Introduction to Endocrinology: The Hypothalamic-Pituitary Axis Flashcards
(142 cards)
1
Q
Anterior lobe (adenohypophysis) consists of:
A
Pars distalis
Pars tuberalis
Pars intermedia
2
Q
Consists of pars nervosa which is connected by infundibulum
(pituitary stalk) to the median eminence (tuber cinereum) of
hypothalamus.
A
Posterior lobe (neurohypophysis)
3
Q
Somatostatin: ____ growth hormone
A
Decrease
4
Q
Somatostatin: _____ TSH
A
Decrease
5
Q
Dopamine: ___ prolactin
A
Decrease
6
Q
Thyrotropin-releasing hormone: ___ prolactin
A
Increase
7
Q
Gonadtropin-releasing hormone: ___ FSH
A
Increase
8
Q
Gonadtropin-releasing hormone: ___ LH
A
Increase
9
Q
Acidophilic hormones:
A
Somatotropes
Mammotropes
10
Q
Basophilic hormones:
A
Thyrotropes
Gonadotropes
Corticotropes
11
Q
single polypeptide chain of 22 kDa; w/ 2 disulfide
bonds, not glycosylated
A
Growth hormone
12
Q
Growth hormone gene resides on the long arm of __________.
A
chromosome 17
13
Q
Most abundant ant. pituitary hormone
A
GH
14
Q
Increased secretion in children
A
GH
15
Q
greatest at night shortly after onset of deep sleep
A
GH
16
Q
GH stimulus
A
Main GHRH and ghrelin
17
Q
Minor stimulus of GH:
A
DA 5HT a2 receptor agonists Hypoglycemia Exercise Stress Emotional excitement Ingestion of protein-rich meals
18
Q
Major peripheral effector of GH
A
IGF-1
19
Q
GH suppressors
A
IGF-1 (from peripheral tissues)
Somatostatin (from hypothalamus)
GH levels (from anterior pituitary)
20
Q
Stimulates longitudinal growth of bones
A
GH
21
Q
increase bone mineral density
A
GH
22
Q
myeloblast differentiation & increased mm mass
A
GH
23
Q
Increases GFR
A
GH
24
Q
preadipocytes to adipocyte differentiation
A
GH
25
GH ____ glucose utilization
Decrease
26
GH ____ lipolysis
Increase
27
Anti-insulin action
GH
28
Induction of insulin-like growth factor (IGF-1)
GH
29
Height diagnosis of GH deficiency
>2 to 2.5 SD below normal
30
“provocative testing”
<10ng/ml
31
severe deficiency
<5 ng/mL
32
Human GH by recombinant DNA Technology
Somatotropin
33
Somatotropin dosage in children
25-50ug/kg/day SQ in the evening
34
Somatotropin dosage in adults
150-300 ug/d
35
used to monitor initial response
| & compliance
Normalization of serum IGF-1 levels
36
Long term monitoring
Evaluation of height
37
Increase in growth velocity occurs w/in the ______ of therapy
first 2 yrs
38
Continued until closure of ________
epiphysis
39
Somatostatin pharmacokinetics
70% bioavailability
| Once daily dosing
40
For adults
Normalization of GH levels
41
________ inhibit GH action so that a
larger dose of GH is needed to maintain the same
IGF-1 level
Estrogens (e.g., birth control medications and
| estrogen supplements)
42
Recombinant Human IGF-1
Mecasermin
43
For patients with impaired growth secondary to mutations
| in the GHR or postreceptor signaling pathway
Mecasermin
44
patients who develop antibodies against GH that interfere
| with its action
Mecasermin
45
patients with IGF-1 gene defects that lead to primary IGF-1
| deficiency
Mecasermin
46
Less effective than recombinant GH for impaired growth
secondary to GH deficiency or with idiopathic short
stature
Mecasermin
47
Dose of mecasermin
40 to 80 ug/kg SQ twice daily
48
Max dose of mecasermin
120 ug/kg/dose BID
49
Adverse effects of Mecasermin:
Hypoglycemia
Lipodystrophy
Lymphoid tissue hypertrophy
50
Contraindications of mecasermin:
Closed epiphysis
| Active or suspected neoplasia
51
synthetic human GHRH
Tesamorelin
52
increases GH and IGF-1 levels
Tesamorelin
53
its clinical effects are primarily to reduce visceral fat
| accumulation, with minimal effects on insulin resistance
Tesamorelin
54
FDA-approved for treatment of HIV-associated lipodystrophy
| but not for GH deficiency
Tesamorelin
55
If epiphyses are unfused
Gigantism
56
In adults (epiphyses have fused)
Acromegaly
57
Gold standard of growth hormone excess
Oral glucose tolerance test
58
Normal response
Suppression of GH level to <1 ng/mL
59
fail to suppress GH level or + paradoxical increase in GH
| level
acromegaly
60
Octreotide (Sandostatin) dosage
100 ug SQ TID
61
Octreotide (Sandostatin) bioavailability
100%
62
Octreotide (Sandostatin) peak effect
30 mins
63
Octreotide (Sandostatin) half life
90 mins
64
Octreotide (Sandostatin) Duration of action
12 hours
65
Octreotide (Sandostatin) LAR
10
20
30 mg
once every 4 weels
66
efficacy similar to Octreotide LAR
Lanreotide (Somatuline LA)
67
binds to multiple SST receptors; better than O and L
Pasireotide
68
Goal of treament of Pasireotide:
Decrease GH levels to <2.5 ng/mL after OGTT or normal IGF-1 level
69
more problem with glucose tolerance
Pasireotide
70
Somatostatin analogs
Octreotide
Lanreotide
Pasireotide
71
a recombinant pegylated variant of
| human GH
Pegvisomant
72
For Acromegaly
Pegvisomant
73
Pegvisomant dosage
40mg SQ loading dose then 10mg/day
74
Not to be used in pts w/ liver dse
Pegvisomant
75
Lipohypertrophy at injection sites
Pegvisomant
76
May increase growth of GH secreting adenomas
Pegvisomant
77
for pts who do not respond to SST analogues or given
| as adjunct
Pegvisomant
78
23,000-dalton protein of 199 AA w/ 3 intramolecular di-sulfide
bonds
prolactin
79
the synthesis and secretion starts on the _____ week of gestation.
5th
80
Caused by prolactin secreting pit. Adenoma (Prolactinomas)
Hyperprolactinemia
81
suppress prolactin
production by activation of D2 dopamine receptors: also ↓ the
size of the tumor (TOC for most patients)
Dopamine receptor agonist
82
Dopamine receptor agonists:
1. Bromocriptine (Parlodel)
2. Carbegoline (Dostinex)
3. Quinagolide (Norpralac)
83
more potent than Bromocriptine
Carbegoline (Dostinex)
84
```
Activates D2 (Dopamine) receptors to inhibit spontaneous &
TRH-induced release of prolactin
```
Bromocriptine (Parlodel)
85
Normalizes prolactin level (70 to 80%)
Bromocriptine (Parlodel)
86
Decrease tumor size in >50% of pts
Bromocriptine (Parlodel)
87
To avoid side effects of bromocriptine: Start at low dose (______) at bedtime; after
1 week increase to ____ daily: gradually increase every _______
up to ________ or until prolactin becomes normal
1.25mg
2x
3 to 7 days
5 mg 2x daily
88
Bromocriptine at higher concentrations:
Treatment of acromegaly and parkinsons disease
89
Safe to use in pregnancy
Bromocriptine
90
Longer half-life, higher affinity and greater selectivity to D2
receptors
Carbegoline
91
Preferred drug for Hyperprolactinemia (greater efficacy and lower adverse effects)
Carbegoline
92
Carbegoline dose:
0. 25 mg 2x a week
0. 5 mg once a week
May increase once every 4 weeks
93
Doses of ______ or less normalize PRL levels in 80% of patients
2 mg/week
94
At higher doses – can be used in some patients with
| acromegaly alone or in conjunction with SST analogues
Carbegoline
95
linked to valvular heart disease at high doses
Carbegoline
96
______ acts on testicular Leydig cells to stimulate de novo synthesis of Androgens (primarily testosterone) from
cholesterol
LH
97
required for gametogenesis & for
| maintenance of libido & secondary sexual characteristics
testosterone
98
acts on the Sertoli cells; stimulates production of proteins &
nutrients for sperm maturation
FSH
99
– stim. the growth of developing ovarian follicles &
induces expression of LH receptors on theca &
granulosa cells
FSH
100
also regulates the activity of aromatase in
| granulosa cells
FSH
101
FSH stimulates production of ________
17 B estradiol
102
Precursor of ovarian 17B-estradiol
Androstenedione
103
required for the rupture of the dominant follicle
during ovulation & for the synthesis of progesterone by
the corpus luteum
LH
104
A synthetic GnRH stimulate gonadotropin release
Gonadorelin acetate (Lutrepulse)
105
diagnostically to differentiate between GnRH-dependent and
| GnRH-independent precocious puberty
Leuprolide
106
As management of precocious puberty
pharmacologic castration
107
GnRH agonist (long acting)
```
Lueprolide
Goserelin
Histrelin
Nafarelin
Triptorelin
```
108
GnRH agonists treatment for endometriosis and uterine fibroids limited to _____ due to adverse effects
6 months
109
GnRH antagonists
Ganirelix (Antagon)
| Cetrorelix (Cetrotide)
110
Suppress the LH surge; prevent premature follicular
| luteinization in ovarian stimulation protocol
Ganirelix (Antagon)
| Cetrorelix (Cetrotide)
111
Treatment for advanced prostate CA
Degarelix
112
suppresses testosterone levels to 50 ng/dL or less (i.e.,
| medical castration)
Degarelix
113
lowers prostate-specific antigen more rapidly than GnRH
| agonists without an initial testosterone surge
Degarelix
114
Therapeutic Uses of Gonadotropins
Male infertility
| Cryptorchidism
115
A cyclic nonapeptide
Oxytocin
116
Differs from vasopressin by 2 AA
Oxytocin
117
stimulate the frequency & force of uterine contractions
Oxytocin
118
Milk ejection in breast
Oxytocin
119
Estrogen dependent because estrogen increases the expression of ______ receptors.
Oxytocin
120
Inhibitory action to oxytocin
Relaxin
121
_______ antagonizes the stimulant effect of oxytocin
Progesterone
122
CNS regulator of trust and in the autonomic NS
| – linked to anxiety and fear
oxytocin
123
Drug of choice for induction of labor
Oxytocin (Pitocin, Syntocinon)
124
no sig. increase in uterine contraction;
| higher rates are unlikely to be successful
If at 40mIU/min
125
If uterine tetany develops – stop infusion (half-life: _______)
3 minutes
126
Dose of ________, decrease water clearance by the
| kidney
>20mIU/min
127
If hypotonic fluids like _____ is infused rapidly - increased risk
of water intoxication (convulsion, coma, even death)
D5W
128
Augmentation of dysfunctional labor dose usually does not exceed ________.
10 mIU/min
129
Prevention and treatment of post-partum hemorrhage
10 iu IM or 20iu of Oxytocin in 1L of IV fluid at
10ml/min until the uterus is contracted then ↓ to 1-
2ml/min
130
Oxytocin antagonist
Atosiban
131
Tocolytic therapy for established preterm labor
Atosiban
132
Other Tocolytics
```
β adrenergic receptor agonists
MgSO4
Ca2+ channel blockers
COX inhibitors
NO donors
```
133
Vasopressin agonist
Desmopressin
134
Vasopressin antagonist
Conivaptan
135
Oxytocin antagonist
Atosiban
136
Oxytocin agonist
Oxytocin
137
GnRH receptor antagonist
Ganirelix
138
GnRH receptor agonist
Leuprolide
139
GnRH agonist
Gonadorelin
140
Prolactin antagonist
Bromocriptine
141
GH antagonist
Octreotide
| Pegvisomant
142
GH agonist
Somatotropin
| Mecasermin
