Pituitary and Hypothalamus Flashcards
1
Q
ventral lateral preoptic area (VLPO)
A
GABAergic neurons in VLPO contribute
to nonREM sleep by inhibiting the arousal systems including histaminergic
neurons in the tuberomammillary nucleus (TMN) and orexin-containing
neurons in the posterior lateral hypothalamus, as well as brainstem serotonergic, noradrenergic, dopaminergic and cholinergic nuclei
2
Q
lesions of the anterior hypothalamus including the VLPO
A
tend to cause insomnia
3
Q
lesions of the posterior hypothalamus
A
destroy the histaminergic neurons in the TMN and orexin-containing
neurons, tend to cause hypersomnia
4
Q
lateral hypothalamus
A
important in
appetite, and lateral hypothalamic lesions cause a decrease in body weight; lesions
of the lateral hypothalamus decrease water intake.
5
Q
medial hypothalamus, especially the ventromedial nucleus
A
appears
to be important in inhibiting appetite, and medial hypothalamic lesions can
cause obesity
6
Q
leptin
A
hormone that is produced by adipose tissue; leptin binds to Ob receptors in the hypothalamus and plays
an important role in feedback regulation of food intake, reducing appetite and
obesity
7
Q
Ghrelin
A
opposing hormone to leptin; elaborated by gastric mucosal cells,
binds in the hypothalamus, and stimulates appetite
8
Q
Thirst appears to result
from ___________
A
activation of osmoreceptors in the anterior regions of the hypothalamus
Hypovolemia or elevated body temperature can also activate thirst
Lesions
of the lateral hypothalamus decrease water intake.
9
Q
Thermoregulation involves the control of multiple systems including
A
including sweat
production; smooth muscles that affect core and surface blood flow; skeletal
muscles involved in shivering, panting, and other motor activity; and endocrine
systems that control the metabolic rate
10
Q
anterior hypothalamus appears to ___________
A
detect increased body temperature and activates mechanisms of heat dissipation.
Anterior hypothalamic lesions can cause hyperthermia
11
Q
posterior hypothalamus
A
functions to conserve heat; bilateral lesions of the
posterior hypothalamus usually cause poikilothermia, in which the body temperature
varies with the environment because these lesions destroy both heat
conservation mechanisms of the posterior hypothalamus and descending pathways
for heat dissipation arising from the anterior hypothalamus.
12
Q
The hypothalamus
probably also participates in circuitry involved in ________
A
sexual desire and
other complex motivational states
In addition, sexual development and differentiation
involve an interplay of neural and endocrine signals, many of which
appear to be regulated by the hypothalamus.
13
Q
oxytocin
A
hormone produced
in the hypothalamus and released in the posterior pituitary has been shown
to increase nurturing behaviors
14
Q
anterior pituitary hormones are
A
adrenocorticotropic
hormone (ACTH), growth hormone (GH), prolactin, thyroid-stimulating hormone
(TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)
15
Q
intermediate lobe is rudimentary in humans, produces
A
pro-opiomelanocortin
POMC) and melanocyte-stimulating hormone (MSH
16
Q
Two hormones are released in the posterior
pituitary:
A
(1) oxytocin and (2) vasopressin, which is also called arginine vasopressin
(AVP) or antidiuretic hormone (ADH)
17
Q
Release of the anterior pituitary hormones by glandular cells is controlled
by
A
neurons in the hypothalamus through the hypophysial portal system
18
Q
pituitary receives arterial blood from
A
inferior and superior hypophysial
arteries, both of which are branches of the internal carotid artery.
19
Q
first capillary plexus of the portal system occurs in the
A
median eminence
20
Q
Neurons
lying adjacent to the third ventricle in several hypothalamic nuclei project
to the median eminence, where they
A
secrete inhibitory and releasing factors
21
Q
Nuclei projecting to the median eminence include the
A
arcuate nucleus, periventricular nucleus, medial preoptic nucleus, and medial
parvocellular portions of the paraventricular nucleus
22
Q
Anterior Pituitary Hormones: Adrenocorticotropic hormone (ACTH)
Hypothalamic Releasing Factor: _____________
A
Corticotropin-releasing hormone (CRH),
vasopressin, and
other peptides
No Hypothalamic Inhibitory Factors
23
Q
Anterior Pituitary Hormones: Thyroid-stimulating hormone (TSH)
Hypothalamic Releasing Factor: ____________
Hypothalamic Inhibitory Factor: ____________
A
Thyrotropin-releasing
hormone (TRH)
Growth hormone–inhibiting hormone
(GIH, somatostatin)
24
Q
Anterior Pituitary Hormones: Growth Hormone (GH)
Hypothalamic Releasing Factor: ____________
Hypothalamic Inhibitory Factor: ____________
A
Growth hormone– releasing hormone (GHRH)
Growth hormone
inhibiting hormone
GIH, somatostatin
25
Anterior Pituitary Hormones: Prolactin
Hypothalamic Releasing Factor: ____________
Hypothalamic Inhibitory Factor: ____________
Prolactin-releasing
factor (PRF) and thyrotropin-releasing hormone (TRH)
```
Prolactin release–
inhibiting factor (PIF, dopamine)
```
26
Anterior Pituitary Hormones: Luteinizing hormone (LH)
Hypothalamic Releasing Factor: ____________
Luteinizing hormone–
releasing hormone
(LHRH)
27
Anterior Pituitary Hormones: Follicle-stimulating hormone (FSH)
Hypothalamic Releasing Factor: ____________
Luteinizing hormone–releasing hormone
| LHRH
28
Inhibitory and releasing factors enter the capillary plexus of the median eminence and are carried by
the hypophysial
portal veins to the anterior pituitary
Most of these factors are peptides, except
for prolactin release–inhibiting factor (PIF), which is dopamine.
29
Hormones released in the anterior pituitary are picked up by the secondary capillary
plexus of the portal system and carried by draining veins to the cavernous
sinus.
Recall that the cavernous sinus drains primarily via the superior and inferior
petrosal sinuses to reach the internal jugular vein
30
posterior pituitary also has a capillary plexus
picks up oxytocin and vasopressin and carries these hormones into the systemic
circulation
31
Oxytocin and vasopressin are secreted in the posterior pituitary
by terminals of neurons whose cell bodies lie in
the supraoptic and paraventricular
nuclei. Both nuclei contain both hormones, but separate neurons
appear to contain either oxytocin or vasopressin, not both.
32
ACTH stimulates the adrenal cortex to produce
corticosteroid hormones, especially the glucocorticoid hormone cortisol, and to
a lesser extent the mineralocorticoid hormone aldosterone.
These steroid hormones
are important for maintaining blood pressure, controlling electrolyte balance,
promoting glucose mobilization into the bloodstream, and a variety of
other functions.
33
adrenal medulla, which is under direct control
| of the preganglionic sympathetic neurons, releases
epinephrine and norepinephrine
34
TSH stimulates the thyroid gland to produce
thyroxine
(T4), and triiodothyronine (T3)
These hormones promote cellular metabolism.
35
Growth hormone causes the liver, kidneys, and other organs to produce
somatomedins or insulin-like growth factors (IGF),
which promote increased
| growth of the long bones and other tissues
36
Prolactin causes
the mammillary
| glands to produce milk
37
LH and FSH regulate
ovarian hormones responsible for
the menstrual cycle and oogenesis in females, and they regulate testicular hormones
and spermatogenesis in males
38
Oxytocin causes
contractions of smooth
| muscle in the breast for milk letdown and contractions of the uterus during labor.
39
Vasopressin, or ADH, participates
osmotic regulation by promoting
| water retention by the kidneys, allowing concentration of the urine
40
Release of hormones in the hypothalamic–pituitary axis is regulated by
multiple
| neuroendocrine feedback loops
41
release of
corticotropin-releasing hormone (CRH) by the hypothalamus and release of
ACTH by the anterior pituitary both receive feedback inhibition from
circulating
| cortisol in the bloodstream
42
Chronic administration of exogenous steroids
| can suppress
ACTH production to the point that the adrenals atrophy and
are unable to provide sufficient cortisol to support life if the exogenous steroids
are abruptly discontinued
43
Pituitary adenoma is a
slow-growing, histologically benign tumor arising
from glandular epithelial cells in the anterior pituitary. It is a fairly common
tumor, accounting for about 12% of all intracranial neoplasms in adults. Mean age at the time of diagnosis is 40 years, although cases occasionally
occur in adolescents or in the elderly. Pituitary adenomas can arise
from any of the endocrine cell types in the anterior pituitary, and 85% secrete
one or more pituitary hormones. Hormone secretion by pituitary adenomas
is often in excess of normal levels and is not under normal hypothalamic
control, resulting in several endocrinological syndromes. Even small pituitary microadenomas less than 1 millimeter
in diameter can cause significant endocrinological abnormalities.
44
nonfunctioning (nonhormone-secreting, or “silent”) adenomas
| often
grow larger before causing symptoms. Headache may be present
even in small pituitary adenomas because of irritation of pain fibers in the
adjacent cavernous region; however, headache is more common in large pituitary
tumors. In addition, large tumors can compress the optic chiasm and
cause visual disturbances, including a characteristic bitemporal hemianopia. If left untreated, large pituitary adenomas can eventually
cause hydrocephalus and brainstem compression.
45
Prolactin is the most commonly secreted
hormone in pituitary adenomas,
| accounting for about 50% of all pituitary adenomas.
46
The next most common
| is growth hormone, followed by
ACTH. TSH-, LH-, and FSH-secreting tumors
are more rare, as are tumors secreting more than one hormone. “Nonfunctioning
tumors” that secrete no active hormones account for about 15%
of pituitary adenomas.
47
Treatment options for pituitary adenomas include
medication, surgery,
| and radiotherapy
48
Prolactin-secreting tumors (prolactinomas) often show a
| good response to treatment with
dopaminergic agonists such as bromocriptine
or cabergoline, which inhibit prolactin release and
shrink tumors. Treatment of non–prolactin-secreting tumors is usually with
surgery, since pharmaceutical treatment is less effective. The somatostatin
analogue octreotide, which inhibits growth hormone release and shrinks tumors, has shown some promising results in treatment of
growth hormone–secreting tumors. Surgical resection offers the advantages
of potential immediate cure and relatively low risk.
49
Surgery is also used for
prolactin-secreting tumors that do not respond adequately to medical therapy.
Usually, a
transsphenoidal approach is taken, in which, under general
anesthesia, the floor of the pituitary fossa is entered through the roof of the
sphenoid sinus with instruments inserted through the
nose. With suprasellar pituitary tumors (extending above the sella turcica),
an intracranial approach is sometimes necessary to attain adequate tumor
removal, although recent advances in endoscopic neurosurgery have enabled
greater access to skull-base structures even in the suprasellar region using
the transsphenoidal approach. Radiotherapy with gamma knife is used mainly for cases that fail to respond to surgery or in patients
who cannot undergo surgery due to operative risk.
50
Prolactin-secreting adenomas typically
| cause
amenorrhea in women; hypogonadism in men; and galactorrhea, infertility,
hair loss, decreased libido, and weight gain in both sexes. Some of
these effects of elevated prolactin are mediated by inhibition of hypothalamic
LHRH, which in turn leads to decreased LH and FSH levels. In normal women this effect of prolactin on LH and FSH delays the resumption
of menses during lactation. As with all other pituitary tumors,
headache and visual symptoms can also occur.
51
Elevated prolactin levels can have many causes, but very high levels
(>150 micrograms per liter in nonpregnant patients) are virtually diagnostic
of pituitary adenoma. MRI is useful for diagnosis and can now be used to
detect microadenomas as small as
0.5 to 1 millimeter in diameter through indirect
effects on pituitary shape, although smaller tumors may not be visualized
despite significant endocrine abnormalities. Hypothalamic lesions can
also sometimes cause elevated prolactin levels due to decreased PIF
(dopamine) production, but the increase is not as high as is typically seen in
pituitary adenomas.
52
Growth hormone–secreting adenomas in adults cause
acromegaly, a slowly
progressive overgrowth of bones and soft tissues. Acromegaly is characterized
by enlarged hands and feet, coarsened facial features, and a protuberant
jaw.
53
Growth hormone excess in children beginning before epiphyseal
closure (adolescence) causes
gigantism. Other common problems in patients
with growth hormone excess include carpal tunnel syndrome, arthritis, infertility,
hypertension, and diabetes. Diagnosis is by typical clinical features,
elevated IGF-1, elevated GH levels of greater than 2 micrograms per liter
even after glucose administration, and MRI.
54
ACTH-secreting adenomas cause
Cushing’s disease. Cushing’s syndrome is
a general term for the clinical features of glucocorticoid excess of any cause,
inlcuding endogenous cortisol excess or exogenous administration of glucocorticoid
medications (such as prednisone, methylprednisolone, dexamethasone,
or hydrocortisone).
55
Cushing’s disease is an important cause of
Cushing’s
syndrome and means specifically that the syndrome is caused by an
ACTH-secreting pituitary adenoma. In Cushing’s syndrome there is a characteristic cushingoid appearance, with a round “moon-shaped” facies and
deposition of fat on the trunk more than the extremities, resulting in truncal
obesity. The body habitus of the cushingoid patient has therefore been described
as “spiderlike.”
56
Glucocorticoid excess can also cause
acne, hirsutism,
purplish skin striae, thin-appearing skin, easy bruising, poor wound healing,
hypertension, diabetes, edema, immunosuppression, osteoporosis, avascular
necrosis of the femoral head, amenorrhea, decreased libido, myopathy,
fatigue, and psychiatric disturbances including mania, psychosis, and depression.
57
Endogenous Cushing’s syndrome is caused
by primary adrenal
adenomas or adenocarcinomas in only about 15% of cases. The remaining
85% are caused by ACTH oversecretion by pituitary adenomas (70%) or by
nonpituitary tumors that secrete ACTH, such as bronchial carcinoma (15%),
referred to as “ectopic” ACTH production.
58
A series of endocrinological tests is done to localize the cause of endogenous
cortisol excess. Very low ACTH levels usually suggest an adrenal
source, since adrenal cortisol excess will cause feedback reduction of ACTH
production. If an ACTH producing tumor is suspected, the
dexamethasone suppression test can be useful. This test works on the principle
that administration of a dose of dexamethasone at midnight normally
acts through negative feedback, like cortisol to suppress
cortisol levels or urine cortisol metabolites measured the next morning. A
low-dose (1 to 3 milligram) overnight dexamethasone suppression test is
often used as an initial screening test for excess cortisol production. If cortisol
production is not suppressed with the low-dose test, the high-dose (8
milligram) dexamethasone suppression test is then helpful because ACTHsecreting
pituitary tumors are usually suppressible with this dose, while ectopic
ACTH-secreting tumors and adrenal tumors are not.
59
Another strategy
| is to administer
CRH, which causes an excessive
rise in plasma ACTH and cortisol in pituitary adenomas but not in ectopic
ACTH or adrenal tumors. MRI is useful in diagnosis as well. Finally, when
results of these tests are equivocal, petrosal sinus sampling can be helpful to
distinguish pituitary from nonpituitary ACTH overproduction. In addition,
petrosal sinus sampling can often correctly localize the side of a microadenoma
not visible on MRI. In this way, selective surgery on the side of the microadenoma
may be possible while function of the remaining pituitary
gland is spared.
60
In petrosal sinus sampling, catheters are
inserted through the femoral
veins and passed upward under radiological guidance through the internal
jugular veins to reach the inferior petrosal sinuses on both sides
61
Aliquots are first removed to determine baseline ACTH levels. In
ACTH-secreting pituitary adenomas, ACTH levels in at least one petrosal
sinus should be more than two times the ACTH levels in a peripheral vein.
An intravenous dose of CRH is then given, and ACTH
measurements from each inferior petrosal sinus are taken approximately
every 5 minutes. A threefold increase in ACTH is diagnostic of a pituitary
adenoma. In addition, the ACTH rise is usually 2 to 20 times higher on the
side of the tumor than on the contralateral side.
62
TSH-secreting adenomas are a rare cause of hyperthyroidism. Hyperthyroidism
is much more commonly caused by primary thyroid disorders such
as Graves’ disease, thyroiditis, toxic multinodular goiter, and thyroid adenomas.
Clinical manifestations of hyperthyroidism include
nervousness, insomnia,
weight loss, tremor, excessive sweating, heat sensitivity, increased
sympathetic output, and frequent bowel movements. Note that thyroid ophthalmopathy
can occur in Grave’s disease but not in TSH-secreting adenomas.
63
Graves’ disease is characterized by
inflammatory involvement of the thyroid gland, skin, and orbital tissues leading to proptosis, and, ultimately,
extraocular muscle fibrosis. Other important neurologic manifestations of
hyperthyroidism include proximal muscle weakness, tremor, dyskinesias,
and dementia. Particularly in the elderly, many of the other clinical manifestations
of hyperthyroidism may be absent, and hyperthyroidism can mimic
dementia or depression. In hyperthyroidism caused by primary
thyroid disorders, TSH levels are completely suppressed, while in
TSH-secreting pituitary adenomas, TSH levels may be elevated.
64
Hypothyroidism is also usually caused by
primary thyroid disorders such
as autoimmune thyroid disease, iodine deficiency, or previous ablative treatment
for hyperthyroidism and rarely is caused by pituitary or hypothalamic
insufficiency. However, when lesions of the hypothalamus or pituitary are
present, including medium-to-large pituitary adenomas of any type, it is relatively
common for TSH production to be impaired, resulting in hypothyroidism.
65
Manifestations of hypothyroidism of any cause include
lethargy,
weight gain, cold intolerance, smooth, dry skin, hair loss, depression, and
constipation. Eventually, myxedema coma and cardiac involvement can
occur. Other important neurologic manifestations include neuropathy, carpal
tunnel syndrome, myalgias, ataxia, and dementia. Like hyperthyroidism,
hypothyroidism can present in the elderly with a dementia-like or depression-
like picture. Untreated hypothyroidism in utero or in infancy can cause
cretinism, which is characterized by mental retardation, short stature, microcephaly,
and other abnormalities.
66
LH- or FSH-secreting adenomas often cause
infertility, although tumors can
reach a relatively large size before being detected clinically. Interestingly,
these tumors may produce either high or low testosterone and estradiol levels.
Because LH- or FSH-secreting tumors are often large, patients may present
with headache and visual changes as the major manifestations.
67
Other lesions can also occur in the sellar and suprasellar region, causing
endocrine disturbances or compressing the optic chiasm. Although pituitary
adenoma is the most common, other lesions seen in this region include
craniopharyngioma,
aneurysms, meningioma, optic glioma, hypothalamic
glioma, chordoma, teratoma, epidermoid, dermoid, Rathke’s pouch cysts,
empty sella syndrome, sarcoidosis, lymphocytic hypophysitis, Langerhans
cell histiocytosis, lymphoma, and metastases.
68
Finally, it should be noted that up to 10% of patients who undergo MRI
scans for any reason may have pituitary incidentalomas, meaning endocrinologically
inert and clinically benign tumors of the pituitary that are discovered
as “incidental findings” on MRI scans. The majority pituitary incidentalomas
are small and are
generally addressed by basic clinical evaluation, endocrine
| hormone measurements when indicated, and periodic follow-up.
69
Diabetes insipidus (DI) is the production of
large amounts of dilute urine.
This condition can be caused by deficiency of ADH (central or neurogenic DI)
or by insensitivity of the kidneys to ADH (nephrogenic DI).
70
Symptoms of DI
| include
severe thirst, polyuria, and polydipsia. Patients who are able to
drink consume large amounts of water to maintain fluid balance. Patients
who cannot drink adequately become dehydrated rapidly and die if not
treated.
71
The diagnosis of DI is established if a patient with polyuria has
relatively
low urine osmolality despite increased plasma osmolality. To detect
this condition, sometimes the patient must be asked to temporarily stop drinking while in a supervised setting.
72
A dose of subcutaneous vasopressin
| will cause urine osmolality to rise in
neurogenic but not in nephrogenic DI.
73
Common causes of neurogenic DI include
neurosurgery, head trauma, and
infiltrative or neoplastic lesions in the pituitary–hypothalamic region or in the third ventricle. Interestingly, lesions of the posterior pituitary
do not cause DI unless the lesion is high enough in the pituitary stalk
to result in retrograde degeneration of hypothalamic neurons in the
supraoptic and paraventricular nuclei. This suggests that
neurons in these nuclei are capable of releasing vasopressin in locations
other than the posterior pituitary. Treatment of DI is with subcutaneous or
intranasal administration of synthetic vasopressin analogs
74
In the syndrome of inappropriate antidiuretic hormone (SIADH)
excess
ADH production causes a low serum sodium (hyponatremia), together with
inappropriately elevated urine osmolality. Note that hyponatremia with elevated
urine osmolality is not always caused by SIADH, and it can also be
seen in hypovolemia or in edematous states such as heart failure or cirrhosis.
75
SIADH can be caused by many neurologic and non-neurologic conditions,
including
head trauma, meningitis, and numerous other neurologic disorders,
pulmonary disorders, medication side effects, and ADH-secreting neoplasms.
76
Severe hyponatremia can cause
lethargy, coma, or seizures
77
When
| SIADH is the cause of hyponatremia, it should be treated by
restriction of
daily fluid intake. Treatment can also include vaprisol, which acts as vasopressin
blocker. In severe cases, infusions of hypertonic saline are sometimes
used, but care must be taken not to correct hyponatremia too rapidly because
central pontine myelinolysis can result from this approach.
78
Some conditions can cause the consecutive appearance of SIADH and DI
in a single patient. For example, following surgery in the pituitary region
there is occasionally a triphasic response, with DI shortly after surgery, followed
by SIADH, and finally DI again, which may then gradually improve.
Patients with other intracranial disorders, such as
catastrophic hemorrhage
or infarct, may initially have SIADH. If brain death then ensues, all ADH
production ceases, resulting in DI
79
Deficiency of multiple pituitary hormones can occur in several conditions of
the pituitary and hypothalamic regions. When all pituitary hormones are involved,
the condition is
called panhypopituitarism.
80
ACTH deficiency causes
hypocortisolism, with fatigue, weakness, decreased appetite, and impaired
response to stress resulting in hypotension, fever, hypoglycemia, and a high
mortality rate
81
TSH deficiency causes hypothyroidism, and
ADH deficiency causes diabetes insipidus. LH and FSH deficiencies
cause hypogonadism, including decreased libido, amenorrhea, and infertility.
GH deficiency in children causes abnormally short stature. Prolactin
deficiency in women causes
inability to lactate, and oxytocin deficiency can
| cause impaired milk letdown.
82
There are multiple possible causes of panhypopituitarism, however, primary
pituitary tumors and their treatment are the most common. Other lesions
in this region include
large, nonfunctioning pituitary
adenomas, meningioma, craniopharyngioma, hypothalamic tumors, metastases,
and other infiltrative processes, including sarcoidosis, lymphocytic hypophysitis,
infections, and autoimmune disorders. On rare occasions, pituitary
tumors can undergo spontaneous hemorrhage, resulting in pituitary apoplexy
83
Patients with pituitary apoplexy often present with
sudden
headache, meningeal signs, unilateral or bilateral cavernous sinus syndrome
(see KCC 13.7), visual loss, hypotension, and depressed level of consciousness.
Panhypopituitarism is a common sequela of pituitary apoplexy.
84
Other
| causes of panhypopituitarism include
head trauma, surgery, radiation therapy,
pituitary infarct, postpartum pituitary necrosis (Sheehan’s syndrome),
and congenital abnormalities.
85
Panhypopituitarism is treated by
exogenous replacement of pituitary hormones.
ACTH insufficiency is treated by daily administration of steroids
such as prednisone or hydrocortisone, with increased doses given in situations
of stress such as infection or surgery.
86
Diabetes insipidus is treated with
synthetic ADH analogs, and hypothyroidism is treated with synthetic thyroid
hormones. Hypogonadism is treated with testosterone or estrogen–progesterone
combinations, and fertility can sometimes be achieved with LH and
FSH substitution therapy. GH replacement is used in children to improve
growth and in adults because of beneficial effects on lipid profile and on
other systems
