Introduction: Analytical problems should be considered in case of a discrepancy between the results of biochemical tests and the clinical findings. Macro-hormones often artefactually elevate biochemical tests. Case Presentation: A young male was referred with persistently elevated TSH (148 mIU/L) measured by a sandwich electrochemiluminescence immunoassay, ECLIA (Cobas; Roche, Basel, Switzerland). The patient’s complaints were unspecific, and he appeared clinically euthyroid. The plasma levels of free T4 and free T3 were within the normal range, thyroid autoantibodies were negative, and thyroid ultrasonography was normal. During a short trial of thyroid hormone substitution, the level of TSH decreased to near-normal levels, but hyperthyroid symptoms emerged. TSH analysed by a different immunoassay (Architect; Abbott, Chicago, IL, USA) yielded similar results. In addition, serial dilutions were performed showing linearity, without detection of heterophilic antibody interference. Gel filtration chromatography confirmed the presence of macro-TSH. Conclusion: The patient harboured macro-TSH, which is a rare condition. The complex binding of TSH to other plasma proteins, most often immunoglobulins, results in elevated plasma TSH. However, the biologically active fraction of TSH is normal, reflected by clinical and biochemical euthyroidism.

Introduction: Myxedema coma is an endocrine emergency with a very high mortality rate. As per the American Thyroid Association, initial thyroid hormone replacement for myxedema coma should be intravenous levothyroxine (LT4). However, in India, the availability of intravenous LT4 is limited. Often, crushed LT4 tablets are given through the enteral route when parenteral therapy is unavailable. No data or protocol is available for the administration of oral LT4 in myxedema coma. The aim of this study was to assess the effectiveness of oral LT4 in patients diagnosed with myxedema coma and to formulate a protocol for oral LT4 that can be used to guide the treatment of patients when intravenous LT4 is unavailable. Methods: This retrospective observational study included patients diagnosed with myxedema coma between January 2010 and December 2019. The diagnosis of myxedema coma was based on the diagnostic scoring system for myxedema coma proposed by Popoveniuc et al. [Endocr Pract. 2014 Aug;20(8):808–17]. Dosing of oral LT4 was decided as per our institutional protocol. Results: Fourteen patients (11 males and 3 females) with a median age of 67.5 years (range 11–82) with myxedema coma were included. All patients had central nervous system manifestations, and sepsis was the most common precipitating factor. The median myxedema score was 72.5 (normal ≤25), and the median length of hospital stay was 12 days (range 3–18). The oral LT4 regimen consisted of a loading dose of 300–500 μg, followed by taper over the next 3–5 days. With this regimen, 13 patients survived, and only 1 patient died. Conclusion: Oral LT4 is an effective treatment option for myxedema coma when intravenous LT4 is unavailable.

Background: A new liquid levothyroxine (LT4) dissolved in glycerol and water has recently been developed by a Greek pharmaceutical company (Uni-Pharma, Athens, Greece). Objectives: To evaluate the therapeutic equivalence of this new liquid LT4 preparation versus the already existing tablet formulation of the same manufacturer, in order to obtain approval by the Greek National Organization for Medicines. Methods: This was a prospective, randomized, cross-over phase III study. The study included 50 patients (9 men and 41 non-pregnant women, with a mean age of 42.5 ± 12.5 years), with documented overt primary hypothyroidism. All subjects were well controlled on substitution therapy with various LT4 formulations. None of the patients had known LT4 malabsorption. The patients were randomized into 2 groups (A and B). The individuals of group A initially received T4® tablets for 10 ± 2 weeks and subsequently switched to T4® drops (100 μg/mL solution) at the same dose for another 10 ± 2 weeks. In group B, the reverse procedure was followed. Total T3 (T3), free T4 (fT4), and TSH were measured in all participants at enrollment and at the end of each 10 ± 2-week trial period. Results: Out of the 50 recruited patients, 6 were lost to follow-up and 5 were excluded due to non-compliance with the study protocol. In the 39 patients who completed the study, the serum TSH levels after 10 ± 2 weeks of treatment either with T4® tablets or with T4® drops did not differ (1.759 ± 1.104 vs. 2.076 ± 1.334 mIU/L, mean ± SD). Conclusions: In hypothyroid patients, the new liquid LT4 preparation (T4® drops) is therapeutically equivalent to the tablet form (T4® tablets).