Levothyroxine malabsorption or pseudomalabsorption? A question in the management of refractory hypothyroidism.

Purpose: The levothyroxine absorption test (LT4AT) is an important tool for distinguishing hypothyroidism due to malabsorption from 'pseudomalabsorption' conditions. Our aim was to review our institution's LT4AT results and assess its role in the management of patients with refractory hypothyroidism. Methods: We performed a retrospective study of all patients evaluated for refractory hypothyroidism who underwent LT4AT in our tertiary center between 2014 and 2020. Its results and the impact on thyroid function management during follow-up were assessed. Results: Ten female patients were included with a mean age of 40 years (min-max: 26-62). Mean weight was 72 kg (min-max: 43-88) and baseline LT4 dosage ranged from 2.5 to 5.3 µg/kg/day. The most common causes of hypothyroidism were postsurgical in 50% (n = 5) and autoimmune in 20% (n = 2). During LT4AT, normal LT4 absorption was found in all but one individual (mean FT4 increase of 231%, min-max: 85-668). The only patient with objective LT4 absorption impairment (maximal increase of 48% by hour 5) presented also Helicobacter pylori gastritis and prior history of 'intestinal surgery' during childhood. No adverse events were reported during any of the LT4ATs. During follow-up (median 11.5 months (IQR 23)), three patients obtained euthyroidism and six had improved their hypothyroidism state. Conclusions: The LT4AT is an effective and safe way to assess refractory hypothyroidism and provides valuable information to distinguish LT4 malabsorption from 'pseudomalabsorption'. Our data suggest that most patients with suspicious LT4 malabsorption perform normally during LT4AT. This test provides relevant information for better management of patients with refractory hypothyroidism.

Papillary thyroid carcinoma: the impact of histologic vascular invasion.

OBJECTIVE: The American Thyroid Association (ATA) recurrence risk prediction system considers vascular invasion (VI) as a relative indicator for adjuvant radioactive iodine (RAI) treatment, nevertheless VI final role in PTC management is yet to be defined. This study aims to assess the impact of histologic VI in PTC. METHODS: A retrospective study with PTC patients admitted in our Thyroid Cancer Unit, between January 1960 and December 2016 was performed. We reviewed 905 patient records with 275 having full information about VI on their pathological reports. Demographic and clinical variables were obtained, and univariate/multivariate analysis was performed in order to obtain potential predictive prognostic factors. RESULTS: Fifty-one out 275 patients presented VI (18.5%; 95% CI 14.4 - 23.6%), these individuals had larger tumors (median 19mm vs 12 mm, p < 0.001) with more frequent extraglandular invasion (54.0% vs 17.1%, p<0.001), regional lymph nodes involvement (29.8% vs 12.6%, p = 0.003)and distant metastasis (10.9% vs 1.9%, p = 0.003) at diagnosis. Vascular invasion was an independent predictor for regional lymph node and/or distant metastasis at diagnosis [OR 2.93 (IC95% 1.16 - 7.41, p = 0.008)]. After a median follow-up time was 68.5 months patients with VI presented higher rates of local recurrence and lymph node metastasis recurrence. CONCLUSIONS: In this study, the presence of VI in PTC is associated to higher rate of lymph node and distant metastasis at diagnosis. Its presence should be probably considered an adverse prognostic factor in PTC, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Non-thyroidal second primary malignancy in papillary thyroid cancer patients.

Introduction: The occurrence of non-thyroidal second primary malignancy (NTSPM) in patients with papillary thyroid cancer (PTC) is well documented, but epidemiological data are conflicting. Objective: The aim of this study was to evaluate the incidence of NTSPM in a large series of patients with PTC and to assess its potential risk factors. Methods: Single-center cohort study with retrospective data collection conducted on consecutive PTC patients diagnosed from 1988 to 2018 with a minimum follow-up time of 2 years. NTSPM was defined as any primary malignancy with histological confirmation occurring in an anatomical site other than the thyroid. According to the timing of occurrence, NTSPM were subdivided into anachronous, synchronous or metachronous (diagnosed >6 months before, within 6 months and >6 months after PTC diagnosis, respectively). Results: We included 773 individuals (83.3% females), median age at PTC diagnosis was 47.0 (IQR: 37.0-58.0) years and median follow-up time was 9.9 (6.2-16.3) years. Incidence of NTSPM was 15.5% (n = 120) and its standard incidence ratio (SIR) was higher when compared to the general population (SIR: 2.70). Family history of malignancy and younger age at diagnosis were associated respectively with 206 and 4% increased risk of developing metachronous neoplasia (HR: 2.06 (95% CI: 1.10-3.86) and 1.04 (95% CI: 1.02-1.05), respectively). Conclusion: In our series, the occurrence of NTSPM was not uncommon and its incidence was higher compared to the general population. First-degree family history of malignancy was a strong risk factor for multiple primary malignancies.