Recurrence of thyroid nodules after surgical removal in patients irradiated in childhood.
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Biomedical subjects
Publications and source records attributed to E D Murphy.
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In a recall clinic for patients at risk for thyroid carcinoma due to a history of radiation in infancy or childhood, a group of patients were randomly offered prospective suppressive L-thyroxine therapy and matched to a radiated nontreated group. With an average of more than two years' follow-up, the thyroid hormone-treated radiated group developed fewer nodules and abnormalities to palpation and also had a statistically significant lessening of minimal palpable abnormalities compared to the nonthyroxine-treated radiated group.
We have recently described 2 histopathologic types of inflammatory vascular disease (IVD) in patients with Sjögren's syndrome (SS): neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). Autoimmune MRL/Mp mice, which have many features of SS, spontaneously develop IVD which is histopathologically indistinguishable from that observed in human SS patients. Both MRL/Mp-+/+ and MRL/Mp-lpr/lpr mice develop MIVD which evolves into NIVD and results in decreased survival; the transition to NIVD is accelerated by the lpr gene. The presence of the lpr gene on other genetic backgrounds does not result in a similar acceleration of IVD and associated decreased survival. Thus, the spontaneous autosomal recessive mutation lpr appears to modulate the development of IVD in a strain of mice with an underlying propensity for vasculitis. Based on our observations on IVD in SS patients and MRL/Mp mice, we propose a new model which may enhance our understanding of the immunopathogenesis of IVD in connective tissue disease.
The most common complication of total thyroidectomy is hypocalcemia. Following thyroidectomy, especially total thyroidectomy, the serum calcium usually falls gradually and patients do not usually require supplementary medication before 24 hours. Two cases of total thyroidectomy are presented in which the preoperative serum calcium levels were normal and hypocalcemic tetany developed in the recovery room immediately after the operation. The hypocalcemia was a temporary phenomenon, and neither patient requires supplementary calcium at the present time. There is no good explanation for this precipitous drop in the serum calcium levels in these two patients.
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Strain BXSB/Mp mice develop a spontaneous lupus-like syndrome which is strikingly accelerated in males. The accelerated autoimmune disease occurs in male F1 hybrids with strains NZB/BINJ, SJL/J, and C57BL/6J when the male parent is BXSB but not in the reciprocal hybrid male nor in females. The pattern is similar in F2 hybrids with strains NZB and SJL. The accelerated disease in males occurs only when the Y chromosome is derived from recombinant inbred strain BXSB and ultimately from strain SB/Le.
The Evanston Hospital maintains an Irradiated Thyroid Evaluation Clinic that has evaluated 695 patients since 1975. One hundred fourteen patients were retrospectively analyzed, and an attempt was made to correlate the preoperative physical examination with the pathologic specimen after thyroidectomy. There was no statistically significant difference between the incidence of carcinoma in glands containing a single nodule (23 per cent) and in multinodular glands. Postirradiation thyroiditis complicated the physical description of glands preoperatively. The categorization of physical findings served only to identify persistent thyroid abnormalities, which must be explored surgically. The overall incidence of carcinoma in the 114 available cases was 34 per cent, with nodal metastases in 18 per cent of the patients with carcinoma.
MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.
One hundred twenty-five patients with a history of prior irradiation to the head and neck region for benign disease underwent thyroidectomies between 1967 and 1976 at Evanston Hospital. One hundred twenty-four had a palpable abnormality. Forty-two had carcinoma, and nine of these had nodal metastases. Palpation was found to be more accurate than thyroid isotope scan in finding carcinoma within an abnormal gland. Some form of irradiation thyroiditis was found in one half of the resected specimens.
Mutant alleles at the steel locus produce the pleiotropic effects of congenital anemia, sterility, and lack of hair pigmentation. Strain (WC/Re X C57BL/6)F1 Sl/Sld mice lived only half as long as heterozygotes and homozygous normal controls, differing only at the steel locus. Lymphocytic leukemia developed spontaneously in 37% of mice of the Sl/Sld genotype at an average age of 370 +/- 25 days and in 5% of heterozygotes and homozygous normal controls at 965 +/- 41 days. Severe ulcerative dermatitis occurred in 56% of Sl/Sld mice at an average age o4f 441 +/- 21 days and in 20% of heterozygotes and homozygous normal controls at 722 +/- 50 days. The mutant steel alleles provided an opportunity for study of the role of chronic anemia in life shortening and of a mechanism of gene action in spontaneous leukemogenesis.
Electron microscopic determination of C-type virions in gut-associated and genital tract epithelia was made in various murine strains. The number of morphologically identifiable C-type virus particles varied more than 100-fold among strains, being high in all strains exhibiting immunologic disease, as well as several immunologically normal strains, and low in other immunologically normal strains. No relationship was seen between the number of virions found in epithelial and lymphoid tissues. There was, however, a direct correlation between numbers of virions in epithelial tissues and levels of serum gp70.
Tumors of the mouse possess 2 isozymic forms of L-glycerol-3-phosphate dehydrogenase (alpha-GPDH) (EC 1.1.1.8) that can be distinguished from each other by their heat inactivation and electrophoretic properties. These isozymes share certain structural features, since dissociation and reassociation of mixtures of the 2 isozymes lead to the generation of a hybrid molecular species. This finding suggests that the structural genes for these isozymes are closely related. A number of spontaneous and transplantable tumors of the mouse have been analyzed in order to assess whether the pattern of embryonic and adult alpha-GPDH isozyme expression is correlated with the degree of tumor differentiation. The results indicate that no correlation between the type of isozyme expressed and the degree of tumor differentiation or growth rate was evident. A striking correlation exists, however, between the physical form of the tumor and isozyme expression; all solid tumors possess, predominantly, the adult isozymic form of L-glycerol-3-phosphate dehydrogenase, whereas all ascites tumors, including embryoid bodies from ovarian and testicular teratomas, possess the embryonic form. A solid tumor, the C1300 neuroblastoma, that initially possessed the adult isozyme, was cultured in vitro; this resulted in the disappearance of the adult isozyme and predominant expression of the embryonic isozyme. Reinjection of cultured neuroblastoma cells into a host mouse produced a solid tumor that possessed the adult isozyme. The exclusive presence of either adult alpha-GPDH in solid tumor growths or embryonic alpha-GPDH in ascites tumor growths after converting from one physical forms of the tumor to the other, strongly supports a genetic regulatory mechanism which depends on the reversible repression and activation of the structural loci for these isozymes.
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Among mice of strain SB/Le, homozygous for the mutant genes beige (bg), satin (sa), and white-bellied agouti (A(w)), 70% developed progressive pneumonitis by 6 months of age. Among backcross offspring from an outcross to C57BL/6J-A(w-J), 49% of homozygous beige and 11% of nonbeige genotypes developed pneumonitis by 6 months of age. The evidence indicates that a specific action of the beige gene increases susceptibility to progressive pneumonitis. Lymphadenopathy, including reticulum cell neoplasms and atypical lymphoproliferative lesions, was observed in high incidence in sa+/sa bg males, suggesting a closer association with satin than with beige. Beige mice show giant lysosomal granules in the leukocytes and pigment dilution closely analogous to the Chediak-Higashi syndrome in man and similar disorders in mink and cattle. Strain SB/Le provides a convenient model in a laboratory animal for study of the increased susceptibility to infection analogous to that of the Chediak-Higashi syndrome.
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