Thyroid Gland Testing - LASSEN NIELSEN
Transcript of Thyroid Gland Testing - LASSEN NIELSEN
2011-10-05 Thyroid Gland 1
The Investigations of the Thyroid gland
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Essential for understanding this presentation:
1) Anatomy: The Thyroid Gland and it’ssurroundings
2) Biochemistry: Hormones produced bythe Thyroid Gland
3) Physiology: Function of the hormonesproduced by the Thyroid Gland
First then can one start on a journey toinvestigate abnormal functions of the Thyroidgland
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The Investigations of the Thyroid Gland
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Objectives:
1) Describe the mechanisms of endocrinehypofunction and hyperfunction.
2) Differentiate among primary, secondaryand tertiary endocrine disorders.
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The Investigations of the Thyroid Gland
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Discuss - based on the normalphysiology - the rationale behind
4) The investigations the Thyroid Gland.
3) Symptoms of a dysfunctional Thyroid Gland.
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The Investigations of the Thyroid Gland
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Essential for understanding the investigations
1) Anatomy:
2) Biochemistry:
3) Physiology:
4) Diseases
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Essential anatomy
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Connections to/fromhypothalamus (nerveand vessels) to theThyroid gland
The hypophysealportal system
AnteriorPosterior
From Porth and Matfin Pathophysiology –Concepts of Altered Health states 2009
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Essential anatomy
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Relations
Trachea
Muscles
Main Arteries
Anterior
http://fitsweb.uchc.edu/student/selectives/Luzietti/Thyroid_anatomy.htm
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Essential anatomy
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Anterior
http://fitsweb.uchc.edu/student/selectives/Luzietti/Thyroid_anatomy.htm
Relations
Main Arteries
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Essential anatomy
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Anterior
http://fitsweb.uchc.edu/student/selectives/Luzietti/Thyroid_anatomy.htm
Relations
Main veins
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Essential anatomy
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Anterior
http://fitsweb.uchc.edu/student/selectives/Luzietti/Thyroid_anatomy.htm
Relations
Lymph drainage
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Essential anatomy
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Anterior
http://fitsweb.uchc.edu/student/selectives/Luzietti/Thyroid_anatomy.htm
Relations
Nerves
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Essential anatomy
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Vagus Nerves
Whichnerves aremissing?
RecurentLaryngealNerves
Always double check that you have it all
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Essential anatomy
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Any otherglands closeby?
Parathyroidgland
Posterior view
http://www.mhhe.com/biosci/esp/2001_saladin/folder_structure/in/m5/s5/index.htm
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Essential anatomy - Development
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Why is itimportant?
Aberrant tissue
The thyroid gland begins todevelop as a median thickening ofendoderm on the floor of thepharynx between the first andsecond pharyngeal pouches. Thisarea later invaginates to form themedian diverticulum, whichappears in the later half of thefourth week. This thyroiddiverticulum grows further,becoming a solid cellular cordcalled the thyroglossal duct. Theduct grows caudally and bifurcatesto give rise to the thyroid lobesand the isthmus.
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The Investigations of the Thyroid Gland
©lassen-nielsen.com
Essential for understanding the investigations
1) Anatomy:
2) Biochemistry:
3) Physiology:
4) Diseases
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Essential biochemistry
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Orientation
Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
Follicle lumen
Capillary
Thyrocyte
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
TSH signaling via the TSHreceptor controls thyroidhormone synthesis,
TSH-r
Uptake of iodide into thethyrocytes is mediatedby an intrinsic membraneglycoprotein, the sodium-iodide symporter (NIS),which actively cotransportstwo Na+ per each iodideanion.NIS is dependent on the Nagradient created by theNa/K-ATPase
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
TSH can increaseexpression of NIS in thebasolateral membrane ofthyrocytes.
TSH-r
Transcription
m-RNA
Protein synthesis
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
H2O2 is produced by thecalcium- and reducednicotinamide adeninedinucleotide phosphate-dependent (NADPH)enzyme DUOX2.
TSH-r At the apical membrane,iodide efflux is, in part,mediated by pendrin(PDS/SLC26A4)
DUOX2 requires a specificmaturation factor, DUOXA2
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
H2O2 At the cell-colloidinterface, iodide is oxidizedby TPO (thyroid peroxidaseor thyroperoxidase) in thepresence of H2O2
TSH-r
Thyroglobulin (TG), whichis secreted into thefollicular lumen, serves asmatrix for synthesis ofT4 and T3.
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
TG secreted into the follicu-lar lumen, serves as matrixfor synthesis of T4 and T3.
TSH-r
TPO catalyzes iodination ofselected tyrosyl residues(organification), whichresults in the formation ofMIT and DIT.
TSH-r
Two iodotyrosines arecoupled to form either T4or T3 (catalyzed by TPO).Iodinated thyroglobulin isstored as colloid in thefollicular lumen.
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
TSH-r
Iodinated thyroglobulin isstored as colloid in thefollicular lumen. Upon ademand for thyroidhormone secretion,thyroglobulin isinternalized into thefollicular cell by pinocytosisand digested in lysosomes,which generates T4 and T3that are released into thebloodstream throughunknown mechanisms.
TSH-r
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Essential biochemistry
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Bizhanova A , Kopp P Endocrinology 2009;150:1084-1090
TSH-r
The unused MIT and DITare retained in the cell anddeiodinated by theiodotyrosine dehalogenase1 (DEHAL1).
The released iodide isrecycled for thyroidhormone synthesis.
TSH-r
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Essential biochemistry
What does thisfigure show?
Basically the same asthe previous 8 slides
Other growth factorssimulates TSH:1 Insulin-like growth factor I (IGF-1)2 Epidermal growth factor3 Transforming growth factor ß4 Endothelins
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The Investigations of the Thyroid Gland
©lassen-nielsen.com
Essential for understanding the investigations
1) Anatomy:
2) Biochemistry:
3) Physiology:
4) Diseases
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The Investigations of the Thyroid Gland
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The T3 and T4 feedback
Don’t forget the Pituitarygland feedback
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The Investigations of the Thyroid Gland
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The T3 and T4 are protein bound99.8% of T4
99.7% of T3
The binding proteins are:• Thyroxine-binding globulin (TBG)• Transthyretin (TTR) formerly known as
thyroxine-binding pre-albumin (TBPA)• Albumin
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The Investigations of the Thyroid Gland
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Hormone property T4 T3
Serum Concentration total hormone 8 μg/dL 0.14 μg/dL
Fraction of total hormone in free form 0.02% 0.3%
Free (unbound) hormone 21 x 10-12 M 6 x 10-12 M
Half-life 7 d 0.75 d
Fraction directly from the thyroid 100% 20%
Production rate, including peripheral conversion 90 μg/d 32 μg/d
Intracellular hormone fraction ~ 20% ~ 70%
Relative metabolic potency 0.3 1
Receptor binding 10-10 M 10-11 M
From Harrison’s principles of Internal Medicine 18th edition
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Mechanism of thyroid hormone receptor action
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The thyroid hormone receptor (TR)and retinoid X receptor (RXR) formheterodimers that bind specificallyto thyroid hormone responseelements (TRE) in the promoterregions of target genes.In the absence of hormone, TRbinds co-repressor (CoR) proteinsthat silence gene expression.
The numbers refer to a series of orderedreactions that occur in response tothyroid hormone:(1) T4 or T3 enters the nucleus;(2) T3 binding dissociates CoR from TR;(3) Coactivators (CoA) are recruited to
the T3-bound receptor;(4) Gene expression is altered.
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The Investigations of the Thyroid Gland
©lassen-nielsen.com
Essential for understanding the investigations
1) Anatomy:
2) Biochemistry:
3) Physiology:
4) Diseases
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Hyper - & Hypo-functions
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In principle only two things can go wrong:
Increased production (over production) ofhormones: Hyper…..dism
Decreased production (under production) ofhormones: Hypo…..dism
Of cause there can be many underlying causes:Tumor, starvation, infections …….
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Hormone prioritizing
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Hor-mone
Function(Stimulates)
Releasingfactors
Hypo function Hyper –Function
Priority
ACTH Adrenal corticalhormone
CRH Second. Adrenalhypofunction
Cushing disease 1
MSH Melanocytes CRH Skin pigmentation 1?
TSH Thyroid hormone TRH Second.Hypothyroidism
Second.Hyperthyroidism
2
FSH F: Ovulation,M: Sperm
GnRH Infertility Precociouspupperty
3
LH Corpus luteum GnRH Sec. hypogonadism 4
GH Growth GHRH Short statute Acromegaly orgigantism
5
PRL Breast feeding Lactation failure AmenorrhoeaGalactorrhoea
6?
ADH Water reabsorb neurogenic Diabetesinsipidus
Hyponatremia
Oxytocin Uterus Contract neurogenic Uterinecontractions
decreased bonedensity and fat ?
Mnemonic: Go Look For The Adenoma
Meaning first goes GH then LH ……. Last ATCH
2011-10-05 Thyroid Gland 34
The Investigations of the Thyroid Gland
©lassen-nielsen.com
Essential for understanding the investigations
1) Anatomy:
2) Biochemistry:
3) Physiology:
Diagnose
4) Diseases
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Hyperthyroidism
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From Porth and Matfin Pathophysiology –Concepts of Altered Health states 2009
Fine Hair
Exophtalmos
Muscle wasting
Oligomenorrhea
NervousnessRestlessnessEmotional instabilityInsomnia
Goiter
Tachycardia, palpitations,high output failure
Sweating,Heat intoleranceIncreasedappetite
Weight loss
Fine tremor
Pretibialmyxedema
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Hyperthyroidism
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Total T4 Total T3 FreeT4
FreeT3
TBG TSH
Euthyroid Normal Normal normal normal normal normal
Hyperthyroid ˄ ˄ ˄ ˄ normal ˅ if primary˄ if Secondary
T3 toxicosis Normal ˄ normal ˄ normal ˅
Hypothyroid ˅ ˅ ˅ ˅ normal ˄ if primary˅ if secondary
TBG excess ˄ ˄ normal normal ˄ Normal
TBG deficiency ˅ ˅ normal normal ˅ Normal
T4 displacementby drugs
˅ normal Normal or ˅
normal normal Normal
Diagnose ?
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Hyperthyroidism
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Total T4 Total T3 FreeT4
FreeT3
TBG TSH
Euthyroid Normal Normal normal normal normal normal
Hyperthyroid ˄ ˄ ˄ ˄ normal ˅ if primary˄ if Secondary
T3 toxicosis Normal ˄ normal ˄ normal ˅
Hypothyroid ˅ ˅ ˅ ˅ normal ˄ if primary˅ if secondary
TBG excess ˄ ˄ normal normal ˄ Normal
TBG deficiency ˅ ˅ normal normal ˅ Normal
T4 displacementby drugs
˅ normal Normal or ˅
normal normal Normal
Diagnose ?
˄ = high ˅ = low
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Hyperthyroidism
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Total T4 Total T3 FreeT4
FreeT3
TBG TSH
Euthyroid Normal Normal normal normal normal normal
Hyperthyroid ˄ ˄ ˄ ˄ normal ˅ if primary˄ if Secondary
T3 toxicosis Normal ˄ normal ˄ normal ˅
Hypothyroid ˅ ˅ ˅ ˅ normal ˄ if primary˅ if secondary
TBG excess ˄ ˄ normal normal ˄ Normal
TBG deficiency ˅ ˅ normal normal ˅ Normal
T4 displacementby drugs
˅ normal Normal or ˅
normal normal Normal
Diagnose ?
˄ = high ˅ = low
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Hyperthyroidism
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Total T4 Total T3 FreeT4
FreeT3
TBG TSH
Euthyroid Normal Normal normal normal normal normal
Hyperthyroid ˄ ˄ ˄ ˄ normal ˅ if primary˄ if Secondary
T3 toxicosis Normal ˄ normal ˄ normal ˅
Hypothyroid ˅ ˅ ˅ ˅ normal ˄ if primary˅ if secondary
TBG excess ˄ ˄ normal normal ˄ Normal
TBG deficiency ˅ ˅ normal normal ˅ Normal
T4 displacementby drugs
˅ normal Normal or ˅
normal normal Normal
Diagnose ?
˄ = high ˅ = low
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Hyperthyroidism
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Total T4 Total T3 FreeT4
FreeT3
TBG TSH
Euthyroid Normal Normal normal normal normal normal
Hyperthyroid ˄ ˄ ˄ ˄ normal ˅ if primary˄ if Secondary
T3 toxicosis Normal ˄ normal ˄ normal ˅
Hypothyroid ˅ ˅ ˅ ˅ normal ˄ if primary˅ if secondary
TBG excess ˄ ˄ normal normal ˄ Normal
TBG deficiency ˅ ˅ normal normal ˅ Normal
T4 displacementby drugs
˅ normal Normal or ˅
normal normal Normal
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Hyperthyroidism Graves Disease
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Ginsberg J CMAJ 2003;168:575-585
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Hypothyroidism
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From Porth and Matfin Pathophysiology –Concepts of Altered Health states 2009
Gland
Target Organ
TSH
ControllingGland
TRH
T3 + T4
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Hypothyroidism
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From Porth and Matfin Pathophysiology –Concepts of Altered Health states 2009
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Hypothyroidism
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TSH T3 T4 TRH Conclusion
Slightlyelevated
normal Normal Compensated hypothyroidismTest for antiTBO and antiTg
Raised Low fT4 Normal/elevated
Primary hypothyroidismTest for antiTBO and antiTg
Low Low fT4 low Tertiary hypothyroidism
Low Low fT4 High Secondary hypothyroidism
Raised Raised/normal
Normal But patient has hypothyroidismsymptomsConsider thyroid hormone resistance
Diagnose ?
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Hypothyroidism
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TSH T3 T4 TRH Conclusion
Slightlyelevated
normal Normal Compensated hypothyroidismTest for antiTBO and antiTg
Raised Low fT4 Normal/elevated
Primary hypothyroidismTest for antiTBO and antiTg
Low Low fT4 low Tertiary hypothyroidism
Low Low fT4 High Secondary hypothyroidism
Raised Raised/normal
Normal But patient has hypothyroidismsymptomsConsider thyroid hormone resistance
Diagnose ?
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Hypothyroidism
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TSH T3 T4 TRH Conclusion
Slightlyelevated
normal Normal Compensated hypothyroidismTest for antiTBO and antiTg
Raised Low fT4 Normal/elevated
Primary hypothyroidismTest for antiTBO and antiTg
Low Low fT4 low Tertiary hypothyroidism
Low Low fT4 High Secondary hypothyroidism
Raised Raised/normal
Normal But patient has hypothyroidismsymptomsConsider thyroid hormone resistance
Diagnose ?
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Hypothyroidism
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TSH T3 T4 TRH Conclusion
Slightlyelevated
normal Normal Compensated hypothyroidismTest for antiTBO and antiTg
Raised Low fT4 Normal/elevated
Primary hypothyroidismTest for antiTBO and antiTg
Low Low fT4 low Tertiary hypothyroidism
Low Low fT4 High Secondary hypothyroidism
Raised Raised/normal
Normal But patient has hypothyroidismsymptomsConsider thyroid hormone resistance
Diagnose ?
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Hypothyroidism
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TSH T3 T4 TRH Conclusion
Slightlyelevated
normal Normal Compensated hypothyroidismTest for antiTBO and antiTg
Raised Low fT4 Normal/elevated
Primary hypothyroidismTest for antiTBO and antiTg
Low Low fT4 low Tertiary hypothyroidism
Low Low fT4 High Secondary hypothyroidism
Raised Raised/normal
Normal But patient has hypothyroidismsymptomsConsider thyroid hormone resistance
Diagnose ?
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Hashimoto’s thyroiditis
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Antibodies mostlikely directedagainst TBO