Cognitive functioning and well-being in euthyroid patients on thyroxine treated replacement therapy for primary hypothyroidism
EM Wekking, BC Appelhof, E Fliers, AH Schene, J Huyser, JGP Tijssen, WM Wiersinga
IntroductionOvert hypothyroidism is associated with deficits in general intelligence, memory, attention, psychomotor speed, visuoperceptual and constructional skills (1). Thyroxine (T4) replacement therapy is the standard treatment of hypothyroidism that appears effective in restoring biochemical euthyroidism as evidenced by serum thyrotropin (TSH), and free T4 and triiodothyronine (T3) concentrations within the normal range. Although hormonal substitution therapy has been very successful in reducing morbidity and mortality of primary hypothyroidism, it is well known in clinical practice that a minority of patients have persistent symptoms despite adequate T4 replacement therapy. These are often vague, aspecific complaints about fatigue, muscle aches, depressed mood or decreased memory function.
- This is the first study to evaluate neurocognitive functioning after long-standing T4 therapy (median duration of substitution therapy 5.5 years).
- Secondly, we investigated whether psychological well-being in this patient group differs from healthy subjects.
- Finally, we examined whether serum TSH or thyroid peroxidase antibodies (TPO-ab) are determinants of neurocognitive performance and well-being.
A recent community study (2) provided the first evidence to indicate that patients on thyroxine replacement even those with a normal serum TSH display significant impairment in psychological well-being compared with controls of similar age and sex. These findings raise the question whether neurocognitive functioning in T4-treated hypothyroid patients might also be impaired.
A review of neurocognitive aspects of hypothyroidism suggested that successful treatment of hypothyroidism might be associated with only partial and typically inconsistent patterns of recovery of overall neurocognitive functioning (1). However, this conclusion was reached from only a few studies on neurocognitive functioning carried out shortly after re-establishing euthyroidism with thyroid replacement therapy in hypothyroid patients.
In 1969, Whybrow et al. reported on four such patients, and concluded that when the hypothyroidism had been long-standing, brain impairment persisted after thyroid replacement therapy (3). Osterweil et al. reported on neurocognitive functioning of 54 patients with overt or minimal hypothyroidism (4). A subset of 11 to 34 patients was available for neurocognitive retesting. It was concluded that the deleterious effect of hypothyroidism is at least partly reversible, but possibly not completely, as some test results remained significantly impaired compared with euthyroid controls without hypothyroidism (4). A single case report by Mennemeier et al. reported similar conclusions (5).
As almost no data are available concerning neurocognitive functioning of patients with T4-treated hypothyroidism, we investigated the level of cognitive functioning in a large group of Dutch patients, all adequately treated for primary autoimmune hypothyroidism, and compared the results with the normal reference values for these tests.
Also read ...Abstract, Subjects and methods, Results and Discussion.
- Dugbartey AT. Neurocognitive aspects of hypothyroidism. Archives of Internal Medicine. 1998 158 1413–1418.
- Saravanan P. Chau WF, Roberts N, Vedhara K, Greenwood R, Dayan CM. Psychological well-being in patients on ‘adequate’ doses of L-Thyroxine: results of a large , controlled community-based questionnaire study. Clin Endocrinol (Oxf) 2002;57(5): 577-585.
- Whybrow PC, Prange AJ, Jr. Treadway CR. Mental changes accompanying thyroid gland dysfunction. A reappraisal using objective psychological measurements. Arch Ge. Psychiatry 1969; 20(1):48-63.
- Osterweil D, Syndulko K, Cohen SN, Pettler-Jennings, Hershman JM, Cummings JL et al. Cognitive function in non-demented older adults with hypothyoïdism. Journal of the American Geriatrics Society 1992; 40(4):325-335.
- Mennemeier M, Garner RD, Heilman KM. Memory, mood and measurement in hypothyroidism. Journal of Clinical & Experimental Neuropsychology 1993; 15(5):822-831.