Decreased sensitivity of thyrotropin-thyroid hormone feedback control in hypothyroid and athyreotic patients treated with levothyroxine. Is serum triiodothyronine involved?

OBJECTIVES: The search for optimal therapy for hypothyroidism is challenging and complex and is still going on. We investigated TSH-thyroid hormone feedback control in hypothyroid and athyreotic patients properly treated with levothyroxine (LT4), based on normal TSH values. MATERIAL AND METHODS: We randomly selected 150 hypothyroid, 110 athyreotic and 210 euthyroid subjects, determined their serum T4, T3 and TSH values and calculated T4/TSH and T3/T4 ratios. RESULTS: The TSH distribution in hypothyroidism was significantly shifted to the higher and that in athyreosis to the lower values from the normal distribution in euthyroid controls. This TSH-thyroid hormone dissociation in hypothyroidism was characterized with higher T4 and higher matched TSH values. We found 5% hypothyroid and 10% athyreotic patients normalize TSH only with hyperthyroxinemia. Serum T3 was lower in both hypothyroid groups and unaffected by a higher LT4 dose and higher serum T4 in athyreosis. CONCLUSION: Our results suggest that the decreased serum T3 is a major cause of impaired TSH-thyroid hormone feedback control in hypothyroidism treated with LT4.

Thyrotropin and thyroid hormone economy in euthyroid Hashimoto's thyroiditis.

Little is known about thyrotropin (TSH) and thyroid hormones in euthyroid Hashimoto's thyroiditis (HT), thus the aim was to investigate TSH and thyroid hormone economy in euthyroid HT and its relation to thyroid function. Ninety-five patients with euthyroid HT with normal TSH and thyroid hormones on the last follow up between 2009 and 2011 were investigated. Previous observation period ranged from 1.5 to 4.8 (mean 2.8) years, and they had never been treated with levothyroxine. The results of TSH and thyroid hormones were compared with 210 healthy subjects and expressed as median (25%-75%). According to TSH value, the subjects were divided into quartiles: TSH 0.4-0.99 (1q), 1.0-1.99 (2q), 2.0-2.99 (3q) and 3.0-4.0 mIU/L (4q). Euthyroid HT patients had higher TSH (2.53 [1.79-3.14] vs.1.95 [1.24-2.72], p < 0.001). T4 and T3 were not different. The distribution of TSH in HT patients was significantly shifted to the right; 71% of patients were in the 3q and 4q groups. When HT patients with higher TSH (3q and 4q) were compared with those with lower TSH (1q and 2q), significant differences emerged in TSH (3.01 [2.48-3.48] vs.1.45 [1.07-1.71] mIU/L), T4 (99.0 [88.2-112.0] vs.112.0 [105.0-122.0] nmol/L) and T3 (1.78 [1.48-2.05] vs. 2.10 [1.85-2.21] nmol/L; p < 0.01). TPO values were similar in both groups. A gradually increasing proportion of euthyroid HT patients with at least one supranormal TSH during the observation period were found: 0% in 1q, 10% in 2q, 15% in 3q and 44% in 4q TSH group. Euthyroid HT patients maintain euthyroidism only under strenuous TSH stimulation. The patients with high normal TSH are identified as those with a major risk of hypothyroidism in the near future.

Remission of Graves' disease is not related to early restoration of euthyroidism with high-dose methimazole therapy.

UNLABELLED: Introduction and aims: The most recent hypothesis postulated that early restoration of euthyroid state in patients with Graves' disease changes the course of the disease and leads to better disease control. Therefore, we analyzed the efficacy of methimazole therapy and the course of disease in patients with restored euthyroidism and in patients with active disease on first control visit. PATIENTS AND METHODS: We included 63 patients with total T4 level >190 nmol/L or T3 >7 nmol/L and diffuse goiter with no previous episodes of hyperthyroidism. All patients received initially high doses of methimazole (60-80 mg) followed by a rapid dose reduction. RESULTS: Ten percent of patients were excluded from the study due to side effects. Two different groups emerged after 5 weeks of treatment with same dose of methimazole: group 1 with active disease (48%) and group 2 with restored euthyroidism. Further controls on 12th, 24th and 68th weeks of treatment showed no difference in remission rates, number of iatrogenic hypothyroid episodes, and number of exacerbations between the two groups, regardless of methimazole dose. There was no association between age, gender, thyroid hormone levels, and remission and exacerbation rates. CONCLUSIONS: Initially, higher methimazole doses with rapid progressive decrease to maintenance dose result in similar remission rates and are followed by similar incidence of adverse side-effect as fixed low dose therapy. Our results indicate that neither an early restoration of euthyroidism nor the difference in methimazole doses influence the course of Graves' disease.

Incidentally elevated thyrotropin in otherwise properly treated hypothyroid patients does not require higher levothyroxine dose.

In 20 properly treated hypothyroid patients with normal thyrotropin (TSH) values during previous observation, TSH was incidentally mildly/moderately elevated (4.5-8.0 mIU/L; normal values 0.4-4.0) on the last follow up. However, they were continuously treated with the same levothyroxine (LT4) dose (mean: 95 µg) and six months later all TSH values normalized. The authors suggest that the physicians, in response to incidentally increased TSH value in otherwise properly treated hypothyroid patients, refrain from prompt increasing the LT4 dose unless TSH values are persistently elevated or/and progressing.

Do we treat hypothyroidism properly? A survey of 2488 patients from University Hospital Center, Zagreb, Croatia.

OBJECTIVES: The objective was to examine the effectiveness of levothyroxine treatment in hypothyroid patients in achieving normal thyroid stimulating hormone (TSH), T4 and T3. MATERIAL AND METHODS: Results of the treatment of 2448 hypothyroid patients treated with LT4 for at least 12 months between 2006 and 2011 (1920 with spontaneous hypothyroidism and 528 with hypothyroidism following surgery or 131I) are presented. Serum TSH, T4 and T3 were analyzed and referred as normal, increased or decreased. RESULTS: Normal TSH was found in 75 and 68% of patients respectively. In subgroups with increased TSH, 15% and 14% of patients showed borderline or only mildly increased TSH (4.1-5.5 mIU/L). T4 (94 and 86%) and T3 (93 and 90% respectively) were normal in the majority of patients from both groups. LT4 over-treatment is observed in only 4 and 6% of patients respectively. CONCLUSION: The results are less favorable for the group with hypothyroidism following surgery or (131)I than in spontaneous hypothyroidism, but in about 90% of patients with spontaneous hypothyroidism and 82% with hypothyroidism following surgery or (131)I, the LT4 dose could remain unchanged. It is discussed whether standard LT4 replacement could render normal TSH and thyroid hormone patterns in all hypothyroid patients.

Brain tumor as a prototype of severe brain lesion in patients with "low T3 syndrome".

The purpose of our study was to contribute to better understanding of cerebrospinal fluid (CSF) as a valuable biological material in the research of brain tumors within the "low T3 syndrome", and to discuss the role of thyroid hormones in the central nervous system in subjects with severe cerebral lesions. We studied the levels of total triiodothyronine (tT3), total thyroxine (tT4), free triiodothyronine (fT3), free thyroxine (fT4), reverse triiodothyronine (rT3) and thyrotropin (TSH) in serum, and fT3, fT4, rT3 and TSH levels in CSF of patients with brain tumor, and compared the results with control group. Study results indicated a statistically significantly higher level of rT3 in serum and CSF of brain tumor patients vs. control group (p < 0.05). The rT3/fT3 ratio was highest in CSF and serum of brain tumor patients, yielding a statistically significant difference (p < 0.05). These results could suggest higher permeability of the blood-brain barrier in brain tumor patients. We also assume that rT3, in the framework of"cerebral low T3 syndrome", is also generated through local intracerebral conversion. Disruption of this process in severe cerebral lesion can lead to increased rT3 concentrations, i.e. development of the "low T3 syndrome".

Development of Graves' disease following radioiodine treatment for autonomously functioning thyroid adenoma: case report.

A patient with development of autoimmune hyperthyroidism following radioiodine treatment for autonomously functioning thyroid adenoma is presented. This is a rare occurrence, probably as a consequence of shedding of the thyroid-stimulating hormone receptor, which is a source of antigen leading to activation of the autoimmune response in susceptible individuals.

[Croatian Thyroid Society guidelines for rational detection of thyroid dysfunction]. / Smjernice hrvatskog drustva za stitnjacu za racionalnu dijagnostiku poremecaja funkcije stitnjace.

Thyroid dysfunction is common in the population, especially in women, and thyroid diagnostic tests are among the most often used diagnostic procedures nowadays. Many thyroid societies developed guidelines for the detection of thyroid dysfunction. An interdisciplinary team of experts from the Croatian Thyroid Society studied guidelines of other thyroid societies and international publications, and according to our tradition and clinical practice developed guidelines for rational detection of thyroid dysfunction; hypothyroidism and hyperthyroidism. The aim of these guidelines is to recommend evidence-based and rational approach to the detection of thyroid dysfunction.

Why does the patient with Graves' disease remain euthyroid/mildly hyperthyroid following total thyroidectomy--the role of thyrotropin receptor antibodies (TRAb) and vestigial remnants of the thyroglossal tract.

A young female patient suffering from Graves' disease is presented, who raised some diagnostic and therapeutic dilemmas after being diagnosed with subclinical hyperthyroidism following total thyroidectomy. This 20-year-old female patient, carrier of HLA B8 DR3 genes, was referred to our hospital for total thyroidectomy after developing severe leukopenia on both methimazole and propylthiouracil therapy. A high postoperative titer of thyrotropin receptor antibodies and positive scintigraphy finding of the pyramidal lobe and remnant thyroid tissue in the left thyroid lobe led to the administration of radioiodine. Despite further enlargement of the remnant thyroid tissue on post-radioiodine scintiscanning, the patient is currently euthyroid, with normal thyroid-stimulating hormone levels; however, her long-term prognosis remains uncertain.