Hypothalamic and Pituitary Hormones Flashcards Preview

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Flashcards in Hypothalamic and Pituitary Hormones Deck (98):
1

What is a negative regulator of GH?

Somatostatin

2

What is a negative regulator of prolactin?

Dopamine

3

The effects of GH are mediated through

IGF-1

4

Physiological Actions of GH in childhood

Promotes linear growth
Growth of long bones, cartilage, muscle, organ systems

5

Physiological Actions of GH in adulthood

Increases protein synthesis and bone density
Promotes lipolysis, inhibits lipogenesis
Promotes gluconeogenesis and glucose release
Opposes insulin-induced glucose uptake in adipose tissue, reduces insulin sensitivity

6

Features of GH deficiency in children

short stature
Adiposity
hypoglycemia

7

Features of GH deficiency in adults

increased generalized adiposity
Decreases skeletal muscle mass
decreased bone density
Cardiac muscle atrophy
Atherogenic blood lipid profile
Fatigue, weakness, depression, malaise

8

synthetic GHRH

Sermorelin

9

Sermorelin (synthetic GHRH) indication

used if defective GHRH release but normally functioning anterior pituitary somatotrophs

10

Recombinant human GH

Somatropin
Somatrem

11

Recombinant IGF-1

Mecasermin

12

Mecasermin (recombinant IGF-1) indication

Used in children where IGF-1 deficiency is due to mutations of GH receptor: Laron dwarfism or Ab against GH

13

Somatropin formulation

191-amino acid peptide, identical to native hGH

14

Somatrem

192-amino acid peptide consistign of 191aa of GH plus extra methionine residue at N-terminus (for stability, less allergic response)

15

Recombinant hGH (somatropin, somatrem) MOA

replaces GH

16

Recombinant hGH (somatropin, somatrem) Indications

Documented growth failure in pediatric pts with:
GH deficiency
Chronic renal failure
Prader-Willi syndrome
Turner syndrome

SGA w/ failure to catch up by 2
Idiopathic short stature, non GH-deficient (>2.25 S.D. below mean height)

GH deficiency in adults
Wasting in AIDS pts
Short bowel syndrome

17

Recombinant hGH (somatropin, somatrem) efficacy in children

Increases linear growth
Weight gain
Increases muscle mass, organ size, RBCs

18

Recombinant hGH (somatropin, somatrem) efficacy in adults

Increases bone mineral density
Decreased central adiposity
Increases muscle mass
Improves lipid profile
Improves cardiac function
Improves sense of well being

19

Recombinant hGH (somatropin, somatrem) side effects

Leukemia
Rapid growth of melanocytic lesions
Hypothyroidism (GH counteracts TSH)
Insulin resistance
Arthralgia
Increase in cytochrome p450 activity

20

Recombinant hGH (somatropin, somatrem) contraindications

Ped pts with closed epiphyses
Intracranial lesion
Active malignancy
Proliferative diabetic retinopathy
Cautin in diabetes

21

What is the effect of glucocorticoids on somatropin

Inhibit growth-promoting effect

22

What is the most common cause of growth hormone excess

Benign anterior pituitary tumor

23

Growth hormone excess in children

Gigantism
Occurs before the closure of epiphyses because excess IGF1 causes excessive longitudinal bone growth

24

Growth hormone excess in adults

Acromegaly
Occurs after epiphyses close, IGF-1 promotes growth of deep organs and cartilaginous tissue

25

Characteristics of acromegaly

thickening of bone (face, hands)
Large facial structure
Macroglossia
Hepatomegaly

26

Standard treatment for larger pituitary adenoma

Transsphenoidal surgery to remove the tumor

27

Medical options for smaller adenomas

Somatostatin analogues
GH receptor antagonist
Dopamine receptor agonist

28

Somatostatin analogues

Octreotide
Lanreotide (Europe)

29

GH receptor antagonist

Pegvisomant

30

Dopamine receptor agonist

Bromocriptine

31

Octreotide

Synthetic long-lasting peptide analogue of somatostatin

32

Octreotide MOA

Inhibits GH secretion

33

Octreotide indication

Control pituitary adenoma growth in acromegalic patients
Carcinoid crisis (flushing, diarrhea)
Secretory diarrhea from VIPoma
To control acute GI bleeding

34

Octreotide Side Effects

Nausea, vomiting, abdominal cramps, GI discomfort
Cardiac effects
Hypoglycemia
Gallstones

35

Octreotide Therapeutic Considerations

Decreases cyclosporin levels
Increases the availability of bromocriptine

36

GH Receptor Antagonist

Pegvisomant

37

Pegvisomant structure

Recombinat protein of 191 aa with mutliple polyethylene glycol (PEG) residues -prolongs half life

38

Pegvisomant MOA

Normally GH binds 2 receptors, dimerizes > signal transduction. Pegvisomant does not bind to the 2nd receptor, blocks signal transfuction = competitive antagonist of GH
Decreases serum IGF-1

39

Pegvisomant Indications

Acromegaly that is refractory to other treatment

40

Pegvisomant side effects

Increased pituitary adenoma size
Elevated serum aminotransferase levels

41

Pegvisomant Therapeutic Considerations

Should have yearly MRI to exclude enlarging adenoma
Liver function tests periodically

42

What do the gonadotroph cells in the pituitary secrete in response to pulsatile GnRH?

LH and FSH

43

What is the function of FSH in women?

Ovarian follicle development
FSH stimulates conversion of androgens to estrogens in the granulosa cells

44

What is the function of LH in women?

Stimulates androgen production in the ovary (theca cells)

45

What is the function of FSH in men?

Regulates spermatogenesis
Produces androgen binding protein

46

What is the function of LH in men?

Stimulates production of testosterone by the Leydig cells

47

Gonadotropins

Human menopausal gonadotropins, menotropins
Human chorionic gonadotropin
Urofollitropin
Follitropin

48

Gonadotropin Releasing Hormone analogue (short half-life)

Gonadorelin
(stimulatory-pulsatile form)

49

Gonadotropin Releasing Hormone analogue (long half-life)

Goserelin, Histrelin, Leuprolide, Nafarelin, Triptorelin
(inhibitory-continuous form)

50

GnRH receptor antagonists

Ganirelix, Cetrorelix, Abarelix

51

Menotropins

Obtained from the urine of menopausal women
Contain FSH and LH

52

hCG

placental hormone and LH agonist

53

Urofollitropin

Purified FSH isolated from urine of postmenopausal women

54

Follitropin

Recombinant form of human FSH

55

Gonadotropin MOA

Replaces FSH and LH

56

Gonadotropin indications

Ovulation induction in women with anovulation (hypogonadotropic hypogonadism, PCOS, obesity)
Controlled ovarian hyperstimulation in IVF
Infertility in male hypogonadotropic hypogonadism

57

Gonadotropin Side Effects

Ovarian hyperstimulation syndrome
Increase in multiple pregnancies
Increased risk of gynecomastia
Ovarian cancer
Ovarian cysts and hypertrophy

58

Gonadotropin Contraindications

Any endocrine disorder other than anovulation
Primary gonadal failure
Pituitary tumor or sex-hormone dependent tumors
Ovarian cyst/enlargement
Pregnancy

59

Gonadorelin (synthetic GnRH, short acting) MOA

"Pulsatile GnRH secretion"
Stimulates gonadotroph cells to produce and release LH and FSH

60

Gonadorelin Indication

Mostly for diagnosis of hypogonadism
Stimulate ovulation
Infertility in men with hypothalamic hypogonadotropic hypogonadism

61

Gonadorelin Side Effects

Anaphylaxis
Lightheadedness, flushing
Hypersensitivity dermatitis

62

GnRH Agonist, Long acting

Goserelin, Histrelin, Leuprolide, Nadarelin, Triptorelin

63

GnRH Agonist, Long acting MOA

Sustained, nonpulsatile administration of GnRH inhibits the release of FSH and LH, desensitizes GnRH receptors
1st transient increase in gonadal hormone levels (flare), then long lasting suppression of gonadotropins and gonadal hormones

64

GnRH Agonist, Long acting, indication

Keep LH low in ovarian hyperstimulation for multiple mature oocytes for assisted repro tech (IVF)--> leuprolide, nafarelin

Endometriosis and uterine fibroids (leuprolide, nafarelin, goserelin)

Adjunct in prostate cancer (leupro, goserelin, histrelin, triptorelin)

Central precocious puberty (leupro, nafarelin)

Advancer breast and ovarian cancer, amenorrhea and infertility in women with PCOS

65

GnRH Agonist, Long acting, side effects

hot flashes, sweats, headache (lack of estrogen, menopause)
osteoporosis
urogenital atrophy

66

GnRH Agonist, Long acting, contraindications

Pregnancy
Breast feeding

67

GnRH receptor antagonists

Ganirelix, Cetrorelix, Abarelix

68

GnRH receptor antagonists MOA

Competitive antagonists of GnRH receptors
Inhibits secretion of FSH, LH
No flare effect

69

Ganirelix and Cetrorelix indications

Keeps LH low in controlled ovarian hyperstimulation for assisted repro tech (IVF)

70

Abarelix

Metastatic prostate cancer

71

GnRH receptor antagonists side effects

Ovarian hyperstimulation syndrome
QT interval prolongation (abarelix)
Ectopic pregnancy, thrombotic disorder, spontaneous abortion (ganirelix)
Anaphylaxis (cetrorelix)

72

Abarelix side effect

QT interval prolongation

73

Ganirelix side effects (3)

Ectopic pregnancy, thrombotic disorder, spontaneous abortion

74

Cetrorelix side effect

Anaphylaxis

75

GnRH receptor antagonists Contraindications

Pregnancy, lactation, ovarian cysts or enlargement (not due to PCOS)
Primary ovarian failure
Thyroid of adrenal dysfunction
Vaginal bleeding of unknown etiology

76

Which cells of the anterior pituitary produce and secrete prolactin?

Lactotrophs

77

Prolactin release is inhibited by ____

dopamine secreted by hypothalamus

78

Prolactin release is increased by

Thyrotropin-releasing hormone (TRH)

79

Is there any negative feedback regulation on prolaction?

no- does not stimulate hormone secretion in target organ (mammary gland)

80

What stimulates prolactin production during pregnancy?

Increasing estrogen levels

81

What effect does estrogen have on prolactin during pregnancy?

Increases production but antagonizes its action, preventing lactations until after parturition

82

What action is the powerful stimulus for prolactin release?

Suckling

83

Physiological actions of prolaction

Regulates mammary gland development, milk protein biosynthesis and secretion

Increased prolactin inhibits GnRH release (suppresses ovulation during lactation)

84

Causes of hyperprolactinemia

Rarely due to hypothalamic destruction
More commonly due to prolactin secreting adenomas

85

Hyperprolactinemia produces

Amenorrhea, galactorrhea, and infertility in women
Loss of libido and infertility in men
If large tumor > visual changes due to compression of the optic nerves

86

Dopamine Receptor Agonists

Bromocriptine, Cabergoline, Pergolide
Quinagolide (Europe)

87

Treatment of prolactin deficiency

No preparation of prolactin is available to treat these patients

88

Dopamine Receptor Agonists MOA

High affinity for dopamine D2 receptors
Inhibit pituitary prolactin release

89

Dopamine Receptor Agonists Indications

Amenorrhea, galactorrhea, infertility from hyperprolactinemia, premenstrual syndrome (Bromocriptine, Cabergoline)

Acromegaly (high doses, helpful only if tumor secretes prolactin and GH, use in combo with Octreotide (Bromocriptine)

Parkinson's Disease (Bromocriptine, Pergolide, Cabergoline)

90

Dopamine Receptor Agonists Side Effects

Orthostatic hypotension
Cerebral vascular accident, seizure, acute MI (Bromo)
Arrhythmia, MI, heart failure (pergo)
Pulmonary fibrosis and pleural effusion (cabergo)

91

Bromocriptine side effects

Cerebral vascular accident, seizure, acute MI

92

Pergolide side effects

Arrhythmia, MI, heart failure

93

Cabergoline side effects

Pulmonary fibrosis and pleural effusion

94

Dopamine Receptor Agonists Contraindications

Hypersensitivity to ergot derivatives
Uncontrolled hypertension
Toxemia of pregnancy

95

Which of the 3 dopamine receptor agonists causes less nausea?

Cabergoline

96

How can you reduce nausea with the dopamine receptor agonists? What is the potential side effect?

Intravaginal administration
May cause local irritation

97

What are the effects of dopamine receptor agonists and alcohol?

Alcohol intolerance may occur

98

What is the concern with giving dopamine receptor agonists and a antihypertensive?

Coadministration can potentiate hypotension