Thyroid Hormone Flashcards
H-P-Thyroid axis activated by (3)
circadian rhythm
cold exposure
acute psychosis
H-P-Thyroid axis suppressed by
Severe stress
Thyroid hormone release chain
TRH (hypothalamus) –> TSH (pituitary –> TH (thyroid)
Thyroid Stimulating Hormone inhibited by
somatostatin, dopamine, glucocorticoids
Biosynthesis of TH (4 steps), regulated by TSH
(Regulated step) Uptake of iodide into gland.
Iodide placed onto thyroglobulin molecules via thyroid peroxidase (MIT and DIT).
Coupling of precursors, via thyroid peroxidase, MIT+DIT=T3, DIT+DIT=T4.
Released from gland by pinocytosis.
TRH (synthetic) MOA
activates phospholipase C –> increases IP3 —> increases intracellular calcium. Stimulates production of TSH
Synthetic TRH Uses
test for pituitary reserve of TSH in suspected hypothyroidism and hyperthyroidism
Synthetic TSH Use
Therapy for thyroid carcinoma – increases the uptake of radioactive I- into thyroid
Synthetic TSH MOA
stimulates cAMP production via adenylyl cyclase–> increased uptake of iodine and production of TH
Thyroid hormone MOA
Enters cell via active transport. T4 converted to T3, which enters nucleus and binds to receptor. Ultimately increases RNA and protein synthesis
Thyroid Hormone effects
Growth via protein synthesis, development, function of all tissues.
Myelination of the NS, ossification of epiphyses, reproductive system development.
Influences secretion and degradation of all other hormones.
SNS activity is increased in response - especially cardiovascular
Hypothyroidism presents as
a multisystem disorder of reduced metabolism
Hypothyroidism replacement therapy
Levothyroxine (T4)
adults: 1.6-1.8 mcg/kg/day. May need higher doses when treating pregnant women
children: need more… 10mcg/kg
Myxedema Coma is an acute medical emergency occurs in untreated hypothyroidism. Presents with:
Hyponatremia, hypoglycemia, hypothermia, shock
Levothyroxine (t4) and Triiodothyronine (T3) ABS
Ileum and colon. Should be taken alone on an empty stomach with water
Imparied by metal ions, ciprofloxacin, bile acid sequesterants, raloxifene, soy, dietary fiber
Levothyroxine (t4) and Triiodothyronine (T3) transport
Bound to thyroid-binding-globulin. ONLY unbound has metabolic effects.
Pituitary only responds to FREE hormone
T3 and T4 binding increased by
Estrogens/ SERMs/ Tamoxifen
T3 and T4 binding decreased by
Salicylates/ antiseizures
T3 is the active hormone
:)
Levothyroxine is synthetic T4
treatment of choice
many formulations - none are superior but you should use the SAME one once started
Liothyronine is synthetic T3
not recommended in routine replacement
Liotrix 4:1 ratio of T4 and T3
Not recommended in routine replcement
T4 toxicity presents like acute hyperthyroid crisis
:)
Grave’s DIsease (hyperthyroidism) is the most common cause. Etiology:
Thyroid stimulating antibody that mimics TSH
SSx of Hyperthyroidism
Metabolic and CVS hyperactivity
Symptomatic treatment of Grave’s DZ
beta blockers and corticosteroids
Tx of Grave’s DZ with hormone production interference and glandular destruction with:
Thionimide, iodide, surgery, radioactive iodide
Methimazole (Tapazole) is a thionimide MOA
Leaves gland intact, is a large chance of relapse. Control symptoms until resolved (synthesis, not release, is blocked)
Blocks TH synthesis by not allowing precursor coupling
Thionamides are treatment of choice in hyperthyroidism of pregnancy
:)
Iodide therapy in high doses can inhibit hormone synthesis, but variable effects
Should not be used alone
Radioactive iodine PO concentrated in thyroid and slowly destroys parenchyma. Complication:
Hypothyroidism.
NOT for use in pregnant women
Thyroidectomy is treatment of choice if large gland, but radioactive iodine works best
most patients will need TH supplements after surgery
Thyroid storm treatment
Propranolol for cardiovascular manifestations
Hydrocortisone to protect against shock
Sodium iodide to block release of TH
Thionamide to block TH synthesis
