Approccio terapeutico non chirurgico al paziente con oftalmopatia basedowiana

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Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients

CONTEXT: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. OBJECTIVE: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. MEASUREMENTS: TSH, FT4 and FT3 concentrations by immunoassays. RESULTS: FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients. CONCLUSIONS: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients

Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy

BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therap

IGF2: A Role in Metastasis and Tumor Evasion from Immune Surveillance?

Insulin-like growth factor 2 (IGF2) is upregulated in both childhood and adult malignancies. Its overexpression is associated with resistance to chemotherapy and worse prognosis. However, our understanding of its physiological and pathological role is lagging behind what we know about IGF1. Dysregulation of the expression and function of IGF2 receptors, insulin receptor isoform A (IR-A), insulin growth factor receptor 1 (IGF1R), and their downstream signaling effectors drive cancer initiation and progression. The involvement of IGF2 in carcinogenesis depends on its ability to link high energy intake, increase cell proliferation, and suppress apoptosis to cancer risk, and this is likely the key mechanism bridging insulin resistance to cancer. New aspects are emerging regarding the role of IGF2 in promoting cancer metastasis by promoting evasion from immune destruction. This review provides a perspective on IGF2 and an update on recent research findings. Specifically, we focus on studies providing compelling evidence that IGF2 is not only a major factor in primary tumor development, but it also plays a crucial role in cancer spread, immune evasion, and resistance to therapies. Further studies are needed in order to find new therapeutic approaches to target IGF2 action

Correlation between TSH and free thyroid hormones in euthyroid controls and in athyreotic patients.

<p>The correlation between TSH serum levels (log values) and FT3 and FT4 serum levels in 3,875 euthyroid controls (solid lines) and 1,811 athyreotic patients under levothyroxine monotherapy (dotted lines). The linear regression equations between FT4 and log TSH levels in the euthyroid controls and the levothyroxine (L-T4)-treated patients were <i>y</i> = 14.0−1.1<i>x</i> (95%: slope −1.4 to −0.74) and <i>y</i> = 16.1−2.01<i>x</i> (95% CI: slope −2.48 to −1.53), respectively. The same curve fitting analysis was used between FT3 and log-TSH levels and resulted in the following: <i>y</i> = 4.4−0.029<i>x</i> (95% CI: slope −0.128 to 0.063) for euthyroid controls and <i>y</i> = 3.84−0.575<i>x</i> (95% CI: slope −0.697 to −0.453) for L-T4-treated patients. R square and <i>P</i> values are reported in the graph.</p

FT3/FT4 ratio in levothyroxine-treated athyreotic patients at different daily dose.

<p>Median FT3/FT4 ratio in levothyroxine (L-T4) treated athyreotic patients with respect to the administered daily dose of L-T4. The median and interquartile range in the euthyroid controls are indicated by the shaded area. The number of patients with a FT3/FT4 ratio lower than the 2.5 percentile of the euthyroid controls is indicated in the right panel.</p

Orbital metastasis from thyroid cancer: a case report and review of the literature.

BACKGROUND: Differentiated thyroid cancer (DTC) is generally associated with an excellent prognosis. However up to 20% of DTC patients have disease events during subsequent follow-up; rarely patients present an aggressive disease with distant metastases (DM), mainly in the lung and bone. Metastases at unusual sites may also occur, generally in patients with disseminated disease. Orbital localization is rare and only few cases have been described so far. CASE DESCRIPTION: A 36 years-old man, treated with chemo and radiotherapy during childhood for non-Hodgkin lymphoma, was referred for suspicious lymph node (LN) and multiple lung metastases. Total thyroidectomy and latero-cervical (LC) lymphadenectomy were performed: papillary thyroid cancer (PTC), 25 mm, 11/17 LN metastases; pT2N1bM1. Post-treatment total body scan with I-131 showed LN and lung uptake. Eighteen months from diagnosis he presented progressive diplopia, proptosis and right exophthalmos due to an 18 mm orbital metastasis. Hence, due to I-131 refractoriness for structural disease progression despite I-131 therapy, he started therapy with Lenvatinib for 6 months, with initial partial response followed by disease progression, and then with Cabozantinib, which he stopped after 6 months for adverse events and disease progression after therapy reduction. Currently, the patient is receiving Lenvatinib, rechallenge therapy, with disease stabilization and biochemical response. Molecular analysis, performed on both primary and relapsed tumor didn't show any significant pathogenic alteration. CONCLUSIONS: This case of DTC with an unusual metastasis in the orbit, may suggest that patient's exposure to chemo- and radiotherapy during pediatric age might have played a role in the subsequent development of this unusually aggressive tumor, reinforcing the recommendation of long-term and intensive follow-up of these patients

Free thyroid hormones and FT3/FT4 ratio frequency distribution.

<p>FT3 and FT4 serum levels and FT3/FT4 ratio distribution in 1,811 athyreotic patients under levothyroxine (L-T4) monotherapy. Shaded areas indicate the normal range (2.5–97.5 percentiles) calculated in 3,875 euthyroid controls. Vertical dotted lines indicate the median of the normal values. Percentages indicate the patients with values under or above the normal values.</p

TSH, FT4, FT3 levels in studied subjects by age and gender.

<p>Values indicate median and interquartile ranges (IQR). FT3 = free triiodothyronine; FT4 = free thyroxine; TSH = thyroid-stimulating hormone; L-T4 = levothyroxine.</p><p>*p<0.001: males <i>vs.</i> females in the same age groups.</p>†<p>p<0.001: females≤60 yr <i>vs</i>. females>60 yr and males, both age groups.</p>‡<p>p = 0.027: males <i>vs.</i> females.</p>§<p>p<0.001: ≤60 yr <i>vs.</i> >60 yr of the same gender.</p>∥<p>p<0.001: L-T4 treated athyreotic patients <i>vs.</i> euthyroid controls.</p>¶<p>p<0.001: males ≤60 yr vs. females in the same age range.</p