Why Hypothyroidism Drugs Act up

Researchers explain how different brands of the same thyroxine work differently.

Published: 13th August 2015 01:21 AM  |   Last Updated: 13th August 2015 01:21 AM   |  A+A-

MALLESWARAM:  When patients switch brands of their drug for hypothyroidism, they receive either too much or too little of this life-saving hormone.

Dr Govindasamy Mugesh’s laboratory at the Department of Inorganic and Physical Chemistry, Indian Institute of Science, has recently come up with an explanation for this highly variable therapeutic property of generic thyroxine between brands.

In their recent paper published in the journal Angewandte Chemie, Mugesh and his student Santanu Mondal discovered that synthetic thyroxine could be present in two different forms called ‘polymorphs’ (poly= multiple; morphs=forms) that vary in their three-dimensional structures.

Using sophisticated techniques such as single-crystal and high-resolution powder X-ray diffraction (PXRD), Raman spectroscopy, solid-state nuclear magnetic resonance (SS-NMR) spectroscopy, and differential scanning calorimetry (DSC), the scientists studied the stability and molecular conformations of these two polymorphs.The solubility measurements showed that the polymorphs dissolve differently in water. This not only causes them to be differentially absorbed in the human body, but could also ultimately affect their activity in the body.

Synthetic thyroxine is a drug with a narrow therapeutic index, which means that small changes in its concentrations or activity can lead to large effects.

Therefore, the small conformational variations between the two polymorphs affect not only the hormone’s dissolution in water and bioavailability, but also its metabolism and downstream effects on the body.

This could be the leading cause of the major differences observed in the therapeutic properties of different brands of the drug.

Thyroid hormones act on every cell in the body. They are responsible for maintaining body temperature, growth, heart rate, and  also for modulating our bodies’ responses to other hormones.

Therefore, they are important regulators of metabolism, and are crucial to the proper development and function of most body organs including the brain.

Over 200 million people worldwide suffer from thyroid hormone deficiencies or hypothyroidism, a condition that manifests as mental slowness, depression, fatigue and weight gain. The condition is treated using synthetic thyroxine that is administered as tablets available from a variety of brands.

“We do need further studies in animal models to confirm our findings," says Mugesh.

Understanding the properties of thyroxine conformational polymorphs will be the first step in designing a more uniform formulation of the drug to cut down on side effects when patients switch between brands of thyroxine tablets.


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