Download Neuroanatomy Ch 17 792-805 [4-20

Neuroanatomy Ch 17 792-805
Pituitary and Hypothalamus
-pituitary and hypothalamus form link between neural and endocrine systems, and
hypothalamus is regulator of homeostasis through controlling: hunger, thirst, sexual desire,
endocrine control, autonomic control, and limbic mechanisms
Anatomy of Pituitary and Hypothalamus –
-anterior pituitary (adenohypophysis) formed by ectoderm on roof of developing pharynx that
forms Rathke’s pouch
-secretes hormones controlled by hypothalamus through vascular portal system
-posterior pituitary (neurohypophysis) forms from floor of developing ventricular system and
contains axons whose cell bodies are located in hypothalamus: secrete oxytocin and vasopressin
-Hypothalamus – part of diencephalon and lies under the thalamus; forms walls and floor of
third ventricle; separated from thalamus by the hypothalamic sulcus
-Tuber Cinereum – bulge between optic chiasm and mammillary bodies, which are
paired structures that form posterior portion of hypothalamus
-Infundibulum – means funnel, arises from tuber cinereum; connects as pituitary stalk
-anterior portion of infundibulum is raised, called median eminence - where
hypothalamus releases regulating factors carried by portal vessels to pituitary
-pituitary lies inside the pituitary fossa bounded by the anterior and posterior clinoid process
which form the sphenoid bone, forming the sella turcica
-sphenoid sinus is underneath sella turcica, allowing it to be accessed surgically
-pituitary covered by dura, called diaphragma sella (superior portion of pituitary fossa)
-pituitary stalk communicates with cranial cavity through the diaphragma sella
-pituitary fossa bounded laterall by the cavernous sinus
-tumors in the area can compress optic chiasm to cause bitemporal hemianopia
Important Hypothalamic Nuclei – hypothalamus is divided into 4 major regions from antpost
and 3 areas from medial  lateral
-most medially is periventricular nucleus, closest to 3rd ventricle, fibers of fornix pass through
hypothalamus to mammillary body, dividing hypothalamus into medial hypothalamic area and a
lateral hypothalamic area
-lateral hypothalamic area consists of lateral hypothalamic nucleus, and through the
area runs the medial forebrain bundle (MFB), a diffuse group of fibers
-MEDIAL forebrain runs through the LATERAL hypothalamus
-medial hypothalamic area has several nuclei that divide into 4 regions from anterior to
posterior; from most anterior back, you have
1. Preoptic area derived from telencephalon (hypothalamus from diencephalon)
2. lateral preoptic nucleus and medial preoptic nucleus are rostral continuations of
lateral and medial hypothalamic areas
3. anterior hypothalamic region (supraoptic region) contains:
-anterior hypothalamic nucleus, supraoptic nucleus, paraventricular nucleus,
and suprachiasmatic nucleus
-supraoptic and paraventricular nuclei contain oxytocin or vasopressin
-suprachiasmatic nucleus is master clock for circadian rhythms by
receiving inputs from retinal ganglion cells containing melanopsin
4. middle hypothalamic region (tuberal) – has arcuate nucleus, ventromedial nucleus,
and dorsomedial nucleus
-arcuate nucleus projects to median eminence to control anterior pituitary
5. posterior hypothalamic region (mammillary) – medial mammillary nucleus,
intermediate mammillary nucleus, lateral mammillary nucleus and posterior
hypothalamic nucleus
Hypothalamic Control of Autonomic Nervous System – hypothalamus projects into both
sympathetic and parasympathetic divisions
-fibers originate from paraventricular nucleus as well as dorsomedial nucleus and from
lateral/posterior hypothalamus
-fibers travel in medial forebrain bundle  dorsolateral brainstem  synapse on preganglionic
parasympathetic nuclei in brainstem and intermediate zone of sacral spinal cord, and onto
preganglionic sympathetic neurons in intermediolateral cell column of thoracolumbar spine
-important source of inputs to hypothalamus is from amygdala and limbic cortex
Hypothalamic-Limbic Pathways – subiculum of hippocampal formation (limbic structure)
projects to mammillary bodies of hypothalamus via the fornix
-mammillary bodies project via mammillothalamic tract  anterior thalamic nucleus,
which projects  limbic cortex in cingulate gyrus
-amygdala has reciprocal connections to hypothalamus through two pathways:
1. stria terminalis and 2. Ventral amygdalofugal pathway
-all of these pathways are important mechanisms for emotional influences on autonomic
pathways (stomach churns when anxious, sweaty palms) and on homeostatic pathways such as
immune system
-hypothalamic hamartoma – benign tumor that causes unusual seizures consisting of laughing
episodes beginning in early childhood, associated with irritability and aggression with cognitive
impairment; some hypothalamic hamartomas secrete gonadotropin releasing hormone
Other regionalized functions of hypothalamus – regulates variet of appetitive, homeostatic and
other behaviors
-suprachiasmatic nucleus in anterior hypothalamus regulates circadian rhythms
-GABAergic neurons in the ventral lateral preoptic area (VLPO) contribute to nonREM
sleep by inhibiting arousal systems such as histaminergic neurons in tuberomammillary
nucleus (TMN) and orexin-containing neurons in the posterior lateral hypothalamus, as
well as brainstem serotonergic noradrenergic, dopaminergic, and cholinergic nuclei
**LESIONS of ANTERIOR HYPOTHALAMUS (including VLOP) – cause Insomnia**
**Lesions of POSTERIOR HYPOTHALAMUS, which destroys histaminergic neurons in
TMN and orexin-containing neurons causes HYPERSOMNIA**
-the Lateral Hypothalamus is important in appetite, and lesions here would cause DECREASE IN
BODY WEIGHT
-the Medial Hypothalamus, especially in the ventromedial nucleus, inhibits appetite, and
LESIONS here can cause OBESITY
-leptin – hormone produced by adipose, binds to Ob receptors on hypothalamus and plays role
in feedback regulation of food intake, INHIBITS APPETITE and obesity
-ghrelin – produced by gastric mucosal cells binds hypothalamus; STIMULATES appetite
-thirst – results from activation of osmoreceptors in anterior regions of hypothalamus,
stimulated by hypovolemia or elevated body temperatures. **LESIONS of LATERAL
HYPOTHALAMUS DECREASE WATER INTAKE**
-thermoregulation involves sweat production, smooth muscle affecting core and surface blood
flow, skeletal muscles involved in shivering, and endocrine systems
-anterior hypothalamus detects increased body temperature and activates mechanisms
of heat dissipation **lesions in ANTERIOR HYPOTHALAMIC region causes hyperthermia
-posterior hypothalamus functions to conserve heat, and bilateral lesions of the
posterior hypothalamus causes poikilothermia, where body temp varies with
environment because lesions destroy both heat conserving mechanisms of post
hypothalamus and descending pathways for heat dissipation form ant hypothalamus
Endocrine Functions of Pituitary and Hypothalamus –
-anterior pituitary produces 6 hormones: ACTH, GH, prolactin, TSH, LH, and FSH
-intermediate lobe is rudimentary and produces pro-opiomelanocortin (POMC) and melanocyte
stimulating hormone (MSH)
-posterior pituitary produces oxytocin and vasopressin (ADH)
-release of anterior pituitary hormones is controlled by neurons in hypothalamus through
hypophysial portal system
-pituitary receives arterial blood from inferior/superior hypophysial arteries which are
branches of internal carotid artery
-first capillary plexus of portal system occurs in the median eminence
-neurons adjacent to 3rd ventricle project to median eminence, secreting inhibitory and releasing
factors; nuclei are: arcuate nucleus, periventricular nucleus, medial preoptic nucleus, and
paraventricular nucleus
-carried by hypophysial portal veins to anterior pituitary; most are peptides except for
prolactin release-inhibiting factor (PIF)
-hormones released in the ant pituitary are picked up by capillary plexus of portal system and
carried to cavernous sinus
-posterior pituitary also has capillary plexus that picks up oxytocin and vasopressin and carries
them into circulation
-cell bodies secreting oxytoxin/vasopressin are located in supraoptic and
paraventricular nuclei, and each cell is specific to only one hormone
-ACTH – stimulates adrenal cortex to produce corticosteroids like cortisol and aldosterone
-maintain blood pressure, control electrolyte balance, promote glucose mobilization
-adrenal medulla, under control of preganglionic sympathetic neurons, releases epinephrine
and norepinephrine
-TSH stimulates thyroid to produce thyroxine/triiodothyronine to promote metabolism
-Growth hormone – causes liver/kidneys to produce somatomedins (IGFs) to promote growth
of long bones and itissues
-Prolactin – causes mammillary bodies to produce milk
-LH and FSH regulate ovarian hormones responsible for menstrual cycle/oogenesis in females
and testicular hormones and spermatogenesis in males
-Oxytocin – causes contractions of smooth muscle in breast for milk letdown and contractions of
uterus during labor
-Vasopressin (ADH) – osmotic regulation by promoting H2O retention by kidneys to concentrate
urine
-hormones in hypothalamic-pituitary axis – is regulated by feedback loops such as CRH release
by hypothalamus and release of ACTH by ant pituitary both receive negative feedback from
circulating cortisol
Pituitary Adenoma and Related Disorders – pituitary adenoma is slow growing benign tumor
arising from glandular epithelial cells of anterior pituitary; 12% of all cranial neoplasms, and can
arise from any of the endocrine cell types, and 85% secrete one or more pituitary hormones
-hormone secretion is often in excess of normal levels and NOT under hypothalamic control
-even small microadenomas (<1mm) can cause endocrine abnormalities
-non-functioning adenomas often grow large before causing symptoms, and large tumors can
compress the optic chiasm which can cause bitemporal hemianopia – can eventually cause
hydrocephalus and brainstem compression
-prolactin is most commonly secreted hormone in pituitary adenomas (50%), next common is
GH, followed by ACTH, TSH, LH, and FSH; non-functioning tumors are 15% of adenomas
Treatment Options – medication, surgery, radiotherapy
-prolactin-secreting tumors show response to dopaminergic agonists bromocriptine or
cabergoline which inhibit prolactin release and shrink tumors
-GH-secreting hormones are treated with octreotide to inhibit release of GH + shrink tumor
-surgery takes a transsphenoidal approach where pituitary fossa is entered through the roof of
sphenoid sinus through the nose
-suprasellar tumors require intracranial approach, maybe with endoscopic neurosurgery
Clinical Presentation/Diagnosis of Hormone Secreting Tumors:
1. Prolactin-secreting adenomas – cause amenorrhea in women, hypogonadism in men,
galactorrhea, infertility, hair loss, decreased libido, weight gain
a. Mediated by inhibition of hypothalamic LHRH which leads to decreased LH and
FSH levels
b. Effect of prolactin on normal women’s LH/FSH delays menses during lactation
c. High levels (>150ug/L) is diagnostic of pituitary adenoma
2. Growth hormone-secreting adenomas – causes acromegaly in adults, slow/progressive
overgrowth of bones and soft tissues
a. Characterized by enlarged hands/feet, coarsened facial features, and
protuberant jaw
b. In children, before epiphyseal closure, causes gigantism
c. Carpal tunnel, arthritis, infertility, hypertension, and diabetes present
3. ACTH-secreting adenomas – cause Cushing’s disease – another word for glucocorticoid
excess of any kind, including endogenous cortisol or exogenous administration of
glucocorticoid medication
a. In Cushing’s Syndrome, there is a characteristic cushingoid appearance, with
round, moon-shaped facies and deposition of fat on trunk more than
extremities; body described as “spider-like”
b. Glucocorticoid excess can cause acne, hirsutism, skin striae, thin-appearing skin,
brusing, poor wound healing, hypertension, diabetes, edema,
immunosuppression,
i. Endogenous Cushing’s syndrome caused by primary adrenal adenomas
or adenocarcinomas in 15% of cases; remaining 85% caused by ACTH
oversecretion by pituitary adenomas or by nonpituitary tumors
secreting ACTH, such as bronchial carcinoma
c. Low ACTH levels suggest adrenal source since adrenal cortisol will cause
feedback reduction of ACTH production
d. Dexamethasone suppression test is used if ACTH producing tumor is suspected;
give dexamethasone at midnight which normally acts through negative
feedback like cortisol to suppress cortisol levels in the morning
e. Administering CRH causes a rise in ACTH and cortisol in pituitary adenomas but
not ectopic ACTH or adrenal tumors
f. Petrosal sinus sampling can help determine pituitary from nonpituitary ACTH
overproduction
4. TSH-secreting adenomas – rare cause of hyperthyroidism, which is more commonly
caused by primary thyroid disorders like graves disease, thyroiditis, toxic multinodular
goiter,
a. Clinical manifestations include nervousness, insomnia, weight loss, tremor,
sweating, heat sensitivity, increased sympathetic output, bowel movements
b. Graves disease is characterized by inflammatory involvement of thyroid gland,
skin, and orbital tissues leading to extraocular muscle fibrosis
c. Muscle weakness, tremor, dyskinesias, and dementia
d. In hyperthyroidism via primary thyroid disorders, TSH levels are suppressed,
while TSH secreting pituitary adenomas cause TSH levels to be elevated
5. Hypothyroidism – usually caused by primary thyroid disorders such as autoimmune
thyroid disease, iodine deficiency, or surgical removal
a. Lesions of hypothalamus/pituitary including adenomas, it is common for TSH
production to be impaired to cause hypothyroidism
b. Weight gain, lethargy, cold intolerance, dry skin, hair loss, constipation, and
myxedema coma can occur
c. In utero, can cause cretinism characterized by mental retardation, microcephaly
6. LH/FSH secreting adenomas – often cause infertility although large tumors will occur
before being detected
a. In sellar and suprasellar region, adenomas can compress optic chiasm or cause
endocrine disturbances; other lesions in this area include craniopharyngioma,
aneurysms, meningioma, optic glioma, hypothalamic glioma, chordoma,
teratoma, cysts, and metastases
-10% of all patients undergoing MRI scans may have pituitary incidentalomas, which are inert,
benign tumors of pituitary discovered as incidental findings
Diabetes Insipidus – diabetes insipidus (DI) is production of large amounts of dilute urine, and
can be caused by deficiency of antidiuretic hormone (ADH, causing central or neurogenic DI), or
by insensitivity of kidneys to ADH (nephrogenic DI)
-symptoms include thirst, polyuria, polydipsia; patients consume large amounts of water, and
those that do not drink, die if not treated
-diagnosed when patient with polyuria has low urine osmolality and increased plasma osmolality
-exogenous vasopressin will cause urine osmolality to rise in neurogenic DI but not nephrogenic
-lesions of posterior pituitary do NOT usually cause DI unless lesion is high enough in pituitary
stalk to result in retrograde degeneration of hypothalamic neurons in supraoptic or
paraventricular nuclei
-neurons in these nuclei can release vasopressin in areas other than posterior pituitary
Syndrome of inappropriate antidiuretic hormone (SIADH) – excess ADH causes low Na
(hyponatremia) together with elevated urine osmolality
-SIADH can be caused by head trauma, meningitis, other neuro, pulmonary conditions, and ADHsecreting neoplasms
-when SIADH is cause of hyponatremia, should be treated by restriction of daily fluid intake or
administration of vaprisol (vasopressin blocker)
-Central pontine myelinosis can result from too quick hypertonic saline administration
-following surgery, sometimes both DI and SIADH may occur
Panhypopituitarism – when all pituitary hormones are deficient, it is called panhypopituitarism;
-ACTH deficiency causes hypocortisolism; fatigue, weakness, decreased appetite, impaired stress
response resulting in hypotension, fever, hypoglycemia
-TSH deficiency causes hypothyroidism
-ADH deficiency causes diabetes insipidus
-LH/FSH cause hypogonadism, decreased libido, amenorrhea, infertility
-GH deficiency in children causes abnormal short stature
-Prolactin deficiency causes inability to lactate
-Oxytocin deficiency causes impaired milk letdown
-primary pituitary tumors and treatment are the most common causes of panhypopituitarism,
with other tumors as possibilities
-if pituitary tumors undergo spontaneous hemorrhage, it results in pituitary apoplexy, and often
present with sudden headache, meningeal signs, unilateral or bilateral cavernous sinus
syndrome, visual loss, hypotension, and depressed consciousness
-treated by exogenous replacement of pituitary hormones