ENDOCRINES ENDOCRINES • Thyroglobulin is a large Thyroglobulin is a large protein molecule synthesized by protein molecule synthesized by the thyroid gland: Tyrosine in the thyroid gland: Tyrosine in this molecule is iodinated and this molecule is iodinated and coupled by peroxidase enzyme coupled by peroxidase enzyme • Tetra-iodothyronine is T4 Tetra-iodothyronine is T4 • Tri-iodothyronine T3 is the Tri-iodothyronine T3 is the active molecule active molecule
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ENDOCRINES Thyroglobulin is a large protein molecule synthesized by the thyroid gland: Tyrosine in this molecule is iodinated and coupled by peroxidase.
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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
• 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
•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
•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
•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
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) =
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
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/
• 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
• 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
Male HormonesMale Hormones• TESTOSTERONE: TESTOSTERONE: • 25-50 mg IM thrice weekly25-50 mg IM thrice weekly• Androgen deficiency/Delayed male Androgen deficiency/Delayed male
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,
• 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