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Thursday, 22 November 2012

HYPOTHYROIDISM



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

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
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

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

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