THYROID Volume 2, Number Mary Ann Liebert,
2, 1992 Inc., Publishers
Thyroid Nodules
in
Pregnancy
JOEL I. HAMBURGER
ABSTRACT
Thyroid nodules are common in pregnant women. Most of them are benign. Toxic autonomous nodules may be infrequently, and the diagnosis is supported by elevated free thyroid hormone levels and undetectable levels of TSH. The most common and most important problem is the diagnosis of thyroid cancer. FNB is the most reliable diagnostic tool. FNB findings also can be used to indicate the urgency for surgery and the appropriate extent of the operation when surgery is indicated. Best use of FNB data requires that the cytopathologist provide tissue diagnoses and that there has been enough experience to permit reasonable inferences of cancer probability for each diagnosis. seen
EVALUATION OF A THYROID NODULE IN PREGNANCY
INTRODUCTION NODULES ARE VERY COMMON. They occur at all are about three times more common in women and ages than in men. Most thyroid nodules are discovered in the course of routine examinations. As prenatal care becomes more sophisticated, it is inevitable that thyroid nodules will be discovered in increasing numbers in pregnant women. In spite of the fact that only about 5% of all thyroid nodules are malignant, the detection of a thyroid nodule immediately raises the fear of cancer. This may be an especially unpleasant problem for a young woman who is preoccupied with the ordinary concerns of forthcoming motherhood. Since thyroid cancers in young people are nearly always the low-grade, differentiated papillary or follicular types, the urgency for prompt diagnosis may be argued. Indeed, at the 1989 meeting of the American Thyroid Association, some authorities suggested that it might be suitable to defer the diagnostic workup until after the pregnancy terminates. The idea is that the patient can be reassured and will then defer her concerns until after her child is delivered. To me this seems like a bad idea. Once a woman knows that she has a thyroid nodule (tumor), she simply is not going to forget about it, regardless of any reassurance. Furthermore, why should her anxiety be extended for the rest of the pregnancy, perhaps 6 months or more, when that anxiety can be dispelled rather simply in many cases?
THYROID
Farmbrook Medical Two, Southfield,
Clinical
assessment
The first order of business is a history and physical examination. Most of the time, the patient will have been unaware of the nodule previously. However, if the nodule had been present for some extended period of time, it is possible that records of previous evaluations might clarify the nature of the lesion, and these should be obtained and reviewed. If the nodule had been present for several years, a history of progressive enlargement is worrisome, especially if the patient had been treated with thyroxine. However, lack of any growth does not exclude
malignancy. Assuming that we are dealing with a new finding, one would ask whether the patient detected the nodule or if it was found by her physician. If she found it, did it seem to "pop up overnight" (suggesting hemorrhage into a cystic or predominantly cystic nodule), or was it painful and tender (suggesting subacute granulomatous thyroiditis)? Is there a family history of thyroid swelling (suggesting Hashimoto's thyroiditis)? Have any family members had thyroid cancer? Although rare, medullary carcino-
must be considered, and there are occasional reports of familial papillary carcinomas. Hoarseness is considered a sign of possible malignancy, but hardly any thyroid malignancies produce hoarseness, and some benign thyroid conditions, espemas
Michigan. 165
HAMBURGER
166
cially bulky goiters, can cause hoarseness by compressing or stretching the recurrent nerve. A history of radiation therapy to the upper body is widely regarded as increasing the risk of thyroid cancer. Less well appreciated is the fact that radiation also increases the frequency of benign thyroid nodules. In our practice, the prevalence of malignant nodules was the same ( 10%) whether there was a history of radiation therapy or not ( 1 ). Hence, the probability of malignancy for any given nodule was not altered by such a history. Since it is possible that the impact of radiation therapy on thyroid cancer frequency may vary from one location to another depending on the intensity of the radiation, physicians must consider the experience in their own locale before assigning any weight to a history of radiation therapy. Most cancers feel hard, especially papillary carcinomas. Cancers may feel softer if they have undergone central degeneration. This may be more common in follicular neoplasms. The detection of adjacent enlarged, firm cervical lymph nodes is a telltale sign of malignancy. However, this is an uncommon finding. Probably 90% of the new cancers we detect occur as solitary discrete thyroid nodules, 1-3 cm in diameter, with no other signs of malignancy.
Laboratory
tests
of thyroid function
Laboratory testing is not very helpful. Nevertheless, sometimes thyroid function tests and antithyroid antibody determinations give evidence for Hashimoto's thyroiditis with impaired thyroid function. In this setting, a thyroid nodule may be representative of the underlying inflammatory and autoimmune process rather than a neoplasm. On rare occasions, thyroid function tests will disclose the low-level hyperthyroidism that may be seen with toxic autonomous nodules. Sometimes, the hyperthyroidism is so mild that observation will be adequate treatment. For more severe hyperthyroidism, antithyroid drugs usually are effective until the pregnancy is concluded. Then the patient can be treated either with radioiodine or surgically. Although autonomous nodules, by definition, are not depen-
dent on TSH for their function and are less responsive to TSH than normal thyroid tissue, these facts do not preclude a response if they are exposed to stimulating hormones (2). The autonomous secretion of thyroid hormone suppresses pituitary TSH release. However, in pregnant women there is an abundant supply of chorionic gonadotropin (hCG), which has intrinsic thyroid-stimulating activity. Hence, with advancing pregnancy, there may be enough stimulation of an autonomous nodule to induce hyperthyroidism even though the prepregnancy hormone
output was inadequate to produce thyrotoxicosis.
One of my patients had mild reversible hyperthyroidism pregnancy in this setting. Before conception, she was demonstrated by suppression studies to have an autonomously functioning 2.5 cm thyroid nodule and two other impalpable areas of autonomous function. Her serum free T3 levels rose from midnormal before conception to values 20%-30% above the upper limit of normal in all three trimesters of pregnancy, returning to the midnormal range postpartum. Serum free T4 levels were near the lower limit of normal before, during, and after pregnancy. The serum TSH level was below normal, but detectable, before conception. TSH values were undetectably
during
low during and after pregnancy. hCG is the most likely cause of the temporary T3-thyrotoxicosis during this pregnancy.
Other
diagnostic
tests
A serum calcium test is important. Some so-called thyroid nodules turn out to be parathyroid lesions. Also, whenever one is considering possible thyroid surgery, it is important to know the status of parathyroid function in advance. Having failed to heed this principle, I once had to inform a patient that she needed a second neck operation when an elevated serum calcium led to a diagnosis of hyperparathyroidism after a thyroidectomy. Although thyroid imaging is not very sensitive for the exclusion of malignancy, it can be reassuring for the 5%—10% of thyroid nodule patients who have nodules that concentrate the tracer more avidly than the extranodular thyroid tissue (generally called "hot nodules"). These lesions are nearly always benign (3). Unfortunately, thyroid imaging using radioactive tracers is contraindicated in pregnancy. Ultrasound determinations are used widely in the evaluation of thyroid nodules. However, since they can neither diagnose nor exclude thyroid cancer, I cannot advise them. It is probably true that purely cystic lesions are seldom malignant, although occasionally one will encounter a small focus of carcinoma in the wall of a predominantly cystic tumor. These mini- or microcancers seldom, if ever, behave as clinically significant cancers. Less than 10% of thyroid nodules are purely cystic or nearly so. Solid or mixed cystic and solid nodules may be
malignant or benign. Experienced ultrasonographers using the best equipment can reliably differentiate among cystic, solid, and mixed thyroid nodules. However, ultrasound as employed in ordinary clinical practice often is far less reliable. Reliability aside, ultrasound is costly and regardless of findings, seldom will eliminate the necessity for needle aspiration. Cystic lesions are aspirated as an attempted curative procedure, with a success rate of about 50%. The character of the fluid may be revealing, since a colorless, watery clear to opalescent fluid is pathognomonic for a parathyroid cyst. Spun sediment from cyst fluid may reveal psammoma bodies or malignant cells, but most of the time, examination of the fluid is not helpful. Solid nodules, of course, will be studied by fine needle biopsy (FNB). Without ultrasound, the insertion of a needle into a nodule will readily differentiate a cystic from a solid nodule. If fluid aspiration produces collapse of the nodule, it was obviously a cyst. Otherwise, it is solid or at least partly solid. Hence, needle aspiration of cystic lesions is both diagnostic and therapeutic and also less costly than ultrasound. Some maintain that ultrasound guidance for FNB is helpful for small, deep, difficult to palpate nodules. I would suggest that it is better to put more effort into upgrading one's skill in nodule palpation. I consider it safe to observe nodules that are too small for conventional FNB. If they enlarge, FNB is performed. Since more than 90% of nodules are benign, it is obvious that small nodules will not get larger very often. Fine needle
biopsy
The most important diagnostic tool in the evaluation of a thyroid nodule in a pregnant patient, as well as for one who is not pregnant, is needle biopsy, especially FNB. As already noted,
THYROID NODULES IN PREGNANCY favor FNB as soon as a nodule is discovered. However, the to be made of the findings requires some discussion. I base this discussion on the FNB diagnosis, assuming that the cytopathologist will be making specific tissue diagnoses. Some cytopathologists lump a disparate group of lesions under the designation of suspicious. In one institution (4), the category included the highly suspicious lesions that I find are malignant 50% of the time, with lesser risk nodules that are malignant only about 15% of the time. It is more useful from the management perspective to segregate these lesions by their more specific tissue diagnoses (5). Specimens inadequate to exclude malignancy in both a preliminary and a repeat FNB. A fundamental limiting factor in FNB is that one cannot aspirate from a nodule anything other than the contents of that nodule. If the nodule has undergone extensive degenerative or fibrotic change, there may be too few viable thyroid epithelial cells to permit any diagnosis. This may be the case for up to 20% of thyroid nodules if physicians adhere to our rather strict criterion for the exclusion of cancer, i.e., at least six clusters of benign thyroid epithelial cells on at least two smears made from separate aspirates taken from different parts of the nodule (6). Many physicians regard this criterion as unncessarily limiting. However, I established this criterion after making false negative diagnoses based on less material. Others have come to similar conclusions after making the same kind of errors on their own material or when reviewing slides on our
167
we
definitive
primary operative procedure,
use
minimal,
to a 10%
patients (4,6). Samples that
are inadequate for the exclusion of malignancy leave the patient in the same position as if no biopsy had been done. Assuming a solid nodule, the chance of malignancy is about 10%. One may try treatment with thyroxine in the hope that the patient may be one of the 20%-30% who respond to this treatment with nodule regression (1). If there is no regression but no growth over a period of years, that too may be taken as suggestive (but not conclusive) evidence that the nodule is benign. Of course, enlargement would call for at least repeat FNB and, in the absence of findings of a benign nodule, surgery. This approach is suitable for the patient who is anxious to avoid an operation unless there are positive indications for it and is willing to accept the risks of observing a malignant nodule. Since nearly all malignancies in young people are the differentiated carcinomas, a delay in surgical treatment for even a few years will not alter the favorable prognosis
materially.
In any event, we prefer to defer a trial of thyroxine treatment until after delivery because we do not wish to introduce any medication during pregnancy that might be incriminated (even irrationally) in the event of a defective fetus. If the patient prefers the diagnostic certainty that thyroidectomy can provide, the operation can be performed electively at any time. For nodules smaller than 1.5 cm, a lobectomy (usually including the isthmus) nearly always will be an adequate operation whether the nodule is benign or malignant. For larger nodules, we prefer a total lobectomy, isthmectomy, and near total contralateral lobectomy. Then, if the nodule is malignant, the patient is ready for further treatment with radioiodine if appropriate. A second operation is unnecessary. This approach is suitable only if an experienced thyroid surgeon is available and only after careful discussion of surgical risks and options with the patient. In our experience, most patients prefer such a
chance that
a
if the increase in risk is second operation will be
needed. The FNB diagnosis is benign. Assuming that the roughly 99% reliability of this diagnosis that we achieve is applicable to the experience in your facility, observation clearly is indicated. If your results are not that reliable, you may have to alter your practice accordingly. In addition, you should be looking into why your diagnoses are not as reliable as they might be. The FNB diagnosis is a malignancy, either definite (about 99% confirmed in our practice) or strongly suspected (about 50% confirmed in our practice). For these patients, an operation, usually an appropriate cancer operation, will be needed. (For lymphomas, radiation therapy may be suitable. For undifferentiated carcinomas, rare in the childbearing population, perhaps the extent of the disease might make more than a palliative decompression procedure futile.) Knowing her diagnosis, the patient can participate intelligently in the decision-making process of when the operation should be done. The FNB diagnosis is a Hurthle cell lesion. About 20% of these lesions are malignant. Furthermore, there may be some uncertainty about the future behavior of Hurthle cell tumors that appear to be benign at the time of excision if they were not excised but left in situ for many years, during which they would have the opportunity to express any latent potential for malignant transformation. For both of the foregoing reasons, operation usually is advised for young healthy patients with Hurthle cell tumors. Since the cytology findings are mostly unreliable in differentiating benign from malignant lesions and Hurthle cell carcinomas are more aggressive than most papillary and many follicular carcinomas, it is advisable to have the operation at the earliest safe opportunity. The FNB diagnosis is follicular neoplasm, microfollicular, or mixed micromacrofollicular. Note that our cytopathologist segregates follicular tumors with obvious features compatible with malignancy from those follicular neoplasms that have no such findings. Hence, our FNB diagnoses of follicular neoplasm are associated with cancer only about 15% of the time, and these are nearly always low-grade tumors. In our opinion, this risk is high enough to warrant operation. However if the patient requests operation, since 85% of these tumors are benign, it would be reasonable to perform a lobectomy (usually including the isthmus) as the initial procedure. In most cases, this will be an adequate operation even for the malignant lesions because the invasiveness of the tumors is so minimal. For a small proportion of larger tumors in older patients that have more extensive malignant features, a second operation will be needed. This may be anticipated if the nodule is 3.5 cm or larger and the patient 35 years old or older. These patients may be presented with the option of having a near-total thyroidectomy as the initial procedure to obviate the need for a second operation. Although frozen sections (FS) have been used to provide guidance to the extent of the operation, they are seldom helpful in thyroid nodule patients (7). FNB diagnoses of benign lesions almost never are reversed correctly by FS. FNB diagnoses of malignancy are more reliable than those by FS. For the follicular or Hurthle cell tumors for which FNB is indecisive, FS is equally indecisive (the diagnoses frequently are deferred pending study of permanent sections), and there are frequent false negative diagnoses and occasional false positive diagnoses. Hence, I
HAMBURGER
168
prefer to plan the extent of operation on the basis of the FNB findings and our understanding of the probabilities of a need for a cancer operation if the tumor is malignant. These matters are discussed with the patient in advance of the operation so both patient and surgeon understand the plan, as well as its risks and advantages. When should the operation be performed? For these low-risk lesions, greater flexibility in timing is possible. Although some patients prefer to have the problem dealt with at the earliest safe opportunity, others may wish to defer operation for months or years. Some will refuse operation unless future developments indicate the need for it (e.g., growth of the nodule in spite of thyroxine therapy or more suspicious findings on a repeat FNB). It is reasonable to accommodate all of these patient attitudes as long as the risks are clearly understood.
3. Miller JM, Hamburger Jl 1965 The thyroid scintigram. I. The hot nodule. Radiology 84:66-74. 4. Goellner JR, Gharib H, Grant CS, Johnson DA 1987 Fine needle aspiration cytology of the thyroid, 1980 to 1986. Acta Cytol 31:587-590. 5. Hamburger JI 1991 Effective use of fine-needle biopsy in the management of thyroid nodules. Diag Oncol 1:177-180. 6. Hamburger JI, Husain M, NishiyamaR, NunezC, Solomon D 1989 Increasing the accuracy of fine-needle biopsy for thyroid nodules. Arch Pathol Lab Med 113:1035-1041. 7. Hamburger JL Husain M 1990 Contribution of intraoperative pathology evaluation to surgical management of thyroid nodules. Endocrinol Metab Clin North Am 19:509-522. 8. Walfish PG, Strawbridge HTG, Rosen IB 1985 Management implications from routine needle biopsy of hyperfunctioning thyroid nodules. Surgery 98:1179-1188. 9. Hamburger JI 1988 Needle aspiration for thyroid nodules. Postgrad Med 84:61-66.
REFERENCES 1.
Hamburger Jl, Husain M 1989 Fine-needle biopsy: Extended observations. In: Hamburger JI (ed) Diagnostic Methods in Clinical Thyroidology. Springer-Verlag, New York, pp 221-249.
2. Larsen PR, Yamashita K, Dekker A, Field JB 1973 Biochemical observations in functioning human thyroid adenomas. J Clin EndocrinolMetab 36:1009-1018.
Address reprint requests to: Joel I. Hamburger, M.D. Farmbrook Medical Two, Suite 303 29877 Telegraph Road Southfield, MI 48034
2, 1992 Inc., Publishers
Thyroid Nodules
in
Pregnancy
JOEL I. HAMBURGER
ABSTRACT
Thyroid nodules are common in pregnant women. Most of them are benign. Toxic autonomous nodules may be infrequently, and the diagnosis is supported by elevated free thyroid hormone levels and undetectable levels of TSH. The most common and most important problem is the diagnosis of thyroid cancer. FNB is the most reliable diagnostic tool. FNB findings also can be used to indicate the urgency for surgery and the appropriate extent of the operation when surgery is indicated. Best use of FNB data requires that the cytopathologist provide tissue diagnoses and that there has been enough experience to permit reasonable inferences of cancer probability for each diagnosis. seen
EVALUATION OF A THYROID NODULE IN PREGNANCY
INTRODUCTION NODULES ARE VERY COMMON. They occur at all are about three times more common in women and ages than in men. Most thyroid nodules are discovered in the course of routine examinations. As prenatal care becomes more sophisticated, it is inevitable that thyroid nodules will be discovered in increasing numbers in pregnant women. In spite of the fact that only about 5% of all thyroid nodules are malignant, the detection of a thyroid nodule immediately raises the fear of cancer. This may be an especially unpleasant problem for a young woman who is preoccupied with the ordinary concerns of forthcoming motherhood. Since thyroid cancers in young people are nearly always the low-grade, differentiated papillary or follicular types, the urgency for prompt diagnosis may be argued. Indeed, at the 1989 meeting of the American Thyroid Association, some authorities suggested that it might be suitable to defer the diagnostic workup until after the pregnancy terminates. The idea is that the patient can be reassured and will then defer her concerns until after her child is delivered. To me this seems like a bad idea. Once a woman knows that she has a thyroid nodule (tumor), she simply is not going to forget about it, regardless of any reassurance. Furthermore, why should her anxiety be extended for the rest of the pregnancy, perhaps 6 months or more, when that anxiety can be dispelled rather simply in many cases?
THYROID
Farmbrook Medical Two, Southfield,
Clinical
assessment
The first order of business is a history and physical examination. Most of the time, the patient will have been unaware of the nodule previously. However, if the nodule had been present for some extended period of time, it is possible that records of previous evaluations might clarify the nature of the lesion, and these should be obtained and reviewed. If the nodule had been present for several years, a history of progressive enlargement is worrisome, especially if the patient had been treated with thyroxine. However, lack of any growth does not exclude
malignancy. Assuming that we are dealing with a new finding, one would ask whether the patient detected the nodule or if it was found by her physician. If she found it, did it seem to "pop up overnight" (suggesting hemorrhage into a cystic or predominantly cystic nodule), or was it painful and tender (suggesting subacute granulomatous thyroiditis)? Is there a family history of thyroid swelling (suggesting Hashimoto's thyroiditis)? Have any family members had thyroid cancer? Although rare, medullary carcino-
must be considered, and there are occasional reports of familial papillary carcinomas. Hoarseness is considered a sign of possible malignancy, but hardly any thyroid malignancies produce hoarseness, and some benign thyroid conditions, espemas
Michigan. 165
HAMBURGER
166
cially bulky goiters, can cause hoarseness by compressing or stretching the recurrent nerve. A history of radiation therapy to the upper body is widely regarded as increasing the risk of thyroid cancer. Less well appreciated is the fact that radiation also increases the frequency of benign thyroid nodules. In our practice, the prevalence of malignant nodules was the same ( 10%) whether there was a history of radiation therapy or not ( 1 ). Hence, the probability of malignancy for any given nodule was not altered by such a history. Since it is possible that the impact of radiation therapy on thyroid cancer frequency may vary from one location to another depending on the intensity of the radiation, physicians must consider the experience in their own locale before assigning any weight to a history of radiation therapy. Most cancers feel hard, especially papillary carcinomas. Cancers may feel softer if they have undergone central degeneration. This may be more common in follicular neoplasms. The detection of adjacent enlarged, firm cervical lymph nodes is a telltale sign of malignancy. However, this is an uncommon finding. Probably 90% of the new cancers we detect occur as solitary discrete thyroid nodules, 1-3 cm in diameter, with no other signs of malignancy.
Laboratory
tests
of thyroid function
Laboratory testing is not very helpful. Nevertheless, sometimes thyroid function tests and antithyroid antibody determinations give evidence for Hashimoto's thyroiditis with impaired thyroid function. In this setting, a thyroid nodule may be representative of the underlying inflammatory and autoimmune process rather than a neoplasm. On rare occasions, thyroid function tests will disclose the low-level hyperthyroidism that may be seen with toxic autonomous nodules. Sometimes, the hyperthyroidism is so mild that observation will be adequate treatment. For more severe hyperthyroidism, antithyroid drugs usually are effective until the pregnancy is concluded. Then the patient can be treated either with radioiodine or surgically. Although autonomous nodules, by definition, are not depen-
dent on TSH for their function and are less responsive to TSH than normal thyroid tissue, these facts do not preclude a response if they are exposed to stimulating hormones (2). The autonomous secretion of thyroid hormone suppresses pituitary TSH release. However, in pregnant women there is an abundant supply of chorionic gonadotropin (hCG), which has intrinsic thyroid-stimulating activity. Hence, with advancing pregnancy, there may be enough stimulation of an autonomous nodule to induce hyperthyroidism even though the prepregnancy hormone
output was inadequate to produce thyrotoxicosis.
One of my patients had mild reversible hyperthyroidism pregnancy in this setting. Before conception, she was demonstrated by suppression studies to have an autonomously functioning 2.5 cm thyroid nodule and two other impalpable areas of autonomous function. Her serum free T3 levels rose from midnormal before conception to values 20%-30% above the upper limit of normal in all three trimesters of pregnancy, returning to the midnormal range postpartum. Serum free T4 levels were near the lower limit of normal before, during, and after pregnancy. The serum TSH level was below normal, but detectable, before conception. TSH values were undetectably
during
low during and after pregnancy. hCG is the most likely cause of the temporary T3-thyrotoxicosis during this pregnancy.
Other
diagnostic
tests
A serum calcium test is important. Some so-called thyroid nodules turn out to be parathyroid lesions. Also, whenever one is considering possible thyroid surgery, it is important to know the status of parathyroid function in advance. Having failed to heed this principle, I once had to inform a patient that she needed a second neck operation when an elevated serum calcium led to a diagnosis of hyperparathyroidism after a thyroidectomy. Although thyroid imaging is not very sensitive for the exclusion of malignancy, it can be reassuring for the 5%—10% of thyroid nodule patients who have nodules that concentrate the tracer more avidly than the extranodular thyroid tissue (generally called "hot nodules"). These lesions are nearly always benign (3). Unfortunately, thyroid imaging using radioactive tracers is contraindicated in pregnancy. Ultrasound determinations are used widely in the evaluation of thyroid nodules. However, since they can neither diagnose nor exclude thyroid cancer, I cannot advise them. It is probably true that purely cystic lesions are seldom malignant, although occasionally one will encounter a small focus of carcinoma in the wall of a predominantly cystic tumor. These mini- or microcancers seldom, if ever, behave as clinically significant cancers. Less than 10% of thyroid nodules are purely cystic or nearly so. Solid or mixed cystic and solid nodules may be
malignant or benign. Experienced ultrasonographers using the best equipment can reliably differentiate among cystic, solid, and mixed thyroid nodules. However, ultrasound as employed in ordinary clinical practice often is far less reliable. Reliability aside, ultrasound is costly and regardless of findings, seldom will eliminate the necessity for needle aspiration. Cystic lesions are aspirated as an attempted curative procedure, with a success rate of about 50%. The character of the fluid may be revealing, since a colorless, watery clear to opalescent fluid is pathognomonic for a parathyroid cyst. Spun sediment from cyst fluid may reveal psammoma bodies or malignant cells, but most of the time, examination of the fluid is not helpful. Solid nodules, of course, will be studied by fine needle biopsy (FNB). Without ultrasound, the insertion of a needle into a nodule will readily differentiate a cystic from a solid nodule. If fluid aspiration produces collapse of the nodule, it was obviously a cyst. Otherwise, it is solid or at least partly solid. Hence, needle aspiration of cystic lesions is both diagnostic and therapeutic and also less costly than ultrasound. Some maintain that ultrasound guidance for FNB is helpful for small, deep, difficult to palpate nodules. I would suggest that it is better to put more effort into upgrading one's skill in nodule palpation. I consider it safe to observe nodules that are too small for conventional FNB. If they enlarge, FNB is performed. Since more than 90% of nodules are benign, it is obvious that small nodules will not get larger very often. Fine needle
biopsy
The most important diagnostic tool in the evaluation of a thyroid nodule in a pregnant patient, as well as for one who is not pregnant, is needle biopsy, especially FNB. As already noted,
THYROID NODULES IN PREGNANCY favor FNB as soon as a nodule is discovered. However, the to be made of the findings requires some discussion. I base this discussion on the FNB diagnosis, assuming that the cytopathologist will be making specific tissue diagnoses. Some cytopathologists lump a disparate group of lesions under the designation of suspicious. In one institution (4), the category included the highly suspicious lesions that I find are malignant 50% of the time, with lesser risk nodules that are malignant only about 15% of the time. It is more useful from the management perspective to segregate these lesions by their more specific tissue diagnoses (5). Specimens inadequate to exclude malignancy in both a preliminary and a repeat FNB. A fundamental limiting factor in FNB is that one cannot aspirate from a nodule anything other than the contents of that nodule. If the nodule has undergone extensive degenerative or fibrotic change, there may be too few viable thyroid epithelial cells to permit any diagnosis. This may be the case for up to 20% of thyroid nodules if physicians adhere to our rather strict criterion for the exclusion of cancer, i.e., at least six clusters of benign thyroid epithelial cells on at least two smears made from separate aspirates taken from different parts of the nodule (6). Many physicians regard this criterion as unncessarily limiting. However, I established this criterion after making false negative diagnoses based on less material. Others have come to similar conclusions after making the same kind of errors on their own material or when reviewing slides on our
167
we
definitive
primary operative procedure,
use
minimal,
to a 10%
patients (4,6). Samples that
are inadequate for the exclusion of malignancy leave the patient in the same position as if no biopsy had been done. Assuming a solid nodule, the chance of malignancy is about 10%. One may try treatment with thyroxine in the hope that the patient may be one of the 20%-30% who respond to this treatment with nodule regression (1). If there is no regression but no growth over a period of years, that too may be taken as suggestive (but not conclusive) evidence that the nodule is benign. Of course, enlargement would call for at least repeat FNB and, in the absence of findings of a benign nodule, surgery. This approach is suitable for the patient who is anxious to avoid an operation unless there are positive indications for it and is willing to accept the risks of observing a malignant nodule. Since nearly all malignancies in young people are the differentiated carcinomas, a delay in surgical treatment for even a few years will not alter the favorable prognosis
materially.
In any event, we prefer to defer a trial of thyroxine treatment until after delivery because we do not wish to introduce any medication during pregnancy that might be incriminated (even irrationally) in the event of a defective fetus. If the patient prefers the diagnostic certainty that thyroidectomy can provide, the operation can be performed electively at any time. For nodules smaller than 1.5 cm, a lobectomy (usually including the isthmus) nearly always will be an adequate operation whether the nodule is benign or malignant. For larger nodules, we prefer a total lobectomy, isthmectomy, and near total contralateral lobectomy. Then, if the nodule is malignant, the patient is ready for further treatment with radioiodine if appropriate. A second operation is unnecessary. This approach is suitable only if an experienced thyroid surgeon is available and only after careful discussion of surgical risks and options with the patient. In our experience, most patients prefer such a
chance that
a
if the increase in risk is second operation will be
needed. The FNB diagnosis is benign. Assuming that the roughly 99% reliability of this diagnosis that we achieve is applicable to the experience in your facility, observation clearly is indicated. If your results are not that reliable, you may have to alter your practice accordingly. In addition, you should be looking into why your diagnoses are not as reliable as they might be. The FNB diagnosis is a malignancy, either definite (about 99% confirmed in our practice) or strongly suspected (about 50% confirmed in our practice). For these patients, an operation, usually an appropriate cancer operation, will be needed. (For lymphomas, radiation therapy may be suitable. For undifferentiated carcinomas, rare in the childbearing population, perhaps the extent of the disease might make more than a palliative decompression procedure futile.) Knowing her diagnosis, the patient can participate intelligently in the decision-making process of when the operation should be done. The FNB diagnosis is a Hurthle cell lesion. About 20% of these lesions are malignant. Furthermore, there may be some uncertainty about the future behavior of Hurthle cell tumors that appear to be benign at the time of excision if they were not excised but left in situ for many years, during which they would have the opportunity to express any latent potential for malignant transformation. For both of the foregoing reasons, operation usually is advised for young healthy patients with Hurthle cell tumors. Since the cytology findings are mostly unreliable in differentiating benign from malignant lesions and Hurthle cell carcinomas are more aggressive than most papillary and many follicular carcinomas, it is advisable to have the operation at the earliest safe opportunity. The FNB diagnosis is follicular neoplasm, microfollicular, or mixed micromacrofollicular. Note that our cytopathologist segregates follicular tumors with obvious features compatible with malignancy from those follicular neoplasms that have no such findings. Hence, our FNB diagnoses of follicular neoplasm are associated with cancer only about 15% of the time, and these are nearly always low-grade tumors. In our opinion, this risk is high enough to warrant operation. However if the patient requests operation, since 85% of these tumors are benign, it would be reasonable to perform a lobectomy (usually including the isthmus) as the initial procedure. In most cases, this will be an adequate operation even for the malignant lesions because the invasiveness of the tumors is so minimal. For a small proportion of larger tumors in older patients that have more extensive malignant features, a second operation will be needed. This may be anticipated if the nodule is 3.5 cm or larger and the patient 35 years old or older. These patients may be presented with the option of having a near-total thyroidectomy as the initial procedure to obviate the need for a second operation. Although frozen sections (FS) have been used to provide guidance to the extent of the operation, they are seldom helpful in thyroid nodule patients (7). FNB diagnoses of benign lesions almost never are reversed correctly by FS. FNB diagnoses of malignancy are more reliable than those by FS. For the follicular or Hurthle cell tumors for which FNB is indecisive, FS is equally indecisive (the diagnoses frequently are deferred pending study of permanent sections), and there are frequent false negative diagnoses and occasional false positive diagnoses. Hence, I
HAMBURGER
168
prefer to plan the extent of operation on the basis of the FNB findings and our understanding of the probabilities of a need for a cancer operation if the tumor is malignant. These matters are discussed with the patient in advance of the operation so both patient and surgeon understand the plan, as well as its risks and advantages. When should the operation be performed? For these low-risk lesions, greater flexibility in timing is possible. Although some patients prefer to have the problem dealt with at the earliest safe opportunity, others may wish to defer operation for months or years. Some will refuse operation unless future developments indicate the need for it (e.g., growth of the nodule in spite of thyroxine therapy or more suspicious findings on a repeat FNB). It is reasonable to accommodate all of these patient attitudes as long as the risks are clearly understood.
3. Miller JM, Hamburger Jl 1965 The thyroid scintigram. I. The hot nodule. Radiology 84:66-74. 4. Goellner JR, Gharib H, Grant CS, Johnson DA 1987 Fine needle aspiration cytology of the thyroid, 1980 to 1986. Acta Cytol 31:587-590. 5. Hamburger JI 1991 Effective use of fine-needle biopsy in the management of thyroid nodules. Diag Oncol 1:177-180. 6. Hamburger JI, Husain M, NishiyamaR, NunezC, Solomon D 1989 Increasing the accuracy of fine-needle biopsy for thyroid nodules. Arch Pathol Lab Med 113:1035-1041. 7. Hamburger JL Husain M 1990 Contribution of intraoperative pathology evaluation to surgical management of thyroid nodules. Endocrinol Metab Clin North Am 19:509-522. 8. Walfish PG, Strawbridge HTG, Rosen IB 1985 Management implications from routine needle biopsy of hyperfunctioning thyroid nodules. Surgery 98:1179-1188. 9. Hamburger JI 1988 Needle aspiration for thyroid nodules. Postgrad Med 84:61-66.
REFERENCES 1.
Hamburger Jl, Husain M 1989 Fine-needle biopsy: Extended observations. In: Hamburger JI (ed) Diagnostic Methods in Clinical Thyroidology. Springer-Verlag, New York, pp 221-249.
2. Larsen PR, Yamashita K, Dekker A, Field JB 1973 Biochemical observations in functioning human thyroid adenomas. J Clin EndocrinolMetab 36:1009-1018.
Address reprint requests to: Joel I. Hamburger, M.D. Farmbrook Medical Two, Suite 303 29877 Telegraph Road Southfield, MI 48034
