ESPE Abstracts (2014) 82 P-D-3-3-698

TSH/fT4 Ratio as a Marker of TSH Resistance in Pseudoparathyroidism 1A and Obesity

Aurélia Alimia, Danielle Rodriguea, Agnès Linglarta,b & Gianpaolo De Filippoa

aAssistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Sud, Hôpital Bicêtre, Service d’Endocrinologie et Diabétologie de L’enfant, Le Kremlin-Bicêtre, France; bCentre de Référence des Maladies Rares du Calcium et du Phosphore, Le Kremlin-Bicêtre, France

Introduction: Gsα is imprinted in human thyroid glands and this appears to be important in the development of moderate TSH resistance in pseudohypoparathyroidism (PHP) 1A and less severe TSH resistance in some, but not all, other forms of PHP. Obesity is a clinical condition in which subclinical alterations of thyroid function have been reported, although the relationship between thyroid status and obesity remains unclear. It is uncertain if this biochemical abnormality may be a secondary phenomenon of obesity or a real hypothyroid state.

Methods: To investigate the correlation between TSH and circulating levels of fT4 (i.e. TSH/fT4 ratio; mUI/l per pmol/l) in patients with mild hypothyroidism (i.e. TSH value <10 μIU/ml) affected with PHP1A (n=7: mean age 7.3±5.6 years), obesity (n=8: mean age 10.4±3.2 years) and hypothyroidism secondary to Hashimoto’s thyroiditis (n=8: mean age 11.3±3.6 years). Subjects were matched for TSH levels (mean TSH 5.4±2.4, 5.5±1.5 and 4.9±0.6 μIU/ml, respectively: P=0.533 ANOVA). Patients with PHP1A or obesity were negative for thyroid autoimmunity. Ten healthy age and fT4 matched subjects were included as controls.

Results: The TSH/fT4 ratio was higher in hypothyroid patients (0.45±0.16) than in PHP and obese subjects (0.37±0.18 and 0.38±0.13) showing a trend without reaching statistic significance. The latter subjects presented a very similar hormonal phenotype. TSH/fT4 ratio in control subjects was 0.15±0.06 (P<0.001 vs patients with mild hypothyroidism). The observed trend could suggest that a ratio <0.40 in presence of TSH levels higher than 2.5 could indicate a resistance phenotype requiring further explorations.

Conclusions: The strong similarity between PHP and obese thyroid hormonal phenotype could be supplementary evidence that obesity is associated with TSH resistance rather than a real hypothyroid state.

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