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PubMed2004

Modified TC for MICA offenders: crime outcomes.

The study randomly assigned male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders to either modified therapeutic community (MTC) or mental health (MH) treatment programs. On their release from prison, MICA inmates who completed the prison MTC program could enter the MTC aftercare program. The results, obtained from an intent-to-treat analysis of all study entries, showed that inmates randomized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group. The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes (i.e. any criminal activity, and alcohol or drug related criminal activity) are consistent and significant, and persist after an examination of various threats to validity (e.g. initial motivation, duration of treatment, exposure to risk). This study provides some support for the effectiveness of the prison TC only condition. The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders, although qualified by the possibility that selection bias (i.e. differences in motivation on entry into aftercare) may be operating. Nevertheless, given the available evidence and the need for effective programming for MICA offenders, program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders.

Adult↗
PubMed2002

Combining radioimmunotherapy and chemotherapy for treatment of medullary thyroid carcinoma: effectiveness of dacarbazine.

BACKGROUND: To enhance the efficacy of chemotherapy for medullary thyroid carcinoma (MTC), we evaluated the effect of combining radioimmunotherapy (RAIT) with 90Y-anticarcinoembryonic antigen (CEA) monoclonal antibody MN-14 and chemotherapy in nude mice bearing human MTC xenografts. A preliminary study evaluated doxorubicin, dacarbazine (DTIC), cyclophosphamide, and vincristine, singly and in combination, for their effect on the growth of MTC xenografts (TT) in nude mice. Given individually, DTIC yielded the most effective tumor growth inhibition, delaying the mean time to doubling from 1 week for untreated tumor-bearing mice to 7.5 weeks. Administering either the 4 drugs in combination or a 2-drug combination comprised of doxorubicin and DTIC significantly improved the efficacy compared with any single drug alone, increasing the mean doubling time to 10-12 weeks. METHODS: Drug doses were selected to conform to the doses of each drug given clinically. For the combined modality therapy, administration of 90Y-labeled anti-CEA monoclonal antibody MN-14 to nude mice bearing established TT tumors was followed by various chemotherapy regimens initiated 24 hours after RAIT. Chemotherapy protocols combined with RAIT included doxorubicin or DTIC alone and in combination, and the doxorubicin, DTIC, cyclophosphamide, and vincristine 4-drug protocol. Tumor volumes were measured weekly, and toxicity was evaluated by measuring blood counts and body weight. RESULTS: Combinations of RAIT and chemotherapy with DTIC or RAIT and chemotherapy with the drug combinations were found to augment the antitumor effects of RAIT or chemotherapy alone, without a significant increase in toxicity. The mean tumor volume doubling times were increased up to 100% compared with the results of chemotherapy alone. No significant differences in tumor growth were observed between the RAIT plus DTIC protocol and the RAIT plus two- or four-drug protocols. CONCLUSIONS: The superiority of the combined modality treatment argues for the integration of RAIT into chemotherapeutic regimens for MTC treatment. Clinical trials are needed to assess these principles in MTC patients.

Animals↗
PubMed1995

Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin alpha M290 beta 7 (alpha E beta 7).

The integrin alpha M290 beta 7 on the surface of a T cell hybridoma, MTC-1, mediated adhesion of these cells to the mouse epithelial cell line CMT93. This interaction was critically dependent on the presence of divalent cations; Mn2+ strongly promoted adhesion, Ca2+ was ineffective and Mg2+ gave intermediate results. Antibodies to molecules on the surface of CMT93 cells were tested for inhibition of adhesion. One monoclonal antibody (mAb) against E-cadherin, ECCD-2, was found to have significant inhibitory activity. Other mAb to E-cadherin and antibodies to other molecules had no effect. To show that inhibition by ECCD-2 was specific for adhesion mediated by alpha M290 beta 7, MTC-1 cells were induced to adhere to CMT93 via the LFA-1/ICAM-1 pathway. For this purpose, the epithelial cells were treated with interferon-gamma and tumor necrosis factor-alpha to induce ICAM-1 expression and, in addition, alpha M290 beta 7 on MTC-1 cells was down-regulated by culturing the cells in the absence of transforming growth factor beta. Under these circumstances adhesion of MTC-1 cells to CMT93 was inhibited by an antibody to LFA-1 but not by ECCD-2. Transfection of mouse L cells with cDNA for mouse E-cadherin enabled MTC-1 cells to adhere to them through the alpha M290 beta 7 integrin; this interaction was inhibited both by ECCD-2 and by blocking antibody against the integrin. These data strongly suggest that E-cadherin is a principal ligand for alpha M290 beta 7.

Animals↗
PubMedDate not supplied

Magnetization transfer imaging with pulsed off-resonance saturation: variation in contrast with saturation duty cycle.

Magnetization transfer contrast (MTC) can be generated in magnetic resonance images of water-containing macromolecular structures. Results obtained with the pulsed off-resonance saturation technique for achieving MTC are presented, allowing comparison of this technique with others. The magnetization transfer effect is demonstrated in newborn piglet brain and bovine muscle tissue, as well as in human subjects. MTC increases nonlinearly with the duty cycle of the off-resonance irradiation, approaching a maximum value corresponding to continuous irradiation. However, approximately half of the available contrast can be obtained at a given saturation offset frequency, with 16% irradiation duty cycle. Examples of MTC in various human tissues demonstrate the specificity of this technique at power levels within U.S. Food and Drug Administration guidelines. Plots of MTC versus the irradiation offset frequency demonstrate the effects of magnetization transfer and are compared with the curve generated by a control phantom that does not show magnetization transfer. Magnetization transfer imaging with pulsed off-resonance saturation is effective and easily implemented and may be useful in the investigation of saturation transfer phenomena in tissue.

Animals↗
PubMedDate not supplied

Incidental magnetization transfer contrast in fast spin-echo imaging of cartilage.

In this article, the authors illustrate the contributions of incidental magnetization transfer contrast (MTC) to the signal characteristics of patellar cartilage on routine, multiplanar fast spin-echo (FSE) images. Incidental MTC diminishes the signal of patellar cartilage by 30% on routine FSE scans. Spectral fat saturation does not significantly increase incidental MTC on multislice FSE acquisitions. By increasing the contrast between synovial fluid and patellar cartilage, incidental MTC may account for greater conspicuousness of chondromalacia on FSE as compared to conventional spin-echo images. Incidental MTC may also alter or obscure the normal, laminar appearance of hyaline cartilage on short-TE, FSE images.

Cartilage, Articular↗
PubMed2005

Preoperative diagnosis of medullary thyroid carcinoma: fine needle aspiration cytology as compared with serum calcitonin measurement.

BACKGROUND AND OBJECTIVES: Preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC) has mainly relied on fine needle aspiration cytology (FNAC). The present study aimed to compare the sensitivity of this technique with serum calcitonin (CT) measurement and to assess the therapeutic implications of an inadequate preoperative diagnosis. METHODS: We reviewed the clinical records of 91 MTC patients treated and/or followed at our institution between January 1990 and December 2003. RESULTS: After revision of clinical records, 77 individuals were considered eligible for the study. FNAC was performed in 67 patients (87%) with a sensitivity of 63%; serum CT was measured in 56 patients (73%) with a sensitivity of 98%. Both FNAC and serum CT were assessed in 51 patients (66%). FNAC detected only 74.5% of MTCs suspected by elevated serum CT. Among patients with a cytological diagnosis of MTC, total thyroidectomy (TT) was performed in 95% of patients. Among patients without a cytological diagnosis of MTC, TT was performed in 83% of patients in whom serum CT was evaluated prior to surgery whereas it was performed in only 46% of patients in whom CT evaluation was lacking. CONCLUSIONS: Despite the higher sensitivity of serum CT measurement, as compared with FNAC to diagnose MTC (98% vs. 63%), only 9% of patients might have escaped to surgery based on FNAC results. However, indication for surgery based on suspicious FNAC may not alert the surgeon for the need of a TT and exploration of nodes at least in the central compartment.

Adult↗
PubMed1997

Dispersion in magnetization transfer contrast at a given specific absorption rate due to variations of RF pulse parameters in the magnetization transfer preparation.

The effects of RF pulse parameters on magnetization transfer contrast (MTC) were investigated using a magnetization prepared segmented fast gradient echo sequence. MTC was found not to be uniquely determined by the specific absorption rate (SAR). RF pulse parameters (RF amplitude, number of RF pulses and RF duration) also affect MTC. There can be 40% variation in MTC due to differences in RF parameters at SAR = 1 W/kg for a 70-kg subject. Increasing the number of RF pulses is a more efficient way to increase MTC than increasing RF amplitude. This phenomenon is likely caused by the fact that the time scale for magnetization transfer between the free and restricted proton pools is on the same order or longer than the duration of the MT pulse. Accordingly, increase in the MT pulse duration by increasing the number of RF pulses in the MT pulse allows more effective magnetization transfer. Such information can be used as a guide to select RF pulse parameters for a magnetization transfer (MT) pulse. An off-resonance MT pulse designed under this guide for coronary MR angiography improved the depiction of distal vessels.

Animals↗
PubMed1995

Calcitonin secretion, C cell differentiation and proliferation during the spontaneous development of murine medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC), a C cell neoplasm, synthesizes large amounts of calcitonin (CT), its biological marker. However, in some cases with a poor prognosis, MTC is associated with low basal CT levels owing to a decrease in the thyroid CT content. Using a murine model of human MTC, we studied the relationships between CT biosynthesis, C cell proliferation, and the circulating CT level during MTC progression. Cell proliferation was revealed by autoradiography of radioactive thymidine incorporation in dividing nuclei, after CT or CT mRNA detection by immunocytochemistry (ICC) or in situ hybridization (ISH). All rat thyroids showed a severe hyperplasia of C cells containing significant amounts of CT and CT mRNA, and a very low mitotic index. Tumours were found in 68% of the thyroids. In the strongly immunoreactive small nodules (ICC+), many labelled nuclei were observed. Subsequently some nodular cells, still containing detectable CT mRNA (ISH+), were not detected by immunocytochemistry (ICC-) owing to a dramatic decrease in secretory granules. Their mitotic index increased, and a rise of the basal CT plasma level was noted. These ISH+, ICC- tumour MTC cells represent a modified aggressive tumour C cell population exhibiting an increased ability to proliferate and were detected by the rise in the basal circulating CT level.

Animals↗
PubMed1984

Importance of early diagnosis and follow-up in multiple endocrine neoplasia (MEN II B).

Three patients with a sporadic form of multiple endocrine neoplasia (MEN) IIb are presented. MEN IIb is the association of medullary carcinoma of the thyroid (MTC), pheochromocytoma and multiple mucosal neuromata. The age at diagnosis and primary therapy of MTC was relatively late (8, 16, 18 years) although thyroid enlargement (two cases), typical marfanoid habitus (two cases) or multiple mucosal neuromata (one case) had been evident since early childhood. The diagnosis was confirmed by measurements of tumour markers like calcitonin (CT) and carcinoembryonic antigen (CEA) for MTC, measurements of vanillylmandelic acid for pheochromocytoma, evaluation of the thyroid gland by sonography, scintigraphy and fine needle biopsy, and investigation of the adrenals by computer tomography and meta-(I-131) iodobenzylguanidine (I-131-MIBG) scintigraphy. After surgical treatment determinations of tumour markers confirmed relapses of MTC in all cases. Early diagnosis of MEN IIb, which could be made by recognition of the typical clinical appearance, is of special importance because of the poor prognosis of MTC.

Adolescent↗
PubMed1990

The diagnostic and therapeutic utility of radioiodinated metaiodobenzylguanidine (MIBG). 5 years of experience.

The authors' experience of more than 5 years in the diagnostic and therapeutic use of radioiodinated MIBG in neural crest tumors is reported. 123I/131I-MIBG scintigraphy was performed in 158 patients: 75 suspected (24 proven) pheochromocytomas (pheos), 43 neuroblastomas (NB), 20 medullary thyroid carcinomas (MTC), 6 ganglioneuromas, 5 carcinoids and 1 insulinoma. Eight cases of tumors not originating from the neural crest were also investigated. The diagnostic sensitivity of the method was above 90% both in pheos and NB (primary tumors and bone metastases). The examination was less effective in localizing MTC (sensitivity = 64.4% in primary or residual/recurrent tumors). The scintigraphic outcome was negative in ganglioneuromas, carcinoids and insulinoma. Specificity was very high (greater than 95%), and no false positive results were found in tumors not deriving from the neural crest. 131I-MIBG treatment was administered to four patients with malignant pheo, nine with NB and four with MTC. Therapy resulted in a complete response in one pheo, two NB and one MTC treated after surgery or at diagnosis (one NB); it gave partial response and prolonged remission in five advanced cases (one pheo, two NB and two MTC); it resulted in temporary stabilization of the disease in one pheo and two NBs; it was ineffective in four cases.

3-Iodobenzylguanidine↗
PubMed1987

Investigations on the possible involvement of the dopaminergic system in the modulation of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa: a coupled morphometric and biochemical study.

The effects of metoclopramide (MTC) and bromocriptine (BRC) (two drugs which act as antagonist and agonist of DOPA-receptors, respectively) on the zona glomerulosa of dexamethasone/ACTH-treated rats were investigated by coupled biochemical and morphometric techniques. Short-term (1-h) MTC administration significantly increased the plasma concentration of aldosterone, while long-term (7-day) MTC administration, as well as short- and long-term treatment with BRC did not cause any apparent change. Long-term MTC administration was found to significantly potentiate both the rise in the plasma level of aldosterone and the hypertrophy of the zona glomerulosa and its parenchymal cells induced by a prolonged treatment with angiotensin II (AII), but not those evoked by a chronic sodium deprivation alone or combined with AII infusion. Long-term BRC administration notably counteracted the effects of sodium restriction (coupled or not with AII infusion), but not those induced by the administration of AII alone. Long-term MTC administration partially reversed both the lowering of the plasma concentration of aldosterone and the atrophy of the zona glomerulosa and its parenchymal cells caused by a prolonged sodium-loading (combined or not with captopril infusion), but not those produced by the administration of captopril alone. On the other hand, long-term BRC treatment induced a further significant reduction in the blood level of aldosterone and the volume of zona glomerulosa and its cells only in captopril-treated animals. These findings are consistent with the view that the dopaminergic system exerts a maximal tonic inhibitory effect not only on the secretory activity, but also on the growth and steroidogenic capacity of the rat zona glomerulosa. Furthermore, they suggest that the activity of the dopaminergic system is in turn controlled by the sodium balance, being almost completely suppressed by a prolonged sodium deprivation.

Adrenal Cortex↗
PubMed1994

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma.

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n = 57) and hereditary (n = 25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P < 0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P < 0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.

Adolescent↗
PubMed1992

Blood group antigen expression in medullary carcinoma of the thyroid. An immunohistochemical study on the occurrence of type 1 chain-derived antigens.

Using monoclonal antibodies (MoABs) against blood group determinants and related carbohydrate sequences, it is now possible to clarify their carcinoma-associated modulation at a molecular level. In the present study a panel of MoABs against different type 1 chain derived blood group antigens, comprising A, B, H type 1, Le(a), sialyl-Le(a) (CA 19-9), sialyl type 1 structure (CA 50), and Le(b) was used to investigate their immunoreactivity in 38 medullary carcinomas of the thyroid (MTC) and in normal thyroid tissue. The antigens were not expressed in normal follicular or C-cells but were expressed to a various extent in MTC. The studies revealed some characteristic anomalies in the frequency and patterns of tumor-associated antigen expression. The MoAB C 50 stained 32 of the 38 tumors, H type 1 (Le(d)) was demonstrated in 21 and the Le(b) antigen in 27. The Le(a)- and the A antigen were detected in 10 and 12 tumors and the B antigen in one. From the results some rules about the pathways for tumor-associated re-expression of these antigens can be deduced. Le(a) antigen expression was significantly correlated with the CA 50 and Le(b) antigens. The significant relation observed between A-, H1-, and Le(b) antigen formation in MTC suggests the existence of a carcinoma-associated fucosyltransferase committing the type 1 precursor chain along the H1-antigen pathway, and by further glycosylation to an A-, B-, or a Le(b) antigen. Comparative studies of tumor-associated H type 1 and H type 2 antigen expression revealed that H type 2 antigen synthesis was significantly related to a blood type 0 in the host. On the other hand, H1 antigen reactivity was independent of the AB0 blood type of the hosts and was also detected in H type 2 antigen-negative tumors. These findings support the proposal that even in tumor tissue, H antigen expression is still determined by the interaction of at least two different genes. Despite the occurrence of the precursor substance (CA 50) and the formation of the Le(a)- and Le(b) antigens, indicating the presence of a alpha 1,4-fucosyl-transferase (Lewis-enzyme), only two tumors showed the formation of CA 19-9. In conclusion, the investigations demonstrated the dominant re-expression of three type 1 chain-derived structures in MTC, namely H type 1, Le(b), and CA 50. These findings support the general concept demonstrated in other carcinomas, that fucosyl- and sialyltransferases are preferentially activated in MTC.(ABSTRACT TRUNCATED AT 400 WORDS)

ABO Blood-Group System↗
PubMed2002

The finding of a somaticdeletion in RET exon 15 clarified the sporadic nature of amedullary thyroid carcinoma suspected to be familial.

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between both is important for future clinical management. We report a family initially described as a familial MTC by pentagastrin stimulation test and clinical outcome, in which we found a 12 bp deletion within the catalytic domain of the protooncogene RET in the index case tumor alone. Linkage study suggests that it is a sporadic MTC. Therefore, in view of these results, in kindred with just one MTC case, borderline pentagastrin test values must be carefully assessed. In addition, this and other mutations can help us to understand some features about domains that play an important role in the normal function of this tyrosine kinase receptor and involved in MTC.

Adult↗
PubMed1987

Human medullary thyroid carcinoma in tissue culture; secretion of calcitonin and carcinoembryonic antigen.

Monolayer cultures of medullary thyroid carcinoma (MTC) cells were prepared from 5 patients with familial and 4 with sporadic MTC. Basal calcitonin (CT) release decreased rapidly during 17 days in culture. Addition of extra calcium (2 mmol/l) or dibutyryl cyclic AMP (dBcAMP, 3 mmol/l) increased CT release in all investigated cultures (p less than 0.01). No significant differences were observed between cell suspensions prepared from familial and those from sporadic MTC. Carcinoembryonic antigen (CEA) was found in 3 out of 5 MTC cell suspensions from patients with familial tumors and in 2 out of 2 sporadic tumors. Only two cultures secreted measurable amounts of CEA, which decreased with culture time but at a much slower rate than that of CT release. CEA release was not affected by the addition of calcium and dBcAMP. This study shows an absent relation between basal and stimulated CT and CEA release by cultured MTC cells.

Bucladesine↗
PubMed1992

Evaluation of sensitive PDN-21 (katacalcin) determination as tumor marker in medullary thyroid carcinoma.

PDN-21 (katacalcin), a peptide from the calcitonin (CT) gene, was measured in plasma from healthy persons and patients with medullary thyroid carcinoma (MTC). PDN-21 was detectable (greater than or equal to 10 ng/l) in 73% of normal persons (n = 40). In 17 normal persons with undetectable basal plasma levels, PDN-21 became detectable (greater than or equal to 10 ng/l) by stimulation with iv pentagastrin in 7 cases. Basal levels were more often detectable in men than in women. In 65 patients with MTC, PDN-21 levels were highly correlated with CT levels as determined by an "in house" RIA (r = 0.99); the mean ratio of CT/PDN-21, on a molar base, was 0.96 +/- 0.33 over the entire range. In iv stimulation tests with pentagastrin, PDN-21 and CT showed good parallelism (mean ratio of CT/PDN-21: 1.1 +/- 0.62); in MTC patients with normal basal levels, however, peak to basal ratios during iv pentagastrin testing were higher for PDN-21 than for CT, due to the more sensitive PDN-21 assay. In a selective venous catheter study of a patient with MTC, the mean CT/PDN-21 ratio for all samples was 1.04 +/- 0.12, but the peak to peripheral levels were higher for PDN-21 (4.1-fold) than for CT (2.8-fold). In conclusion, determination of PDN-21 by RIA is equivalent to determination of CT in diagnosing MTC patients. In few patients, it might be even slightly more sensitive. PDN-21 should be determined in all cases with borderline CT results.

Biomarkers, Tumor↗
PubMed1997

The value of new MRI techniques in adrenoleukodystrophy.

PURPOSE: To evaluate the significance of new techniques in MRI examinations of the brain in children with X-linked adrenoleukodystrophy (ALD). MATERIALS AND METHODS: Five patients aged between 2 and 15 years with childhood ALD were examined with MRI. Following conventional spin-echo (CSE) sequence, a fast spin-echo (FSE) sequence with T2 contrast was performed in four patients, an FSE turbo-inversion-recovery (TIR) sequence in two, magnetization transfer contrast (MTC) imaging in two, and localized proton spectroscopy (MRS) in four patients. RESULTS: FSE compared favorably with CSE with a time saving of 70%. On TIR images the contrast between normal and demyelinated white matter was greater than on CSE and FSE images. Calculated MTC values revealed a severe MTC loss within the demyelinated regions and a moderate reduction in the border zones. In this way, calculation of MTC might be useful to differentiate between edematous changes and areas of irreversible demyelination. MRS revealed a reduction in N-acetylaspartate and an elevation in choline (Cho). The degree of MRS changes paralleled the severity of demyelination. A Cho elevation may precede visible demyelination on T2-weighted images. CONCLUSIONS: T2-weighted FSE sequences can replace CSE without any disadvantages and with effective time saving. The indication for MTC imaging and MRS in children with ALD is not yet finally defined. These new techniques may reveal the earliest signs of cerebral involvement or of disease progression, a matter of great importance in selecting the optimal therapeutic approach.

Adolescent↗
PubMed2002

Surgical strategy in a kindred with a rare RET protooncogene mutation of variable penetrance with regard to multiple endocrine neoplasia.

Prophylactic thyroidectomy is recommended for carriers of RET protooncogene mutations owing to their nearly complete penetrance for medullary thyroid carcinoma (MTC). However, this guideline is challenged by mutations exhibiting variable penetrance of C-cell pathology. A 38-year-old woman presented with pathologic basal and pentagastrin-stimulated calcitonin levels. Genetic analysis revealed a heterozygous RET protooncogene germline mutation in codon 791 (exon 13) (TAT(Tyr)-->TTT(Phe)), followed by thyroidectomy and systematic central lymph node dissection. Histology showed C-cell hyperplasia (CCH) only. Three additional carriers were identified among family members. The 71-year-old father refused surgery despite pathologic calcitonin levels. The index patient's 37-year-old sister had normal basal and stimulated calcitonin levels, and her 6-year-old son had a 10-fold rise of calcitonin after pentagastrin stimulation. Both patients underwent the same operation as the index patient. The sister had 25 hyperplastic C-cells, but the her son had extensive CCH without MTC. The eldest uncle of the index patient had died of metastatic MTC at the age of 52 with unknown carrier status. Despite variable penetrance, each carrier of a RET protooncogene germline mutation should undergo thyroidectomy, even if basal and stimulated calcitonin levels are normal because at present no test can exclude or predict the age of development of MTC. Moreover, pathologic calcitonin levels cannot differentiate between CCH and MTC. Central lymph node dissection is recommended, as lymph node metastases occur early, significantly worsening the prognosis.

Adult↗