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PubMed2000

Thyroid suppression test with L-thyroxine and [99mTc] pertechnetate.

OBJECTIVE: The thyroid suppression test is still used in some centres as an adjunt in the diagnosis of autonomous functioning thyroid nodules. With the purpose of minimizing the disadvantages of the original T3 suppression test, we have evaluated the efficacy of a method using L-thyroxine as TSH suppression agent and [99 mTc] pertechnetate as radiopharmaceutical. DESIGN: Open nonrandomized prospective study MATERIALS AND METHODS: A control group of 15 normal volunteers (11 males, 4 females; 21-35 years, mean 26.4 years) and a patient group of 20 patients (18 females, 2 males; 27-83 years, mean 53.6 years) divided into 4 subgroups, were studied: 7 patients with autonomous functioning nontoxic nodules, 3 with autonomous functioning toxic nodules, 7 with Graves disease and 3 with nonautoimmune diffuse toxic goitre. Baseline thyroid uptake and imaging were begun 20 minutes after an intravenous injection of 370 MBq (10 mCi) of [99 mTc] pertechnetate. This was followed by a single daily intake of 2 microg/kg of L-thyroxine, for 10 days. Thyroid imaging and uptake were then repeated. RESULTS: In the control group [99 mTc] pertechnetate uptake after L-thyroxine suppression had a mean reduction of 75.8 +/- 7.69% (58-87%) in comparison to the baseline level. All subjects were euthyroid by clinical and laboratory criteria and none complained of side-effects, despite significant suppression of TSH levels. In the patient group, thyroid uptake after suppression decreased in 10 patients (maximum reduction 39%), was unchanged in 2 patients and increased in the remaining 8 patients. CONCLUSION: The method described was efficient for demonstration of autonomous thyroid tissue, since none of the patients showed significant reduction of thyroid uptake after L-thyroxine suppression compared with the control group. This test was as effective as the original T3 suppression test, but more convenient to the patient: no side-effects, ease of hormonal intake, low dosimetry and short stay in the nuclear medicine laboratory.

Adult↗
PubMed1998

Surgical management of patients with persistent or recurrent medullary thyroid cancer.

Residual or recurrent medullary thyroid carcinoma (MTC), manifested by elevated calcitonin levels, occurs commonly following primary treatment of MTC. Re-operation in appropriately selected patients is the only treatment modality which consistently and reliably reduces stimulated calcitonin levels, and results in excellent local disease control. We report improved results of surgical management of recurrent MTC in two consecutive series of patients. In our most recent series (1992-96), 38% of patients (17 out of 45) had normal postoperative stimulated calcitonin levels, compared to 28% (nine of 32) in our first series (1990-92). In the most recent series, only 13% (six of 45) of patients had no decrease in calcitonin levels following re-operation, compared to 31% (10 of 32) in our first series (P = 0.07, Fisher's exact test). This improvement has mainly occurred through better preoperative selection of patients, and the institution of routine laparoscopic liver examination preoperatively, which identified metastases in 10 patients, nine of whom had normal CT or MRI imaging.

Adolescent↗
PubMedDate not supplied

Kinetic modeling of continuous flow peritoneal dialysis.

Kinetic models have been derived for analysis of the effects on peritoneal urea clearance (Kp) of continuous single-pass flow of fresh peritoneal dialysate and continuous flow of peritoneal dialysate recirculating through an external dialyzer. Generalized solution of the models shows that both predict Kp to be a well-defined function of the peritoneal mass transfer coefficient (MTC) and the dialysance (D) of the external dialyzer, while the MTC is a function of the rate and distribution of dialysate flow. Thus the models should be useful to guide studies to optimize CFPD. Analysis of reported in vivo data indicate that with dialysate flow rate and D both in the range of 200 ml/min, MTC levels of 60-70 ml/min and Kp levels of 50 ml/min can be achieved. If the model predictions are verified in vivo, 8-hour overnight CFPD 6 nights/week could provide the average-size anephric patient a weekly stdKt/V of 3.2 which is competitive with daily hemodialysis. Kinetic modeling of ultrafiltration indicated ultrafiltration rates 0.2-0.3 L/hr should be achieved with 1.0-1.25% dextrose dialysate. The model shows average rates of glucose absorption can theoretically be reduced by 33% compared to CAPD with the same amount of fluid removal.

Absorption↗
PubMed1998

A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis.

The presence of germline and somatic mutations in the RET proto-oncogene (RET) in patients with hereditary and sporadic medullary thyroid carcinoma (MTC) may have important ramifications for patient management. It has been suggested that the presence of the mutation ATG-->ACG at codon 918 in sporadic MTC is associated with a worse prognosis, and hence the need for more aggressive surgical, or other, treatment. Since fine-needle aspiration biopsy (FNAB) is an important component of the preoperative management of patients with thyroid tumors, we developed a rapid (20-min) method that enables extraction of DNA from FNABs for RET mutation analysis. The method allows preoperative genetic analysis to aid in management of patients with MTC, and may be applied to other tumor types where a preoperative mutation analysis based on polymerase chain reaction amplification is desired.

Biopsy, Needle↗
PubMed2000

Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival.

AIMS: The aims of this study were to assess the long-term results of treatment of medullary thyroid carcinoma (MTC) and to define prognostic factors. METHODS: Retrospective analysis of all patients diagnosed with MTC between 1949 and 1998 and treated in our unit was carried out. RESULTS: One hundred and sixty-two patients (87 females, 75 males) were identified; 52 patients (32%) had familial disease. Median follow-up was 9 years (2-20 years). The majority of patients (90%) presented with a thyroid mass or enlarged neck nodes. Total/subtotal thyroidectomy was performed in 129/18 patients respectively; 45 patients also underwent neck dissection while 52 had simple nodal excision. External beam radiotherapy (RT) was given to 76 patients with advanced disease at presentation. Overall survival was 72% at 5 years and 56% at 10 years; case-specific survival was very similar. In multivariate analysis the factors which were significant predictors of survival were age at diagnosis, extent of nodal disease, extent of surgery and metastases at presentation. RT significantly reduced local relapse in patients with ipsilateral nodal disease. CONCLUSIONS: MTC may be associated with prolonged survival; the best prognosis occurs in young patients undergoing total thyroidectomy and neck dissection. External beam RT significantly reduces local relapse in patients with limited nodal disease.

Adolescent↗
PubMed2005

Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis: role of vascular endothelial growth factor.

BACKGROUND: During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids that cause epithelial-to-mesenchymal transition of mesothelial cells, fibrosis, and angiogenesis. Ultrafiltration failure is associated with high transport rates and increased vascular surface, indicating the implication of vascular endothelial growth factor (VEGF). Sources of VEGF in vivo in PD patients remain unclear. We analyzed the correlation between epithelial-to-mesenchymal transition of mesothelial cells and both VEGF level and peritoneal functional decline. METHODS: Effluent mesothelial cells were isolated from 37 PD patients and analyzed for mesenchymal conversion. Mass transfer coefficient for creatinine (Cr-MTC) was used to evaluate peritoneal function. VEGF concentration was measured by using standard procedures. Peritoneal biopsy specimens from 12 PD patients and 6 controls were analyzed immunohistochemically for VEGF and cytokeratin expression. RESULTS: Nonepithelioid mesothelial cells from effluent produced a greater amount of VEGF ex vivo than epithelial-like mesothelial cells (P < 0.001). Patients whose drainage contained nonepithelioid mesothelial cells had greater serum VEGF levels than those with epithelial-like mesothelial cells in their effluent (P < 0.01). VEGF production ex vivo by effluent mesothelial cells correlated with serum VEGF level (r = 0.6; P < 0.01). In addition, Cr-MTC correlated with VEGF levels in culture (r = 0.8; P < 0.001) and serum (r = 0.35; P < 0.05). Cr-MTC also was associated with mesothelial cell phenotype. VEGF expression in stromal cells, retaining mesothelial markers, was observed in peritoneal biopsy specimens from high-transporter patients. CONCLUSION: These results suggest that mesothelial cells that have undergone epithelial-to-mesenchymal transition are the main source of VEGF in PD patients and therefore may be responsible for a high peritoneal transport rate.

Adult↗
PubMed1998

Clinical usefulness of a new chemiluminescent two-site immunoassay for human calcitonin.

The introduction of two-site immunoassays has greatly improved the measurement of human calcitonin (CT). But even within the two-site assays differences in sensitivity and ease of performance are noted. We evaluated the clinical usefulness of a new sensitive chemiluminescence two-site immunoassay for CT (Nichols) in comparison to an established two-site elisa (Medgenix). The range of measurement spans from 0.7 to 2500 pg/ml after 4h incubation for the chemiluminescent assay, compared to 2.0 to 1000 pg/ml after overnight incubation for the elisa. We investigated 179 healthy subjects (55 males, 124 females) to assess the upper limit of normal for CT values obtained by the chemiluminescence assay, which was defined as the 95th percentile of the distribution. The values obtained were 6.55 pg/ml for males and 4.13 pg/ml for females (p < 0.0005, Mann Whitney test). After pentagastrin-stimulation of 19 healthy volunteers (9 male, 10 female), the upper limit of normal for pentagastrin-stimulated CT was found at 43.0 pg/ml for males and 36.8 pg/ml for females (p < 0.05, Mann Whitney test). CT values obtained in patients with proven medullary thyroid carcinoma (MTC) or in subjects with suspected familial disease were positively correlated between both two-site assays (rho 0.961, p < 0.0001, Spearman rank correlation). More importantly the results led to the same clinical decision (normal vs. elevated) in 92.5% (37 of 40) patients. In all three patients with discordant results, clinical follow up supported the decision based on the chemiluminescence assay. Pentagastrin stimulation tests in MTC patients and localization studies of occult MTC tissue by selective venous catheterization led to concordant results in both assays. The new Nichols chemiluminescence assay demonstrated advantages in handling, a lower detection limit and a slightly higher sensitivity than the Medgenix elisa. CT values obtained by the chemiluminescence assay were on average 1.4-fold lower, which may be due to a slightly superior specificity of the assay, although this problem was not specifically addressed in this study. The clinical usefulness of both assays is highly satisfactory. In all cases, however, where clinically meaningful differences occurred, follow up proved the results obtained with the chemiluminescence assay to be correct.

Adolescent↗
PubMed1999

cAMP-synthesis in a medullary thyroid carcinoma cell line: response to adrenergic agents and prostaglandines.

Calcitonin secretion by C-cells is mediated through intracellular 3'5'-cyclic adenosine monophosphate (cAMP) and calcium signaling. Calcitonin release stimulation tests may take advantage of both signaling cascades in screening for medullary thyroid carcinomas (MTC). To elucidate the regulation of the adenylyl cyclase system we have determined cAMP levels of a calcitonin-expressing MTC cell line (RG) after exposure to adrenergic agents and prostaglandines. In early passages (20-30) cAMP concentrations were significantly elevated in RG cells after exposure to beta-adrenergic agents and prostaglandines E1 and E2. In advanced passages (60-80) the beta-adrenergic response was no longer detectable and adrenergic receptors were uncoupled from the adenylyl cyclase complex; while the effect of prostaglandines E1 and E2 remained unaffected. Preincubation with dexamethasone, in a process requiring protein new synthesis, re-established the adrenergic response in later passages, indicating that RG cells dedifferentiated in culture over time. Our in vitro findings suggest that MTC cell dedifferentiation may be accompanied by adrenergic receptor-uncoupling from the adenylate cyclase system and that this process may be reversed by dexamethasone incubation.

Adenylyl Cyclases↗
PubMed2002

Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TT.

Somatostatin (SRIH) analogs are commonly used to treat symptoms in medullary thyroid carcinoma (MTC), that expresses SRIH receptors (SSTR1 to SSTR5), as does the human MTC cell line TT. The aim of this work was to evaluate whether SRIH, SSTR2 and SSTR5-selective agonists influence calcitonin (CT) secretion and gene expression in the TT cell line. CT secretion was evaluated by chemiluminescence, and gene expression was analyzed by Northern blot. TT cell line proliferation was also assessed by [(3)H] thymidine ([(3)H]thy) incorporation and viable cell number count. SRIH significantly (p < 0.05) reduced [(3)H]thy incorporation (approx. 50 %), viable cell number (approx. 20 %), CT secretion (-30 %) and CT gene expression (approx. 2-fold). Exposure to the SSTR2-selective agonist, BIM-23 120, and to the SSTR5-selective agonist, BIM-23 206, did not modify CT secretion and mRNA levels in TT cells. Thus, SRIH inhibits DNA synthesis, cell proliferation, CT secretion and CT gene expression in the TT cell line, while SSTR2 and 5 selective agonists, although influencing DNA synthesis and cell proliferation, do not modify CT gene expression, suggesting that SRIH may influence gene expression acting through SSTRs other than subtypes 2 and 5. Furthermore, these findings may explain the erratic response of MTC patients in terms of CT plasma levels to treatment with SRIH analogs, like octreotide and lanreotide, which interact mainly with SSTR2 and 5.

Blotting, Northern↗
PubMed2006

[Clinical impact of operative multidisciplinarity for severe defect injuries of the lower extremity].

BACKGROUND: The aim of this study was to examine the impact of our multidisciplinary therapeutical concept (MTC) on the clinical outcome in posttraumatic defect injuries of the lower extremity. PATIENTS AND METHODS: Since 1999, we have performed a free tissue transfer in 37 patients. In group 1 (n = 21), our MTC was started more than two weeks (range: 17 to 83 days) after trauma and in group 2 (n = 16) within two weeks (range: four to twelve days) after trauma. Both groups were comparable with respect to trauma severity. RESULTS: 100 % patients of group 1 and 25 % patients of group 2 had clinical and microbiological manifestations of wound infection after admission in our clinic. Significantly more operations were necessary in group 1 compared to group 2 (7.3 +/- 2.6 versus 2.9 +/- 0.8; p < 0.05), until definitive wound closure could be achieved. The postoperative course was uneventful in 35 cases. All injured extremities could be salvaged. Multistaged bone reconstructions by means of spongious or tricortical bone from the iliac crest were successful in all cases. Hospital stay after admission to our clinic was significantly longer in group 1 compared to group 2 (57 +/- 12 days versus 31 +/- 7 days, p < 0.05). CONCLUSIONS: In our study, the early start of MTC significantly reduced the risk for wound infection, the number of surgical revisions before definite wound closure and time until bone and wound healing was completed.

Adolescent↗
PubMed1986

[Mastopathy and breast cancer: is there a typical hormone profile?].

Carcinoma of the breast and mastopathy are statistically correlated with the functioning of the gonads. The authors studied whether in 58 women with carcinoma of the breast and in 36 patients with mastopathy any change was seen in the secretory pattern of gonadal steroids and whether there were any latent changes in the secretion of prolactin and TSH. A group of 43 women with benign gynaecological diseases served as controls. Before making the diagnosis via immediate section for microscopic examination we determined the basal values of prolactin, LH, FSH, TSH and the oestrogen fractions E1, E2, E3, total oestrogens and progesterone. In addition, we measured the increase in prolactin and TSH after stimulation with metoclopramide. Postoperatively this was followed by measuring the basal values of prolactin and TSH and their secretory performance in respect of TRH. All histological diagnoses were made by an experienced pathologist. Examinations were performed under strictly standardised conditions, taking into account stress, circadian variation and the nutritional status. The following group-specific significant results were obtained (p less than 0.05-0.01): Mastopathy: high serum values of all oestrogen fractions and of total oestrogens, high PRL release through MTC stimulation, prolactin secretory effect after MTC in accordance with the degree of severity of epithelial proliferation, early onset of menopause. Carcinoma of the breast: Low PRL and TSH release on MTC stimulation, low progesterone concentrations during the second cycle phase, relatively high serum concentrations of oestradiol during the first cycle phase, PRL basal values increased postoperatively, compared with preoperative values. The results led to the following conclusions: In mastopathy patients there is a connection between high oestrogen concentrations and consecutively high prolactin release. The morphological substrate is represented by an enhanced proliferation of epithelium. In patients with cancer of the breast reduced progesterone concentrations during the second half of the cycle lead us to suspect an increased incidence of luteal insufficiency; in addition, it appears that the daily prolactin secretion rate in this group is on a reduced level.

Adult↗
PubMed2002

RET mutation profile and variable clinical manifestations in a family with multiple endocrine neoplasia type 2A and Hirschsprung's disease.

BACKGROUND: RET proto-oncogene germ line mutations are associated with the inherited multiple endocrine neoplasia type 2 syndromes (MEN 2), as well as with familial and sporadic Hirschsprung's disease (HSCR). In this study, we report a family in which the MEN 2A and the HSCR phenotypes are associated with a single point mutation in exon 10 of the RET proto-oncogene. Furthermore, we have investigated polymorphic sequence variants of the RET proto-oncogene. METHODS: Family members were tested for RET proto-oncogene mutations in exons 10, 11, 13, 14, 15, and 16 by double-gradient denaturing-gradient gel electrophoresis, nucleotide sequence analysis, and restriction endonuclease digestion of polymerase chain reaction products. The status of exon 2 and 13 polymorphic sites was investigated by EagI and TaqI digestion in 12 selected patients. RESULTS: A heterozygous C618R mutation of RET exon 10 was identified in 12 family members. Five out of 7 children with mildly elevated pentagastrin-stimulated calcitonin levels who carried the mutation underwent prophylactic thyroidectomy before the age of 12. C-cell hyperplasia (CCH) was found in 4 children and a microscopic medullary thyroid carcinoma (MTC) in an 8-year-old female. Neither CCH nor MTC was found in the only family member affected with HSCR, an 8-year-old male. This patient inherited the mutated RET allele from his mother, who had MTC but not HSCR, together with a rare allelic variant at codon 45 of RET exon 2. CONCLUSIONS: This report of a newly-described kindred with the infrequent clinical association between MEN 2A and HSCR confirms the risk of the latter phenotype among carriers of RET exon 10 cysteine codon mutations. Nevertheless, the influence of other genetic or environmental factors cannot be excluded.

Adult↗
PubMed2003

Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations.

BACKGROUND: Hereditary medullary thyroid carcinoma (MTC) is the most common and potentially life-shortening phenotypic manifestation of RET (rearranged during transfection) germline mutations. If a distinct time lag between the successive stages of malignant progression were identifiable, the information could be used to individualize prophylactic surgery. The study objective was to investigate the impact of RET genotype on disease progression from C-cell hyperplasia (CCH) to MTC. METHODS: An institutional series of 167 (67 index, 100 nonindex) consecutive carriers of RET gene point mutations in exons 10, 11, 13, 14, or 16 who underwent total thyroidectomy between November 1994 and November 2002. RESULTS: Regarding codons 618, 620, 634, 768, 790, and 804, patient age at diagnosis differed significantly depending on the type of pathology encountered (CCH, MTC without and with nodal metastasis). The variability in age, which may reflect the number of necessary somatic mutations, explained the pathological strata in 38% (codon 634) to 77% (codon 768) of patients. Conversely, 62% (codon 634) to 23% (codon 768) of variability in age at different pathological strata may have been determined by the RET genotype. CONCLUSIONS: The pace of malignant progression of the RET genotype should be taken into account when considering prophylactic thyroidectomy in RET gene carriers.

Adolescent↗
PubMed1999

MalK forms a dimer independent of its assembly into the MalFGK2 ATP-binding cassette transporter of Escherichia coli.

The maltose transport complex (MTC) is a member of the ATP-binding cassette superfamily of membrane transport proteins and is a model for understanding the folding and assembly of hetero-oligomeric membrane protein complexes. The MTC is made up of two integral membrane proteins, MalF and MalG, and a peripheral membrane protein, MalK. These proteins associate with a stoichiometry of 1:1:2 to form the complex MalFGK2. In our studies of the oligomerization of this complex, we have shown that the ATP-binding component, MalK, forms a dimer in the absence of MalF and MalG. Epitope-tagged MalK coimmunoprecipitated with wild-type MalK, indicating that the MalK protein forms an oligomer. The relative amounts of tagged and wild-type MalK that were present in the whole cell extracts and in the immunoprecipitated complexes show that the MalK oligomer is a dimer. These hetero-oligomers can also be formed in vitro by mixing two extracts, each containing either tagged or wild-type MalK. The dimerization of MalK was also demonstrated in vivo using the bacteriophage lambda repressor fusion assay. The formation of a MalK dimer in the absence of MalF and MalG may represent an initial step in the assembly pathway of the MTC.

ATP-Binding Cassette Transporters↗
PubMed2001

Studies made to assess risk concerning a 'dioxin' contamination incident near Bolsover, Derbyshire, UK.

During 1990 and 1991, milk samples were collected from farms in Derbyshire, a county in the UK, as part of a study designed to establish background concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) in cows' milk produced in the area. The concentrations found in two samples, both taken from farms near the town of Bolsover, were significantly elevated (40.0-42.0 ng TEQ kg(-1) fat) when compared with the normal range for these compounds in milk from the surrounding area (1.1-7.1 ng TEQ kg(-1) fat). An immediate intensive programme commenced in April 1991 to test milk from a further 27 dairy farms close to those where the original 'high' samples were obtained. A maximum tolerable concentration (MTC) was calculated to be 17.5 ng/TEQ kg(-1) fat. This was derived by using the tolerable daily intake (TDI) for 2,3,7,8-TCDD of 0.01 ng kg(-1) body weight day(-1) set by the World Health Organization in 1990 and accepted by the UK government (this figure has since been revised to 1-4 pg kg(-1) body weight day(-1)). MTC is defined as the amount of PCDD/Fs that could be present and still ensure that high-level (97.5 pecentile) consumers of milk would not exceed the TDI. Milk originating from dairies supplied by these farms and others contained PCDD/F in the range 1.8-3.1 ng TEQ kg(-1) fat, which indicated there was no risk to health for consumers purchasing milk in the normal manner. Milk from the two dairy farms was removed from the food supply until concentrations of PCDD/Fs were consistently below the MTC. The UK Department of Health monitored the blood concentrations of PCDD/Fs in individuals who had consumed milk produced on the affected farms and the Department of the Environment initiated a programme of work to identify and reduce the source of pollution.

Animals↗
PubMed2001

Medullary carcinomas of the thyroid: a monoclonal origin.

We studied the clonality of medullary thyroid carcinomas (MTC) from 16 female patients by determining X chromosome inactivation by polymerase chain reaction (PCR) amplification of a CAG repeat in exon 1 of the human androgen-receptor gene. One patient with sporadic medullary thyroid carcinoma (MTC) was homozygous for this microsatellite and was not considered for the assessment of clonality. Sixteen tumor samples from the informative 15 patients were studied: 11 were from sporadic cases and 5 were from familial cases (3 cases of multiple endocrine neoplasia type 2A [MEN 2A]; 1 case of familial medullary thyroid carcinoma [FMTC]). Fourteen tumor samples (10/11 sporadic, 3/4 MEN 2A and 1/1 FMTC) were clearly monoclonal with allelic cleavage ratios between 2.5 and 49.1. Sixty-four percent of these cases (9/14) had the preferential amplification of the shorter allele while 36 percent (5/14) had the preferential amplification of the longer allele. Two frozen tumor samples (1 sporadic and 1 MEN 2A) were polyclonal. However, the corresponding tumor embedded in paraffin from the sporadic case was monoclonal. The other polyclonal tumor was found in the right thyroid lobe of a patient with MEN 2A who had a monoclonal tumor in the left lobe. Our results clearly demonstrate that MTC have a monoclonal origin in the majority of the cases.

Adolescent↗
PubMed2001

Elevation of serum pro-gastrin-releasing peptide in patients with medullary thyroid carcinoma and small cell lung carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.

Adult↗
PubMed2003

Calcitonin precursor levels in human medullary thyroid carcinoma.

DESIGN: The hormonal serum marker for the presence and course of patients with medullary thyroid cancer (MTC) is the mature calcitonin (CT) peptide. Other CALC-1 gene products such as the 116-amino acid polypeptide prohormone, procalcitonin, as well as its component calcitonin precursors (CTpr) may also be increased in their sera. We performed a study to evaluate the clinical utility of serum levels CTpr in these patients. METHODS: Twenty-one patients with MTC (9 males, 12 females; 23-76 years of age) were evaluated. The diagnosis was confirmed by histologic examination, except for 2 (a proven RET mutation plus an abnormal pentagastrin-stimulated CT level). Nine patients had postoperative hypercalcitoninemia and 3 of these died. The specific assay for mature CT was a commercial immunoradiometric assay (hCT-IRMA); the immunoluminometric assay for CTpr (B.R.A.H.M.S Diagnostica, Berlin, Germany) detects intact procalcitonin and the free CT:CT carboxypeptide-1. RESULTS: All patients had detectable serum CTpr. These levels considerably exceeded those of mature CT, averaging 7.6-fold greater. CTpr levels correlated positively with mature CT (r = 0.61; p < 0.001). After pentagastrin administration, there was a parallelism of response between the two assays. Whenever there were known metastases, CTpr increased markedly. CONCLUSION: This study demonstrates the universal presence of CTpr in the blood of patients with MTC. The measurement of these peptides may offer a new dimension to the clinical evaluation of this malignancy.

Biomarkers, Tumor↗