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

Psychological treatment of patients with chronic toxic encephalopathy:Lessons from studies of chronic fatigue and whiplash

Background. Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed treatment outcome studies of CTE and comparable syndromes, namely, chronic whiplash-associated disorder (WAD) and chronic fatigue syndrome (CFS), with a view to providing recommendations for the psychological treatment of patients with CTE. Methods: PubMed and PsychLIT were systematically searched and reference lists of retrieved articles were studied. The articles were classified according to study design and level of evidence. Results: The studies of CFS provided high-level evidence for the effectiveness of cognitive-behavior therapy (CBT) in challenging dysfunctional cognitions regarding the effectiveness of rest and in stimulating graded activity. The studies of WAD were methodologically weaker, and most evaluated a combination of CBT and graded activity training. There was some evidence that changing fatigue- or pain-related behaviors may result in cognitive improvement. Two uncontrolled studies of CTE evaluated cognitive rehabilitation techniques but yielded inconsistent findings. Conclusions: CBT techniques focusing on changing illness attributions and on stimulating graded activity might be useful for patients with CTE, diminishing fatigue-related problems of concentration and memory. Future studies should evaluate whether cognitive deficits of CTE patients as a result of neurotoxic effects of exposure should be treated by cognitive rehabilitation. Copyright (C) 2003 S. Karger AG, Basel

Autobiographical memory in the euthymic phase of recurrent depression.

The authors investigated autobiographical memory specificity in subjects who formerly had depression. In 122 euthymic patients with at least two previous major depressive episodes, memory specificity was significantly impaired compared to matched control participants but not related to residual symptoms and illness characteristics, was not differentially affected by cognitive therapy, and was also not predictive of relapse/recurrence during the 2-year follow-up. However, memory specificity was associated with age, education, and immediate and delayed memory recall. The results suggest that memory specificity may reflect a global cognitive impairment that remains in patients who (formerly) had depression but does not constitute a trait marker for vulnerability for relapse/recurrence

Polymorphisms in the brain-specific thyroid hormone transporter OATP1C1 are associated with fatigue and depression in hypothyroid patients

Introduction Some hypothyroid patients continue to have significant impairments in psychological well-being, despite adequate treatment with levothyroxine (LT4). T4 transport across the blood-brain barrier is one of the crucial processes for thyroid hormone action in the brain. OATP1C1, a thyroid hormone transporter expressed at the blood-brain barrier, is considered to play a key role in delivering serum T4 to the brain. Objective To examine whether polymorphisms in OATP1C1 are determinants of well-being, neurocognitive functioning and preference for replacement therapy with a combination of LT4 and liothyronine (LT3). Design and participants We studied 141 patients with primary autoimmune hypothyroidism, adequately treated with LT4 monotherapy and participating in a randomized clinical trial comparing LT4 therapy with LT4-LT3 combination therapy. Outcome measurements Different questionnaires on well-being and neurocognitive tests were performed at baseline. Serum thyroid parameters, OATP1C1-intron3C > T, OATP1C1-Pro143Thr and OATP1C1-C3035T polymorphisms were determined. Results Allele frequencies of the OATP1C1 polymorphisms in patients with primary hypothyroidism were similar to those of healthy controls. Both the OATP1C1-intron3C > T and the OATP1C1-C3035T polymorphism, but not the OATP1C1-Pro143Thr polymorphism, were associated with symptoms of fatigue and depression. OATP1C1 polymorphisms were not associated with measures of neurocognitive functioning or preference for combined LT4-LT3 therapy. Conclusions OATP1C1 polymorphisms are associated with fatigue and depression, but do not explain differences in neurocognitive functioning or appreciation of LT4-LT3 combination therapy. Future studies are needed to confirm these findings