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Hypothalamic and Pituitary Hormones Flashcards

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1
Q

What is a negative regulator of GH?

A

Somatostatin

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2
Q

What is a negative regulator of prolactin?

A

Dopamine

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3
Q

The effects of GH are mediated through

A

IGF-1

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4
Q

Physiological Actions of GH in childhood

A

Promotes linear growth

Growth of long bones, cartilage, muscle, organ systems

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5
Q

Physiological Actions of GH in adulthood

A

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

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6
Q

Features of GH deficiency in children

A

short stature
Adiposity
hypoglycemia

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7
Q

Features of GH deficiency in adults

A 
increased generalized adiposity
Decreases skeletal muscle mass
decreased bone density
Cardiac muscle atrophy
Atherogenic blood lipid profile
Fatigue, weakness, depression, malaise
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8
Q

synthetic GHRH

A

Sermorelin

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9
Q

Sermorelin (synthetic GHRH) indication

A

used if defective GHRH release but normally functioning anterior pituitary somatotrophs

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10
Q

Recombinant human GH

A

Somatropin

Somatrem

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11
Q

Recombinant IGF-1

A

Mecasermin

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12
Q

Mecasermin (recombinant IGF-1) indication

A

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

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13
Q

Somatropin formulation

A

191-amino acid peptide, identical to native hGH

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14
Q

Somatrem

A

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

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15
Q

Recombinant hGH (somatropin, somatrem) MOA

A

replaces GH

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16
Q

Recombinant hGH (somatropin, somatrem) Indications

A 
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

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17
Q

Recombinant hGH (somatropin, somatrem) efficacy in children

A

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

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18
Q

Recombinant hGH (somatropin, somatrem) efficacy in adults

A 
Increases bone mineral density
Decreased central adiposity
Increases muscle mass
Improves lipid profile
Improves cardiac function
Improves sense of well being
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19
Q

Recombinant hGH (somatropin, somatrem) side effects

A 
Leukemia
Rapid growth of melanocytic lesions
Hypothyroidism (GH counteracts TSH)
Insulin resistance
Arthralgia
Increase in cytochrome p450 activity
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20
Q

Recombinant hGH (somatropin, somatrem) contraindications

A 
Ped pts with closed epiphyses
Intracranial lesion
Active malignancy
Proliferative diabetic retinopathy
Cautin in diabetes
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21
Q

What is the effect of glucocorticoids on somatropin

A

Inhibit growth-promoting effect

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22
Q

What is the most common cause of growth hormone excess

A

Benign anterior pituitary tumor

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23
Q

Growth hormone excess in children

A

Gigantism

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

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24
Q

Growth hormone excess in adults

A

Acromegaly

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

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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

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