Thyrotoxicosis is symptom complex due to raised levels of thyroid hormones. Thyrotoxicosis refers to biochemical and physiological mani- festations of excessive thyroid hormones. Hyperthyroidism is the term used for overproduction of thehormones bythyroid gland. In hyperthyroidism pathology is in thyroid gland itself. Hyperthy- roidism is one of the causes of thyrotoxicosis. Thyrotoxicosis can also occur due to other causes other than hyperthyroidism. 
Other causes of thyrotoxicosis without hyperthyroidism are-ectopic functioning thyroid, struma ovarii, functioning metastatic follicular carcinoma, trophoblastic tumours, thyro- toxicosis factitia. 

1.Diffuse toxic goitre-(Graves' disease, Basedow's disease. Primary thyrotoxicosis)-60%. 
2. Toxic multinodular goitre (Secondary thyrotoxicosis) (Plummer disease)-20%. 
3. Toxic nodule (Goetsch's disease)-5%. 4. Thyrotoxicosis due to rarer causes: 
a. Thyrotoxicosis factitia-drug induced. Due to intake of L-thyroxine more than normal. 
b. Jod-Basedow effect/phenomenon is hyperthyroidism occurs in a goitre patient (not normal thyroid gland) after administration of increased doses of iodides (in hyper- plastic endemic goitre). It is also seen after administra- tion of iodine contrast agents or amiodarone drug. Jod in Germany means iodine. 
c. Autoimmune thyroiditis or de Quervain's thyroiditis.
d. Neonatalthyrotoxicosis.It subsides in 3-4 weeks as TsAb titres fall in the baby's serum.
e. Struma ovarii.
f. Drugs like amiodarone-an antiarrhythmic agent. Amiodarone is rich in iodine having structural similarity to T4 causing thyrotoxicosis.
g. Very rarely, well-differentiated carcinoma can cause thyrotoxicosis-metastatic type. 
h. Patients with hydatidiform mole or choriocarcinoma with high levels of 13 HCG which can stimulate TSH receptor and can cause thyrotoxicosis. 

It is eight times more common in females.
It occurs in any age group. Primary type is seen commonly in younger age group. Secondary type is common in older age group.
Graves's disease often presents without any obvious thyroid swelling in the neck. Whenever, there is unexplained behavioural problem, insomnia, myopathy, unexplained diarrhoea or loss of weight, tachycardia, Graves's disease should be suspected and evaluated.
The degree of thyrotoxicosis is determined by estimation of thyroid hormone levels; the severity of clinical manifesta- tions may not correlate with the degree of thyroid hormone elevation. 
A.SymptomsofHyperthyroidism/Toxicosis

Gastrointestinal system: Weight loss in spite of increased appe- tite; diarrhoea (due to increased activity at ganglionic level). Cardiovascular system: Palpitations; shortness of breath at rest or on minimal exertion; angina; irregularity in heart rate; cardiac failure in the elderly (CCF).
Neuromuscular system: Undue fatigue and muscle weak- ness; tremor.
Skeletal system: Increase in linear growth in children. Genitourinary system: Oligo or amenorrhoea; occasional urinary frequency.
Integument: Hair loss, gynaecomastia; pruritus; palmar erythema.
Psychiatry: Irritability; nervousness; insomnia. Sympathetic overactivity: It causes dyspnoea, palpitation, tiredness, heat intolerance, sweating, hyperactivity, iriitability, nervousness, increased appetite and decrease in weight. Because of the increased catabolism, they have increased appetite, decreased weight and so also increased creatinine level which signifies myopathy (due to more muscle catabo- lism).
Fine tremor is due to diffuse irritability of grey matter. 
B. Signs of Hyperthyroidism/Toxicosis
   1. Eye signs in toxic goitre 
Eye signs are common in primary thyrotoxicosis. Lid lag, lid spasm can occur in secondary thyrotoxicosis also. 
1. lid retraction: Here upper eyelid is higher than normal; lower eyelid is in normal position. It is due to sympa- thetic overactivity causing spasm of involuntary smooth muscle part of the levator palpebrae superioris (Muller's muscle). It is a sign of thyrotoxicosis, not a sign of exophthalmos. 
2. von Graefe's sign {lid Lag's sign): It is inability of the upper eyelid to keep pace with the eyeball when it looks downwards to follow the examiner'sfinger. It is contraction/ overactivity of the involuntary part of the levator palpebrae superioris muscle-Muller's muscle 
3. Oalrymple's sign: Upper eyelid retraction, so visibility of upper sclera. 
4. Stellwag's sign: Absence of normal blinking-so staring look. Firstsigntoappear.Itisduetowideningofpalpebral fissure due to lid retraction and also due to contraction of voluntary part of levator palpebrae superioris muscle. 
5. Joffroy's sign: Absence of wrinkling on forehead when patient looks up (frowns) with head in bent down/flexed position. 
6. Moebiussign:It is lack of convergenceof eyeball. Defective convergence is due to lymphocytic infiltration of inferior oblique and rectus muscles in case of primary thyro- toxicosis. There will be diplopia. It may be an early sign of eventual ophthalmoplegia. 
 7. Naffziger's sign: With patient in sitting position and neck fully extended, protruded eyeball can be visualized when observed from behind. 
8. Jellinek's sign: Increased pigmentation of eyelid margins. 
9. Enroth sign: Oedema of eyelids and conjunctiva.
10. Rosenbach's sign: Tremor of closed eyelids.
11. Gifford's sign: Difficulty in everting upper eyelid in primary toxic thyroid. Differentiates from exophthalmos of other causes.
12. Loewi'ssign:Dilatation of pupil with weak adrenaline solution .
13. Knie's sign: Unequal pupillary dilatation.
14. Cowen's sign: Jerky pupillary contraction to consensual light. 
    2. Cardiac Manifestations 
• Tachycardia is common.
As per Crile's grading; Sleeping pulse rate is usually checked for three consecutive nights and average is taken as the value. 
• Others: Ectopic; Pulsus paradoxus; Wide pulse pressure; Multiple extrasystoles; Paroxysmal atrial tachycardia; Paroxysmal atrial fibrillation.; Persistent atrial fibrillation (not responsive to digoxin). 
     3.Myopathy
Weakness of proximal muscles occurs, i.e. the front thigh muscles, arm muscles.
Weakness is more when muscle contracts isometrically either whilegetting down steps, or lifting afull bucket.
Often whenit issevereit resembles myasthenia gravis. Once hyperthyroidism is controlled, recovery occurs. 
      4. Pretibial Myxoedema 
It is a misnomer. Pretibial myxoedema is often a feature of primary thyrotoxicosis: 
• Is usually bilateral, symmetrical, shiny, red thickened dry skin with coarse hair in the feet and ankles.
• In severe cases skin of entire leg below the knee with involve- ment of foot and ankle can occur. 
• It is due to deposition of myxomatous tissues (mucin-like deposits) in skin and subcutaneous plane. Glycosaminogly- cans (hyaluronic acid) deposition occurs.
• It might or might not regress completely after treatment for toxicity. 
• It is associated with exophthalmos withhigh levelsof thyroid stimulating antibodies.
• Skin becomes cyanotic when cold. Skin changes in toxicosis are called as thyroid dermopathy. They include-pretibial myxoedema, pruritus, palmar erythema, hair thinning, Dupuytren's contracture (fascial). 
      5. Thyroid Acropachy
Thyroid acropachyis clubbing of fingers and toes in primary thyrotoxicosis. Hypertrophic pulmonary osteoarthropathy can develop. 
      6. Others      
• Thrill is felt in the upper pole of the thyroid and also bruit on auscultation. It is because in upper pole, superior thyroid artery enters the gland superficially and so thrill and bruit can easily befelt. In lower poleinferior thyroid artery enters the gland from deeper plane and so thrill cannot be felt. 
• Hepatosplenomegaly. 

Thyroid function tests 
Serum T3 and T4 levels are very high. TSH is very low or undetectable. Sometimes, only T3 level is increased and is called as T3 toxicosis. Here in T3 toxicosis, free T3 estimation is important. Free T3, free T4 estimation is done as total T3 and total T4 levels wi ll vary depending on the amount of thyroid binding globulin (TBG). TBG wi ll be raised in pregnancy, cirrhosis, hyperestrogenism. It decreases in conditions with high androgen level, hypoproteinaemia, acromegaly. Free T3 and free T4 are measured using radioimmunoassay. Normal free T3 is 3.0-9.0 pmol/L;free T4 is 8-26 nmol/L. 
Radioisotope study
• Radioisotope study by 1131 (Diagnostic dose -5 microcurie is used) shows more uptake, i.e. hot nodules or hot areas. This is very useful in autonomous solitary toxic nodule.
• 1131 causes more irradiation and its half-life is 8 days. So intravenous 99mTc is used for diagnostic purpose. 99m technetium has become isotope of choice for diagnosis as it is cheap, less radiation, scanning is done 20 minutes after IVinjection of 99mTc (half-lifeis 6 hours). Drawback of technetium is that it concentrates in carcinoma, so forms hot nodule (means hot nodule need not be benign in Tc scanning). Warm nodule in Tc scan may appear as cold nodule in RAI scan and so is called as discordant nodule which suggests malignancy. If radioacti ve iodine is used for diagnosis, then 112 3 is better as it has got short half-life (13 hours).
• Autonomous toxic nodule is absolute indication for radioisotope scan in toxic thyroid showing hot nodule. Graves disease shows diffuse overactivity (uniform) ; hypofunc- tioning coldnodulein Graves disease could be malignant. In secondary thyrotoxicosis internodular tissues are overactive (heterogeneous activity). Non-hyperthyroid toxicosis shows increased uptake in non-thyroid areas of toxicity like struma ovarii in pelvis. 
TRH estimation.

ECG-to look for cardiac involvement; if required opinion from cardiologists is taken and cardiac problems are managed.

Total count and neutrophil count are very essential base-line investigations before starting antithyroid drugs (as it may cause agranulocytosis).

Thyroid antibodies estimation-antithyroglobulin antibody, TSH receptor antibody, antithyroid peroxidase (anti-TPO) antibody. 

Relief of symptoms:
- Beta blockers-propranolol , nadolol , metoprolol-Control cardiovascular and hyperadrenergic manifestations. Bronchial Asthma, heart Block, Cardiac failure are contraindications.
- Calcium channel blockers (e.g. verapamil and diltiazem) can be used
- Oral rehydration 
Antithyroid pharmacotherapy. It prevents the-. 
• Release of hormones. Lugol's iodine (potassium iodide and iodine)10drops- 3timesday
• Production of thyroxine : Methimazole: long-acting, 20-40 mg OD; more potent; but not used in pregnancy; Tapazole 5 or10mgtablets.Carbimazole20mgthreetimesadayupto 120mg. Propylthiouracil(PTU)100mgthreetimesaday, used in pregnancy; 50 mg tablets 
• Action of thyroxine on end organs: Propranolol--40 mg tid up to 120-160 mg; PTU 
• Production ofantibodies: Steroids, methimazole, carbimazole; Levels of TSH R Ab fal l and permanent cure may occur in 50% of patients in Grave's 
Radioactive iodine therapy Thyroidectomy 



Resource : SRB's Manual of surgery,6th edition