The document provides a comprehensive overview of hypothyroidism, detailing its anatomy, physiology, causes, classifications, symptoms, and treatments. It highlights the significance of thyroid hormones in the regulation of metabolism and various bodily functions, as well as the potential complications that arise from both hypo- and hyperthyroid states. The treatment emphasizes the importance of monitoring TSH levels and adjusting levothyroxine dosages based on patient needs and circumstances, particularly in special populations such as pregnant women.

1. HYPOTHYROIDISM
MODERATOR: DR PRABHU
ASSOC.PROFFESSOR ,DEPT OF MEDCINE
PRESENTER: DR BHARATH
POST GRADUATE ,DEPT OF MEDICINE

2. THYROID GLAND
ANATOMY
• Consists of two lobes connected by an
isthmus
• Located anterior to trachea between
cricoid cartilage and supra sternal notch
• 12-20 g, highly vascular, soft
• 4 parathyroid glands are located
posterior at each pole of thyroid

3. Thyroid produces ….
T3
T4
CALCITONIN-REGULATION OF
CALCIUM
LEVELS

4. Physiology

5. SYNTHESIS OF THYROID HARMONE

6. CHARACTERISTICS OF CIRCULATING T3 AND T4
Hormone property t4 t3
Serum concentration
total hormone
8 μg/dL 0.14 μg/dL
Fraction bound 99.98 % 99.86 %
Unbound free harmone 0.8-1.8ng/ml ( fun:1.0-1.8ng/ml) 2.3-4.2pg/ml (fun:3.0-4.0pg/ml)
Half life 7DAYS 14 HOURS
Metabolic potency 1 3
TSH- .5-5mIU/L

7. T4 to T3 conversion
By deiodinases(I and II)
Inhibited in
a. Systemic illness
b.Acute infection and trauma
Drugs
1.B- Blocker-Propranol 2.PTU 3.Amiodarone 4. Steroids
Thus,Don’t measure T3 and T4 levels in systemic illness,acute infection because they show false
values.

8. Thyroid Hormone receptor:
TSH receptor- (a cell membrane receptor ) acts via CAMP
T3/T4 acts on Intranuclear receptors -TR
T3 and T4 are bound to 3 proteins
TBG(70%).
Albumin(20-10%).
Transthyretin (10%).

9. Maintains Basal metabolic rate
1.Carbohydrate metabolism:
Increase glucose uptake in tissues
gluconeogenesis and glycogenolysis
Hypothyroidism(myxedema coma) -
hypoglycemia fatigue
2.Protein metabolism
Catabolic action proteolysis
Hyperthyroidism-osteopenia
myopathy
fat metabolism
Increases lipolysis
Increase clearance of cholesterol
hypothyroid -
Hypercholesterolemia (SUS)
6.GROWTH
Causes bone growth
CNS myelination
Hypothyroidism-
Short stature and mental
retardation(children).
8.Liver
It converts B-carotene to Vit A
Also stimulates erythropoiesis
Hypothyroidism-
Anaemia fatigue
NOTE-ETC
7.HEART
Increases sensitivity to
catecholamines and myocardial
contractibility.
Hypothyroidism-
bradycardia
Fatigue

11. Wolf chaikoff effect
Excessive Iodine inhibits iodine organification and synthesis of T4 and T3.
(Hypothyroidism)
Most patients quickly recover from this effect.
However Patients with abnormal thyroid gland can develop hypothyroid if Iodine is given
more than a few days.
Risk factors are
1. Autoimmune Thyroiditis
2. Partial thyroidectomy
3. Previous history of radioiodine therapy
4. Subacute thyroiditis

12. Classification of Hypothyroidism
Primary hypothyroidism :(90%) high serum TSH (symptoms present)
low serum free thyroxine(T4)
Subclinical Hypothyroidism : high TSH concentration.
normal free T4 (symptoms absent)
Secondary hypothyroidism : serum TSH concentration( normal low high)
low serum T4

14. CAUSES OF HYPOTHYROIDISM

15. AUTOIMMUNE HYPOTHYROIDISM
 May be associated with goitre
 PREVALANCE: 4/ 1000 women, 1/ 1000 men,
Mean age of diagnosis is 60 years, subclinical
hypothyroidism is 6-8%.
 Risk of developing clinical hypothyroidism is 4%
when subclinical hypothyroidism ,

16. PATHOGENESIS
• In Hashimoto's thyroiditis, marked lymphocytic
infiltration of thyroid with germinal centre
formation, atrophy of thyroid follicles abscence of
colliod and mild to moderate fibrosis
• In atrophic thyroiditis- extensive fibrosis, less
lymphocytic infiltration and absent thyroid follicles
• HLA-DR polymorphisms are the best documented
risk factors, especially HLA-DR3,4,5 in Caucasians
• The female preponderance sex steroid effects on
the immune response.
• Useful markers of thyroid autoimmunity- Antibodies
to TPO and Tg
• 20% have antibodies against TSH-R which prevent
binding of TSH to receptor

17. Associated conditions
Other Autoimmune disorders:
Type 1 diabetes mellitus
Addison's disease
Pernicious anemia
Vitiligo

19. OTHER CAUSES OF
HYPOTHYROIDISM
• IATROGENIC: radioiodine treatment, subtotal
thyroidectomy, drugs like lithium
• IODINE DEFICIENCY: Endemic goitre, cretinism,
associated with consumption of thiocyanates in
cassava or selenium deficiency in adults
• CHRONIC IODINE EXCESS: Intracellular events are
unclear, patients with autoimmune thyroiditis are
susceptible, iodine excess causes hypothyroidism
in upto 13% patients treated with amiodarone
• SECONDARY HYPOTHYROIDISM: Anterior
pituitary hormone deficiencies, isolated TSH
deficiency- rare

20. DRUGS CAUSING HYPOTHYROIDISM
DECREASE THE CONVERTION OF T4 TO T3
STERIODS
PROPRANOLOL
IODINE
AMIODARONE
PROPYLTHIOURACIL
ENZYME INDUCERS
PHENYTOIN
CARBAMAZEPINE
RIFAMPICIN
SERTRALINE
RITONAVIR
CAUSES HYPOTHYROIDISM
LITHIUM
D2 BLOCKER
CLOMIPHENE CITRATE
SPIRNOLACTONE
DECREASE THE ABSORPTION
AL(OH)3
CHOLESTYRAMINE
CALICIUM CARBONATE
FERROUS SULPHATE

21. CLINICAL PICTURE
Goitre
generalized slowing
of BMR
Accumulation of
matrix
glycosaminoglycans
DECRESED BMR
FATIGUE,SLOWING OF
SPEECH, COLD
INTOLERANCE,
CONSTIPATION ,WEIGHT
GAIN DEPISTE NOR
APPETITE,
BRDAYCARDIA,
ACCUMULATION OF
GAGS
INCR TSH-STIMUATES
FIBROBLAST-
PRODUCTION OF GAGS
FACIAL PUFFINESS
MACROGLOSSIA
PERIORBITAL EDEMA
NON PITTING EDEMA
Reproductive system
(oligo- or amenorrhea –
(rare)menorrhagia
Hyperprolactinemia
Decreased libido,
erectile dysfunction
Musculoskeletal
Joint pains,
Woltmans sign(Hung up
ankle jerk) due to
decresed myosin
ATPase
Hoffman’s syndrome
Metabolic changes
Hyponatremia
reduction in free
water clearance.
(SIADH)
Hypercholesterolemi
a and
hypertriglyceridemia
Neurological system
Intellectual (<3 years)
Carpal tunnel syndrome
Slow relaxation of DTR
Memory and
concentration are
impaired,psychosis, and
myxedema coma.
Hematologic
Normochromic,
normocytic anaemia
Pernicious anemia
iron deficiency anemia,
secondary to
menorrhagia.
Cardiovascular system
Reduced CO
Diastolic Hypertension
ECG : Low voltage, sinus
bradycardia,
Pericardial effusion
Respiratory system
Dyspnea due to
Hypoventilation and
decreased pulmonary
responses to hypoxia
and hypercapnia
Sleep apnea due to
macroglossia.

23. SREAT
• Hashimoto’s encephalopathy(Old term)
• Steroid responsive encephalopathy with autoimmune thyroid disease [new term]
• Autoimmune vasculitis unrelated to thyroid function.
• Hashimoto’s encephalopathy can occur with a normal TFT
• HLA-B-8 associated
• Elevated antibody titres.
• PRESENTATION
• Subacute onset of confusion/altered level of consciousness
or seizure/myoclonus
or small vessel stroke
• Good response to steroids
• Treatable condition

24. Other points of Hashimoto’s
encephalopathy
Anti Enolase antibody
Can occur in Euthyroid state
Background slowing of EEG
Anybody presenting with subacute dementia and alt sensorium ,rule out thyroid
illness, however don’t be foxed by normal tft, it is the antibody titre which is
important,it is one treatable causes of alt sensorium.

25. TSH T4 FT4 T3 FT3 Condition
Increased Normal Normal Normal Normal Subclinical
hypothyroidism
Recovery from
acute illness
Increased Decreased Decreased Decreased Decreased Primary
hypothyroidism
Increased Increased Increased Increased Increased Thyroid hormone
resistance
/thyroid
adenoma
Normal or low Decreased Decreased Decreased Decreased TSH appropriately
normal;secondar
y hypothyroidism

26. Approach
Signs
slow DTRs, bradycardia, facial and periorbital edema, dry skin, and
nonpitting edema. Mild weight gain (not marked obesity).
hypoventilation, pericardial or pleural effusions, deafness, and signs
carpal tunnel syndrome.
Laboratory findings may include hyponatremia and elevated plasma
levels of cholesterol, triglycerides, and creatine kinase.

27. What tests should I order ?
TSH and free T4 for initial evalution
For follow-up of treatment only TSH
Don't order for Total T4 or Total T3
Never order RIU in pregnancy or lactation

28. TSH Shouldn’t be used alone…….
Use of TSH as a screening test may be misleading…
TSH FREE T4 T3 DISEASE
INCREASED 1 HYPOTHYROIDISM
INCREASED RTH
NORMAL DECREASED
INCREASED
DECREASED 2 HYPOTHYROIDISM

29. Thyroid function test
TSH-Better if done while fasting
Free T3,T4-no relation to food
A normal TSH excludes primary abnormality of thyroid function

30. TPO AB+
SYM(+)
TPO AB-
SYM (-)
SUBCLINICAL
1*
HYPOTHYROIDISM
TPO
AB+ TPO-
AUTOIMMUNE
HYPOTHYROIDISM
(OTHER?)
LOOK FOR OTHER
CAUSES

31. Thyroid Antibodies
Anti Thyroglobulin (TG) Antibodies
Anti Thyroperoxidase (TPO) Ab
Thyroid receptor (TRH-A) Antibodies

32. Treatment : Outline
Goal : normalize TSH level,ideally in the lower half of the reference range.
Single daily dose of levothyroxine as half life is 7 days.
Empty stomach -30 mins before BF.
Starting dose-healthy patients <60 years and no cardio issue
1.6 ug/kg/day.(50 to 100 ug/day)
Starting dose for healthy patients > 60 OR cardio issue - <50 ug/day.
TSH levels measured after 2 months.(after initiation and altering the
dose)
Dose should be increased or decresed by 12.5-25 ug/day(basis of TSH)
Once stabilized TSH-annual follow up

33. For monitoring the patient on treatment ,TSH is the best choice
patients who miss a dose can take two doses of the skipped tablets at once.
For TSH to normalize it will take 2-3months
For symptoms to subside it will take 2 months after the normalization of TSH
Most common treatment failure: Non compliance
however, Increased t4 requirements must be excluded
1. malabsorption
2. ingestion with a meal
3. drugs that interfere with T4 absorption or metabolism

34. TREATMENT
SUBCLINICAL HYPOTHYROIDISM:
Levothyroxine is considered in
(high TSH levels should be there for 3months before rx)
1. Planning to conceive pregnant
2. TSH levels >10 mU/L,
3. Symptoms
4. antibodies positive
Low dose levothyroxine (25-50 micrograms/day).
If T4 is not given , then annual follow up is recommended.

35. SPECIAL TREATMENT CONSIDERATIONS
Every planning to conceive- thyroid profile has be checked
if hypothyroid-maintain pre conceptional TSH-2.5mIU/L
After pregnancy is confirmed – immediately get thyroid profile done ,then once in 1month till
20weeks f/b 2 months thereafter. (goal of TSH < 2.5 mIU/L )
Levothyroxine dose - increased by upto 45% during pregnancy
Imp:separate ingestion of iron supplements from levothyroxine by at least 4 hours
ELECTIVE surgery in a hypothyroid patient should be deferred until euthyroidism is achieved.

36. Over- and Under-Replacement Risks
Over-replacement Risks: Reduced bone density/osteoporosis Tachycardia,
arrhythmia : Atrial fibrillation
In elderly or patients with heart disease- angina, arrhythmia, or myocardial
infarction.(wise to start with less dose)
Under-replacement Risks:
Continued hypothyroid state
Long-term end-organ effects of hypothyroidism
Increased risk of hyperlipidemia

37. Before and After of L-Thyroxine

38. MYXEDEMA COMA
• Almost always occurs in elderly
• Seen in long standing hypothyroid
History of treated hypothyroidism (very poor compliance)
might be previously undiagnosed also
20-40% mortality even with treatment
• doesn’t relate T4 and TSH levels
• Precipitated by factors that impair respiration- drugs ( sedatives, anesthetics and
antidepressants), infection, CAD, GI bleed or CVA, exposure to cold
• CLINICAL MANIFESTATIONS- Reduced level of consciousness, seizures
Bradycardia
hyponatremia
hypothermia can reach 23°C
hypoglycemia and otherfeatures of hypothyroidism

39. TREATMENT:MYXEDEMA COMA
Levothyroxine single IV bolus of 500 ug( loading dose) followed by a daily oral dose of 1.6
μg/kg/day
IV preparation is not available - can be given by nasogastric tube (though absorption may be
impaired in myxedema).
Because T4 → T3 conversion is impaired (myxedema coma) adding liothyronine i.v or via nasogastric
tube (excess arrhythmias).
loading dose of 5–20 μg
Maintaince dose: 2.5–10 μg 8 hourly(consider cardiovascular issues)

40. Supportive Treatment: Myxedema coma
External warming (temperature is <30 °C) due to risk of cardiovascular collapse.
(Space blankets to prevent)
Parenteral hydrocortisone (50 mg every 6 h) decresed adrenal reserve in
profound hypothyroidism.
Any precipitating factors like infection to be treated with broad-spectrum
antibiotics.
Ventilatory support - regular blood gas analysis
Hypertonic saline or IV glucose .hypotonic IV fluids should be avoided(RAAS)
Sedatives should be avoided if possible or used in reduced doses and monitor
blood levels of drugs.

41. THANK YOU