Hypothyroidism is a condition characterized by thyroid hormone deficiency. It ranges from subclinical to myxedema coma. Common causes include iodine deficiency, autoimmune disease like Hashimoto's thyroiditis, and treatment of hyperthyroidism. Symptoms vary but can include fatigue, dry skin, weight gain, constipation, joint pain, and cognitive impairment. Diagnosis is made through blood tests of thyroid hormones and TSH. Treatment involves lifelong levothyroxine replacement therapy to normalize TSH levels. The dosage needs monitoring and adjustment based on repeat testing.

1. HYPOTHYROIDSM

2. DEFINITION
 It is a syndrome characterised by the
clinical and biochemical
manifestations of thyroid hormone
deficiency in the target tissues of
thyroid hormone.
 Hypothyroidsm is a graded
phenomenon ranges from subclinical
hypothyroidsm to myxedema coma.

3. HISTORY
 GULL (1874) – Defined hypothyroidsm as clinical
syndrome (myxedema)
 Murray (1891) – cured myxedema by hypodermic
inj of sheep thyroid extract
 Kendall (1914) – isolated thyroxine
 Harrington (1926) – identified constitution of
thyroxine and synthesize it
 1960s – levothyroxine sodium used for treatment

4. HYPOTHYROIDISM
 Iodine deficiency remains a common cause
of hypothyroidism worldwide.
 In areas of iodine sufficiency, autoimmune
disease (Hashimoto’s thyroiditis) and
iatrogenic causes (treatment of
hyperthyroidism) are most common

7. GOITROUS HYPOTHYROIDISM
 Associated with enlargement of
thyroid
◦ Hashimoto thyroiditis
◦ Iodine deficiency
◦ Drugs (lithium, iodides, p-aminosalicylic
acid)
◦ Congenital biosynthetic defect
(dyshormonogenetic goiter) (rare)

8. CONGENITAL
HYPOTHYROIDISM
 transient, especially if the mother has TSH-R blocking antibodies or
has received antithyroid drugs
 Neonatal hypothyroidism is due to
◦ thyroid gland dysgenesis in 80–85%,
◦ inborn errors of thyroid hormone synthesis in 10–15%(dyshormonogenetic
goiter)
◦ TSH-R antibody-mediated in 5% of affected newborns.
 The developmental abnormalities are twice as common in girls.
 Transplacental passage of maternal thyroid hormone occurs
before the fetal thyroid gland begins to function and provides
partial hormone support to a fetus with congenital
hypothyroidism

9. CONGENITAL
HYPOTHYROIDISM

10. CONGENITAL HYPOTHYROIDISM
Clinical Manifestations
 appear normal at birth,
 prolonged jaundice, feeding problems,
 hypotonia, enlarged tongue,
 delayed bone maturation, and umbilical hernia.
 permanent neurologic damage results if treatment
is delayed.
 Typicalfeatures of adult hypothyroidism may also
be present
 Other congenital malformations, especially cardiac,
are four times more common in congenital
hypothyroidism.

11. CRETINISM
 Cretinism: (from the French chrétien, meaning
“Christian” or “Christlike,” mentally retarded as to
be incapable of sinning)
◦ hypothyroidism that develops in infancy or
early childhood
◦ mental and growth retardation
◦ coarse facial features, a protruding tongue, and
umbilical hernia.
◦ often born to mothers with iodine deficiency
◦ Concomitant selenium deficiency may also
contribute to the neurologic manifestations

12. CRETINISM

13. CONGENITAL HYPOTHYROIDISM
Diagnosis and Treatment
 Neonatal screening programs measurement of
TSH or T4 levels in heel-prick blood specimens.
 T4 requirements are relatively great during the
first year of life (dose of 10–15 μg/kg per day,
and titrated according to tsh)
 Early treatment with T4 results in normal IQ
levels

14. AUTOIMMUNE
HYPOTHYROIDISM
 -Hashimoto’s,or goitrous thyroiditis
 -Atrophic thyroiditis.
 Because the autoimmune process gradually reduces
thyroid function, there is a phase of compensation
when normal thyroid hormone levels are maintained by
a rise in TSH-subclinical hypothyroidism.
 Later, unbound T4 levels fall and TSH levels rise further;
symptoms become more readily apparent at this stage
(usually tsh >10 mIU/l), which is referred to as clinical
hypothyroidism or overt hypothyroidism.

15. Hashimoto thyroiditis/
struma lymphomatosa
 An autoimmune disease that results in destruction
of the thyroid gland and gradual and progressive
thyroid failure
 Between 45 and 65 years
 Female predominance of 10 : 1 to 20 : 1. Also in
children
 Circulating autoantibodies:
 Antimicrosomal,
 Antithyroid peroxidase, and
 Antithyroglobulin antibodies
 Abnormalities of regulatory T cells (Tregs), or exposure
of normally sequestered thyroid antigens
 The thyroid follicles are atrophic and are lined by
epithelial cells distinguished by the presence of
abundant eosinophilic, granular cytoplasm, termed
hürthle cells in conjunction with a heterogeneous
population of lymphocytes

17. RISK FACTORS FOR AUTOIMMUNE
HYPOTHYROIDISM
◦ A high iodine intake
◦ decreased exposure to microorganisms in childhood
◦ HLA-DR3, -DR4, and -DR5 in Caucasians
◦ CTLA-4, a T cell–regulatory gene
◦ Protein tyrosine phosphatase-22 (PTPN22),
◦ Down’s syndrome(A gene on chromosome 21)
 Female preponderance of thyroid autoimmunity due to
◦ sex steroid effects on the immune response,
◦ X chromosome–related genetic factor(Turner’s syndrome)

18. Hashimoto’s thyroiditis-
pathogenesis

19. Clinical Manifestations
Hashimoto’s thyroiditis
 Insidious onset
 Painless enlargement of the thyroid
 Goiter -irregular and firm
 Complicated hashimoto’s
thyroiditis:associated with pain
 Patient may become aware of symptoms
only when euthyroidism is restored
 Hypothyroidism develops gradually
preceded by transient thyrotoxicosis caused
by disruption of thyroid follicles, leading to
release of thyroid hormones

21. Clinical Manifestations
atrophic thyroiditis
 Dry skin
 decreased sweating,
 thinning of the epidermis,and
 Increased dermal glycosaminoglycan content traps
water, giving rise to skin thickening without pitting
(myxedema).
 Typical features include a puffy face with edematous
eyelids and nonpitting pretibial edema
 pallor
 yellow tinge to the skin due to carotene accumulation.
 Nail growth is retarded
 hair is dry, brittle, difficult to manage, and falls out easily
 diffuse alopecia
 thinning of the outer third of the eyebrows

22. NEUROLOGIC PROBLEMS
 Carpal tunnel and other entrapment
syndromes
 Impairment of muscle function with
stiffness, cramps, and pain.
 Slow relaxation of tendon reflexes
 Pseudomyotonia.
 Memory and concentration are impaired.
 Reversible cerebellar ataxia,
 Dementia,
 Psychosis, and
 Myxedema coma

23. CLINICAL PRESENTATION-
SKIN
 PUFFY FACE, HANDS, FEET- NON PITTING
 ENLARGED TONGUE
 COOL PERIPHERY
 DRY COARSE SKIN
 HAIR- DRY, BRITTLE, FALLS OUT
 MADAROSIS- NOT SPECIFIC
 BRITTLE NAILS
 VITILIGO
 MYXEDEMA- ACCUMULATION OF
HYGROSCOPIC GLYCOSAMINOGLYCAN
 PRETIBIAL MYXEDEMA- GRAVES’
DISEASE

24. RESPIRATORY SYSTEM
 PLEURAL EFFUSION
 ALVEOLAR HYPOVENTILATION
 OBSTRUCTIVE SLEEP APNOEA

25. GASTROINTESTINAL
 WEIGHT GAIN, REDUCED
APPETITE
 CONSTIPATION
 MYXEDEMA MEGACOLON
 MYXEDEMA ILEUS
 CELIAC DISEASE, PERNICIOUS
ANAEMIA
 ASCITES- UNUSUAL

26. CENTRAL AND PERIPHERAL
NERVOUS SYSTEM
 DEMENTIA
 MYXEDEMA MADNESS
 SEIZURES
 SLURRED SPEECH, HOARSENESS
 CEREBELLAR ATAXIA
 TINGLING AND NUMBNESS
 CARPAL TUNNEL SYNDROME
 HUNG UP REFLEX
 HASHIMOTO’S ENCEPHALOPATHY

27. HASHIMOTO
ENCEPHALOPATHY
 STEROID RESPONSIVE
 TPO ab POSITIVE
 MYOCLONUS
 SLOW WAVE ACTIVITY IN EEG

28. Skeletal system
 GROWTH FAILURE
 EPIPHYSEAL DYSGENESIS
 CALCIUM SLIGHTLY INCREASED

29. RENAL
 DECREASED RENAL FLOW
 RENAL PARAMETERS NORMAL
 SIADH
 MILD PROTEINURIA

30. HEMATOPOIETIC SYSTEM
 NORMOCYTIC/ NORMOCHROMIC
 MACROCYTIC
 MICROCYTIC/ HYPOCHROMIC
 DECREASED FACTOR VIII, IX

31. REPRODUCTIVE FUNCTION
 DELAYED PUBERTY
 MENSTRUAL IRREGULARITY
 REDUCED FERTILITY
 PRETERM, SPONTANEOUS
ABORTIONS
 PRIMARY OVARIAN FAILURE
 ERECTILE DYSFUNCTION

32. MYXEDEMA
 Hypothyroidism developing in the older child or adult.
 Reduced cardiac output probably contributes to shortness of
breath and decreased exercise capacity,
 Hypothyroidism promotes an atherogenic profile—an
increase in total cholesterol and LDL levels
 Accumulation of matrix substances, such as
glycosaminoglycans and hyaluronic acid, in skin,
subcutaneous tissue, and a number of visceral sites. 
◦ Nonpitting edema,
◦ Broadening and coarsening of facial features,
◦ Enlargement of the tongue, and
◦ Deepening of the voice.

34. LABORATORY EVALUATION
 A normal TSH level excludes primary (but not
secondary) hypothyroidism
 Circulating unbound T3 levels are normal in
about 25% of patients, reflecting adaptive
deiodinase responses to hypothyroidism
 T3 measurements
 TPO antibodies, present in >90% o
 Tbii found in 10–20%
 FNA biopsy
 Increased creatine phosphokinase,
 Elevated cholesterol and triglycerides,
 Anemia (usually normocytic or macrocytic).

35. SUBCLINICAL
HYPOTHYROIDISM
 Refers to biochemical evidence of thyroid hormone
deficiency in patients who have few or no apparent
clinical features of hypothyroidism.
 4–10% of the general population but increases to
20% in women older than age 50
 Levothyroxine is recommended if the patient is A
woman who wishes to conceive or is pregnant, or
when TSH levels are above 10 miu/L.

36. Thyroid Preparations
 Synthetic(levothyroxine, liothyronine, liotrix) or of
animal origin (desiccated thyroid).
 Liotrix :more expensive;mixture of thyroxine and
liothyronine
 Synthetic levothyroxine is the preparation of choice
◦ Stability
◦ Content uniformity,
◦ Low cost,
◦ Lack of allergenic foreign protein,
◦ Easy laboratory measurement of serum levels,
and
◦ Long half-life (7 days), which permits once-daily
administration

37.  Although liothyronine is three to four times more
potent than levothyroxine, it is not recommended
for routine replacement because of
◦ shorter half-life (24 hours), which requires
multiple daily doses;
◦ Its higher cost; and
◦ The greater difficulty of monitoring its adequacy
of replacement by conventional laboratory tests.
◦ Greater risk of cardiotoxicity, avoided in patients
with cardiac disease.
◦ Best used for shortterm suppression of tsh.

38.  Desiccated thyroid:disadvantages:
◦ Protein antigenicity,
◦ Product instability,
◦ Variable hormone concentrations, and
◦ Difficulty in laboratory monitoring far outweigh the advantage of
lower cost
 Equi-effective doses are 100 mg of desiccated thyroid,100 mcg of
levothyroxine, and 37.5 mcg of liothyronine
 The shelf life of synthetic hormone preparations is about 2 years,
 Particularly if they are stored in dark bottles to minimize
spontaneous deiodination.
 The shelf life of desiccated thyroid is not known with certainty, but its
potency is better preserved if it is kept dry
 Infants and children require more T4 per kilogram of body weight
than adults.
 Average dosage for an infant 1–6 months of age is 10–15 mcg/kg/d,
whereas the average dosage for an adult is about 1.7 mcg/kg/d.
 Older adults (> 65 years of age) may require less thyroxine for
replacement

39.  Certain foods (eg, bran, soy, coffee) and drugs can impair its
absorption,
◦ Thyroxine should be administered on an empty stomach
(eg, 30 minutes before meals or 1 hour after meals or at
bedtime).
 Tsh maintained within an optimal range of 0.5–2.5 mu/L. It
takes 6–8 weeks after starting a given dose of thyroxine to
reach steady-state levels in the bloodstream
 In older patients, the heart is very sensitive to the level of
circulating thyroxine, and if angina pectoris or cardiac
arrhythmia develops, it is essential to stop or reduce the dose
of thyroxine immediately

40.  Dosage of 12.5–25 mcg/d for 2 weeks, increasing the
daily dose by 12.5–25 mcg every 2 weeks until
euthyroidism or drug toxicity is observed
 Chronic overtreatment with T 4 ,particularly in elderly
patients, can increase the risk of atrial fibrillation and
accelerated osteoporosis
 If coronary artery surgery is indicated, it should be
done first, prior to correction of the myxedema by
thyroxine administration.

41. TREATMENT Hypothyroidism
CLINICAL HYPOTHYROIDISM
 If there is no residual thyroid function, the daily
replacement dose of levothyroxine is usually 1.6
μg/kg body weight (typically 100–150 μg), ideally
taken at least 30 min before breakfast.
 If patients develop hypothyroidism after the
treatment of graves’ disease, there is often
underlying autonomous function, necessitating
lower replacement doses (typically 75–125 μg/d).

42.  Adult patients under 60 years old without evidence
of heart disease may be started on 50–100 μg
levothyroxine (T4) daily.
 Tsh responses should be measured about 2
months after instituting treatment or after any
subsequent change in levothyroxine dosage.
 Patients may not experience full relief from
symptoms until 3–6 months after normal tsh levels
are restored.

43.  Adjustment of levothyroxine dosage is made in
12.5- or 25-μg increments if the TSH is high;
 Patients with a suppressed TSH of any cause,
including T4 overtreatment, have an increased risk
of atrial fibrillation and reduced bone density.
 Once full replacement is achieved and tsh levels
are stable, follow-up measurement of tsh is
recommended at annual intervals and may be
extended to every 2–3 years if a normal tsh is
maintained over several years.

44.  In patients of normal body weight who are
taking ≥200 μg of levothyroxine per day, an
elevated tsh level is often a sign of poor
adherence to treatment.
 Because t4 has a long half-life (7 days),
patients who miss a dose can be advised to
take two doses of the skipped tablets at
once.

45. Other causes of increased
levothyroxine requirements
 malabsorption(e.g., celiac disease, small-bowel surgery),
 estrogen or selective estrogen receptor modulator therapy,
 ingestion with a meal,
 drugs that interfere with T4 absorption or metabolism such as
◦ cholestyramine,
◦ ferrous sulfate,
◦ calcium supplements,
◦ proton pump inhibitors,
◦ lovastatin,
◦ aluminum hydroxide,
◦ rifampicin,
◦ amiodarone,
◦ carbamazepine,
◦ phenytoin, and
◦ tyrosine kinase inhibitors.