In the early 1960s, desiccated thyroid hormones (thyroid extract) began to be replaced by  levothyroxine (synthetic T4), or by combinations of T4 and T3. Replacement occurred faster in the United Kingdom than in North America, but by the 1980s more patients were being prescribed synthetic T4 (levothyroxine) or synthetic T4/T3 combinations than desiccated thyroid extract.Several reasons have been identified as to why prescriptions changed from desiccated thyroid treatment. Although thyroid extract was useful and usually effective, some patients continued to complain of fatigue, weight gain, or other symptoms. Dosing until the 1960s was often a matter of prolonged adjustment trials. It was known that not all of the iodine content of thyroid extract was in the form of effective T4 and T3 and that actual content of available preparations varied more than the permitted 15%. It was hoped that better dosing precision with levothyroxine (synthetic) alone would increase the proportion of patients effectively treated. In 1980, a widely publicized investigation published in JAMA revealed continued large ranges of hormone content and potency in all of the available thyroid extracts on the American market. By the 1960s, it was known that thyroxine was the essential hormone produced by the thyroid gland, and that most T3 was manufactured in other parts of the body by deiodination of thyroxine. It was demonstrated in hypothyroid animals and people that replacement of thyroxine alone corrected the measurable manifestations (laboratory test results) of hypothyroidism.
Hypoproteinemia is a condition where there is an abnormally low level of protein in the blood. There are several causes that all result in edema once serum protein levels fall below a certain threshold. Causes
Nutritional hypoproteinemia is due to severe limitation of protein intake in the diet. An example of nutritional hypoproteinemia is Kwashiorkor, a type of protein energy malnutrition affecting young children. Malabsorption
Liver disease can also cause hypoproteinemia by decreasing synthesis of plasma proteins like albumin. Renal disease like nephrotic syndrome can also result in hypoproteinemia because plasma proteins are lost in the urine. Sepsis (whole body infection) – macrophages activated in the liver and spleen secrete TNF-alpha into the bloodstream resulting in hypoproteinemia. Pathophysiology
Decreased serum protein reduces the oncotic pressure of the blood, leading to loss of fluid from the intravascular compartment, or the blood vessels, to the interstitial tissues, resulting in edema. This is termed as hypoproteinemia. Diagnosis
Hypoproteinemia is often confirmed by testing for serum albumin and total protein levels. References


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