Last Updated on


see iodine

  • both Cl and Na are requried to optimally transport iodide around the the thyroid

The Sodium-Iodide Symporter NIS and Pendrin in Iodide Homeostasis of the Thyroid
... pendrin is able to mediate transport of chloride and iodide (5) and that it can act as a chloride/formate exchanger
In contrast, cells expressing NIS and pendrin show a significant increase in iodide transport into the apical chamber and consequently a significant decrease in the intracellular iodide content.
The partial organification defect found in patients with Pendred syndrome suggests, however, that iodide can reach the follicular lumen independently of the presence of pendrin.


A possible function of thiols, including glutathione, as cofactors in the conversion of thyroxine to 3,3',5-triiodothyronine in rat liver microsomes.
Imai Y, Kataoka K, Nishikimi M.
Thyroxine (T4) is known to be converted to triiodothyronine (T3) in rat liver microsomes. An endogenous stimulatory factor for the conversion of T4 to T3 was identified as reduced glutathione (GSH) by Sephadex G-15 gel chromatography of rat liver extract. The production of T3 in rat liver microsomes was maximally stimulated above a GSH concentration of 4mM, and an approximately 5-fold stimulation was attained. This degree of stimulation was approximately 10 time less than that observed with dithiothreitol (DTT). Activity in the conversion of T4 to T3 was solubilized from the microsomes using 0.1% deoxycholate. When the solubilized microsomal preparation, pre-treated with DTT or GSH, was subjected to gel filtration on a Sepharose CL-6B column to separate the preparation from the thiol, almost no T3 producing activity was observed in any of the collected fractions. However, when DTT or GSH was added to the fractions containing high molecular weight components, the activity of the production of T3 was sustained. This finding indicates that these thiols play an essential role in the conversion of T4 to T3, possibly acting as cofactors.

PMID: 7408784
  • This finding indicates that these thiols play an essential role in the conversion of T4 to T3, possibly acting as cofactors.
    • glutathione useful for T4 to T3 conversion


Hypothyroidism and the Heart

  • Hypothyroidism is associated with decreased cardiac output due to impaired relaxation of vascular smooth muscle and decreased availability of endothelial nitric oxide. This produces a cascade effect of increased arterial stiffness that leads to increased systemic vascular resistance. On a molecular level, these alterations result from reduced expression of sarcoplasmic reticulum Ca2+-ATPase and increased expression of phospholamban, which inhibits ATPase
    • stiffer blood vessels
  • Thyroid hormones also impact the renin-angiotensin-aldosterone system. Renin substrates are synthesized in the liver under the stimulus of T3. Thus, in a hypothyroid state, diastolic blood pressure increases, pulse pressure narrows, and renin levels decrease. This results in diastolic hypertension that is often sodium sensitive
    • higher blood pressure
  • Erythropoietin secretion is increased by T3, which can explain the normochromic, normocytic anemia often found in hypothyroidism.
    • normocytic anemia
  • Thyroid hormones also regulate pacemaker-related genes through transcription as well as the beta-adrenergic system in cardiomyocytes. As a result of these mechanisms, heart rate increases in the presence of thyroid hormones and decreases in hypothyroidism (Table 1)
    • decreased heart rate
  • elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B. A hypothyroid state results in decreased expression of hepatic LDL receptors and reduced activity of cholesterol-α-monooxygenase, which breaks down cholesterol, resulting in decreased LDL clearance
    • less LDL clearance
  • Also noted are elevations in both C-reactive protein and homocysteine (Table 2).1,5
    • higher C-reactive protein and homocysteine
  • Thyroid hormones affect endothelial functions mediated by thyroid hormone receptor (THR)-α1 and THR-β.
    • Activation of THR-α1 increases coronary blood flow, decreases coronary resistance in mouse models, and increases production of nitric oxide in endothelial and vascular smooth muscle cells
      • less heart blood flow
    • Thyroid hormone activation of THR-β induces angiogenesis by initiating the mitogen-activated protein kinase pathway.
      • less angiogenesis
  • Though the mechanism is unclear, increased capillary permeability and reduced lymphatic drainage from the pericardial space have been suggested
    • redueced lymphatic drainage, increased capillary permeability
  • Hypothyroidism can also be associated with a decrease in insulin sensitivity due to downregulation of glucose transporters and direct effects on insulin secretion and clearance
    • decreased insulin sensitivity


See Hashimoto’s Thyroiditis