Subclinical hypothyroidism is defined as an elevated thyroid-stimulating hormone level with a normal free thyroxine level. It has a prevalence of 3-8% that increases with age and is more common in women. While some cases resolve on their own, others may progress to overt hypothyroidism at a rate of 2.6-4.3% per year depending on thyroid antibody status. Treatment with levothyroxine is generally recommended for levels over 10 mIU/L and is also considered case-by-case for levels between 4.5-10 mIU/L based on risk factors and symptoms. Special consideration is given to treating subclinical hypothyroidism during pregnancy to prevent

1. Subclinical
Hypothyroidism

2. Background
•Hypothalamic
Pituitary
Thyroid Axis

3. Thyroid Hormone Synthesis and Secretion

4. Background
• Effects of
Thyroid
Hormones in
Health & Diseases

5. Definitions
• Subclinical hypothyroidism (SCH) is defined as a serum thyroid-stimulating
hormone (TSH) level above the upper limit of normal despite normal levels
of serum free thyroxine for a given population reference.
• Overt hypothyroidism is defined as a serum thyroid-stimulating hormone
(TSH) level above the upper limit of normal with decreased levels of serum
free thyroxin for a given population reference.

6. Spectrum of Thyroid Diseases
Diseases TSH (0.45 – 4.5 mIU/L) Free T4 (9.0 – 25.0 pmol/L)
Free T3 (3.5 – 7.8 pmol/L)
Overt Hypothyroid High or Very High Low
Subclinical Hypothyroid High Normal
Euthyroid Normal Normal
Subclinical Hyperthyroid Low Normal
Overt Hyperthyroid Low or Very Low High
Thyroid Hormone Resistance Normal High or Normal

7. Epidemiology
• Subclinical hypothyroidism or mild thyroid failure is a common problem, with
a prevalence of 3% to 8% in the population without known thyroid disease.
• The prevalence increases with age and is higher in women. After the sixth
decade of life, the prevalence in men approaches that of women, with a
combined prevalence of 10%.

8. Risk Factors
• Family history of thyroid disease
• Personal history of thyroid disease
• Presence of antithyroid antibodies
• Radiation treatment to head, neck or chest
• Other autoimmune disease
• Medications: lithium, amiodarone (Cordarone), iodine
• Old age

9. Causes
Chronic autoimmune thyroiditis
Treated Graves' disease
Radioactive iodine
therapy
Subtotal thyroidectomy
Antithyroid drugs
Head and neck surgery
Radiation therapy to the head, neck or chest area
Iodine deficiency
Medications: lithium, iodine, amiodarone
(Cordarone)
Idiopathic
Congenital

10. Course of Disease
• In some cases, the TSH level will be normal if measured again several months later;
we would then attribute the initial elevation to laboratory error or, perhaps, to an
episode of silent thyroiditis with a transient hypothyroid phase.
• In other cases, the subclinical hypothyroidism remains unchanged and doesn’t
progress.
• Patients with SCH have a high rate of progression to clinically overt
hypothyroidism, 2.6% each year if thyroperoxidase (TPO) antibodies are absent
and 4.3% if they are present.
• In a study in men and women older than 55 years with a mean follow-up of 32
months, the TSH level normalized in 52% of those with a serum TSH of less than
10 mIU/L. [JCEM 2004]

11. Natural History of
disease
• Progression of euthyroid
state to subclinical
hypothyroidism and to
overt hypothyroidism
depending on serum TSH
levels and antithyroid
antibody status

12. Clinical Diagnosis
• The clinical signs and symptoms of hypothyroidism manifest when the disease is fully
developed. But even in the earliest (subclinical stage), one or more of these findings
may occur.
• Dry skin, cold intolerance and easy fatigability are significantly more common in the
patients with raised TSH levels, and these symptoms improve after treatment with
thyroid hormone. [Annals of Internal Medicine 2004]
• Some patients with subclinical hypothyroidism do indeed have clinical manifestations
of mild thyroid failure in relation to their serum TSH levels.
• Progression to overt disease can manifest with menorrhagia, neck swelling, delayed
relaxation of deep tendon reflexes and bradycardia.

13. Symptoms &
Signs
A study conducted in Mumbai compares
symptoms and signs of thyroid disease
among two groups; euthyroid status
(blue) and subclinical hypothyroidism
(red). [IJEM 2013]

14. Complications
• Progression to overt hypothyroidism with systemic manifestations of the disease leading to
thyroid failure.
• Increase risk of metabolic syndrome.[ IJEM 2010, CSHR 2017]
• Cardiac dysfunction in form of slow LV relaxation time, LV systolic dysfunction and
impaired endothelial function eventually leading to IHD and Cardiomyopathies [Thyroid
2007]
• Neuromuscular dysfunction [Endocrinologist 2004]
• Psychiatric and Cognitive dysfunction in form of depression, bipolar disorder [IJPM2000]

15. Question
• A 64 year old women is referred for possible hypothyroidism, after her primary care provider ordered a
serum TSH for screening. She feels well and has no major medical problems. She is taking no
medications.
• PE: P 80 BP 140/70 Wt 65 kg. The thyroid is normal to palpation. Skin cool, dry. Reflexes
normal.
• Serum TSH 5.5, repeat 6.1 mU/l, FT4 12.87 pmol/L; antiTPO antibodies are negative
✓ Should she be treated with L-thyroxine?

16. Laboratory Diagnosis
• Patients with subclinical hypothyroidism can be categorized into those with mildly
elevated TSH (4.5–10 mIU/L), and those with markedly increased serum TSH levels
(>10 mIU/L), along with free T4/T3 levels within the reference range for the
population.
• Elevated serum TSH on two separate occasions 6 weeks apart is required for
diagnosis of SCH.
• Antithyroperoxidase antibodies
• USG neck for thyroid swelling
• Thyroid scan with radioactive iodine

17. Management
• Management of SCH differs depending on whether the serum TSH
concentration is 5.0 to 10 mIU/L, or higher than 10 mIU/L.
• Most thyroidologists agree that all patients with SCH and a serum TSH level
above 10 mIU/L should be treated with levothyroxine. [JCEM 2001]
• Studies have shown that levothyroxine therapy results in an 8-mg reduction in
low-density lipoprotein levels. [JCEM 2000]
• Levothyroxine therapy has been also shown to reduce neuromuscular
dysfunction, psychiatric and cognitive dysfunction.

18. Management
Clinical Condition
Strength of
association
Benefits of
treatment
Progression to overt
hypothyroidism
Good Variable
Adverse cardiac end points Insufficient No evidence
Elevation in serum total
cholesterol and LDL-C levels
Insufficient Insufficient
Cardiac dysfunction Insufficient Insufficient
Systemic hypothyroid
symptoms
No clear evidenceInsufficient
Psychiatric symptoms No clear evidenceInsufficient
Large-scale randomized studies to
conclusively show reduction of cholesterol
with levothyroxine therapy in this subgroup
are lacking.
Quality of Evidence on the Strength of
Association and Risks/Benefits of
Levothyroxine Treatment of Subclinical
Hypothyroidism for Patients With
a Serum TSH Level of 5.0 to 10.0 mIU/L
[JCEM 2001]

19. Management
• Pregnancy or intention of pregnancy
• Goiter
• Therapeutic trial for possible hypothyroid
symptoms
• Childhood and adolescence
• TSH levels >4.5 mIU/L on 2 occasions
• Bipolar disorder, depression
• Infertility
• Presence of antithyroid antibodies
• Progressive TSH increase
• Ovulatory dysfunction Young age of the
patient Hyperlipidemia?
Factors Favoring
Levothyroxine Therapy in
Patients With a Thyroid-
Stimulating Hormone (TSH)
Level of 4.5 to 10 mIU/L
[JCEM 2001]

20. Management
• For all patients with SCH and a serum TSH concentration above 10 mIU/L and for patients
with serum TSH concentrations of 4.5 to 10.0 mIU/L in whom individualized decision for
therapy is made, therapy should be started with levothyroxine.
• Daily dose of levothyroxine is 1.5mcg/kg
• Dose should be titrated according to patients age, serum TSH levels and serum free T4 levels.
• In old patients with cardiac comorbidities levothyroxine should be started in minimal dose;
25 – 50 mcg/day and gradually escalated to achieve the target response.
• Thyroid profile should be checked every 8 weeks. Once a normal TSH level is achieved it
should be checked every 6 months thereafter..

21. Management
European Thyroid
Association
Guidelines 2013

22. Subclinical
Hypothyroidism in
Pregnancy
Prevalence of thyroid
dysfunction in pregnancy
[JCEM 2012, IJEM
2013]

23. Subclinical Hypothyroidism in Pregnancy
• A seminal study by Haddow et al showed a 7-point reduction in intelligence quotient
in children aged 7 to 9 years whose mothers had SCH at pregnancy compared with
the children of euthyroid mothers. [NEJM 1999]
• Although this was a single study, it nevertheless points to the need for screening of
pregnant women and therapy for mild thyroid failure in women who are pregnant or
planning on becoming pregnant.
• SCH is associated with multiple adverse outcomes in the mother and fetus including
spontaneous abortion, preeclampsia, gestational hypertension, gestational diabetes,
preterm delivery, and decreased intelligence quotient (IQ) in the offspring. [Oxf Clin
Endocr 2003]

24. Subclinical Hypothyroidism in Pregnancy
• Recent Endocrine Society guidelines also suggested 0.1-2.5 mIU/L as the “normal”
range for TSH values in the first trimester and <3 mIU/L in the second and third
trimester. [BMJ 2015]
• Adequate levothyroxine replacement in early pregnancy with SCH can reduce
chances of preterm delivery. But there is no conclusive evidence of reduced chances
of other fetal & maternal complications with the therapy. [Thyroid 2002]
• The Indian guideline is still not clear about treating women with TSH between 2.5
and 4.5 μIU/ml, but Indian Thyroid Society guidelines have suggested that universal
screening for thyroid profile during pregnancy at the first antenatal visit should be
the norm. [Ind J Endocr Metab 2013]

25. THANK YOU