Basic laboratory tests Basic laboratory tests in endocrinologyin endocrinology

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Hormones

Hormones are chemical messengers secreted into blood or extracellular fluid by one cell that affect the functioning of other cells

One hormone type usually affects only target cells.

A target cell has receptors for the hormone

3

Pineal gland It produces melatonin, a hormone that affects the

modulation of wake/sleep patterns and photoperiodic (seasonal) functions

Thymus located posterior to the sternum ater puberty begins to decrease in size the primary function is the processing and maturation of T-

lymphocytes produces a hormone, thymosin, which stimulates the

maturation of lymphocytes in other lymphatic organs

•Endocrine action: the hormone is distributed in blood and binds to distant target cells. •Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. •Autocrine action: the hormone acts on the same cell that produced it.

Hormonal pathway

Structural groups of hormonsStructural groups of hormons Peptides and proteinsPeptides and proteins

mmany protein hormones are synthesized as prohormonesany protein hormones are synthesized as prohormones circulate unbound to other proteins, exceptioncirculate unbound to other proteins, exception – IGF 1 – IGF 1 the halflife of circulating peptide hormones is only a few minutesthe halflife of circulating peptide hormones is only a few minutes

Steroids - Steroids - derivatives of cholesterolderivatives of cholesterol GlucocorticoidsGlucocorticoids (cortisol), (cortisol), mineralocorticoidsmineralocorticoids (aldosterone), (aldosterone),

androgensandrogens (testosterone), (testosterone), estrogensestrogens, (estradiol), , (estradiol), progestogensprogestogens (progesterone) (progesterone)

Amino acid derivatives Amino acid derivatives Thyroid hormonesThyroid hormones are basically a "double" tyrosine with the critical incorporation are basically a "double" tyrosine with the critical incorporation

of 3 or 4 iodine atomsof 3 or 4 iodine atoms CatecholaminesCatecholamines include epinephrine and norepinephrine, which are used as both include epinephrine and norepinephrine, which are used as both

hormones and neurotransmittershormones and neurotransmitters Fatty acid derivatives – EicosanoidsFatty acid derivatives – Eicosanoids

prostaglandins, prostacyclins, leukotrienes and thromboxanesprostaglandins, prostacyclins, leukotrienes and thromboxanes

Concentration of hormonsConcentration of hormons

Rate of production:Rate of production: Synthesis and secretion of hormones Synthesis and secretion of hormones areare mediated by positive and negative feedback circuits mediated by positive and negative feedback circuits

Rate of delivery:Rate of delivery: high blood flow delivers more hormone high blood flow delivers more hormone than low blood flowthan low blood flow to a target organ to a target organ

Rate of degradation and elimination:Rate of degradation and elimination: Hormones Hormones are are metabolized and secretedmetabolized and secreted from the body through several from the body through several routes. routes. IIf a hormone's biological halflife is long, effective f a hormone's biological halflife is long, effective concentrations persist for some time after secretion ceasesconcentrations persist for some time after secretion ceases

HHypothalamusypothalamus

SSecrete hormones that strictly control secretion ecrete hormones that strictly control secretion of hormones from the anterior pituitaryof hormones from the anterior pituitary

TheThey arey are referred to as referred to as releasing hormonesreleasing hormones and and inhibiting hormonesinhibiting hormones, reflecting their , reflecting their influence on anterior pituitary hormones.influence on anterior pituitary hormones.

PPituitary glandituitary gland anterior and posterior pituitary secrete a battery anterior and posterior pituitary secrete a battery

of hormones that collectively influence all cells of hormones that collectively influence all cells and affect virtually all physiologic processesand affect virtually all physiologic processes

Anterior PituitaryAnterior PituitaryHormone Major target organ(s) Major Physiologic Effects

Growth hormone

Liver, adipose tissue

Promotes growth (indirectly), control of protein, lipid and carbohydrate metabolism

Thyroid-stimulating hormoneThyroid gland

Stimulates secretion of thyroid hormones

Adrenocorticotropic hormoneAdrenal gland (cortex)

Stimulates secretion of glucocorticoids

ProlactinMammary gland Milk production

Luteinizing hormoneOvary and testis

Control of reproductive function

Follicle-stimulating hormoneOvary and testis

Control of reproductive function

Posterior PituitaryPosterior Pituitary

Hormone Major target organ(s)Major Physiologic

Effects

Antidiuretic hormoneKidney

Conservation of body water

OxytocinOvary

Stimulates milk ejection and uterine contractions

Hypothalamus

Pituitary

Target Gland

CNS inputs

Hypothalamichormones

Intrapituitarycytokines

Peripheralhormones

Pituitarytrophichormones

Secretion of pituitary hormones determined by- hypothalamic hormones- intrapituitary factors- peripheral feedback

Synthesis of Pituitary HormonesSynthesis of Pituitary Hormones

Cell typeCell type % in % in pituitarypituitary

LHLH GonadotrophsGonadotrophs 5 - 105 - 10

FSHFSH

ProlactinProlactin LactotrophsLactotrophs 10 - 2510 - 25

TSHTSH ThyrotrophsThyrotrophs 5 - 155 - 15

GHGH SomatotrophsSomatotrophs 35 - 4535 - 45

ACTHACTH CorticotrophsCorticotrophs 1 - 21 - 2

Growth hormoneGrowth hormone

role in stimulating body growthrole in stimulating body growth stimulate the liver and other tissues to secrete stimulate the liver and other tissues to secrete

IGF-I, resulting in bone growthIGF-I, resulting in bone growth important effect on protein, lipid and important effect on protein, lipid and

carbohydrate metabolismcarbohydrate metabolism

Growth hormoneGrowth hormone Protein metabolismProtein metabolism

stimulates protein anabolism in many tissuesstimulates protein anabolism in many tissues increases amino acid uptake and protein synthesisincreases amino acid uptake and protein synthesis decreases oxidation of proteins.decreases oxidation of proteins.

Fat metabolismFat metabolism enhances the utilization of fatenhances the utilization of fat

Carbohydrate metabolismCarbohydrate metabolism maintain blood glucose within a normal range maintain blood glucose within a normal range has anti-insulin activity, supresses the abilities of insulin to has anti-insulin activity, supresses the abilities of insulin to

stimulate uptake of glucose in peripheral tissues and enhance stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liverglucose synthesis in the liver

Control of GH secretionControl of GH secretion stress, exercise, nutrition, sleep and growth hormone itselfstress, exercise, nutrition, sleep and growth hormone itself Growth hormone-releasing hormoneGrowth hormone-releasing hormone (GHRH) (GHRH)

hypothalamic peptide that stimulates both the synthesis and hypothalamic peptide that stimulates both the synthesis and secretion of GHsecretion of GH

SomatostatinSomatostatin (SS) (SS) peptide produced by several tissues in the body, including the peptide produced by several tissues in the body, including the

hypothalamushypothalamus inhibits GH release in response to GHRH and to other stimulatory inhibits GH release in response to GHRH and to other stimulatory

factors such as low blood glucose concentration. factors such as low blood glucose concentration. GhrelinGhrelin

peptide hormone secreted from the stomachpeptide hormone secreted from the stomach stimulates secretion of growth hormone.stimulates secretion of growth hormone.

Disease States

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

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

Giantism and Acromegaly

Giantism

Excessive growth hormone Excessive growth hormone secretion that begins in young secretion that begins in young children or adolescents. It is a very children or adolescents. It is a very rare disorder, usually resulting from rare disorder, usually resulting from a tumor of somatotropesa tumor of somatotropes

220-240 cm220-240 cm Lower Lower IQIQ metabolic malfunctionsmetabolic malfunctions

AcromegalyAcromegaly

excessive secretion of GH in adultsexcessive secretion of GH in adults usually benign pituitary tumorsusually benign pituitary tumors onset of this disorder occurring over several yearsonset of this disorder occurring over several years overgrowth of extremities, soft-tissue swelling, overgrowth of extremities, soft-tissue swelling,

abnormalities in jaw structure and cardiac diseaseabnormalities in jaw structure and cardiac disease excessive GH and IGF-I also lead to a number of excessive GH and IGF-I also lead to a number of

metabolic derangements, including hyperglycemia.metabolic derangements, including hyperglycemia.

IGF-1IGF-1

insuline like growth factor – I insuline like growth factor – I stimulates proliferation stimulates proliferation of chondrocytes (cartilage cells), resulting in bone of chondrocytes (cartilage cells), resulting in bone growth growth

key player in muscle growthkey player in muscle growth, i, it stimulates both the t stimulates both the differentiation and proliferation of myoblasts. It also differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in stimulates amino acid uptake and protein synthesis in muscle and other tissues.muscle and other tissues.

Transport protein - IGFBP 3Transport protein - IGFBP 3 Primary investigation for acromegaly and giantism Primary investigation for acromegaly and giantism

diagnosisdiagnosis

ACTHACTH

Adrenocorticotropic hormoneAdrenocorticotropic hormone secreted from the anterior pituitary in response to secreted from the anterior pituitary in response to

corticotropin-releasing hormone (CRH) from the corticotropin-releasing hormone (CRH) from the hypothalamus - response to stresshypothalamus - response to stress

stimulates the adrenal cortex - secretion of stimulates the adrenal cortex - secretion of glucocorticoids - cortisol glucocorticoids - cortisol

CRH CRH is inhibited by glucocorticoids – negative is inhibited by glucocorticoids – negative

feedback loopfeedback loop

ProlactinProlactin

Secreted by the anterior pituitary under the control of prolactin inhibitory factor secreted by the hypothalamus

levels rise during pregnancy and cause stimulation of milk production after childbirth

elevated serum prolactin levels are the most common disorder of the hypothalamic-pituitary axis

inhibits the release of other gonadotropic hormones Dopamine serves as the major prolactin-inhibiting factor

Estrogens provide a positive control over prolactin synthesis and secretion

MacroprolactinMacroprolactin Prolactin in human serum exists as multiple forms of Prolactin in human serum exists as multiple forms of

different molecular sizes of which the predominant species different molecular sizes of which the predominant species (90%) is the monomeric form (MW - 22.5kD)(90%) is the monomeric form (MW - 22.5kD)

In some individuals, however, the predominant circulating In some individuals, however, the predominant circulating prolactin is the very high molecular weight form prolactin is the very high molecular weight form (macroprolactin, MW >100kD)(macroprolactin, MW >100kD)

This phenomenon, termed macroprolactinaemia, is a non-This phenomenon, termed macroprolactinaemia, is a non-pathological cause of persistent, and often asymptomatic pathological cause of persistent, and often asymptomatic hyperprolactinaemiahyperprolactinaemia

A method for assessing prolactin recovery based on A method for assessing prolactin recovery based on precipitation of macroprolactin by polyethylene glycol precipitation of macroprolactin by polyethylene glycol (PEG) has been proposed as a simple test for detection of (PEG) has been proposed as a simple test for detection of macroprolactinaemiamacroprolactinaemia

HyperprolactinaemiaHyperprolactinaemia

relatively common disorder in humans condition - prolactin-secreting tumors and therapy with

certain drugs Women

amenorrhea -lack of menstrual cycles galactorrhea - excessive or spontaneous secretion of milk

Men Hypogonadism decreased sex drive, impotence, decreased sperm production breast enlargement (gynecomastia), but very rarely produce

milk.

TSHTSH

Thyroid-stimulating hormone, Thyroid-stimulating hormone, thyrotropinthyrotropin stimulates the thyroid gland to synthesize and stimulates the thyroid gland to synthesize and

release thyroid hormonesrelease thyroid hormones glycoprotein hormone composed of two glycoprotein hormone composed of two

subunits, non-covalently bound to one. The subunits, non-covalently bound to one. The alpha subunit is also present FSH, LH and in alpha subunit is also present FSH, LH and in the placental hormone chorionic gonadotropin. the placental hormone chorionic gonadotropin.

GonadotropinsGonadotropins

stimulate the gonadsstimulate the gonads in men - the testesin men - the testes in women - the ovariesin women - the ovariesThey are not necessary for life, but are essential for They are not necessary for life, but are essential for

reproductionreproduction TSH, LH and FSH are large glycoproteins TSH, LH and FSH are large glycoproteins

composed of composed of and and subunits subunits subunit is identical in all three hormonessubunit is identical in all three hormones subunit is unique and endows each hormone subunit is unique and endows each hormone

with the ability to bind its own receptor.with the ability to bind its own receptor.

FSHFSH ovaries contain follicles, (fluid-filled sacs in which eggs grow)ovaries contain follicles, (fluid-filled sacs in which eggs grow)

in the female, FSH stimulates a follicle to mature during each in the female, FSH stimulates a follicle to mature during each menstrual cycle menstrual cycle

follicles mature in the ovary and continue to develop in the follicles mature in the ovary and continue to develop in the fallopian tube, which connects the ovary to the uterusfallopian tube, which connects the ovary to the uterus

FSH is also critical for sperm production. It supports the FSH is also critical for sperm production. It supports the function of Sertoli cells, which in turn support many function of Sertoli cells, which in turn support many aspects of sperm cell maturationaspects of sperm cell maturation

LLHH

Luteinizing hormoneLuteinizing hormone Stimulates secretion of sex steroids from the gonadsStimulates secretion of sex steroids from the gonads

In the testes - secretion of testosteroneIn the testes - secretion of testosterone in the ovary - secretion of estrogenin the ovary - secretion of estrogen

ovulation of mature follicles on the ovary is induced by a large ovulation of mature follicles on the ovary is induced by a large burst of LH secretionburst of LH secretion

LH is required for continued development and function of LH is required for continued development and function of corpora luteacorpora lutea

Measurement of anterior Measurement of anterior pituitary hormonespituitary hormones

1.1. Baseline measurementsBaseline measurements

ACTH (Cortisol 9am, 12mn), TSH (ACTH (Cortisol 9am, 12mn), TSH (FFT4), Prolactin, LH/FSH T4), Prolactin, LH/FSH (Testosterone, (Testosterone, EEstradiol)stradiol)

2.2. Dynamic function testsDynamic function tests

Why?Why?

-- low pituitary hormone levels not diagnosticlow pituitary hormone levels not diagnostic

- - normal levels do not exclude pituitary diseasenormal levels do not exclude pituitary disease

- - pulsatile excretion + diurnal variation confuse interpretation of pulsatile excretion + diurnal variation confuse interpretation of baseline levelsbaseline levels

- - if baseline levels are high dynamic tests can aid in if baseline levels are high dynamic tests can aid in differentialdifferential diagnosisdiagnosis

Hypofunction Hypofunction stimulation tests stimulation tests

HyperfunctionHyperfunction suppression tests suppression tests

Types of pituitary adenomasTypes of pituitary adenomasProlactinomas

50-55%Somatotroph

20-23%Gonadotroph

< 5%Non-functional

20-25%Corticotroph

5-8%Thyrotroph

< 1%

ThyroidThyroid

Thyroid HormonesThyroid Hormones Triiodothyronine (T3)Triiodothyronine (T3) Thyroxine (T4)Thyroxine (T4) Principal actionsPrincipal actions

Stimulate energy useStimulate energy use Cardiac stimulation Cardiac stimulation Promote growth & Promote growth &

developmentdevelopment

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

stimulating hormone (TSH). TSH binds to receptors on epithelial cells in the thyroid gland, stimulating

synthesis and secretion of thyroid hormones, which affect probably all

cells in the body. When blood concentrations of

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

CalcitoninCalcitonin

TThe major source of calcitonin is from the he major source of calcitonin is from the parafollicular or C cells in the thyroiparafollicular or C cells in the thyroid gd glandland

participate in calcium and phosphorus metabolismparticipate in calcium and phosphorus metabolism BoneBone: suppresses resorption of bone: suppresses resorption of bone, , releasing releasing CaCa and and P P

iinto bloodnto blood KidneyKidney: Calcitonin inhibits tubular reabsorption : Calcitonin inhibits tubular reabsorption CaCa and and PP

Elevated blood Elevated blood ionized ionized calcium levels strongly calcium levels strongly stimulate calcitonin secretionstimulate calcitonin secretion

DISORDERS OF THE DISORDERS OF THE THYROIDTHYROID

DISORDERS OF THE DISORDERS OF THE THYROIDTHYROID

HYPERFUNCTION: HyperthyroidismHYPERFUNCTION: Hyperthyroidism

HYPOFUNCTION: HypothyroidismHYPOFUNCTION: Hypothyroidism AdultAdult

ChildChild

GOITER:GOITER: SimpleSimple

ToxicToxic

HYPERTHYROIDISM:HYPERTHYROIDISM:DefinitionDefinition

HYPERTHYROIDISM:HYPERTHYROIDISM:DefinitionDefinition

A state of hypermetabolism and hyperactivity of A state of hypermetabolism and hyperactivity of

cardiovascular and neuromuscular systems induced cardiovascular and neuromuscular systems induced

by high levels of circulating Tby high levels of circulating T33 , T , T44 , or both. , or both.

Major cause: Graves DiseaseMajor cause: Graves Disease

Young to middle-aged adultsYoung to middle-aged adults

Females more often affectedFemales more often affected

Familial incidenceFamilial incidence

GRAVES DISEASE:GRAVES DISEASE:PrevalencePrevalence

GRAVES DISEASE:GRAVES DISEASE:PrevalencePrevalence

Behavior changesBehavior changes

GoiterGoiter

Ocular manifestationsOcular manifestations

Insomnia, restlessnessInsomnia, restlessness

PPalpitations, hand tremors, nervousnessalpitations, hand tremors, nervousness

Increased body temperatureIncreased body temperature

GRAVES DISEASEGRAVES DISEASEGRAVES DISEASEGRAVES DISEASE

Life threatening form of thyrotoxicosis.Life threatening form of thyrotoxicosis. Exagerated clinical features:Exagerated clinical features:

Increased temperatureIncreased temperature Tachycardia and cardiac arrhythmiasTachycardia and cardiac arrhythmias Congestive heart failureCongestive heart failure Extreme restlessness, agitation, psychosesExtreme restlessness, agitation, psychoses Nausea and vomiting, severe diarrheaNausea and vomiting, severe diarrhea

GRAVES DISEASE:GRAVES DISEASE:Thyroid StormThyroid Storm

GRAVES DISEASE:GRAVES DISEASE:Thyroid StormThyroid Storm

Congenital: CretinismCongenital: Cretinism

AcquiredAcquired Hashimoto thyroiditisHashimoto thyroiditis

Iodine deficiency or impeded utilizationIodine deficiency or impeded utilization

Iatrogenic events: XRT, thyroidectomyIatrogenic events: XRT, thyroidectomy

Goitrogen ingestionGoitrogen ingestion

Secondary (pituitary origin)Secondary (pituitary origin)

HYPOTHYROIDISM:HYPOTHYROIDISM:EtiologyEtiology

HYPOTHYROIDISM:HYPOTHYROIDISM:EtiologyEtiology

Older age group (60s)Older age group (60s)

Females more often affectedFemales more often affected

Pregnant womenPregnant women

HYPOTHYROIDISMHYPOTHYROIDISMHYPOTHYROIDISMHYPOTHYROIDISM

Decreased metabolism, reduced appetiteDecreased metabolism, reduced appetite Slow mentation, speech, movementSlow mentation, speech, movement Goiter (optional)Goiter (optional) Skin cool and drySkin cool and dry Weakness, lethargy, fatigabilityWeakness, lethargy, fatigability Intolerance to coldIntolerance to cold Deepened voice Deepened voice HypercholesterolemiaHypercholesterolemia Menstrual irregularitiesMenstrual irregularities In advanced disease: MYXEDEMAIn advanced disease: MYXEDEMA

HYPOTHYROIDISMHYPOTHYROIDISMHYPOTHYROIDISMHYPOTHYROIDISM

GOITERGOITERGOITERGOITER

Definition: Definition: Thyroid enlargement, with (toxic goiter) or without (simple goiter) increased Thyroid enlargement, with (toxic goiter) or without (simple goiter) increased

hormone production.hormone production.

Types of goiter:Types of goiter: DiffuseDiffuse

NodularNodular

Etiology:Etiology: Inflammatory process (thyroiditis)Inflammatory process (thyroiditis)

Functional disordersFunctional disorders

NeoplasmsNeoplasms

Etiology: autoimmuneEtiology: autoimmune Prevalence:Prevalence:

Females are more often affectedFemales are more often affected Disease in males is more severeDisease in males is more severe

Clinical characteristics:Clinical characteristics: Thyroid enlargementThyroid enlargement

Symptoms of tracheal/esophageal compressionSymptoms of tracheal/esophageal compression

Malignant transformation risk: 5%Malignant transformation risk: 5%

Association with other autoimmune diseasesAssociation with other autoimmune diseases

Hashimoto ThyroiditisHashimoto ThyroiditisHashimoto ThyroiditisHashimoto Thyroiditis

Benign tumors: Benign tumors: follicular adenomasfollicular adenomas

Malignant tumors:Malignant tumors: Papillary carcinomaPapillary carcinoma Follicular carcinomaFollicular carcinoma Anaplastic carcinomaAnaplastic carcinoma Medullary carcinomaMedullary carcinoma

NeoplasmsNeoplasmsNeoplasmsNeoplasms

Parathyroid glands Parathyroid glands

The 4 parathyroid glands The 4 parathyroid glands (4x2 (4x2 mm) mm) are located near or attached are located near or attached to the back side of the thyroid to the back side of the thyroid glandgland

The The glandglands synthesize and secrete s synthesize and secrete parathyroid hormone that controls parathyroid hormone that controls blood levels of calcium.blood levels of calcium.

The structure of a parathyroid The structure of a parathyroid gland is distinctly different from a gland is distinctly different from a thyroid gland. thyroid gland. The cellsThe cells are arranged in are arranged in rather dense cords or nests around abundant rather dense cords or nests around abundant capillaries. capillaries.

Parathyroid hormoneParathyroid hormone

TThe most important endocrine regulator of he most important endocrine regulator of CaCa and and PP concentration in extracellular fluid concentration in extracellular fluid

PTH PTH is released in response to low is released in response to low extracellular concentrations of free calciumextracellular concentrations of free calcium

PTH has a circadian rhythmPTH has a circadian rhythm Max 14. – 16.hMax 14. – 16.h Min 8.hMin 8.h Sampling in ice, plasma or serum, -20Sampling in ice, plasma or serum, -20ooCC

Parathyroid hormoneParathyroid hormone

Mobilization of calcium from boneMobilization of calcium from bone: stimulate: stimulatess osteoclasts to reabsorb bone mineral, liberating osteoclasts to reabsorb bone mineral, liberating calcium into blood. calcium into blood.

Enhancing absorption of calcium from the small Enhancing absorption of calcium from the small intestineintestine: : PTH PTH stimulates production of the active stimulates production of the active vvitamin Ditamin D. It. It induces synthesis of a calcium-binding induces synthesis of a calcium-binding proteinprotein

Suppression of calcium loss in urineSuppression of calcium loss in urine

HyperparathyroidismHyperparathyroidism

Primary hyperparathyroidism Primary hyperparathyroidism most commonly due to a parathyroid tumor (adenoma) most commonly due to a parathyroid tumor (adenoma)

which secretes the hormone without proper regulationwhich secretes the hormone without proper regulation chronic elevations chronic elevations CaCa (hypercalcemia), kidney stones and (hypercalcemia), kidney stones and

decalcification of bonedecalcification of bone Secondary hyperparathyroidismSecondary hyperparathyroidism

kidney disease - unable to reabsorb kidney disease - unable to reabsorb CaCa iinadequate nutrition – diets deficient in nadequate nutrition – diets deficient in CaCa or vitamin D, or or vitamin D, or

which contain excessive phosphoruswhich contain excessive phosphorus decalcification of bonedecalcification of bone ( ("rubber bones„"rubber bones„))

Adrenal glandsAdrenal glands

CortexCortex MedullaMedulla

Adrenal glandAdrenal gland

Cortex (steroid hormon)Cortex (steroid hormon) glucocorticoids glucocorticoids mineralocorticoids mineralocorticoids From cholesterol - steroidogenesisFrom cholesterol - steroidogenesis

Medulla ( derivates of aminoacids)Medulla ( derivates of aminoacids) epinephrine and norepinephrineepinephrine and norepinephrine

Adrenal mAdrenal meedduullalla circulating epinephrine and norepinephrine released from the circulating epinephrine and norepinephrine released from the

adrenal medulla have the same effects on target organs as direct adrenal medulla have the same effects on target organs as direct stimulation by sympathetic nervesstimulation by sympathetic nerves

Increased rate and force of contraction of the heart muscleIncreased rate and force of contraction of the heart muscle - -epinephrine epinephrine Constriction of blood vesselsConstriction of blood vessels - - norepinephrine, increase norepinephrine, increase blood pressureblood pressure Dilation of bronchiolesDilation of bronchioles - - assists in pulmonary ventilation assists in pulmonary ventilation Stimulation of lipolysis in fat cellsStimulation of lipolysis in fat cells - - energy production energy production Increased metabolic rate:Increased metabolic rate: oxygen consumption and heat production increase oxygen consumption and heat production increase

throughout the body in response to epinephrinethroughout the body in response to epinephrine Dilation of the pupilsDilation of the pupils Inhibition of certain "non-essential" processesInhibition of certain "non-essential" processes - - gastrointestinal secretion and gastrointestinal secretion and

motor activity. motor activity.

Adrenal cortexAdrenal cortex

CortisolCortisol circadian rhythm min. 12 mn, max. about 6 amcircadian rhythm min. 12 mn, max. about 6 am, by stress maintain normal concentrations of glucose in blood Stimulation of gluconeogenesis, particularly in the liver Mobilization of amino acids from extrahepatic tissues Inhibition of glucose uptake in muscle and adipose tissue Stimulation of fat breakdown in adipose tissue

Cortisol

Effects on inflammation and immune function Glucocorticoids have potent anti-inflammatory and

immunosuppressive properties glucocorticoids are also among the most frequently used

drugs, and often prescribed for their anti-inflammatory and immunosuppressive properties

AldosteronAldosteron

MineralocorticoidMineralocorticoid critical role in regulating concentrations of minerals - critical role in regulating concentrations of minerals -

particularly particularly NaNa and and K K - in extracellular fluids- in extracellular fluids The major target is the distal tubule of the kidney, where The major target is the distal tubule of the kidney, where

it stimulates exchange of it stimulates exchange of NaNa and and KK Increased resorption of sodiumIncreased resorption of sodium Increased resorption of waterIncreased resorption of water

an osmotic effect directly related to increased resorption of an osmotic effect directly related to increased resorption of NaNa

Increased renal excretion of Increased renal excretion of KK

Addison's diseaseAddison's disease

hypoadrenocorticismhypoadrenocorticism this disease is a result of infectious disease this disease is a result of infectious disease

(e.g. tuberculosis in humans) or autoimmune (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortexdestruction of the adrenal cortex

cardiovascular disease, lethargy, diarrhea, and weakness. Aldosterone deficiency can be acutely life threatening due to disorders of electrolyte balance and cardiac function

Cushing’s Syndrome

hyperadrenocorticism Excessive endogenous production of cortisol,

which can result from a primary adrenal defect (ACTH-independent) or from excessive secretion of ACTH (ACTH-dependent)

Administration of glucocorticoids for theraputic purposes. This is a common side-effect of these widely-used drugs.

Cholesterol

Pregnenolon

Progesteron

11deoxykortikosteron

Kortikosteron

18 hydroxykortikosteron

Aldosteron

17 hydroxypregnenolo

n

17 hydroxyprogesteron

11 deoxykortizol

Kortizol

DHEA

Androstendion

EstradiolTestoste

ron

Desmoláza

21 hydroxyláza

11 hydroxyláza

18 hydroxyláza

21 hydroxyláza

11 hydroxyláza

11 hydroxyláza

Steroidogenesis in adrenal gland

PancreasPancreas

The bulk of the pancreas is composed of pancreatic exocrine cells and their associated ducts. Embedded within this exocrine tissue are roughly one million small clusters of cells called the Islets of Langerhans, which are the endocrine cells of the pancreas

Islets of LangerhansIslets of Langerhans

only 1-2% of the mass of the pancreasonly 1-2% of the mass of the pancreas

Alpha cellsAlpha cells (A cells) secrete (A cells) secrete glucagonglucagon.. Beta cellsBeta cells (B cells) produce (B cells) produce insulininsulin and are the most and are the most

abundant of the islet cells abundant of the islet cells Delta cellsDelta cells (D cells) secrete (D cells) secrete somatostatinsomatostatin

F cells F cells secretesecrete pancreatic polypeptid (PP)pancreatic polypeptid (PP)

PancreasPancreas

Insulin and glucagon are critical participants in Insulin and glucagon are critical participants in

glucose homeostasis and serve as acute regulators glucose homeostasis and serve as acute regulators

of blood glucose concentrationof blood glucose concentration

AA deficiency in insulin or deficits in insulin deficiency in insulin or deficits in insulin

responsiveness lead to the disease diabetes responsiveness lead to the disease diabetes

mellitusmellitus

Glucose from the ingested lactose or sucrose is absorbed in the intestine and the level of glucose in blood rises

Elevation of blood glucose concentration stimulates endocrine cells in the pancreas to release insulin

Insulin has the major effect of facilitating entry of glucose into many cells of the body - as a result, blood glucose levels fall

When the level of blood glucose falls sufficiently, the stimulus for insulin release disappears and insulin is no longer secreted

InsulinInsulin

synthesized in significant quantities only in synthesized in significant quantities only in beta cells in the pancreasbeta cells in the pancreas

facilitates entry of glucose into muscle, facilitates entry of glucose into muscle, adipose and several other tissuesadipose and several other tissues

stimulates the liver to store glucose in the form stimulates the liver to store glucose in the form of glycogenof glycogen

Insulin and lipid metabolismInsulin and lipid metabolism

Insulin promotes synthesis of fatty Insulin promotes synthesis of fatty acids in the liveracids in the liver

Insulin inhibits breakdown of fat in Insulin inhibits breakdown of fat in adipose tissueadipose tissue

Insulin facilitates entry of glucose Insulin facilitates entry of glucose into adipocytes and glucose can be into adipocytes and glucose can be used to synthesize glycerolused to synthesize glycerol

indirectly stimulates accumulation indirectly stimulates accumulation of fat in adipose tissueof fat in adipose tissue

Types of DMTypes of DM

Type 1 (IDDM) Insulin dependentType 1 (IDDM) Insulin dependent Destruction of pancreatic beta cellsDestruction of pancreatic beta cells No insulin producedNo insulin produced

Type 2 (NIDDM) Non-insulin dependentType 2 (NIDDM) Non-insulin dependent Cells are less responsive to insulinCells are less responsive to insulin Altered insulin secretionAltered insulin secretion

GlukagonGlukagon Glucagon has a major role in maintaining normal Glucagon has a major role in maintaining normal

concentrations of glucose in bloodconcentrations of glucose in blood - - increasing blood increasing blood glucose levelsglucose levels

Glucagon stimulates breakdown of glycogen stored in the Glucagon stimulates breakdown of glycogen stored in the liverliver

Glucagon activates hepatic gluconeogenesisGlucagon activates hepatic gluconeogenesis -- non-hexose non-hexose substrates such as amino acids are converted to glucosesubstrates such as amino acids are converted to glucose

Diseases associated with excessively high or low secretion Diseases associated with excessively high or low secretion of glucagon are rareof glucagon are rare

SSomatostatinomatostatin

secreted by a broad range of tissues, including secreted by a broad range of tissues, including pancreas, intestinal tract and regions of the pancreas, intestinal tract and regions of the central nervous system outside the central nervous system outside the hypothalamushypothalamus

Somatostatin was named for its effect of Somatostatin was named for its effect of inhibiting secretioninhibiting secretion of GH of GH

Somatostatin appears to act primarily in a Somatostatin appears to act primarily in a paracrine manner to inhibit the secretion of paracrine manner to inhibit the secretion of both insulin and glucagonboth insulin and glucagon

Fertility

Ovarian Hormones Two classes of ovarian sex hormones: Estrogens and progestins The most important of the estrogens is estradiol The most important progestin is progesterone Estrogens: Promote proliferation and growth of sex related cells;

cause secondary sexual characteristics

Progestins: Important for preparation of the uterus for pregnancy

and the breast for lactation

EstradiolEstradiol

Principal Function: cellular proliferation; growth of the tissues of sexual organs; growth of other tissues related to reproduction

ProgesteroneProgesterone

Residual cells within ovulated follicles proliferate to Residual cells within ovulated follicles proliferate to form corpora lutea, which secrete the steroid form corpora lutea, which secrete the steroid hormones progesterone and estradiolhormones progesterone and estradiol

Progesterone is necessary for maintenance of Progesterone is necessary for maintenance of pregnancypregnancy secreted by the corpus luteum secreted by the corpus luteum it prepares the uterus for the it prepares the uterus for the development of the fertilised eggdevelopment of the fertilised egg

this is called the proliferative this is called the proliferative phase of the uterus since there is a phase of the uterus since there is a proliferation of blood vessels in the uterine liningproliferation of blood vessels in the uterine lining

these blood vessels serve as a nutrient source for the developing these blood vessels serve as a nutrient source for the developing embryoembryo

Circulating levels (LH,FSH, Prog and Estradiol)Circulating levels (LH,FSH, Prog and Estradiol)

1 14 287 21

Day of menstrual cycle

10

20

30

40

50LH and FSH (IU/L)

LH

FSH

Progesterone

ovulation

5

10

15

20

251850

1500

740

1100

370

Estradiol

Estradiol (pmol/L)

Progesterone (nmol/L)

Investigation of amenorrhoeaInvestigation of amenorrhoea

Causes of amenorrhoeaCauses of amenorrhoea

physiological e.g prepuberty, pregnancy, lactation, post physiological e.g prepuberty, pregnancy, lactation, post menopausemenopause

anatomical e.g. absence of uterusanatomical e.g. absence of uterus

structural endocrine disorders e.g. Kallman’s syndrome structural endocrine disorders e.g. Kallman’s syndrome (congenital lack of GnRH), severe head injury, pituitary (congenital lack of GnRH), severe head injury, pituitary adenoma, Sheehan’s syndromeadenoma, Sheehan’s syndrome

functional endocrine disorders e.g. weight loss, anorexia functional endocrine disorders e.g. weight loss, anorexia nervosa, excessive exercise, stressnervosa, excessive exercise, stress

all above result in all above result in decreased LH and FSHdecreased LH and FSH

Causes of amenorrhoeaCauses of amenorrhoea

premature ovarian failure (depletion of primordial premature ovarian failure (depletion of primordial oocytes)oocytes)

associated with autoimmune disorders (Addison’s associated with autoimmune disorders (Addison’s disease)disease)

also caused by radiation/cytotoxic drug therapy for also caused by radiation/cytotoxic drug therapy for Ca breastCa breast

increased LH and FSH seenincreased LH and FSH seen

The menopause The menopause

time of permanent cessation of menstruation time of permanent cessation of menstruation

normally occurs between ages 40-55 yrs, average normally occurs between ages 40-55 yrs, average age of onset 49 - 51 yrsage of onset 49 - 51 yrs

decline in follicles leads to lower estradioldecline in follicles leads to lower estradiol

FSH levels rise progressively from 41 yrs to 47 yrsFSH levels rise progressively from 41 yrs to 47 yrs

rise in FSH related to time of menopauserise in FSH related to time of menopause

Testosterone

Androgen testosterone is primarily secreted in the testes

of males and the ovaries of females Necessary for normal sperm development Libido Mental and physical energy Maintenance of muscle trophism

InfertilityInfertility

The failure to achieve pregnancy after one year of The failure to achieve pregnancy after one year of unprotected intercourseunprotected intercourse

the consistent failure to carry a pregnancy to termthe consistent failure to carry a pregnancy to term treatable condition; > 50% of couples can achieve treatable condition; > 50% of couples can achieve

pregnancypregnancy