The Endocrine SystemThe Endocrine System

Hypophyseal-Pituitary Hypophyseal-Pituitary AxisAxis

Site of Neural – Hormonal interactionSite of Neural – Hormonal interaction Sets temporal release of hormonesSets temporal release of hormones Responsible for stress reaction of Responsible for stress reaction of

hormoneshormones

The Hypothalamus & the The Hypothalamus & the Pituitary Gland-- Master Pituitary Gland-- Master Endocrine Glands!Endocrine Glands!The Hypothalamus:The Hypothalamus: Located in the brain, Located in the brain,

this region controls this region controls most endocrine most endocrine secretionssecretions

Mainly regulatory Mainly regulatory hormones are hormones are released here. Most released here. Most control the pituitary control the pituitary glandgland

The Pituitary GlandThe Pituitary Gland Descending from the Descending from the

hypothalamus, this gland hypothalamus, this gland has two halves: anterior has two halves: anterior & posterior& posterior

The anterior half The anterior half secretes mainly secretes mainly regulatory hormonesregulatory hormones

The posterior half The posterior half secretes hormones, but secretes hormones, but manufactures nonemanufactures none

Hormones secreted by the Hormones secreted by the Hypothalamus & Anterior Hypothalamus & Anterior Pituitary GlandPituitary Gland

HypothalamusHypothalamus Anterior PituitaryAnterior Pituitary

GHRH GHRH (GH-releasing)(GH-releasing) GH GH (growth hormone)(growth hormone)

SS SS (somatostatin, GH-inhib)(somatostatin, GH-inhib) “ “

CRHCRH (corticotropin-rel)(corticotropin-rel) ACTH ACTH (adrenocorticotropic)(adrenocorticotropic)

GnRH GnRH (gonadotropin-rel)(gonadotropin-rel) LH LH (luteinizing hormone)(luteinizing hormone)

““ FSH FSH (follicle-stimulating)(follicle-stimulating)

PRH PRH (PRL-releasing)(PRL-releasing) PRL PRL (prolactin)(prolactin)

PIHPIH (PRL rel-inhibiting) (PRL rel-inhibiting) “ “

TRH TRH (thyrotropin-rel)(thyrotropin-rel) TSH TSH (thyroid stimulating)(thyroid stimulating)

What do these anterior What do these anterior pituitary hormones do?pituitary hormones do?

Growth HormoneGrowth Hormone:: stimulates cells to grow stimulates cells to grow

and divideand divide increases amino acid increases amino acid

transport rate and protein transport rate and protein synthesissynthesis

increases fat metabolismincreases fat metabolism

Typically, GH is secreted Typically, GH is secreted during sleep.during sleep.

GH secretion increases when GH secretion increases when malnourishedmalnourished

GH influences bone GH influences bone growth via growth via somatomedin:somatomedin:

GH in bloodGH in blood

GH arrives in liverGH arrives in liver

liver secretes liver secretes somatomedinsomatomedin

cartilage dividescartilage divides

bones grow!bones grow!

Problems with GHProblems with GH

Too much GH in children leads to Too much GH in children leads to gigantismgigantism

Too much GH in adults leads to Too much GH in adults leads to acromegalyacromegaly

Too little GH in children leads to Too little GH in children leads to dwarfismdwarfism

Other Anterior Pituitary Other Anterior Pituitary Hormone FunctionsHormone Functions

ACTHACTH:: works on the cortex of works on the cortex of

the adrenal gland, the adrenal gland, influencing the release of influencing the release of cortisolcortisol

stress can increase CRH stress can increase CRH secretion which will secretion which will increase ACTH secretionincrease ACTH secretion

negative feedback when negative feedback when adrenal cortex hormones adrenal cortex hormones in blood decrease CRH in blood decrease CRH secretionsecretion

LH & FSHLH & FSH:: LH in females and in males LH in females and in males

leads to sex hormone secretionleads to sex hormone secretion FSH in females causes growth FSH in females causes growth

and development of egg cell-and development of egg cell-containing follicles in the ovary, containing follicles in the ovary, and causes estrogen secretionand causes estrogen secretion

FSH in males instigates sperm FSH in males instigates sperm productionproduction

both hormones are regulated by both hormones are regulated by GnRH, which is not significant GnRH, which is not significant in concentration until pubertyin concentration until puberty

More Anterior Pituitary More Anterior Pituitary Hormone FunctionsHormone Functions

PRLPRL:: In females, PRL In females, PRL

promotes lactationpromotes lactation In males, PRL decreases In males, PRL decreases

LH secretion LH secretion (note that (note that too much PRL would too much PRL would then decrease androgen then decrease androgen levels and cause sterility)levels and cause sterility)

Controlled by both PRH Controlled by both PRH and PIHand PIH

TSHTSH:: works on thyroid gland to works on thyroid gland to

either cause or inhibit its either cause or inhibit its secretion of hormonessecretion of hormones

works on thyroid gland to works on thyroid gland to affect its growthaffect its growth (too much (too much TSH leads to a goiter)TSH leads to a goiter)

negative feedback via negative feedback via thyroid hormones in bloodthyroid hormones in blood

stress or cold temperatures stress or cold temperatures can change TSH secretioncan change TSH secretion

The Posterior Pituitary The Posterior Pituitary LobeLobe

No hormones are No hormones are mademade here. They are made here. They are made in the hypothalamus and just released here.in the hypothalamus and just released here.

Two peptide hormones are released from the Two peptide hormones are released from the posterior pituitary lobe posterior pituitary lobe (the neurohypophysis)(the neurohypophysis)::

ADH ADH (antidiuretic hormone or vasopressin)(antidiuretic hormone or vasopressin) OT OT (oxytocin)(oxytocin)

Function of Posterior Function of Posterior Pituitary Lobe Pituitary Lobe HormonesHormones

ADHADH:: as an “antidiuretic,” ADH as an “antidiuretic,” ADH

decreases urine formation by decreases urine formation by having kidneys conserve waterhaving kidneys conserve water

also can contract smooth also can contract smooth muscle cells, as found in blood muscle cells, as found in blood vessels-- this causes an vessels-- this causes an increase in blood pressureincrease in blood pressure

ADH release triggered by ADH release triggered by osmoreceptors and inhibited osmoreceptors and inhibited by stretch receptors in blood by stretch receptors in blood vesselsvessels

OTOT:: In females, contracts In females, contracts

the uterine wall smooth the uterine wall smooth musclesmuscles

In females, helps to In females, helps to eject milk when eject milk when lactatinglactating

No known function in No known function in males, although in both males, although in both males and females, OT males and females, OT can have some can have some antidiuretic effectsantidiuretic effects

Hypothalamus & Anterior Hypothalamus & Anterior PituitaryPituitary

HypothalamusHypothalamus Anterior PituitaryAnterior Pituitary

GHRH GHRH (GH-releasing)(GH-releasing) GH GH (growth hormone)(growth hormone)

SS SS (somatostatin, GH-inhib)(somatostatin, GH-inhib) “ “

CRHCRH (corticotropin-rel)(corticotropin-rel) ACTH ACTH (adrenocorticotropic)(adrenocorticotropic)

GnRH GnRH (gonadotropin-rel)(gonadotropin-rel) LH LH (luteinizing hormone)(luteinizing hormone)

““ FSH FSH (follicle-stimulating)(follicle-stimulating)

PRH PRH (PRL-releasing)(PRL-releasing) PRL PRL (prolactin)(prolactin)

PIHPIH (PRL rel-inhibiting) (PRL rel-inhibiting) “ “

TRH TRH (thyrotropin-rel)(thyrotropin-rel) TSH TSH (thyroid stimulating)(thyroid stimulating)

Your book’s review Your book’s review diagram:diagram:

HPA BasicsHPA Basics

HypophysisHypophysis Third VentricleThird Ventricle GRH, TRH, CRH, GnRH, Dopamine, SomatostatinGRH, TRH, CRH, GnRH, Dopamine, Somatostatin

NeurohypophysisNeurohypophysis Derived from HypophysisDerived from Hypophysis ADH, OxytocinADH, Oxytocin

AdenohypophysisAdenohypophysis Derived from Rathke’s pouchDerived from Rathke’s pouch ACTH, LH, FSH, TSH, GH, PRLACTH, LH, FSH, TSH, GH, PRL

Pituitary DiseasesPituitary Diseases

Primary TumorsPrimary Tumors AdenomasAdenomas CraniopharyngiomaCraniopharyngioma

MetastasisMetastasis Empty SellaEmpty Sella

Surgical, post-Sheehand’sSurgical, post-Sheehand’s HemorrhageHemorrhage

Sheehand’s syndromeSheehand’s syndrome HyperfunctionHyperfunction

ProlactinProlactin InsufficiencyInsufficiency

The Endocrine Glands The Endocrine Glands and Their Hormonesand Their Hormones

Pituitary GlandPituitary Gland A marble-sized gland at the base of the brainA marble-sized gland at the base of the brain Controlled by the hypothalamus or other neural Controlled by the hypothalamus or other neural

mechanisms and therefore the middle man.mechanisms and therefore the middle man. Posterior LobePosterior Lobe

Antidiuretic hormone: responsible for fluid Antidiuretic hormone: responsible for fluid retentionretention

Oxytocin: contraction of the uterusOxytocin: contraction of the uterus

The Endocrine Glands The Endocrine Glands and their Hormonesand their Hormones

Pituitary GlandPituitary Gland Exercise appears to be a strong stimulant Exercise appears to be a strong stimulant

to the hypothalamus for the release of all to the hypothalamus for the release of all anterior pituitary hormones anterior pituitary hormones Anterior LobeAnterior Lobe

AdrenocorticotropinAdrenocorticotropin Growth hormone *Growth hormone * ThyropinThyropin Follicle-stimulating hormoneFollicle-stimulating hormone Luteinizing hormone *Luteinizing hormone * ProlactinProlactin

The Endocrine Glands The Endocrine Glands and Their Hormonesand Their Hormones

Thyroid GlandThyroid Gland Located along the midline of the neckLocated along the midline of the neck Secretes two nonsteroid hormonesSecretes two nonsteroid hormones

Triiodothyronine (T3)Triiodothyronine (T3) Thyroxine (T4)Thyroxine (T4)

Regulates metabolismRegulates metabolism increases protein synthesisincreases protein synthesis promotes glycolysis, gluconeogenesis, glucose promotes glycolysis, gluconeogenesis, glucose

uptakeuptake Calcitonin: calcium metabolismCalcitonin: calcium metabolism

ThyroidThyroid

ThyroidThyroid

Largest Endocrine organ in the bodyLargest Endocrine organ in the body Involved in production, storage, and Involved in production, storage, and

release of thyroid hormonerelease of thyroid hormone Function influenced byFunction influenced by

Central axis (TRH)Central axis (TRH) Pituitary function (TSH)Pituitary function (TSH) Comorbid diseases (Cirrhosis, Graves, etc.)Comorbid diseases (Cirrhosis, Graves, etc.) Environmental factors (iodine intake)Environmental factors (iodine intake)

The Thyroid GlandThe Thyroid Gland

StructureStructure: : This bilobed gland contains many follicles. A This bilobed gland contains many follicles. A folliclefollicle is a group of cells encircling a lumen. The lumen is a group of cells encircling a lumen. The lumen contains material called contains material called colloidcolloid (a glycoprotein) within it. As (a glycoprotein) within it. As hormones are produced by the cells, the hormones are hormones are produced by the cells, the hormones are either released into the colloid or directly into the blood.either released into the colloid or directly into the blood.

There are also extrafollicular hormone-secreting cells, There are also extrafollicular hormone-secreting cells, called called C cellsC cells. These are found between lumina.. These are found between lumina.

Hormones ProducedHormones Produced:: Thyroxine (TThyroxine (T44)) made in folliclemade in follicle

Triiodotyronine (TTriiodotyronine (T33)) made in folliclemade in follicle

Calcitonin Calcitonin made by C cellsmade by C cells

About the Thyroid About the Thyroid Hormones...Hormones...TT33 and T and T44:: Function: metabolism regulation Function: metabolism regulation

(break down carbohydrates and (break down carbohydrates and fats, synthesize proteins)fats, synthesize proteins)

Can only be made by follicular Can only be made by follicular cells when iodides are availablecells when iodides are available

Somewhat hydrophobic and get Somewhat hydrophobic and get carried by proteins in the blood.carried by proteins in the blood.

Controlled by anterior pituitary Controlled by anterior pituitary lobe TSHlobe TSH

TT33 more effective, T more effective, T44 more more

abundantabundant

CalcitoninCalcitonin:: Function: decrease Function: decrease

blood calcium levels blood calcium levels and blood phosphate and blood phosphate levels (by helping them levels (by helping them get deposited in bone, get deposited in bone, and by stimulating and by stimulating excretion of them by excretion of them by kidneys)kidneys)

Controlled by blood Controlled by blood calcium levels and calcium levels and digestive chemicalsdigestive chemicals

Problems with the Problems with the Thyroid GlandThyroid Gland

HyperthyroidismHyperthyroidism:: high metabolic rate, hyperactivity, sensitivity to heat, protruding high metabolic rate, hyperactivity, sensitivity to heat, protruding

eyeseyes Grave’s diseaseGrave’s disease: when hyperthyroidism is due to an autoimmune : when hyperthyroidism is due to an autoimmune

problem (TSH is mimicked by autoantibodies)problem (TSH is mimicked by autoantibodies)

HypothyroidismHypothyroidism:: in the adult: low metabolic rate, sensitivity to cold, sluggishnessin the adult: low metabolic rate, sensitivity to cold, sluggishness in an infant: in an infant: cretinismcretinism-- stunted growth, mental retardation, -- stunted growth, mental retardation,

abnormal bone formationabnormal bone formation Hashimoto’s diseaseHashimoto’s disease: when hypothyroidism is due to an : when hypothyroidism is due to an

autoimmune problem (autoantibodies attack and destroy follicular autoimmune problem (autoantibodies attack and destroy follicular cells)cells)

goitergoiter: no T3 and T4 can be made because not enough iodides : no T3 and T4 can be made because not enough iodides were ingested. were ingested.

Thyroid (cont)Thyroid (cont)

Regulates basal metabolic rateRegulates basal metabolic rate Improves cardiac contractilityImproves cardiac contractility Increases the gain of catecholaminesIncreases the gain of catecholamines Increases bowel motilityIncreases bowel motility Increases speed of muscle contractionIncreases speed of muscle contraction Decreases cholesterol (LDL)Decreases cholesterol (LDL) Required for proper fetal neural growthRequired for proper fetal neural growth

Thyroid PhysiologyThyroid Physiology

Uptake of Iodine by thyroidUptake of Iodine by thyroid Coupling of Iodine to ThyroglobulinCoupling of Iodine to Thyroglobulin Storage of MIT / DIT in follicular spaceStorage of MIT / DIT in follicular space Re-absorption of MIT / DITRe-absorption of MIT / DIT Formation of TFormation of T33, T, T44 from MIT / DIT from MIT / DIT

Release of TRelease of T33, T, T44 into serum into serum

Breakdown of TBreakdown of T33, T, T44 with release of Iodine with release of Iodine

Iodine uptakeIodine uptake

NaNa++/I/I-- symport symport protein controls protein controls serum Iserum I-- uptake uptake

Based on NaBased on Na++/K/K++ antiport potentialantiport potential

Stimulated by TSHStimulated by TSH Inhibited by Inhibited by

PerchloratePerchlorate

Secretion of Thyroid Secretion of Thyroid HormoneHormone

Stimulated by TSHStimulated by TSH Endocytosis of colloid on apical membraneEndocytosis of colloid on apical membrane Coupling of MIT & DIT residuesCoupling of MIT & DIT residues

Catalyzed by TPOCatalyzed by TPO

MIT + DIT = TMIT + DIT = T33

DIT + DIT = TDIT + DIT = T44

Hydrolysis of ThyroglobulinHydrolysis of Thyroglobulin Release of TRelease of T33, T, T44

Release inhibited by LithiumRelease inhibited by Lithium

Thyroid HormonesThyroid Hormones

Thyroid HormoneThyroid Hormone

Majority of circulating hormone is TMajority of circulating hormone is T44

98.5% T98.5% T44

1.5% T1.5% T33

Total Hormone load is influenced by serum Total Hormone load is influenced by serum binding proteins (TBP, Albumin, ??)binding proteins (TBP, Albumin, ??) Thyroid Binding Globulin 70%Thyroid Binding Globulin 70% Albumin 15%Albumin 15% Transthyretin 10%Transthyretin 10%

Regulation is based on the free component Regulation is based on the free component of thyroid hormoneof thyroid hormone

Hormone Binding FactorsHormone Binding Factors

Increased TBGIncreased TBG High estrogen states (pregnancy, OCP, HRT, Tamoxifen)High estrogen states (pregnancy, OCP, HRT, Tamoxifen) Liver disease (early)Liver disease (early)

Decreased TBGDecreased TBG Androgens or anabolic steroidsAndrogens or anabolic steroids Liver disease (late)Liver disease (late)

Binding Site CompetitionBinding Site Competition NSAID’sNSAID’s Furosemide IVFurosemide IV Anticonvulsants (Phenytoin, Carbamazepine)Anticonvulsants (Phenytoin, Carbamazepine)

Hormone DegredationHormone Degredation

TT44 is converted to T is converted to T33 (active) by (active) by 5’ deiodinase5’ deiodinase

TT44 can be converted to rT can be converted to rT33 (inactive) by (inactive) by 5 deiodinase5 deiodinase

TT33 is converted to rT is converted to rT22 (inactive)by (inactive)by 5 deiodinase5 deiodinase

rTrT33 is inactive but measured by serum tests is inactive but measured by serum tests

Thyroid Hormone ControlThyroid Hormone Control

TRHTRH

Produced by HypothalamusProduced by Hypothalamus Release is pulsatile, circadianRelease is pulsatile, circadian Downregulated by TDownregulated by T44, T, T33

Travels through portal venous system to Travels through portal venous system to adenohypophysisadenohypophysis

Stimulates TSH formationStimulates TSH formation

TSHTSH

Produced by Adenohypophysis ThyrotrophsProduced by Adenohypophysis Thyrotrophs Upregulated by TRH Upregulated by TRH Downregulated by TDownregulated by T44, T, T33

Travels through portal venous system to Travels through portal venous system to cavernous sinus, body.cavernous sinus, body.

Stimulates several processesStimulates several processes Iodine uptakeIodine uptake Colloid endocytosisColloid endocytosis Growth of thyroid gland Growth of thyroid gland

TSH ResponseTSH Response

Iodine statesIodine states

Normal ThyroidNormal Thyroid

Inactive ThyroidInactive Thyroid

Hyperactive ThyroidHyperactive Thyroid

HypothyroidHypothyroid

Symptoms – fatigability, coldness, weight gain, Symptoms – fatigability, coldness, weight gain, constipation, low voiceconstipation, low voice

Signs – Cool skin, dry skin, swelling of Signs – Cool skin, dry skin, swelling of face/hands/legs, slow reflexes, myxedemaface/hands/legs, slow reflexes, myxedema

Newborn – Retardation, short stature, swelling of Newborn – Retardation, short stature, swelling of face/hands, possible deafnessface/hands, possible deafness

Types of HypothyroidismTypes of Hypothyroidism Primary – Thyroid gland failurePrimary – Thyroid gland failure Secondary – Pituitary failureSecondary – Pituitary failure Tertiary – Hypothalamic failureTertiary – Hypothalamic failure Peripheral resistancePeripheral resistance

HypothyroidHypothyroid

Cause is determined by Cause is determined by geographygeography

DiagnosisDiagnosis Low FTLow FT44, High TSH , High TSH

(Primary, check for (Primary, check for antibodies)antibodies)

Low FTLow FT44, Low TSH , Low TSH (Secondary or Tertiary, (Secondary or Tertiary, TRH stimulation test, MRI)TRH stimulation test, MRI) TreatmentTreatment

Levothyroxine (TLevothyroxine (T44) due to longer half life) due to longer half life Treatment prevents bone loss, cardiomyopathy, Treatment prevents bone loss, cardiomyopathy,

myxedemamyxedema

GoiterGoiter

Endemic goiterEndemic goiter Caused by dietary deficiency of IodideCaused by dietary deficiency of Iodide Increased TSH stimulates gland growthIncreased TSH stimulates gland growth Also results in cretinismAlso results in cretinism

Goiter in developed countriesGoiter in developed countries Hashimoto’s thryoiditisHashimoto’s thryoiditis Subacute thyroiditisSubacute thyroiditis

Other causesOther causes Excess Iodide (Amiodarone, Kelp, Lithium)Excess Iodide (Amiodarone, Kelp, Lithium) Adenoma, MalignancyAdenoma, Malignancy Genetic / Familial hormone synthesis defectsGenetic / Familial hormone synthesis defects

HyperthyroidHyperthyroid

Symptoms – Palpitations, nervousness, fatigue, Symptoms – Palpitations, nervousness, fatigue, diarrhea, sweating, heat intolerancediarrhea, sweating, heat intolerance

Signs – Thyroid enlargement (?), tremorSigns – Thyroid enlargement (?), tremor Lab workupLab workup

TSHTSH FT4FT4 RAIURAIU

Other LabsOther Labs Anti-TSH-R Ab, Anti-TPO Ab, Anti-TBG AbAnti-TSH-R Ab, Anti-TPO Ab, Anti-TBG Ab FT3FT3 FNAFNA MRI, USMRI, US

HyperthyroidHyperthyroid

Common CausesCommon Causes *Graves*Graves Adenoma Adenoma Multinodular GoiterMultinodular Goiter *Subacute Thyroiditis*Subacute Thyroiditis *Hashimoto’s Thyroiditis*Hashimoto’s Thyroiditis

Rare CausesRare Causes Thyrotoxicosis factitia, struma ovarii, thyroid Thyrotoxicosis factitia, struma ovarii, thyroid

metastasis, TSH-secreting tumor, hamburgermetastasis, TSH-secreting tumor, hamburger

The Endocrine GlandsThe Endocrine Glands

Parathyroid GlandsParathyroid Glands Secretes parathyroid hormoneSecretes parathyroid hormone

regulates plasma calcium (osteoclast activity) regulates plasma calcium (osteoclast activity) regulates phosphate levelsregulates phosphate levels

Calcium Calcium RegulationRegulationParathyroidParathyroid

CalciumCalcium

Required for muscle contraction, intracellular Required for muscle contraction, intracellular messenger systems, cardiac repolarization.messenger systems, cardiac repolarization.

Exists in free and bound statesExists in free and bound states Albumin (40% total calcium)Albumin (40% total calcium) Phosphate and Citrate (10% total calcium)Phosphate and Citrate (10% total calcium)

Concentration of iCa++ mediated byConcentration of iCa++ mediated by Parathyroid glandParathyroid gland Parafollicular C cellsParafollicular C cells Kidney Kidney BoneBone

Parathyroid GlandParathyroid Gland This gland only This gland only

secretes one secretes one hormone: hormone: Parathyroid Parathyroid Hormone (or PTH)Hormone (or PTH)

PTH function PTH function (we (we began learning this when began learning this when

we studied bone)we studied bone):: increases blood increases blood

calcium (Cacalcium (Ca2+2+) ) levels and levels and decreases blood decreases blood phosphate (POphosphate (PO44

2-2-) )

levelslevels

PTH function PTH function (continued)(continued)

How does PTH work?How does PTH work? PTH causes CaPTH causes Ca2+2+ & PO & PO44

2-2- to be released from bone to be released from bone

into blood (by increasing osteoclast activity)into blood (by increasing osteoclast activity) PTH causes the kidneys to remove POPTH causes the kidneys to remove PO44

2-2- ions from ions from

the urinethe urine PTH increases vitamin D production, so that you PTH increases vitamin D production, so that you

absorb more Caabsorb more Ca2+2+ during digestion during digestion

PTH is regulated by blood calcium levels-- not PTH is regulated by blood calcium levels-- not by other glands!by other glands!

Parathyroid HormoneParathyroid Hormone

Produced by Parathyroid Chief cellsProduced by Parathyroid Chief cells Secreted in response to low iCaSecreted in response to low iCa++++

Stimulates renal conversion of 25-(OH)DStimulates renal conversion of 25-(OH)D33 to to

1,25-(OH)1,25-(OH)22D which increases intestinal CaD which increases intestinal Ca++++

absorptionabsorption Directly stimulates renal CaDirectly stimulates renal Ca++++ absorption and absorption and

POPO443-3- excretion excretion

Stimulates osteoclastic resorption of boneStimulates osteoclastic resorption of bone

CalcitoninCalcitonin

Produced by Parafollicular C cells of Thyroid Produced by Parafollicular C cells of Thyroid in response to increased iCain response to increased iCa++++

ActionsActions Inhibit osteoclastic resorption of boneInhibit osteoclastic resorption of bone Increase renal CaIncrease renal Ca++++ and PO and PO44

3-3- excretion excretion Non-essential hormone. Patients with total Non-essential hormone. Patients with total

thyroidectomy maintain normal Cathyroidectomy maintain normal Ca++++ concentrationsconcentrations

Useful in monitoring treatment of Medullary Useful in monitoring treatment of Medullary Thyroid cancerThyroid cancer

Used in treatment of Pagets’, OsteoporosisUsed in treatment of Pagets’, Osteoporosis

Vitamin DVitamin D

SourcesSources Food – Vitamin DFood – Vitamin D22

UV light mediated cholesterol metabolism – DUV light mediated cholesterol metabolism – D33

MetabolismMetabolism DD22 and D and D33 are converted to 25(OH)-D by the liver are converted to 25(OH)-D by the liver

25(OH)-D is converted to 1,25(OH)25(OH)-D is converted to 1,25(OH)22-D by the Kidney-D by the Kidney

FunctionFunction Stimulation of OsteoblastsStimulation of Osteoblasts Increases GI absorption of dietary CaIncreases GI absorption of dietary Ca++++

HypocalcemiaHypocalcemia

Decreased PTHDecreased PTH SurgerySurgery HypomagnesemiaHypomagnesemia IdiopathicIdiopathic

Resistance to PTHResistance to PTH Genetic disordersGenetic disorders BisphosphonatesBisphosphonates

Vitamin D abnormalitiesVitamin D abnormalities Vitamin D deficiencyVitamin D deficiency Rickets (VDR or Renal hyroxylase abnormalities)Rickets (VDR or Renal hyroxylase abnormalities)

Binding of CalciumBinding of Calcium Hyperphosphate states (Crush injury, Tumor lysis, etc.)Hyperphosphate states (Crush injury, Tumor lysis, etc.) Blood Transfusion (Citrate)Blood Transfusion (Citrate)

HypercalcemiaHypercalcemia

HyperparathyroidismHyperparathyroidism Primary, Secondary, TertiaryPrimary, Secondary, Tertiary MEN SyndromesMEN Syndromes

MalignancyMalignancy Humoral HypercalcemiaHumoral Hypercalcemia PTHrP (Lung Cancer)PTHrP (Lung Cancer) Osteoclastic activity (Myeloma, Lymphoma)Osteoclastic activity (Myeloma, Lymphoma)

Granulomatous DiseasesGranulomatous Diseases Overproduction of 1,25 (OH)Overproduction of 1,25 (OH)22DD

Drug-InducedDrug-Induced ThiazidesThiazides LithiumLithium Milk-AlkaliMilk-Alkali Vitamin A, DVitamin A, D

Renal failureRenal failure

Hypercalcemia Hypercalcemia

Signs & SymptomsSigns & Symptoms Bones (Osteitis fibrosa cystica, osteoporosis, rickets)Bones (Osteitis fibrosa cystica, osteoporosis, rickets) Stones (Renal stones)Stones (Renal stones) Groans (Constipation, peptic ulcer)Groans (Constipation, peptic ulcer) Moans (Lethargy, depression, confusion)Moans (Lethargy, depression, confusion)

Medical TreatmentMedical Treatment SERM’s (Evista)SERM’s (Evista) Bisphosphonates (Pamidronate)Bisphosphonates (Pamidronate) Calcitonin (for severe cases)Calcitonin (for severe cases) Saline diuresisSaline diuresis Glucocorticoids (for malignant/granulomatous diseases)Glucocorticoids (for malignant/granulomatous diseases) Avoid thiazide diureticsAvoid thiazide diuretics

Surgical TreatmentSurgical Treatment Single vs. Double adenoma – simple excisionSingle vs. Double adenoma – simple excision Multiple Gland hyperplasia – total parathyroid with autotransplant vs. Multiple Gland hyperplasia – total parathyroid with autotransplant vs.

3½ gland excision3½ gland excision

Primary Primary HyperparathyroidismHyperparathyroidism DiagnosisDiagnosis

Signs & SymptomsSigns & Symptoms Elevated serum calciumElevated serum calcium Elevated PTHElevated PTH

EtiologyEtiology Solitary Adenoma (80-85%)Solitary Adenoma (80-85%) Double Adenomas (2-4%)Double Adenomas (2-4%) Muliple Gland Hyperplasia (10-30%)Muliple Gland Hyperplasia (10-30%) Parathyroid Carcinoma (0.5%)Parathyroid Carcinoma (0.5%) MEN syndromes (10% of MGH have MEN 1)MEN syndromes (10% of MGH have MEN 1)

ParathyroidectomyParathyroidectomy

1990 NIH Guidelines1990 NIH Guidelines Serum Ca++ > 12 mg/dlSerum Ca++ > 12 mg/dl Hypercalciuria > 400 mg/dayHypercalciuria > 400 mg/day Classic symptoms Classic symptoms

NephrolithiasisNephrolithiasis Osteitis fibrosa cysticaOsteitis fibrosa cystica Neuromuscular diseaseNeuromuscular disease

Cortical bone loss with DEXA Z score < -2Cortical bone loss with DEXA Z score < -2 Reduced creatinine clearanceReduced creatinine clearance Age < 50Age < 50

Other considerationsOther considerations Vertebral osteopeniaVertebral osteopenia Vitamin D deficencyVitamin D deficency PerimenopausePerimenopause

The Endocrine GlandsThe Endocrine Glands Adrenal MedullaAdrenal Medulla

Situated directly atop each kidney and Situated directly atop each kidney and stimulated by the sympathetic nervous systemstimulated by the sympathetic nervous system

Secretes the catecholaminesSecretes the catecholamines EpinephrineEpinephrine: elicits a fight or flight response: elicits a fight or flight response

Increase H.R. and B.P.Increase H.R. and B.P. Increase respirationIncrease respiration Increase metabolic rateIncrease metabolic rate Increase glycogenolysisIncrease glycogenolysis VasodilationVasodilation

NorepinephrineNorepinephrine House keeping systemHouse keeping system

The Endocrine GlandsThe Endocrine Glands Adrenal CortexAdrenal Cortex Secretes over 30 different steroid hormones Secretes over 30 different steroid hormones

(corticosteroids)(corticosteroids) MineralocorticoidsMineralocorticoids

Aldosterone: maintains electrolyte balanceAldosterone: maintains electrolyte balance

GlucocorticoidsGlucocorticoids Cortisol: Cortisol:

Stimulates gluconeogenisisStimulates gluconeogenisis Mobilization of free fatty acidsMobilization of free fatty acids Glucose sparingGlucose sparing Anti-inflammatory agentAnti-inflammatory agent

GonadocorticoidsGonadocorticoids testosterone, estrogen, progesteronetestosterone, estrogen, progesterone

The Endocrine GlandsThe Endocrine Glands

Pancrease:Pancrease: Located slightly behind the stomachLocated slightly behind the stomach InsulinInsulin: reduces blood glucose: reduces blood glucose

Facilitates glucose transport into the cellsFacilitates glucose transport into the cells Promotes glycogenesisPromotes glycogenesis Inhibits gluconeogensisInhibits gluconeogensis

Glucagon: increases blood glucoseGlucagon: increases blood glucose

The Endocrine GlandsThe Endocrine Glands GonadsGonads

testes (testes (testosteronetestosterone) = sex characteristics) = sex characteristics muscle development and maturitymuscle development and maturity

ovaries (estrogen) = sex characteristicsovaries (estrogen) = sex characteristics maturity and coordinationmaturity and coordination

Kidneys (Kidneys (erythropoietin)erythropoietin) regulates red blood cell productionregulates red blood cell production

The Endocrine Response to The Endocrine Response to ExerciseExercise

Table 5.3 Page 172Table 5.3 Page 172

Regulation of Glucose Regulation of Glucose Metabolism During ExerciseMetabolism During Exercise Glucagon secretion increases during exercise Glucagon secretion increases during exercise

to promote liver glycogen breakdown to promote liver glycogen breakdown (glycogenolysis)(glycogenolysis)

Epinephrine and Norepinephrine further Epinephrine and Norepinephrine further increase glycogenolysisincrease glycogenolysis

Cortisol levels also increase during exercise for Cortisol levels also increase during exercise for protein catabolism for later gluconeogenesis.protein catabolism for later gluconeogenesis.

Growth Hormone mobilizes free fatty acidsGrowth Hormone mobilizes free fatty acids Thyroxine promotes glucose catabolismThyroxine promotes glucose catabolism

Regulation of Glucose Regulation of Glucose Metabolism During ExerciseMetabolism During Exercise

As intensity of exercise increases, so does As intensity of exercise increases, so does the rate of catecholamine release for the rate of catecholamine release for glycogenolysisglycogenolysis

During endurance events the rate of glucose During endurance events the rate of glucose release very closely matches the muscles release very closely matches the muscles need. (fig 5.9, pg. 174)need. (fig 5.9, pg. 174)

When glucose levels become depleted, When glucose levels become depleted, glucagon and cortisol levels rise significantly glucagon and cortisol levels rise significantly to enhance gluconeogenesis.to enhance gluconeogenesis.

Regulation of Glucose Regulation of Glucose Metabolism During ExerciseMetabolism During Exercise

Glucose must not only be delivered to the Glucose must not only be delivered to the cells, it must also be taken up by them. cells, it must also be taken up by them. That job relies on That job relies on insulininsulin..

Exercise may enhance insulin’s binding to Exercise may enhance insulin’s binding to receptors on the muscle fiber.receptors on the muscle fiber.

Up-regulation (receptors) occurs with Up-regulation (receptors) occurs with insulin after 4 weeks of exercise to increase insulin after 4 weeks of exercise to increase its sensitivity (diabetic importance). its sensitivity (diabetic importance).

Regulation of Fat Regulation of Fat Metabolism During ExerciseMetabolism During Exercise

When low plasma glucose levels occur, the When low plasma glucose levels occur, the catecholamines are released to accelerate catecholamines are released to accelerate lypolysis.lypolysis.

Triglycerides are reduced to free fatty acids by Triglycerides are reduced to free fatty acids by lipase which is activated by: (fig. 5.11, pg. lipase which is activated by: (fig. 5.11, pg. 176)176) CortisolCortisol EpinephrineEpinephrine NorepinephrineNorepinephrine Growth HormoneGrowth Hormone

Hormonal Effects on Fluid Hormonal Effects on Fluid and Electrolyte Balanceand Electrolyte Balance

Reduced plasma volume leads to release of Reduced plasma volume leads to release of aldosteronealdosterone which increases Na+ and H2O which increases Na+ and H2O reabsorption by the kidneys and renal reabsorption by the kidneys and renal tubes.tubes.

Antidiuretic HormoneAntidiuretic Hormone (ADH) is released (ADH) is released from the posterior pituitary when from the posterior pituitary when dehydration is sensed by osmoreceptors, dehydration is sensed by osmoreceptors, and water is then reabsorbed by the and water is then reabsorbed by the kidneys.kidneys.

Adrenal GlandsAdrenal Glands An adrenal gland is found on top of each kidney. Each adrenal gland has two regions that carry out separate functions!

•The adrenal medulla•The adrenal cortex

We will cover each of these two regions separately in the next few slides.

The Adrenal MedullaThe Adrenal Medulla

Acts very much like a part of the sympathetic Acts very much like a part of the sympathetic nervous system (fight or flight)nervous system (fight or flight)

Secretes two amines:Secretes two amines: norepinephrinenorepinephrine (20%) (20%) epinephrineepinephrine (80%) (80%)

Stimulated by preganglionic neurons directly, so Stimulated by preganglionic neurons directly, so controlled by the hypothalamus as if part of the controlled by the hypothalamus as if part of the autonomic nervous system, NOT by tropic autonomic nervous system, NOT by tropic hormoneshormones

The Adrenal CortexThe Adrenal Cortex

Acts like a regular endocrine organActs like a regular endocrine organ

Secretes many hormones, but most importantly Secretes many hormones, but most importantly secretes the following steroids:secretes the following steroids: aldosteronealdosterone cortisolcortisol sex hormonessex hormones

Aldosterone and cortisol require further Aldosterone and cortisol require further explanationexplanation (while sex hormone production will be (while sex hormone production will be covered later this semester)covered later this semester)

More about Adrenal Cortex More about Adrenal Cortex HormonesHormonesAldosteroneAldosterone::Considered a Considered a

mineralocorticoidmineralocorticoidRegulates “mineral electrolyte” levels Regulates “mineral electrolyte” levels

in the blood (for example: Nain the blood (for example: Na++ and and KK++ ions) ions)

How is aldosterone controlled?How is aldosterone controlled? blood plasma ion concentrations blood plasma ion concentrations

affect its secretion directly (but affect its secretion directly (but not always strongly)not always strongly)

kidney secretes kidney secretes reninrenin in in response to altered electrolyte response to altered electrolyte levels, which triggers levels, which triggers angiotensinangiotensin activation in the activation in the blood, which leads to blood, which leads to aldosterone secretionaldosterone secretion

ACTH from the anterior pituitary ACTH from the anterior pituitary can cause aldosterone secretioncan cause aldosterone secretion

CortisolCortisol::Considered a Considered a glucocorticoidglucocorticoidOverall effect of cortisol:Overall effect of cortisol: Helps to keep blood glucose Helps to keep blood glucose

concentration within a normal concentration within a normal range between mealsrange between meals

Specific actions of cortisol:Specific actions of cortisol: increases amino acid increases amino acid

concentration in the blood (by concentration in the blood (by inhibiting protein synthesis in inhibiting protein synthesis in select tissues)select tissues)

promotes use of fat for energy promotes use of fat for energy production in our bodies (rather production in our bodies (rather than glucose)than glucose)

stimulates the liver to synthesize stimulates the liver to synthesize glucose (not from carbohydrates, glucose (not from carbohydrates, but from amino acids and but from amino acids and glycerol), called glycerol), called gluconeogenesisgluconeogenesis

The PancreasThe Pancreas This gland has both endocrine and exocrine This gland has both endocrine and exocrine

functions… we’ll only cover the endocrine portion functions… we’ll only cover the endocrine portion now now (exocrine is for digestion)(exocrine is for digestion)

The endocrine portion of the gland contains three The endocrine portion of the gland contains three types of cells, each making a different hormone, types of cells, each making a different hormone, arranged into groups called Islets of Langerhansarranged into groups called Islets of Langerhans alpha cellsalpha cells: secrete glucagon: secrete glucagon beta cellsbeta cells: secrete insulin: secrete insulin delta cellsdelta cells: secrete SS (somatostatin): secrete SS (somatostatin)

Note that these pancreatic hormones are involved Note that these pancreatic hormones are involved in blood glucose regulation, and problems with in blood glucose regulation, and problems with them can lead to diabetes.them can lead to diabetes.

Blood Glucose Regulation by Blood Glucose Regulation by the Pancreasthe PancreasGlucagonGlucagon::

It works on the liver to cause It works on the liver to cause the production of glucose the production of glucose via:via: glycogenolysisglycogenolysis gluconeogenesisgluconeogenesis

It is regulated by blood It is regulated by blood glucose levels directly:glucose levels directly: secreted when blood secreted when blood

glucose drops (before next glucose drops (before next meal)meal)

Prevents Prevents hypoglycemiahypoglycemia

InsulinInsulin::

It works on the liver to It works on the liver to remove glucose from the remove glucose from the blood via:blood via: making glycogenmaking glycogen preventing preventing

gluconeogenesisgluconeogenesis increasing glucose increasing glucose

transport into cellstransport into cells

It is also regulated by blood It is also regulated by blood glucose levels directlyglucose levels directly

Prevents Prevents hyperglycemiahyperglycemia

Note: glucagon and insulin work in opposition, and their combined effects control blood glucose

Pineal GlandPineal Gland

Secretes only one hormone: melatoninSecretes only one hormone: melatonin

Involved in your circadian rhythm (your Involved in your circadian rhythm (your recognition of day and night times):recognition of day and night times): melatonin secretion decreases in the daymelatonin secretion decreases in the day melatonin secretion increases at nightmelatonin secretion increases at night

Melatonin is also involved in longer rhythms, Melatonin is also involved in longer rhythms, like monthly and seasonal… and is thought like monthly and seasonal… and is thought to be involved in the female menstrual cycle to be involved in the female menstrual cycle and maybe in the onset of pubertyand maybe in the onset of puberty

Other Endocrine GlandsOther Endocrine Glands

Thymus Gland: secretesThymus Gland: secretes thymosins thymosins which are involved in white blood cell which are involved in white blood cell productionproduction

Reproductive glands (the gonads): the Reproductive glands (the gonads): the ovaries and the testes produce sex ovaries and the testes produce sex hormoneshormones

Others: too specific for now, we’ll get to Others: too specific for now, we’ll get to them as we continue this semester.them as we continue this semester.