Endocrine Flashcards
examples of lipid-soluble hormones
- steroids
- thyroid hormones
examples of water-soluble hormones
- peptides
- proteins
Lipid-soluble Hormones
- receptor location
- intracellular action
- storage
- plasma transport
- half-life
- inside the cell (usually nucleus)
- stimulated synthesis of specific new proteins
- synthesized as needed (exception = thyroid hormones)
- attached to proteins (made by liver) that serve as carriers for plasma transport (exception: adrenal androgens)
- ex) cortisol-binding globulin; thyroid-binding globulin; sex hormone-binding globulin (SHBG)
- the lipid-soluble hormone circulating in plasma (bound to protein) is in equilibrium with a small amount of free hormone (total hormone = bound + free)
- it is the FREE hormone that is available to tissues and normally determines the plasma activity
- half-life: long (hours/days); proportional to the affinity for the protein carrier
Water-soluble Hormones
- receptor location
- intracellular action
- storage
- plasma transport
- half-life
- outer surface of cell membrane
- production of 2nd messangers (i.e. cAMP)
- 2nd messengers modify action of intracellular proteins )(enzymes)
- insulin does not utilize cAMP, instead activates membrane-bound tyrosine kinase
- stored in vesicles
- in some cases, pro hormone stored in vesicle along w an enzyme that splits off the active hormone, releasing inactive peptide
- dissolved in plamsa (free, unbound) for plasma transport
- short half-life (minutes); proportional to molecular weight
Effect of estrogen on the circulating levels of binding protein
- a rise in circulating estrogen causes the release of more binding protein by the liver
- which binds more free hormone
- the transient decrease in free hormone reduces negative feedback to the hormone-secreting tissue
- the increased secretion of free someone quickly returns the free plasma hormone to normal.
- this is why during pregnancy and other states w a rise in estrogen levels :
1. total plasma lipid-soluble hormone increases
2. free plasma hormone remains constant at a normal level; thus the individual does not show signs of hyperfunctionm
failure of glucose to suppress growth hormone is diagnostic for
acromegaly
failure of (low dose) dextromethasone to suppress cortisol is diagnostic for
hypercortisolism
TRH
= thyrotropin-releasing hormone
- water-soluble hormone
- released by the hypothalamus
1. targets thyrotrophs in pituitary - causes secretion of TSH
2. when TRH is elevated: - targets lactotrophs in pituitary
- causes secretion of Prolactin
CRH
= corticotropin-releasing hormone
- water-soluble hormone
- released by the hypothalamus
- targets corticotrophins in pituitary
- causes secretion of ACTH
GnRH
= Gonadotropin-releasing hormone
- water-soluble hormone
- released by the hypothalamus
- targets gonadotrophs in pituitary
- causes secretion of LH (high-frequency pulses), FSH (low-frequency pulses)
GHRH
= growth hormone-releasing hormone
- water-soluble hormone
- released by the hypothalamus
- targets somatotrophs in pituitary
- causes secretion of GH
- GHRH is the main controlling factor for GH secretion
PIF
= prolactin-inhibiting factor, aka dopamine
- water-soluble hormone
- released by the hypothalamus
- targets lactotrophs in pituitary
- INHIBITS secretion of Prolactin
Somatostatin
- released by the hypothalamus
- water-soluble hormone
- targets somatotrophs in pituitary
- INHIBITS secretion of GH
Characteristic sequential loss of function in hypopituitarism
- GH and gonadotropin, followed by
- TSH, then
- ACTH, and finally
- prolactin
- deficiencies in ACTH, TSH and prolactin are extremely rare. Usually a sign of panhypopituitarism
MCC of hypopituitarism
- head trauma, other causes include:
- mass effects of tumors
- inflammation
- vascular damage
isolated deficiency in gonadotropins
- Kallman syndrome
- tertiary defective GnRH synthesis
- decreased: LH, FSH, sex steroids
MC tumor affecting the hypothalamic-pituitary system in children
- craniopharyngioma
- pituitary adenomas are rare
Pituitary Adenomas
- MCC of hypothalamic-pituitary dysfunction
- microadenomas (less than 1cm in diameter): characterized by hormonal excess, no panhypopituitarism, treatable (i.e. ACTH causing Cushing’s Disease)
- Macroadenomas (more than 1cm in diameter): mass effect, larger tumors w suprasellar extension, associated with panhypopituitarism and visual loss
- hypogonadism = MCC manifestation
- uslally benign and can autonomously secrete hormone leading to hyperprolactinemia (60%), acromegaly (GH 20%) and Cushing disease (ACTH 10%)
- prolactinomas assoc w hypogonadism and galactorrhea
- MEN1 assoc
- Hypothalamic hormones affecting the pituitary are synthesized in the
- but are stored and released from
- ventromedial, arcuate and preoptic nuclei
2. the median eminence
Pulsatile system and the pulsatile release of GnRH…
prevents down regulation of gonadotroph receptors
- Ant Pit hormones are regulated primarily by ____
2. except ___
- hypothalamic releasing hormones
2. except prolactin, which is mainly under the influence of PIF (an inhibiting hormone)
Damage to the pituitary stalk causes a decrease in
- all ANT pituitary hormones
- except prolactin (which increases)
acromegaly is associated w excess secretion of
GH (20%)
Cushing syndrome is associated w excess secretion of
ACTH (10%)
MCC of anterior pituitary dysfunction
pituitary adenomas
- MC tumor of anterior pituitary
2. MC manifestation
- prolactinomas
2. hypogonadism
How do you evaluate hormonal hyperfunction
- a suppression test
- a stimulation test is used to evaluate hormonal hypofunction
lack of glandular stimulation causes
a reversible atrophy
overstimulation of a gland can cause
hypertrophy or hyperplasia
The posterior pituitary secretes
- Arginine vasopression (ADH) = major controller of H20 excretion and ECF volume (also controls osmolality)
- oxytocin
- both are peptide hormones
The hormonal release by the hypothalamic- anterior-pituitary system is
mostly pulsatile
- possible exception = thyroid system
Sheehan syndrome
- in pregnancy, pituitary is enlarged and thus more vulnerable to infection
- if delivery assoc w severe blood loss, the ensuing shock causes arteriolar spasm in the pituitary w subsequent ischemic necrosis
- failure to resume normal menstrual cycle after weaning = strong sign of potential pituitary damage
Cell bodies for the posterior pituitary located in the
suporaoptic nucleus and paraventricular nucleus of the hypothalamus
The osmoreceptor neurons in the hypothalamus are extremely sensitive and are able to maintain ECF osmolarity within a very narrow range.
- there is a resting of the osmostat downward in
- pregnancy, the menstrual cycle and w volume depletion*
* = osmoregulation 2ndary to volume regulation; return of circulating volume occurs even though osmolarity decreases
____ receptors are less sensitive than _____
Volume receptors are less sensitive than osmoreceptors
- a change of 10-15% in volume = required to produce a measurable change in ADH
_______ restrains the release of ADH
Cortisol and Thyroid Hormone
ADH is:
- synthesized in the
- released from the
- synthesized in the hypothalamus
2. stored and released from the posterior pituitary
Major action of ADH
= passive reabsorption of water and urea (but not electrolytes) in the renal collecting duct
osmoreceptors
= very sensitive and normally maintain osmolarity in a very narrow range
Reduced input from the low-pressure stretch receptors is a strong stimulus for
the release of ADH
ADH levels in:
- Central DI
- nephrogenic DI
- Central = low plasma ADH
- nephrogenic = high plasma ADH
- easily separated by measuring plasma ADH or injection of desmopressin
- D/D following water deprivation
SIADH
- inappropriate elevated secretion of ADH
- characterized by euvolemia and hyponatremia*
- acute hyponatremia = life threatening if severe; treat aggressively
Acute hyponatremia vs Chronic hyponatremia
- acute hyponatremia = life threatening if severe; treat aggressively
- Chronic hyponatremia: usually well-tolerated.
- Aggressive treatment is assoc w central pontine myelinosis
Permeability of collecting ducts to H2O in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
Permeability of collecting ducts to H2O in:
- DI: decreases
- Dehydration: increases
- SIADH: increases
- Primary Polydipsia: decreases
Urine Flow in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
Urine Flow in:
- DI: increases
- Dehydration: decreases
- SIADH: decreases
- Primary Polydipsia: increases
Urine osmolarity in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
Urine osmolarity in:
- DI: decreases
- Dehydration: increases
- SIADH: increases
- Primary Polydipsia: decreases
ECF volume in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
ECF volume in:
- DI: decreased
- Dehydration: decreased
- SIADH: increased
- Primary Polydipsia: increased
ECF osmolarity* (Na concentration) in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
ECF osmolarity* (Na concentration) in:
- DI: increased
- Dehydration: increased
- SIADH: decreased
- Primary Polydipsia: decreased
ICF volume in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
ICF volume in:
- DI: decreased
- Dehydration: decreased
- SIADH: increased
- Primary Polydipsia: increased
ICF osmolarity in:
- DI
- Dehydration
- SIADH
- Primary Polydipsia
ICF osmolarity in:
- DI: increased
- Dehydration: increased
- SIADH: decreased
- Primary Polydipsia: decreased
hypervolemia cause
- caused by marked reduction in water retention and/or increased rate of water ingestion
- ie CHF, cirrhosis
hypovolemia
- indicates sodium depletion
- ie mineralcorticoid deficiency,
- diuretic abuse
- renal disease
- diarrhea
- hemorrhage
clinical euvolemia
ie SIADH
- clinically equivalent presentation may occur in glucocorticoid deficiency
Hyponatremia
- one of the MC disorders of fluid and electrolyte balance in hospitalized pts
1. involves?
- usually = to a hypo-osmolar state (exception = hyperglycemia)
- involves both solute depletion and water retention
- but water retention is usually the more important factor
2. Solute depletion can occur from any significant loss of ECF fluid - the hyponatremia = result of replacement by more hypotonic fluids
- when develops rapidly (less than 48h) and is severe (Na less than 120) pt is at risk for seizures and respiratory arrest
- often treated aggressively with hypertonic saline and diuretics or ADH antagonists
Rapidly developing Hyponatremia (develops in less than 48h) that is severe (Na less than 120)
- pt is at risk for seizures and respiratory arrest
- often treated aggressively with hypertonic saline and diuretics or ADH antagonists
- aggressive treatment may result in Central Pontine Myelinolysis
- General recommendation: slowly raise [Na] over a period of days
- (more slowly developing hyponatremia appears to be well-tolerated and pt is asymptomatic)
SIADH treatment
- fluid restriction but not salt restriction
- Na+ disorders cause neurological symptoms
- only mild hyponatremia from SIADH can be managed w fluid restriction
- severe disease needs 3% hypertonic saline or V2 receptor antagonists
- Conivaptan and tolvaptan are V2 receptor antagonists
- they stop ADH effect on kidney tubule
circulating levels of brain natriuretic peptide (BNP) correlated well w
- the degree of heart failure
- although very little BNP is synthesized and released in the normal heart, there is a marked elevation as the ventricle dilates (hence the correlation)
Synthesis and release of ADH
- synthesized in the supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus
- it is stored and released from the posterior pituitary
- osmoreceptors synapse w neurons of the SO and PVN and stimulate them to secrete ADH from the posterior pituitary.
- also stimulate consumption of H20 through the hypothalamic centers that regulate thirst
- the SO and PVN also receive input from cardiopulmonary mechanoreceptors as well as arterial baroreceptors.
- high blood volume or BP tends to inhibit the secretion of ADH
Secretion of ADH is most sensitive to
- plasma osmolarity (1%), however,
- if blood volume decreases by 10% (i.e. hemorrhage)
- or CO falls,
- high levels of ADH are secreted (even if it causes abnormal plasma osmolarity)
Osmoreceptors
- neurons that respond to increased plasma osmolarity (principally increased [Na+]
- synapse w neurons of the SO and PVN and stimulate them to secrete ADH from the posterior pituitary.
- also stimulate consumption of H20 through the hypothalamic centers that regulate thirst
Ex of V2 receptor antagonists
- Conivaptan and tolvaptan
- used to treat SIADH
Action of ADH
- main target tissue = renal collecting duct (V2 receptors)
- ADH increases the permeability of the duct to water by placing water channels in the luminal membrane
- H20 reabsorbed passively, drawn across the membranes by the higher osmolarity of the interstitium
- urea can pass with the water, but electrolytes cannot
- ADH stimulates the urea transporter, increasing urea reabsorption
- in severe hemorrhage, high levels of ADH (via V1 receptors on vascular SM) cause vasoconstriction
Volume regulation via ADH
- stimuli arising from stretch receptors act to chronically inhibit ADH secretion
- decreases in blood vol cause venous and arterial stretch receptors to send fewer signals to the CNS
- decreasing chronic inhibition of ADH secretion
- this mechanism = esp important for restoring ECF volume following hemorrhage.
Osmoregulation
- an increase of only 1% in the osmolality of the ECF bathing the hypothalamic osmoreceptors will evoke an increased rate of ADH secretion
- similarly sized decreased in osmolality will decrease ADH secretion
- ECF osmolality is kept very close to 285 most/Kg
Ingesting ethyl alcohol or being in a weightless environment ____ ADH secretion
- suppresses ADH secretion
- in weightlessness, there is a net shift of blood from the limbs to the abdomen and chest.
- this results in greater stretch of the volume receptors in the large veins and atria
- thus suppressing ADH secretion
ANP (ANF)
1. stimuli for release
- secreted by heart; found mainly in R atrium
1. stretch (independent of nervous system)
2. increased salt intake
3. CHF and all fluid overload states - ANP (ANF) increases Na loss (natriuresis) and water loss by the kidney
- also
ANP (ANF) increases Na loss (natriuresis) and water loss by the kidney because of
- an increase in glomerular filtration rate due to:
1. ANP-mediated dilation of the afferent arteriole
2. ANP-mediated constriction of the efferent arteriole - also increases Na loss and water loss (diuresis) by the kidney bc it inhibits
1. inhibits aldosterole release as well as
2. inhibits the reabsorption of Na and H20 in the collecting duct - ANP tends to antagonize the effects of ATII and ADH
normal ANP level is used to exclude
CHF as a cause of dyspnea
Central DI
- CDI = ADH deficiency; not enough ADH available to affect the renal collecting ducts
- Tx: replacing ADH as vasopressin or DDVAP (desmopressin)
- causes: familial, tumors (craniopharyngioma) autoimmune, trauma
1. pituitary trauma — transient DI
2. Sectioning of Pituitary stalk — triphasic response: DI, followed by SIADH, followed by a return of DI
3. destruction of the hypothalamus from any cause can lead to DI. - ex) stroke, hypoxia, head trauma, infection, cancer, mass lesion
SIADH
- excessive secretion of ADH causes inappropriate increased reabsorption of water in the renal collecting duct
- SIADH = any urine Osm greater than 100 w hyponatremia
- w Hyponatremia, a normal person should have urine Na and Osmolarity that are low
- in SIADH, it’s a disease bc urine Na and osmolarity are inappropriately high
Nephrogenic DI
- due to inability of kidneys to respond to ADH
- causes: familial, acquired, drugs (lithium)
- hypokalemia
- hypercalcemia
Causes of SIADH
- ectopic production of ADH (any CNS or small cell lung pathology)
- Drug induced: SSRi, carbamazepine
- lesions in pathway of the baroreceptor system
Sectioning of pituitary stalk
triphasic response:
- DI,
- followed by SIADH,
- followed by a return of DI
Pathophysiology of SIADH
- increased water retention, hyponatremia, but clinically euvolumic
1. Vol expansion increases ANP, decreases renin creating a natriuresis, which contributes to the nyponatremia
2. inappropriate [urine] can be greater than plasma osmolarity - any urine Osm greater than 100 w hyponatremia is SIADH
