Hypothyroidism is a condition caused by reduced production of thyroid hormones. The main types are primary hypothyroidism due to permanent thyroid damage or failure, and central/secondary hypothyroidism due to pituitary or hypothalamic issues. Hashimoto's disease is the most common cause of primary hypothyroidism. Symptoms include fatigue, dry skin, constipation, weight gain and slowed heart rate. Treatment involves thyroid hormone replacement via levothyroxine. Subclinical hypothyroidism may also be treated depending on risk factors. Hypothyroidism in pregnancy requires careful management to prevent complications. In severe cases, myxedema coma can develop with risk of high mortality and requires urgent

1. HYPOTHYROIDISM
Presented by - Dr.Tapas Tripathi
Moderator – Prof (Dr).Pankaj Bansal

2. Hypothroidism
 Reduced production of thyroid hormone is the central feature of the clinical
state termed hypothyroidism.
 Permanent loss or destruction of the thyroid through processes such as
autoimmune destruction, referred to as Hashimoto disease or irradiation
injury is described as primary hypothyroidism.
 Hypothyroidism due to transient or progressive impairment of hormone
biosynthesis is typically associated with compensatory thyroid
enlargement.

3.  Central or secondary hypothyroidism due to insufficient stimulation of a
normal gland is the result of hypothalamic or pituitary disease or defects in
the TSH molecule.
 Primary hypothyroidism is the cause in approximately 99% of cases of
hypothyroidism, with less than 1% being due to TSH deficiency or other
causes.

4. Cause of hypothyroidism

6. Symptoms of hypothyroidism
 Thyroid hormone maintains basal metabolic rate . Its deficiency causes –
Generalised slowing of metabolic process(mc in both primary and
secondary hypothyroidism).

7.  Accumulation of glycosaminoglycans – mostly hyaluronic acid – in
interstitial space of many tissues that causes -
1. Macroglossia
2. Periorbital edema
3. Non pitting edema
4. Puffiness of face
5. Carpal tunnel syndrome

8. Clinical Manifestations of Hypothyroidism –
Skin
 Cool and pale skin due to reduced blood flow .
 Glycosaminoglycans is hygroscopic, producing the mucinous edema that is
responsible for the thickened features and puffy appearance (myxedema) .
 Enlargement of the tongue ,thickening of the pharyngeal and laryngeal
mucous membranes due to GAG deposition .

9.  Hypercarotenemia gives the skin a yellow tint but does not cause scleral
icterus .
 Skin becomes dry and coarse due to reduced secretions of the sweat
glands and sebaceous glands .
 Wounds of the skin tend to heal slowly. Easy bruising is due to an increase
in capillary fragility.
 Head and body hair becomes dry and brittle, lacks luster, and tends to fall
out.

11. Clinical Manifestations of Hypothyroidism –
Cardiovascular System
 Reduced myocardial contractility ,pulse rate, stroke volume and
bradycardia.
 Increased peripheral resistance leads to hypertension, particularly diastolic
HTN.
 Pericardial effusions seen in up to 30% of patients.
 Chest x rays findings are cardiomegaly , interstitial edema, myofibrillary
swelling, LV dilatation and pericardial effusion.
.

12.  Ecg changes are –
 Sinus bradycardia, prolongation of the PR interval
 Low amplitude of the P wave and QRS complex,
 Alterations of the ST segment
 Flattened or inverted T waves.

13. Clinical Manifestations of Hypothyroidism –
Respiratory System
 Lung volumes - normal, but maximal breathing capacity and diffusing
capacity are reduced.
 In severe case, involvement of respiratory muscles and depression of both
the hypoxic and hypercapnic ventilatory drives leads to alveolar
hypoventilation and carbon dioxide retention.
 Obstructive sleep apnea is due to macroglossia.

15. Clinical Manifestations of Hypothyroidism –
Muscular System
 Stiffness and aching of muscles and are worsened by cold temperatures.
 Delayed muscle contraction and relaxation cause slowness of movement
and delayed tendon jerks.
 Muscle mass may be reduced or enlarged due to interstitial myxedema.
Myoclonus may be present.
 The electromyogram may be normal or may exhibit disordered discharge,
hyperirritability, and polyphasic action potentials.

16. Clinical Manifestations of Hypothyroidism
Skeletal System
 Thyroid hormone is essential for normal growth and maturation of the
skeleton.
 Growth failure is due to impaired protein synthesis and reduction in
growth hormone, but especially of insulin-like growth factor 1 .
 Before puberty, thyroid hormone plays a major role in the maturation of
bone.
 Deficiency of thyroid hormone in early life leads to both a delay in
development and epiphyseal dysgenesis.

17.  Impairment of linear growth leads to dwarfism, in which the limbs are
disproportionately short but cartilage growth is unaffected .
 Children with prolonged hypothyroidism, even after adequate treatment, do
not reach predicted height based on midparental height calculations.

19. Clinical Manifestations of Hypothyroidism
Reproductive System
 Infantile hypothyroidism leads to sexual immaturity and delay in puberty
followed by anovulatory cycles in girls.
 Libido is decreased in both sexes, and there may be oligomenorrhea or
amenorrhea in long-standing disease.
 Fertility is reduced, and incidence of miscarriage is increased.
 Prolactin levels are increased and may contribute to alterations in libido
and fertility and cause galactorrhea.

20.  In adult women, severe hypothyroidism may be a/w diminished libido and
failure of ovulation.
 Hypothyroidism in men may cause diminished libido, erectile dysfunction,
and oligospermia.

21. Clinical Manifestations of Hypothyroidism
Central and Peripheral Nervous Systems
 Thyroid hormone is essential for the development of the CNS.
 Deficiency in fetal life or at birth impairs neurologic development,
including hypoplasia of cortical neurons with poor development of cellular
processes, retarded myelination, and reduced vascularity.
 If the deficiency is not corrected in early postnatal life, the damage is
irreversible.
 All intellectual functions, including speech, are slowed in thyroid hormone
deficiency.

22.  In severe cases, decreased cerebral blood flow may lead to cerebral
hypoxia.
 Loss of initiative is present and memory defects are common, lethargy and
somnolence are prominent.
 Psychiatric disorders are common and are usually of the paranoid or
depressive type and may induce agitation (myxedema madness).
 Headaches are frequent. Cerebral hypoxia may predispose to confusional
attacks and syncope, which may be prolonged and lead to stupor or coma.

23.  Epileptic seizures can occur in myxedema coma.
 Night blindness is due to deficient synthesis of the pigment required for
dark adaptation.
 Hearing loss of the perceptive type is frequent due to myxedema of the
eighth cranial nerve and serous otitis media.

24.  Numbness and tingling sensation of the extremities are frequent.
 Due to compression by glycosaminoglycan deposits around the median
nerve leads to carpal tunnel (carpal tunnel syndrome).
 Electroencephalographic changes include slow alpha-wave activity and
general loss of amplitude.

25. Clinical Manifestations of Hypothyroidism
Gastrointestinal System
 Most patients experience a modest gain in weight which is caused by
retention of fluid by the hydrophilic glycoprotein deposits in the tissues .
 Decreased peristaltic activity and decreased food intake leads to
constipation. The latter may lead to fecal impaction (myxedema
megacolon).
 Ascites is unusual in hypothyroidism, but it can occur, usually in
association with pleural and pericardial effusions.

26.  In a population study of those without diagnosed thyroid disease, men (but
not women) with an elevated TSH had a 3.8-fold increased risk of
cholelithiasis.
 Hypothyroidism is being recognized as a predisposing factor for NAFLD.
 Circulating antibodies against gastric parietal cells about 1/3rd of patients
and may be secondary to atrophy of the gastric mucosa.
 Overt pernicious anemia is reported in about 12% of patients with primary
hypothyroidism.

27. Metabolic Abnormalities
 Hyponatremia may result from a reduction in free water clearance.
 Reversible increases in serum creatinine occur in 20 ~ 90% of hypothyroid
patients.
 lipid clearance may be decreased, resulting in an elevation in the serum
concentrations of free fatty acids , total and LDL cholesterol.
 Plasma homocysteine concentrations are increased in some hypothyroid
patients.

30. Treatment of Hypothyroidism
 Replacement does of levothyroxine in adults range from 0.05 to 0.2
mcg/kg/day. It varies according to the patient’s age and body weight.
 In young children: 4-5 mcg/kg/day
 In adults: average 1.6 - 1.7 mcg/kg/day
 In elders ( >60 yrs) or cardiac disease patient start with lower dose, ex.
25mcg daily, increase the dose at 4- to 6-week intervals based on serum
FT4 and TSH levels
 Dose should be increased about 25% during pregnancy.

31.  TSH will take minimum 12 -16 weeks to normalizes.
 Clinical relief 3-6 months after TSH normalizes.
 For monitoring the patient ,TSH is the best choice.
 Most common cause for treatment failure is non- compliance.

33. Hashimoto’s Thyroiditis
 Autoimmunity is responsible for over 90% of non iatrogenic
hypothyroidism in countries with iodine sufficiency.
 Average age of onset is between 40 and 60 years.
 More common in female as compare to male
 Juvenile and adolescent autoimmune thyroiditis may be self-limiting.
 Hashimoto thyroiditis is the commonest cause of goiter in iodine-sufficient
regions, atrophic thyroiditis (primary myxedema)presents a hypothyroidism
without a goiter.

34.  Risk factor –Genetic susceptibility
 HLA DR3,HLADR4,HLADR5
 CTLA4 , PTPN22 and MAGI3 Polymorphism
 It is associated with other autoimmune disorders like-
 Pernicious anemia
 Systemic lupus erythematosus
 Addison disease
 Celiac disease,
 Diabetes mellitus type 1
 Vitiligo.
 Increased risk of pre malignant condition :
 Extra nodal marginal zone B cell lymphoma
 Papillary carcinoma of Thyroid

35. Pathophysiology
 T-cell–mediated tissue injury is believed to be the most important cause of
autoimmune thyroid follicular cell destruction.
 Perforin-containing cytotoxic CD8+ T cells are abundant in the
intrathyroidal lymphocytic infiltrate in Hashimoto thyroiditis.
 These T cells increase during the evolution of disease and recognize both
thyroglobulin and TPO.
 Cytokines released by T cells and other inflammatory cells cause Hürthle
cell formation and thyroid dysfunction.
 Apoptosis is an additional pathway for thyroid cell destruction.

36.  Characteristic finding:
Deposition of glycosaminoglycans – mostly hyaluronic acid – in interstitial
space of many tissues that causes-
 Macroglossia
 Periorbital edema
 Non pitting edema and puffiness.
 The accumalation is due not to excessive synthesis but to decreased
destruction of glycosaminoglycans.
 Sign and symptoms – Fatigue (mc) Slowing of speech Cold intolerence
Constipation Weight gain Delayed DTR
Hair loss Bradycardia Dry & coarse skin

37. Subclinical Hypothyroidism
 By definition, subclinical hypothyroidism refers to biochemical evidence of
thyroid hormone deficiency in patients who have few or no apparent
clinical features of hypothyroidism.
 There are no universally accepted recommendations for the management of
subclinical hypothyroidism, but levothyroxine is recommended if the
patient is a –
1. Woman who wishes to conceive
2. Pregnant
3. TSH levels are above 10 mIU/L.
4. Symptomatic
5. Positive TPO abtibody

38.  Otherwise, when TSH levels are below 10 mIU/L, a trial of treatment may
be considered when patients have suggestive symptoms of hypothyroidism,
positive TPO antibodies, or any evidence of heart disease.
 It is important to confirm that any elevation of TSH is sustained over a 3-
month period before treatment is given.
 Treatment is administered by starting with a low dose of levothyroxine
(25–50 μg/day) with the goal of normalizing TSH.
 If levothyroxine is not given, thyroid function should be evaluated
annually.

40. Hypothyroidism in pregnancy
 Maternal hypothyroidism may both adversely affect fetal neural
development and be a/w adverse gestational outcomes (miscarriage,
preterm delivery).
 The presence of thyroid autoantibodies alone, in a euthyroid patient, is also
associated with miscarriage and preterm delivery.
 Prior to conception, levothyroxine therapy should be targeted to maintain a
serum TSH in the normal range but <2.5 mIU/L for hypothyroid women.
 Thyroid function should be evaluated immediately after pregnancy is
confirmed and every 4 weeks during the first half of the pregnancy, with
less frequent testing after 20 weeks’ gestation (every 6–8 weeks).
 The levothyroxine dose may need to be increased by up to 45% during
pregnancy.

41.  After delivery, levothyroxine doses typically return to prepregnancy levels.
 Pregnant women should be counseled to separate ingestion of prenatal
vitamins and iron supplements from levothyroxine.

42. Myxedema Coma
 Myxedema coma is the ultimate stage of severe long-standing
hypothyroidism.
 Affects older patients, occurs most commonly during the winter months
and is a/w a high mortality rate (20-40%).
 Triggers factors – Exposure to cold Infection
Trauma Myocardial infarction ,
Stroke CNS depressants or anesthetics.

44.  Presentation – Reduced level of Consciousness/seizure
 Hypothermia
 Hypoglycemia
 Hypoventilation (leads to carbon dioxide retention and narcosis)
 Hyponatremia
 Bradycardia ( decreased CO)

45. Treatment
 Levothyroxine can initially be administered as a single IV bolus of 200–
400 μg, which serves as a loading dose, followed by a daily oral dose of 1.6
μg/kg/day, reduced by 25% if administered IV.
 If suitable IV preparation is not available, the same initial dose of
levothyroxine can be given by nasogastric tube
 An initial loading dose of 5–20 μg liothyronine should be followed by 2.5–
10 μg 8 hourly, with lower doses for those at cardiovascular risk.

46.  Hydrocortisone (50 mg iv Q6H) should also be given because of the
possibility of relative adrenocortical insufficiency as the metabolic rate
increases.
 Hypotonic fluids should not be given because of the danger of water
intoxication owing to the reduced free water clearance of the hypothyroid
patient.
 External warming is indicated only if the temperature is <30°C, as it can
result in cardiovascular collapse.
 Hypertonic saline or IV glucose may be needed if there is severe
hyponatremia or hypoglycemia.

47. Thank you