Lect. 4 - Thyroid Flashcards
cretinism
a condition of abnormal mental and physical development resulting from a deficiency of thyroid hormone in fetal or early life.
typically characterized by intellectual disability, small stature, and thickening of the facial features.
predominant structures in the thyroid glands
thyroid follicles filled with protein rich colloid
thyroid medullary cells produce what
also known as C cells
produce calcitonin
identify the molecule
thyroxine, T4
Theterm‘thyroidhormone’
encompassesbothT3and T4.
identify the molecule
triiodothyronine or T3
Theterm‘thyroidhormone’encompassesbothT3and T4.
themainprecursortothyroid
hormones
Thyroglobulin
is the main precursor to thyroid hormones.
Iodineistransferredacross
theepithelium
intothethyroid follicular lumen
whereitisconjugated
tothyroglobulin.
percentage output of T4 and T3 from thyroid gland
T4(90%ofoutput)
T3(10%ofoutput)
arebiologicallyactive,
andT3isfarmoreactivethan
T4becauseofahigheraffinityfor
thyroidhormonereceptors
What secretes thyrotropin releasing hormone?
NeuronsofthehypothalamussecreteTRH whichiscarriedtothe anteriorpituitary.
After thyrotropin releasing hormone is secreted from thehypothalamusandcarriedtothe adenohypophysis, what occurs?
Thyrotrophs are stimulated by TRH to synthesize and release Thyroid-stimulating hormone (TSH).
Thehypothalamic‐pituitary‐thyroid(HPT)axis
thyrotropin releasing hormone TRH, hypothalamus
thyroid-stimulating hormone TSH, adenohypophysis
thyroxine & triiodothyronine T4 & T3, thyroid gland
Function of TSH
TSHbindstoreceptorsonthebasolateral
membraneofthyroidfollicularcells,
stimulates the synthesis and
release of T4andT3.
Cell receptors for T3 & T4 are located where?
areintracellular so T3 andT4 arehydrophobic/lipophilic(cancrosscellmembranes)
thyroid hormone primary binding protein differs between species
More than 99% of T3 and T4 are protein‐bound for transport within the blood by:
Thyroid‐binding globulin (TBG) (primary binder in dogs).
Cats do not appear to have a high‐affinity TBG.
Prealbumin is the primary binder in cats.
Other plasma proteins such as transthyretin and albumin bind thyroid hor
Factors affecting thyroid hormone concentration and/or capacity of circulating binding compounds (3)
diseases
Pharmacologicagents (e.g. glucocorticoids, acetylsalicyclic acid both lower plasma TT4 without affecting free T4)
breed differences (e.g. TT4 low in some whippets sled dogs & greyhounds; small breeds tend to have higher TT4)
the most significant metabolic transformation of the thyroid
hormones is
deiodination
About80%ofthesecreted
T4isdeiodinated toformT3andreverse-T3,
predominantlyin
theliverandkidney.
Factors that impair T3 formation,
such as fasting and nonthyroidal disease, almost invariably increase what
plasma reverseT3 concentration.
name 2 FactorsthatimpairT3formation
fastingandnonthyroidaldisease,
almostinvariablyincrease
plasmarT3concentration.
Illnessleadstoincreased
activityoftype3
deiodinase(D3),
whichprimarily
deiodinates theinnerring.
T4bindsmoretightlyto
bindingproteinsinplasmathandoes what?
T3,whichresultsinT4havinga
lowermetabolicclearance
rateandlongerhalf‐life.
Overall,thekineticsofthyroid
hormonedistributionand
turnoveraremuchmorerapidin
dogsthaninhumans,
inpartbecauseofthe
lowerbindingofbothT4
andT3incanineplasma.
Theplasmahalf-lifeofT4isabout
0.6daysindogs,
comparedtoabout
sevendaysinhumans.
Thus, levothyroxine(T4)
therapeuticdosage
ishigherindogs
comparedtohumans.
T3orT4activatesthyroidhormonereceptorsandregulatesthetranscriptionofthesegenes to produce proteins with what effects?
These proteins generally:
↑Cellularmetabolism
↑CellularoxygenconsumpƟon
↑Cellular glucose
↑ Circulation and respiration
Promote nervoussystem and skeletaldevelopment.
Clinically,thyroidhormones help maintainnormal:
- Energylevels
- Weight
- Thermoregulation
- Heartrates
- Bowelmovements
- Mood
Inmanyrespectsthyroidhormonescanbeviewedastissuegrowthfactors,thisbeingbestexemplifiedbytheconsequencesofthyroidhormonedeficiencyatayoungage.
Hypothyroidisminyounganimals, name the potential diseases (4)
- Acquired juvenile hypothyroidism
- Thyroid dysgenesis
- Defective thyroid hormone synthesis
- Central hypothyroidism (problem not in gland itself)
In all forms of hypothyroidism, treatment consists of oral administration of l‐thyroxine except in the case of
hypothyroidism due to iodine deficiency.
L-thyroxine administration will lower thyroid-stimulating hormone secretion and as a result the goiter will shrink.
Earlyinlifethepresenceofthyroid
hormonesiscrucialfor
growth and development of all body tissues and particularly the skeleton.
Disproportionate dwarfism may be a prominent sign of congenital or
juvenile‐onset hypothyroidism, in addition to the signs also seen in
adult‐onset hypothyroidism.
cause of Acquiredjuvenilehypothyroidism
Iodine deficiency is the classic cause of acquired juvenile hypothyroidism e.g. a diet consisting of meat alone is deficient in iodine.
lackofiodineresultsin
TSH‐induced thyroid hyperplasia.
In mild deficiencies the increased capacity for hormone production compensates sufficiently and euthyroidism is maintained.
In severe iodine deficiency there is insufficient production of thyroid hormone despite the compensatory thyroid hyperplasia.
Lymphocyticthyroiditis is
inflammation of the thyroid gland due to lymphocytic infiltration, an autoimmune disease. Thyroid tissue is destroyed and hypothyroidism is the result.
Thyroiddysgenesis
the term used to describe abnormalities in thyroid gland development
Ectopiaofthyroidtissueiscommoninthedogandisalsoknowntooccurincats. Ectopia meaning the thyroid tissue is outside of the gland.
Glandfunctionmaybeinsufficienttopreventhypothyroidism.
Completeathyreosishasalsobeenfound meaning no thyroid gland whatsoever present (but in some cases thyroid tissue can still be present somewhere).
Abnormalitiesinthenewbornthatmaysuggesthypothyroidisminclude: (5)
Alargefontanel(soft spot in the skull whichshouldbeclosedatbirthindogsbutnotincats)
- Hypothermia
- Hypoactivity
- Sucklingdifficulties
- Abdominaldistension
besides dysngenesis, Congenitalhypothyroidismmayoccurbecauseof
anenzymedeficiencythatpreventssynthesisofthyroidhormones.
Suchcongenitaldefectsarerareandalthoughinprincipleanystepinthyroidhormonesynthesismaybeaffected.
OnlyunresponsivenesstoTSHanddefectiveperoxidaseactivity(thyroidhormoneisnotsynthesized)havebeenfoundthusfarinthedogandthecat.
Central(secondary)hypothyroidism is due to
thyroid-stimulting hormone deficiency
central hypothyroidism can be classified as one of two
pituitary (secondaryhypothyroidism)
hypothalamic (tertiaryhypothyroidism)
(primary would indicate an issue with the gland itself)
HyposecretionofTSHisusuallyaccompaniedby what other hormonal issues?
HyposecretionofTSHisusuallyaccompaniedbydecreasedsecretionofotherpituitaryhormones.
e.g. lack of GH usually go hand in hand with lack of T4 “combineddeficiencyof
adenohypophyseal hormones.” (e.g. in the dwarf animals)
hypothyroidismduetocentralcausesislessseverethan
primaryhypothyroidism.
Hypothyroidisminadultanimals is classed as either
primary or central
Inabout95%ofcasesofadultonset hypothyroidism,itis
aprimarythyroiddisorder.
Inabout5%or less of casesofadultonset hypothyroidism,itisdue to
a TSH deficiency (so pituitary or hypothalamic).
Primaryhypothyroidism pathogenesis is typically due to
progressiveautoimmuneprocesswhichleadstolymphocyticinfiltrationanddisappearanceofthyroidfollicles.
Theimmune‐mediateddestructionisaslowprocessandclinicalmanifestationsofthyroidhormonedeficiencyonlybecomeevidentafterdestructionofabout75%ofthethyroidfollicles.
In primary hypothyroidism, as theautoimmunedestructionprogresses,thyroidfolliclesarereplacedby
fibrousandadiposetissueandtheinflammatorycellsdisappear,resultingin
thehistologicalappearanceofnoninflammatoryatrophy.
polyglandularfailuresyndrome
involve deficiencies in the function of several endocrine glands, which may occur simultaneously or sequentially.
E.g. in primary hypothyroidism theimmunologicdamagemayalsoinvolveoneormoreotherendocrineglandsandleadtomultipleendocrinedeficiencies,knownaspolyglandularfailuresyndrome.
Schmidt’ssyndrome
Thecombinationofhypothyroidismandhypoadrenocorticism (Addison’s)isknownasSchmidt’ssyndrome.
a polyglandualr failure syndrome
Sometiems includes type 1 diabetes mellitus too.
Iatrogenichypothyroidism
Iatrogenic hypothyroidism (IH) results when treatment for hyperthyroidism causes suppression of total thyroxine (T4) below normal levels.
occurs speciallyincatstreatedforhyperthyroidism
Thehypothyroidismmaybeanadverseeffectofradioiodinetherapyorbilateralsurgicalthyroidectomy.
Acquiredprimaryhypothyroidism typical to what type of animal
aconditionofyoung‐adultandmiddle‐ageddogs.
dogsoflargebreedsmaybeaffectedmorefrequentlythanthoseofsmallbreeds.
thereisnopronouncedbreedpredispositionandisequallydistributedbetweenmalesandfemales.
either due to lymphocytic thyroiditis or thyroid gland atrophy.
Clinicalmanifestationsofprimaryhypothyroidisminadult dogs
weight gain
course coat, nonpruritic symmetrical alopecia
myxedema (skin thickening)
bradycardia
lethargy
persistent anestrus
95% of hypothyroidism is
primary hypothyroidism meaning the issue is on the glandular level
e.g. autoimmune thyroiditis, thyroid tumor etc.
secondary hypothyroidism refers to
inadequate TSH secretion or thyroid trauma, cysts/nodules/tumors etc.
tertiary hypothyroidism refers to ?
DeficiencyinthesecretionofTRH(extremelyrareindogs)
(thyrotropin releasing hormone)
Hyperthyroidism in cats is typically caused by
Athyroidhormoneexcessproducedbythyroidadenomatoushyperplasiaoradenoma,involvingoneor,moreoften,boththyroidlobes.
Thyroidcarcinoma, in dogs vs cats
ThyroidcarcinomaisthemaincauseofhypeRthyroidismindogs,but accountsforonly3%ofcasesincats.
Feline hyperthyroidism is typically caused by thyroid adenomatous hyperplasia or thyroid adenomas.
Theclassicpresentationofahyperthyroidcatis
a skinny,restless,elderlycatwithanincreasedappetiteandpolyuria.
Clinicalmanifestationsofhyperthyroidismincats (6)
weight loss despite polyphagia
tachycardia with potential LV hypertrophy
restlessness
panting
poor hair coat
polyuria
leukocytosis
elevated ALT etc.
Inabout10%offeline hyperthyroid casestheclinicalpicturemaybe atypical in what way?
Inthesecatsweightlossremainsanimportantfeature butthereislethargyandanorexiaratherthanhyperactivityandincreasedappetite.
This form is called apathetic hyperthyroidism.
“apathetichyperthyroidism”,andmayrepresent what?
anend‐stageofthediseaseandmayalsobeassociatedwithcardiacdisorders.
“thyroidstorm”
Thyroid storm (also called thyroid crisis and thyrotoxic crisis) happens when your thyroid gland releases a large amount of thyroid hormone in a short amount of time. It’s a rare complication of hyperthyroidism. Thyroid storm is a medical emergency and is life-threatening.
Thesevereformoffelinehyperthyroidismhasalsobeencalled
“thyroidstorm”.
Radioactiveiodinetherapy,thyroidsurgery,vigorousthyroid
palpation,andstressmaycause
acuteelevationofplasmathyroid
hormoneconcentrationandhavebeenimplicatedaspossible
precipitatingfactorsfor“thyroidstorm”.
diagnosis of feline hyperthyroidism (3)
clinical picture
palpation of thyroid for enlargement
directmeasurementofthyroidfunction, biochemistry
Radioiodineuptakestudies
Radioactive Iodine Uptake, or RAIU, is a test of thyroid function. The test measures the amount of radioactive iodine (taken by mouth) that accumulates in the thyroid gland.
Scintigraphy
Scintigraphy, also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally and the emitted gamma radiation is captured by external detectors (gamma cameras) to form two-dimensional images in a similar process to the capture of x-ray images.
TherearethreeoptionsforeliminatingtheexcessproductionofT4:
(1)radioiodineablationofthethyroid
(2)surgicalthyroidectomy
(3)inhibitionofsecretionbyantithyroiddrugs(methimazole,carbimazole)
the first option is preferable if available
How does radioiodine therapy of the thyroid work?
Radioiodine(131I)byitsβ‐radiationselectivelydestroyshyperfunctioningthyroidcellswhilesparingthesuppressednormalthyroidtissueandtheparathyroidglands.
Thenormalfolliclesgraduallyresumefunctionandthereisusuallynoneedforadministrationofthyroxine.
prognosis is excellent if no concurrent disease (renal etc.). recurrence possible.
Thyroidneoplasiaaccountsforwhat%ofallcaninetumors.
about2%ofallcaninetumors.
Mostofthebenigntumors(adenomas)aresmallandcommonlynot detectedduringlife. Benign can also cause hyperthyroidisim.
Thyroidtumorsarisenotonlyfromfollicularepitheliumbutalsofrom
theparafollicularCcells.
Theseso‐calledmedullarythyroidtumorsarerelativelyrareindogs.
Clinicalfeatures of dogs presenting with thyroid tumors (4)
meanageisnineyears(range5–15years)
Boxersareoverrepresented.
Thereisnosexpredilection.
Thesignsandsymptomsaredueto:
* (1)thyroidenlargement
* 2)hypersecretionofthyroidhormones.
What is a “cold” thyroid tumor?
Thyroid nodules that do not absorb the radioiodine are called cold.
typically not hormonally active
Alargeandinvasivethyroid tumormayevendamagethecervicalsympathetictrunk,causing what
Horner’ssyndrome
ManifestationsofNONhypERfunctioning thyroidtumorsindogs (?)
a usually large unilateral tumor is common.
can be accompanied by weight loss, resp. distress, dysphagia, anorexia, horner’s syndrome
Hypersecretionofthyroidhormoneoccursinwhat percentage of canine thyroid tumors?
about10%ofcasesofthyroidtumorindogs.
Itmayresultinthesyndromeofhyperthyroidism,verysimilartothatcatsbutoftenlesssevere.
Manifestationsofhyperfunctioningthyroidtumorsindogs (?)
Occasionallythereresymptomsofhyperthyroidismwithoutpalpable thyroid
enlargement,inwhichcasewhat should be considered?
anintrathoracichyperfunctioning
tumorinectopicthyroidtissue
shouldbeconsidered.
AlowplasmaT4andhighplasmaTSH,indicates?
hypothyroidism
canbefoundindogsinwhichthenormalthyroidtissueisreplacedbybilateralthyroidcarcinomaorpreexistingthyroiditis.
highplasmaT4andlowplasma
TSH, indicates?
hyperthyroidism from e.g. hyperfunctioning thyroid tumor
treatment of Hyperfunctioningthyroidtumors (in dogs)
undelayed surgical resection if possible.
Administrationofradioiodide isanalternative.
Chemotherapy witheitherdoxorubicinorcisplatinmaybeconsideredindogswithahighriskofdevelopingmetastases,namelythosewithlargeandbilateralthyroidcarcinoma.
Thyroid‐cellproliferationisdependent on what
TSHdependentandcarcinomatousthyrocytesdohaveTSHreceptors too.
prognosisof treatment of thyroid carcinoma in dogs canbeinfluencedfavorablybyTSH‐suppressivetreatmentwithl‐thyroxine.
TSH‐suppressivetreatment hastwoobjectives:
(1)hormonereplacement(correctionofinducedhypothyroidism)
(2)hormonesuppression(reductionofplasmaTSHlevelsthatmightstimulate
growthofpersistentorrecurrentneoplastictissue).
what mediators inhibitTSHrelease
Somatostatinanddopamine releasedbyhypothalamicneurons inhibitTSH
release
What plasma proteins in addition to thyroid-binding globulin (TBG) bind thyroid hormones?
- Transthyretin
- Albumin
- Prealbumin(primarybinderincats).
- Lipoproteins
Protein‐bound hormones areinactive,servingasa reservoir.
Freeandboundformsareinan equilibrium →levelsoffreehormoneremainfairlyconstant.
Ofthetotalthyroidhormoneboundtointracellular receptors, what percentage is T3
~90%
explaincentralhypothyroidism
thethyroid isnotaffectedprimarilybutaredeprivedofstimulationbyTSH.
Theconditionisrarecomparedwithprimarythyroidfailure.
Spontaneouscausesincludetumorofthepituitaryoradjacentregionsandheadtrauma.
Centralhypothyroidismcanalsoresultfromsurgicalremovalofapituitarytumor.
