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