Clinical Factors Affecting Thyroid Hormone Action and Treatment Outcome of Thyroid Diseases

Thyroid hormones are crucial for the function of almost every organ system in the human body. In this PhD project, the cl

Serum microRNA profiles in athyroid patients on and off levothyroxine therapy

Background Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. Objective To study if serum miRNA profiles are changed in different thyroid states. Design and methods We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. Results Mean age of the subjects was 44.0 years (range 20–61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls

Background: For progressive metastatic medullary thyroid carcinoma (MTC), the available treatment options with tyrosine kinase inhibitors result in grade 3–4 adverse events in a large number of patients. Peptide Receptor Radionuclide Therapy (PRRT), which has also been suggested to be a useful treatment for MTC, is usually well tolerated, but evidence on its effectivity is very limited. Methods: Retrospective evaluation of treatment effects of PRRT in a highly selected group of MTC patients, with progressive disease or refractory symptoms. In addition, a retrospective evaluation of uptake on historical 111InDTPA-octreotide scans was performed in patients with detectable tumor size > 1 cm. Results: Over the last 17 years, 10 MTC patients were treated with PRRT. Four out of 10 patients showed stable disease at first follow-up (8 months after start of therapy) whereas the other 6 were progressive. Patients with stable disease were characterized by a combination of both a high uptake on 111In-DTPA-octreotide scan (uptake grade ≥ 3) and a positive somatostatin receptor type 2a (SSTR2a) expression of the tumor by immunohistochemistry. Retrospective evaluation of historical 111In-DTPA-octreotide scans of 35 non-treated MTC patients revealed low uptake (uptake grade 1) in the vast majority of patients 31/35 (89%) with intermediate uptake (uptake grade 2) in the remaining 4/35 (11%). Conclusions: PRRT using 177Lu-octreotate could be considered as a treatment in those patients with high uptake on 111In-DTPA-octreotide scan (uptake grade 3) and positive SSTR2a expression in tumor histology. Since this high uptake was present in a very limited number of patients, this treatment is only suitable in a selected group of MTC patients. Keywords: Thyroid cancer, medullary, Peptide receptor radionuclide therapy, Lutetium, Receptors, somatostati