THYROID Volume 2, Number Mary Ann Liebert,
2, 1992 Inc., Publishers
Commentary Thyroid Nodules DEMETRIOS A.
WRITING First,
THIS commentary is difficult, for two reasons. my views generally are similar to those of Dr. Hamburger, and since there is no basic disagreement, it becomes difficult to find points to criticize or comment on. Second, there is a dearth of valid data (e.g., controlled trials) on the management of nodules in general and in pregnancy more specifically. Thus, I must rely on the uncontrolled data of my clinical experience as a physician dealing frequently with thyroid nodules, in pregnancy in a country where endemic goiter is not a
rarity.
DIAGNOSTIC APPROACH The first diagnostic step is careful palpation of the neck. In this way, most clinically important nodules can be detected. Clinical examination can also detect thyroglossal duct cysts and local lymph nodes. Hence, the entire neck should be palpated
carefully. In a nonpregnant woman, the next step after the discovery of nodule should be the performance of a scintigram. In this way, hot nodules, especially frequent in areas with moderate iodine deficiency, will be discovered. These nodules are practically always benign (1,2), and these patients can be spared a fine needle aspiration biopsy (FNB). Furthermore, these hot nodules usually are autonomous. They do not respond to thyroxine treatment. Exogenous thyroxine is additive to the endogenous secretion instead of suppressing it. Therefore, treatment with thyroxine is not indicated. On the other hand, ifthe nodule is warm or cold,an FNB is immediately advised. In our experience, if cytology shows nodular hyperplasia, malignancy can be excluded with a certainty of more than 98%, but in patients with a report of thyroiditis, a neoplasm (usually a papillary cancer) cannot be excluded confidently (3). a
Athens
University.
Pregnancy
KOUTRAS, M.D.
INTRODUCTION
Department of Clinical Therapeutics,
in
Ultrasound (US) studies should be used rarely. As stressed by Hamburger, they can neither exclude nor confirm malignancy. Being more sensitive than palpation, US will detect many impalpable small nodules (< 1 cm), which are especially frequent in persons more than 30 years old and in countries with moderate or definite iodine deficiency. Once such small nodules are detected, what should one do? Should one recommend a US-guided FNB, prescribe thyroxine and monitor its effect by US, i.e., treat the US scan, or consider surgery? I think that none of these procedures is cost effective. The discovery of one or more palpable nodules with US will simply alarm the patient, and often the physician regrets that the US was ever obtained. This basic approach must be modified in pregnancy. Isotopic imaging is not allowed. For this reason, many physicians are tempted to order the US scans that they normally would not request. These US scans not only do not exclude malignancy, but they also do not exclude autonomy, as an isotope scan would. So the physician can only rely on serum hormone levels and FNB. In pregnancy, total serum T4 and T3 levels are increased because of the increase in thyroxine-binding globulin (TBG), and the free hormone levels (FT4 and FT3) or a free thyroxine index (FTI) should be assessed. In case of doubt, the TRH test can be performed in pregnancy without side effects (4). If hyperthyroidism is found, presumably due to an autonomous hot nodule, it should be treated as will be described. If hyperthyroidism is excluded, the nodule presumably is cold, and FNB should be ordered immediately. The patient should be managed as advised by Hamburger.
TREATMENT Ifthe nodule is accompanied by significant hyperthyroidism, should be prescribed. Physicians in the past were sometimes reluctant to treat, but now it has been firmly established that treatment of maternal hyperthyroidism is preferable to nontreatment for both the mother and the fetus (5).
antithyroid drugs
Alexandra General
169
Hospital, Athens, Greece.
KOUTRAS
170 Some special precautions in pregnancy include the following. 1. The pregnant
woman
should be more closely monitored than
in most cases until after parturition. For benign nodules, treatment with thyroxine is debatable but may be considered if the serum TSH is high normal.
nonpregnant persons.
2. The lowest effective dose of the antithyroid drugs should be prescribed, aiming at keeping the FT4 and FT3 at the high normal rather than low normal range. 3. Propylthiouracil seems preferable to methimazole, since it crosses the placenta less readily than methimazole. 4. Thyroxine or T, or both should not be added to the antithyroid drugs. These thyroid hormones cross the placenta poorly. Their addition increases the dose of antithyroid drugs needed, resulting in higher levels in the fetus, without significant protection by the exogenous thyroid hormones
given. Recently, percutaneous alcohol injection has been advocated for the treatment of autonomous nodules (6,7). If the nodule is benign and apparently nonautonomous, thyroxine treatment could be considered. There are no solid data on which to base such a decision. In nonpregnant persons with such a nodule, 24% of European clinicians advise surgery, 48% suppression with T4, and 28% only follow-up (8). The benefit of thyroxine treatment is debatable. Gharib et al. (9) and Cheung et al. ( 10) found no significant difference between thyroxine and placebo. These studies, however, can be criticized because hot nodules, which are usually autonomous and not responsive to thyroxine, were not always excluded and because the dose of thyroxine given may not have been optimal. With these considerations in mind, it is difficult to be certain if thyroxine treatment is beneficial in pregnant women with benign nodules. Nevertheless, such treatment may be considered if the serum TSH is in the upper normal range. If given at all, thyroxine should be administered in rather small doses (11), aiming at keeping the serum TSH at the low normal range rather than suppressing it, with the hope that this will prevent a further increase in the nodule size. An attempt to shrink the nodule with higher thyroxine doses may be postponed until after pregnancy. DISCUSSION I am in basic agreement with Dr. Hamburger. FNB is the main diagnostic procedure, together with serum T4, T3, and TSH levels, used to exclude hyperthyroidism and hypothyroidism. If the nodule is malignant or suspicious, surgery may be postponed
REFERENCES 1. Koutras DA, Livadas D, Sfontouris J, Messaris G, Statherou PK 1968 A study of 408 cold thyroid nodules in a country with endemic goitre. Nuclear Med 7:165. 2. Psarras A, Papadopoulos SN, Livadas DP, Pharmakiotis AD, Koutras DA 1972 The single thyroid nodule. Br J Surg 59:545. 3. Tseleni-Balafoutas S, Koutras DA 1987 Fine-needle biopsy in the evaluation of thyroid nodules. J Med Pharm Vet Afrique 9:18. 4. Koutras DA, Pharmakiotis AD, Koliopoulos N, Tsoukalos J, Souvatzoglou A, Sfontouris J 1978 The plasma inorganic iodine and the pituitary thyroid axis in pregnancy. J Endocrinol Invest
1:227. 5. Matsuura N, Konishi J, Fujieda K, et al 1988 TSH-receptor antibodies in mothers with Graves' disease and outcome in their offspring. Lancet 1:14. 6. Livrachi T, Paracchi A, Ferrari C, et al 1990 Treatment of autonomous thyroid nodules with percutaneous injection: Preliminary results. Work in progress. Radiology 175:827. 7. Kim CS, Lee SH 1991 Percutaneous alcohol injection (PAI) of thyroid nodule. 10th International Thyroid Conference, The Hague/ Netherlands, Feb 3-8, Abstract 359. 8. Baldet L, Manderscheld JC, Glinoer D, Jaffiol C.Costeseignovert B, Percheron C 1989 The management of differentiated thyroid cancer in Europe in 1988. Results of an international survey. Acta Endocrinol 120:547. 9. Gharib H, James EM, Charboneau JW, Naessens JM, Offord KP, Gorman CA 1987 Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study. N Engl J Med 317:70. 10. Cheung P, Boey J, Lee J 1988 Natural course of benign thyroid nodules and the effect of thyroxine therapy. International Thyroid Symposium, Tokyo/Japan, July 13-15, Abstract V-3-3. 11. Koutras DA 1991 Prevention and treatment of nontoxic goiter during pregnancy. Merck symposium: The Thyroid and Pregnancy. Brussels, Jan 31-Feb 2.
Address reprint requests to: Demetrios A. Koutras, M.D. Professor of Medicine, Athens University Department of Clinical Therapeutics Alexandra General Hospital 80, Vas. Sofias Avenue GR-115 28 Athens, Greece
2, 1992 Inc., Publishers
Commentary Thyroid Nodules DEMETRIOS A.
WRITING First,
THIS commentary is difficult, for two reasons. my views generally are similar to those of Dr. Hamburger, and since there is no basic disagreement, it becomes difficult to find points to criticize or comment on. Second, there is a dearth of valid data (e.g., controlled trials) on the management of nodules in general and in pregnancy more specifically. Thus, I must rely on the uncontrolled data of my clinical experience as a physician dealing frequently with thyroid nodules, in pregnancy in a country where endemic goiter is not a
rarity.
DIAGNOSTIC APPROACH The first diagnostic step is careful palpation of the neck. In this way, most clinically important nodules can be detected. Clinical examination can also detect thyroglossal duct cysts and local lymph nodes. Hence, the entire neck should be palpated
carefully. In a nonpregnant woman, the next step after the discovery of nodule should be the performance of a scintigram. In this way, hot nodules, especially frequent in areas with moderate iodine deficiency, will be discovered. These nodules are practically always benign (1,2), and these patients can be spared a fine needle aspiration biopsy (FNB). Furthermore, these hot nodules usually are autonomous. They do not respond to thyroxine treatment. Exogenous thyroxine is additive to the endogenous secretion instead of suppressing it. Therefore, treatment with thyroxine is not indicated. On the other hand, ifthe nodule is warm or cold,an FNB is immediately advised. In our experience, if cytology shows nodular hyperplasia, malignancy can be excluded with a certainty of more than 98%, but in patients with a report of thyroiditis, a neoplasm (usually a papillary cancer) cannot be excluded confidently (3). a
Athens
University.
Pregnancy
KOUTRAS, M.D.
INTRODUCTION
Department of Clinical Therapeutics,
in
Ultrasound (US) studies should be used rarely. As stressed by Hamburger, they can neither exclude nor confirm malignancy. Being more sensitive than palpation, US will detect many impalpable small nodules (< 1 cm), which are especially frequent in persons more than 30 years old and in countries with moderate or definite iodine deficiency. Once such small nodules are detected, what should one do? Should one recommend a US-guided FNB, prescribe thyroxine and monitor its effect by US, i.e., treat the US scan, or consider surgery? I think that none of these procedures is cost effective. The discovery of one or more palpable nodules with US will simply alarm the patient, and often the physician regrets that the US was ever obtained. This basic approach must be modified in pregnancy. Isotopic imaging is not allowed. For this reason, many physicians are tempted to order the US scans that they normally would not request. These US scans not only do not exclude malignancy, but they also do not exclude autonomy, as an isotope scan would. So the physician can only rely on serum hormone levels and FNB. In pregnancy, total serum T4 and T3 levels are increased because of the increase in thyroxine-binding globulin (TBG), and the free hormone levels (FT4 and FT3) or a free thyroxine index (FTI) should be assessed. In case of doubt, the TRH test can be performed in pregnancy without side effects (4). If hyperthyroidism is found, presumably due to an autonomous hot nodule, it should be treated as will be described. If hyperthyroidism is excluded, the nodule presumably is cold, and FNB should be ordered immediately. The patient should be managed as advised by Hamburger.
TREATMENT Ifthe nodule is accompanied by significant hyperthyroidism, should be prescribed. Physicians in the past were sometimes reluctant to treat, but now it has been firmly established that treatment of maternal hyperthyroidism is preferable to nontreatment for both the mother and the fetus (5).
antithyroid drugs
Alexandra General
169
Hospital, Athens, Greece.
KOUTRAS
170 Some special precautions in pregnancy include the following. 1. The pregnant
woman
should be more closely monitored than
in most cases until after parturition. For benign nodules, treatment with thyroxine is debatable but may be considered if the serum TSH is high normal.
nonpregnant persons.
2. The lowest effective dose of the antithyroid drugs should be prescribed, aiming at keeping the FT4 and FT3 at the high normal rather than low normal range. 3. Propylthiouracil seems preferable to methimazole, since it crosses the placenta less readily than methimazole. 4. Thyroxine or T, or both should not be added to the antithyroid drugs. These thyroid hormones cross the placenta poorly. Their addition increases the dose of antithyroid drugs needed, resulting in higher levels in the fetus, without significant protection by the exogenous thyroid hormones
given. Recently, percutaneous alcohol injection has been advocated for the treatment of autonomous nodules (6,7). If the nodule is benign and apparently nonautonomous, thyroxine treatment could be considered. There are no solid data on which to base such a decision. In nonpregnant persons with such a nodule, 24% of European clinicians advise surgery, 48% suppression with T4, and 28% only follow-up (8). The benefit of thyroxine treatment is debatable. Gharib et al. (9) and Cheung et al. ( 10) found no significant difference between thyroxine and placebo. These studies, however, can be criticized because hot nodules, which are usually autonomous and not responsive to thyroxine, were not always excluded and because the dose of thyroxine given may not have been optimal. With these considerations in mind, it is difficult to be certain if thyroxine treatment is beneficial in pregnant women with benign nodules. Nevertheless, such treatment may be considered if the serum TSH is in the upper normal range. If given at all, thyroxine should be administered in rather small doses (11), aiming at keeping the serum TSH at the low normal range rather than suppressing it, with the hope that this will prevent a further increase in the nodule size. An attempt to shrink the nodule with higher thyroxine doses may be postponed until after pregnancy. DISCUSSION I am in basic agreement with Dr. Hamburger. FNB is the main diagnostic procedure, together with serum T4, T3, and TSH levels, used to exclude hyperthyroidism and hypothyroidism. If the nodule is malignant or suspicious, surgery may be postponed
REFERENCES 1. Koutras DA, Livadas D, Sfontouris J, Messaris G, Statherou PK 1968 A study of 408 cold thyroid nodules in a country with endemic goitre. Nuclear Med 7:165. 2. Psarras A, Papadopoulos SN, Livadas DP, Pharmakiotis AD, Koutras DA 1972 The single thyroid nodule. Br J Surg 59:545. 3. Tseleni-Balafoutas S, Koutras DA 1987 Fine-needle biopsy in the evaluation of thyroid nodules. J Med Pharm Vet Afrique 9:18. 4. Koutras DA, Pharmakiotis AD, Koliopoulos N, Tsoukalos J, Souvatzoglou A, Sfontouris J 1978 The plasma inorganic iodine and the pituitary thyroid axis in pregnancy. J Endocrinol Invest
1:227. 5. Matsuura N, Konishi J, Fujieda K, et al 1988 TSH-receptor antibodies in mothers with Graves' disease and outcome in their offspring. Lancet 1:14. 6. Livrachi T, Paracchi A, Ferrari C, et al 1990 Treatment of autonomous thyroid nodules with percutaneous injection: Preliminary results. Work in progress. Radiology 175:827. 7. Kim CS, Lee SH 1991 Percutaneous alcohol injection (PAI) of thyroid nodule. 10th International Thyroid Conference, The Hague/ Netherlands, Feb 3-8, Abstract 359. 8. Baldet L, Manderscheld JC, Glinoer D, Jaffiol C.Costeseignovert B, Percheron C 1989 The management of differentiated thyroid cancer in Europe in 1988. Results of an international survey. Acta Endocrinol 120:547. 9. Gharib H, James EM, Charboneau JW, Naessens JM, Offord KP, Gorman CA 1987 Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study. N Engl J Med 317:70. 10. Cheung P, Boey J, Lee J 1988 Natural course of benign thyroid nodules and the effect of thyroxine therapy. International Thyroid Symposium, Tokyo/Japan, July 13-15, Abstract V-3-3. 11. Koutras DA 1991 Prevention and treatment of nontoxic goiter during pregnancy. Merck symposium: The Thyroid and Pregnancy. Brussels, Jan 31-Feb 2.
Address reprint requests to: Demetrios A. Koutras, M.D. Professor of Medicine, Athens University Department of Clinical Therapeutics Alexandra General Hospital 80, Vas. Sofias Avenue GR-115 28 Athens, Greece
