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PubMed2005

Iodine 123 metaiodobenzylguanidine radio-guided navigation surgery for recurrent medullary thyroid carcinoma in a girl with multiple endocrine neoplasia type 2B.

Multiple endocrine neoplasia type 2B (MEN 2B) is an inherited cancerous syndrome characterized by medullary thyroid carcinoma (MTC), adrenal pheochromocytoma, marfanoid habitus, and enteric ganglioneuromatosis. In this syndrome, a high frequency of persistent elevation of the serum calcitonin level, a sensitive marker for MTC, after total thyroidectomy has been reported, and the prognosis of such patients depends upon complete resection of recurrent MTC by repeated surgery. The authors performed iodine 123 metaiodobenzylguanidine ((123)I-MIBG) radio-guided navigation surgery for recurrent MTC in a 14-year-old girl with MEN 2B. She had undergone 4 neck operations, including total thyroidectomy at the age of 7 years. An intravenous injection of 100 MBq (123)I-MIBG was followed by the fifth surgery. At surgery, the cervical and upper mediastinal areas were filled with adhesional scar tissue, in which a gamma-scintillation probe conducted hot spots of isotope uptake by cancerous cells. Histopathology of resected specimens showed scattered nests of MTC cells corresponding to gamma-scintillation counts. Intraoperative (123)I-MIBG scanning is of substantial benefit for children with MEN 2B undergoing surgery for recurrent MTC.

3-Iodobenzylguanidine↗
PubMed2006

Study of the gyrB gene polymorphism as a tool to differentiate among Mycobacterium tuberculosis complex subspecies further underlines the older evolutionary age of 'Mycobacterium canettii'.

The present investigation evaluated the PCR-restriction fragment length polymorphism (RFLP) analysis of hsp65 and gyrB targets for differentiation of the species within the Mycobacterium tuberculosis complex (MTC) both by including new restriction enzymes and previously unstudied species. The hsp65 restriction analysis using HhaI resulted in a characteristic 'Mycobacterium canettii' pattern. A study of the gyrB gene polymorphism using TaqIalpha and HinfI allowed the initial division of MTC into two major groups, one consisting of M. tuberculosis and 'M. canettii' as opposed to another single group with other species. Three different patterns were observed with RsaI, the first characteristic of Mycobacterium microti, the second with Mycobacterium bovis, M. bovis BCG and Mycobacterium caprae (M. caprae was easily separated from M. bovis, and M. bovis BCG by SacII digestion), and the third with M. tuberculosis, 'M. canettii', Mycobacterium africanum, Mycobacterium pinnipedii, and the dassie bacillus. Although further discrimination within the last group was not obtained using additional restriction enzymes, the HaeIII and RsaI digestions highlighted an important gyrB polymorphism among 'M. canettii' strains. A study of the single nucleotide polymorphisms (SNP) within the gyrB by sequence analysis not only confirmed the results of the restriction analysis, but showed further differences among 'M. canettii' isolates that were not picked up using the existing battery of restriction enzymes. As many as 11 different SNPs were identified in the collection of eight 'M. canettii' isolates studied. Considering that gyrB variability among MTC member species other than 'M. canettii' is as restricted as hsp65 variability among MTC, our data corroborate a recent proposition that the 'M. canettii' group is evolutionary much older than the other MTC members. In conclusion, gyrB PCR-RFLP is a simple and rapid low-cost method that combined with phenotypic characteristics, may be helpful to differentiate most of the subspecies within the MTC.

Bacterial Typing Techniques↗
PubMed1997

Advances and controversies in the diagnosis and management of medullary thyroid carcinoma.

Recent advances in the diagnosis and treatment of medullary thyroid carcinoma (MTC) have been significant, but some issues remain controversial. MTC may occur either as a hereditary or a nonhereditary entity. Hereditary MTC can occur either alone--familial MTC (FMTC)--or as the thyroid manifestation of multiple endocrine neoplasia type 2 (MEN 2) syndromes (MEN 2A and MEN 2B). These hereditary disorders are due to germline mutations in the RET proto-oncogene. Early diagnosis and treatment considerably improve the prognosis in patients with MTC. Genetic testing can identify almost all affected individuals with hereditary disease and permits early thyroidectomy in gene carriers. Plasma CT is an excellent marker for postoperative follow-up. Imaging studies help delineate recurrent or metastatic lesions. Treatment of recurrent or metastatic disease is primarily surgical, including either palliative or microdissective surgery. Radiation therapy is reserved for skeletal metastasis or nonresectable metastatic MTC. Efficacy of current chemotherapy programs is not well established. Overall, the 10-year survival rates are approximately 65%.

Carcinoma, Medullary↗
PubMed2004

The oncogenic activity of RET point mutants for follicular thyroid cells may account for the occurrence of papillary thyroid carcinoma in patients affected by familial medullary thyroid carcinoma.

Activating germ-line point mutations in the RET receptor are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma (MTC), whereas somatic RET rearrangements are prevalent in papillary thyroid carcinomas (PTCs). Some rare kindreds, carrying point mutations in RET, are affected by both cancer types, suggesting that, under specific circumstances, point mutations in RET can drive the generation of PTC. Here we describe a family whose siblings, affected by both PTC and MTC, carried a germ-line point mutation in the RET extracellular domain, converting cysteine 634 into serine. We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. We show that the various RET point mutants, but not wild-type RET, scored constitutive kinase activity and exerted mitogenic effects for thyroid PC Cl 3 cells, albeit at significantly lower levels compared to RET/PTC1. The low mitogenic activity of RET point mutants paralleled their reduced kinase activity compared to RET/PTC. Furthermore, RET point mutants maintained a protein domain, the intracellular juxtamembrane domain, that exerted negative effects on the mitogenic activity. In conclusion, RET point mutants can behave as dominant oncogenes for thyroid follicular cells. Their transforming activity, however, is rather modest, providing a possible explanation for the rare association of MTC with PTC.

Adenocarcinoma, Follicular↗
PubMed2000

The effects of mitomycin-C and stenting on airway wound healing after laryngotracheal reconstruction in a pig model.

OBJECTIVE: To assess the effects of mitomycin-C (MTC) and endoscopic stenting on airway wound healing after laryngotracheal reconstruction. DESIGN: A prospective, blinded, randomized controlled animal study. SUBJECTS: Twenty-six domestic pigs (Sus scrofula) divided into four groups. INTERVENTIONS: Each animal underwent single-stage laryngotracheal reconstruction (SSLTR) with auricular cartilage grafts and stenting. Group 1 animals were sacrificed on postoperative day 3, and group 2 animals on postoperative day 7. On postoperative day 7, groups 3 and 4 underwent endoscopy, stent removal, and application of MTC (0.5 mg/ml) or placebo (normal saline). Group 3 animals were sacrificed on postoperative day 14, group 4 animals on day 21. Two additional animals from each experimental group were prepared for election microscopy studies. Segments of reconstructed airway were evaluated grossly and histologically for all animals. Additional tonometric evaluation was performed on two stents to determine their compressive strength. MAIN OUTCOME MEASURES: Healing, reepithelization, graft incorporation, and airway diameter. RESULTS: Two-thirds of the animals demonstrated some degree of stent collapse on endoscopy. Granulation tissue formation was seen in all animals, and resolved with stent removal. No animal experienced airway compromise due to granulation tissue formation. Stenting was seen to induce a submucosal fibroproliferative response and scarring, with loss of normal glandular architecture, in all animals. MTC did not affect the acute inflammatory response, reepithelization of the graft site, or formation of the subepithelial fibroproliferative response. MTC treated animals, however, demonstrated better graft incorporation with fibrocartilage proliferation of the graft. Untreated animals demonstrated liquefactive necrosis of the graft, without evidence of neochondrification of the graft. CONCLUSIONS: The pig airway is an adequate model of wound healing following SSLTR and stenting. Metallic ballon expandable stents can be successfully used following SSLTR, allowing for immediate postoperative extubation. However, the formation of a submucosal fibroproliferative response and mucosal scarring seen in our study raises some concerns with the current stent design. Before stenting is widely clinically applied, the optimum stent design needs to be developed. Finally, MTC seems to prevent the liquefactive necrosis of SSLTR grafts and promote neochondrification, allowing improved graft incorporation. Further studies are needed to asses the long-term effects of MTC on healing and restenosis, and its effects on cartilage growth and formation, following SSLTR.

Animals↗
PubMed1995

Proliferative activity in C-cell hyperplasia and medullary thyroid carcinoma. Evaluation by PCNA immunohistochemistry and AgNORs staining.

C cell hyperplasia (CCH) is a preneoplastic lesion that precedes the development of medullary thyroid carcinoma (MTC) in familial cases. It has been hypothesized that CCH progressively acquires the neoplastic phenotype after presenting some genetic changes that involve oncogenes and tumor suppressor genes. The proliferative activity of nodular C cell hyperplasia (NCCH) and early MTC has been assessed by PCNA (Proliferating Cell Nuclear Antigen) immunohistochemistry and nucleolar organizer regions silver staining (AgNOR) in surgical specimens of seven patients with familial MTC. The ratios of PCNA-positive nuclei in NCCH (mean 1.2, range 0.2-4) were lower than in MTC (mean 2, range 1-7%). The AgNOR scores for NCCH (mean 1.53, range 1.10-1.90) were also lower than for MTC (mean 2.10, range 1.90-2.64). The results suggest that C cells progressively acquire a higher proliferative activity in agreement with the severity of the morphologic changes in the process of hyperplasia-neoplasia that leads to widely invasive MTC.

Adolescent↗
PubMed1992

Chromogranin A immunoreactivity compared with argyrophilia, calcitonin immunoreactivity, and amyloid as tumour markers in the histopathological diagnosis of medullary (C-cell) thyroid carcinoma.

Applying the WHO criteria for the histopathological diagnosis of medullary thyroid carcinoma (MTC)--as well as the criterion that a significant amount of argyrophil cells, amyloid deposits, or calcitonin (CT) immunoreactive cells shall be present--122 cases were identified from the files of the Swedish Cancer Registry. Both non-occult (n = 110) and "occult" (less than 1 cm in diameter) (n = 12) MTCs were included. Both primary tumours (n = 91) and metastatic lesions (n = 31) were investigated. The specimens available were all only conventionally formalin-fixed and paraffin-embedded. The presence of neoplastic cells immunoreactive with antisera against chromogranin A (Chr A) was compared with that of the other three MTC markers. Chr A immunoreactive cells were present in practically all the cases. Similar results were obtained when the argyrophil reaction alone and CT immunoreactivity alone were used as markers. When two of the three MTC markers were combined, it was found that virtually everyone of the 122 tumours could be identified as a MTC. In contrast, the presence of amyloid deposits was found to be a less constant MTC marker; whereas 94% of the primary tumours had amyloid deposits, they were present in only approximately 70% and 60% of the metastatic and "occult" tumours respectively. No differences in the staining reaction patterns were found between familial (n = 18) and the sporadic (n = 104) types of MTC.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1996

Multilocular thymic cysts associated with thymoma. A case report.

The association of multilocular thymic cysts (MTC) with thymoma is exceedingly rare, and the pathogenesis of this combination is controversial. We describe the case of a 42-year-old man with an anterior mediastinal mass found to contain MTC and thymoma. A multilocular cystic mass, measuring 13 x 6.5 x 2 cm, was found in the right lobe of the thymus, and contained a 4.7 x 2 cm thymoma in its center. Microscopic thymomas, lipomatously involuted remaining thymic tissue, and lymphoid follicles with germinal centers were found in the walls of MTC as well as in the left thymic lobe. Non-specific chronic inflammation was also present in the walls. In addition, microcysts, which were only found at the periphery of the thymoma and covered with epithelium, might have been formed secondarily by dilatation of the perivascular spaces and of Hassall's corpuscles. These findings suggest that a chronic inflammatory process was responsible for the early formation and enlargement of this patient's MTC, and that while the cavities of the MTC expanded to various degrees, the thymoma, which originated from one of the microscopic thymomas in the walls of MTC, increased in size, and grew to involve the remaining thymic tissue.

Adult↗
PubMed2002

Prophylactic thyroidectomy in MEN 2A syndrome: experience in a single center.

BACKGROUND: Genetic study of the RET proto-oncogene has modified the management, treatment, and prognosis of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia 2A (MEN 2A), for patients with less advanced tumor stages. Classically, the diagnosis was based on an increase in basal and poststimulus peak calcitonin (bCT and pCT). Prophylactic thyroidectomy, based on results of genetic testing, may reduce recurrences in MTC. STUDY DESIGN: Of 82 MTC (MEN 2A) patients genetically diagnosed and surgically treated at our center, 22 received a prophylactic thyroidectomy (RET +, bCT and pCT with normal values and asymptomatic). We analyzed age, gender, phenotype, RET mutation, cervical ultrasound, laboratory tests (bCT, pCT, and CEA), surgery, histologic data, TNM, and followup. RESULTS: The 22 patients belonged to 8 families with MTC (MEN 2A). Mean age was 15.2 years (range 5 to 36 years). The RET mutation in 21 patients was Cys-->Tyr and in the remaining patient both in codon 634 in exon 11. The median values of bCT and pCT were 38 pg/mL (range < 15 to 75 pg/mL) and 148.5 pg/mL (range < 15 to 250 pg/mL), respectively. Total thyroidectomy was performed in 8 patients (age < or = 10 years) and associated central neck dissection in 14 patients (age> 10 years). Histologic study showed 7 C-cell hyperplasias and 15 MTCs (8 bilateral); the median size was 0.2 cm (range < 0.1 to 0.7cm); 1 patient had metastatic adenopathies. According to TNM, 7 were stage 0, 14 were stage I, and 1 was stage III. Postsurgery bCT and pCT values were normal in all patients, with a curative rate of 100%. MTC patients compared with C-cell hyperplasia patients were older on average, had higher mean bCT, mean pCT, and mean CEA. CONCLUSIONS: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease and decreases recurrence rates. pCT values above the upper limit of normal may be markers for the presence of MTC and should be considered in selecting operative procedures for these patients.

Adolescent↗
PubMed2003

Segregation of the V804L mutation and S836S polymorphism of exon 14 of the RET gene in an extended kindred with familial medullary thyroid cancer.

In multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid cancer (FMTC), the majority of germline mutations are restricted to specific positions in exons 10 and 11 of the RET gene. However, germline mutations may very occasionally occur in other exons, including exon 14 of the RET gene. Interestingly, an increased frequency of a rare germline sequence variant of the RET exon 14, S836S, has been detected in patients with sporadic medullary thyroid cancer (MTC), and this variant has been proposed to play a role in the genesis of MTC and, perhaps, FMTC. In this study we report the segregation of a germline V804L mutation and a germline sequence variant S836S in exon 14 of the RET gene in an extended Hungarian FMTC kindred comprising 80 individuals of four generations. Molecular analysis of the RET gene was performed by direct DNA sequencing in 23 family members, of whom 12 had the V804L mutation, three had the V804L mutation and S836S polymorphism in separate alleles, and six had the S836S polymorphism, all in heterozygous forms. Two of the family members had neither mutation nor polymorphism of the RET gene. Three of the family members who had the V804L mutation and one member who could not be tested for mutation were operated for non-metastatic MTC, while one member with MTC who had the V804L mutation refused surgery. In all patients affected with MTC, the disease developed relatively late in life and never caused death. None of the other family members carrying the V804L mutation and/or the S836S polymorphism had clinical or biochemical evidence of MTC. These observations suggest that the co-existence of the V804L mutation and S836S polymorphism in separate alleles does not seem to aggravate the relatively low-risk disease phenotype characteristic in most patients with codon 804 mutations of the RET exon 14.

Carcinoma, Medullary↗
PubMed2002

Molecular and biochemical screening for the diagnosis and management of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A.

Patients with Multiple Endocrine Neoplasia (MEN) type 2A are at risk for early medullary thyroid carcinoma (MTC). We performed different screening tests for MTC--a recently reported biochemical screening test using omeprazole-induced calcitonin (CT) stimulation and DNA analysis--in fifteen members of two non-consanguineous Brazilian families with MEN 2A. RET proto-oncogene analysis was carried out by direct DNA sequencing of PCR-amplified products for exons 10 and 11. Family 1 showed a germline mutation (C634Y) in three individuals; a sister and a brother with symptomatic MTC; the former also presented with pheochromocytoma and hyperparathyroidism, and her son was a nine-year-old boy of previously unknown status. Family 2 showed the C634R mutation only in the index case, who presented with cutaneous lichen amyloidosis in addition to MTC, pheochromocytoma and hyperparathyroidism. Neither her parents nor her four brothers showed this genetic abnormality, suggesting a de novo RET proto-oncogene mutation in this patient. The controls and patients presented normal basal gastrin levels and a significant increase after omeprazole. Basal CT levels were elevated in patients with MTC and undetectable in control and asymptomatic family members. No subject showed any increase in CT levels after omeprazole treatment. In conclusion, the two most frequent RET proto-oncogene mutations in MEN 2A are present in Brazilian families. In addition, the specificity of basal and omeprazole-stimulated calcitonin is rather limited, and the efficacy of the omeprazole test still needs to be systematically examined. Therefore, RET proto-oncogene analysis must be the first choice for a screening procedure to identify gene carriers in MEN 2A family members and to permit early prophylactic treatment of MTC.

Adolescent↗
PubMed2004

Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter: German evidence-based consensus recommendation.

Serum calcitonin (CT) has become a very specific and sensitive marker for human medullary thyroid carcinoma (MTC), a neuroendocrine tumor affecting about 1 % of patients with nodular thyroid disease. MTC is characterized by early micrometastasis and a lack of curative non-surgical treatment, so that early diagnosis is desirable. Based on a systematic review of scientific evidence, we propose multidisciplinary consensus recommendations for the clinical use of CT in patients with nodular goiter. To exclude MTC, serum CT should be determined in patients with nodular thyroid disease, using a two-site CT immunoassay. If basal serum CT exceeds 10 pg/ml, CT should be analysed by pentagastrin stimulation testing, after renal insufficiency and proton pump inhibitor medication have been ruled out. As the risk for MTC is higher than 50 % in patients with stimulated CT values > 100 pg/ml, thyroidectomy is advised in these individuals. If stimulated CT exceeds 200 pg/ml, thyroidectomy and lymphadenectomy is strongly recommended. Pentagastrin-stimulated CT values < 100 pg/ml are associated with a low risk of MTC, or very rarely, non-metastasizing micro-MTC (size < 10 mm). Therefore, regular clinical and biochemical follow-up is the preferred treatment in such patients, unless thyroid malignancy is suspected otherwise.

Calcitonin↗
PubMed1997

[Mutations of ret-proto-oncogene in thyroid medullary carcinoma].

OBJECTIVE: To determine the importance of the molecular-genetic demonstration of germ-line mutation in the ret protooncogene for therapeutic measures in sporadic and hereditary medullary thyroid carcinoma (MTC). PATIENTS AND METHODS: Several molecular-genetic tests were performed on DNA of 35 families with hereditary and 81 patients with the sporadic form of MTC (isolation of genomic DNA; PCR amplification; DNA sequencing: demonstration of mutation in codon 918 with restriction enzyme FOK 1). RESULTS: A disease risk was demonstrated in 178 individuals among the 35 families, 159 of whom were investigated by molecular-genetic tests: 84 family members were found to be gene carriers. Germ-line mutation had already been suspected on clinical grounds in 76% of the carriers, 24% being discovered in a presymptomatic stage. Six children among the latter were treated prophylactically by thyroidectomy, histological evidence of C-cell hyperplasia being found in all of them, microcarcinomas in three of the older children. There were four patients among the non-carriers on whom thyroidectomy had been performed previously because of a false-positive pentagastrin-test; but germ-line mutation was now excluded. In one family, with familial MTC in two brothers, no mutation in ret-proto-oncogene has been demonstrated. The members of this family must now, as used to be routine, undergo a pentagastrin-test. Three of the 81 patients with "sporadic" MTC had a germ-line mutation, presumably a new one. CONCLUSION: Molecular-genetic tests have further improved the management of families with hereditary MTC and they thus take first place among essential diagnostic procedures. The diagnosis of sporadic MTC can be confirmed by excluding germ-line mutation in the ret-proto-oncogene.

Adolescent↗
PubMed2000

The helix-loop-helix transcription factor, Id-1, is overexpressed in medullary thyroid cancer.

BACKGROUND: The Id-1 helix-loop-helix protein inhibits differentiation and enhances cell proliferation. It is required for cell cycle progression. The Id-1 gene is highly expressed in a variety of tumor-derived cell lines. It increases after mitogen stimulation and is overexpressed in some human neoplasms. Therefore, we hypothesized that the Id-1 gene may play a role in medullary thyroid carcinogenesis. METHODS: The expression of the Id-1 protein in human medullary thyroid cancer (MTC) and the corresponding normal thyroid tissue was determined by Id-1 immunohistochemistry. In a human MTC cell line (TT), the effects of growth stimulation and redifferentiation on Id-1 expression were determined by Northern blot analysis. RESULTS: Id-1 immunostaining intensity in 9 MTC samples (6 sporadic, 2 familial, and 1 MEN 2A) was moderate to strong. However, it was absent or faint in the corresponding normal thyroid tissue. The Id-1 protein was significantly overexpressed in MTC compared with corresponding normal thyroid tissue on the basis of the percentage of positive cells and immunostaining intensity (P =.002). In the TT cell line, Id-1 messenger RNA (mRNA) expression was increased 4-fold after growth stimulation with serum. Phorbol ester (which induces redifferentiation in the TT cell line) downregulated Id-1 mRNA expression. CONCLUSIONS: Id-1 is overexpressed in MTC. The Id-1 gene may play a role in the regulation of MTC differentiation and proliferation.

Adult↗
PubMed2001

Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer.

Despite the fact that several recent studies report an expression of somatostatin receptors in nonmedullary thyroid cancer (non-MTC), there is still no consensus concerning the diagnostic and therapeutic usefulness of radionuclide-labeled somatostatin analogues in non-MTC. We present the results of 50 scintigraphic studies with (111)In-Pentetreotide ((111)In-P) in 48 patients with metastasizing non-MTC (n = 9 papillary, n = 9 follicular, n = 29 Hurthle cell, n = 1 insular carcinoma). The findings were compared with histology and with other imaging modalities. (111)In-P provided unequivocally positive results in 37 of 50 (74%) of the patients (27% in the 11 patients with current thyroglobulin levels <10 ng/mL and 85% in the patients with thyroglobulin >10 ng/mL). Histopathology demonstrated that maximal uptake was observed in Hurthle cell carcinoma (95% positive examinations if thyroglobulin exceeds 10 ng/mL). We also describe for the first time dosimetric and clinical data from the courses of 90Y-DOTATOC therapy in three patients with progressive, somatostatin-receptor-positive non-MTC (up to 9.3 GBq per 4 cycles). Tumor progression could not be stopped in any of the patients treated with 90Y-DOTATOC. We conclude that (111)In-P is a promising tool for whole-body diagnosis in nonradioiodine-accumulating non-MTC, especially in Hürthle cell cancer, and if 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is not available. Although the number of patients treated with 90Y-DOTATOC is still limited, our applied treatment protocol appears to be ineffective in metastasizing non-MTC.

Adult↗
PubMed1995

Evaluation of somatostatin as a plasma tumor marker in medullary thyroid carcinoma.

Somatostatin (SRIF) immunoreactivity has been frequently reported in tumor tissues of cell types, belonging to the APUD system, including medullary thyroid carcinoma (MTC). However, the value of SRIF as a plasma tumor marker for MTC is controversial. We have measured SRIF plasma levels in 35 patients with different stages of MTC to evaluate the use of SRIF as a plasma tumor marker compared to the current "gold standard" calcitonin (CT). The median SRIF value in healthy controls was 36.5 pg/mL, the upper limit of normal was defined at the controls. The median value was 28 pg/mL (p = 0.37, Mann-Whitney U test). Five patients in the control group and three in the MTC group had SRIF levels that exceed the 95th percentile. SRIF and CT levels correlated only weakly (0.38), as determined by the Spearman rank order correlation test. Pentagastrin stimulation led to a diagnostic increase in SRIF levels in only one of five MTC patients. During selective venous catheterization, diagnostic gradients for CT, allowing tumor localization, could be demonstrated, whereas measurement of SRIF levels did not aid in tumor detection. Although SRIF immunostaining may be valuable as an additional marker in the histochemical diagnosis of MTC, SRIF has no value as a plasma tumor marker in the diagnosis of this disease.

Adult↗
PubMed1995

Medullary thyroid carcinoma: recent advances and management update.

Medullary thyroid carcinoma (MTC) is a malignancy of the thyroid C-cells that comprises 5-10% of all thyroid cancers. MTC occurs in both sporadic and familial forms, the latter making up 25% of all MTCs and being comprised of three distinct syndromes--multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). To date, screening for MTC has been performed using the pentagastrin stimulation test, which is a provocative test for calcitonin release. Germline mutations in the RET protooncogene have been identified in families manifesting these syndromes and genetic screening of individuals at risk of one of these syndromes has become integral to their clinical management. The majority of the mutations associated with MEN 2A and FMTC are tightly clustered in a cysteine-rich region of the RET receptor. A single mutation associated with MEN 2B is in the the tyrosine kinase domain of the RET receptor. Somatic mutations have been identified in the tumor tissue of individuals with sporadic MTC and may prove to be helpful markers in discerning the hereditary or sporadic nature of the MTC. There is general agreement that the primary operation for MTC should include total thyroidectomy and central neck lymph node clearance. The role of microdissection for recurrent disease awaits longitudinal evaluation. External radiotherapy, radionuclide therapy, and chemotherapy may have a role in palliation, but have not been proven to have a curative value. Prognostic factors are discussed.

Animals↗
PubMed1998

Papillary thyroid carcinoma, parathyroid adenoma, and unexplained hypercalcitoninemia: an unusual presentation of multiple endocrine neoplasia type 2A?

Multiple endocrine neoplasia type 2 (MEN 2) is a rare syndrome of medullary thyroid carcinoma (MTC) with pheochromocytoma and/or primary hyperparathyroidism (PHP), usually due to multigland hyperplasia. MEN 2 is associated with several RET protooncogene mutations. A 61-year-old woman with a family history of RET-positive MTC presented with a solitary thyroid nodule. Fine-needle aspiration biopsy was suspicious for neoplasm. Biochemical studies revealed basal hypercalcitoninemia (116 pg/mL [normal <26]) and PHP (serum calcium, 10.9 mg/dL; intact PTH, 113.2 pg/mL [10.0-65.0]). Pheochromocytoma screening was negative. A provisional diagnosis of MEN 2 was made, but at surgery, a single parathyroid adenoma was resected and frozen sections of several lymph nodes revealed papillary thyroid carcinoma (PTC). A total thyroidectomy was performed. Final histological diagnosis was PTC and parathyroid adenoma with no evidence of MTC. Postoperatively, RET mutation testing was positive. The basal calcitonin (CT) fell to 25 pg/mL, but peaked at 935 (normal <105) after pentagastrin infusion, consistent with occult MTC. After radioiodine ablation, CT decreased further. Octreotide scanning was negative. Faced with PHP, a thyroid nodule, and a family history of MTC, clinicians tend to diagnose MEN 2. This patient had a single parathyroid adenoma and nonmedullary thyroid cancer, which the literature actually suggests to be an association more frequent than MEN 2. Yet, there remains compelling data in favor of occult MTC, leaving open the possibility of an MEN 2 variant with the rare association of PTC.

Adenoma↗