Hypothyroidism is a common endocrine disorder where the thyroid gland produces insufficient hormones. It affects 1.8% of the population and is more prevalent in females and the elderly. The most common cause is Hashimoto's thyroiditis which results in lymphocytic infiltration and thyroid damage. Symptoms of hypothyroidism are non-specific but include fatigue, weight gain, dry skin, and low heart rate. Treatment involves lifelong thyroid hormone replacement therapy with levothyroxine to normalize thyroid levels. Special care is needed in pregnancy, myxedema coma, and avoiding overtreatment.

1. Hypothyroidism
DR. S. ASWINI KUMAR. MD
Professor of Medicine
Medical College Hospital
Thiruvananthapuram
Learning objectives:
• Understand thyroid hormone function
• Narrate the causes of hypothyroidism
• Describe the pathophysiology of hypothyroidism
• Identify risk factors for hypothyroidism
• Describe optimal approaches to treatment
• Understand side effects relevant to the treatment
• Describe consequences of minor deficiency of hormones
• Know effects of excess thyroxin dosage in clinical practice
Thyroid Hormone Physiology:
• Thyroid hormones are necessary for the normal metabolism of human body
• They have an important role to play in acceleration of growth and development
• They have a role in increasing body’s calorie production as per requirement
• Every tissue of body is affected directly or indirectly by the actions of the hormones
• The functions of thyroid hormones include:
• regulation of basal metabolic rate and adjustments of resting oxygen consumption
• increased uptake, synthesis and utilization of glucose and heat production
• sympathomimetic effects including increased heart rate and force of contraction
Thyroid Hormone Control:
• Hypothalamic-pituitary-thyroid axis controls synthesis and release of thyroid hormones
• The hypothalamus synthesizes a peptide thyrotropin releasing hormone (TRH)
• TRH stimulates pituitary thyrotrophs to produce thyroid stimulating hormone (TSH)
• TSH travels to and stimulates the thyroid gland, trophically to produce T4 and T3
T4 - T3 conversion:
• The major product of thyroid gland is T4. It accounts for 85% of thyroid hormone output
• T4 is metabolized by mono-deiodination to T3 , the more potent, biologically active form
• Circulating T4 has a half-life of seven days, whereas T3 has a half life of only one day
Thyroid Hormone Receptors:
• 3 receptors mediate the primary actions of thyroid hormone
• These are named as TRa1, TRß1, and TRß2
• Interaction of T3 with its receptor promotes binding of cofactors
• These cofactors regulate expression of thyroid-hormone-responsive genes
• They act either through activation or repression of transcription
Hypothyroidism:
• Definition: It is the manifestation of effects of reduced thyroid hormones in human tissues
• 1.8% of total population affected and 2nd only to DM as commonest endocrine disorder
• Incidence increases with age and it is more common in females - 2-3% of older women
Classification of Hypothyroidism:
• Clinical Hypothyroidism (Overt Hypothyroidism)
• Symptoms are manifest - TSH is high and serumT3 and T4 are low
• Subclinical Hypothyroidism (Mild Hypothyroidism)
• No symptoms - Mild TSH and Normal T3 & T4
• Euthyroid individual –
• Normal thyroid function Normal TSH – Normal T4 and T3

2. Etiology:
• PRIMARY HYPOTHYROIDISM - 99%
• Hoshimoto’s thyroiditis is the most common cause
• Idiopathic hypothyroidism is also probably cases of old Hoshimoto’s Thyroiditis
• Irradiation or Surgical removal of thyroid or Drug therapy
• Iodine deficiency is still the most common cause of hypothyroidism
• Infiltrative Diseases: Sarcoidosis, Amyloidosis
• SECONDARY HYPOTHYROIDISM [1%]
• Decreased TSH production and resultant reduction in T4
• Pituitary neoplasm, Pituitary necrosis (Sheehan’s syndrome)
• Congenital hypopituitarism
• Hypothalmic dysfunction (Teritiary Hypothyroidism)
Hashimoto’s Thyroiditis:
• Dr. Hakaro Hashimoto was born in Iga-Ueno in Japan in the year 1881
• He graduated in Medicine form Kyushu Imperial Medical University
• In 1912, he described the chronic thyroid disorder
• He termed it as Struma Lymphamatosa; but now called as Chronic Lymphocytic Thyroiditis
• It is characterized by diffuse lymphocytic infiltration, fibrosis and parenchymal atrophy
Pathogenesis:
• Reduced metabolic rate causes reduced performance
• Hence weight gain occurs despite a poor appetite
• The pathology is deposition of Glycos-Amino Glycans(GAG) in tissues
• GAG is hygroscopic and causes mucinous edema
• Hence this results in a boggy non-pitting edema in tissues which are lax
• Skin and hair effects:
• Skin has reduced sweating and sebaceous secretions
• And there is thinning of epidermis, hyperkeratosis of stratum corneum
• Hence the skin is pale, cool, dry and coarse
• Capillary fragility causes easy bruisability
• Scalp and body hair as well as the nails are dry and brittle
• Cardiovascular effects:
• Decrease in heart rate, pulse pressure and ↓ in the cardiac output
• ↓ blood supply and vasoconstriction of skin – results in cold intolerance
• Increased systemic vascular resistance – leads to increase in DBP
• Flabby myocardium and pericardial effusions are common
• ECG changes – sinus bradycardia, low voltage, ST & T changes
• Respiratory and GIT effects:
• Hoarseness of voice – due to GAG deposition in larynx
• Obstructive sleep apnoea to a thick tongue falling back
• Constipation due to reduced gut peristalsis
• Myxedema megacolon and Myxedema ileus are uncommon
• Neuromuscular effects:
• Slowed physical and mental functions leads to lethargy and increased somnolence
• Carpel tunnel syndrome due to deposition of GAG
• Delayed relaxation of ankle jerk is a useful bed side clinical finding
• Deafness and depression and rarely Myxedema madness may occur
Signs and Symptoms:
• These are non-specific and gradual in onset
• May be confused with other conditions like postpartum depression and Alzheimer’s
• One must maintain high index of suspicion

3. Common signs and symptoms:
Laboratory values
Additional Tests:
• Once diagnosis of primary hypothyroidism is made,
• Additional imaging or serologic testing are unnecessary if gland is WNL
• In secondary cases, further testing with pituitary provocative testing
• imaging with CT scan annd or MRI to rule out microadenoma
• Evidence of ↓ of >1pituitary hormone indicates a panhypopituitary problem
• Serum cholesterol may be elevated. Complete lipid profile and ECG studies
• Prolactin levels are elevated in Secondary Hypopiuitarism
• Blood Haemoglobin and ferritin testing for anaemia are indicated in most cases
Antibodies in hypothyroidism:
• Anti Thyroid Per-Oxidase [anti microsomal] antibodies – Anti-TPO in most cases
• Anti thyroglobulin antibodies – Anti TG. Also found elevated in Hashimoto’s Thyroiditis
• Anti bodies against T3 and T4 in auto immune disease.
• Anti TSH Receptor and Anti-T3 T4 Receptor antibodies are also sometimes seen
• Anti gastric parietal cell antibodies are seen in 10% and this may lead to Pernicious Anemia
Thyroid Hormone Replacement:
• Most healthy adults require 1.7 ugm/kg/day – 100-150ug/day
• Levothyroxine cause increases in resting heart rate and BP
• Start at low doses in older and if cardiovascular compromise
• Elderly, dosage falls down to – 1.0 ugm/kg/day -50-100ug/day
• For full replacement children need up to 4ugm /kg/day

4. Monitoring thyroid function:
• Followed by serial TSH measurements
• Changes in TSH levels lag behind serum T3 T4
• Resetting pituitary gland takes about 1 month
• So TSH not be checked sooner than 4 weeks
• Goal to keep TSH in lower half of normal range
• No need to monitor the T3 T4 levels normally
• In pituitary insufficiency T3 & T4 are followed
• Goal to keep T3 T4 in upper range of normal
• Once stable TSH or Free T4 monitored yearly
• Once stable it remains stable until 60-70 yrs
Pregnancy and Thyroid:
• During pregnancy the requirement for FT4 increases by 25-50%
• Estrogens → TBG → ↓FT4 → TSH + TPO Ab →Hypothyroidism
• Miscarriage, preterm delivery, preeclampsia & placental abruption
• Can lead to ↓intellectual capacity & developmental delay in children
• (AACE) recommend universal thyroid testing for pregnant women
Myxedema coma:
• High mortality rate, despite intensive treatment
• Myxedema coma almost always occurs in the elderly
• Reduced consciousness, seizures + other features of hypothyroidism
• Precipitated by factors that impair respiration like sedatives
• Other precipitating factors - MI, CCF, CVA, UGIB and Pneumonia
• Myxedema coma-Treatment:
• Levothyroxine A single IV bolus of 500 g loading dose
• Levothyroxine is continued at a dose of 50 to 100 g/day
• If IV is not available the same initial dose by NG tube
• Supportive therapy:
• Correct metabolic disturbances & precipitating factors
• Hydrocortisone 50mg q6h should be administered
• Early use of broad-spectrum antibiotics for infection
• Space blankets should be used to prevent heat loss
• External warming for <300C, otherwise CV collapse
• Hypertonic saline if there is hyponatremia
• Hypotonic IV fluids avoided because water retention
• Intravenous glucose if there is hypoglycemia
• Sedatives avoided and blood levels monitored
• Ventilator support with regular blood gas analysis
Subclinical Hypothyroidism
• Definition: Biochemical evidence but no clinical evidence
• No universal consensus in treatment of mildly elevated TSH
• Little risk if excessive treatment is avoided and clinical benefits
• Patients will progress to overt HYPO if TSH is >6mU/l
• Start with low dose 25-50 ug/day and slowly titrate upwards
Risk of over treatment
• Over treatment may result in atrial fibrillation
• Otherwise there is a risk of development of osteoporosis
• Then there is a possibility of inducing frank hyperthyroidism
• Emotional lability, nervousness, irritability, poor concentration
• Start with low dose 25-50 ug/day and slowly titrate upwards