1. thyroid gland the metabolism of virtually all nucleated cells of many tissues in the body is...
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Thyroid GlandThe metabolism of Virtually all nucleated cells of many tissues in the body is controlled by thyroid hormone
Over activity (Hyperthyroidism) and under activity (Hypothyroidism) of the gland are most common of all endocrine problems
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Thyroid GlandAnatomy:
It has two lateral lobes connected by Isthmus
It moves on swallowing as it is attached to thyroid cartilage and trachea
Embryologically it originates from the base of the tongue and then descends therefore sometimes remnants of thyroid can be found at the base of tongue (Lingual thyroid)
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Thyroid GlandAnatomy:
Thyroid gland has follicles lined by cuboidal epithelial cells. Inside the follicle is colloid (Iodinated glycoprotein Thyroglobulin) which is synthesized by follicular cells.
Each follicle is surrounded by basement membrane, between follicular cells there are parafollicular cells containing calcitonin secreting C cells
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Follicular & parafollicular cells
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Thyroid GlandPhysiology:
Thyroid gland synthesizes two hormones T3 – Triiodothyronin: acts at Cellular level
T4 - L – Thyroxin: which is prehormone
More T4 is produced than T3 in thyroid but T4 is converted to T3 in periphery
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Thyroid Gland
Physiology:In Plasma more than 99% of T4 and T3 is
bound to protein (Thyroxin Binding Globulin TBG, Thyroid Binding PreAlbumin TBPA) and Albumin
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Thyroid GlandPhysiology:Control of hypothalamic–pituitary–thyroid axis:Hypothalamus produces TRH – Thyrotropin releasing hormone, it stimulates pituitary to secrete TSH – Thyroid Stimulating Hormone.TSH stimulates activity of Thyroid Follicular cells T3 & T4 are secreted in circulation by follicular cellsT3 & T4 has negative feedback effect on Hypothalamus and pituitary
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Physiological Effect of Thyroid Hormone
Thyroid GlandThyroid Function Test:
Free T4 Free T3 and TSH are available and test can be done at anytime of the day
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1 Thyrotoxicosis ↓TSH Free T4 ↑ Free T3 ↑
2Primary
HypothyroidismTSH ↑
Free T4 ↓Or Low Normal
T3 N or Low
3TSH Deficiency
(Pituitary) ↓TSH
Free T4 ↓ or Low Normal
T3 N or Low
HYPOTHYROIDSM
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HypothyroidismIt is usually primary due to disease of thyroid, but may be secondary to hypothalamic – pituitary disease (decreased TSH drive)
It is more common in females
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HypothyroidismAutoimmune Hypothyroidism
It is most common cause and associated with antithyroid antibodies
It is six time more common in females
It has association with other autoimmune diseases e.g. pernicious anemia, Vitiligo etc.
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HypothyroidismHashimotos Thyroiditis
This is a form of autoimmune thyroiditis, more common in females and occurs in late middle age
Causes atrophic changes and regeneration leading to goiter formation
TPO ( Thyroid per oxidase) antibodies are present in high titer (> 1000 IU/L)
Patient may be hypothyroid or Euthyroid, though they may go through initial toxic phase
Levothyroxin is given when patient is hypothyroid
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HypothyroidismPost Partum Thyroiditis
This is transient phenomena, observed after pregnancy
It may cause Hyperthyroidism, Hypothyroidism
It is due to result of modifications to the immune system in pregnancy
It is usually self limiting or leads to hypothyroidism
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Defects of Thyroid Hormone SynthesisDefects of Thyroid Hormone SynthesisIodine Deficiency
Iodine is required for synthesis of T3 & T4
We take iodine in diet, if deficient than people get goiter ( due to TSH stimulation)
Patient may be euthyroid or hypothyroid Iodine deficiency is problem in many
countries e.g. Netherlands, India, Asia, Africa, Russia
Efforts are made to prevent iodine deficiency by adding iodine in common salt. 17
Defects of Thyroid Hormone SynthesisDefects of Thyroid Hormone SynthesisDyshormonogenesis
Rare condition, due to genetic defect in the synthesis of thyroid hormone
Patient develops hypothyroidism with goiter
Note—Some people have Genetic defect causing sensorineural deafness due to mutation at chromosome 7, they have goiter( hypothyroid) also and this condition is called Pendred Syndrome
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Hypothyroidism Symptoms and Signs
*Bold type indicate important symptoms and signs
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Hypothyroidism
HypothyroidismHypothyroidismMyxoedema:
It refers to Hypothyroidism plus accumulation of mucopolysaccharide in subcutaneous tissue
Patient is slow, thick skin, dry hair, deep voice, weight gain, cold intolerance, bradycardia, constipation
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HypothyroidismHypothyroidismChildren with Hypothyroidism:Have slow growth velocityHave poor school performance
Young Females with HypothyroidismHypothyroidism should be excluded
in all women with Oligomenorrhoea, amenorrhoea, menorrhagia, infertility, Hyperprolactinimia
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HypothyroidismHypothyroidismInvestigations:
Serum Free T3, Free T4 and TSH High TSH confirms primary
Hypothyroidism, free T4 is low Other investigations:
Anemia – usually normocytic normochromic
But may be Macrocytic (due to associated Pernicious anemia )
Microcytic – in women due to menorrhagia
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HypothyroidismHypothyroidismOther Investigations:
Increase serum creatinine Kinase – with associated Myopathy
Hypercholesterolemia and hypertriglyceridaemia
Hyponatremia – due to increase ADH
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HypothyroidismHypothyroidismTreatment:
Thyroxin – T4 is given for life Dose 100 Micrgram daily for young patients 50 microgram for small, old patient to be
increased to 100 microgram after 2 – 4 days If patient has IHD start with 25 Microgram
daily and increase dose at 3 – 4 week interval ( monitor by serial ECG)
Aim of treatment is to restore T4 & TSH within normal range
Improvement on T4 takes 2 weeks or more and resolution of symptoms takes about 6 months
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HypothyroidismHypothyroidismTreatment for Myxoedema:
It is severe hypothyroidism and patient may present with confusion or even COMA
Myxoedema Coma is very rare, hypothermia is often present and patient may have severe cardiac failure, pericardial effusion, hypoventilation, hypoglycemia, hyponatremia
Mortality is high26
HypothyroidismHypothyroidismTreatment for Myxoedema:
T3 orally or IV 2.5-5 microgram 8 hourly
O2 Hydrocortisone 100 mg IV 8 HourlyGlucose infusionGradual rewarming
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HyperthyroidismHyperthyroidism (Thyrotoxicosis) is common,
affecting 2-5% of all females Female-Male ratio 5:1 Age 20-40 years More than 99% cases are caused by intrinsic
thyroid disease, pituitary cause is extremely rare
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Graves DiseaseThis is most common cause of hyperthyroidism
and is due to autoimmune process IgG antibodies bind to TSH receptors in the
thyroid and stimulate thyroid hormone production (IgG behaves like TSH)
TSH receptor antibodies (TSHR – Ab antibodies) are specific for Graves Disease
Graves Disease is associated with autoimmune disorders such as pernicious anemia, Vitiligo and myasthenia gravis
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Other Causes of Hyperthyroidism/ThyrotoxicosisSolitary toxic adenoma/nodule It is cause of 5% cases of hyperthyroidism usually
remit after antithyroid drugs Toxic multinodular goitreCommonly occurs in older womanAnti thyroid drugs control hyperthyroidism
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Other Causes of Hyperthyroidism/ThyrotoxicosisDe Quervain’s thyroditis This is transient hyperthyroidism due to
inflammatory process, probably viral in origin
There is fever, maliase, pain in the neck, tachycardia and local thyroid tenderness
Thyroid function test show - Hyperthyroidism - Increased ESR 33
Other Causes of Hyperthyroidism/ThyrotoxicosisDe Quervain’s thyroditis Thyroid function test show (cont) - Thyroid uptake show suppression of uptake in
acute phase - Hypothyroidism, usually transient, may follow
after few weeks Treatment of acute phase - Aspirin - Predinisolone
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Other Causes of Hyperthyroidism/ThyrotoxicosisAmiodarone – induced thyrotoxicosis (AIT)Amiodarone is anti arrhythmic drug – class
111 and causes hyperthyroidism
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Symptoms and Signs of Hyperthyroidism
36*Bold type indicate important symptoms and signs
Clinical Features of HyperthyroidismThe eye signs of lid lag and stare May occur with hyperthyroidism of any cause Graves dermopathy Pretibial myxoedema – is in filtration of the skin
on the shin Thyroid Acropachy – very rare and consist of
clubbing, swollen fingers and periosteal new bone formation
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Clinical Features of Hyperthyroidism (cont)
Atrial Fibrillation in the elderly Is frequent presentation Children with hyperthyroidism May present – excessive height,
hyperactivity
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Pretibial myxoedema
Differential Diagnosis Anxiety (Sympathetic Stimulation) There is tachycardia, tremor, but cold
clammy hand
In hyperthyroidism, there is tachycardia tremor, warm hands, eye
signs, diffused goitre, weight loss despite increase appetide
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Hyperthyroidism InvestigationsSerum TSH is suppressed, free T4 or T3 are
raised Thyroid per oxidase (TPO) and thyroglobulin
antibodies are present in most cases of Graves disease
Thyroid stimulating immunoglobulin (TSI) are present in Graves disease
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HyperthyroidismTreatmentThree options are available 1. Anti thyroid drugs 2. Radio active iodine 3. Surgery
1. Anti thyroid drugs Carbimazole – 20-40mg/day 8 hourly or single dose Propylthioracial (PTU) – 100-200mg 8 hourly They inhibit the formation of thyroid hormonesPropranolol (Beta Blocker) is used for symptomatic relief
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HyperthyroidismTreatmentSide effects of drugs Carbimazole – rash, nausea, vomiting,
arthralgia, agranulocytosis, jaundice PTU – rash, nausea, vomiting, agranulocytosis NOTE – As agranulocytosis is the side effect,
therefore, patient is advised if he has sore throat, he should report to hospital for investigation
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HyperthyroidismTreatment (cont)2. Radioactive Iodine – 131Iodine Can be given to all patientsIs contraindicated in pregnancy and during
breast feeding3. SurgerySubtotal thyroidectomy/thyroidectamy Side effects – laryngeal nerve palsy occur in 1%Transient hypocalcemia up to 10%
Permanent hypoparathyroidism < 1%
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Hyperthyroidism in PregnancyDuring pregnancy Propylthioracial (PTU) is
preferred because there are reports of congenital abnormalities with Carbimazole
TSI – thyroid stimulating immunoglobulin cross the placenta and stimulate fetal thyroid
Carbimazole and PTU cross the placenta T4 (Thyroxin) very poorly crosses the placentaIf necessary surgery can be performed in
second semester of the pregnancy
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