Hypothyroidism: Evaluation & Management by Dr Selim

Hypothyroidism: Evaluation & Management by Dr Shahjada Selim

1. Hypothyroidism:
Evaluation & Management
Dr Shahjada Selim
Associate Professor, Department of Endocrinology, BSMMU
Visiting Professor in Endocrinology, Texila American University, USA
Website:http://shahjadaselim.com

2. Definition
Hypothyroidismmeansthatthethyroidgland
can’tmakeenoughthyroidhormonetokeep
thebodyrunningnormally.Inhypothyroidism
thyroidglandisunderactivethetissuesareto
toolittlethyroidhormone.
ATA 2021: https://www.thyroid.org/hypothyroidism/Accessedon 21/01/2021

3. Epidemiology
-Hypothyroidism occurs in 3 to
6% for the adult population, but
is symptomatic only in a minor
of them.
-Usually develops after the age
of 30
-It occurs 8 to 10 times more
often in women than in men

4. Classification of Hypothyroidism
I. Congenital
II. Acquired
1. Subclinical hypothyroidism
2. Clinical hypothyroidism
1. Primary(thyroid gland disturbances).
2. Secondary(due to pituitary disease).
3.Tertiary(due to hypothalamic disease).
4.Peripheral.

5. Etiology of Hypothyroidism
Congenital
-Maldevelopment –hypoplasia or aplasia
-Inborn deficiencies of biosynthesis or action of thyroid
hormone
-Atypical localization of thyroid gland
-Severe iodine deficiency
Primary Hypothyroidism

6. Acquired
-iodine deficiency
-autoimmune processes (Hashimoto’s thyroiditis):
MAE 1 & 2
-surgical -total thyroidectomy
-irradiation therapy (organs of the neck)-I131
therapy
-during or after therapy with propylthyouracil,
methimazole, iodides for hyperthyroidism
-infiltrative diseases (tuberculosis, actynomycosis)
-trauma
-medications such as amiodarone, interferon alpha,
thalidomide

7. Etiology of Peripheral Hypothyroidism
peripheral tissue resistance to thyroid hormones
decreasing of T4 peripheral transformation into
T3 (in liver or in kidneys)
production of antibodies to thyroid hormones

8. Clinical Features of Hypothyroidism

9. Skin &
Hair
-Skin is dry, thick and silk, is often cool and
pale.
-Nonpitting edema of the hands, feet and
periorbital regions (myxedema). Pitting
edema also may be present.
-The faces are puffy and features are
coarse.
the loss of the lateral aspect
of the eyebrow, sometimes
termed Queen Anne's sign

10. -Skin may be orange due
to accumulation of
carotene.
-Hair may become course
and brittle, hair growth
slows and hair loss may
occur. Lateral eyebrows
thin out and body hair is
scanty.
-Hypothyroidism does not
cause obesity, but
modest weight gain from
fluid retention and fat
deposition often occurs
Skin & Hair

11. NERVOUS
SYSTEM
Patientscomplainonfatigue,lossof
energy,lethargy,forgetfulness,
reducedmemory.
-Theirlevelofphysicalactivity
decreases,andtheymayspeakand
moveslowly.Mentalactivitydeclines
andthereisinattentiveness,
decreasedintellectualfunction,and
sometimesmaybedepression.
-Neurologicalsymptomsincludealso
hearingloss,parasthesias,objective
neuropathy,particularlythecarpal
tunnelsyndrome,ataxia.
-Tendonreflexshowsslowedorhung-
uprelaxation.

12. CARDIOVASCULAR
SYSTEM
Complains on: dyspnea, pain in the
region of the heart
Objective examination:
Increased peripheral resistance
Hypertension (Diastolic)
Bradycardia
LV hypertrophy with decreased
contractility, reduced cardiac output
Pericardial effusion
Congestive heart failure
-The ECG may show low voltage
and/or non-specific ST segment
and T wave changes.
-Hypercholesterolemia

13. Gastrointestinal System
-Gastrointestinal motility is
decreased loading to constipation
and abdominal distension,
pseudoobstruction of intestines,
paralytic ileus.
-Abdominal distension may be
caused by ascities as well. Ascitic
fluid, like other serous effusions in
myxedema, has high protein
content.
-Achlorhydria occurs, often
associated with pernicious anemia.

14. RENAL SYSTEM
-Reduced excretion of a water load may be
associated with hyponatriemia
-Renal blood flow and glomerular filtration rate are
reduced, but serum creatinine is normal
-May be mild proteinuria and infections of urinary
tract

15. -Dyspnea of effort is common.
This complaint may be caused by enlargement of the
tongue and larynx, causing upper airway obstruction, or
by respiratory muscle weakness, interstitial edema of
the lungs, and for plural effusions which have high
protein content
-Hoarseness from vocal curt enlargement often occurs
Respiratory system

16. Musculoskeletal System
-Muscleandjointaches,painsandstiffnessare
common
-Objectivemyopathyandjointswellingoreffusions
arelessoftenpresent
-Therelaxationphaseofthetendonreflexesis
prolonged
-Serumcreatinephosphokinaseandalanine
aminotransferaseactivitiesareoftenincreased,
probablyasmuchtoslowedenzymedegradation
astoincreasedreleasefrommuscle

17. BLOOD DISORDERS
-Anemia,usuallynormocytic,
causedbydecreasedredblood
cellproduction,mayoccur.
Itisprobablyfromdecreasedneedofperipheral
oxygendeliveryratherthanhematopoeticdefect
-Megaloblasticanemiasuggestscoexistentpernicious
anemia
-Mostpatientshavenoevidenceiron,folicacidor
cyancobalamindeficiency

18. Endocrine System
-Thyroid gland:nonpalpable or enlargement.
-Adrenal glands: hypofunction
-Pituitary system: secretion of growth hormone is
deficient because thyroid hormone is necessary for
synthesis of growth hormone. Growth and development
of
children are retarded. Epiphyses remain open.
-Gonadal glands: menorrhagia (from
anovulatory cycles), secondary amenorrhea,
infertility and galactorrhea; decreased fertility in men

19. Metabolic System
-Hypothermiaiscommon
-Hyperlipidemiawithincreaseofserum
cholesterolandtriglycerideoccursbecause
ofreducedlipoproteinlipaseactivity

20. CLINICAL FEATURES
Hypothyroidism can be presented in many
different ways and can mimic other disorders
Because many manifestations of
hypothyroidism
are non-specific,
the diagnosis is particularlylikely to be
overlooked
in patients with otherchronic illnesses and
elderly
and can lead to significant morbidity and even
mortality

21. Subclinical Hypothyroidism
ItisanasymptomaticstateinwhichserumT4andfree
T4arenormal,butserumTSHiselevated.This
designationisonlyapplicablewhenthyroidfunction
hasbeenstableforweeksormore,thehypothalamic-
pituitary-thyroidaxisisnormal,andthereisnorecent
orongoingsevereillness.
Itisastateinwhichclinicalfeaturesofhypothyroidism
areusuallyabsentandeuthyroidismisreachedby
compensatoryincreasingofTSHsecretionandthat’s
whysynthesisandsecretionofsuchlevelofthyroid
hormonethatwillbeenoughfororganism.

23. Potential benefits from treatment
Prevent progression to overt hypothyroidism
Improve serum lipid profile, which may reduce the
risk of death from cardiovascular causes
Reduce symptoms, including psychiatric and
cognitive abnormalities
Better fertility outcome
Improves menstrual irregularities
Cooper DS. N Engl J Med. 2001;345:260-264.
Rationale for Treating
Subclinical Hypothyroidism

24. Recommendations Organizations Regarding Screening of
Asymptomatic Adults for Thyroid Dysfunction
Organization Screening Recommendations
American Thyroid
Association
Women and men >35 years of age
should be screened every 5 years.
American Association of
Clinical Endocrinologists
Older patients, especially women,
should be screened.
American Academy of
Family Physicians
Patients ≥60 years of age should be
screened.
American College of
Physicians
Women ≥50 years of age with an
incidental finding suggestive
of symptomatic thyroid disease
should be evaluated.
U.S. Preventive Services
Task Force
Insufficient evidence for or against
screening
Royal College of
Physicians of London
Screening of the healthy adult
population unjustified

25. Diagnosis: Algorithm

26. Treatment of Hypothyroidism
No specific diets are
required for
hypothyroidism.
Regimen is not restricted
Therapy of
the cause
Pathogenetic
replacement therapy
Thyroid
hormones
Symptomatic
Treatment
of complications

27. HYPOTHYROIDISM TREATMENT GOAL
EUTHYROIDISM
Thegoalofhypothyroidismtherapyisto
replacethyroxinetomimicnormal,
physiologiclevelsandalleviatesigns,
symptoms,andbiochemicalabnormalities
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

28. Hypothyroidism TREATMENT
Levothyroxine sodium is the treatment of choice for
the routine management of hypothyroidism
Adults:about 1.7 g/kg of body weight/d
Children up to 4.0 g/kg of body weight/d
Elderly <1.0 g/kg of body weight/d
Clinical and biochemical evaluations at 6-to 8-week
intervals until the serum TSH concentration is
normalized
Given the narrow and precise treatment range for
levothyroxine therapy, it is preferable to maintain the
patient on the same brand throughout treatment
Singer PA, et al. JAMA. 1995;273:808-812.
Endocr Pract. 2002;8:457-469.

29. Primary Hypothyroidism Treatment Algorithm
TSH >3.0 IU/mL TSH <0.5 IU/mL
Initial Levothyroxine Dose
Increase
Levothyroxine
Dose by
12.5 to 25 g/d
Repeat TSH Test
6-8 Weeks
TSH 0.5-2.0 IU/mL
Symptoms Resolved
Measure TSH at 6 Months,
Then Annually or
When Symptomatic
Continue Dose Decrease
Levothyroxine
Dose by
12.5 to 25 g/d
Singer PA, et al. JAMA. 1995;273:808-812.
Demers LM, Spencer CA, eds. The National Academy of Clinical
Biochemistry Web site. Available at:
http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.

30. Therapy Monitoring
Clinical and laboratory monitoring enable
Evaluation of the clinical response
Assessment of patient compliance
Assessment of drug interactions, if applicable
Adjustment of dosage, as needed
Clinical and laboratory evaluations should be
performed
At 6-to 8-week intervals while titrating
Every 6 –12 months once a euthyroid state is established
Singer PA, et al. JAMA. 1995;273:808-812. Demers LM, Spencer CA, eds.
Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at:
http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.

31. Caution in Patients with Underlying
Cardiac Disease
UsingLT
4inthosewithIHDincreasestheriskofMI,
aggravationofangina,orcardiacarrhythmias
Forpatients<50yearsofagewithunderlying
cardiacdisease,initiateLT
4at25-50g/dwith
gradualdoseincrementsat6-to8-weekintervals
Forelderlypatientswithcardiacdisease,startLT
4at
12.5-25g/d,withgradualdoseincrementsat4-to
6-weekintervals
TheLT
4doseisgenerallyadjustedin12.5-25g
increments
Braverman LE, et al. Werner & Ingbar’sThe Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Kohno A, et al. EndocrJ. 2001;48:565-572.
Synthroid
®
[package insert]. Abbott Laboratories; 2003.

32. Factors That May Reduce Levothyroxine Effectiveness
Malabsorption Syndromes
Post-jejunoileal bypass
surgery
Short bowel syndrome
Celiac disease
Reduced Absorption
Colestipol hydrochloride
Sucralfate
Ferrous sulfate
Food (eg, soybean formula)
Aluminum hydroxide
Cholestyramine
Sodium polystyrene
sulfonate
Drugs That Increase
Clearance
Rifampin
Carbamazepine
Phenytoin
Factors That Reduced T
4to
T
3Clearance
Amiodarone
Selenium deficiency
Other Mechanisms
Lovastatin
Sertraline
Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8
th
ed. 2000.
Synthroid
®
[package insert]. Abbott Laboratories; 2003.

33. Is There Any Role for T3
Supplementation in The
Management of Hypothyroidism?

34. NO!

35. Congenital Hypothyroidism (CH)
Congenital hypothyroidism (CH) is defined as
thyroid hormone deficiency present at birth
It can occur because of an anatomic defect in the
gland, an inborn error of thyroid metabolism, or
iodine deficiency.
Diseases may manifest from birth or
later

36. EPIDEMIOLOGY
Incidenceincreasedtoabout1in2,000dueto
morestringentscreeningstrategies.
IncidenceinBangladesh1:1,300,Accordingto
theresearchpaperof'InstituteofNuclear
Medicine,Dhaka,Bangladesh'.
Male:Female=1:2
1: 4000

37. Neonatal Physiology
Surge in
TSH
30 mins
after
delivery
peak at
6 hours
rapiddecline
over24hrs.
T3 and
T4 levels
increasesharply
within 24 hours slow decline
Preterm infant-TSH
surge is less
marked
T4 and T3 responses are blunted.

38. Permanent
Primary
Secondary
Peripheral
Transient
Classification

39. Etiology of Congenital Hypothyroidism
Primary CH
Thyroid
dysgenesis: 85% -
agenesis, hypoplasia,
ectopia
dyshormonogenesi
s-15%
Resistance to TSH
binding
Secondary
(central) CH
TSH
deficiencies
Congenital
hypopituitarism
(multiple pituitary
hormone
deficiencies)
Peripheral CH
Thyroid
hormone
-transport defect
-metabolism
defect
-Thyroid
hormone
resistance

40. Clinical Manifestations..
95%-asymptomaticatbirth
Someinfantsescapenewbornscreening,and
laboratoryerrorsoccur,sopediatriciansmuststill
bealertforsymptoms andsignsof
hypothyroidismiftheydevelop.

41. Clinical Manifestations…..
Early
Prolong gestation
Large poteriorfontanelle
Hypotonia
Feeding / respiratory difficulty
Delayed passage of meconeum
Constipation
Umbilical hernia
Prolonged neonatal jaundice
Hypotharmia
•Late
Coarse/puffy face
Coarse hair
Large Tongue
Myxedema, Hoarse
cry
Hearing Impairment
Speech delay

42. Newborn Screening
Screening Technique
Specimen is blood spot in filter paper
Obtained by heel prick
and Cord blood

43. Screening Protocols for CH:
Threeapproachesrebeingusedforscreening:
1.PrimaryTSH,Backupt4
2.PrimaryT4,BackupTSH
3.ConcomitantT4andTSH
Optimum time 2-5 days of age

44. American Academy of Pediatrics
Recommended Screening
NICU/Preterm/Home delivery –
5 to 7 days of birth.
Mother on thyroid medication/
Family history of CH –
screen cord blood.
For infants 1,500 g birth weight,
repeat specimens should be sent at
2, 6, and 10 weeks of age due to
the risk of delayed TSH elevation.

45. Who Needs Special Attention
Pretermandlowbirthweightinfants
Infantswithtrisomy21orcardiacdefectshave
anincreasedriskofcongenitalhypothyroidism.
Monozygotictwins,iftheyaremonochorionic,
fetalhypothyroidismintheaffectedtwinmay
getcompensatedbythenormaltwinthrough
theirsharedfetalcirculation.

46. AcordbloodTSHvalueof>20mIU/Lcan
beusedforthepurposeofscreeningfor
congenitalhypothyroidism.
Forlogisticangles,ahighercutoffof>30
mIU/Lcanbeused.

47. Serum thyroglobulin
Anti thyroid antibody (TBG-AB)-In case of maternal
autoimmune disease
CBC with PBF-anaemia(normo, micro and macro)
CXR-Cardiomegaly
ECG-bradycardiaand low voltage ECG
CT Scan and MRI
Other relevant Investigation

48. New born screening
TSH > 20 MIU/L
High TSH
Low T4
TransientHypothyroidismor
permanentHypothyroidism
Start treatment soon,
Further investigation to identify the cause
High TSH
Normal T4
FT4, TSH again
TSH > 20mIU/L
TSH 6 -20 mIU/L:
Repeat FT4, TSH weekly until
normal,
≥10 mIU/L Persistently consider
Rx
When To Start Treatment?
CH?

49. Levothyroxine
TherecommendeddoseofLT4is10-15μg/kg/daygiven
orally
Rapidnormalizationofthyroidfunction(ideallywithin2
wk)isimportantinachievingoptimalneuro-developmental
outcome.
Levothyroxinmustbeingestedintheemptystomach,
avoidsoya,calciumandironcontainingdiet
Treatment..

50. FOLLOW-UP
CLINICAL FOLLOW-UP
Clinicalassessmentofgrowthanddevelopment,
shouldbeperformedeveryfewmonthsduring
thefirst3yearsoflife.

51. Lab Follow-up
Serum T4 and TSH measurements should be performed
1.2 and 4 weeks after the initiation of L-T4 treatment
2.4 weeks after any change in LT4 dosage.
3.every 1 to 2 months during the first 6 months of life
4.every 3 to 4 months between 6 months and 3 years
5.every 6 to 12 months until growth is completed; and
6.at more frequent intervals when compliance is questioned, or
abnormal values are obtained.

52. Need A Life Long Therapy?
About35%ofinfantswithcongenital
hypothyroidismmayhavetransientdiseaseand
donotrequirelifelongtherapy.
Inpatientswithtransientdisease,atrialoffLT4
for4wkmaybeundertakenafter3yrofageto
assesswhethertheTSHrisessignificantly,
indicatingthepresenceofpermanent
hypothyroidism.
Butthisisunnecessaryininfantswithproven
thyroiddysgenesis.Needlifelongtherapy.

53. Prognosis
Developmental Outcome: The best outcome occurred
with replacement therapy:
-started by 2 weeks of age, and
-At a dose of ≥ 9.5 microg/kg /day , compared with lower
doses or later start of therapy.
SchokkingJJB,KootHM,WiersmaD,VerkerkPH,deMuinckKSSM.Influenceoftiminganddoseofthyroid
hormonereplacementondevelopmentininfantswithcongenitalhypothyroidism.JPediatr.)2000.

54. Precipitating Factors Include
exposure to cold
infection
Trauma
Surgery
Myocardial infarction
Bleeding
Stress situation
Drugs that suppress the CNS
Myxedemacoma -is a life-threatening
complication of hypothyroidism

55. -Slow development (weakness, somnolence, coma)
-extreme hypothermia (temperatures 24 to 32°C)
-Areflexia
-Seizures
-Bradycardia, hypotension
-Polyserositis
-CO2 retention, and respiratory depression caused by
decreased cerebral blood flow, nonreversible brain
changes
-Rapid diagnosis (based on clinical judgment, history, and
physical examination) is imperative because early death is
likely.
Clinical Features

56. Treatment of Myxedema Coma
-largedosesofT4(200-500mcgi/v
bolus3–4timesaday)orT3if
available(40–100mcgi/vbolus3
timesaday),becauseTBGmustbe
saturatedbeforeanyfreehormoneis
availableforresponse.
-ThemaintenancedoseforT4is50
mgm/kg/dayi/vandforT310-20
mcg/dayi/vuntilthehormonecanbe
givenorally.

57. TREATMENT OF MYXEDEMA COMA
-Corticosteroidtherapy(hydrocortisone
200–400–600mg/dayi/v).
-Thepatientshouldnotberewarmed
rapidlybecauseofthethreatofcardiac
arrhythmia.
-Hypoxemiaiscommon,soPaO2
shouldbemeasuredattheoutsetof
treatment.Ifalveolarventilationis
compromised,immediatemechanical
ventilatoryassistanceisrequired.

58. Case1:
A35-year-oldladycomplainedofweightgain
andmenorrhagiafor6months,onexamination
herskiniscoldandrough,pulse59per
minute,BP145/95mmHg,eyesarebaggy
withsparsehair,nothyromegaly.
FurtherEvaluation
DifferentialDiagnosis
ConfirmedDiagnosis

59. Case2:
A55-year-oldmancametoyouwiththe
complaintoflegswelling,weaknessand
somnolence.Onexaminationhewasmildly
anemic,hypertensiveandascarmarkwas
presentinfrontofhisneck.Hehadno
breathlessnessandurinaryproblem?