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Dr. Shah Pathology Endocrine Lab

J Assoc Physicians India. 1999 Mar;47(3):275-9.

Sub-biochemical hypothyroidism:

an exaggerated thyroid stimulating hormone response to thyrotrophin releasing hormone.
Sheth JJ, Thakore PB, Trivedi BB, Shah NN, Vaidya RA.


Endocrine Unit, Medicare Centre, Ellisbridge, Ahmedabad, India.



The availability of sensitive and specific assays for evaluation of the thyroid axis has allowed definition of thyroid disorders at subclinical stage. This has almost obviated the use of thyrothrophin releasing hormone (TRH) study. We describe here a group of patients with minimal signs of hypothyroidism having normal thyroid function tests (T3, T4, thyroid stimulating hormone (TSH)) and have shown exaggerated TSH response to TRH.


Total 82 subjects were studied. Of these, 11 were age and sex matched controls, and 71 were patients. In all subjects TSH and other thyroid assays (T3, T4, FT4) were done by immunoradiometric assay (IRMA), and radioimmunoassay (RIA) respectively. Thyroid antibody was carried out by haemagglutination method. Results were compared to age and sex related normal ranges. To further investigate the status of thyroid axis, TRH study was carried out using standard protocol.


Based on TRH study patients were grouped in three categories. Group 1 included 29 patients whose TSH response to TRH was normal. Group 2 included 20 patients with normal baseline TSH and exaggerated TSH response to TRH and Group 3 included 18 patients with baseline TSH in the range of 5 to 10 mu IU/ml and exaggerated TSH response to TRH. There was a significant difference to total T3 between group 1 and 3 (p < 0.05) but mean values were within normal limits. While no significant difference was observed in total T4 between controls and patient's group. Serum TSH values were high in group 3 as compared to controls and Group 1 and 2 (p < 0.0001). For Free T4 no statistical significance was observed between Group 1, 2 and 3. Thyroid antibodies were positive in 22.7% of patients in Group 2 and 33.33% in Group 3.


We conclude from the present study that even with sensitive TSH assays TRH study still has a role to mark the early stage of hypothyroidism. Those with a normal or upper normal TSH with exaggerated response to TRH are termed as sub-biochemical hypothyroidism and can be considered for thyroid replacement therapy.