anterior pituitary disorders Flashcards
(104 cards)
1
Q
5 types of endocrine cells in the anterior pituitary that are defined by the hormones they secrete:
A
somatotrophs = GH
lactotrophs = LH
gonadotrophs = LH & FSH
corticotroph = ACTH
thyrotroph = TSH
2
Q
Inadequate production of Anterior Pituitary Hormones
A
hypopituitarism
3
Q
causes of hypopituitarism
A
- congenital
- gene mutations
- Prader Willi
- Kallmann syndrome - acquired
- Radiation
- TBI
- Chemotherapy
- Ischemic stroke - functional
- Opioid use
- Aging
- Malnutrition
- CKD
4
Q
what hormone deficiency would cause:
growth disorders in children and abnormal body composition in adults
A
GH deficiency - Hypopituitarism
5
Q
what hormone deficiency would cause:
menstrual disorders and infertility in women and decreased sexual function, infertility, and loss of secondary sex characteristics in men
A
Gonadotropin deficiency -Hypopituitarism
6
Q
what hormone deficiency would cause:
Hypothyroidism in children and adults
A
TSH deficiency - Hypopituitarism
7
Q
what hormone deficiency would cause:
Hypocortisolism
A
ACTH deficiency - Hypopituitarism
8
Q
what hormone deficiency would cause:
Failure of lactation
A
Prolactin deficiency - Hypopituitarism
9
Q
what anterior pituitary hormone is released do these hypothalamic releasing hormones trigger?
CRH
TRH
GnRh
GHRH
Dopamine (inhibits)
A
ACTH
TSH
LH & FSH
GH
Prolactin
10
Q
Significant lactotrope cell hyperplasia develops during when?
A
- pregnancy
- first months of lactation
11
Q
what state is PRL usually in?
A
inhibited
12
Q
PRL is mediates by what?
A
dopamine
(D2 receptors)
13
Q
Serum PRL levels rise mildly and transiently with the following:
A
- Exercise, meals, sexual intercourse
- Breast exam, chest wall injury
- Minor surgical procedures, general anesthesia
- Stress of any kind
14
Q
PRL secretion is pulsatile, with the highest secretory peaks occurring ?
A
non-REM sleep
- Peak serum levels 4:00 - 6:00 a.m.
- Circulating ½ life ~ 50 min
15
Q
PRL levels increase about tenfold during ____ and decline rapidly within 2 weeks of _____.
A
pregnancy
parturition
16
Q
The magnitude of PRL increase is directly proportional to
A
the degree of preexisting lactotroph hyperplasia due to estrogen
17
Q
The surge in prolactin in response to sucking is due to ?
A
decrease in the amount of dopamine released by the hypothalamus
18
Q
what hormone is responsible for the milk release from the breast?
A
oxytocin
19
Q
acts to induce and maintain lactation, decrease reproductive function, and suppress sex drive
A
PRL
20
Q
how does PRL inhibit reproductive function
A
- suppresses hypothalamic GnRH and pituitary gonadotropin secretion
- impairs gonadal steroidogenesis in both women and men.
21
Q
In the ovary, PRL leads to what?
A
hypoestrogenism and anovulation.
22
Q
MC pituitary hormone hypersecretion syndrome in both men and women
A
Hyperprolactinemia
23
Q
MC cause of PRL levels >200 μg/L
(normal = ~ 10-20 (M) and 10-25 for (W))
A
PRL-secreting pituitary adenomas (prolactinomas)
More common in women
24
Q
Less pronounced PRL elevation can also be seen with microprolactinoma but is more commonly caused by:
A
drugs, pituitary stalk compression, hypothyroidism, or renal failure
25
a woman presents with:
Amenorrhea, galactorrhea, and infertility
what could it be?
other s/s?
1. **hyperprolactinemia**
2. s/s
- decreased libido
- wt gain
- hirsutism
- vaginal dryness/atrophy
- irritability, anxiety and depression (due to estrogen deficiency)
- long-lasting - osteopenia, reduced muscle mass
26
a male pt presents with:
Decreased libido
Impotence/erectile dysfunction
Infertility
Gynecomastia
Galactorrhea
what could it be?
- hyperprolactinemia
- long-lasting - osteopenia, reduced muscle mass, and decreased facial hair growth
27
work up for hyperprolactinemia
1. **_Serum Prolactin concentration_**
- Basal, fasting morning PRL levels (normally <20 μg/L)
- *MOST ACCURATE*
2. **TSH** and **T4** levels - r/o hypothyroidism
3. Serum **hCG**
4. **CMP** - r/o liver and kidney disease
5. serum **total and free testosterone, LH, and FSH**
- for men evaluated for hypogonadism
6. serum **estradiol, LH, and FSH**
- Women who have amenorrhea are assessed for hypogonadism
7. **MRI**
- if PRL level elevated w/ no other cause, or if _PRL > 200_
28
Pt has a slightly high value for their serum prolactin of 30 (normal: 21 to 40 ng/mL)
what is the next step?
_repeated to confirm_ before the patient is considered to have hyperprolactinemia.
(A persistently elevated serum prolactin value should prompt a search for its cause)
29
a mass lesion in the region of the sella turcica was found in an MRI for possible hyperprolactinemia, what is the next step?
secretion of other pituitary hormones should also be evaluated
30
an MRI shows normal hypothalamic-pituitary anatomy and there is no identifiable secondary cause of hyperprolactinemia, what is the diagnosis?
idiopathic hyperprolactinemia
(Can be due to microadenomas that are too small to be seen on imaging)
31
tx for hyperprolactinemia
1. treat identifiable cause (if there is one)
2. _**Dopamine agonists** - Most effective_
- Cabergoline
- Bromocriptine
3. estrogen, estrogen/progesterone, or testosterone replacement
- for microprolactinomas (< 1cm)
- _AVOID MACROprolactinomas_ (risk of progressive growth)
32
what med is a _LA dopamine agonist_ and suppresses PRL for >14 d after a single dose
Cabergoline
33
what med is _SA dopamine agonist_ and is _preferred when pregnancy is desired_
Bromocriptine
administer a low dose PM with snack, followed by gradually increasing the dose
34
which dopamine agonist has SE and drug intolerance less commonly encountered than the other?
_Cabergoline_ (than Bromocriptine)
35
SE of dopamine agonists
- _constipation, nasal stuffiness/congestion, dry mouth, nightmares, insomnia, and vertigo_
- N/V and postural hypotension may occur. Give at bedtime.
- rare: leukopenia, thrombocytopenia, pleural fibrosis, arrhythmias, and hepatitis
36
Patients with Parkinson's disease who receive at least 3 mg of cabergoline daily have been reported to be at risk for development of
cardiac valve insufficiency
(Recommend echo prior to starting to document no valvular abnormalities and repeat if clinically warranted)
37
Women with ademonas who desire fertility / are pregnant who take dopamine agonists, what are the considerations?
1. _Microadenoma_ – safe with dopamine agonist held, conceive, and even safely breastfeed
2. _Macroadenoma_ – if dopamine agonist is stopped, monitor with:
- serum PRL levels
- visual-field testing
38
Low serum prolactin levels due to damaged lactotroph cells in ant. pit.
hypoprolactinemia
39
the inability to lactate after delivery is the hallmark manifestation of what condition?
hypolactinemia
40
most pts with acquired prolactin deficiency have evidence of other pituitary hormone deficiencies, indicative of ?
panhypopituitarism or possibly macroadenoma of another cell line
41
causes of hypoprolactinemia
1. Sheehan’s Syndrome
2. Meds
- Dopamine agonists
--- antiparkinsonian drugs
3. Tumors
42
postpartum hypopituitarism caused by necrosis of the pituitary gland
Usually the result of severe hypotension or shock caused by massive hemorrhage during or after delivery
Sheehan’s Syndrome
43
tx for hypoprolactinemia
1. Dopamine antagonists
2. Surgery
44
direct effects of GH
_stimulates cellular metabolism_
1. adipose tissue
- lipolysis - fuels metabolism
2. liver
- promotes gluconeogenesis and glycogenolysis
3. tissues
- diabetogenic: insulin resistance - insulin is less effective in moving glucose into cells
45
indirect effects of GH
1. muscles
- stimulates AA uptake into muscle cells = protein production and muscle growth
2. growth of long bones
- acts on epiphyseal cartilage = stimulates osteoblasts and chondrocytes = boosts growth
46
the most abundant anterior pituitary hormone
GH
GH-secreting somatotrope cells constitute up to 50% of the total anterior pituitary cell population
47
GH secretion is controlled by what 2 factors
complex hypothalamic and peripheral factors
- **GHRH** stimulates GH synthesis and release
- **Somatostatin** is synthesized in the medial preoptic area of the hypothalamus and inhibits GH secretion
48
GH secretion is pulsatile, with highest peak when?
at night, generally correlating with sleep onset.
49
GH secretory rates decline markedly with what?
_age_
hormone levels in middle age are about 15% of pubertal levels
- These changes are paralleled by an age-related decline in lean muscle mass.
50
A potent growth and differentiation factor
Somatomedin C (Insulin-like growth factor 1)
51
what organ is the major source of circulating IGF-1
liver
52
what is the relationship between GH and IGF-1?
proportional:
As GH levels _increase_, the liver synthesizes _more_ IGF-1. As GH levels decrease, the liver synthesizes less IGF-1.
53
Serum IGF-I concentrations are affected by physiologic factors:
1. Levels increase during puberty, peak at 16 years, and subsequently decline by >80% during the aging process.
2. IGF-I concentrations are higher in women than in men.
3. Abnormalities of GH synthesis or action (pituitary failure, GHRH receptor defect, GH receptor defect) reduce IGF-I levels.
54
what condition may result from disruption of the growth hormone axis in the hypothalamus or pituitary, and can be congenital or acquired.
GH deficiency
55
Acquired growth hormone deficiency may result from ?
1. trauma
2. infections (encephalitis, meningitis)
3. cranial irradiation (somatotrophs are the most radiation-sensitive cells)
4. other systemic disease
56
short stature, micropenis, increased fat, high-pitched voice, and hypoglycemia are characteristics commonly in what condition?
Isolated GH deficiency
57
what are the familial modes of inheritance of GH deficiency aka how can it be passed down?
autosomal dominant, recessive, or X-linked
- Genetic mutations of GH producing or secreting cells
- May also involve other pituitary hormone deficiencies
- Recessive mutations of the GHRH receptor gene can lead to severe dwarfism
58
Caused by defects of GH receptor structure or signaling
GH insensitivity
59
GH insensitivity is diagnosed based on what?
**normal or high GH levels**, with decreased circulating growth hormone binding protein (GHBP), and **low IGF-I levels**
60
growth failure is an important clinical manifestation for what condition
**GHD**
careful documentation of _growth rate_ is critical to making the correct diagnosis
61
hx in pts with suspected GHD should focus on the following issues:
Birth weight and height
Height of parents
Timing of puberty in parents
Previous growth points
General health of child
Nutritional history
62
PE for GHD should focus on the following:
1. **Proper height and wt measurement**
- The best way to evaluate height or weight measurements is to plot the points on a _growth chart_
2. Proportionality
3. Pubertal status
4. Evidence of genetic syndromes
63
when should GHD evaluation be done for children?
1. Marked short stature, _more than 2.5 SD below the mean_ for age, sex, and ethnic background.
2. Growth failure, defined as _height velocity < 25th percentile_ whether or not short stature is present.
3. _Less severe short stature_ for age, sex and ethnic background, _combined with growth failure_ in the _absence_ of an alternative explanation.
4. Evidence suggesting _hypothalamic-pituitary dysfunction_ (*hypoglycemia, microphallus, cryptorchidism, optic nerve hypoplasia, intracranial tumor, or history of cranial irradiation*), with decelerating growth, even if the child's height is within the normal range.
5. Evidence for deficits in other hypothalamic-pituitary hormones, either congenital or acquired.
64
work up for GHD
1. evaluate for other causes of growth failure
- chronic systemic disease, hypothyroidism, Turner Syndrome, and skeletal disorders
2. If there is no evidence, investigate for GHD with: (*diagnostic*)
- **GH stimulation test** -
- Insulin-like growth factor-1 (**IGF-I**)
- Insulin-like growth factor binding protein-3 (**IGFBP-3**). Main carrier of IGF-I in body.
- Bone age
3. MRI/CT
4. genetic testing - if no other causes found
65
Why is assessing GH production difficult?
**GH secretion is pulsatile**
the most consistent surges during stages 3 and 4 of sleep
- Between normal pulses, serum GH levels are too low for sensitivity of most conventional assays
--- a random serum GH level is not helpful in diagnosing GHD
66
what is also a useful predictor of response during the first year of treatment with GH
Provocative testing
67
GH Stimulation Test relies upon the use of what 2 factors?
physiological or pharmacological stimuli
1. physiological - sleep, fasting, and exercise
2. Pharmacological - L-dopa, clonidine, propranolol, arginine, and insulin-induced hypoglycemia
68
A diagnosis of impaired GH secretion can be confirmed only if ?
subnormal GH secretion is observed during **_two_** different GH stimulation tests
- tests are performed after an overnight fast
- _Lack of increase of GH = positive test_
69
tx for GHD
1. **Recombinant GH**
- **Somatropin** (Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, TevTropin)
2. correct associated hormones with pituitary insufficiency - esp adrenal steroids
3. GH insensitivity or mutations of the GH receptor = **IGF-I**
- GH levels _normal or elevated_ in these pts
69
This disorder usually is caused by hypothalamic or pituitary somatotrope damage.
GHD (adults)
70
The sequential order of hormone loss is usually GH →
FSH/LH → TSH → ACTH
71
an adult pt notes:
changes in body composition, lipid metabolism, and cardiovascular dysfunction
what could be their condition?
what other signs could be found on PE
AGHD
- reduced lean body mass, increased fat mass, increased waist-to-hip ratio
- Hyperlipidemia, LV dysfunction, and HTN
- increased fractures
- Depression, social isolation, fatigue
72
Testing for AGHD should be limited to pts with the following predisposing risk factors:
pituitary surgery
pituitary or hypothalamic tumor or granulomas
history of cranial irradiation
radiologic evidence of a pituitary lesion
childhood requirement for GH replacement therapy
unexplained low age- and sex-matched IGF-I levels
73
tx for AGHD
dosing?
1. **recombinant human GH (rhGH, somatropin)**
- starting dose of **0.1–0.3 mg/d** should be titrated (up to a max **1.25 mg/d**) to maintain IGF-I levels in the mid-normal range for age- and sex-matched controls
74
CI of recombinant human growth hormone therapy
presence of an active neoplasm
intracranial HTN
uncontrolled DM and retinopathy
75
what tx assists growth of linear bone, skeletal muscle, and organs by stimulating chondrocyte proliferation, lipolysis, protein synthesis, and hepatic glucose output
Recombinant human growth hormone rhGH (Somatropin)
76
indications and dosing for rhGH (somatropin)
1. indications
- children - growth failure, short stature
- adults - GH deficiency, hypopituitarism
2. dosing:
- Adults: IGF-1 every 1-2 months during titration, then semiannually at maintenance
- Children: Monitor growth curve and physical exam with skeletal assessment with every visit
77
monitoring for rhGH (somatropin)
fundoscopic exam
start of therapy and periodically during tx (intracranial hypertension)
78
SE and what to watch for during AGHD tx
SE: HA, Increased ICP (usually in first 8-12 weeks of treatment), HTN, Tinnitus, Slipped Capital Femoral Epiphysis
what to watch for:
1. fluid retention
2. joint pain
3. CTS
4. myalgias
5. paresthesias
Patients requiring insulin need careful monitoring for dose adjustments
- GH is a potent counter-regulatory hormone for insulin action = Hyperglycemia and DM can develop
79
A result of too much GH / excess GHRH production
acromegaly/gigantism
80
GH hypersecretion is usually the result of a ?
**somatotrope adenoma**
but may rarely be caused by extrapituitary lesions
81
ectopic GH secretion can happen by tumors of ?
pancreatic, ovarian, lung, or hematopoietic origin
82
The most common cause of GHRH-mediated acromegaly is ?
chest or abdominal carcinoid tumor
83
frontal bossing, increased hand and foot size, mandibular enlargement with prognathism, and widened space between the lower incisor teeth
Acral bony overgrowth
84
Manifestations of GH and IGF-I hypersecretion are ___ and often are not clinically diagnosed for ____
slow-moving
10 yrs or more
85
initiation of GH hypersecretion before epiphyseal long bone closure is associated with development of
pituitary **gigantism**
86
Generalized visceromegaly occurs, including ?
cardiomegaly, macroglossia, and thyroid gland enlargement
87
The most significant clinical impact of GH excess occurs with what?
**_CV system_**
- _Cardiomyopathy with arrhythmias_, left ventricular hypertrophy, decreased diastolic function, and hypertension ultimately occur in most patients if untreated.
88
clinical features with GH excess
1. _arrhythmias_
2. sleep apnea
3. DM
4. colon polyps
89
work up for GH excess
1. elevated age- and sex-matched serum IGF-I (in acromegaly)
2. **the failure of GH suppression to <0.4 μg/L within 1–2 h of an oral glucose load (75 g)**
- High glucose stimulates somatostatin release
3. Thyroid function, gonadotropins, and sex steroids may be attenuated because of tumor mass effects
Measurement of a single random GH level is _not_ useful
90
tx for GH excess
1. **Transsphenoidal surgical resection**
- for both micro- and macroadenomas
- GH levels return to normal within an hour, and IGF-I levels are normalized within 3–4 days.
2. radiation
- External radiation therapy or high-energy stereotactic techniques = adjuvant therapy
3. Somatostatin analogues: Decrease GH secretion
- lanreotide, octreotide, pasireotide, Sandostatin, Sandostatin LAR, Signifor, Somatuline Depot
4. Dopamine Agonists
- Combined tx with octreotide and cabergoline may induce additive biochemical control compared with either drug alone.
91
SE of Somatostatin analogues
N/D, abd discomfort, fat malabsorption, and flatulence
- happens in 1/3 of patients
- remits within 2 weeks.
92
what Somatostatin analogues
suppresses postprandial gallbladder contractility and delays gallbladder emptying;
octreotide
93
The most common presenting feature of adult hypopituitarism
Hypogonadism
94
a woman presents:
oligomenorrhea, amenorrhea, infertility, decreased vaginal secretions, decreased libido, osteoporosis
what could be the condition?
Hypogonadism
95
a male presents with:
testicular failure associated with decreased libido, impotency, infertility, decreased muscle mass, reduced beard and body hair growth
what could be the condition?
Hypogonadism
96
labs with hypogonadism
1. low or inappropriately normal serum gonadotropin levels in the setting of low sex hormone concentrations (testosterone/estradiol)
- IV GnRH should stimulate secretion of LH/FSH = increased serum levels
- normal response to GnRH indicates intact pituitary function with hypothalamic abnormality
97
Lab Evaluation of Hypogonadism for males and females
males
1. AM serum testosterone and free testosterone
- Low - repeat testosterone, along with serum LH and PRL levels.
females
1. hCG (r/o pregnancy)
2. serum PRL
3. FSH and LH
4. TSH
98
tx for hypogonadism
male
1. Testosterone replacement
2. human chorionic gonadotropin (hCG) (equivalent to LH) - infertility due to oligospermia
3. leuprolide (GnRH analog) - with intact pituitary
4. Clomiphene - stimulate men’s own pituitary gonadotropins (if pituitary is intact)
female
1. **estrogen** and **progesterone**
- _Gonadotropin therapy_ - ovulation induction
--- _human menopausal gonadotropin (hMG) or recombinant FSH_ - Follicular growth and maturation
--- _LH_ - induce ovulation
2 Pulsatile GnRH therapy - treat hypothalamic causes of infertility
99
synthesized in the hypothalamus and stimulates the release of ACTH by the anterior pituitary
CRH
100
ACTH is released by the anterior pituitary and stimulates the adrenal cortex to secrete ?
corticosteroids (cortisol)
101
ACTH secretion is pulsatile and peaks at
~ 6 A.M.
102
ACTH levels are increased by:
physical and psychological stress, exercise, acute illness, and insulin-induced hypoglycemia
103
how does cortisol affect CRH and ACTH
Cortisol provides negative regulation and inhibits both CRH in the hypothalamus and ACTH release by the pituitary
