ENDOCRINESENDOCRINES

• Thyroglobulin is a large protein Thyroglobulin is a large protein molecule synthesized by the molecule synthesized by the thyroid gland: Tyrosine in this thyroid gland: Tyrosine in this molecule is iodinated and molecule is iodinated and coupled by peroxidase enzymecoupled by peroxidase enzyme

• Tetra-iodothyronine is T4Tetra-iodothyronine is T4• Tri-iodothyronine T3 is the active Tri-iodothyronine T3 is the active

moleculemolecule

THYROID HORMONESTHYROID HORMONES

• ACTIONS ACTIONS • Regulates growth and developmentRegulates growth and development• ^BMR^BMR• ^CHO utilization^CHO utilization• ^ Lipolytic action^ Lipolytic action• Reduces plasma cholesterolReduces plasma cholesterol• Negative feed backNegative feed back• CVS stimulantCVS stimulant• Necessary for normal GH secretionNecessary for normal GH secretion

Thyrotoxicosis: Thyrotoxicosis: TreatmentTreatment

• ClassClass• PropylthiouracilPropylthiouracil• MethimazoleMethimazole

• Lugol’s iodine (5% Lugol’s iodine (5% iodine/10% K iodide)iodine/10% K iodide)

• Beta Blockers:Beta Blockers:• PropranalolPropranalol

• Radioactive iodineRadioactive iodine

• MOAMOA• Peroxidase inhibitor: prevents Peroxidase inhibitor: prevents

peripheral conversion of T4 to T3peripheral conversion of T4 to T3• Side effects: Pruritus/ Dizziness/ Side effects: Pruritus/ Dizziness/

Leukopenia/JaundiceLeukopenia/Jaundice• Dosage:15-60mg/dayDosage:15-60mg/day

• Inhibits release of T3 and T4Inhibits release of T3 and T4

• Reduces T3 activity on target Reduces T3 activity on target organsorgans

• Rapidly concentrates in the gland Rapidly concentrates in the gland and destroys the thyroxine and destroys the thyroxine producing cellsproducing cells

THYROID HORMONESTHYROID HORMONES

• Indications:Indications:• Myxedema therapyMyxedema therapy• Prevents cretinismPrevents cretinism• Goiter managementGoiter management• Thyroid tablets–gland extracts-Thyroid tablets–gland extracts-60 mg60 mg• Levothuyroxine sodium (T4)-Levothuyroxine sodium (T4)-100 mcg100 mcg• Liothyronine (T3)-Liothyronine (T3)-25 mcg25 mcg• Adverse effects: Cardiac side effectsAdverse effects: Cardiac side effects

Adrenal GlandsAdrenal Glands

• Adrenal Cortex: Adrenal Cortex: • Steroid hormones derived from Steroid hormones derived from

cholesterol - "long term response”cholesterol - "long term response”

• Adrenal Medulla :Adrenal Medulla :• Epinephrine - Neuronal release due Epinephrine - Neuronal release due

to stress "short term response"to stress "short term response"

CHRONO BIOLOGICAL RHYTHMSCHRONO BIOLOGICAL RHYTHMS

• CIRCADIANCIRCADIAN• 24 HOUR CYCLE24 HOUR CYCLE• DARK / LIGHTDARK / LIGHT• SLEEP / AWAKESLEEP / AWAKE

PATTERNSPATTERNS• PEAK HOURS OF PEAK HOURS OF • COPRTISOL COPRTISOL

SECRETIONSSECRETIONS• 4 AM - 8 AM4 AM - 8 AM

• ULTRADIANULTRADIAN• 4 - 8 SECRETORY 4 - 8 SECRETORY

“BURSTS” IN 24 HOUR “BURSTS” IN 24 HOUR PERIODPERIOD

• TRIGGERED BY CRH TRIGGERED BY CRH AND ACTH BURSTS AND ACTH BURSTS

• CLUSTERED AT PEAK CLUSTERED AT PEAK CIRCADIAN TIMESCIRCADIAN TIMES

GLUCOCORTICOIDS:‘CORTISONE’GLUCOCORTICOIDS:‘CORTISONE’

• Gluco - regulate blood glucose, CHO Gluco - regulate blood glucose, CHO and Protein metabolismand Protein metabolism

•Cortisol (hydrocortisone) Cortisol (hydrocortisone)

10 - 25 mg / day10 - 25 mg / day•Cortisone – Cortisone –

0.5 - 2 mg / day0.5 - 2 mg / day•Corticosterone –Corticosterone –

30 - 150 mcg / day30 - 150 mcg / day

GLUCOCORTICOIDS GLUCOCORTICOIDS FUNCTIONSFUNCTIONS

Increase liver glycogen storesIncrease liver glycogen stores Increase gluocneogenesisIncrease gluocneogenesis Increase lipolysisIncrease lipolysis CNS mood effects: Depression/EuphoriaCNS mood effects: Depression/Euphoria Assists CVS functions: potentiates NEAssists CVS functions: potentiates NE Increased hemoglobin synthesisIncreased hemoglobin synthesis Inhibits prostaglandins and leukotrenesInhibits prostaglandins and leukotrenes

Glucocorticoid functionsGlucocorticoid functions Anti-inflammatory and Anti-allergic:Anti-inflammatory and Anti-allergic:

•Suppress leukocyte migration Suppress leukocyte migration •Stabilize cell membranesStabilize cell membranes•Decrease fibroblast activityDecrease fibroblast activity•Reverse capillary permeability induced by Reverse capillary permeability induced by histamine releasehistamine release

•Suppress immune response by inhibiting Suppress immune response by inhibiting antibody synthesisantibody synthesis

•Inhibits cell growth and cell divisionInhibits cell growth and cell division

AVOID Pituitary-Adrenal Axis suppression

•Once suppressed it will take more Once suppressed it will take more than 1 year for normal function to than 1 year for normal function to returnreturn

•<25mg of prednisolone /day taken at 8 <25mg of prednisolone /day taken at 8 am for < 10-15 days usually does not am for < 10-15 days usually does not suppresssuppress

•To minimize suppression taper of the To minimize suppression taper of the dose rather than stopping abruptlydose rather than stopping abruptly

GLUCOCORTICOIDSGLUCOCORTICOIDS

Glucocorticoid Anti-inflammatory

Potency

Equivalentoral

Potency

SodiumRetenti

onShort acting (<12 hrs)HydrocortisoneCortisone

1.00.8

2025

2+2+

Intermediate acting(12-24hrs)PrednisolonePrednisoneMethylprednisoloneTriamcinolone

5.04.05.05.0

5544

1+1+00

Long acting (>24 hrs)BetamethasoneDexamethasone

40.030.0

0.60.75

00

MineralocorticoidsMineralocorticoids

• RENAL• electrolyte and water excretion

Na+, Phosphate, Ca+, Bicarbonate Retention

Reduction of Serum K+

Aldostrone:Aldostrone:

•Secreted by adrenal cortexSecreted by adrenal cortex•^ Na tubular reabsorption ^ Na tubular reabsorption •^ serum levels of Na^ serum levels of Na•^K and H ions excretion by ^K and H ions excretion by

kidneyskidneys

Fludrocrotisone ‘Florinef Fludrocrotisone ‘Florinef ‘‘

•Acts on distal tubule -Acts on distal tubule -^reabsorption of Na and K^reabsorption of Na and K

•Side effects-Headaches/HTNSide effects-Headaches/HTN• Indication: Indication: •Addison' s diseaseAddison' s disease

Anti Adrenals:Anti Adrenals:• AminoglutehemideAminoglutehemide• MOA- prevents enzymatic action to convert MOA- prevents enzymatic action to convert

cholesterol to steroidscholesterol to steroids• Inhibits peripheral tissue conversion of anjdrogens Inhibits peripheral tissue conversion of anjdrogens

to estrogens to estrogens

• (useful in breast cancer treatment)(useful in breast cancer treatment)• Side effects: ataxia, dizziness, nausea, Side effects: ataxia, dizziness, nausea,

vomiting,rash, jaundice, bruising vomiting,rash, jaundice, bruising • Trilostane another compound which blocks steroid Trilostane another compound which blocks steroid

synthesissynthesis

• Used in Cushing's syndromeUsed in Cushing's syndrome

PreparationsPreparations

• SystemicSystemic• TopicalTopical• Inhaled varieties – Inhaled varieties –

Beclomethasone Beclomethasone

Budesonide Budesonide

FlunisolideFlunisolide• Risk of: Risk of:

oropharyngeal candidiasis oropharyngeal candidiasis

dysphoniadysphonia

Steroid IndicationsSteroid Indications

• Addison’sAddison’s• Rheumatoid Rheumatoid

arthritisarthritis• Rheumatic Rheumatic

carditiscarditis• Nephrotic Nephrotic

syndromesyndrome• SLESLE• Severe allergySevere allergy

• Ocular Ocular

inflammationinflammation• SkinSkin• IBDIBD• Cerebral edemaCerebral edema• AsthmaAsthma• RhinitisRhinitis

STEROID SIDE EFFECTSSTEROID SIDE EFFECTS

PITUITARY SUPPRESSION

RISK OF INFECTIONPEPTIC ULCERATIONMYOPATHYSTEROID PSYCHOSIS

IN CHILDREN: GROWTH ARREST SUBCAPSULAR CATARACTS

OSTEOPOROSIS – INHIBITS:INHIBITS:

OSTEOBLAST FORMATION OSTEOBLAST FORMATION

INTESTINAL Ca ABSORPTIONINTESTINAL Ca ABSORPTION

HYPERGLYCEMIA

PANCREAS / DIABETESPANCREAS / DIABETES

• 16 million Americans and increasing 16 million Americans and increasing • 77thth leading cause of death leading cause of death• Blindness/ESRD/Limb amputationsBlindness/ESRD/Limb amputations• Insulin(Beta cells) = Insulin(Beta cells) =

GlycogenesisGlycogenesis• Glucagon(Alpha cells)= Glucagon(Alpha cells)=

GlycogenolysisGlycogenolysis

Lack of insulin causes:Lack of insulin causes: Reduced rate of glucose transport Reduced rate of glucose transport across cell membranesacross cell membranes

Reduced enzyme activity in Reduced enzyme activity in converting glucose to glycogenconverting glucose to glycogen

Hyperlipemia, ketonemia, Acidosis Hyperlipemia, ketonemia, Acidosis due to increased lipase activitydue to increased lipase activity

Leads to increased glucagon activity Leads to increased glucagon activity causing increased proteolysis and causing increased proteolysis and uremiauremia

• TYPE I / IDDTYPE I / IDD• < 30 YEARS AGE< 30 YEARS AGE• NONOBESENONOBESE• 10% OF PATIENTS10% OF PATIENTS• LOW / ABSENT LOW / ABSENT

INSULIN LEVELSINSULIN LEVELS• REQUIRES REQUIRES

INSULININSULIN• NORMAL NORMAL

RECEPTORSRECEPTORS• DKADKA

• TYPE II / NIDDMTYPE II / NIDDM• > 35 YEARS AGE> 35 YEARS AGE• OBESEOBESE• 90% OF PATUIENTS90% OF PATUIENTS• NORMAL / HIGH NORMAL / HIGH

INSULIN RESISTANTINSULIN RESISTANT• ORAL AGENTS / ORAL AGENTS /

DIETDIET• DECREASED / DECREASED /

DEFECTIVE RECPETORSDEFECTIVE RECPETORS• NON KETOTICNON KETOTIC

TYPES OF INSULINTYPES OF INSULIN

• SOURCE- BEEF / PORK / HUMANSOURCE- BEEF / PORK / HUMAN

• PORK LESS ALLERGENIC THAN BEEFPORK LESS ALLERGENIC THAN BEEF

• RAPID ACTINGRAPID ACTING

• INTERMEDIATE ACTINGINTERMEDIATE ACTING

• LONG ACTINGLONG ACTING

• COMBINATIONSCOMBINATIONS

TYPE OF INSULIN ONSET OFACTION

(Hr)

PEAKEFFECT

(Hr)

DURATION OFACTION (Hr)

Rapid ActingInsulin lisproRegular Insulin

0.251/2 - 1

12-4

45-7

IntermediateActingIsophaneInsulin Zinc (Lente)

3-41-3

6-128-12

18-2818-28

Long ActingExtended Zincinsulin (Ultralente)

4-6 18-24 36

CombinationIsophane +Regular'Humalin 50/50Isophane +Regular'Humalin 70/30''Novalin 70/30'

1/2

1/2

3

4-8

22-24

24

Emergencies in DiabetesEmergencies in Diabetes

• HYPOGLYCEMIAHYPOGLYCEMIA• INSULIN SHOCKINSULIN SHOCK• SWEATINGSWEATING• ^ANXIETY^ANXIETY• BLURRED VISIONBLURRED VISION• WEAKNESSWEAKNESS• HEADACHEHEADACHE• DROWSINESSDROWSINESS

• HYPERGLYCEMIAHYPERGLYCEMIA• DIABETIC COMADIABETIC COMA• RED DRY SKINRED DRY SKIN• FRUITY ODORFRUITY ODOR• ABD. PAIN NAUSEA ABD. PAIN NAUSEA

VOMITINGVOMITING• RAPID DEEP RAPID DEEP

BREATHINGBREATHING

ORAL ANTI DIABETIC ORAL ANTI DIABETIC AGENTSAGENTS

• SULFONYLUREAS-SULFONYLUREAS-• Chlorpropamide / Glipizide / Chlorpropamide / Glipizide /

GlyburideGlyburide• BIGUANIDES-BIGUANIDES-• MetforminMetformin• ALPHA GLUCOSIDASE INHIBITOR-ALPHA GLUCOSIDASE INHIBITOR-• AcarboseAcarbose

DRUGS TO ^BLOOD SUGAR

• GLUCAGON - GLUCAGON -

0.5-1Mg IV/IM/SC prn every 20 mins0.5-1Mg IV/IM/SC prn every 20 mins• Contraindication: Contraindication:

pheochromocytoma/insulinomapheochromocytoma/insulinoma• DIAZOXIDE - 1 mg/kg every 8hrs (3-DIAZOXIDE - 1 mg/kg every 8hrs (3-

8mg/kg daily) 8mg/kg daily) • contraindication: CHF/HTNcontraindication: CHF/HTN• GLUCOSE- 10-20 gm oral or GLUCOSE- 10-20 gm oral or

50 cc 50% IV50 cc 50% IV

REPRODUCTIVEHORMONESREPRODUCTIVEHORMONES

• FSH - FSH - • OVUM AND SPERNATOGENSISOVUM AND SPERNATOGENSIS• LH (ICSH)- SEX HORMONES LH (ICSH)- SEX HORMONES

PRODUCTIONPRODUCTION• ANDROGENSANDROGENS• ESTROGENSESTROGENS• PROGESTOGENSPROGESTOGENS

FEMALE HORMONESFEMALE HORMONES

• GnRH-’Gonadorelin’ ‘Factrel’- GnRH-’Gonadorelin’ ‘Factrel’- LH/ICSH release - a diagnostic agent LH/ICSH release - a diagnostic agent for hypogonadismfor hypogonadism

• Histrelin - synthetic GnRH agonistHistrelin - synthetic GnRH agonist• Indication-10 mcg/kg/ scIndication-10 mcg/kg/ sc• Precocious puberty - decreases Precocious puberty - decreases

LH/FSH/estrogen/testosterone levelsLH/FSH/estrogen/testosterone levels• AE: vaginal dryness/breast AE: vaginal dryness/breast

edema/hot flashesedema/hot flashes

FEMALE HORMONESFEMALE HORMONES• CHORIONIC GnH: in decreased LH-CHORIONIC GnH: in decreased LH-• Undescended testesUndescended testes• ^Secondary male sex characteristics^Secondary male sex characteristics• Male and female infertilityMale and female infertility• AE:Edema/Depression/Gynecomastia/ AE:Edema/Depression/Gynecomastia/

Aggression/Arterial Aggression/Arterial thromboembolismthromboembolism

• 1000-4000 units IM thrice weekly1000-4000 units IM thrice weekly

FEMALE HORMONESFEMALE HORMONES

• MENOTROPINS: (HMG)- FSH and LH MENOTROPINS: (HMG)- FSH and LH activityactivity

• from urine of post menopausal from urine of post menopausal womenwomen

• Female infertilityFemale infertility• Male infertilityMale infertility• AE: wt gain/ edema/ oligurea / AE: wt gain/ edema/ oligurea /

gynecomastiagynecomastia• 75 units IM daily x 7 days75 units IM daily x 7 days

FEMALE HORMONESFEMALE HORMONES

• Estrogens: atrophic vaginitis/ Estrogens: atrophic vaginitis/ abnormal uterine bleeding/abnormal uterine bleeding/

• Post menopausal states/ Post menopausal states/ OsteoporosisOsteoporosis

• Metastatic breast cancerMetastatic breast cancer• AE:gastric/<libido/edema/AE:gastric/<libido/edema/• breast pain/ thrombophlebitisbreast pain/ thrombophlebitis

FEMALE HORMONESFEMALE HORMONES• Progesterone: endometrial hormone• complement estrogen effects on

uterus/ suppresses ovulation/relaxes uterine smooth muscle/

• Indications- dysmenorrhea/endometriosis/

• AE: wt gain/ edema/breast pain• Contraindication: breast cancer/

liver disease/thromboembolism

Oral ContraceptivesOral Contraceptives• Low dose E & P combination benefits:Low dose E & P combination benefits:• < CVS effects< CVS effects• ^ of MI in smokers and >35 years of age^ of MI in smokers and >35 years of age• <risk of stroke and thromboembolism<risk of stroke and thromboembolism• <ectopic pregnancies<ectopic pregnancies• <ovarain cysts/ ovarain cancer/ <ovarain cysts/ ovarain cancer/

endometrial cancerendometrial cancer• >risk of cervical cancer/liver cancer/>risk of cervical cancer/liver cancer/

breast cancerbreast cancer

Oral ContraceptivesOral Contraceptives• MonophasicMonophasic- fixed ratio x 21 days- fixed ratio x 21 days• Biphasic- different progestin levels- Biphasic- different progestin levels-

low for 7-10 days/high for next 11-14 low for 7-10 days/high for next 11-14 daysdays

• TriphasicTriphasic- simulates normal cycle-- simulates normal cycle-

constant low estrogen level/ constant low estrogen level/ progestin increased 3 times during progestin increased 3 times during 21 days21 days

• LongactingLongacting- progestin only - - progestin only -

Norplant / Depo-Provera/Norplant / Depo-Provera/

Oral ContraceptivesOral Contraceptives

• SELECTION of ‘Right’ ONE:SELECTION of ‘Right’ ONE:• ‘‘SAFe’(18-35)- SAFe’(18-35)-

Low E(30-35mcg)/Low P /NO Low E(30-35mcg)/Low P /NO SMOKINGSMOKING

• Smokers and >35-Smokers and >35-• ^CVA side effects^CVA side effects• Use other methodsUse other methods

Oral ContraceptivesOral Contraceptives

• If Cancer + If Cancer +

(Breast, Uterus, Cervix, Liver)(Breast, Uterus, Cervix, Liver)• CVA, CAD, Thrombosis +CVA, CAD, Thrombosis +• Oral contraception is Oral contraception is

contraindicatedcontraindicated• Use other methodsUse other methods

Oral ContraceptivesOral Contraceptives• Liver impaired, Smokers >35, Liver impaired, Smokers >35,

CVA/HTN/Migraine-CVA/HTN/Migraine-• Use progestin only minipill Use progestin only minipill

(< effective)(< effective)

PROBLEMS: PROBLEMS:

Acne, Oily skin, Wt. Gain Acne, Oily skin, Wt. Gain Breakthrough bleedingBreakthrough bleeding

Drugs for infertilityDrugs for infertility• CLOMIPHENE- CLOMIPHENE- • ESTROGEN COMPETITORESTROGEN COMPETITOR• ^FSH/LH SECRETION^FSH/LH SECRETION• ^CORPUS LUTEUM^CORPUS LUTEUM• AE:HEADACHE /NAUSEA/ AE:HEADACHE /NAUSEA/

VOMITING/DEPRESSION/VOMITING/DEPRESSION/• ^OVARIAN CYST /FIBROIDS^OVARIAN CYST /FIBROIDS• HEPATOTOXICHEPATOTOXIC

• UROFOLLITROPIN :UROFOLLITROPIN :^FSH ^FSH

Labor and DeliveryLabor and Delivery

• ““OXYTOCICS”-Induce stimulation OXYTOCICS”-Induce stimulation of uterine smooth muscle of uterine smooth muscle contractions and spontaneous contractions and spontaneous labor. ERGOT/OXYTOCINlabor. ERGOT/OXYTOCIN

• ““TOCOLYTICS”- TOCOLYTICS”-

Inhibit premature labor and Inhibit premature labor and suppress lactation. TERBUTALINE suppress lactation. TERBUTALINE / RITODRINE/ RITODRINE

OXYTOCICS and TOCOLYTICSOXYTOCICS and TOCOLYTICS• Oxytocin “Syntocinon”Oxytocin “Syntocinon”• Acts on pregnant Acts on pregnant

uterusuterus• Impedes uterine blood Impedes uterine blood

flowflow• Labor/PPH/ ^LactationLabor/PPH/ ^Lactation• 0.5-2mU/min0.5-2mU/min• IV 30-60 minsIV 30-60 mins• AE:Nausea/vomiting/AE:Nausea/vomiting/• tachycardiatachycardia

• Ritodrine/TerbutaliuneRitodrine/Terbutaliune• B2 adrenergic agonist B2 adrenergic agonist

-inhibits uterine -inhibits uterine contractioncontraction

• To prevent unwanted To prevent unwanted labor/premature labor labor/premature labor after 20 weeks after 20 weeks

• ^Heart rate/^BP^Heart rate/^BP• Trembling tremorsTrembling tremors• 50-100 mcg/min 50-100 mcg/min

IV(150-350mcg) then IV(150-350mcg) then oraloral

Male HormonesMale Hormones• TESTOSTERONE: TESTOSTERONE: • 25-50 mg IM thrice weekly25-50 mg IM thrice weekly• Androgen deficiency/Delayed male Androgen deficiency/Delayed male

pubertypuberty• Breast cancerBreast cancer• AnemiaAnemia• AE: abdominal pain/ headaches/jaundice/ AE: abdominal pain/ headaches/jaundice/

edema/breast swelling/ frequent erectionsedema/breast swelling/ frequent erections• Females: oily skin/ deep voice/ hirsuitism/ Females: oily skin/ deep voice/ hirsuitism/

male type baldness/ enlarged clitoris/male type baldness/ enlarged clitoris/

irregular mensesirregular menses

Enlarged ProstateEnlarged Prostate

• Benign: Hytrin is usedBenign: Hytrin is used• Finasteride- inhibits 5 alpha Finasteride- inhibits 5 alpha

reductase and prevents testosterone reductase and prevents testosterone conversion to dihydrotestosterone conversion to dihydrotestosterone which causes prostatic growthwhich causes prostatic growth

• AE: Gynecomastia, back pain, AE: Gynecomastia, back pain, diarrhea, <libido, impotency, diarrhea, <libido, impotency,

< ejaculation qty< ejaculation qty

Altering sexual Altering sexual behaviorbehavior

•HTN- HTN-

aldomet,reserpin, thiazidesaldomet,reserpin, thiazides•Antihistamines- BenadrylAntihistamines- Benadryl•Psychotropics- Psychotropics-

Chlorpromazine, valium, Chlorpromazine, valium, haloperidol, imipramine, haloperidol, imipramine, alcoholalcohol

Altering sexual Altering sexual behaviorbehavior

• Amylnitrite-^male orgasmAmylnitrite-^male orgasm• Viagra- ^Nitric oxide release Viagra- ^Nitric oxide release • ^cGM P <phophodiesterase in penis^cGM P <phophodiesterase in penis• AE: caution with cardiac patients on AE: caution with cardiac patients on

nitratesnitrates• Causes hypotension, headache, Causes hypotension, headache,

nasal congestion, flushing, flu nasal congestion, flushing, flu syndrome, angina, tachycardia, syndrome, angina, tachycardia, priapism , Peyronie’s diseasepriapism , Peyronie’s disease