GENERAL EXAMINATION general examination one should look for (i) primary toxic manifestations in case of goiters affecting the young, (ii) econdary toxic manifestations in nodular goiter and (iii) metastasis in case of malignant thyroid diseases. i) Primary toxic manifestations: One should look for five Cardinal signs (Fig. 27.17): 1. Eye signs: There are four important changes that may occur n the eyes in thyrotoxicosis (Figs. 27.18A to C). Each one may De unilateral or bilateral: 1. Lid retraction: This sign is caused by over- activity of the involuntary (smooth muscle) part of the levator palpebrae Superioris muscle. When the upper eyelid is higher than normal and the lower eyelid is in its normal position this condition is called lid retraction. 'Lid lag' is a different term. This means the upper eyelid cannot keep pace with the eyeball when it Fig. 27.17: The four cardinal of primary toxic goiter are shown numbers. 1. Exophthalmos 2 ty swelling with or without thrill ycardia and 4, tremor. C Figs. 27.18A to C: (A) Normal eye. (B) Lid retraction of the upper eyelid, whereas lower lid is normal. This is not exophthalmos. (C) Exophthalmos, where both lids are moved away showing sclera both below and above the iris. looks down following an examiner's finger moving downwards from above. Both lid retraction and lid lag are not exophthalmos. (1) Exophthalmos (Fig. 27.19A and B): When eyeball is pushed forwards due 10 increase in fat or edema or cellular infiltration in the retro-orbital space the eyelids are retracted and sclera becomes visible below the lower edge of the iris B Figs. 27.19A and B (A) Progressive (malignant) exophthalmos which developed over a period of 3 months following radioiodine therapy for thyrotoxicosis. Extensive chemosis and periorbital edema obscures the degree of exophthalmos (8) A typical ex ophthalmic goiter. first followed by above the upper edge of the iris. Now the following tests or signs are: (a) Von Graefe's sign: The upper eyelid lags behind the eyeball as the patient is asked to look downwards. (b) Joffroy's sign: Absence of wrinkling on the forehead when the patient looks upwards with the face inclined downwards. (c) Stelluvag's sign: This is staring look and infrequent blinking of eyes with widening of palpebral fasure. This is due to toxic contraction of striated fibres of levator palpebrae superioris. (d) Moebius sign: This means inability or failure to converge the eyeballs. (e) Dalrymple's sign. This means the upper sclera is visible due to retraction of upper eyelid. (Ophthalmoplegia: There may be weakness of the ocular muscles due to edema and cellular infiltration of these muscles. Most often the superior and lateral rectus and inferior oblique muscles are affected. Paralysis of these muscles prevents the patient looking upwards and outwards (iv) Chemosis: This is edema of the conjunctiva. The conjunctiva becomes edematous, thickened and crinkled. Chemosis is caused by obstruction of the venous and lymphatic drainage of the conjunctiva by the increased retro-orbital pressure Tachycardia or increased pulse rate without rise of temperature is constantly present in primary toxic goiter. Sleeping pulse rate is more confirmatory in thyrotoxicosis. Regularity of the pulse may be disturbed and a rapid irregular pulse should arouse suspicion of auricular fibrillation (Fig. 27.20). 3. Tremor of the hands (a fine tremor) (Figs. 27.21 to 27.23) is almost always present in a primary thyrotoxic case. Ask the patient to straight out the arms in front and spread the fingers. Fine tremor will be exhibited at the fingers. The patient is also asked to put out the tongue straight (Fig. 27.21B) and to keep it in this position for at least 1/2 a minute. Fibrillary twitching will be observed. In severe cases the tongue and fingers may tremble. Moist skin particularly of the hands and feet are quite common in primary thyrotoxic cases. It should be a routine practice to feel the hands just after feeling the pulse at the wrist. The palms are hot and moist and the patients cannot tolerate hot weather, on the contrary tolerance to cold is increased. Dyroid bruit is also quite characteristic in Graves' disease (primary thyrotoxic goiter). This due to increased vascularity of the gland (Fig. 27.15). But this sign is a relatively late sign and mostly heard on the lateral lobes near their superior poles. (1) Secondary thyrotoxicosis may complicate multinodular goiter or adenoma of the thyroid. The cardiovascular system is mainly affected. Auricular fibrillation is quite common. The heart may be enlarged. Signs of cardiac failure such as edema of the ankles, orthopnea, dyspnea while walking up the stairs may be observed. Exophthalmos and tremor are usually absent. Patients in this group are generally elderly. 21218. 12/1 med molla (1) Search for metastasis: When the thyroid swelling appears to be stony hard, irregular and authe spread of the disease. Besides examining the cervical lymph nodes, one should also look ord losing its mobility even during deglutition a careful search should be made to know about for distant metastasis such as bony metastasis which is quite common in thyroid carcinoma particularly the follicular type. The skull, the spine, the ends of the long bones, the pelvis, etc.. should be examined for metastasis. Lastly metastasis in the lungs, which is not uncommon, should also be excluded. SPECIAL INVESTIGATIONS THYROID FUNCTION TESTS The most important investigation of thyroid function is meticulous clinical assessment of the patient. But clinical diagnosis has to be confirmed by investigations to know exactly the hormonal status of the thyroid and also its relation with the anterior pituitary and hypothalamus. The following tests are useful to detect the function of the thyroid gland. A Invitro tests: L SERUM PROTEIN BOUND IODINE (PBI): In euthyroid condition, the range is 3.5-8 µg per 100 mL.. It is cheap and can be easily assessed, but it lacks specificity in that it measures nonhormonal forms of iodine in the blood. False positive results are found in pregnancy, persons taking iodides in various forms particularly the contrast media, expectorants containing potassium iodide and in those taking oral contraceptives. False negative results are found in persons taking salicylates, androgens, hydantion-like drugs and in nephrotic syndrome. 2. SERUM THYROXIN (T4): Thyroxin is transported in the plasma mainly in the bound form with the thyroxin binding globulin (TBG) and by thyroxin binding prealbumin. Only a small amount circulates in the blood in the free form. Measurement is more difficult and can be measured only by competitive protein binding or radioimmunoassay method. The normal range varies from 3.0-7.5 µg per 100 ml. 3. TOTAL SERUM TRI-IODOTHYRONINE (T3): The estimation is very difficult and is only possible by radioimmunoassay method. This test is more effective in the sense that some cases of hyperthyroidism are due to excessive production of T3 without any accompanying rise in the level of serum T4. 4 T3 RESIN UPTAKE: The patient's serum is incubated with radioactive T3 so that the latter becomes fixed to any thyroid-binding protein not carrying T3 or T4. The amount so fixed can be measured and thus the number of binding sites in the serum which are unoccupied can measured. Naturally in hyperthyroidism the number of free binding sites is low and in hypothyroidism this number is high. The secondary binder, where the unutilized radioactive T become fixed, was a resin previously and later on Thyopac or Sephadex was used. The fraction of labelled T3 taken up by the resin can be compared with that of a standard serum and this test goes by the name of "resin uptake ratio". The normal range being.91-1.21 µg While using the Thyopac method one may take 100% as the mean normal value for free binding sites. In this case 85% or less will suggest hyperthyroidism as in this case the number of free sites will be less and a figure of 120% or more will suggest hypothyroidism as the number of free sites is high in this case. 5. FREE THYROXIN INDEX (FTI): This is calculated from the formula that FTI is equal to serum T4 (or PBI) T3 uptake percent. The normal range is from 3.5 to 8. It correlates closely with the level of free T4 in serum and thus accurately reflects the thyroid status of an individual This can be considered as the best single test available at present. 6. SERUM THYROID STIMULATING HORMONE (TSH): The serum concentration of TSH is measured by immunoassay. The normal level is about 1 pu/mL. It is raised in primary hypothyroidism and almost undetectable in hyperthyroidism. This test is more of help in the diagnosis of hypothyroidism rather than hyperthyroidism. It is also of value to measure TSH level following radioiodine therapy and subtotal thyroidectomy. 7. TEST OF HYPOTHALAMIC-PITUITARY AXIS: When thyrotrophin-releasing hormone (TRH) is given IV. in a dose of 200 µg to a normal individual, the level of TSH in the serum rises from a basal level of about 1 pu/ml. to a mean pick concentration of about 10 pu/ml. at 20 minutes and returned to normal by 120 minutes. In hypothyroidism there is an exaggerated rise of an already elevated TSH level but in hyperthyroidism there is no response of a depressed TSH level. Its importance remains to certain extent in the diagnosis of T3 thyrotoxicosis if it is not possible to measure the circulating level of T3. Many drugs interfere with the result. e.g. T antithyroid drugs, corticosteroids, estrogens and levodopa. These modify the TSH response to TRH. Probably its main indications remain in cases of mild hyperthyroidism when diagnosis is in doubt, in hypopituitarism and in ophthalmic Graves' disease. B. In vivo tests: These tests hardly help in the diagnosis of hypothyroidism. These are mainly used in the diagnosis of thyrotoxicosis and in the assessment of functional activity of thyroid nodules by scanning. The radioisotopes are mainly used and "mTc (Technetium) is gradually replacing iodine isotopes because of the low energy and short half-life of the former. The radiation dose to the thyroid is about 1/10000 time that of I. Moreover Technetium is concentrated in the thyroid gland in the same way as jodine but is not bound to tyrosine. Therefore, it gives more accurate measure of the iodine trap. 1. UPTAKE TESTS: The rate at which the thyroid gland traps iodine reflects the rate of secretion of the thyroid hormone. In hyperthyroidism both the proportion of the tracer dose taken up and the rate at which this takes place are increased. The best time to measure the isotope uptake is between 10-120 minutes after administration. At this stage there is no additional discharge of radioactivity from the gland. The tracer dose of TI is 5 microcuries. The uptake is first measured and then the radioisotope passes back into the serum being incorporated into the T3 and 14 molecules and can be measured as protein bound may also be used as a diagnostic tracer but only for thyrotoxicosis as it has a short life (2.3 hours as opposed to 8 days of One point must be remembered that in case of hyperplastic nontoxic goiter of iodine deficiency will show an increase uptake and lead to an erroneous diagnosis of toxic goiter. This test cannot be performed immediately after contrast medium X-rays such as IV pyelography, cholecystogram The contrast medium is excreted in about 2 weeks time after IV pyelography and more than a month after cholecystogram and even years after bronchography and myelography. This test should not be performed in children or during pregnancy because of whole body dation. But isotopes with shorter half-life. e.g., or " mTc may be used 273 SUPPRESSION TEST (WERNER): This test differentiates thyrotoxicosis from other ses of raised uptakes, e.g., iodine deficiency and the autonomous thyroid nodules. This test dangerous in elderly patients and those with heart failure as there always remains a potential of inducing transient hyperthyroidism. test available at pre HORMONE (TSH) The The initial uptake is measured. 40 µg of tri-iodothyronin is given 8 hourly by mouth for Sdays after which the uptake is repeated. T3 is used because of its more