Natural course of subclinical hypothyroidism in Down’s syndrome: Prospective study results and therapeutic considerations
Pathogenesis, natural course and therapeutic management of subclinical hypothyroidism (SH) in Down’s syndrome (DS) remain object of debate in literature. In the present study thyroid function, antithyroid antibody (ATA) prevalence and serum lipid concentrations were investigated in a group of 344 Down patients (DP) and data were compared with those obtained from a control group of 257 age and sex matched healthy subjects. Thyroid function and ATA prevalence were also studied in 120 parents of DP. SH prevalence was clearly higher in DP (32.5% of cases) than in controls (1.1%) and parents (0%). Similarly, ATA prevalence was higher in DP (18% of cases) than in controls (5.8%) and parents (6.6%). In spite of this, no correlation was found in DP between SH and ATA prevalences, since ATA were detected in 18.7% of SH-DP and in 15.8% of euthyroid DP. Thus, circulating ATA were not detected in the majority of SH-DP. No significant differences regarding T4, FT4, T3 and serum lipid levels among SH and euthyroid DP and controls were found. Moreover, TSH levels were only slightly increased, generally less than 10 μU/ml, in most cases of SH-DP. Follow-up was longer than 24 months (range 2–7 years, mean 3.1) in a group of 201 DP: two different patterns of SH course were observed, mainly depending on the presence or the absence of circulating ATA. In particular, 35.7% of ATA-positive SH-DP developed a clinically evident thyroid disease (overt hypothyroidism or hyperthyroidism), while no similar case was recorded among ATA-negative SH-DP. On the contrary, a significant number of these patients (33.9% of cases) showed a spontaneous normalization of TSH levels. The present data suggest that: a) DS per se seems to be a clinical risk condition in developing thyroid autoimmune diseases, b) SH represents a very common conditions in DP and in most cases it appears to be independent of the presence of circulating ATA, c) SH alone, that is in the absence of detectable ATA, does not seem to be predisposing condition to develop a clinically evident thyroid disease, as a spontaneous normalization of TSH levels is often observed. From the therapeutic point of view, it seems unlikely that L-thyroxine substitutive therapy could lead to some improvement in SH-DP in the absence of detectable ATA. A wait and see policy with frequent thyroid function screening could be considered adequate, thus avoiding chronic hormonal therapy at least in DP in whom TSH levels tend to spontaneously normalize. On the contrary, L-thyroxine should not be delayed in ATA-positive SH-DP due to the frequent evolution towards an overt thyroid disease.
Key-wordsDown’s syndrome hypothyroidism autoimmunity L-thyroxine therapy
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