1

PITUITARY & PITUITARY & THYROID THYROID

HORMONESHORMONES

2

3

Neuroendocrine system is mainly Neuroendocrine system is mainly controlled by pituitary and controlled by pituitary and hypothalamus, which coordinates hypothalamus, which coordinates many of the body functions by many of the body functions by transmitting the messages to the transmitting the messages to the individual cells and tissues.individual cells and tissues.

4

1 1 Thyrotropin-realising hormoneThyrotropin-realising hormone – –

is to control the release of TSH from is to control the release of TSH from the the

adenohypophysis.adenohypophysis.

2 2 Gonadotropin-releasing hormoneGonadotropin-releasing hormone ––

to control gonadotropin secretion to control gonadotropin secretion

3 3 Corticotropin releasing hormoneCorticotropin releasing hormone – –

to control ACTH secretion to control ACTH secretion

4 4 Growth hormone releasing Growth hormone releasing hormonehormone -major role is to control GH -major role is to control GH releaserelease

5

ANTERIOR Pituitary Gland ANTERIOR Pituitary Gland Six hormones Six hormones TSH- TSH- Thyroid stimulating hormoneThyroid stimulating hormone ACTH-ACTH-Adreno corticotrophin Adreno corticotrophin

hormonehormone LH - LH - Luteinizing hormoneLuteinizing hormone FSH- FSH- follicle stimulating hormonefollicle stimulating hormone

PROLACTIN PROLACTIN GH- GH- growth hormonegrowth hormone

6

POSTERIOR PITUITARY POSTERIOR PITUITARY HORMONESHORMONES – Oxytocin, – Oxytocin, vasopressinvasopressin..

Hormones secreted by the Hormones secreted by the hypothalamus and pituitary are all hypothalamus and pituitary are all peptides peptides

Hormones of the anterior and Hormones of the anterior and posterior pituitary are administered posterior pituitary are administered either IM, SC or intranasally but not either IM, SC or intranasally but not orally orally

7

Growth Growth hormone(somatotropin, hormone(somatotropin,

somatrem)somatrem) Released by the ant. Pituitary following Released by the ant. Pituitary following stimulation by GHRH of the hypothalamusstimulation by GHRH of the hypothalamus

GH is released in a pulsatile manner, with GH is released in a pulsatile manner, with the highest levels occurring during sleepthe highest levels occurring during sleep

It is inhibited by the hormone somatostatin It is inhibited by the hormone somatostatin It mediates it action directly at its target It mediates it action directly at its target

tissues, as well as others through tissues, as well as others through somatomedins (IGF-I, IGF-II)somatomedins (IGF-I, IGF-II)

pharmacokineticspharmacokinetics

Plasma half life: 20-25 minutes Plasma half life: 20-25 minutes Clearance: hepatic Clearance: hepatic Administration: Mostly I.M Administration: Mostly I.M

8

THERAPEUTIC USESTHERAPEUTIC USES

Somatotropin is used to treat growth Somatotropin is used to treat growth deficiency in children (pituitary deficiency in children (pituitary dwarfism), osteoporosisdwarfism), osteoporosis

Somatotropin and somatrem Somatotropin and somatrem should not be used in individuals should not be used in individuals with closed epiphysis or an with closed epiphysis or an enlarging intracranial mass.enlarging intracranial mass.

9

10

SomatostatinSomatostatin -Growth -Growth hormone-inhibiting hormonehormone-inhibiting hormone

It suppresses GH and TSH It suppresses GH and TSH releaserelease

half-life-- 1-3 minutes half-life-- 1-3 minutes Has limited clinical useHas limited clinical use OcreotideOcreotide the synthetic analog of the synthetic analog of

somatostatin has a longer half-somatostatin has a longer half-life than the natural compound.life than the natural compound.

Therapeutic uses of Therapeutic uses of OcreotideOcreotide

Treatment of Treatment of acromegalyacromegaly Treatment of Treatment of secretory diarrhea secretory diarrhea

associated with tumors producing associated with tumors producing vasoactive intestinal peptidevasoactive intestinal peptide

Treatment of Treatment of acute esophageal acute esophageal variceal bleedingvariceal bleeding

Carcinoid syndromeCarcinoid syndrome Side effectsSide effects: flatulence, nausea, : flatulence, nausea,

steatorrheasteatorrhea and and gall stone formationgall stone formation

11

12

pegvisomantpegvisomant

Treatment of acromegaly that is Treatment of acromegaly that is refractory to other modes of refractory to other modes of surgical, radiologic or surgical, radiologic or pharmacologic interventionpharmacologic intervention

13

Adrenocorticotropic Adrenocorticotropic hormone(corticotropin)hormone(corticotropin)

CRH is responsible for the synthesis and CRH is responsible for the synthesis and release of ACTH causing the synthesis of release of ACTH causing the synthesis of adrenocorticosteroids and adrenal androgensadrenocorticosteroids and adrenal androgens

CRH is used to diagnostically differentiate CRH is used to diagnostically differentiate between cushing’s disease and ectopic ACTH between cushing’s disease and ectopic ACTH –producing cells–producing cells

ACTH is released from the pituitary in pulses ACTH is released from the pituitary in pulses with the highest being around 6am , and with the highest being around 6am , and lowest in the eveninglowest in the evening

Synthetic form of ACTH--Synthetic form of ACTH--cosyntropincosyntropin

15

AdrenocorticotropAdrenocorticotropinin, , ACTHACTH

SYNTHETIC - COSYNTROPINSYNTHETIC - COSYNTROPIN Clinical Use:Clinical Use: To differentiate between To differentiate between

primary(↑ACTH) and secondary adrenal primary(↑ACTH) and secondary adrenal insufficiency(insufficiency(↓ACTH)↓ACTH)

following cosyntropinfollowing cosyntropin:: In primary adrenal insufficiencyIn primary adrenal insufficiency: no : no

change in cortisol levels (i.e., still change in cortisol levels (i.e., still reduced)reduced)

In secondary adrenal insufficiencyIn secondary adrenal insufficiency: : ↑cortisol levels↑cortisol levels

Therefore cosyntropin is used for Therefore cosyntropin is used for diagnosis of adrenal insufficiency as well diagnosis of adrenal insufficiency as well as treatment of infantile spasmas treatment of infantile spasm

Gonadotropin releasing Gonadotropin releasing hormones (GnRH) hormones (GnRH)

Also called GonadorelinsAlso called Gonadorelins Pulsatile secretion is important for Pulsatile secretion is important for

the release of gonadotropins (FSH, the release of gonadotropins (FSH, LH) from the pituitary.LH) from the pituitary.

Continuous administration inhibits Continuous administration inhibits gonadotropin release.gonadotropin release.

16

Synthetic forms of Synthetic forms of gonadorelinsgonadorelins

Leuprolide Leuprolide Nafarelin Nafarelin Buserelin Buserelin Goserelin Goserelin Histrelin Histrelin

17

18

ROUTE : I V, I M , S C , NASALROUTE : I V, I M , S C , NASAL Pulsatile IV administration Pulsatile IV administration FSH & LH secretion stimulation FSH & LH secretion stimulation

Continuous GnRH administration Continuous GnRH administration Inhibition of Gonadotropin release Inhibition of Gonadotropin release

19

Therapeutic Therapeutic Applications: GnRH Applications: GnRH

StimulationStimulation: pulsatile admin.: pulsatile admin. To treat Infertility and To treat Infertility and

hypogonadism in males and femaleshypogonadism in males and females

Inhibition: Inhibition: Continuous admin.Continuous admin. Prostate cancer, Prostate cancer, Uterine fibroids, EndometriosisUterine fibroids, Endometriosis Precocious puberty Precocious puberty

20

  adverse effects: GnRH adverse effects: GnRH

Dermatitis, hypersensitivity and Dermatitis, hypersensitivity and headache.headache.

In womenIn women: hot flushes, sweating, : hot flushes, sweating, diminished libido, depression and diminished libido, depression and ovarian cystovarian cyst

In menIn men: bone pain, edema, : bone pain, edema, gynecomastia and diminished libidogynecomastia and diminished libido

Contraindicated in pregnancy and Contraindicated in pregnancy and breastfeeding.breastfeeding.

21

GonadotropinsGonadotropins

hMG - - Menotropins hMG - - Menotropins FSH -- Urofollitropin FSH -- Urofollitropin hCG – LH agonisthCG – LH agonist LHLH

Therapeutic uses of Therapeutic uses of gonadotropinsgonadotropins

Infertility in men and womenInfertility in men and women

22

23

  Toxicity: Gonadotropins Toxicity: Gonadotropins

Hyperstimulation syndrome Hyperstimulation syndrome Ovarian Hyper Stimulation syndrome (OHSS)Ovarian Hyper Stimulation syndrome (OHSS) hMG -induced ovarian enlargement hMG -induced ovarian enlargement Hemoperitoneum (secondary to ruptured Hemoperitoneum (secondary to ruptured

ovarian cyst) ovarian cyst) Arterial thromboembolism Arterial thromboembolism Multiple birthsMultiple births

In men: gynecomastia In men: gynecomastia

24

prolactinprolactin

Similar in structure to GHSimilar in structure to GH Secreted by the ant. Pituitary whose Secreted by the ant. Pituitary whose

secretion is inhibited by dopamine secretion is inhibited by dopamine and stimulated by TRHand stimulated by TRH

FUNCTIONFUNCTION: to stimulate and : to stimulate and maintain lactationmaintain lactation

Decreases sexual drive and Decreases sexual drive and reproductive functionreproductive function

25

26

Prolactin Prolactin

Abnormal prolactin levels: Abnormal prolactin levels: DeficiencyDeficiency: hypoProlactinemia--: hypoProlactinemia--

Manifestations: Manifestations:   lactation failure lactation failure

Excess: Excess: hyperProlactinemia hyperProlactinemia Galactorrhea Galactorrhea Hypogonadism Hypogonadism Amenorrhea Amenorrhea

27

Bromocriptine and Bromocriptine and cabergoline -Dopamine cabergoline -Dopamine

AgonistsAgonistsActions Actions Dopamine-like action Dopamine-like action Used to treat hyperprolactinemic Used to treat hyperprolactinemic

statesstates as well as microadenomas and as well as microadenomas and

macroprolactinomasmacroprolactinomas

28

Side effectsSide effectsGI side effects: GI side effects: constipation, dyspepsia, symptoms constipation, dyspepsia, symptoms

of reflux esophagitis of reflux esophagitis peptic ulceration with bleeding peptic ulceration with bleeding Psychiatric problemsPsychiatric problems

CVS:CVS: Common: postural/orthostatic Common: postural/orthostatic

hypotension hypotension ArrhythmiasArrhythmias

Posterior pituitary Posterior pituitary hormoneshormones

Release of these hormones are not Release of these hormones are not regulated by the releasing hormones regulated by the releasing hormones of the hypothalamusof the hypothalamus

Are instead synthesized in the Are instead synthesized in the hypothalamus and stored in the post. hypothalamus and stored in the post. Pituitary till when needed in Pituitary till when needed in response to signals such asresponse to signals such as

High urine osmolality or parturition.High urine osmolality or parturition.

29

30

Posterior Pituitary Posterior Pituitary HormoneHormone

OxytocinOxytocin :: Uses : stimulate uterine contraction to Uses : stimulate uterine contraction to

induce laborinduce labor Milk ejectionMilk ejection

SESE: HTN crisis,: HTN crisis, Uterine ruptureUterine rupture Fetal deathFetal deathCI: premature delivery,CI: premature delivery, Abnormal fetal presentation, fetal distressAbnormal fetal presentation, fetal distress

31

Vasopressin Vasopressin

ActionsActions : has both : has both antidiureticantidiuretic and well as and well as vasopressor effectsvasopressor effects

V 1 recep V 1 recep – found in the liver and vascular smooth muscle – found in the liver and vascular smooth muscle (vasoconstriction)(vasoconstriction)

V 2 recep V 2 recep – renal system, water reabsop.– renal system, water reabsop.

SE: SE: Water intoxication, hyponatremia, headache, tremor. Water intoxication, hyponatremia, headache, tremor. Care : CAD, asthma, epilepsy.Care : CAD, asthma, epilepsy.

Uses: Uses: Diabetes insipidusDiabetes insipidus Nocturnal enuresisNocturnal enuresis To control bleeding due to esophageal varices and colonic To control bleeding due to esophageal varices and colonic

diverticulardiverticular

desmopressindesmopressin

Synthetic form of vasopressinSynthetic form of vasopressin Has minimal to no activity on V1 Has minimal to no activity on V1

receptor resulting in minimal to no receptor resulting in minimal to no pressor effectpressor effect

It is now preferred for diabetes It is now preferred for diabetes insipidus and nocturnal enuresisinsipidus and nocturnal enuresis

Treatment of Von-Willibrand DiseaseTreatment of Von-Willibrand Disease Longer acting than vasopressinLonger acting than vasopressin Administered intranasallyAdministered intranasally

32

Thyroid hormonesThyroid hormones

Secreted by the thyroid gland Secreted by the thyroid gland Facilitates normal growth and Facilitates normal growth and

maturation in tissues that needs it for maturation in tissues that needs it for their normal functiontheir normal function

Secretes Two major thyroid Secretes Two major thyroid hormones: hormones: T3 and TT3 and T₄ but can also secrete ₄ but can also secrete calcitonincalcitonin

Not essential for life, but under and over Not essential for life, but under and over secretion could result in disease statesecretion could result in disease state

33

34

Symptoms of Symptoms of hypothyroidismhypothyroidism

BradycardiaBradycardia Poor resistance to coldPoor resistance to cold Mental and physical slowingMental and physical slowing In children can result in dwarfism In children can result in dwarfism

and mental retardationand mental retardation Menstrual irregularitiesMenstrual irregularities Weigh gain despite decreased intakeWeigh gain despite decreased intake Diagnosed by an ↑TSH & Diagnosed by an ↑TSH & ↓T3, T4↓T3, T4

35

Symptoms of Symptoms of hyperthyroidismhyperthyroidism

TachycardiaTachycardia ArrhythmiasArrhythmias Body wasting despite adequate intakeBody wasting despite adequate intake NervousnessNervousness TremorsTremors Intolerance to heatIntolerance to heat Exolphthalmus Exolphthalmus Diagnosed by a Diagnosed by a ↓TSH & ↓TSH & ↑ T3, T4↑ T3, T4

36

pharmacokineticspharmacokinetics T3 & T4 given orallyT3 & T4 given orally IV-myxedemaIV-myxedema T3 – the most active formT3 – the most active form Food, calcium preparations and Food, calcium preparations and

aluminum antacids can decrease aluminum antacids can decrease absorption of T4 but not T3absorption of T4 but not T3

Are metabolized via through microsomal Are metabolized via through microsomal P450 system.P450 system.

Therefore inducers of P450 accelerates Therefore inducers of P450 accelerates the metabolism of thyroid hormones.the metabolism of thyroid hormones.

37

Treatment of Treatment of hypothyroidismhypothyroidism

LEVOTHYROXINELEVOTHYROXINE, , LIOTHYRONINELIOTHYRONINE

Given once dailyGiven once daily Toxicity manifests as: symptoms of Toxicity manifests as: symptoms of

hyperthyroidism.hyperthyroidism.

38

Treatment of Treatment of hyperthyroidism hyperthyroidism (thyrotoxicosis)(thyrotoxicosis)

Goal Goal : : Removing part or all of the thyroid Removing part or all of the thyroid

glandgland Inhibiting synthesis of hormonesInhibiting synthesis of hormones Blocking release of hormones from Blocking release of hormones from

the folliclesthe follicles

39

surgerysurgery

Removal of part or all of the Removal of part or all of the thyroidthyroid: done surgically or by : done surgically or by destruction of the gland by destruction of the gland by radioactive iodineradioactive iodine

40

41

Antithyroid Drugs Antithyroid Drugs

Thioamides Thioamides Iodides Iodides Radioactive iodineRadioactive iodine Anion inhibitorAnion inhibitor

42

Thioamides Thioamides pharmacokineticspharmacokinetics

PropylthiouracilPropylthiouracil MethimazoleMethimazole CarbimazoleCarbimazole

Both Crosses placenta but PTU is Both Crosses placenta but PTU is safer in pregnancy safer in pregnancy

Inhibition of thyroid hormone Inhibition of thyroid hormone synthesissynthesis: using thioamides such as : using thioamides such as propylthiouracilpropylthiouracil ( (PTU)PTU)and and methimazolemethimazole

PTU & methimazole PTU & methimazole inhibits the inhibits the oxidation(peroxidase), iodination oxidation(peroxidase), iodination and coupling (condensation)step and coupling (condensation)step of tyrosine synthesisof tyrosine synthesis

PTU & propanolol PTU & propanolol can also block can also block deiodinase deiodinase in the conversion of in the conversion of T4 to T 3T4 to T 3

43

SIDE EFFECTS OF SIDE EFFECTS OF THIOAMIDESTHIOAMIDES

Agranulocytosis: Agranulocytosis: ↓neutrophil ↓neutrophil count(<500)count(<500)

RashRash edemaedema

44

Iodide Iodide Used for treatment hyperthyroidism Used for treatment hyperthyroidism MOAMOA: blocks the iodination of tyrosine : blocks the iodination of tyrosine

as well as the release of the hormones as well as the release of the hormones into the bloodinto the blood

Used prior to surgery to decrease the Used prior to surgery to decrease the vascularity of the glandvascularity of the gland

Not useful for long term therapy because Not useful for long term therapy because thyroid gland ceases to respond after a thyroid gland ceases to respond after a few weeksfew weeks

SE: SE: sore mouth and throat, rashes, sore mouth and throat, rashes, metallic taste in mouthmetallic taste in mouth 45

46

Anion InhibitorsAnion Inhibitors Competitive inhibition:Competitive inhibition:

PerchloratePerchlorate PertechnetatePertechnetate ThiocyanateThiocyanate

Inhibits iodide uptake by thyroidInhibits iodide uptake by thyroid

Thyroid stormThyroid storm

A rare but severe complication of A rare but severe complication of untreated hyperthyroidism in which the untreated hyperthyroidism in which the thyroid gland secretes excess thyroid thyroid gland secretes excess thyroid hormones resulting widespread hormones resulting widespread sympathetic symptomssympathetic symptoms

Treatment: Treatment: ββ-blockers such as -blockers such as propanololpropanolol

Calcium channel blockers, Calcium channel blockers, diltiazemdiltiazem in in pts suffering from severe heart failure pts suffering from severe heart failure and asthmaand asthma

47