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Author: HENNING ANDERSEN, M.D.
Date Published: 01-Jan-1955
Publication: Journal Clinical Endocrinology 15:459-468, 1955
Title: HISTOPATHOLOGIC EXAMINATION OF THE SKIN IN THE DIAGNOSIS OF MYXEDEMA IN CHILDREN
Category: diagnosing
Keywords: MYXEDEMA, ANDERSEN, skin, mucin, dermal, connective, tissue, hypothyroidism, children, hyaluronic acid, mast cells, mucinous, gland, skin, intelligence, skin biopsy
Text: 1955 HISTOPATHOLOGIC EXAMINATION OF THE SKIN IN THE DIAGNOSIS OF MYXEDEMA IN CHILDREN HENNING ANDERSEN, M.D., GUSTAV ASBOE-HANSEN, M.D. AND FLEMMING QUAADE, M.D. Children's Endocrine Clinic, Dronning Louises Børnehospital, and the Connective Tissue Research Laboratory, University Institute of Medical Anatomy, Copenhagen, Denmark Journal Clinical Endocrinology 15:459-468, 1955
p459
FOR years it has been known that hypothyroidism may be associated with an accumulation of a mucinous substance in the dermal connective tissue.
p460
Since hyaluronic acid has a marked capacity to bind water (Ropes et al.(13)), its accumulation in the tissues explains the large water content. These alterations in the connective tissue are not signs of degeneration, but of lively cellular activity, and the condition is reversible.
Myxedematous connective tissue shows accumulations of mast cells, partly in a perivascular position and partly free in the tissue. Several investigations indicate that these cells are the origin of hyaluronic acid in the mesenchymal tissues. Chemical and histochemical studies have shown that they contain a mucopolysaccharide and that they are the only type of cell in the connective tissue containing this substance.
....Pathologic accumulations of mucinous substances in the connective tissue occur when the function of the pituitary is increased in relation to the thyroid gland. This state is in most cases a result of reduced inhibition, due to a reduced production of thyroxine from the thyroid gland. The thyrotropic hormone is known to act directly on the connective tissue, without the intermediary of the thyroid gland.
p462
CLINICAL MATERIAL
The series comprised 99 children, ranging in age from 3 months to 15 years, from various children's hospitals and out-patient departments in Copenhagen. A distinction was made between the following three groups:
1. Definite clinical signs f hypothyroidism (26 children). As we felt that it was essential to define a group of children in whom the diagnosis of hypothyroidism was beyond doubt, this group includes only patients who fulfilled the ordinary criteria of thyroid hypofunction and who exhibited nothing of any relevance which could contradict the diagnosis. Particular stress was laid on the following signs: stunted growth, retarded osseous development and dentition, epiphyseal dysgenesis, the appearance of the skin, the temperature and moisture of the skin, typical facies, bodily proportions and appearance on the whole, bradycardia, low pulse pressure, constipation, subnormal temperature, increased sensitivity to cold, sluggish mentality and low intelligence. All the children were observed in the hospital for long periods and all gave a convincing response to the administration of thyroidin.
2. Suspected hypothyroidism (21 children). In these children a definite diagnosis could not be made on the basis of the foregoing criteria. The clinical data in this group are given in Table 1.
3. No signs of thyroid hypofunction (52 children).
p463
....DISCUSSION
It is possible that the following factors may have caused the negative result of the histologic examination in nearly half the children with definite clinical signs of hypothyroidism:
1. Failure to withdraw thyroidin therapy in children treated in outpatient departments. The children whose mothers admitted such failure were excluded.
2. Thyroidin may have been withheld for too brief a period. According to our latest experience, the histologic changes may take up to six weeks to re-appear, especially following overdosage of thyroidin.
3. Provided increased metachromasia and accumulation of mast cells in the skin are results of the action of thyrotropic hormone - as indicated by many findings - a negative result of histologic examination must be expected in cases of pituitary insufficiency. As there was no possibility of examining the patients by determining thyroidal I131 uptake, serum protein-bound iodine concentration, or the blood level of thyrotropic hormone, we did not feel justified in distinguishing between pituitary and thyrogenic hypothyroidism.
CONCLUSION
The histologic findings on examination of a skin biopsy specimen were positive in more than half the children with unmistakable clinical hypothyroidism, whereas they were negative in children without a reduction in thyroid function. In a group of 21 children with doubtful hypothyroidism,
p 467
the findings were positive in 8. When compared with previous reports on hypothyroidism in adults, our results warrant the following conclusions:
1. A skin biopsy specimen which shows the foregoing characteristic changes appears to afford a reliable diagnostic criterion for hypothyroidism, provided certain local dermal changes can be ruled out.
2. Negative skin biopsy findings do not exclude hypothyroidism.
SUMMARY
The histologic structure of the dermal connective tissue in hypothyroidism is described, with special reference to the ground substance, mast cells, fibrillar structure, vessel walls, and epidermis, as well as the action of the thyrotropic hormone on these tissue elements.
Histologic examination is evaluated as a diagnostic test of hypothyroidism, and the technique is described.
By this method 99 infants and children were examined. The results were as follows:
In 15 of 26 patients with definite clinical hypothyroidism the skin biopsies showed changes in the epithelial and connective tissue structures of the skin. In 8 of 21 patients suspected of hypothyroidism skin biopsies showed similar findings. A control group of 52 euthyroid children had normal skin.
In all patients with a pathologic condition of the skin, the changes disappeared during administration of thyroidin, and could be reproduced by its withdrawal.
The possible causes of negative results in hypothyroidism are discussed.
The method is a simple and handy aid in the diagnosis of hypothyroidism, especially in children. Positive findings seem to indicate hypothyroidism; negative findings do not exclude it.