1. ABSTRACT Background: calcitonin is an excellent tumor marker of medullary thyroid carcinoma (MTC). It makes early diagnosis of MTC possible with increased overall survival. It is a very sensitive marker however, its specificity is low: several physiological and pathological conditions have been associated with increased calcitonin levels, among which are often cited chronic thyroiditis and chronic hypergastrinemia, like those related to chronic autoimmune gastritis (GAI). However, there are few studies in Literature on this subject, characterized by low patient numbers. Furthermore, while an acute hypergastrinemia has been proven, both in-vitro and in-vivo, to represent a stimulus for calcitonin secretion, the effect of chronic hypergastrinemia on humans has still to be demonstrated. The objective of the study: The aims of the study are 1) to evaluate serum calcitonin levels in patients with chronic hypergastrinemia secondary to GAI; 2) to verify whether chronic hypergastrinemia in patients with GAI is associated with increased serum calcitonin values; 3) to evaluate serum calcitonin levels in patients with TH, with GAI and without GAI; 4) to verify whether the presence of TH is associated with increased serum calcitonin values. Patients and methods: We conducted a multicentric retrospective study, consecuitively enrolling 142 patients divided into three groups: group A including patients with a histological diagnosis of GAI (n=13, 11 men, 2 women), group B including patients with a histological diagnosis of GAI and autoimmune thyroiditis (n=92, 15 men, 77 women) and group C including patients with autoimmune thyroiditis without GAI (n=37, 6 men and 31 women). Exclusion criteria were; 1) age less than 18 years 2) presence of renal failure, hyperparathyroidism or lung cancer 3) refuse to give the informed consent to the study. Serum calcitonin and gastrin were assayed in all patients. Results: Calcitonin median levels did not differ in the three groups, being its median value equal to 1,0 ng/L in all three groups (p=0,1), although gastrin values were high in groups A and B and normal in group C, being its median values equal to 584,2 pmol/L (interquantile range, IQR 457,3 - 715,5 pmol/L), 540,0 pmol/L (243,3 - 736,4 pmol/L), 23,0 pmol/L (IQR 16,8 - 33,1 pmol/L) in group A, B and C respectively (p<0,001). Calcitonin resulted in group A, B, C respectively: undetectable in 8/13 (61,5%), 70/92 (76,1%) and 27/37 (73,0%); detectable but <10 ng/L in 4/13 (30,8%), 20/92 (21,7%) and 8/37 (21,6%); and >10 ng/L in 1/13 (7,7%), 2/92 (2,2%) and 2/37 (5,4%) (p=0,1). Only three patients had high calcitonin levels (>10 ng/L) and elevated gastrin levels: these patients carried a nodular thyroid disease and underwent calcium gluconate testing which resulted consistent with MTC. The patients underwent surgery, and histological examination confirmed the diagnosis of MTC. No correlation was found between calcitonin and gastrin either considering them as quantitative variables (p=0,27, R=0,09 at Spearman’s rank correlation test) or categorical variables (p=0,52). No correlation was found between calcitonin and being affected by TH (p=0,79). The median levels were the same in the group of patients with TH (group B and C) and the group of patients with only GAI (group A), being its median value equal to 1,0 ng/L. Conclusions: In this study, conducted on a relevant number of patients with histological diagnosis of GAI and TH, it was shown that neither chronic hypergastrinemia secondary to GAI nor autoimmune thyroiditis correlated with an increase in serum calcitonin. Therefore, in the evaluation of a patient with GAI or TH, increased calcitonin cannot be attributed to the presence of these diseases, and the presence of a MTC should always be investigated to enable early diagnosis and appropriate treatment.
1. RIASSUNTO Presupposti dello studio: La calcitonina è un eccellente marcatore tumorale del carcinoma midollare della tiroide (MTC). Rende possibile una diagnosi precoce di MTC con aumento della sopravvivenza. È un marcatore molto sensibile tuttavia la sua specificità è bassa: diverse condizioni fisiologiche e patologiche sono state associate ad un aumento dei livelli di calcitonina, tra le quali sono spesso citate la tiroidite cronica e l’ipergastrinemia cronica (come quella in corso di gastrite cronica autoimmune (GAI)). Tuttavia, in Letteratura gli studi in merito sono pochi e caratterizzati da una bassa numerosità di pazienti. Inoltre, mentre è stato dimostrato che un’ipergastrinemia acuta, sia in-vitro che in-vivo rappresenta uno stimolo per la secrezione di calcitonina, l’effetto di un’ipergastrinemia cronica sull’uomo è ancora da dimostrare. Scopo dello studio: Scopi dello studio sono: 1) valutare i livelli di calcitonina sierica in pazienti con ipergastrinemia cronica secondaria a GAI; 2) verificare se l’ipergastrinemia cronica nei pazienti con GAI sia associata ad un aumento dei valori di calcitonina sierica; 3) valutare i livelli di calcitonina sierica nei pazienti con TH, con GAI e senza GAI; 4) verificare se le presenza di TH sia associata ad un aumento dei valori di calcitonina sierica. Pazienti e metodi: Abbiamo condotto uno studio retrospettivo multicentrico, arruolando consecuitivamente 142 pazienti distinti in tre gruppi: gruppo A comprendente pazienti con diagnosi istologica di GAI (n=13, 11 uomini, 2 donne), gruppo B comprendente pazienti con diagnosi istologica di GAI e tiroidite autoimmune (n=92, 15 uomini, 77 donne) e gruppo C comprendente pazienti con tiroidite autoimmune senza GAI (n=37, 6 uomini e 31 donne). I criteri di esclusione erano: 1) età minore di 18 anni 2) presenza di insufficienza renale, iperparatiroidismo o tumore al polmone 3) rifiuto di dare il consenso informato allo studio. In tutti i pazienti è stata dosata la calcitonina e la gastrina sieriche. Risultati: I livelli mediani di calcitonina non sono risultati diversi nei tre gruppi, con un valore mediano di 1 ng/L in tutti e tre i gruppi (p=0,1), nonostante i valori di gastrina fossero elevati nel gruppo A e B e normali nel gruppo C, con valori mediani di 584,2 pmol/L (range interquartile, IQR 457,3 - 715,5 pmol/L), 540,0 pmol/L (243,3 - 736,4 pmol/L), 23,0 pmol/L (IQR 16,8 - 33,1 pmol/L) nel gruppo A, B e C, rispettivamente (p<0,001). La calcitonina è risultata nel gruppo A, B, C rispettivamente: non dosabile in 8/13 (61,5%), 70/92 (76,1%) e 27/37 (73,0%); dosabile ma <10 ng/L in 4/13 (30,8%), 20/92 (21,7%) e 8/37 (21,6%); e > 10 ng/L in 1/13 (7,7%), 2/92 (2,2%) e 2/37 (5,4%) (p=0,1). Solo tre pazienti hanno presentato elevati livelli di calcitonina (>10 ng/L) ed elevati livelli di gastrina: questi pazienti presentavano una patologia nodulare tiroidea e sono stati sottoposti a test con calcio gluconato che è risultato compatibile con MTC. I pazienti sono stati sottoposti a intervento chirurgico e l’esame istologico ha confermato la diagnosi di MTC. Non è stata trovata una correlazione tra calcitonina e gastrina sia considerandole come variabili quantitative (p=0,27, R=0.09 secondo la correlazione per ranghi di Spearman) che categoriche (p=0,52). Non è stata trovata una correlazione tra calcitonina e l’essere affetti da TH (p=0,79). I livelli mediani sono risultati uguali nel gruppo di pazienti affetti da TH (gruppo B e C) e nel gruppo di pazienti affetti solo da GAI (gruppo A), con un valore di 1,0 ng/L. Conclusioni: In questo studio, condotto su un numero rilevante di pazienti con diagnosi istologica di GAI e TH, è stato dimostrato che né l’ipergastrinemia cronica secondaria a GAI né la tiroidite autoimmune sono correlate ad un aumento della calcitonina sierica.
Livelli di calcitonina circolante nei pazienti con ipergastrinemia secondaria a gastrite autoimmune
FISCATO, MATTEO
2021/2022
Abstract
1. ABSTRACT Background: calcitonin is an excellent tumor marker of medullary thyroid carcinoma (MTC). It makes early diagnosis of MTC possible with increased overall survival. It is a very sensitive marker however, its specificity is low: several physiological and pathological conditions have been associated with increased calcitonin levels, among which are often cited chronic thyroiditis and chronic hypergastrinemia, like those related to chronic autoimmune gastritis (GAI). However, there are few studies in Literature on this subject, characterized by low patient numbers. Furthermore, while an acute hypergastrinemia has been proven, both in-vitro and in-vivo, to represent a stimulus for calcitonin secretion, the effect of chronic hypergastrinemia on humans has still to be demonstrated. The objective of the study: The aims of the study are 1) to evaluate serum calcitonin levels in patients with chronic hypergastrinemia secondary to GAI; 2) to verify whether chronic hypergastrinemia in patients with GAI is associated with increased serum calcitonin values; 3) to evaluate serum calcitonin levels in patients with TH, with GAI and without GAI; 4) to verify whether the presence of TH is associated with increased serum calcitonin values. Patients and methods: We conducted a multicentric retrospective study, consecuitively enrolling 142 patients divided into three groups: group A including patients with a histological diagnosis of GAI (n=13, 11 men, 2 women), group B including patients with a histological diagnosis of GAI and autoimmune thyroiditis (n=92, 15 men, 77 women) and group C including patients with autoimmune thyroiditis without GAI (n=37, 6 men and 31 women). Exclusion criteria were; 1) age less than 18 years 2) presence of renal failure, hyperparathyroidism or lung cancer 3) refuse to give the informed consent to the study. Serum calcitonin and gastrin were assayed in all patients. Results: Calcitonin median levels did not differ in the three groups, being its median value equal to 1,0 ng/L in all three groups (p=0,1), although gastrin values were high in groups A and B and normal in group C, being its median values equal to 584,2 pmol/L (interquantile range, IQR 457,3 - 715,5 pmol/L), 540,0 pmol/L (243,3 - 736,4 pmol/L), 23,0 pmol/L (IQR 16,8 - 33,1 pmol/L) in group A, B and C respectively (p<0,001). Calcitonin resulted in group A, B, C respectively: undetectable in 8/13 (61,5%), 70/92 (76,1%) and 27/37 (73,0%); detectable but <10 ng/L in 4/13 (30,8%), 20/92 (21,7%) and 8/37 (21,6%); and >10 ng/L in 1/13 (7,7%), 2/92 (2,2%) and 2/37 (5,4%) (p=0,1). Only three patients had high calcitonin levels (>10 ng/L) and elevated gastrin levels: these patients carried a nodular thyroid disease and underwent calcium gluconate testing which resulted consistent with MTC. The patients underwent surgery, and histological examination confirmed the diagnosis of MTC. No correlation was found between calcitonin and gastrin either considering them as quantitative variables (p=0,27, R=0,09 at Spearman’s rank correlation test) or categorical variables (p=0,52). No correlation was found between calcitonin and being affected by TH (p=0,79). The median levels were the same in the group of patients with TH (group B and C) and the group of patients with only GAI (group A), being its median value equal to 1,0 ng/L. Conclusions: In this study, conducted on a relevant number of patients with histological diagnosis of GAI and TH, it was shown that neither chronic hypergastrinemia secondary to GAI nor autoimmune thyroiditis correlated with an increase in serum calcitonin. Therefore, in the evaluation of a patient with GAI or TH, increased calcitonin cannot be attributed to the presence of these diseases, and the presence of a MTC should always be investigated to enable early diagnosis and appropriate treatment.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/30539