Normal Serum Calcitonin Levels Research Articles

SAT309 Clinical And Genetic Profiling Of Patients With Multiple Endocrine Neoplasia Type 2 Syndrome And Screening for Medullary Thyroid Carcinoma In Asymptomatic First-degree Relatives

Abstract Disclosure: K. Kumar P: None. Y. Gupta: None. A. Goyal: None. D. Kandasamy: None. N. Tandon: None. Background: Multiple endocrine neoplasia type 2 (MEN2) syndrome is a rare disorder with autosomal dominant inheritance, characterised by the presence of two of the following three endocrine manifestations: medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and primary hyperparathyroidism (PHPT) [1-2]. There is a paucity of data on clinical and genetic profile of MEN2 syndrome in the Indian subcontinent. Objectives: We aimed to evaluate the clinical and genetic profile of patients with MEN2 syndrome and perform screening for MTC among asymptomatic family members with serum calcitonin. Materials and Methods: This was an ambispective study conducted in the Department of Endocrinology at AIIMS New Delhi, involving diagnosed patients of MEN2 syndrome between January 2016 and December 2022. Results: We evaluated a total of 24 families with MEN2 syndrome comprising 61(MEN2A, n=56; MEN2B, n=5) patients, 18 patients were diagnosed as index cases. Data were derived retrospectively for 46 patients (MEN2A, n=43 MEN2B, n=3) and prospectively for 15 patients (MEN2A, n=13; MEN2B, n=2). The mean age at presentation of MEN2A and MEN2B were 28.6 ± 13.52 years and 22 ± 4.44 years, respectively. Of the study patients, 35 (57.38%) were females, among them 32 were MEN2A. Among 18 index patients 67% were synchronously detected to have MTC and PCC while 33% had MTC preceding PCC. Among patients with MEN2A syndrome 33 (59%) had MTC, 21(38%) had simultaneous PCC and MTC and one patient had PCC as presentation. We noted PHPT in 5 (9%) patients with MEN2A syndrome. Of the 5 patients with MEN2B syndrome, 4 (80%) presented with synchronous MTC and PCC and one (20%) presented with MTC aloneMetastatic MTC was noted in six patients with MEN2A syndrome and two patients with MEN2B syndrome. Median baseline Sr calcitonin level was 42 (4-1721) pg./ml in non-Metastatic group vs 3945(928-35572) pg./ml in distant metastasis group. 1 patient had metastasis from PCC to liver. Mutational analysis data are available for 40 patients. The most common mutations in MEN2A and MEN2B groups were C634R (exon 11 of RET gene, n=21) and M918T (exon 16 of RET gene, n=4), respectively.A total of 177 eligible family members of index patients with MEN2A syndrome were contacted, of whom 83 turned up for screening and 42 (50.6%) had elevated serum calcitonin levels (>10 pg./ml). Of the 26 eligible family members of index patients with MEN2B syndrome, only 9 could be screened and all had normal serum calcitonin levels (<10 pg./ml). Discussion & Conclusion: 1) This is the largest study comprising 61 patients after screening 24 family members in India. 2) Synchronous presentation of MEN2 with PCC and MTC is 67% vs 17% in western literature in Index patients. 3) MEN2 syndrome should be suspected in patients with MTC and young-onset PCC and all first-degree relatives of index patients with this syndrome. Presentation: Saturday, June 17, 2023

The RET C611Y mutation causes MEN 2A and associated cutaneous

BackgroundCutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in ‘MEN 2A with CLA’, one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back.Patient FindingsThis study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family’s clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23–73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family.Summary and ConclusionsThis is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype–phenotype spectrum in MEN 2A.

Normal Perioperative Serum Calcitonin Levels in Patients with Advanced Medullary Thyroid Carcinoma: Case Report and Review of the Literature

Medullary thyroid carcinoma (MTC), a tumor of the parafollicular C cells of the gland, comprises 3-5% of all malignant thyroid neoplasms. Calcitonin, a polypeptidic hormone secreted by the neoplastic cells, is considered a very sensitive and specific MTC tumor marker. Patients with MTC usually present elevated serum calcitonin levels, which correlate with tumor burden and prognosis. To describe a case of advanced MTC with normal serum calcitonin and review the literature on this subject. A case study was performed. There were no interventions. A case of advanced MTC with normal serum calcitonin was studied. Serum calcitonin was measured by two distinct assays, a chemiluminescent immunometric and an in-house two-site monoclonal antibody-based immunofluorometric assay. To rule out a "hook effect," or posttranslational modifications of calcitonin molecule, serum dilutions and tumor immunohistochemistry for calcitonin with the same antibodies used for serum calcitonin measurements were performed. Serum calcitonin levels were within the normal range in both assays, whereas the tumor stained strongly positive for calcitonin. These findings suggest that the tumor was able to produce but not to secrete the calcitonin protein. Five other cases of advanced MTC with normal serum calcitonin levels had been previously reported. We present an unusual case of advanced MTC with normal serum calcitonin levels. Awareness of MTC cases presenting with normal serum calcitonin levels is important in clinical practice and is particularly relevant to centers that use this test for screening.

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With Stenotrophomonas maltophilia

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With Stenotrophomonas maltophilia

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With

Life-Threatening Chronic Enteritis Due to Colonization of the Small Bowel With

Ret Germline Mutation In Codon 791 In A Family Representing 3 Generations From Age 5 To Age 70 Years: Should Thyroidectomy Be Performed?

To describe a kindred with a rare RET germline mutation in codon 791 and discuss potential management strategies. We present clinical and biochemical data as well as results of mutation analysis in our study subjects and provide an overview of related published reports. Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia or adenoma. Germline mutations in RET are responsible for this autosomal dominant syndrome. Familial MTC is a variant of MEN 2A and can be caused by RET mutations in codon 791. Deaths from gene carriers with mutations in these codons have not yet been reported. In general, gene carriers with these RET mutations have late-onset MTC. Because only a few kindreds with this specific mutation have been identified and no long-term follow-up data are available, management of these patients can be a challenge. We illustrate the difficulties with decisions about not only when to perform thyroidectomy in these patients but also whether thyroidectomy should even be considered in such gene carriers with a benign course. Our reported kindred included four carriers with a codon 791 RET germline mutation, one of whom had the rare concomitant occurrence of acromegaly and MEN 2A. The 70-year-old mother had acromegaly and hyperparathyroidism but normal serum calcitonin levels and normal findings on thyroid ultrasound examination. She refused pentagastrin testing and any surgical intervention. The 37-year-old daughter had hypothyroidism, a small thyroid gland, and negative results of pentagastrin stimulation testing of calcitonin. The 18-year-old grandson also had a negative pentagastrin test result and normal thyroid ultrasound findings. The 5-year-old granddaughter had normal results of thyroid ultrasonography. In all patients, we recommended thyroidectomy. Prospective studies are needed to clarify which patients with codon 791 RET germline mutation should undergo thyroidectomy.

Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma.

To assess whether routine measurement of serum calcitonin (CT) could improve the preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC), 1385 consecutive patients presenting for nodular thyroid disease during the year 1991 were submitted to serum CT determination and fine needle aspiration cytology (FNAC). The clinical diagnosis was nontoxic nodular goiter in 1197 (86.4%) patients, toxic multinodular goiter in 65 (4.7%), autonomously functioning thyroid nodule (AFTN) in 64 (4.6%), and autoimmune thyroid disease (Graves' disease or Hashimoto's thyroiditis) with nodule(s) in 59 (4.3%). As controls, 177 patients with nonnodular thyroid disease and 32 normal subjects were also studied. Patients with FNAC suspicious of any kind of thyroid carcinoma and patients with elevated basal and pentagastrin-stimulated serum CT, regardless of the results of FNAC, were submitted to surgery. Eight (0.57%) patients (7 with nontoxic nodular goiter and 1 with AFTN) had elevated basal serum CT levels, ranging between 55-10,000 pg/mL. The pentagastrin test was abnormal in all of them. FNAC was suggestive of MTC in 2, thyroid carcinoma in 1, benign nodule in 3, and inadequate in 2. By histology, immunohistochemistry, and Northern blot analysis of total tumor RNAs, MTC was confirmed in all patients, including the 1 with AFTN, who had the association of microfollicular adenoma and a small MTC in the same lobe. After surgery, serum CT decreased to undetectable levels in 7 patients and remained undetectable in 6 of them during a mean follow-up of 22 months, although 1 of them had a positive response to pentagastrin. Forty-four patients in the group with normal serum CT levels had FNAC suspicious for differentiated thyroid carcinoma and were treated by surgery. Differentiated thyroid carcinoma, mostly papillary, was confirmed at histology in 43 subjects (3.1% of all thyroid nodules). In conclusion, the results of our study indicate that serum CT measurement is useful for the screening of sporadic MTC in patients with thyroid nodule(s). The prevalence of MTC, diagnosed by serum CT measurement in a 12-month period, among an unselected series of 1385 patients with nodular thyroid disease was surprisingly high: 0.57% of all thyroid nodules and 15.7% of all thyroid carcinomas. Serum CT measurement was superior to FNAC in suggesting the diagnosis of MTC and was devoid of falsely positive results. Increasing the diagnostic accuracy helped the surgeon to perform more radical treatment of MTC, thus achieving frequent normalization of postoperative serum CT levels. Whether this result indicates definitive cure remains to be established on the basis of longer follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)