Pituitary tumorEnd organ secreting tumorEnd organ secreting tumorAutoimmune diseaseAutoimmune diseaseInflammation/InfectionInflammation/InfectionIatrogenic/FacticiousIatrogenic/FacticiousEctopic hormone secreting tumorEctopic hormone secreting tumor

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Assessment of Glandular Assessment of Glandular ActivityActivity

Measure the end organ hormoneMeasure the end organ hormoneMeasure the pituitary regulating hormoneMeasure the pituitary regulating hormoneSuppression tests-to evaluate for hormone Suppression tests-to evaluate for hormone overactivityoveractivityStimulation tests-to evaluate for Stimulation tests-to evaluate for underactivityunderactivityImaging studiesImaging studies

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PearlsPearlsIf you think its over active try to supressIf you think its over active try to supress

If you think its under active try to stimulateIf you think its under active try to stimulate

Never get imaging before biochemical Never get imaging before biochemical diagnosisdiagnosis

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ConclusionsConclusions

Hormones are essential for normal growth, Hormones are essential for normal growth, development, metabolism, energy, development, metabolism, energy, reproduction etc.reproduction etc.Hormones are tightly regulated by multiple Hormones are tightly regulated by multiple systemssystemsBoth over and underproduction of Both over and underproduction of hormones leads to clinical diseasehormones leads to clinical disease

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FinallyFinallyHormonesHormonesYou can’t live with them but…You can’t live with them but…You can’t live without them!You can’t live without them!

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NEXT WEEK:NEXT WEEK:PITUITARY TUMORSPITUITARY TUMORSREAD UP ON IT!!!!!!!READ UP ON IT!!!!!!!

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