Clinical Flashcards
Cushings disease
pulsatile pattern of pituitary hormone (anterior) release is altered
poor circadian pattern of corticotropin release
acromegaly
GH concentration remains detectable throughout the day
since pulsatile pattern of GH release is altered….sustained hypersecretion of GH
from a slow growing somatotroph tumor
symptoms:
- thickening and oiliness of skin, particularly of the face
- thickening and folding of scalp that are visible on skull Xray
gradual progression of symptoms and signs as a result of diagnosis are often delayed 15-20 years
syndrome of inappropriate ADH secretion (SIADH)
abnormal release of ADH causes water retention, hyponatremia
most common cause is cancer
therapy = must limit water intake to increase serum sodium
block V2 receptors (conivaptan, and tolvaptan)
Diabetes insipidus
deficiency of ADH
characterized by polyuria
caused by destruction of hypothalamic nuclei or defect in the kidney’s to respond to ADH
therapy = desmopressin
oxytocin
causes myoepithelial contractions to force milk from alveoli into ducts
and stimulation of SmM in the uterus
used to stimulate labor contractions and stopping immediate postpartum bleeding
estrogen and catecholamine effects on oxytocin
estrogen augments effects
catecholamines block them
OTC circulation
unbound in plasma and activates a 7 transmembrane domain receptor
causes elevation of Ca2+ and IP3 in target cells
stimuli for OTC release
suckling
uterine and genital stimulation
opoids on OTC
inhibit release
GH deficiency
either cannot secrete enough or cannot respond to its stimuli
short in stature and modestly obese
diagnosis = loss of nocturnal peaks on a diminution of total daily integrated secretion can be used as evidence for a more subtle GH deficiency and for GH replacement therapy
effects of giving GH to patients who are deficient
enhances positive nitrogen balance
decreases urea production
redistributes fats and reduces carbohydrat utilization
does NOT increase incidence of diabetes
giving IGFs to GH deficient people
decreases plasma amino acids due to increased use of amino acids into protein synthesis
GH on insulin function
it stimulates the expression of the insulin gene but
it induces resistance to insulin action
(why can be called a diabetogenic hormone)
disruption of pituitary connections to hypothalamus on prolactin
would leave to increase secretion
whereas, other homrones in the pituitary would decrease to a great extent
excess prolactin –>
inhibits GnRH release
can lead to lack of ovulation and infertility in women and low sperm in men
thiouracils
drugs that block enzyme peroxidases
treat thyroid hyperfunction
iodide treatment for hyper or hypo thryoidism ?
hyper
until more definitive therapy is undertaken
negative feedback by T3 and T4
inhibit synthesis of both TSH and TRH
T3 blocks the effect of TRH and also suppresses its release
actions of TSH on the thyroid cell
(+)cAMP –> (+) Ca2+, phosphoinositol, and growth factors
how TSH stimulates thyroid growth
increased DNA, RNA, protein, and phospholipids
increased cell size, number, and follicle formation
how TSH stimulates TH secretion
increased
- I trap
- iodination
- endocytosis of colloid
- proteolysis of thyroglobulin
- glucose oxidation
- NADPH generation
TRH
from hypothalamus
stimulates release of TSH by increasing ca2+ and IP3
down regulates and/or desensitizes its receptor thereby diminishes its effectiveness
TSH structure
2 peptide subunits that come from separate genes
what keeps T3 and T4 levels relatively constant
negative feedback loop
10-30% changes in TH can change TSH levels in opposite directions
T3 suppresses release of what
TSH –> represses TSH gene and down regulates the receptor
what inhibits TSH secretion
T3 dopamine somatostatin cortisol GH
goiter
TSH hypersecretion is cause
TH deficiency shows what plasma levels of TSH
high TSH
and enlarged pituitary gland containing increased numbers of thyrotrophs
excess TH causes what
low plasma TSH and atrophy of thyrotroph cells
what can cause lower TBG levels
acute liver disease, pregnancies, and estrogen therapy or kidney disease
replacement TH therapy uses T4 or T3
T4
Hyperthyroidism
- increase in metabolic rate –> weight loss and an increased intake of food
- excessive generation of heat causes discomfort in warm environments, sweating, thirst, and increased ventilation
- muscle weakness, atrophy, and osteoporesis
- high cardiac output, increased heart rate, and increased emotional liability
treatment = beta-adrenergic blockers can be used to ameliorate the clinical manifestation
causes of hyperthyroidism
Graves’ disease –> autoimmune disease which an antibody binds to TSH receptors and mimics the effects of TSH
benign neoplasm of thyroid unregulated TSH
inflammation of thyroid, excess TSH, ingestion of excess T3 and T4 and high Iodide intake
treatment of hyperthyroidism
short term iodine excess
treatment with thiouracil for 18mo which blocks synthesis of TH, or ablation of thyroid tissues by radioactive iodine or surgery (most commonly used procedure)
hypothyroidism
mental retardation and delayed body development
lethargy, growth retardation, and poor performance
in both children and adults….the decreased metabolic rate causes intolerance of cold, decreased sweating, dry skin, a low CO, and weight gain
what is hypersecretion of insulin usually caused by?
tumor of beta cells
leads to hypoglycemia
what is a consequence of hypoglycemia (which can be caused by too much insulin)
need to ingest large amounts of carbs
this plus high insulin –> weight gain
effect of sepsis, major fractures, surgery, or hypoglycemia on cortisol production
increases it
negative nitrogen balance from prolonged cortisol exposure
in case of Cushing’s
skin becomes very thin and the loss of CT and capillaries that can rupture spontaneously
causes bruises
long term treatment of pharma doses of glucocorticoids makes patients susceptible to
infection, diabetes, and osteoporesis
cortisol replacement therapy can be used to treat
Addison’s diseaes
cortisol deficiency can lead to (Addison’s)
weight loss, fatigue, poor tolerance to stress, fever, and or low glucose
ANP and BNP effect on aldosterone release
potently inhibit
what are best markers for fetal well being and placental adequacy
rising serum or urine estriol levels
16-OH-DHEA-S –> estriol
Androgenital Syndrome can be caused by…
androgen producing tumors or by the lack of negative feedback on ACTH
androgen deficiencies usually arise from
autoimmune deficiencies of adrenal glands or from congenital enzyme defects
or deficiency in ACTH
Addison’s
progresses slowly with loss of androgens –> anemia and loss of boddy hairs
reduced cortisol –> fatigue, poor stress tolerance
low aldosterone –> low bp etc
low weight
Cushing’s
too much cortisol –> obestity and muscle weakness due to adrenal or pituitary dysfucntions
