
Seromucoid is a heterogenous glycoprotein fraction which accounts for about 10% of the total serum polysaccharide. Numerous investigators have reported that a rise in seromucoid concentration occurs in certain specific diseases, including cancer (Winzler and Smyth, 1948; Lockey, Anderson, and MacLagan, 1956; Cameron, Campbell, and Plenderleith, 1961a and b; Cameron, Campbell, and Plenderleith, 1962; Campbell, Graham, and Cameron, 1962; Cameron and Campbell, 1964) . Many theories have been advanced to explain the origin of the excess of seromucoid in certain conditions, the most ingenious being that of Gersh and Catchpole (1949) who postulated an origin from the interstitial ground substance around the proliferating cells.

In a previous study of seromucoid levels in patients admitted to a general hospital, we have recorded that abnormal seromucoid levels occur in patients with advanced myxoedema (Cameron et al., 1961a CASE 4 A woman aged 55 years presented with signs of hypothyroidism, first diagnosed in 1959. Thyroxine therapy had been instituted, but owing to lack of cooperation on the part of the patient, treatment had been discontinued for at least two years before the commencement of this study. The serum cholesterol level was 600 mg. %.
LABORATORY METHODS
SEROMUCOID Seromucoid ('serum mucoprotein') levels were estimated by a modified Winzler procedure as detailed elsewhere (Cameron et al., 1961a) . Seromucoid levels are conveniently expressed as milligram tyrosine equivalents per 100 ml. serum (mg. SMT/100 ml.). The normal mean value for seromucoid in this laboratory as determined in a group of 60 healthy controls is 3 5± 0 75 mg. SMT/100 ml. UROMUCOID Uromucoid ('urinary mucoprotein') was isolated according to the method of Melo, Mariani, Martirani, and Cintra (1959) , the urine being dialysed for 24 hours against water. The perchloric acid-soluble glycoprotein was then precipitated with phosphotungstic acid. The uromucoid precipitate was determined by Folin-Ciocalteau's reagent on the basis of its tyrosine content. Results are also expressed as mg. SMT per 24 hours. SERUM CHOLESTEROL Serum cholesterol was estimated by Jameson's (1964) modification of the method of Allan Campbell, Ewan Cameron, and Arthur Mollison Pearson, Stern, and McGavack (1953) . This is a Liebermann-Buchard method which uses p-toluene sulphonic acid as a colour stabilizer.
LABORATORY METHODS
All four patients were treated with 1-thyroxine. Seromucoid and serum cholesterol levels were determined at least thrice weekly during the early stages of treatment, and at least weekly thereafter.
RESULTS
Case 1 was the most extensively studied, and the results of six months' observation are presented in Figure 1 . Before treatment commenced, her initial hypothyroid state was associated with a low seromucoid and a high serum cholesterol level. After two months on thyroxine, the patient was free of symptoms and euthyroid in appearance and her serum cholesterol level had dropped to within the normal range. This improvement in her clinical appearance was accompanied by a progressive and sustained rise in the seromucoid level to abnormally high levels.
RESULTS
At this point, thyroxine was withdrawn with the full understanding and consent of the patient. Within a few weeks, clinical signs of hypothyroidism reappeared, accompanied by a steadily falling seromucoid level and rise in cholesterol level. Thyroxine therapy was re-instituted, and her return to a euthyroid state was associated again with an increase in seromucoid as the cholesterol level returned to normal.
RESULTS
Cases 2, 3, and 4 were studied for shorter periods, and the results are shown in Figures 2, 3 , and 4. In these three patients it will be noted that the seromucoid concentrations also rose above normal in response to thyroxine therapy. In case 4, some estimations of urinary mucoprotein output during treatment with thyroxine were performed. It can be seen that changing levels of seromucoid tend to be accompanied by similar changes in the output of urinary mucoprotein. Hypothyroidism is characterized by an absolute increase in the amount of the mucopolysaccharide interstitial ground substance, and the return to the euthyroid state under replacement therapy is accompanied by absorption of these excessive ground substance deposits (Watson and Pearce, 1949; Iversen, 1954 

{'paper_id': '22741737', 'title': 'Seromucoid, ground substance, and hypothyroidism', 's2_url': 'https://api.semanticscholar.org/CorpusID:22741737', 'source': 'S2ORC'}