10/5- Disease of the Hypothalamus and Posterior Pituitary Flashcards
Basics of hypothalamic-pituitary circuit?
Hypothalamus stimulates pituitary, which stimulates endocrine glands to secrete substances to work on distal target organs
- Endocrine glands have negative inhibition back to pituitary and hypothalamus
Important!
Know this
What does GH stimulate downstream?
IGF-1
What hormones are secreted by the anterior pituitary?
- GH
- TSH
- PRL
- LH, FSH
- ACTH
What hormones are inhibited by SS?
- GH
- TSH
What promotes/inhibits prolactin secretion?
Promotes: TRH
Inhibits: DA
What hormones are promoted by TRH?
- TSH
- PRL
Where is the hypothalamus in the brain?
Forms the floor of the 3rd ventricle
Where is the pituitary?
Housed in the base of the skull in the sphenoid bone “sella turcica”
Describe the development/embryological origin of the:
- Hypothalamus
- Posterior pituitary
- Anterior pituitary
- Intermediate lob or “pars intermedia”
Hypothalamus
- derived from the diencephalon (part of the forebrain)
- forms the floor of the third ventricle
Posterior pituitary or ”neurohypophysis”
- arises as an evagination of the ventral hypothalamus and third ventricle
Anterior pituitary or “adenohypophysis” or “pars anterior”
- develops from an evagination of ectoderm from the oropharynx called Rathke’s pouch
Intermediate lobe or “pars intermedia”
- cells eventually integrate into the anterior pituitary in humans
Describe the neurohypophysis of the HT and posterior pituitary
- Neurons organized as paraventricular and supraoptic “nuclei” in the hypothalamus
- Axons travel down stalk to the posterior pituitary
Describe the vascular connection of the hypothalamic-pituitary axis
Rich vascularization (0.8 ml/g/min)
Internal carotid arteries
- Superior hypophyseal artery
- capillary network in hypothalamus
- forms portal veins draining to the anterior pituitary
- second capillary network in anterior pituitary
- Middle and inferior hypophyseal arteries
- posterior pituitary
- pituitary stalk (infundibulum)
Venous channels:
- Cavernous sinus
- Petrosal sinuses
- Jugular vein
What are some input signals received by the hypothalamus?
- Light (circadian rhythms)
- Olfactory
- Neural stimuli
- autonomic
- Molecular stimuli: cytokines, hormones, adipokines and GI peptides, glucose, osmoles
How do the input molecules get through the BBB to the hypothalamus?
- Fenestrated capillaries
- Circumventricular organs
The hypothalamus integrates the signals and sends outgoing messages (neural and hormonal) to regulate what?
- Appetite
- Circadian rhythms (sleep-wake cycles)
- Energy expenditure
- Temperature (fever)
- Endocrine systems (pituitary)
- Sodium and water balance
- Glucose disposal
Describe the basics in the hypothalamic regulation of appetite?
- Leptin (produced by fat cells) stimulates arcuate nucleus, and medial hypothalamus to promote satiety (anorexigenic)
- Ghrelin (produced by stomach) stimulates lateral hypothalamus (feeding center) to promote hunger (orexigenic)
If almost everyone has leptin, why is there an obesity epidemic?
The fatter we get, the more resistant our hypothalamus is to the signal to stop eating
What is the acronym for coming up with a thorough differential diagnosis?
VINDICATE
V- vascular
I- infection/infiltrative/immune
N- neoplastic
D- drugs
I- idiopathic/iatrogenic
C- congenital
A- autoimmune
T- trauma/surgery
E- endocrine & metabolism/electrolytes
What cranial nerves lie in the cavernous sinus that may be impinged upon by large masses in the pituitary (or hypothalamus?)
CNs 3, 4, V1, V2
Dysregulation of hypothalamic function can cause what diseases in relation to its normal functions:
- Appetite
- Energy expenditure
- Circadian rhythms
- Temperature
- Endocrine systems
- Sodium/water balance
- Limbic system
- Appetite: hypothalamic obesity/anorexia
- Energy expenditure
- Circadian rhythms: disturbed sleep-wake signals
- Temperature: fever/hypothermia
- Endocrine systems: panhypopituitarism
- Sodium/water balance: diabetes isnpidus
- Limbic system: emotional liability, apathy, memory loss
Dysfunctional levels of anterior pituitary hormones include what?
- Decreases in: GH, TSH, LH/FSH, ACTH
- Increases in prolactin
What are the posterior pituitary hormones?
- Anti-diuretic hormone (ADH or vasopressin)
- Oxytocin
What is Kallmann’s syndrome?
Isolated hypogonadotropic hypogonadism with anosmia (decreased sense of smell)
- X-linked KAL gene mutation (adhesion molecule) causes abnormal migration of GnRH and olfactory neurons during development
- Hypoplasia of the olfactory lobes
- No GnRH pulsatile secretion; no gonadotropins (LH/FSH)
What is hypothalamic amenorrhea?
Disordered GnRH pulsatility
- Decreased LH surge during menstrual cycle
- Lack of follicle development and anovulation
- Decreased estrogen production (loss of bone mass)
- ?Leptin