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Thyroid function tests (TFTs) (Ref. Hari. 18th ed., Pg - 2917)


Physiology :

  1. The thyroid produces mainly T4, (inactive), & little amount of T3 (Active).
  2. 85% of T3 is formed from peripheral conversion of T4 .  

Drugs which inhibit peripheral conversion of T4 to T3 (FAQ)

  1. Propranolol              
  2. Dexamethasone   
  3. Propylthiouracil    
  4. High dose of iodine
  5. Radiographic contrast media
Extra Edge:

All these drugs are used in hyperthyroid crisis  (MCQ)


Important Points:

  1. Most of T3 and T4 in plasma is protein bound to
    a. Thyroxine-binding globulin (TBG).
    b. Transthyretin (Thyroxine-binding prealbumin, TBPA)
    c. Albumin
  2. The unbound (Free) portion is the active part
  3. T4 and T3 increase cell metabolism, via nuclear receptors, and are thus vital for growth and mental development
  4. They also  catecholamine effects.
Extra Edge:
  1. If we give high dose of iodine for short period it inhibit T4 synthesis (Wolf Chaikoff effect)
  2. If we give low dose of iodine for a long period it increases T4 synthesis (Job Basedow effect)


Basic tests:

  1. Measurement of free T4 and T3 levels is more useful than total T4 & total T3 levels as the latter are affected by TBG.
  2. Total T4 and T3 are when TBG is and vice versa.
  3. But if TBG levels change than free T3 and T4 levels are not affected. 
Extra Edge:
  1. TBG is  in pregnancy, oestrogen therapy (HRT, oral contraceptive pill) and hepatitis.
  2. TBG is  in nephrotic syndrome and malnutrition (protein loss), drugs (eg androgens, corticosteroids, phenytoin), chronic liver disease and acromegaly.


Assessment of thyroid function Test.

  1. T4, and ↑ TSH = Primary Hypothyroidism
  2. Normal T4, ↑ TSH = subclinical hypothyroidism (TSH being the main determinant in deciding) 
  3. TSH T4 = TSH secreting pituitary tumour or thyroid hormone resistance
  4. TSH,  T4 or T3 = Hyperthyroidism
  5. TSH, Normal T4 & T3 = Subclinical hyperthyroidism
  6. TSH,  T4 T3 = Sick euthyroidism, Secondary hypothyroid due to hypopituitary.
Extra Edge:

TSH is the best test to assess hypothyroid.

Normal TSH = 0.5 – 5 mu / l

Normal level of TSH Tested

mu/l Test Name Amonut  of TSH sensitivity
1-2 1st general TSH assay Radio immuno assay (RIA)  0.5
0.1 – 0.2 2nd Immuno radiometric assay (IMRA) 0.05
0.01 – 0.02 3rd Chemi luminescent assay 0.005


Extra edge:

Extremely sensitive fourth-generation assays can detect TSH levels ≤ 0.04 mU/L. but for practical purposes, assays sensitive to ≤ 0.1 mU/L are sufficient. (Ref. Hari. 18th ed., pg-2917)


Sick euthyroidism (Ref. Hari. 18th ed., Pg-2929)

  1. In any systemic illness, TFT may become deranged.
  2. The most common hormone pattern in sick euthyroid syndrome (SES) is a decrease in total and unbound T3 levels (low T3 syndrome) with normal levels of T4 and TSH.
  3. The magnitude of the fall in T3 correlates with the severity of the illness. T4 conversion to T3 via peripheral deiodination is impaired, leading to increased reverse T3 (rT3).
  4. Despite this effect, decreased clearance rather than increased production is the major basis for increased rT3. Also, T4 is alternately metabolized to the hormonally inactive T3 sulfate.
  5. This low T3 state is adaptive, because it can be induced in normal individuals by fasting. Because the fall in T3 may limit catabolism in starved or ill patients.
  6. Very sick patients may exhibit a dramatic fall in total T4 and T3 levels (low T4 syndrome).
  7. In the very advance stage the typical pattern is for 'everything to be low (TSH,  T4 T3) 

Drugs which interfere with thyroid hormone binding with proteins

  1. NSAID            
  2. Phenytoin            
  3. Carbamazepine  

T3 resin uptake test

  1. The binding of the labeled T3 to the resin is increased in.
    1. TBG deficiency          
    2. Hyperthyroidism
  2. The binding of the labeled T3 to the resin is decreased in.
a. Hypothyroid.



  1. This distinguishes cystic (usually, but not always, benign) from solid (possibly malignant) nodules,
  2. If there is a solitary large nodule, or dominant nodule in a multinodular goitre, a fine needle aspiration should be performed to look for thyroid carcinoma.

Isotope scan: (123I, 125I, 131I or 99Technetium pertechnetate). (Ref. Hari. 18th ed., pg - 2917)

  1. Useful for determining the cause of hyperthyroidism.
  2. Detect retrosternal goitre.
  3. Ectopic thyroid tissue
  4. Thyroid metastases (using whole body CT scan).
    1. 20% of 'cold' nodules are malignant. (MCQ)
    2. Few neutral and almost no hot nodules are malignant. (MCQ)

Causes of thyroid enlargement

  1. Diffuse goitre
    1. Simple goitre                                
    2. Hashimoto's thyroiditis
    3. Graves' disease                               
    4. Drugs - Iodine, amiodarone, lithium
    5. Iodine deficiency (endemic goitre)            
    6. Suppurative thyroiditis
    7. Transient thyroiditis                       
    8. Dyshormonogenesis
    9. Infiltrative - Amyloidosis, sarcoidosis                
    10. Riedel's thyroiditis2
  2. Multinodular goitre
  3. Solitary nodule 
    1. Simple cyst                                
    2. Colloid nodule
    3. Follicular adenoma                  
    4. Papillary carcinoma
    5. Follicular carcinoma                  
    6. Medullary cell carcinoma
    7. Anaplastic carcinoma                      
    8. Lymphoma
    9. Metastasis


Table - Causes of Thyrotoxicosis (Ref. Hari. 18th ed. table 341.6, Pg-2922)


  1. Thyrotoxicosis Associated with Hyperthyroidism  
    1. Primary
      1. Diffuse toxic hyperplasia (Graves disease)              
      2. Hyperfunctioning ("toxic") multinodular goiter
      3. Hyperfunctioning ("toxic") adenoma
      4. Iodine-induced hyperthyroidism
      5. Neonatal thyrotoxicosis associated with maternal Graves disease
    2. Secondary
      1. TSH-secreting pituitary adenoma (rare)*
      2. Chorionic gonadotropin-secreting tumors
      3. Gestational thyrotoxicosis  
  2. Thyrotoxicosis Not Associated with Hyperthyroidism
    1. Subacute granulomatous thyroiditis (painful)
    2. Subacute lymphocytic thyroiditis (painless)
    3. Struma ovarii (ovarian teratoma with ectopic thyroid)
    4. Factitious thyrotoxicosis (exogenous thyroxine intake)

Graves Disease

This is an autoimmune disease caused by stimulatory TSH-receptor antibodies (which also react with orbital autoantigens.

These patient have HLA – B8, DR 3 (Ref. Hari. 18th ed., pg-2923)


TSH-receptor antibodies include

  1. TSI (Thyroid stimulating Ig)
  2. TGI (Thyroid growth stimulating Ig)
  3. TBII = TSH binding inhibitor Ig. It can stimulate or inhibit thyroid cell function  

Prevalence of thyroid autoantibodies (%) (Ref. Hari. 18th ed. Pg - 2917)





Antibodies to (Present in % of cases)



Thyroid peroxidase


TSH receptor

Normal population

5-15 %

5-20 %

0 %

Graves' disease

50-80 %

50-70 %

80-95 %

Autoimmune hypothyroidism

90-100 %

80-90 %

10-20 %

Multinodular goitre

<30-40 %

~30-40 %

0 %

Transient thyroiditis

<30-40 %

~30-40 %

0 %


Extra Edge: 

It is associated with other autoimmune diseases: vitiligo, Type 1 DM, Addison's disease.


NB: Grave disease (triad)

  1. Hyperthyroidism
  2. Ophthalmopathy
  3. Dermopathy (MCQ: Pre tibial myxedema occurs in dermopathy of Grave disease) !!!!.
Extra Edge:
  1. (Pre tibial myxedema occurs in dermopathy of Grave disease) !!!!.
  2. Ophthalmopathy & Dermopathy occur only in Grave disease. They do not occur in any other cause of hyperthyroidism.
  3. Grave disease is a type of hyperthyroidism but all hyperthyroid are not Grave Disease !!
  4. Ophthalmopathy can occur in 5% of Hashimoto thyrotoxicosis


Table - Physiologic Effects of Thyroid Hormones.

Target Tissue





Increase number of -adrenergic receptors.



Enhance responses to circulating catecholamines.

Adipose tissue


Stimulate lipolysis.



Increase protein breakdown.



Promote normal growth and skeletal development.

Nervous system


Promote normal brain development.



Increase rate of carbohydrate absorption.



Stimulate formation of LDL receptors.



Stimulate oxygen consumption by metabolically active tissues (exceptions: testes, uterus, lymph nodes, spleen, anterior pituitary).

Increase metabolic rate


Clinical features of hyperthyroidism

  1. Goitre: There is diffuse thyroid enlargement. ± bruit. 
  2. Gastrointestinal
    1. Weight loss despite normal or increased appetite'
    2. Diarrhea, Alimentary glycosuria can occur.  
  3. "Cardiorespiratory”
    1. Palpitations', sinus tachycardia, atrial fibrillation', dancing carotid
    2. Increased pulse pressure, soft systolic murmur.
    3. (Note: diastolic murmur is not a feature)
    4. Angina, cardiomyopathy and cardiac failure
    5. Means Lerman sound (it is scratchy sound heard over the precordium)
    6. Some patients with thyrotoxicosis develop a reversible diastolic dysfunction and a "low-output" failure, so-called thyrotoxic dilated cardiomyopathy. (Ref, Robbins-7th ed., pg - 1166)

Common neurologic manifestations include hyperreflexia, muscle wasting, and proximal myopathy without fasciculation. Chorea is rare. Thyrotoxicosis is associated with a form of hypokalemic periodic paralysis. (LQ 2012)

  1. Neuromuscular
    1. Nervousness, irritability, emotional liability', psychosis
    2. Tremor
    3. Hyperreflexia
    4. Muscle weakness, Hypokalemic Periodic paralysis, bulbar myopathy 
  2. Dermatological
    1. i. Palmar erythema,
      ii. spider naevi,
      iii. Onycholysis,
      iv. Alopecia,
      v. Pigmentation, vitiligo' cosis
    2. Finger clubbing' (Thyroid acropachy), Pretibial myxoedema'
  3. Reproductive
    1. Amenorrhea/oligomenorrhea
    2. Infertility, spontaneous abortion
    3. Loss of libido, impotence 
  4. Ocular (Ref. Hari. 18th ed., page 2923)
Following Eye signs are seen in all cases of hyperthyroid.
  1. Wide staring appearance  (Kocher Sign)
  2. Upper Lid retraction (Dalrymple sign), 
  3. lid lag with down gaze (Von Graefe sign).
  4. Decreased blinking (Stellwag sign)

(All these features are due to sympathetic over stimulation causing levator palpebrae superioris contraction.)

Lid retraction or lid lag are the most common eye signs. (LQ 2012) (Ref. Hari. 18th ed. pg 2923) 


Following Eye signs are seen only in Grave disease.

  1. Chemosis'                       
  2. Exophthalmos             
  3. Corneal ulceration
  4. Ophthalmoplegia,           
  5. Papilledema        
  6. Diplopia (diplopia results, typically when patient looks up and laterally)


  1. Other
    1. Heat intolerance                    
    2. Gynecomastia            
    3. Lymphadenopathy'
Extra Edge: 

Apathetic hyperthyroid


It occurs in elderly people, have thyrotoxicoses due to increase thyroid hormone secretion but there are no features of hyperthyroid except atrial fibrillation or weight loss.

Evaluation of thyrotoxicosis. (Ref. Hari. 18th ed., Pg-2920, Fig 341.6)

  1. TSH  (suppressed), T4 and T3.
  2. Thyroid scan is done for toxic adenoma and multinodular goiter.
  3. Hypercalcemia occur in 5% of patient.


  1. High output Heart failure (thyrotoxic cardiomyopathy)             
  2. Angina    
  3. Osteoporosis
  4. Ophthalmopathy                                              
  5. Gynecomastia.     
  6. Thyroid storm

Non-specific laboratory abnormalities in Thyrotoxicosis

  1. Raised Serum enzymes
    1. alanine aminotransferase,
    2. γ-glutamyl transferase (GGT),
    3. alkaline phosphatase from liver and bone
  2. Raised bilirubin
  3. Mild hypercalcaemia
  4. Glycosuria
    1. Associated diabetes mellitus
    2. 'Lag storage' glycosuria




  1. Beta-blockers (eg propranolol 40mg/6h) for rapid control of symptoms due to sympathetic overstimulation but it does not reduce oxygen consumption in the body.
  2. Anti-thyroid medication:
    1. Carbimazole (crosses placenta).
      S/E: Agranulocytosis, SLE like feature, hepatitis.
    2. Propylthiouracil
      1. Propylthiouracil does not cross placenta so drugs of choice in pregnancy)
      2. PTU also inhibits conversion of T4 to T3.
  3. Radioiodine (131I) :
    1. Patient become hypothyroid in about one year post-treatment.
    2. Radioiodine causes progressive destruction of thyroid cells and can be used as initial treatment or for relapses after a trial of antithyroid drugs.
    3. There is a small risk of thyrotoxic crisis after radioiodine, which can be minimized by pretreatment with antithyroid drugs for at least a month before treatment.
    4. Pregnancy and breast feeding are absolute contraindications to radioiodine treatment, but patients can conceive safely 6 months after treatment.
    5. Radioiodine can be used safely in older children.
  4. Thyroidectomy: Carries a risk of damage to recurrent laryngeal nerve (hoarseness of voice) and hypoparathyroidism.  

Toxic adenoma (Solitary nodule)

  1. There is a solitary hot nodule producing T3 and T4.
  2. On Radio Iodine study the nodule is 'hot' and the rest of the gland is suppressed.
  3. Rx Radioiodine is the treatment of choice. Surgery can be done in some cases.

 Recent Advancement in treatment: (PNQ)


 Injection ethanol is  injected in the adenoma under ultrasound guidance.

Toxic Multinodular Goiter

  1. Seen in the elderly and in iodine-deficient areas-.
  2. There are multiple nodules (hot nodules) that secrete thyroid hormones.
  3. Treatment:
    1. Control the thyrotoxicosis first with medication, then follow with radioiodine.
    2. Surgery is indicated if there are compressive symptoms from the enlarged thyroid (dysphagia or dyspnea)

Recent Advances: Vandetanib has been approved for thyroid cancer.

Factitious Thyrotoxicosis

  1. Seen in nurses
  2. She takes excess thyroxine to loose weight.
  3. But she develops feature of thyrotoxicosis
  4. RAIU is low.

Hyperthyroid in pregnancy:  The drug choice is propylthiouracil because it does not cross placenta.

(Note: Carbimazole crosses placenta so more likely to cause fetal hypothyroid).

Hyperthyroid crisis (thyrotoxic storm)

  1. Thyroid storm occurs in a thyrotoxic patient who has been inadequately prepared for thyroidectomy.
  2. Thyroid storm is an extreme form of thyrotoxicosis that may occur with a variety of conditions.
  3. Conditions that may lead to thyroid storm in thyrotoxic patients.
    1. Stressful illness
    2. Thyroid surgery for hyperthyroid without adequate pre-operation preparation
    3. Radioactive iodine administration 

Sign & symptoms: Severe hyperthyroidism: fever, agitation, confusion, coma, tachycardia, atrial fibrillation, diarrhea, vomiting, thyroid bruit, 'acute pain abdomen'. 


Management plan for thyrotoxic storm

  1. 0.9% saline
  2. If no CHF, give propranolol
  3. If there is heart failure give digoxin intravenous
  4. Antithyroid drugs, propylthiouracil
  5. After 4h give Lugol's solution 0.3mL/8h orally for 1wk to block thyroid hormone synthesis.
  6. Hydrocortisone IV or dexamethasone IV
  7. Treat infection with cefuroxime
Extra Edge:
  1. Thyroiditis may not be necessarily associated with thyrotoxicosis.
  2. Infact many forms of thyroiditis have associated hypothyroidism and hence these patients are unlikely to develop thyroid storm when taken for surgery.
  3. Struma ovari: it is a teratoma of ovary, having ectopic Thyroid tissue. Patient may be thyrotoxic but RAIU is . It is detect by whole body radionuclide study.

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