Calcitonin Stimulation Tests: Rationale, Technical Issues and Side Effects: A Review

Abstract

Calcitonin (CT) stimulation tests have great value and could help to: differentiate thyroid causes of elevated CT apart from non-thyroid sources, determine whether the patients with slightly elevated basal CT could/could not be candidates for surgery, and indicate the right moment for prophylactic thyroidectomy in children with MEN syndromes when with normal basal CT. This triggered the requests for development of CT stimulation tests, taking into consideration their safety and aimed us to write a systematic review of literature regarding the rationale, technical issues, and side effects of CT stimulating tests used for diagnosis of MTC. After a thorough review of the literature, we classified the reported side effects by severity, as defined by United States Food and Drug Administration. A statistical analysis was performed using IBM SPSS Statistics version 20. Various side effects were noticed during stimulation tests that differ by intensity, duration and severity, depending on types of substances and protocols used. The side effects after pentagastrin test were significantly more severe than those reported after calcium stimulation test (p=0.0396). There are also significant gender-specific differences in side effects induced by stimulation tests. In conclusion, we recommend performing Ca CT stimulation test when needed, considering preventive evaluation of some clinical, instrumental, and biochemical aspects of each patient. Precise instructions should be followed before a stimulation test and furthermore continuous cardiac monitoring is essential during and after the test to minimize the possibility of a serious event.

Medullary thyroid carcinoma: recent advances in identification, treatment, and prognosis

“…Measurement of calcitonin after pharmacologic stimulation has been used to differentiate whether calcitonin elevation is derived from thyroid C-cells versus from a non-thyroid origin, to identify patients with normal basal calcitonin and MTC, and to determine timing of thyroidectomy in patients with rearranged during transfection ( RET ) mutations detected on genetic testing. 8,9 Pentagastrin stimulation, now no longer available worldwide, has largely been replaced with calcium stimulation with equivalent results. 10 Multiple studies have attempted to set parameters for detecting MTC using basal calcitonin, stimulated calcitonin, or combined measurements.…”

Determinants of circulating calcitonin value: analysis of thyroid features, demographic data, anthropometric characteristics, comorbidities, medications, and smoking habits in a population with histological full exclusion of medullary thyroid carcinoma

“…Among them, individual determinants hold a main role, and Ctn stimulation tests have been proposed to overcome the limitations of basal Ctn. Nevertheless, although the Ctn stimulation test was conceived to differentiate thyroid causes of elevated Ctn from non-thyroid sources ( 23 ), it requires careful procedure under medical control, and no high evidence of fixed cut-off is available ( 2 ). Therefore, the potential impact of several determinants on circulating basal Ctn may hold a crucial role.…”

Diagnostic tests for medullary thyroid carcinoma: an umbrella review

“…Ctn Ca stimulation test may be useful, when appropriate, but there is no solid evidence about its diagnostic improvement. [ 7 – 9 ] Sometime, MTC presents with normal Ctn (i.e., non-secretory MTC) and these cases may have poorer prognosis. [ 10 , 11 ] Other circulating markers CEA doubling time is more reliable than that of Ctn in identifying progression of disease and poorer prognosis.…”

“…Only one systematic review in the literature examined rationale, technical issues, and side effects of Ctn stimulation tests used to diagnose MTC [ 9 ]. It included 25 studies, 12 reporting calcium (Ca) and pentagastrin (Pg) stimulation separately in the same group and other 4 reporting Ca and Pg in combination.…”

“…However, the Ctn cut-off values should be considered and a wait-and-see strategy should be applied to avoid overtreatment. Baetu [ 9 ] 2021 25 2251 Without Ca stimulated Ctn should be considered, when appropriate. Clinical, instrumental and biochemical assessments before the test, as well as cardiac monitoring during and after the test, should be performed to avoid serious events.…”