1268
DIAGNOSING THYROID NODULES DISCOVERY of a solitary thyroid nodule naturally leads to the question: benign or malignant? If a patient is recommended for operation merely on the basis of a single palpable lesion the yield of malignant disease is unacceptably low.’ What can be done to narrow the selection of patients for surgery? On radioisotope scanning (1311, 1, 1231, 99mTc) a quarter of isolated nodules prove to be (hot) and these are rarely malignant, especially if normal functioning thyroid tissue is also present. The ’
hyperfunctioning
remaining three-quarters are hypofunctioning (cool) or non-functioning (cold), and 10-20% of these are malignant. Two new diagnostic techniques help to show which of these hypofunctioning nodules is a carcinoma-ultrasonography and fine-needle aspiration biopsy. B-mode (two-dimensional) bistable or grey-scale ultrasonography3 will differentiate predominantly cystic lesions from those which are solid or mixed cystic-solid, with an accuracy of around 90%.4,s Ultrasonography is safe, non-invasive, and non-radioactive. With this technique about 20% of hypofunctioning nodules are found to be cystic, and if the cysts are less than 4 cm in diameter there is only a 1-2% chance of malignancy.6 Clearly, the 80% of lesions which are predominantly solid comprise the main clinical problem numerically, and one-fifth of solid nodules are malignant. Ultrasonography does not distinguish a carcinoma from a benign solid lesion; therefore a histological diagnosis is necessary. In the past, the preoperative diagnosis has been made by large-needle biopsy, but lately fine-needle (21 gauge or less) aspiration biopsy has been advocated. Fine-needle biopsy is not strictly new. It was developed in Sweden over twenty years ago’ and has been used extensively in Scandinavia as a diagnostic test for thyroid lesions including medullary carcinoma.8 Aspiration biopsy is readily done under intradermal anxsthesia (or even without anaesthesia) in the outpatient clinic, but physicians outside Scandinavia have seemed reluctant to adopt this method of investigation despite promising initial reports.9,lO Recently, however, fine-needle aspiration biopsy has found more advocates in North America and has been used in conjunction with ultrasonography to select patients for surgery. The results reported by Gershengorn and his colleaguesil and by Walfish’s group12 are encouraging. Adequate material for cytology is obtained in over 90% of cases and overall diagnostic accuracy is also in the region of 90%, being more accurate for solid than for cystic or mixed lesions. False-positives are exceptional and false-negatives are also rare (4-11%). Fears that the procedure might result in seeding of malignant cells have proved unfounded. 13 1. Rosenberg, I. N. New Engl. J. Med. 1972, 287, 1197. 2. Miskin, M., Rosen, I. B., Walfish, P. G. Rad. Clins N. Am. 1975, 13, 479. 3. Leo, F. P., Rao, G. U. V. ibid. p. 403. 4. Blum, M., Goldman, A. B., Herskovic, A., Hernberg, J. New Engl. J. Med.
1972, 287, 1164. Walfish, P. G., Miskin, M., Rosen, I. B., Strawbridge, H. T. G. Can. med. Ass. J. 1976, 115, 35. 6. Miskin, M., Rosen, I. B., Walfish, P. G. Ann. intern. Med. 1973, 79, 505. 7. Söderström, N. Acta med. scand. 1952, 144, 237. 8. Ljungberg, O. Acta cytol. 1972, 16, 253. 9. Crile, G. Jr., Hawk, W. A., Jr. Surgery Gynec. Obstet. 1973, 136, 241. 10. Crockford, P. M., Bain, G. O. Can. med. Ass. J. 1974, 110, 1029. 11. Gershengorn, M. C., McClung, M. R., Chu, E. W., Hanson, T. A. S., Weintraub, B. D., Robbins, J. Ann. intern. Med. 1977, 87, 265. 12. Walfish, P. G., Hazani, E., Strawbridge, T. G., Miskin, M., Rosen, I. B. ibid. p.270. 13. Holm, H. H., Pedersen, J. F., Kristensen, J. K., Rasmussen, S. N., Hancke, S., Jensen, F. Rad. Clins N. Am. 1975, 13, 493. 5.
Aspiration cytology nearly always provides valuable diagnostic information in solid hypofunctioning thyroid nodules. When ultrasonography and fine-needle aspiration biopsy are used conjointly they provide complementary information. 12 Small cystic lesions may be managed conservatively by aspiration while cysts over 4 cm in diameter are usually recommended for surgical excision in view of the higher risk of malignancy. Solid lesions with frankly malignant or suspicious cells are definite indications for operation, and previous histological diagnosis may help the surgeon in planning his operative approach. In patients with a cytological diagnosis of thyroiditis, surgery is not indicated, and patients with benign tumours may also be managed conservatively with long-term thyroid-hormone suppression. Both these groups warrant regular follow-up since any increase in the size of the nodule may indicate malignant change. VITAMIN E FOR BABIES
VITAMIN E is
an
emotive and
enigmatic subject. Some
clinicians, veterinary surgeons, and biochemists regard it as a panacea. In 1922, Evans and Bishop1 described the existence of a "Hitherto unrecognised dietary factor essential for reproduction" ... "Natural foodstuffs contain a substance, X, which prevents ... sterility". A year later Barnett Sure2 proposed the designation E for this new dietary factor. The vitamin’s more formal name, tocopherol, constructed by Evans, reflects the controversy—"tocos" meaning childbirth and "phero" bring forth. (The terminal ol indicated it was an alcohol.) Biological membranes contain phospholipids, and oxidative degradation of these can cause loss of cell integrity. Liability to lipid peroxidation in membranes is a function of the polyunsaturated fatty acid (P.U.F.A.) content of the phospholipids. The rate of peroxidation varies directly with the number of double bonds in the fatty acids present in those phospholipids.3 Membranes with a high P.U.F.A. content are especially likely to become oxidised. Polyunsaturated lipids are essential constituents of all cells; and, in the presence of oxygen, they are autoxidisable (or peroxidisable4). Rancidification of butter is an example of autoxidation. Vitamin E is an efficient antioxidant or preservative in vitro. An antioxidant inhibits the combination of a substance with oxygen. Many phenolic compounds, trace elements, and enzymes have a similar role as inhibitors of autoxidation. Low-cholesterol or fat-modified diets rich in P.U.F.A. raise the body’s need for vitamin E.5 Vitamin E has been credited with many roles apart from its major one of protecting biological membranes. Deficiency causes sterility in rats,1 cerebellar disorders in chicks,6 and myopathy in ducklings.7 In man, tocopherols are not actively transported from the maternal to fetal circulation,8 and they are poorly absorbed by infants whose gestational age is less than 36 weeks.9 A deficiency of tocopherol causes hæmolytic anaemia and widespread œdema and these are reversed by vitamin-E 1. Evans, H. M., Bishop, K. S. Science, 1922, 56, 650. 2. Sure, B. J. biol. Chem. 1924, 58, 693. 3. Witting, L. A. J. Am. Oil. Chem. Soc. 1965, 42, 908. 4. Dormandy, T. L. Proc. R. Soc. Med. 1977, 70, 91. 5. Nutr. Rev. Suppl. 1974, 32, 35. 6. Pappenheimer, A. M., Goettsch, M. ibid. 1931, 53, 11. 7. Pappenheimer, A. M., Goettsch, M. J. exp. Med. 1934, 59, 35. 8. Wright, S. W., Filer, L. J., Jr., Mason, K. E. Pediatrics, 1951, 7, 9. Melhorn, D. K. Ohio St. med. J. 1973, 69, 751.
386.
DIAGNOSING THYROID NODULES DISCOVERY of a solitary thyroid nodule naturally leads to the question: benign or malignant? If a patient is recommended for operation merely on the basis of a single palpable lesion the yield of malignant disease is unacceptably low.’ What can be done to narrow the selection of patients for surgery? On radioisotope scanning (1311, 1, 1231, 99mTc) a quarter of isolated nodules prove to be (hot) and these are rarely malignant, especially if normal functioning thyroid tissue is also present. The ’
hyperfunctioning
remaining three-quarters are hypofunctioning (cool) or non-functioning (cold), and 10-20% of these are malignant. Two new diagnostic techniques help to show which of these hypofunctioning nodules is a carcinoma-ultrasonography and fine-needle aspiration biopsy. B-mode (two-dimensional) bistable or grey-scale ultrasonography3 will differentiate predominantly cystic lesions from those which are solid or mixed cystic-solid, with an accuracy of around 90%.4,s Ultrasonography is safe, non-invasive, and non-radioactive. With this technique about 20% of hypofunctioning nodules are found to be cystic, and if the cysts are less than 4 cm in diameter there is only a 1-2% chance of malignancy.6 Clearly, the 80% of lesions which are predominantly solid comprise the main clinical problem numerically, and one-fifth of solid nodules are malignant. Ultrasonography does not distinguish a carcinoma from a benign solid lesion; therefore a histological diagnosis is necessary. In the past, the preoperative diagnosis has been made by large-needle biopsy, but lately fine-needle (21 gauge or less) aspiration biopsy has been advocated. Fine-needle biopsy is not strictly new. It was developed in Sweden over twenty years ago’ and has been used extensively in Scandinavia as a diagnostic test for thyroid lesions including medullary carcinoma.8 Aspiration biopsy is readily done under intradermal anxsthesia (or even without anaesthesia) in the outpatient clinic, but physicians outside Scandinavia have seemed reluctant to adopt this method of investigation despite promising initial reports.9,lO Recently, however, fine-needle aspiration biopsy has found more advocates in North America and has been used in conjunction with ultrasonography to select patients for surgery. The results reported by Gershengorn and his colleaguesil and by Walfish’s group12 are encouraging. Adequate material for cytology is obtained in over 90% of cases and overall diagnostic accuracy is also in the region of 90%, being more accurate for solid than for cystic or mixed lesions. False-positives are exceptional and false-negatives are also rare (4-11%). Fears that the procedure might result in seeding of malignant cells have proved unfounded. 13 1. Rosenberg, I. N. New Engl. J. Med. 1972, 287, 1197. 2. Miskin, M., Rosen, I. B., Walfish, P. G. Rad. Clins N. Am. 1975, 13, 479. 3. Leo, F. P., Rao, G. U. V. ibid. p. 403. 4. Blum, M., Goldman, A. B., Herskovic, A., Hernberg, J. New Engl. J. Med.
1972, 287, 1164. Walfish, P. G., Miskin, M., Rosen, I. B., Strawbridge, H. T. G. Can. med. Ass. J. 1976, 115, 35. 6. Miskin, M., Rosen, I. B., Walfish, P. G. Ann. intern. Med. 1973, 79, 505. 7. Söderström, N. Acta med. scand. 1952, 144, 237. 8. Ljungberg, O. Acta cytol. 1972, 16, 253. 9. Crile, G. Jr., Hawk, W. A., Jr. Surgery Gynec. Obstet. 1973, 136, 241. 10. Crockford, P. M., Bain, G. O. Can. med. Ass. J. 1974, 110, 1029. 11. Gershengorn, M. C., McClung, M. R., Chu, E. W., Hanson, T. A. S., Weintraub, B. D., Robbins, J. Ann. intern. Med. 1977, 87, 265. 12. Walfish, P. G., Hazani, E., Strawbridge, T. G., Miskin, M., Rosen, I. B. ibid. p.270. 13. Holm, H. H., Pedersen, J. F., Kristensen, J. K., Rasmussen, S. N., Hancke, S., Jensen, F. Rad. Clins N. Am. 1975, 13, 493. 5.
Aspiration cytology nearly always provides valuable diagnostic information in solid hypofunctioning thyroid nodules. When ultrasonography and fine-needle aspiration biopsy are used conjointly they provide complementary information. 12 Small cystic lesions may be managed conservatively by aspiration while cysts over 4 cm in diameter are usually recommended for surgical excision in view of the higher risk of malignancy. Solid lesions with frankly malignant or suspicious cells are definite indications for operation, and previous histological diagnosis may help the surgeon in planning his operative approach. In patients with a cytological diagnosis of thyroiditis, surgery is not indicated, and patients with benign tumours may also be managed conservatively with long-term thyroid-hormone suppression. Both these groups warrant regular follow-up since any increase in the size of the nodule may indicate malignant change. VITAMIN E FOR BABIES
VITAMIN E is
an
emotive and
enigmatic subject. Some
clinicians, veterinary surgeons, and biochemists regard it as a panacea. In 1922, Evans and Bishop1 described the existence of a "Hitherto unrecognised dietary factor essential for reproduction" ... "Natural foodstuffs contain a substance, X, which prevents ... sterility". A year later Barnett Sure2 proposed the designation E for this new dietary factor. The vitamin’s more formal name, tocopherol, constructed by Evans, reflects the controversy—"tocos" meaning childbirth and "phero" bring forth. (The terminal ol indicated it was an alcohol.) Biological membranes contain phospholipids, and oxidative degradation of these can cause loss of cell integrity. Liability to lipid peroxidation in membranes is a function of the polyunsaturated fatty acid (P.U.F.A.) content of the phospholipids. The rate of peroxidation varies directly with the number of double bonds in the fatty acids present in those phospholipids.3 Membranes with a high P.U.F.A. content are especially likely to become oxidised. Polyunsaturated lipids are essential constituents of all cells; and, in the presence of oxygen, they are autoxidisable (or peroxidisable4). Rancidification of butter is an example of autoxidation. Vitamin E is an efficient antioxidant or preservative in vitro. An antioxidant inhibits the combination of a substance with oxygen. Many phenolic compounds, trace elements, and enzymes have a similar role as inhibitors of autoxidation. Low-cholesterol or fat-modified diets rich in P.U.F.A. raise the body’s need for vitamin E.5 Vitamin E has been credited with many roles apart from its major one of protecting biological membranes. Deficiency causes sterility in rats,1 cerebellar disorders in chicks,6 and myopathy in ducklings.7 In man, tocopherols are not actively transported from the maternal to fetal circulation,8 and they are poorly absorbed by infants whose gestational age is less than 36 weeks.9 A deficiency of tocopherol causes hæmolytic anaemia and widespread œdema and these are reversed by vitamin-E 1. Evans, H. M., Bishop, K. S. Science, 1922, 56, 650. 2. Sure, B. J. biol. Chem. 1924, 58, 693. 3. Witting, L. A. J. Am. Oil. Chem. Soc. 1965, 42, 908. 4. Dormandy, T. L. Proc. R. Soc. Med. 1977, 70, 91. 5. Nutr. Rev. Suppl. 1974, 32, 35. 6. Pappenheimer, A. M., Goettsch, M. ibid. 1931, 53, 11. 7. Pappenheimer, A. M., Goettsch, M. J. exp. Med. 1934, 59, 35. 8. Wright, S. W., Filer, L. J., Jr., Mason, K. E. Pediatrics, 1951, 7, 9. Melhorn, D. K. Ohio St. med. J. 1973, 69, 751.
386.
