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D- ENDOCRINE FUNCTION TESTS. Objectives. Review hormone regulation in health and disease Types of endocrine testing Basic principles behind test Considerations in patient preparation and specimen handling Interpretion of tests applying acquired knowledge. Endocrine System.

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D endocrine function tests
D- ENDOCRINE FUNCTION TESTS


Objectives
Objectives

  • Review hormone regulation in health and disease

  • Types of endocrine testing

    • Basic principles behind test

    • Considerations in patient preparation and specimen handling

    • Interpretion of tests applying acquired knowledge


Endocrine system
Endocrine System

  • Composed of different glands that secrete hormones directly in the blood

  • Some hormones are regulatory in nature

    • Trophic hormones, releasing hormones


D endocrine function tests

External stimuli

HYPOTHALAMUS

Feed back

Releasing hormones

PITUITARY GLAND

Trophic hormones

EFFECTOR ORGAN


Diagnosis of endocrine disorders
Diagnosis of Endocrine Disorders feedback control in normal physiologic conditions

  • Normally, hormone concentration in circulation falls within a predictable range

  • Most hormones are conveniently measured by RIA or other immunoassays.


D endocrine function tests


Endocrine disorders
Endocrine disorders allows for screening and establishing diagnosis of most endocrine disorders.

  • 1o excess àhigh target organ hormones; lowtrophic hormone

  • 1o deficiencyàlow target organ hormone; high trophic hormone

  • 2o excessà high trophic hormone and hormones of target gland

  • 2o deficiencyà low trophic hormone and hormones of the target gland

  • 3o deficiencyà low trophic hormone and hormones of the target gland


Assessment of hormone function
Assessment of allows for screening and establishing diagnosis of most endocrine disorders. Hormone Function

1. Direct measurement of hormone concentration

A. Basal serum hormone levels

B. Hormone measurement in the urine.

  • Urinary excretion of hormone or its metabolite

  • Corrects for fluctuations in blood levels

  • Integrates value over longer period

    2. Dynamic tests

    A. Suppressive tests for hormone excess

    (DST; Glucose ST)

    B. Stimulation test for hormone deficiency (Insulin Induced Hypoglycemia to evaluate Hypothal-PG axis

    3. Image Studies


D endocrine function tests

Ad. cortex allows for screening and establishing diagnosis of most endocrine disorders.

Gonads

Breast

Multiple tissues of

the body

Thyroid

Post. PG.

Anterior PG

Hypothalamus

RF

ADH

Oxytocin

TSH

T4

GH

ACTH

LH

FSH

T3

PRL

Cortisol

Female estrogens/progesterones

Male testosterone


Hypothalamic hormones
HYPOTHALAMIC HORMONES allows for screening and establishing diagnosis of most endocrine disorders.


Anterior pituitary hormones
ANTERIOR PITUITARY HORMONES allows for screening and establishing diagnosis of most endocrine disorders.


Adrenocorticotrophic h acth
Adrenocorticotrophic H allows for screening and establishing diagnosis of most endocrine disorders. (ACTH)

  • Regulation:

    • Corticotrophic releasing hormone (CRH) causes secretion in response to biorhythms with circadian variation

    • Production is regulated by glucocorticoid concentration via the negative feedback mechanism

  • Physiologic action:

    • Stimulate secretion of adrenocorticoids

      • Glucocorticoids (cortisol)

      • Mineralocorticoid (aldosterone)

      • Androgens)

    • Causes sedation, increased pain threshold, autonomic regulation of respiration, BP and HR


Adrenocorticotrophic h acth1
Adrenocorticotrophic H ( ACTH ) allows for screening and establishing diagnosis of most endocrine disorders.

  • Episodic secretion in respose to

    • 1. Falling levels of active glucocorticoids

      • Cortisol ( predominant) 90% inactive bound to CBG(Cortisol binding globulin)

    • 2. Stress

    • 3. Cycles of sleeping and waking

  • Display circadian rhythm

    • Peak: bet 4 am and 8am

    • nadir: at midnight


Adrenocorticotrophic h
Adrenocorticotrophic H allows for screening and establishing diagnosis of most endocrine disorders.

  • Patient preparation:

    • Stressful venipuncture inc levels

  • Specimen collection/handing:

    • Collected in prechilled plastic tubes with EDTA or heparin

    • Place immediately on ice

    • Store at -20 C within 15 min of collection


Tsh or thyrotropin
TSH or Thyrotropin allows for screening and establishing diagnosis of most endocrine disorders.

  • Regulation:

    • TRH from hypothalamus causes secretion in response to low levels of thyroid hormones (T3, T4)

  • Physiologic Function:

    • Stimulates secretion of T3, T4


D endocrine function tests
TSH allows for screening and establishing diagnosis of most endocrine disorders.

  • Serum TSH is single best screening test for thyroid fxn followed by FT4

  • Useful for evaluating both thyroid and pituitary function

  • Elevated serum level:

    • sensitive and specific indicator of primary HYPOTHYROIDISM

  • Normal or decreased level: secondary or tertiary hypothyroidism


Growth hormone
Growth Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • AKA : somatotropin

  • Most abundant hormone of ant PG


Growth hormone1
Growth Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • Regulation:

    • GHRH and GHIH regulates its secretion in response to

      • exercise

      • stress,

      • hypoglycemia

      • Amino acids

      • testosterone

      • estrogen levels

  • Physiologic Function:

    • Promotes growth of soft tissue , cartilage and bone

    • Stimulates Pr synthesis , fat and CHO metabolism


Growth hormone2
Growth Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • Increase GH à gigantism in children

    àacromegaly in adults

  • Decrease GH in children à dwarfism


D endocrine function tests


Growth hormone3
Growth Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • Patient preparation:

    • Patient should be fasting

    • Complete rest for 30 min before collection.

      • Spikes occur 3 hr after meals, stress, or exercise and 90 min after onset of sleep,

  • Specimen:

    • Serum preferred; refrigerate immediately; stable at 2-8C for 8 hr.


Prolactin hormone
Prolactin Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • Biochemical properties similar with GH and placental GH

  • Main target organ: adult female mammary gland


D endocrine function tests

  • Regulation: allows for screening and establishing diagnosis of most endocrine disorders.

    • Regulated by TRH, dopamine

  • Physiologic Function:

    • Increased in pregnancy, sucking

    • Initiates lactation ; growth of mammary tissues; controls osmolality, fat , CHO , Vit D metab and steroidogenesis in the ovary and testis


D endocrine function tests

  • Effects : allows for screening and establishing diagnosis of most endocrine disorders.

    • Suppresses ovulation

    • Stimulates growth of prostate

  • Hypersecretion :

    • Females: hypogonadism , infertility, oligo/amenorrhea , galactorrhea

    • Males: inhibits testosterone secretion, decrease spermatogenesis , infertility and galactorrhea


Prolactin hormone1
Prolactin Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • Levels fluctuate; fluctuations occur Q 95 min,

  • Long half life ( approx 50 min )

  • Physiologically stimulated by :

    • Pregnancy, breast feeding, sleep, dietary Pr, hypoglycemia, exercise and stress


Prolactin hormone2
Prolactin Hormone allows for screening and establishing diagnosis of most endocrine disorders.

  • Patient Preparation:

    • Collect 3-4 hr after awakening;

    • levels increased during sleep and peak in early morning.

    • Avoid emotional stress, exercise, ambulation, protein ingestion ( can increase levels).

  • Specimen:

    • fresh nonhemolyzed serum; stable at 4 C for 24 hr.


Follicle stimulating and luteinizining h
Follicle Stimulating and Luteinizining H allows for screening and establishing diagnosis of most endocrine disorders.

  • Regulated by GnRH from hypothalamus

  • Controls the functional activity of gonads

  • Exhibit episodic, circadian and cyclic variations– best to use serial blood tests or timed urine collection

  • Specimen:

    • Serum, plasma and urine acceptable;

    • Stable 8 days at room temp; two weeks at 4C


Hypothalamic pituitary function tests
HYPOTHALAMIC-PITUITARY FUNCTION TESTS allows for screening and establishing diagnosis of most endocrine disorders.


Hyperpituitarism
Hyperpituitarism allows for screening and establishing diagnosis of most endocrine disorders.

  • Most are due to benign tumors that are autonomous and do not respond to negative feedback control

    • GHsecreted by pituitary adenoma is not suppressed by glucose

  • Exception to the rule of suppressibility:

    • Prolactinoma and Pit adenoma that secrete ACTH(Pituitary Cushing); both are partially autonomous


Gh excess acromegaly
GH Excess: Acromegaly allows for screening and establishing diagnosis of most endocrine disorders.

1. Serum GH

  • Elevated basal or random levels in most acromegalics

  • Basal and random GH may also be inc in

    • Normal patients due to episodic secretion

    • Malnourished patients

    • Anorexia nervosa

    • Patients on estrogen therapy


D endocrine function tests

  • Best test to confirm acromegaly: allows for screening and establishing diagnosis of most endocrine disorders.

    • Measurement of GH following a glucose load.

    • GH is normally suppressed to <2ng/ml one hour after a 75 -100g glucose load.

    • Failure to suppress means a functioning pituitary adenoma


Pituitary hyperpituitarism
Pituitary Hyperpituitarism allows for screening and establishing diagnosis of most endocrine disorders.

2. Serum Somatomedin C

  • Synthesized mainly in the liver

  • Mediates most of the major growth promoting effects of GH

  • Involved in negative feedback regulation of Normal GH secretion

  • Serum level of SM-C is a good screening test for acromegaly

    • Basal SM-C is elevated in acromegaly

    • Maybe elevated in adolescents during the peripubertal growth spurt and during pregnancy


Hypopituitarism gh deficiency
Hypopituitarism : GH deficiency allows for screening and establishing diagnosis of most endocrine disorders.

  • GH testing:

    • Shd be routinely included in evaluating children with short stature

    • Not indicated in adults suspected of hypopituitarism

  • Basal GH levels: not reliable to distinguish deficiency from normal;

    • Baseline measurement : fasting morning sample

    • Factors that increase GH secretion:

      • Low serum glucose, dopamine, exercise


Laboratory diagnosis hypopituatarism gh deficiency
Laboratory diagnosis : Hypopituatarism : GH deficiency allows for screening and establishing diagnosis of most endocrine disorders.

  • Screening tests for GH deficiency:

    • GH measurement after 15 min exercise

    • Measurement of somatomedin:

      • Laron Dwarf: normal GH but low somatomedin


Stimulation test to confirm gh deficiency
Stimulation Test to confirm GH deficiency allows for screening and establishing diagnosis of most endocrine disorders.

  • Stimuli

    • 1. Insulin

    • 2. Arginine

    • 3. L-dopa

    • 4. Clonidine

  • GH should be measured every 30 mins for 2-3 hours

    • Normal: GH increment above baseline >5ng/ml or a maximal GH>7ng/ml

    • GH deficiency: failure to respond to at least two independent stimuli; hypothalamic or pituitary gland dysfunction


Stimulation test
Stimulation test: allows for screening and establishing diagnosis of most endocrine disorders.

Insulin induced hypoglycaemia to investigate suspected GH deficiency.

Insulin decreases plasma glucose concentrations and in a normal person this stimulates the release of GH (A)

A reduced or absent response is seen in a GH deficient patient (B)


Stimulation test to confirm gh deficiency1
Stimulation Test to confirm GH deficiency allows for screening and establishing diagnosis of most endocrine disorders.

  • GH stimulation test (After CRH):

    • A CRH injection is given followed by measurement of the blood level

      • Normal: GH elevated

      • Hypopituitarism: no response


D endocrine function tests

Hypothalamus allows for screening and establishing diagnosis of most endocrine disorders.

Feed back

Bolus injection of releasing hormone

PITUITARY GLAND

Measure Growth Hormone

No response or delayed peak response (60 mins vs 20 mins)


Adrenal function tests
ADRENAL FUNCTION TESTS allows for screening and establishing diagnosis of most endocrine disorders.


Hormones of adrenal gland
Hormones of Adrenal Gland : allows for screening and establishing diagnosis of most endocrine disorders.

  • Hormones of adrenal cortex (adrenal corticosteroids) :

    • Glucocorticoid ( cortisol ) secreted by cells in zona fasciculata –

    • Mineralocorticoid ( aldosterone ) secreted by cells in z. glomerulosa-

    • Sex hormones (testosterone and estradiol ) secreted by cells in zona reticularis

  • Catecholamines (dopamine, epinephrine and NE) secreted by chromaffin cells of adrenal medulla


Glucocorticoid cortisol
Glucocorticoid (Cortisol) allows for screening and establishing diagnosis of most endocrine disorders.

  • Physiologic action:

    • Affects metabolism of proteins, CHO and lipids

    • Stimulates gluconeogenesis by the liver, inhibits the effects of insulin and decrease the rate of glucose use in the cells

  • Regulation:

    • Secreted in response to stress and ACTH

    • Normally:

      secretion higher in early morning (6-8am)

      lower in the evening (4-6pm);

      lowest at midnight

  • Cortisol excess (Cushing’s Syndrome and in patients under stress): loss of diurnal variation in secretion


Circadian rhythm of cortisol secretion
Circadian rhythm of cortisol secretion allows for screening and establishing diagnosis of most endocrine disorders.


Feedback control of adrenal corticosteroid synthesis and release
Feedback control of Adrenal Corticosteroid synthesis and release

Decreased blood levels of adrenal corticosteroids, stress

Hypothalamus secretes corticotrophin releasing hormone (CRH)

Hormone secretion suppressed via negative feedback

Ant Pit g gland secretes ACTH

Adrenal cortex secretes hormones (cortisol)


Corticosteroid excess cushing syndrome
Corticosteroid Excess release: Cushing Syndrome:

  • Hyperadrenalism with production of excess cortisol

  • Clinical Presentation:

    • 1. Glucocorticoid Effects: “cushingoid habitus”, bone dimineralization, glucose intolerance

    • 2. Mineralocorticoid effects: HPN, edema, hypokalemic alkalosis

    • 3. Sex steroid effects: hirsutism, acne, amenorrhea, gynecomastia


Cushing syndrome causes
Cushing Syndrome: Causes release

  • Exogenous glucocorticoid therapy (most common cause)

  • Other causes:

    • 1. ACTH Producing pituitary adenoma (60%)

  • ( Cushing disease)

    • 2. Glucocorticoid producing adrenal neoplasm(20%)

  • (adenoma or carcinoma)

    • 3. Ectopic ACTH-producing neoplasm(20%)


Tests for adrenal hormone function
Tests for Adrenal Hormone Function release

1. Serum cortisol

-Secretion is episodic and pulsatile in response to ACTH

-Single determination neither specific or sensitive

-90-97% is bound to CBG or transcortin

- Elevated in adrenal hyperfunction (Cushing’s Sx)

- Decreased in adrenal hypofunction (Addison’s)

- Diurnal rhythm of cortisol secretion is lost in Cushing Sx and patients under stress


D endocrine function tests

2. releaseUrine Free Cortisol (UFC):

**Glucocorticoids:

  • Degraded in the liver and excreted in the urine as Hydroxycorticosteroid (17-OHCS).

  • Urine 17 OHCS is an indirect measurement of excessive plasma Glucorticosteroid

    -indirect measure of the cortisol production rate

    -Normal: <90ug/24hr

    - UFC> 250mg/24 hr is almost always due to Cushing Sx


D endocrine function tests

  • 3 release. Dexamethasone Suppression Test

    • Dexamethasone: cortisol analoque that should suppress ACTH in normal person and reduce cortisol.

  • Rapid DST for screening (low Dose DST)

    • Administer 1 mg dexamethasone at 11pm; measure 8am the following day:

    • Normal: Suppressed cortisol <5ug/dl

    • No suppression in Cushing’s Sx: useful for screening


D endocrine function tests

Dexamethasone releaseSuppression Test

Normal person: dexamethasone will suppress ACTH secretion (feedback) and cortisol production is consequently reduced.

No suppression to low dose: Cushing Syndrome

Ectopic ACTH Syndrome: no suppression even to HDST

In pituitary- dependent Cushings only high doses may suppress ACTH secretion


Adrenal function test
Adrenal Function Test release

1. Plasma ACTH level

  • Increased : pituitary tumors

    ectopic ACTH producing tumors

  • Decreased: cortisol producing tumors in adrenals

    exogenous hormones


Adrenal function test1
Adrenal Function Test release

  • 2. Overnight HIGH DOSE DST:

    • Procedure: Administer 8mg at 11pmà measure serum cortisol 8am before and on the morning following dexamethasone

  • ACTH producing adenoma : Suppression of cortisol to 50% of basal

  • Adrenal neoplasm or ACTH syndrome: No suppression of cortisol


Primary adrenal insufficiency addison s disease
Primary Adrenal Insufficiency (Addison’s Disease) release

  • Deficiency of all adrenal steroids

  • Relatively rare

  • Results from progressive destruction of adrenals by local disease or systemic disorder


Adrenal function test for adrenal insufficiency
Adrenal Function Test for Adrenal Insufficiency release

  • 3. Metyrapone test

    Metapyrone: Blocks 11 beta-hydroxylase in ad. cortex which reduces synthesis of cortisol hence stimulate synthesis of ACTH with proximal buildup of deoxycortisol in adrenal

  • Procedure:

  • 1. Administer 3.0 mg metyrapone at midnight.

  • 2. Measure cortisol and 11 deoxycortisol at 8am baseline

  • and post-metyrapone


D endocrine function tests

deoxycortisol release

Metapyrone

11-β Hydroxylase

Cortisol

  • Metapyrone: Blocks 11 beta-hydroxylase in ad. cortex which reduces synthesis of cortisol hence stimulate synthesis of ACTH with proximal buildup of deoxycortisol in adrenal


D endocrine function tests

  • Metyrapone Test release:

    • Normal response: fall in cortisol to <5ug/dl and increase in ACTH, 11 deoxycortisol and urinary 17-OHCS

    • Cushing’s Dse: Increase in 11-deoxycortisol levels

    • Adrenal tumors/Ectopic ACTH: 11-deoxycortisol fails to increase

    • Failure of cortisol to fall invalidates the test

    • Not routinely used, although maybe better than High dose DST


Adrenal function test2
Adrenal Function Test release

  • Cortisone Stimulation (Cosyntropin); ACTH Stimulation

    • Screening test; less time consuming; can be done on OPD basis

    • Cortrosyn (synthetic subunit of ACTH) have full stimulating effect of ACTH in healthy individuals

      -à failure to respond : adrenal insufficiency

  • Procedure:

  • 1. Get 4ml fasting blood venous sample at 8am

  • 2. Administer cosyntropin IM/IV

  • 3. Get 4ml samples at 30 and 60 mins after


Mineralocorticoid aldosterone
Mineralocorticoid (Aldosterone) release

  • Regulation:

    • ALDOSTERONE (predominant mineralocorticoid) is secreted by cells in the zona glomerulosa in response to ANGIOTENSIN (mainly); and by ACTH (not significant)

  • Clinical effects

    • Retains Na and H20 accompanied by K depletion leads to excess intravascular volumeà HPN


Aldosterone
Aldosterone release

  • Elevated levels (primary aldosteronism)

    • Conn’s disease ( aldosterone producing adenoma)

  • Elevated levels (secondary aldosteronism) because of extenal stimuli or greater activity in the RAS:

    • Salt depletion

    • Potassium loading

    • Cardiac Failure

    • Nephrotic syndrom

    • Diuretic abuse


Aldosterone1
Aldosterone release

  • Decreased levels of aldosterone:

    • Aldosterone deficiency

    • Addison’s disease


Tests for hyperaldosteronism
Tests for hyperaldosteronism: release

  • 1. Basal level of plasma aldosterone

    *limited diagnostic value

  • 2. Urinary Aldosterone

  • 3. Captopril Suppression Test

    • Angiotensin- converting enzyme inhibitor: decrease the renin-stimulated aldosterone production secondary aldosteronism; no response in primary aldosteronism


Test for hyperaldosteronism
Test for hyperaldosteronism: release

  • 5. Aldosterone Suppression test (Isotonic Saline infusion)

    • Normal response à suppress aldosterone release by decreasing renin

    • Primary aldosteronism à lack of aldosterone suppression

  • 6. Aldosterone Stimulation Test ( Sodium restricted from diet)

    • Normal responseà renin level increased

    • Primary aldosteronismà slight or no response in renin level


Adrenal insufficiency
Adrenal Insufficiency: release

  • 1. Serum cortisol decreased

  • 2. Rapid ACTH stimulation test

  • 3. Long ACTH stimulation test

  • 4. Serum ACTH

    • Elevated in primary adrenal insufficiency

    • Decreased in secondary and tertiary

  • 5. Metapyrone test


Pheochromocytoma cathecolamine excess
PHEOCHROMOCYTOMA: release Cathecolamine Excess

  • 1. Increased cathecolamines at all times.

    • Cathecolamines: either epinephrine or norepinephrine is increased and should be assayed separately.

    • Plasma norepinephrine >750pg/ml or

    • Epinephrine >100pg/ml are found in 90-95% of patients

  • 2. Urine test

    • Vanyllmandelic acid

    • Total metanephrine

    • Fractionated cathecholamines


Pheochromocytoma cathecolamine excess1
PHEOCHROMOCYTOMA: release Cathecolamine Excess

  • 3. Clonidine Suppression test:

    • Clonidine (alpha agonist) à decrease efferent symphathetic flow

      • Normal: Norepinephrine level within N range

      • Pheochromocytoma: exaggerated response


Pheochromocytoma patient preparation
PHEOCHROMOCYTOMA: release Patient Preparation

  • Blood should be drawn through a previously inserted catheter from a patient who is fasting, resting quietly and non-stressed.

  • If patient is to kept on antiHPN meds during resting

    • The least interfering agents shld be used:

      • diuretics.

      • Vasodilators, and

      • alpha or Beta adrenergic blockers.




Hormone regulation
Hormone Regulation release

  • TRH à TSH

    • iodine uptake, organification

    • synthesis & release of thyroid hormone

  • T4/T3 Regulate:

    • basal metabolism, thermogenesis, lipogenesis

    • fetal CNS development


Regulation of thyroid hormone secretion
Regulation of thyroid hormone secretion release

  • >99% of thyroid hormones are carried in plasma bound to protein

  • <1% is free & active

    • Thyroxin-binding protein (TBG) binds most of the T4 and T3

      • TBG is synthesed by liver, ∴severe liver disease → ↓TBG → ↓ TT4 due to ↓ protein-bound T4

      • ↑ Estrogen (ex. Pregnancy) → ↑ synthesis of TBG → ↑ total T4 due to ↑ protein-bound T4

    • Albumin and pre-albumin also carry T4 and T3 in plasma


Thyroid hormones
Thyroid Hormones release

  • Triiodothyronine (T3)

    • 80% in Periphery

      • Liver/kidney remove iodine from T4

    • t1/2: 1-1.5 days

  • Thyroxine (T4)

    • Thyroid gland

    • t1/2: 8 days


Binding proteins
Binding Proteins release

  • T4/T3 99% protein bound

    • Prevents excess tissue uptake

    • Maintains accessible reserve


D endocrine function tests

T4 release

Protein* binding + 0.03% free T4

80%

T3

Protein* binding + 0.3% free T3

20%

(10-20x less than T4)

Total T460-155 nM

Total T30.7-2.1 nM

T3RU/THBI0.77-1.23

*TBG 75%

TBPA 15%

Albumin 10%


Thyroid function tests
Thyroid Function Tests : release

  • TSH

  • T3

  • T4

  • FTI ( free thyroxine index ), FT4 ( free thyroxine )

  • TRH

  • TBG ( Thyroid binding globulin )


D endocrine function tests


Thyroid function tests1
THYROID FUNCTION TESTS 200ng/dl)

  • THYROID STIMULATING HORMONE (TSH)

    • Stimulated by TRH (from hypothalamus)

    • Serum TSH is single best screening test for thyroid fxn followed by FT4

    • Useful for evaluating both thyroid and pituitary function

    • Elevated serum level:

      • sensitive and specific indicator of primary HYPOTHYROIDISM

    • Normal or decreased level: secondary or tertiary hypothyroidism


Clinical uses of tsh
Clinical Uses of TSH 200ng/dl)

  • Screening for euthyroidism

  • Initial screening and diagnosis for hyperthyroidism (dec. to undetectable levels except in rare TSH-secreting pituitary adenoma) and hypothyroidism

  • Useful in early or subclinical hypothyroidism before the patient develops clinical findings


Clinical uses of tsh1
Clinical uses of TSH 200ng/dl)

  • Differentiate primary (increased levels) from central [pituitary or hypothalamic] hypothyroidism (decreased levels)

  • Monitor adequate thyroid hormone replacement therapy in primary hypothyroidism


Tsh increased in
TSH increased in : 200ng/dl)

  • Primary untreated hypothyroidism

  • Hypothyroidism receiving insufficient thyroid hormone replacement therapy

  • Hashimoto thyroiditis


Thyroid function tests total t4 and t3
THYROID FUNCTION TESTS 200ng/dl): Total T4 and T3

  • 1. TOTAL THYROXINE(T4) ANDTRIIODOTHYRONINE(T3) LEVELS

    • Total thyroxine (T4) is a good index of thyroid fxn when TBG are normal

    • T3 level- in cases of hyperthyroidisn with normal or low T4: T4; useful in monitoring therapy


Thyroid function tests total thyroxine t4
THYROID FUNCTION TESTS: 200ng/dl)Total Thyroxine ( T4)

  • High: hyperthyroidism and acute thyroiditis

  • Low: hypothyroidism and chronic thyroiditis

  • Affected by concentration of binding proteins (TBG)


Thyroid function tests total serum t3 triiodothyronine
THYROID FUNCTION TESTS: 200ng/dl)Total Serum T3 ( Triiodothyronine )

  • Elevated proportionately to T4 in hyperthyroidism

  • Decreased in hypothyroidism

  • T3 thyrotoxicosis ( 5% of ind.) T3 elevated while T4 is normal

  • Not routinely measured except to monitor tx of T3 thyrotoxicosis


Thyroid function tests thyroxine binding globulin
THYROID FUNCTION TESTS: 200ng/dl)Thyroxine Binding Globulin

  • A glycoprotein: synthesized in the liver

  • Principal serum carrier for T4 ( 75% ) and T3

  • Less than 1% of T3 and T4 are in the free form which determines function

    • Estrogen influences thyroxin binding

    • Phenytoin, coumarin, heparin clofibrate and aspirin compete with T3 & T4 for TBG binding sites

  • Measurement is rarely indicated


T3 uptake
T3 Uptake 200ng/dl)

  • Indirect measurement of unsaturated TBG in blood

  • Determination is expressed in arbitrary terms is inversely proportional to the TBG

    • Low T3U is indicative of conditions where there is elevated levels of TBG uptake


T3 uptake1
T3 Uptake 200ng/dl)

  • Hypothyroidism: insufficient T4 to saturate TBGà unbound TBG is elevated and T3U values are low

  • Pregnant patients: TBG are increased proportionately more than T4 levelsà high levels of unbound TBG reflected in low T3U values

  • Useful only when T4 is done

  • Used to calculate FTI or F7


T3 uptake2
T3 Uptake 200ng/dl)

  • Procedure:

    • Known amount of radiolabeled T3 is added to test serum

    • Available binding sites in test serum combine with labeled T3 inversely proportional to the amount of endogenous T4 already bound


D endocrine function tests


D endocrine function tests

  • Resin is used to measure residual radioctivity react with labeled T3—measured residual radiocativity is low

    • Low residual activity—numerous binding sites unoccupied( low endogenous T4)

    • High residual activity—few binding sites unoccupied( high endogenous T4)

  • Results are expressed as % radioactivity left unbound

  • Hyperthyroidism: both T4 and T3U high values

  • Hypothyroidism: both T4 and T3U have low values


Thyroid function tests free thyroxine index
THYROID FUNCTION TESTS: react with labeled T3—measured residual radiocativity is lowFREE THYROXINE INDEX

  • Correlates better with clinical status

    in the presence of abnormalities in TBG

  • Calculated as the product of absolute thyroid hormone and the binding capacity of TBG

    • FTI= Measured FT4 (T4 x Value of T3 Uptake)

      • (Reference Interval=1-4.2)

      • Normal in pregnancy;

      • low in hypothyroidism;

      • high in hyperthyroidism


Thyroid function tests2
Thyroid Function Tests react with labeled T3—measured residual radiocativity is low


Interpreting thyroid function tests
Interpreting Thyroid Function Tests react with labeled T3—measured residual radiocativity is low


Clinical patterns of thyroid disease
Clinical patterns of react with labeled T3—measured residual radiocativity is lowthyroid disease

  • Hyperthyroidism-

    • Lab: excessive levels of TH ( T3 , T4 ) ;

    • S/sx: heat intolerance, palpitation, weight loss, tachycardia tremors

    • Causes: Graves Ds, toxic adenoma, toxic goiter , TSH secreting pituitary adenoma


D endocrine function tests

  • Hypothyroidism – react with labeled T3—measured residual radiocativity is low

    • Lab: decrease levels of TH

    • S/sx: Bradycardia, cold sensitivity, dry skin, muscle weakness , myxedema, cretinism

    • Causes : TG ablation and destruction ( primary ) ; pituitary hypofuncytion of TSH (secondary )


Laboratory diagnosis of thyroid disease
Laboratory Diagnosis of Thyroid Disease react with labeled T3—measured residual radiocativity is low

  • 1° thyroid dis. is abnormality in the thyroid gland

    • TRH and TSH level just reflect N feedback response

  • 2° thyroid dis. is really an abnormality in pituitary gland which cause error in amount of TSH produced

    • T4 and T3 conc’n just reflect N feedback response

  • 3° thyroid dis. is abnormality in hypothalamus causing error of TRH produced

    • Both TSH and T4 & T3 levels just reflect N feedback response


Measuring trophic hormones and hormones of the peripheral endocrine gland
Measuring trophic hormones and hormones of the peripheral endocrine gland

High TSH - Low T3/T4 1o

Hypothyroidism

Low TSH - High T3/T4 1o

Hyperthyroidism

Low TSH - Low T3/T4 2o

Hypothyroidism


Euthyroid sick syndrome
“Euthyroid Sick Syndrome” endocrine gland

  • Severe illness often results in low serum levels of T3 and T4

  • Causes:

    • 1. Decreased in serum pre albumin in severe illnessà decrease in hormone binding capacity

    • 2. Fall in amount of T4 deiodinatd to T3 with increase in the metabolic pathways leadig to the inactive product reverse T3

  • Diagnosis: demonstrating normal TSH level.


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