Diffuse nontoxic and multinodular goiter.
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Animals↗
Biomedical subjects
H Gharib
Publications and source records attributed to H Gharib.
Management of thyroid nodules in pregnancy.
BACKGROUND: Disorders of the thyroid are common in pregnancy. In particular, a thyroid nodule is frequently discovered before or during pregnancy. OBJECTIVE: To develop guidelines for the management of thyroid nodules during pregnancy. METHODS: We reviewed the cases of 40 pregnant patients with thyroid nodules evaluated during a 10-year period Cytological findings were compared with available histological findings, and concordance rates were determined. The rank sum test was used for statistical analysis. RESULTS: Fine-needle aspirations of thyroid nodules in 62% of patients were benign cytologically (25 patients). Of 8 patients with negative cytological results who had thyroidectomy, all had benign disease histologically (100% concordance rate). Cytological findings of papillary cancer (3 patients) strongly correlated with final histological diagnosis (100% concordance rate), whereas papillary cancer was confirmed histologically in only 2 of 4 patients with cytological findings suspicious for this disease (50% concordance rate). All 3 nodules with cytological findings suspicious for follicular neoplasm were benign adenomas histologically. Of 2 nodules suspicious for Hürthle cell neoplasm, l was Hürthle cell adenoma and the other was Hürthle cell carcinoma (100% concordance rate). Thyroidectomy during the second trimester of pregnancy or the early postpartum period was successful. CONCLUSIONS: The approach to thyroid nodules in pregnancy should be similar to that for nonpregnant patients. Thyroidectomy should be performed (1) during the second trimester for malignant lesions and cytological findings suspicious for papillary cancer and (2) in the postpartum period for cytological findings suspicious for follicular neoplasm.
Adult↗
Primary care diagnosis of thyroid disease.
Recent diagnostic advances include sensitive thyroid-stimulating hormone (TSH) assays, more accurate free thyroxine assays, and fine-needle aspiration biopsy. The workup of patients with suspected thyroid dysfunction generally begins with a TSH assay; guidelines are provided for subsequent thyroid tests. Aspiration biopsy is appropriate for those with a nodular goiter.
Autoantibodies↗
Results of treatment of pituitary disease in multiple endocrine neoplasia, type I.
OBJECTIVE: The aim of the present study was to examine the clinical and pathological features of pituitary disease in patients with multiple endocrine neoplasia, Type I (MEN I) and to assess the prognosis. METHODS: Fifty-two patients with pituitary disease and MEN I were studied retrospectively. Medical records were reviewed, and all of the patients known to be alive were sent a questionnaire to ascertain current disease status. RESULTS: In 12 patients, pituitary disease was the initial manifestation of MEN I. The most common lesion was prolactinoma, followed, in frequency, by acromegaly and nonsecretory adenoma. Thirty-four of the patients had surgical treatment at the Mayo Clinic, Rochester, MN, as primary treatment, 3 had radiotherapy, and 12 received no specific therapy. Twelve patients had adjunctive radiotherapy postoperatively. Of the 34 patients receiving surgical treatment, 33 had adenoma and 1 had adenoma and pituitary hyperplasia. Immunocytochemical examination demonstrated that many tumors showed reactivity for more than one pituitary hormone. On survival analysis, no excess pituitary-related mortality was found, either in the surgically treated group or in the group as a whole. CONCLUSION: On the basis of this study, we conclude that pituitary disease is frequently the initial manifestation of MEN I; that adenomas, particularly prolactinomas, are the rule and hyperplasia is rare; that a significant proportion of tumors are plurihormonal; and that excess pituitary-related mortality is not a factor in patients with MEN I.
Acromegaly↗
Evaluation and management of multinodular goiter.
Nodular goiters are encountered commonly in clinical practice by primary care physicians, endocrinologists, surgeons, and otolaryngologists. Epidemiologic data suggest that in the United States, the incidence of such goiters is approximately 0.1% to 1.5% per year, translating into 250,000 new nodules annually. Nodular goiters are more common in women than in men, with advancing age, and after exposure to external irradiation. These goiters may be asymptomatic, with normal TSH levels (nontoxic), or may be associated with systemic thyrotoxic symptoms (toxic MNG or Plummer's disease). Diagnostic evaluation of patients with nodular goiters consists of clinical evaluation, biochemical testing, FNA, and imaging studies. The serum TSH level is a sensitive and reliable index of thyroid function. FNA results are pivotal to assess cancer risk in patient management for prominent palpable and suspicious nodules. Chest radiography, high-resolution ultrasonography, and computed tomography help to delineate the size and extent of a goiter in evaluating compression symptoms. Indications for treatment in patients with MNG include hyperthyroidism, local compression symptoms attributed to the goiter, cosmesis, and concern about malignancy based on FNA results. The use of levothyroxine suppression therapy to effectively decrease and control MNG size is controversial. Thyroid hormone should not be used, however, in patients with suppressed serum TSH levels, to avoid the development of toxic symptoms. Management of toxic MNG by surgery is well established. Radioiodine is also effective therapy for many of these patients. When treatment is necessary for nontoxic MNG, surgical excision is preferred. Our recommendations are as follows. For patients who have small, nontoxic multinodular goiters that are clinically asymptomatic, who are biochemically euthyroid according to serum TSH levels, and who have prominent palpable or suspicious nodules benign by FNA, yearly evaluation with serum TSH determinations and thyroid palpation is sufficient. Patients with modest but stable MNG size and normal serum TSH levels may also be managed by yearly clinical observation. In this second group, levothyroxine suppression therapy is often unsuccessful and has the potential for untoward effects from exogenous hyperthyroidism. For large nontoxic multinodular goiters with local compression symptoms, the preferred treatment is surgery. In patients with toxic MNG, treatment with either surgery or radioiodine is recommended, although patients with large goiters and large, autonomously functioning nodules become euthyroid more quickly following surgery.
Age Factors↗
Genetic testing in the diagnosis and management of multiple endocrine neoplasia type II.
PURPOSE: To review significant advances in the early diagnosis and treatment of medullary thyroid carcinoma in patients with the multiple endocrine neoplasia II (MEN II) syndromes, advances made possible by the application of recently discovered genetic information. DATA SOURCES: Recently published English-language literature on linkage analysis and DNA analysis in the MEN II syndromes. STUDY SELECTION: Articles on familial and sporadic forms of medullary thyroid carcinoma; pentagastrin-calcitonin determination; and genetic testing. DATA EXTRACTION: Information from recent studies on 1) the usefulness and limitations of genetic testing, especially DNA and linkage analysis, in the early diagnosis of the familial form of thyroid carcinoma and 2) the correlation between the results of genetic testing and the results of biochemical screening. DATA SYNTHESIS: Medullary thyroid carcinoma accounts for most of the morbidity and mortality among patients with the familial medullary thyroid carcinoma syndromes. Multiple endocrine neoplasia IIa and IIb and familial medullary thyroid carcinoma are inherited conditions with autosomal dominance and incomplete penetrance. Traditionally, diagnosis and screening for these conditions have been done using pentagastrin stimulation tests and plasma calcitonin determinations. Recent genetic mapping, however, has assigned the genes responsible for these tumors to the pericentromeric region of chromosome 10. Available data suggest that mutations in exon 10, 11, or 16 of the RET proto-oncogene are responsible for MEN IIa and IIb and familial non-MEN medullary thyroid carcinoma. Thus, genetic testing can identify affected members of a kindred and will probably lead to early thyroidectomy and possible cure for gene carriers. CONCLUSIONS: Early studies confirm the usefulness of DNA analysis in the diagnosis and treatment of patients with familial forms of medullary thyroid carcinoma. We review changes in the diagnosis and treatment of these patients and offer a strategy for operative intervention based on results of genetic testing.
Algorithms↗
Controversies in the management of cold, hot, and occult thyroid nodules.
Some aspects of thyroid nodule evaluation and management remain controversial. Radionuclide scanning provides functional information about nodules and differentiates cold from hot nodules. Although thyroid cancers are cold on scan, most cold nodules are benign. Ultrasonography visualizes the thyroid gland and nodules with remarkable clarity and provides structural information about location, number, size, and consistency of nodules. Widespread application of ultrasonography has resulted in the frequent discovery of incidental (occult) nodules in the general population. The clinical significance of these nodules remains unknown, and their management has created a dilemma for physicians. Current cost-effective evaluation of nodules does not include scanning or ultrasonography as routine frontline tests. In most centers, fine-needle aspiration biopsy has supplanted imaging studies as the routine initial procedure for differentiating benign from malignant nodules. Cytologic diagnosis is reliable and inexpensive, and it results in a better selection of patients for surgery. Limitations include false-negative diagnoses, nondiagnostic results, and indeterminate "suspicious" results. Laboratory test results are usually normal, but determination of serum thyrotropin may identify a hot nodule, and plasma calcitonin may help diagnose medullary thyroid carcinoma. Treatment of thyroid nodules is controversial. In some practices, benign colloid nodules are treated with suppressive doses of levothyroxine. Recent reports cast doubt on the efficacy of this approach, and it is no longer acceptable to select patients for surgical treatment on the basis of suppressive therapy. Furthermore, suppressive levothyroxine therapy may be associated with significant bone and cardiac side effects, especially in elderly patients and postmenopausal women. Our approach is observation for most patients, and we suggest a careful risk-benefit analysis when suppression is considered. Hot (autonomous) nodules can be treated with radioiodine, surgery, or ethanol injection. The use of sensitive thyrotropin assays has revealed that the "euthyroid" hot nodule is often associated with subclinical hyperthyroidism, warranting treatment if risks of osteoporosis are significant. Small (< 1.5 cm) occult nodules can be observed. Larger (> 1.5 cm) nodules can be selectively evaluated by ultrasonographically guided fine-needle aspiration. It is prudent to consider cost of care, risk-benefit analysis, and the low incidence of malignancy in thyroid nodules when diagnostic tests are selected and the treatment plan is outlined.
Biopsy, Needle↗
Multiple endocrine neoplasia type 2B: more than an endocrine disorder.
BACKGROUND: Multiple endocrine neoplasia type 2B (MEN 2B) is a rare disorder differentiated from MEN 2A primarily by its extraendocrine features. This report describes the clinical spectrum and outcome of MEN 2B. METHODS: Twenty-one patients underwent operation for manifestations of MEN 2B between 1970 and 1993. Median follow-up was 16.9 years. Diagnosis was made through family screening in nine, the development of medullary thyroid carcinoma (MTC) in seven, phenotypic features in four, and constipation in one. Median age at presentation of colonic dysfunction, MTC, and pheochromocytoma was 0.1, 16, and 28 years, respectively. RESULTS: Every patient had MTC. Fifteen (94%) of 16 patients undergoing primary thyroidectomies had multicentric disease, and seven (44%) had nodal metastases. Seven patients (33%) had pheochromocytoma, six bilateral and one malignant. Adrenalectomy was curative in every patient. Nineteen patients (90%) had colonic disturbances, typically chronic constipation from birth. Megacolon developed in 14 patients, and eight required colonic surgery. Every patient had the characteristic phenotype. Dominant features included neuromas of the tongue, buccal mucosa, lips, conjunctivae, and eyelids and a marfanoid habitus. Other features included high arched palate, corneal nerve thickening, and dental and skeletal abnormalities. Four patients died, two of metastatic MTC, one after operation for metastatic MTC, and one as a consequence of colonic perforation. Of 17 survivors, three have hepatic metastases from MTC, eight have nodal metastases, and six are well with normal or mildly elevated calcitonin levels. CONCLUSIONS: MEN 2B is characterized by a relatively aggressive form of MTC, bilateral pheochromocytoma, severe colonic dysfunction, and a multitude of other extraendocrine abnormalities. Early recognition of MEN 2B and early prophylactic thyroidectomy are essential. Colonic dysfunction has previously received little attention, and further investigation of the pathogenesis and treatment of this disorder is warranted.
Adolescent↗
Familial medullary thyroid cancer and prominent corneal nerves: clinical and genetic analysis.
A unique kindred manifesting medullary thyroid carcinoma and corneal nerve thickening without other aspects of the multiple endocrine neoplasia syndrome (MEN) was analyzed by linkage analysis using four highly polymorphic (CA)n repeat markers (sTCL-1, D10S141, ZNF22, and sJRH-1). Additionally, the RET protooncogene was examined for specific mutations by DNA sequence analyses in all affected family members. Screening of 11 family members spanning 4 generations revealed 7 subjects with corneal nerve thickening; of these subjects, 3 had abnormal pentagastrin-stimulated calcitonin studies, and these 3 subjects were each found to have C-cell hyperplasia or medullary thyroid carcinoma at surgery. Linkage analysis showed cosegregation of alleles (as defined by the above markers), with the presence of both corneal nerve thickening and medullary thyroid carcinoma/C-cell hyperplasia (maximum LOD score, 2.69; consistent with, but not proving linkage). DNA sequence analysis showed that none of the affected individuals had mutations in either exon 10 or 11, or in exon 16 of the RET protooncogene, regions where mutations have been described for MEN type 2A (MEN-2A) and MEN-2B families, respectively. Thus, compared to the defined syndromes of MEN-2A and MEN-2B, this kindred appears to represent a true clinical overlap syndrome whose genetic basis may be distinct from these two syndromes.
Aged↗
Detection and treatment of hypothyroidism and Graves' disease.
The clinical presentations of thyroid disorders are often subtle in older adults and may be confused with "normal" aging. To avoid delay in diagnosis, we recommend routine TSH screening of all patients age 60 and older in the primary care practice. With hypothyroidism, pursue treatment cautiously; start with small doses of levothyroxine and closely monitor serum TSH values. When hyperthyroidism is caused by Graves' disease, begin symptomatic therapy with a beta blocker or antithyroid drugs, followed by definitive thyroid ablation with radioiodine. Surgical treatment may be indicated if a goiter causes compressive symptoms.
Aged↗
Thyroid nodular disease: is it toxic or nontoxic, malignant or benign?
The thyroid gland is known to become more nodular with age. The clinical questions in a given patient are whether the nodule(s) is benign or malignant and euthyroid or toxic. Toxic multinodular goiter (MNG) is more common in the elderly than Graves' disease but is not associated with the classic eye or skin findings. Drug therapy is usually effective, but total thyroidectomy may be preferred. Nontoxic MNG is common among older women. Treatment remains controversial because of potential side effects of suppressive therapy. Although thyroid carcinoma is rare, most of the more aggressive tumors are seen after age 50. Fine-needle aspiration and cytologic examination are useful in separating benign from malignant tumors.
Aged↗
Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect.
BACKGROUND: The efficacy of fine-needle aspiration (FNA) biopsy and its role in the management of a nodular goiter are clearly established. The accuracy of cytologic diagnosis approaches 95%. FINDINGS: FNA biopsy is a reasonable approach to thyroid nodules; it has decreased costs substantially because it facilitates selection of patients who need to undergo surgical excision. Selecting patients for operation on the basis of results of FNA biopsy has more than doubled the yield of carcinoma. The limitations of cytologic examination, nondiagnostic results, and cellular follicular neoplasms should be remembered but need not negate continued use of FNA biopsy. Negative (benign) and positive (malignant) cytologic results are conclusive; careful clinical follow-up of benign nodules and surgical excision of malignant nodules are recommended. Nondiagnostic results are inconclusive; further evaluation by repeated FNA biopsy, ultrasound-guided biopsy, or radionuclide scanning is necessary. Suspicious cytologic results are also inconclusive and are associated with a 20% chance of malignant involvement; surgical treatment is necessary for clarification. The role of levothyroxine therapy remains uncertain and is not recommended until compelling data are available. CONCLUSION: FNA biopsy is a safe, simple, reliable, and cost-effective means of detecting benign nodules. FNA biopsy, not thyroid scanning or ultrasonography, is the preferred initial diagnostic test in all patients with thyroid nodules.
Biopsy, Needle↗
Increased plasma calcitonin levels in systemic mast cell disease.
Aspirin therapy for patients with systemic mast cell disease (SMCD) decreases the production of prostaglandin D2, which is thought to be a major mediator of flushing. Paradoxically, in 5 to 10% of patients with SMCD, administration of aspirin causes massive mediator release and an anaphylactoid reaction. We attempted aspirin desensitization in a 34-year-old man with SMCD (confirmed by bone marrow biopsy) who was incapacitated by severe flushing episodes and hypotension. His baseline mediator levels of plasma calcitonin, urinary histamine, and urinary N-methyl-imidazoleacetic acid were abnormal. Pentagastrin stimulation increased the plasma level of calcitonin from 47 pg/mL to 130 pg/mL (normal, less than or equal to 110) at 5 minutes. Oral aspirin desensitization was begun; however, after a cumulative dose of 620 mg, an anaphylactoid reaction ensued in conjunction with hypotension, abdominal cramping, and flushing. Coincidentally, 1 hour after the episode, the plasma calcitonin level increased from 37 pg/mL to 540 pg/mL, and the serum tryptase level increased from 1 ng/mL to 3.9 ng/mL. Six hours after the episode, the urine level of histamine increased from 90 micrograms/g creatinine to 337 micrograms/g creatinine, and the urinary N-methylimidazoleacetic acid increased from 32 mg/24 h to 81 mg/24 h. Hence, the patient had increased basal levels of plasma calcitonin that increased substantially during aspirin desensitization and increased to above the upper limit of normal during pentagastrin stimulation. Human mast cells may be capable of producing calcitonin or causing secretion of calcitonin in response to skeletal changes.
Adult↗
Identification of multiple endocrine neoplasia, type 2 gene carriers using linkage analysis and analysis of the RET proto-oncogene.
Ten kindreds (95 individuals) with multiple endocrine neoplasia, type 2 (MEN 2) were analyzed by linkage analysis using four highly polymorphic (CA)n-repeat markers (sTCL-1, D10S141, ZNF22, and sJRH-1). Additionally, we examined the RET proto-oncogene for specific mutations by DNA sequence analyses in these 10 plus 14 members of 3 additional kindred. Nine families had MEN 2A, two had MEN 2B, and two had medullary thyroid cancer alone (FMTC). Using these four markers, all 10 kindreds were informative, with 10 individuals predicted to be presymptomatic MEN 2 gene carriers and 23 individuals predicted not to be carriers. DNA sequence analysis of exons 10 and 11 of the RET proto-oncogene revealed a mutation in all nine MEN 2A kindreds. A missense mutation was found in each case, leading to a loss of a cysteine residue (codon 618 of exon 10 or codon 634 of exon 11). In the MEN 2A families, the linkage analysis and RET mutation analysis gave concordant results for prediction of gene carriers in 100% of the individuals tested. No mutations were found in the two kindreds with FMTC or the two MEN 2B kindreds. Two individuals from two different MEN 2A kindreds were identified who had abnormal calcitonin stimulation tests but were not MEN 2A gene carriers by both linkage analysis and RET mutation analysis. These individuals presumably represented the sporadic occurrence of abnormal calcitonin stimulation tests in the general population. These studies provide further support for a role of the RET proto-oncogene in the pathogenesis of MEN 2A. Additionally, in the absence of identifiable RET proto-oncogene mutations, linkage analysis using (CA)n-repeat markers is a highly accurate alternative for the identification of MEN 2 or FMTC gene carriers.
Drosophila Proteins↗
Diffuse nontoxic and multinodular goiter.
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Diagnosis, Differential↗
Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B.
BACKGROUND: Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN)-related medullary thyroid carcinoma (MTC) during the past two decades. Genetic screening now promises earlier and more accurate diagnosis. We examine our experience with MTC in MEN 2A and MEN 2B and assess the benefits of biochemical screening during the past 20 years. PATIENTS AND METHODS: Seventy-seven patients undergoing 63 primary total thyroidectomies and 14 reoperative procedures for MEN-related invasive MTC and/or preinvasive C-cell hyperplasia are reported. Fifty-eight patients had MEN 2A and 19 had MEN 2B; 79% of patients had a family history of MTC; 27% had pheochromocytoma, and 25% had hyperparathyroidism. RESULTS: Patients with MEN 2B had more advanced disease than those with MEN 2A, in spite of presentation at a younger age (15 years versus 24 years). Every patient with MEN 2B had invasive carcinoma, whereas 14% of patients with MEN 2A had C-cell hyperplasia without invasive disease. Nodal metastases were found less frequently in MEN 2A (14%) than MEN 2B (38%), and biochemical cure was achieved in 56% of patients with MEN 2A compared with none in patients with MEN 2B. Among patients with MEN 2A the occurrence of invasive carcinoma increased with age (p = 0.0003); 40% of patients for less than 5 years had invasive MTC compared with 100% at more than 20 years. Cause-specific mortality among patients with MEN and invasive tumors at 6, 12, and 18 years was 2%, 4%, and 7%, respectively, lower than that of patients with sporadic MTC (12%, 17%, and 23%, respectively) treated during the same time period (p = 0.028). CONCLUSIONS: Intensive biochemical screening of MEN 2 kindreds for MTC can result in detection of early disease and a significant prospect of surgical cure. Genetic testing promises additional benefits through more reliable detection of preinvasive disease, allowing prophylactic thyroidectomy in infancy. In MEN 2B, MTC is considerably more aggressive than in MEN 2A. A policy of routine thyroidectomy in infants with MEN 2B, regardless of serum calcitonin levels, is justified.
Adolescent↗