ABSTRACT
AIM OF THE STUDY: The aim of the project was to investigate regional differences in thyroid stimulating hormone (TSH), and free thyroxine (fT4) concentrations and iodine status in comparable German and European cohort studies. METHODS: Sex- and age-stratified TSH, fT4, and urine iodine concentrations of thyroid-healthy participants (age group 45-75 years) of the HNR (Heinz Nixdorf Recall) Study in the Ruhr region of Germany, the southern German KORA (Cooperative Health Research in the Augsburg Region) and northeastern German SHIP (Study of Health in Pomerania) studies, as well as the Norwegian HUNT (Nord-Trøndelag Health) study (age group 40-79 years), the English EPIC (European Prospective Investigation of Cancer)-Norfolk study, and the Dutch Rotterdam study were compared. The TSH reference range for the HNR study population was calculated and compared to the KORA and SHIP studies. RESULTS: Regional differences showed a stronger influence on TSH and fT4 concentrations than sex and age of the subjects in the 45- to 75-year age group. The estimated difference in medians, as measured by the HNR study, was lowest in the SHIP study, -0.47 (95% CI: -0.53; -0.41) for men and -0.41 (-0.53; -0.41) for women. The Rotterdam study had the highest difference in medians for both men and women (men: 0.56 with 0.44; 0.68 and women: 0.62 with 0.46; 0.78). The lowest median TSH concentrations, across all age categories considered, were seen in the German cohorts. CONCLUSIONS: Comparison of thyroid function parameters and iodine in elderly subjects between six comparable cohort studies from Germany and Europe showed a significant influence of region, which exceeded the sex and age dependence of the parameters.
Subject(s)
Iodine , Thyroid Gland , Male , Humans , Female , Aged , Middle Aged , Adult , Prospective Studies , Germany/epidemiology , Cohort Studies , ThyrotropinABSTRACT
INTRODUCTION: Primary squamous cell carcinoma (PSCC) of the thyroid is an exceptionally rare malignancy accounting for <1% of all primary thyroid cancers. Therapy is multimodal including surgery, radiotherapy, and chemotherapy but with no consensus for management and therapy. Here, we describe a case of a male patient who presented with a BRAF V600E-mutated PSCC of the thyroid gland showing response to combined dabrafenib and trametinib therapy over a period of >12 months. CASE PRESENTATION: A 78-year-old male patient presented with a 3-week history of dysphonia and dyspnoea. Laryngoscopy revealed a mechanical obstruction by a right-sided, subglottical mass, which on cervical ultrasound was highly suggestive of anaplastic thyroid carcinoma. Additional workup including esophagogastroduodenoscopy showed compression of the oesophagus but no oesophageal infiltration by the tumour. Immunohistochemistry displayed CK19-positive cells indicating epithelial origin of the tumour. CK5/6 and P40 immunohistochemistry confirmed the morphological impression of squamous cell differentiation while staining with thyroid markers TTF-1 and TPO was negative and PAX8 showed a nuclear positive signal. Based on immunohistopathology, presence of TP53 and BRAF V600E mutations, and exclusion of metastatic squamous cell carcinoma of other origin, the diagnosis of a PSCC of the thyroid was established. As an individualized treatment concept, we decided to advocate combined BRAF V600E targeting by the multikinase inhibitors dabrafenib and trametinib. This led to drastic improvement in patient's quality of life without severe side effects over a period of >12 months. CONCLUSION: In this case, molecular diagnosis allowed a highly individualized treatment concept with combined dabrafenib and trametinib therapy.
ABSTRACT
Background: The tyrosine kinase inhibitors (TKI) vandetanib and cabozantinib are approved as targeted therapies in advanced medullary thyroid carcinoma (MTC) with symptoms or high tumour burden. Only recently, toxicity in long-time TKI usage was analysed. However, little is known about the impact of TKI discontinuation on MTC disease course after longer-term therapy. Here, we report our experience in a series of 7 MTC patients with vandetanib treatment of up to 87 months followed by discontinuation for concerns of toxicity or due to side-effects. The discontinuation of TKI therapy is a relevant clinical scenario. To our knowledge we present the largest single center series on an important aspect of TKI management. Methods: Retrospective analysis of MTC patients with continued discontinuation of vandetanib treatment in a tertiary referral endocrine tumour centre. Analysis included a review of patients' records for TKI indication, and treatment response as well indications for continued TKI discontinuation and follow-up by clinical assessment, calcitonin and CEA doubling times as well as imaging (ultrasound, CT). Results: Seven MTC patients [6 sporadic MTC, 1 Multiple Endocrine Neplasie Type 2a (MEN2a)] with previous vandetanib treatment (median: 41 months; range 7-87 months) and continued TKI discontinuation were identified out of 161 analysed MTC files. TKI treatment was initiated due to high tumour burden and symptoms or RECIST (Response Evaluation Criteria In Solid Tumors) progression in all patients. Two patients (29%) remained stable after discontinuation of vandetanib until now (follow-up of 47 and 61 months). Both patients had been on TKI therapy for 73 and 58 months. Five patients (71%) developed progressive disease after TKI discontinuation. In 2 patients, vandetanib was restarted after 45 and 52 months resulting again in disease control. One patient was enrolled in a new RET kinase inhibitor trial after 45 months of vandetanib discontinuation. Two patients declined restart of treatment due to mental health issues leading to discontinuation of vandetanib in the first place (after 7 and 38 months of treatment) and both patients died of rapidly progressive disease. At time points of tumour progression, calcitonin-doubling time (CDT) was < 2 years in all patients. Conclusion: This case series suggests that discontinuation of long-term vandetanib treatment with documented stable disease does not automatically result in rapid disease progression but may be followed by prolonged "TKI free" stable disease in individual patients. Analysis of calcitonin and CDT during discontinuation is indicated as it will unmask tumour progression earlier than imaging. Restart with the same TKI is possible in case of progression.
