HYpothyroidism subclinical Hypothyroidism

1. SUBCLINICAL
HYPOTHYROIDISM

2. PHYSIOLOGY OF THYROID GLAND
• HARMONES OF THYROID GLAND
T3 & T4 CALCITONINE
Produced by produced by
Follicular cells parafollicular C cells

3. FOLLICULAR CELLS & SYNTHESIS OF T3 ,T4
• TYROSINE (from thyroglobulin )
follicular cells T3,T4
IODINE (from diet in reduced
form )

5. • COUPLING REACTIONS
oxidised form of Iodine + Tyrosine = MIT (monoiodotyrosine )
MIT + MIT = DIT (diiodotyrosine )
MIT + DIT = T3 (active)
DIT + MIT = reverse T3 (inactive)
DIT + DIT = T4
 T3 &T4 are stored in follicular cells in form of colloid and this colloid
has hormone reserve for 2-3 months ; when colloid breaks down it
releases T3 ,T4 in to blood.

6. REGULATION OF THYROID HARMONE
• HYPOTHALAMUS
TRH TRH ( thyrotropin releasing harmone )
+ - releases TSH from anterior pitutary
- PITUTARY GLAND
TSH - TSH – increases vascularity
+ increases iodine trapping
increases T3 and T4
THYROID GLAND
T3 T4
PERIPHEREL TISSUES
T4 T3

7. DEFINITION
• Subclinical Hypothyroidism (SCH) -defined as a serum thyroid
stimulating hormone (S.TSH) level persistently above the upper limit
of normal despite normal levels of serum free T3 &T4.
• Overt Hypothyroidism – defined as S.TSH level above the upper limit
of normal with decreased levels of serum free T3 & T4.
IJEM2013

8. SPECTRUM OF THYROID DISEASES
DISEASE TSH(0.45-4.5 mIU/l) Free T4 (9.0-25.0pmol/L)
Free T3 (3.5-7.8 pmol/L)
Overt Hypothyroidism High or Very High Low
Subclinical Hypothyroidism High Normal
Euthyroid Normal Normal
Subclinical Hyperthyroid Low Normal
Overt Hyperthyroid Low or very low High
Thyroid Hormone Resistance Normal High or Normal

9. EPIDEMIOLOGY
• Prevalence is 3 – 8% in the population without known thyroid disease
• Prevalence increases with age and is higher in women . After the sixth
decade of life, the prevalence in men approaches to that of women with a
combined prevalence of 10%.
• India has estimated 42 million people suffering from thyroid diseases with
prevalence of SCH as high as 9.4% with female dominance of 11.4 vs 6.2%
in men.
IJEM2013

10. RISK FACTORS
• Family h/o thyroid disease
• Personal h/o of thyroid disease
• Presence of antithyroid antibodies
• Radiation treatment to head , neck or chest.
• Other medical conditions - chronic autoimmune thyroiditis
- persistently high TSH in subacute thyroiditis
- postpartum thyroiditis
- injury to thyroid
• Medications : lithium, amoidarone ,iodine
• Drug interactions – iron , calcium , cholestyramine
• Increased T4 clearance – phenobarbitone , phenytoin , cabamazepine
• Infiltration of thyroid – amyloidosis , sarcoidosis , hemochromatosis,primary thyroid lymphoma
• Old age

11. SCREENING RECOMMENDATION
AMERICAN THYROID ASSOCIATION Women and men > 35 yrs of age should be screened
every 5 yrs
AMERICAN ASSOCIATION OF CLINICAL
ENDOCRINOLOGISTS
Older patients especially women should be screened
AMERICAN COLLEGE OF PHYSICIANS Women > 50 yrs of age with an incidental finding
suggestive of symptomatic thyroid disease should be
evaluated
AMERICAN ACADEMY OF FAMILY PHYSICIANS Patients > 60 years of age should be screened
ROYAL COLLEGEOF PHYSICIANS OF LONDON Screening of healthy adult population unjustified

12. COURSE OF DISEASE
• 1 – measured again after several months if normal can be attributed
to - laboratory error
- episode of silent thyroiditis with transiet hypothyroid
phase.
• 2 – subclinical hypothyroidism remains unchanged and doesn’t progress.
• 3 – subclinical hypothyroidism have a high rate of progression to clinically
overt hypothyroidism - 2.6% in TPO negative
- 4.3% in TPO positive
- in a study in men and women older than 55 yrs with a mean follow up of
32 months ,the TSH level normalized in 52% of those with S.TSH of less
less than 10mIU/L. (JCEM 2004 )

13. SYMPTOMS
• - Dry skin
- cold intolerance
- easy fatigability
• progression to overt disease manifest as – menorrhagia
- neck swelling
- delayed relaxation of DTR
- bradycardia

14. • Study conducted in Mumbai
compares symptoms and signs
of thyroid disease among two
groups euthyroid status (blue) vs
SCH (red)

15. COMPLICATIONS
• Progression to overt Hypothyroidism with systemic manifestations
• Increased risk of metabolic syndrome
• Cardiac dysfunction – slow LV relaxation time
- LV systolic dysfunction
- Cardiomyopathies
• Neuromuscular dysfunction
• Psychiatric and cognitive dysfunction in form of depression, bipolar disorder

16. LABORATORY DIAGNOSIS
• Elevated S.TSH on two separate occasions 6 weeks apart
mildly elevated markedly increased
4.5 – 10 mIU/L >10 mIU/L
normal free T3,T4 normal free T3,T4
• Antithyroperoxidase antibodies
• USG neck for thyroid swelling
• Thyroid scan with radioactive iodine

17. • CERTAIN CONDITIONS WHICH DO NOT QUALIFY TO BE LABELLED AS SCH
- recovery phase of subacute thyroiditis
painless thyroiditis
postpartum thyroiditis
- untreated adrenal insufficiency
- TSH producing pitutary adenomas
- resistance to thyroid harmone
- central hypothyroidism , in which up to 25% of patients have a mildly
elevated S.TSH < 10mIU/L and a low or low normal free T4.

18. MANAGEMENT
• INDICATIONS for sub clinical hypothyroidism treatment
1. TSH >10 mIU/L
2. Antibodies positive
3. Symptoms present
4. Pregnency
• Dose of levothyroxine 1.7 mcg/kg.
• In old patients with cardiac comorbidities levothyroxine should be started in minimal
dose ie 25-50 mcg/day and gradually escalated to achieve the target response.
• Thyroid profile should be checked every 8 weeks. Once normal TSH level is achieved it
should be checked every 6 months thereafter.

19. • Treatment should be initiated if TSH concentration is >10 mIU/L, as there is
enough evidence to support the beneficial effects.
• Treatment of asymptomatic patient with S.TSH values of 4.5-10 mIU/L is
somewhat controversial needed to be followed up every 6 -12 months
with S.TSH and clinical evaluation.
• Pateints with S.TSH values of 4.5-10 mIU/L and symptoms s/o
hypothyroidism , or goiter , high titres of antithyroid peroxidase antibodies
can get benefit from treatment and to kept S.TSH level < 2.5 mIU/L.
IJEM2013

20. DISCUSSION : CONTROVERSIS TO CONSENSUS
• SUBCLINICAL HYPOTHYROIDISM AND PREGNENCY
- studies done in individuals with SCH show an increased risk of preterm
birth , pregnency loss , impaired cognitive development in children.
• SUBCLINICAL HYPOTHYROIDISM AND MENTAL DYSFUNCTION
- SCH females have greater susceptibility for unpleasant emotional
stimulation , inward attention and increased anxiety
- EEG shows reduced alpha activity in resting state and increased beta-2
activity during stimulation suggestive of higher level of arousal and greater
susceptibility to negative emotions.
IJEM2013

21. • SUBCLINICAL HYPOTHYROIDISM AND RISK OF HEART FAILURE
- American Heart Association recommended SCH determination as precipitating
factor in heart failure patients
- results of six prospective cohorts studies in US and Europe revealed the risk of
heart failure were increased in patients with high TSH particulary when it is above
10mIU/L.
• SUBCLINICAL HYPOTHYROIDISM AND CARDIOVASCULAR RISK
- increased risk of coronary heart disease in SCH
- there is increased intima media thickness in SCH females s/o CVD risk
- one meta-analysis shows that participants with TSH > 10 mIU/L had a significant
increase in CHD events, contrary to that of patients having TSH b/w 4.5 to 6.9
were not associated with an increased risk.
IJEM2013

22. • SUBCLINICAL HYPOTHYROIDISM AND CHOLESTEROL METABOLISM
- a cross sectional study revealed individuals with S.TSH level b/w 5.1 and
10 mIU/L had significantly higher mean total cholesterol concentrations.
• SUBCLINICAL HYPOTHYROIDISM AND PCOD
- trials revealed that PCOS females with SCH have higher levels of LDL,
cholesterol while all other parameters of lipid profile are not altered.
• SUBCLINICAL HYPOTHYROIDISM AND METABOLIC SYNDROME
- Weight gain or failure to loose weight
- trial showed metabolic syndrome frequency is increased in overt and SCH.
IJEM2013

23. • SUBCLINICAL HYPOTHYROIDISM AND NEUROPSYCHIATRIC ISSUES
-SCH have increased frequency of weakness , paresthesias ,fatigue
and cramps
- defect in verbal memory and executive functioning
- increased risk of Alzheimer Disease.
IJEM2013

24. THANKYOU