The document discusses hormones of the hypothalamus, pituitary gland, and thyroid gland. It describes how hormones such as growth hormone-releasing hormone, somatostatin, gonadotropin-releasing hormone, and thyroid-stimulating hormone regulate the release of other hormones from these glands. It also summarizes the actions, therapeutic uses, and side effects of hormones including growth hormone, gonadotropins, antidiuretic hormone, oxytocin, and thyroid hormones.

1. Pituitary And Thyroid
Dr. Naim Kittana
Faculty of Medicine & Health Sciences
An-Najah National University 1

2. Hormones of the Hypothalamus & Pituitary gland
Hypothalamus (GHRH,
GnRH, CRH, TRH)
Pituitary
gland
Anterior
Growth
Hormone
Liver
FSH & LH
Ovary &
testis
TSH
Thyroid
ACTH
Adrenal
cortex
Prolactin
Breast
Posterior
ADH
Renal
tubules
Oxytocin
Uterus &
breast
2
PIH, GHIH
Direct action

3. Anterior Pituitary Hormones
3

4. 4

5. Hormones of the hypothalamus
5

6. 1. Agents Affecting Growth Hormone (Somatotropin)
– Growth hormone-releasing hormone (GHRH)
• Released from the hypothalamus
• Binds to specific membrane GHRH receptors on pituitary.
• GHRH rapidly elevates serum growth hormone (somatotropin)
levels with high specificity.
6

7. Growth-promoting and metabolic actions of GH
7

8. Growth hormone (GH)
• Hypersecretion causes
gigantism in children and
acromegaly in adults
• Hyposecretion in children
causes pituitary dwarfism.
8

9. 1. Agents Affecting Growth Hormone (Somatotropin)
– Somatotropin release-inhibiting hormone (SST, somatostatin)
• Example of SST analogue: Octreotide
• Inhibits the release of Somatotropin (GH) & TSH from the pituitary
• Inhibits the release of glucagon and insulin from the pancreas.
• Inhibits the secretion of gut peptides such as vasoactive intestinal
polypeptide (VIP) and gastrin
• It inhibits the growth and proliferation of many cell types.
9

10. 1. Agents Affecting Growth Hormone (Somatotropin)
• Octreotide is an SST analog administered by SC, IM, or IV injection.
• Octreotide is used to treat:
– Acromegaly
– Severe diarrhea associated with hypersecretory states such as VIP-
secreting tumors (VIPomas)
– Gastrinoma
– Glucagonoma
– TSH-secreting adenomas
– Variceal and upper GI bleeding (mediated by a splanchnic vasoconstrictive effect)
10

11. • GnRH Analogs
– GnRH Receptor Agonists
• Leuprolide
• Gonadorelin
• Goserelin
• Nafarelin
• Triptorelin
• Histrelin
11
2. Gonadotropin-releasing Hormone (GnRH) and Analogs

12. 2. Gonadotropin-releasing Hormone (GnRH) and Analogs
Pulsatile administration
– Short-term or pulsatile administration of GnRH agonists (every 1–4 h)
by computerized pump increases the synthesis and release of both LH
& FSH
– Treatment of certain types of infertility
12

13. Chronic administration
– 2–4 weeks of daily administration of GnRH inhibits the release of both
LH & FSH
– Caused by a reduction in the number of GnRH receptors on the
anterior pituitary.
– Leads to reduced production of gonadal steroids; Androgens &
Estrogens (chemical castration).
13
2. Gonadotropin-releasing Hormone (GnRH) and Analogs

14. Chronic administration
• Useful in the treatment of
– Precocciuos puberty
– Hormone-dependent cancers and hyperplasias such as prostate
cancer, breast cancer, endometriosis, and fibroids.
• Available as implantable formulation
14
2. Gonadotropin-releasing Hormone (GnRH) and Analogs

15. Adverse effects in Women:
– Hot flushes and sweating
– Diminished libido and depression
– Ovarian cysts
– Contraindicated in pregnancy and breast-feeding
15
2. Gonadotropin-releasing Hormone (GnRH) and Analogs

16. Adverse effects in Men:
– Hot flushes and edema
– Bone pain due to initial rise in testosterone levels
– Diminished libido
– Gynecomastia
16
2. Gonadotropin-releasing Hormone (GnRH) and Analogs

17. – Common example:
• Ganirelix
• Abarelix
• Cetrorelix
• GnRH antagonists competitively and reversibly bind to GnRH receptors in
the pituitary gland, blocking the release of LH and FSH from the pituitary.
17
GnRH Receptor Antagonists

18. • In men, the reduction in LH subsequently leads to rapid suppression
of testosterone release from the testes
• In women it leads to suppression of estrogen release from the ovaries.
• GnRH antagonists have an immediate onset of action, rapidly reducing sex
hormone levels without an initial surge
• This is unlike the GnRH agonists, which cause an initial surge in
testosterone or estrogen levels
18
GnRH Receptor Antagonists

19. • Prostate cancer
• Hormone-sensitive breast cancer
• Some benign disorders such as endometriosis and uterine fibroids
• Some cases of infertility: Prevents premature LH surge
19
Clinical Uses of GnRH Receptor Antagonists

20. 3. Prolactin-releasing factor (PRF) and prolactin-inhibiting
factor (PIF)
– Secretion of prolactin from the pituitary is controlled by both:
• Stimulation (mediated by PRF)
• Inhibition (mediated by PIF = dopamine)
20

21. Prolactin-releasing factor (PRF)
• Drugs that reduce CNS dopaminergic activity (antidopaminergics) cause an
increase in prolactin secretion:
₋ Antipsychotics
₋ Antidepressants
₋ Anti-anxiety
• Drugs that promote prolactin secretion can be used to treat lactation
failure.
21

22. Prolactin-inhibiting factor (PIF) (dopamine agonists)
• Inhibition of prolactin secretion can be produced by a number of dopamine
agonists:
– Bromocriptine acts as an agonist of dopamine D2-receptors and an
antagonist of D1-receptors.
– Cabergoline (DOSTINEX ®)
A potent D2 agonist with greater D2 selectivity.
It is more effective in reducing hyperprolactinemia than bromocriptine
Has a long half-life that permits twice-weekly dosing.
22

23. Prolactin-inhibiting factor (PIF) (dopamine agonists)
– Therapeutic uses of PIF:
• Inhibition of prolactin secretion in amenorrhea, galactorrhea, and
prolactin-secreting tumors
• The correction of female infertility secondary to hyperprolactinemia
• Treatment of Parkinson disease.
23

24. 24
Hormones of the anterior pituitary

25. Growth hormone
– Growth hormone agonists: (GH, somatotropin), methionyl-growth
hormone (somatrem)
– GH is released in a pulsatile manner, with the highest levels during sleep
– GH secretion decreases with increasing age
– Administered SC or IM
– Half-life: 25 min, but sufficient to induce IGF-1 release by the liver, which
is responsible for the GH-like actions
25

26. – Therapeutic uses of GH:
• Replacement therapy in children with GH deficiency before
epiphyseal closure
• Growth failure due to Prader-Willi syndrome
• To stimulate growth in patients with Turner syndrome
• Other approved uses include long-term replacement of GH
deficiency in adults, treatment of cachexia and AIDS wasting
26
Growth hormone

27. – Side effects of GH:
• Edema
• Arthralgias and myalgias
• Flue-like symptoms
• Increase the risk of Diabetes
• Should not be given to children with closed epiphysis
27
Growth hormone

28. Growth hormone antagonists
– Pegvisomant
• Pegvisomant is a GH receptor antagonist
• Blocks the action of endogenous GH
• Used specifically for the treatment of acromegaly
• Pegvisomant is administered SC
28

29. Gonadotropins (LH & FSH)
• Gonadotropins (Luteinizing hormone and follicle-stimulating hormone)
– Actions and pharmacologic properties:
• In women,
– LH increases estrogen production in the ovary and is required for
progesterone production by the corpus luteum after ovulation
– FSH is required for normal development and maturation of the
ovarian follicles
• In men,
– LH induces testosterone production by the interstitial (Leydig) cells
of the testis
– FSH acts on the testis to stimulate spermatogenesis and the
synthesis of androgen-binding protein
29

30. Regulation of the Ovarian Cycle
30

31. – FSH and LH of pituitary origin are not used pharmacologically.
– Menotropins (human menopausal gonadotropins, hMG) :
• Isolated from the urine of postmenopausal women
• Contain a mixture of LH and FSH
• Urofollitropin (Bravelle) is immunologically purified FSH from the
urine of pregnant women.
– Follitropin α/β are recombinant FSH products
31
Gonadotropins (LH & FSH)

32. – hCG:
• hCG is nearly identical in activity to LH
• Produced by the placenta and can be isolated and purified from the
urine of pregnant women
• The alpha subunit is made by recombinant DNA technology
(choriogonadotropin α)
– All of these hormones must be administered parenterally (SC or IM)
32
Gonadotropins (LH & FSH)

33. • Therapeutic uses of hCG:
– hCG can be used in both M &F to stimulate gonadal steroidogenesis in
cases of LH insufficiency
– hCG can be used to induce external sexual maturation and
spermatogenesis in men with secondary hypogonadism, but this may
require months of treatment
33
Gonadotropins (LH & FSH)
– In the absence of an anatomic block,
hCG can also promote the descent of
the testes in cryptorchidism

34. • Therapeutic uses of hMG:
– Menotropins (hMG) are used in concert with hCG to stimulate
ovulation in women with functioning ovaries:
 Injection of hMG or FSH products over a period of 5-12 days causes
ovarian follicular growth and maturation,
 then hCG is injected one day after the last dose of FSH to induce
ovulation.
34
Gonadotropins (LH & FSH)

35. • Adverse effects of Menotropins and hCG
– Ovarian enlargement in about 20% of treated women
– Ovarian life-threatening hyperstimulation syndrome in up to 1% of
patients:
– Ascites
– Hypovolemia and shock
– Acute respiratory distress
35
Gonadotropins (LH & FSH)

36. Hormones of the posterior pituitary
36

37. Anti-diuretic Hormone (ADH, Vasopressin)
– ADH is synthesized in the hypothalamus and stored in the posterior pituitary
– ADH is released in response to increasing plasma osmolarity or hypotension
– The actions of ADH are mediated by three types of specific receptors:
• V1a: located in vascular smooth muscle, myometrium, and kidney
• V1b: located in the CNS and adrenal medulla
• V2: located in renal tubules
37

38. Anti-diuretic Hormone (ADH, Vasopressin)
• In renal tubules, ADH causes the permeability of water to increase and also
increases the transport of urea in the inner medullary collecting duct, which
increases the urine-concentrating ability of the kidney
• ADH causes vasoconstriction at higher doses
• ADH stimulates the hepatic synthesis of coagulation factor VIII and
von Willebrand factor.
38

39. – ADH preparations
• Aqueous vasopressin (Pitressin),
a short-acting preparation
Acts on both V1 and V2 receptors,
is administered parenterally and lasts 2–6 hours
• Desmopressin acetate (DDAVP, Stimate)
longer lasting (10–20 h) preparation
administered intranasally, parenterally, or orally
Selective on V2 receptors
39
Anti-diuretic Hormone (ADH, Vasopressin)

40. – Therapeutic uses
• Desmopressin is the most effective treatment for severe central diabetes
insipidus
because its V2 activity is 3,000 times greater than its V1 activity;
but it is not effective in the nephrogenic form of the disease
• Desmopressin is useful in nocturnal enuresis by reducing nighttime urine
production
• Vasopressin is included in the advanced cardiac life support protocol as a
substitute for epinephrine in cardiac arrest with asystole
40
Anti-diuretic Hormone (ADH, Vasopressin)

41. Syndrome of inappropriate antidiuretic hormone secretion
(SIADH)
• Hyponatremia is the most frequent electrolyte disorder.
• Therapeutic modalities include nonspecific measures:
• –fluid restriction
• –hypertonic saline
• Vasopressin receptor antagonists, called Vaptans (like Tolvaptan), have been
introduced as specific and direct therapy of SIADH.
• The side effects are thirst, polydipsia and frequency of urination.
41

42. Oxytocin
– Oxytocin is synthesized in the hypothalamus and secreted by the
posterior pituitary.
– Actions and pharmacologic properties
• Elicits milk ejection from the breast.
• Stimulates contraction of uterine smooth muscle.
• The plasma t1/2 of oxytocin is 5–10 minutes.
– Therapeutic uses
• Is used for induction and maintenance of labor.
• Stimulates milk ejection from the breast.
• Postpartum uterine bleeding.
42

43. 43
The Thyroid Gland

44. Synthesis of thyroid hormones
• Thyroid hormones:
 Triiodothyronine (T3)
 Tetraiodothyronine (T4, thyroxine)
• Synthesis materials: iodine & tyrosine
44

45. Synthesis of thyroid hormones
• Steps:
1. Iodide (I-) is trapped by sodium-iodide
2. Iodide is oxidized by thyroidal peroxidase to iodine (I.)
3. Tyrosine in thyroglobulin is iodinated and forms MIT & DIT
4. Iodotyrosines condensation
MIT+DIT→T3; DIT+DIT→T4
45

46. Regulation of Thyroid Hormone
46

47. Physiological actions of thyroid hormones
• To normalize growth and development, body temperature, and energy
levels
• Eitiology of hypothyroidism:
 Hashimoto disease
 Simple goiter
 After surgery and ablation of thyroid after surgery
 Congenital
• Insufficiency (Hypothyroidism) causes:
 Cretinism (infant & child)
 Myxedema (adult)
47

48. • Full-blown hypothyroid syndrome In adults.
• Symptoms include:
 Low metabolic rate
 Feeling chilled
 Constipation
 Thick dry skin
 Puffy eyes
 Edema
 Lethargy
 Mental sluggishness (but not mental retardation)
Myxedema
48

49. Goiter
• An enlarged protruding thyroid gland
• Occurs if myxedema results from lack of Iodine
• The follicular cells produce colloid but cannot
iodinate it and make functional hormones.
• The pituitary gland secretes increasing amounts
of TSH in an attempt to stimulate the thyroid to
produce TH, but the only result is that the
follicles accumulate more and more unusable
colloid.
49

50. Cretinism
• Severe hypothyroidism in infants
• The child is mentally retarded and has a short, disproportionately sized
body and a thick tongue and neck
• Thyroid hormone replacement therapy can prevent cretinism if
diagnosed early enough
50

51. Physiological actions of thyroid hormones
• Excess secretion of thyroid hormone (Hyperthyroidism) most commonly
results from: Graves disease and toxic goiter
• Severe Hyperthyroidism: results in thyrotoxicosis (thyroid storm)
51

52. Graves’ disease
• The most common hyperthyroid disease
• It is an autoimmune condition
• Abnormal antibodies are directed against thyroid follicular cells.
• Rather than marking these cells for destruction as antibodies normally
do, these antibodies mimic TSH and continuously stimulate TH release.
52

53. Typical symptoms of Graves’ disease
• Elevated metabolic rate
• Sweating
• Rapid and irregular heartbeat
• Nervousness
• Weight loss despite adequate food
• Eyeballs may protrude (exophthalmos) if the
tissue behind the eyes becomes edematous
and fibrous
53

54. 54
• Some of T4 are converted to T3
in kidney and liver
• The actions of T3 on several
organ systems are shown
• Mechanism of actions of thyroid
hormones
T3, via its nuclear
receptor, induces new
proteins generation
which produce effects
BMR: basal metabolic rate

55. Thyroid drugs
55
• Representative drugs: levothyroxine (L-T4), liothyronine (T3)
Clinical use:
1. Hypothyroidism: cretinism & myxedema;
2. simple goiter
3. Others
Adverse reactions:
Overdose leads to thyrotoxicosis and angina or MI (usually in ageds)

56. Anti-thyroid drugs
56
Class Representative
Thioamides Propylthiouracil (PTU)
Methimazole
Iodides KI, NaI
Radioactive iodine 131I
β-adrenoceptor blockers Propranolol

57. Thioamides
57
Mechanism of action: All thioamides inhibit
 Peroxidase-catalyzing reactions
 Iodine organification
 Iodotyrosines condensation
 Propylthiouracil also inhibit T4 conversion into T3
Pharmacological action: They inhibit thyroid hormone synthesis

58. Thioamides
58
• Thioamaides have no effects on thyroglobulin already stored in the gland,
• As a result the clinical effects appears slowly until thyroglobulin stores are
depleted.
• Methemazole is preferred over PTU because it has a longer t1/2 (given once
daily)
• PTU is recommended during the first trimester of pregnancy, due to a
greater risk of teratogenecity associated with methimazole.

59. Clinical use of Thioamides
• Mild hyperthyroidism
• For those surgery & 131I are not permitted
• Operation preparation
• Thyroid crisis (comprehensive therapy).
59

60. Adverse effects of Thioamides
• Long-term use leads to thyroid hyperplasia
• Pruritic maculopapular rash is the most common adverse reaction
• Agranulocytosis
60

61. Iodides (NaI, KI)
• Pharmacological action (Wolff-Chaikoff effect): Inhibition of T3 & T4
release and synthesis.
• This effect lasts only for few weeks
• Decrease of size & vascularity of the hyperplastic gland
61

62. Iodides (NaI, KI)
Clinical use
• Treatment of Thyroid Storm
• Prior to surgery (Decrease of size & vascularity of the gland)
62
Adverse reactions
• Acneiform rash
• Swollen salivary glands
• Mucous membrane ulcerations

63. Radioactive iodine (131I)
• 131I is the only isotope for treatment of thyrotoxicosis.
• Its therapeutic effect depends on emission of β rays
• It has an effective half-life of 5 days & a penetration range of 0.4-2 mm.
• Woman in pregnancy or lactation is forbidden!
63

64. β-adrenoceptor blockers
• βblockers are effective in treatment of thyrotoxicosis.
• Propranolol is the most widely studied and used.
64

65. Anti-thyroid drugs
peroxidase
Perchlorates
Thiocynates.
65