Mechanism of development of residual goitre and associated thyroid disorders

Abstract

In post salt iodination period, endemic goiter that generally develops for iodine deficiency is found prevalent in many regions, including India, despite adequate iodine intake. Such goiters are termed as residual goiters. Consumption of dietary goitrogens could be the possible regulator in the persistence of residual goitre and associated disorders. Residual goitres exist in Manipur, India for the consumption of bamboo shoots (BS). Therefore, to study the actions of BS on major thyroid hormone synthesizing regulatory factors at cellular and molecular levels on isolated thyrocytes conducted perusing expression of NIS, TPO, Tg and PDS proteins as well as mRNA and protein expression of NIS, TPO, Tg, PDS, MCT8 and PAX8 with and without extra iodine in in-vitro studies. Simultaneously, ROS generation in terms of H2O2 and antioxidant status, NO, LPO were assayed. Cellular and DNA damage and oxidation, including cell cycle alterations after BS exposure, were also investigated. Precursors and metabolic end products of cyanogenic glycosides on phytochemical analysis found in BS. It has pleiotropic effects on thyrocytes. It repressed the activities of Na+-K+-ATPase, TPO and D2, as well as reduced the expression of NIS, TPO, Tg, PDS proteins and MCT8 and PAX8, at mRNA level. All these effects of BS are mediated through increased ROS levels as H2O2 upsurge leading to a perturbed pro-oxidant antioxidant balance in thyrocytes associated with cellular and DNA damage and oxidation. Increased LPO and NO levels upon exposure of BS extract triggered plasma membrane and organelle damage of thyrocytes, which are major sites of NIS, TPO, PDS and MCT8, leading to thyroid disfunction. Cellular and DNA damage/oxidation was observed that leads to disruption of normal cell cycle pattern of thyrocytes which in turn causes changes in apoptotic proteins Bax, Bcl-2 and p53. These changes imply imbalance of cell death and proliferation equilibrium leading to disease conditions as found in goitre upon exposure to BS extract. Extra iodine prevents goitrogenic/anti-thyroid influences of BS on such actions to an extent. Thyroid diseases among residual goitrous population following consumption of BS evaluated by their iodine nutritional and salt iodization status, serumT3, T4 and TSH profiles, TPO- and Tg-Ab antibodies, thyroid ultrasonography, the prevalence of hypo- and hyperthyroidism and cytomorphological features. Goitrous populations are affected by subclinical and overt hypo- and hyperthyroidism with elevated thyroid autoantibodies, hypoechoic thyroid and thyroiditis. This study concludes that residual goitrous individuals are affected by different autoimmune thyroid disorders. Excess thiocyanate from dietary goitrogens of cyanogenic origin (BS) is responsible for the development of residual goitre followed by its progression towards different thyroid autoimmune disorders.