Endocrine 2

Question 1

Major roles of Hypothalamus master gland

Answer 1

Controlling the internal
environment (homeostasis)
• Regulates the balance of
• Water/salt → thirst
• Nutrients/glucose→ hunger

Question 2

Hypothalamic pituitary axes

Answer 2

• control endocrine system
• operate by negative feedback (short and long loops)
• type :
  • Hypothalamic-Pituitary-Thyroid axis (HPT)
  • Hypothalamic-Pituitary-Adrenal axis (HPA)
  • Hypothalamic-Pituitary-Gonadal axis (HPG)

Question 3

Pathways

Answer 3

1. • Nerve impulse from brain to hypothalamus
   • Hypothalamus secretes regulatory hormones to the anterior pituitary
   • Anterior pituitary releases hormones to target organs/tissues
2. • Nerve impulse from the brain to
   posterior pituitary
   • Posterior pituitary releases
   hormones to target organs/tissues

Question 4

Hypothalamic modulators of anterior pituitary

Answer 4

• Thyrotropin releasing hormone TRH
  Effects : increase release of thyroid stimulating hormone and release of prolactin
• opamine or prolactin inhibiting hormone
  Effects : decrease release of prolactin
• Growth hormone releasing hormone
  Effects : increase release of growth hormone

Question 5

Hypopituitarism

Answer 5

Undersecretion
- decreased tropic hormones (postpartum pituitary necrosis)
- Target organs functioning reduced or lost :
 Adrenal: increased cholesterol, fatigue
 Breasts: no lactation
 Gonads: atrophy, reproductive dysfunction
 Thyroid: muscle weakness, decreased energy
 Liver (GH): reduced energy

Oversecretion
- Acromegaly

Question 6

Prolactin effects

Answer 6

• Promotes breast development and synthesis of milk proteins
  • Levels low in absence of pregnancy due to dominant inhibitory effect
  of dopamine
  • Has been referred to a “parental hormone” because its injection into
  animals can produce parental behavioral patterns such as nest- building

Question 7

Prolactin regulations

Answer 7

Prolactin is under tonic inhibitory
control by the hypothalamus through
release of dopamine

Question 8

Increased prolactin during nursing

Answer 8

decrease release of GnRH from the hypothalamus
• causes decrease in release of LH and FSH
- provides a natural form of contraception

Question 9

Infertility hypothalamic origin

Answer 9

Treated with administration of GnRH (or a synthetic metabolically stable
analogue) given i.m. or nasal spray

Question 10

Infertility

Answer 10

• Hyperprolactinemia: High circulating levels of prolactin – (eg caused
by a small prolactin secreting tumor)
• Treated with bromocriptine – a synthetic orally effective dopamine
agonist

Question 11

Gonadotropic hormones

Answer 11

• Required for ovulation, spermatogenesis, biosynthesis of estrogens and androgens
• Used therapeutically to promote fertility
• Produced and secreted by gonadotrophs in anterior pituitary

Question 12

FSH Follicle Stimulating Hormone

Answer 12

Principle function: stimulate follicular development in females and
spermatogenesis in males
• Actions of FSH on follicle and oocyte require LH
• FSH acts on sertoli cells in testes to stimulate production of androgen binding protein

Question 13

LH Lutenizing Hormone

Answer 13

• Principle function : regulate gonadal steroid hormone production
• Acts on Leydig cells in testes to stimulate androgen production
• Acts on ovary with FSH to stimulate follicular development

Question 14

Human Chorionic Gonadotropin

Answer 14

Glycoprotein hormone produced only during pregnancy by the embryo soon after conception and later by the placenta
• Prevents disintegration of the corpus luteum of the ovary ( involved in progesterone secretion)

Question 15

Therapeutic Uses of Gonadotropic hormones

Answer 15

• Infertility: FSH, LH, and CG used in combination to promote follicular
development and spermatogenesis
• Diagnostic: GnRH used diagnostically to distinguish between delayed
puberty and hypogonadotrophy

Question 16

Clinical applications of agents affecting the endocrine system

Answer 16

Use of hormones (or synthetic analogues) for replacement therapy in stages of congenital or pathogenic hormone deficiency
• Use of competitive hormone antagonists or inhibitors of hormone synthesis
• Use of hormones to decrease secretion of other hormones by negative feedback inhibitory effect

Question 17

To reduce hormone level

Answer 17

• Use of agents interfering with hormone’s biosynthesis
• Use of competitive antagonists
• Reduce secretion of hormone in question by negative feedback inhibition

Question 18

Mechanism of action of steroid hormones

Answer 18

• binds to specific cytoplasmic receptor
• translocation to nucleus
• alteration in gene transcription

Question 19

Estrogen

Answer 19

Natural estrogens
• Estradiol
• Estrone
• Estriol

During the first part of the menstrual
cycle estrogens are produced in the
ovarian follicle by the theca and
granulosa cells

Synthetic estrogens
Steroidal
• Ethinyl estradiol (In oral contraceptives)
• Mestranol
• Quinestrol

Non-steroidal
• Diethylstilbesterol
• Chlorotrianisene
• Methallenestril

Clinical uses
• Primary hypogonadism (estrogen deficiency due to failure of
ovary, castration, premature menopause)
• Postmenopausal hormonal therapy

Question 20

Menopausal hormone therapy

Answer 20

Conjugated equine estrogen, isolated from pregnant mare’s urine, first manufactured 1942, Ayerst
• For symptoms– hot flushes, vaginal dryness, night sweats

Question 21

Selective estrogen receptor modulators SERM

Answer 21

Therapeutic effects
Agonistic :
• Prevention of osteoporosis in bone
• Induction of ovulation in infertility
• But – can result in endometrial hyperplasia (which can lead to cancer)
Antagonistic :
• Treatment of hormone dependent breast and uterine cancers
• Detrimental: osteoporosis

Question 22

Progestin

Answer 22

Progesterone
• Necessary for maintenance of the endometrium during pregnancy

Therapeutic applications
• Contraception – “Norplant”
• Hormone replacement therapy
• Delay premature labor

Diagnostic Uses
• Used to test for estrogen secretion in amennorhic patients

Question 23

Progesterone receptor antagonist

Answer 23

Mifepristone is use to induce first trimester abortion

Question 24

Oral contraceptives

Answer 24

• First half of 28 days cycle called “follicular” or “proliferative” phase
– Developing follicles produce increasing amounts of estrogen, stimulates endometrial lining

• Second half = “luteal” or “secretory” phase where progesterone secretion increases and proteins required for implantation of fertilized egg are synthesized

Question 25

Oral contraceptive moa

Answer 25

• Combination preparations : contain estrogen and progestin • Monophasic – constant dosage of both components during cycle (eg Alesse, Yasmin, Orthocyclin) • Biphasic or triphasic forms – dosage changed once or twice during cycle (Orthonovum, Ortho-Tri-Cyclin) • Progestin only preparations “minipill”: contains only a progestin

Question 26

Combination oral contraceptive

Answer 26

- Exogenous estrogen prevents conception by inhibiting release of LH and FSH • Estrogen component promotes endometrial growth ( increase risk of endometrial cancer) • Addition of progestin limits this proliferative effect on endometrial growth (progesterone is “antiproliferative” – promotes secretion than proliferation)

Question 27

Minipill

Answer 27

- involves exposure to continuous low doses of progestin • Ovulation is prevented 70-80% of the time • Considered > 95 % effective MOA :  inconsistently inhibit ovulation in ~50% of cycles (low dose)  rely on progestogenic effect of thickening cervical mucus SIDE EFFECTS : • breakthrough bleeding in 40% women • amenorrhoea • Weight gain

Question 28

Safety of oral contraceptive

Answer 28

• Decrease risk of endometrial cancer because progestin component inhibits endometrial proliferation • Risk of blood clot formation is increased except for women who smoke • Women over 35 recommended not to take oral contraceptives because of the risk of cardiovascular complications

Question 29

Postcoital contraceptive

Answer 29

• morning after pill • Administration of 2 doses of estrogen alone or in combination of progestins within 72 hours after coitus will induce menstruation 99% of the time

Question 30

Androgens

Answer 30

• dihydrotestosterone • Testosterone enters cell and converted to dihydrotestosterone via 5α-reductase • Dihydrotestosterone binds to the androgen receptor

Question 31

Negative feedback

Answer 31

testosterone is the hormone that controls androgen levels in the body by a negative feedback at the level of both the hypothalamus and anterior pituitary

Question 32

Antiandrogens

Answer 32

Steroid synthesis Inhibitors • Ketoconazole (antifungal) – inhibits adrenal and gonadal steroid synthesis but not ovarian aromatase Conversion of Steroid Precursors to Androgens • Finasteride – steroid like inhibitor of conversion of testosterone to dihydrotestosterone (5α-reductase) • Treatment of benign prostate hypertrophy. Genetic deficiency of this reductase makes males assume a female phenotype • hair loss treatment Receptor Inhibitors • Competitive antagonists compete with dihydrotestosterone and testosterone for binding to the cytoplasmic receptor • Flutamide – treat metastatic prostate cancer and benign prostatic hypertrophy • Spironolactone – inhibitor of aldosterone, competes with dihydrotestosterone for androgen receptors

Question 33

Reproductive pharmacology oral contraceptives pharmacokinetic

Answer 33

Ethinyl estradiol • Well absorbed orally, peak plasma levels reached in 1 hr • Undergoes considerable first pass metabolism • Effective plasma concentrations maintained by enterohepatic circl (low dose prep) Norethisterone (norethindrone) • Derived fr testosterone • Rapidly & completely absorbed fr gut • Extensive first pass metab

Question 34

Oral contraceptive preparation

Answer 34

• The 21-pill pack has 21 "active" pills (with hormones) to take for 3 weeks, followed by 1 week without pill • The 28-pill pack has 21 "active" pills (with hormones) to take for 3 weeks, followed by 1 week of reminder pills • Withdrawal bleed bet day 21- 28

Question 35

When to start oral contraceptives

Answer 35

Day 1 – 5 of menstrual cycle →provide effective contraception • If started at any other time in the menstrual cycle – effective contraception after 7 consecutive days use active pills • Taken the same time every day (12 hr window period)

Question 36

Oc be impaired by

Answer 36

1) missing more than one active pill in a packet 2) delay in starting the next packet of active pills ( extending the pill - free, inactive or placebo pill period beyond 7 days) 3) intestinal malabsorption of active pills due to vomiting or diarrhea

Question 37

Oc adverse effect

Answer 37

Mild • Nausea, mastalgia, oedema • Headache / worsen migraine • Amenorrhoea / breakthrough bleeding Moderate • Breakthrough bleeding • Weight gain, Acne, Hirsutism • Pigmentation

Question 38

Oc contraindication

Answer 38

• Pre-existing cardiovascular disease • Thromboembolic phenomena • thrombophlebitis • severe obesity • hypercholesterolaemia

Question 39

Oc warning signs and must return

Answer 39

• Abdominal pain (sharp) • Chest pain (severe) • Headache (severe) • Eye (blurred vision, brief loss of vision) • Sharp leg pain

Question 40

EHC emergency hormonal contraceptives indication and moa

Answer 40

• Reduced efficacy of other forms of contraception : • Torn, leaking • Missed pills • Late implant or injection • Detached contraceptive Moa • Either prevents or delays ovulation, prevents fertilisation or prevents implantation of fertilised egg

Question 41

Injectable progestin

Answer 41

- for compliance - 150 mg intramuscularly every three months) MOA: • completely inhibit follicular development and ovulation • thicken cervical mucus SIDE EFFECT • weight gain • menstrual cycle changes • Breakthrough bleeding

Question 42

Progestin implant

Answer 42

- implanted in the skin in upper arm by creating a small incision and insert capsules in fanlike shape - Norplant (levonorgesterel) Moa : • Prevent ovulation • Thicken cervical mucous • thinning the lining of the uterus

Question 43

Progestin intrauterine system

Answer 43

- Mirena TM Moa : • inconsistently inhibit ovulation in ~50% of cycles Side effects : • frequent light bleeding first three months after insertion • Three to six months, most women experience dramatically reduced bleeding • 20% of women will have amenorrhea after 12 months