Adult Myxedema Research Articles

The Isolation of Thyroxine

How fitting that on Christmas day, 1914, while the armies of Europe were locked in mortal combat, there was isolated the substance that would be the salvation of unnumbered thousands afflicted with hypothyroidism, bringing to them life and well-being. On that day, Edward C. Kendall crystallized and isolated thyroxine, enabling the determination of its chemistry.¹Within 12 years, Harrington and Barger²were able to delineate its structure and synthesize the hormone. Kendall's accomplishment was the capstone of more than 40 years of work on hypothyroidism. In 1871, Fagge³described spontaneous cretinism and speculated on the appearance of the disease occurring in adults, and three years later, Gull⁴first described adult myxedema. Although thyroid extirpation experiments in animals were occurring about this time, the association between Gull's disease and the thyroid gland was not well established until two Swiss surgeons, Reverdin and Kocher,^5,6reported on the

PUBERTAL HYPOTHYROIDISM. LACK OF GROWTH RESPONSE AFTER THYROID REPLACEMENT.

Thyroidal failure at puberty produces a syndrome with clinical manifestations intermediate between those of cretinism and adult myxedema. In addition to the symptoms of generalized hypometabolism, there are disturbed gonadal maturation, growth failure, and mental retardation, in variable degrees, dependent on the time of onset and extent of thyroprivia. Although it is stated broadly in textbooks that thyroid hormone replacement will reverse all of the hypothyroid changes, there are few reports which document the effect of therapy on growth. The observation of a patient with pubertal hypothyroidism, growth failure, and nonunited epiphyses, and who had no linear growth but epiphyseal fusion after prolonged thyroid medication, prompts this report. Report of a Case This patient, a 22-year-old white man, was admitted to US Naval Hospital, Oakland, Calif, on Jan 22, 1961, following a hypotensive episode. On the day of admission he experienced nausea, vomiting, and periumbilical pain followed by postural syncope.

Deafness with sporadic goiter. Pendred's syndrome.

Deafness is encountered in association with 3 types of thyroid disorders: adult myxedema, endemic cretinism, and Pendred's syndrome. Impairment of hearing occurs in approximately one-half of the patients with adult myxedema; hearing loss improves in about one-half of these patients after treatment with thyroid extract.^1-3Otologic examination shows the auditory impairment to be of perceptive, conductive, or mixed type. The aural anatomical changes and the type of hearing deficit present may vary with the degree of severity of the thyroid disease. Thus, the deafness may be conductive if edema of the middle ear or eustachian tube is present; or perceptive, due to an intralabyrinthine hypertension based upon myxedematous infiltration affecting the endolymphatic circulation. If the myxedema is severe and prolonged, chromatolysis of central nervous system nerve cells may occur and serve as a basis for perceptive deafness.⁴ In endemic cretinism and in Pendred's syndrome,<i>all</i>patients suffer from

Pathologic changes in adult myxedema: survey of 10 necropsies.

THE pathology of adult myxedema as recorded in the literature is based upon the findings of relatively few autopsies. The opportunity has seldom been presented to study at necropsy either untreated or inadequately treated cases. The present study was initiated because of the availability of 10 such cases at the Wayne County General Hospital in a 15-year period. Typical clinical features of the myxedematous state were present in all. The first clinical recognition of myxedema has been attributed to Sir William Gull (1) in 1873. The first autopsy in a case of myxedema was reported in 1877 by Sir William Ord (2). The term “myxedema” was proposed by Ord, because the chief feature appeared to be a mucin-yielding edema involving chiefly the connective tissue. Subsequent authors described the similarity of spontaneous myxedema, cachexia strumipriva (post-thyroidectomy myxedema) and cretinism. Loss of thyroid function later became recognized as the common denominator of these states. The Report of a Committee of the Clinical Society of London (3) published in 1888 included the data on 20 autopsies of cases of myxedema. This publication is the classic source of reference for the pathology of myxedema. Since that time, 10 autopsies have been reported by Bastenie (4), and 9 by Means (5). A few single case reports have appeared (6–14). Two cases were studied by histochemical methods (6, 7).

Therapeutic activity of desiccated thyroid substance, sodium L-thyroxine and D,L-triiodothyronine: A comparative study

T HE development of a commercially practical method for synthesizing thyroxine,’ the identification of 3,5,3’-L-triiodothyronine in human plasma2 and the recognition of its physiologic importance 3,4 have stimulated considerable interest in the re-evaluation of thyroid hormone therapy. Several reports have already appeared describing the oral or intravenous use of sodium L-thyroxine,617 L-triiodothyroninell1a,16--20 and D,L-triiodothyronine16*17 in patients with myxedema. That desiccated thyroid substance, thyroxine and triiodothyronine are all hormonally active in such trials is universally agreed. However, reported investigations with the best human test subject, the myxedematous patient, are not yet of sufficient number to settle completely the relative intensity, speed and duration of action, as well as the variations in responsiveness. The present report deals with experiences with twelve patients suffering from adult myxedema. The manner of approach differs in one respect from most if not all of the other studies of human subjects. In the present work, following attainment of a euthyroid state under therapy, the patient has been allowed to lapse into a measurable degree of hypothyroidism prior to the beginning of therapy with the same or a second thyroid preparation. This has afforded us repeated comparisons under conditions as nearly identical as possible for us to achieve. average age of fifty-three and a half years, were the subjects of this study. Each had the classical symptoms and signs of myxedema. The diagnosis was further confirmed by determination of the basal metabolic rate, serum cholesterol and, in some instances, the serum protein-bound iodine, thyroidal uptake of radioactive iodine and the twenty-four hour excretion of creatine of a person on a meat-free diet. Manifestations of myxedema had been present for periods varying from six months to twelve years prior to recognition, with an average duration of 3.7 years. In seven subjects the development of myxedema was spontaneous; in three it followed thyroidectomy; in one radiation therapy, and in the remaining one the prolonged use of an antithyroid compound. The initial basal metabolic rates of the group ranged from minus 16 to minus 47 per cent, with an average of minus 34.9 per cent. Serum cholesterol values, performed by the method of Pearson, Stern and McGavack,23 varied from 291 to 443 mg. per 100 cc. with an average of 358.4 mg. per 100 cc. The serum protein-bound iodine, carried out by the method of O’Neal and Simmsz4 was initially 3.9 pg. per 100 cc. or less. Because of the changes initially present, serial determinations were made throughout the study, as well as repeated estimations of the urinary 17-ketosteroids, blood counts, electrocardiograms and cardiac roentgenograms.

The metabolism of iodine in cerebrospinal fluid.

L1ITTLE attention has been paid to the penetration of thyroid hormone into cerebrospinal fluid (CSF), although the marked effect of thyroid hormone on the growth, development and function of the central nervous system is well documented. Congenital absence of thyroid hormone may result in the permanently impaired intellect of cretinism. Even adult myxedema results in marked dulling of mental activity, personality changes and occasionally frank psychosis (1). Conversely, overabundance of thyroid hormone, as in Graves' disease, results in mental agitation and occasionally manic or toxic psychosis (2, 3). In myxedema, cerebral blood flow is decreased and cerebral vascular resistance is increased (4, 5). Whether there is a decrease in cerebral oxygen and glucose consumption is in dispute (4, 5). Myxedema causes characteristic changes in the electroencephalogram, consisting of a low voltage, slow frequency, absence of alpha waves, and absence of reaction to light stimulus (5). In hyperthyroidism, cerebral oxyg...

TOOLS AND METHODS OF DIAGNOSIS AND NEW TRENDS IN THE TREATMENT OF ENDOCRINE DISORDERS

I FEEL very proud but most humble on receiving the honor of the Borden Award. My humility arises from the fact that whatever has been accomplished has been due to the painstaking and hard work of a series of faithful collaborators over a period of 18 years. Drs. Walter Fleischmann, Roger Lewis, Lytt Gardner, Claude Migeon, Alfred Bongiovanni and Walter Eberlein have carried out the laboratory studies, while Drs. Robert Klein, John F. Crigler, Jr., Samuel Silverman, George Clayton, Judson Van Wyk and Melvin Grumbach have directed clinical investigations. Visiting Fellows such as Salvador de Majo, Eugenia Rosemberg and José Cara have contributed materially. I gratefully share the honor with all these colleagues. The check, I shall keep myself. I shall seize the singular opportunity of the occasion to discuss the newer tools and methods which have made possible the advances of clinical endocrinology, and to point out new therapeutic approaches rather than to give a factual presentation of our own work. In 1935 when Dr. Park asked me to organize a pediatric endocrine clinic, I hesitated because I felt that at least some clinical endocrinologists were perhaps somewhat overenthusiastic and uncritical, and seemed inclined to let their imaginations run wild. During the previous century great clinical masters had given to the main endocrine disorders classical descriptions which will never be surpassed. One may mention Graves' and Basedow's descriptions of thyrotoxicosis in 1834 and 1840, Addison's of adrenal insufficiency (1854), Gull's of adult myxedema (1873), Osler's of sporadic cretinism (1893), Pierre Marie's of acromegaly (1886) and Froehlich's of the hypothalamic syndrome (1901). It was obvious that less complete forms of these and other endocrine disorders must exist.

Pregnancy in myxedema.

MYXEDEMA in women is usually associated with altered menstrual function, infertility, or repeated abortion.¹Parkin and Greene²described the occurrence of pregnancy in one patient with cretinism, in two with juvenile myxedema, and in three with adult myxedema. Their review of the world's literature revealed 10 previously recorded cases of pregnancy in true hypothyroidism, making a total of 16 cases.³Their methods of diagnosis included determinations of the basal metabolic rate and the serum cholesterol, the clinical appearance, and the response of the patient to thyroid extract. Myxedema cannot always be diagnosed unequivocally by clinical findings plus these laboratory aids. In the past, many, varied disorders of the female reproductive function unfortunately have been attributed to hypothyroidism on the basis of a single basal metabolic rate determination. We agree that the 16 previously reported cases represented true myxedema. One might expect that the increased accuracy of diagnosis

Pregnancy Occurring in Cretinism and in Juvenile and Adult Myxedema

THE IDEA prevails that pregnancy does not occur in women with cretinism or myxedema before thyroid therapy. The reports in the literature, on the other hand, agree that pregnancy can occur but that it is extremely rare. Rolleston (1) was not certain that cretins could become pregnant until after thyroid medication and thought that pregnancy in myxedema without treatment was rare. Goldzieher (2) said that myxedematous women can become pregnant, but that it is exceptional. Herrgott (3) was of the opinion that pregnancy occurred only in the attenuated forms of myxedema. We have been able to find in the literature reports of only 7 cases of adult myxedema and 3 cases of cretinism or juvenile myxedema in which pregnancy occurred before thyroid medication. During the past 12 years we have observed 3 cases of adult myxedema, 2 of juvenile myxedema and 1 of cretinism in which pregnancy occurred after the onset of the disease and before thyroid therapy.

HYPOTHYROIDISM IN CHILDHOOD. I. BASAL METABOLIC RATE, SERUM CHOLESTEROL AND URINARY CREATINE BEFORE TREATMENT1

THYROID DEFICIENCY during childhood often gives rise to physical signs which can be readily recognised. Growth is delayed, the ossification of the epiphyseal cartilages and the eruption of teeth are delayed, the proportions of the upper and lower skeletal segments remain those of a younger child, the nasoorbital configuration fails to mature as in the normal child so that the bridge of the nose remains broad and flat as in the infant. The skin and hair sometimes, but not always, show the changes similar to those of adult myxedema. The lowered metabolism is manifested in mental and physical torpor and a sluggish peripheral circulation, causing pallor of the skin. It is apparent that many of the physical signs upon which the diagnoses of hypothyroidism in childhood depend are due to the retardationor distortion of normal proc esses of growth and development occurring over a considerable period of time. The occurrence of these signs, or their severity, depends upon the age of the patient when thyroid deficie...

A COMPARISON OF THE SYMPTOMS, PHYSICAL AND LABORATORY FINDINGS OF MYXEDEMA AND PERNICIOUS ANEMIA; WITH A REPORT OF THREE CASES

Article1 November 1936A COMPARISON OF THE SYMPTOMS, PHYSICAL AND LABORATORY FINDINGS OF MYXEDEMA AND PERNICIOUS ANEMIA; WITH A REPORT OF THREE CASESJAMES A. GREENE, M.D.JAMES A. GREENE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-5-622 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe clinical manifestations of myxedema and pernicious anemia are sufficiently alike to account for the fact that the former disease is frequently mistaken for the latter. The similarities and differences of the two diseases, however, have not been emphasized. The purpose of this report is (1) to compare the clinical manifestations of the two diseases, (2) to present two cases of myxedema in which it was difficult to exclude pernicious anemia, and (3) to report another case of pernicious anemia and myxedema. The data were obtained from the records of 100 unselected cases of pernicious anemia and 33 cases of...Bibliography1. ALT HL: The metabolism in pernicious anemia, Arch. Int. Med., 1929, xliii, 488-503. CrossrefGoogle Scholar2. BALDRIDGEBARER CWA: Studies on the relationship between oxygen consumption and nitrogen metabolism. I. In pernicious anemia, Jr. Clin. Invest., 1931, x, 529-543. CrossrefGoogle Scholar3. CASTLE WB: Observations on the etiologic relationship of achylia gastrica to pernicious anemia. I. The effect of the administration to patients with pernicious anemia of the contents of the normal human stomach recovered after the ingestion of beef muscle, Am. Jr. Med. Sci., 1929, clxxviii, 748-764. CrossrefGoogle Scholar4. STURGISISAACS CCR: Treatment of the anemia of myxedema with liver extract, Proc. Cent. Soc. Clin. Res., Jr. Clin. Invest., 1929-30, viii, 663. Google Scholar5. MEANSLERMANCASTLE JHJWB: The coexistence of myxedema and pernicious anemia, New Eng. Jr. Med., 1931, cciv, 243-248. CrossrefGoogle Scholar6. BALDRIDGEGREENE CWJA: Absence of response of anemia of myxedema to liver extract, Proc. Soc. Exper. Biol. and Med., 1934, xxxi, 1035-1037. CrossrefGoogle Scholar7. LERMANMEANS JJH: Treatment of the anemia of myxedema, Endocrinology, 1932, xvi, 533-540. CrossrefGoogle Scholar8. MUSSIO-FOURNIER JC: Troubles du systeme nerveux dans le myxoedeme, Encephale, 1933, xxviii, 45-62; ibid., 1933, xxviii, 137-159. Google Scholar9. BRIGGS : Cited by Lisser and Anderson.10 Google Scholar10. LISSERANDERSON HEM: Three cases of adult myxedema in women, reported for the purpose of calling attention to their widely different symptomatology and clinical findings, Endocrinology, 1931, xv, 365-381. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Iowa City, Iowa*Received for publication August 10, 1936.From the Department of Internal Medicine, State University of Iowa Medical School. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAssociation of Gastric Carcinoma with Idiopathic Late-Onset Immunoglobulin DeficiencyPAUL E. HERMANS, M.D., F.A.C.P., KENNETH A. HUIZENGA, M.D.Megaloblastic Anemia Secondary to Folate Deficiency Associated with HypothyroidismJOHN D. HINES, M.D., CHARLES H. HALSTED, M.D., ROBERT C. GRIGGS, M.D., JOHN W. HARRIS, M.D.DEFICIENCY OF VITAMIN B12 IN HYPOTHYROIDISMNeurologic Manifestations of MyxedemaCoincidental Myxoedema and Pernicious Anaemia with Subsequent Development of Polycythaemia after Vitamin B12 TherapyVERONICA HALMOS, M.D., F.R.C.P.(C), ROBERT VOLPÉ, M.D., F.R.C.P.(C)Hypothyroidism with anemia demonstrating abnormal vitamin B12 absorption 1 November 1936Volume 10, Issue 5Page: 622-627KeywordsPernicious anemiaResearch laboratories ePublished: 1 December 2008 Issue Published: 1 November 1936 PDF downloadLoading ...

CHILDHOOD MYXEDEMA OBSERVATIONS THROUGH INFANCY, CHILDHOOD AND EARLY ADULT LIFE

The cerm cretinism implies a congenital disease characterized by physical and mental retardation due to an absence or deficiency of the normal thyroid secretion. The degree of physical and mental infirmity is dependent entirely upon the supply of the thyroid gland product. The disease was described by Paracelsus1 early in the 17th century. He was the first to point out the connection between cretinism of the offspring and goitre of the parents. Wolfgang Hoefer,2 an Austrian physician, published in 1675 his observations on cretinism in the Styrian Mountains. Until the middle of the 19th century, however, the disease was only imperfectly differentiated. Fagge described the sporadic form in 1871 and, in 1873 Gull emphasized the similarity of the disease to adult myxedema. Some years later, following the experiments conducted by Victor Horsley, a Commission appointed by the Clinical Society of London reported that myxedema and cachexia strumipriva were identical, that sporadic cretinism was myxedema occurring...

Influence of Thyroid Administration on Creatin Metabolism in Myxedema of Adults

Little is known of the creatin metabolism of adult myxedema other than the absence of spontaneous creatinuria. In children with cretinism or hypothyroidism, the physiological creatinuria of childhood is absent., When thyroid substance is given to such children, large amounts of creatin appear in the urine., This effect has been interpreted as a restoration of the normal creatinuria of childhood. It is not known, however, how long the creatinuria persists with continued administration of thyroid substance in amounts sufficient to maintain a normal basal metabolism. We have studied the creatin metabolism of 2 typical cases of spontaneous adult myxedema. Their diet was creatin-creatinin-free, and adequate in calories and protein. The ability to retain ingested creatin (1.32 gm.) was tested from time to time. After a control period, thyroid substance was administered in amounts sufficient to restore and maintain a normal basal metabolism. The usual improvement in signs and symptoms took place. Six cases of myxedema following total ablation of the thyroid were studied in the same way, except that no thyroid substance was given. Our findings in spontaneous myxedema are given in Table I and Chart 1. Results. In agreement with other workers, we found no creatinuria in spontaneous adult myxedema. Creatinuria was also absent in myxedema following total ablation of the thyroid. In both groups the retention of ingested creatin was normal. In spontaneous myxedema small doses of thyroid substance caused a pronounced creatinuria and a diminished tolerance to ingested creatin. This was observed before any elevation in the basal metabolism. In one case, at the height of the creatinuria, administration of glycine resulted in an excretion of extra creatin.

Three Cases Of Adult Myxedema In Women, Reported For The Purpose Of Calling Attention To Their Widely Different Symptomatology and Clinical Findings

Geographical peculiarities, such as altitude, latitude, climate or geological formation apparently have no influence on the incidence of adult myxedema. Indeed, Falta states that typical myxedema seems to be relatively rare in districts where goiter is endemic, and Dock mentions its infrequency in Derbyshire, the traditional home of goiter in England. Several American writers have stressed the fact that the disease is almost invariably incorrectly diagnosed and the patient passes through the hands of several consultants before myxedema is recognized. The experience of Anders, Plummer and the writers substantiate this. Moffitt many years ago collected 83 cases in California; many are never reported and many more are never recognized. The disease is probably scattered fairly evenly throughout the world, and impressions of preponderance in certain localities are apt to originate from the fact that a few physicians in these regions have been sufficiently alert to have collected many cases and placed them on r...

THREE CASES OF ADULT MYXEDEMA IN WOMEN, REPORTED FOR THE PURPOSE OF CALLING ATTENTION TO THEIR WIDELY DIFFERENT SYMPTOMATOLOGY AND CLINICAL FINDINGS:

Geographical peculiarities, such as altitude, latitude, climate or geological formation apparently have no influence on the incidence of adult myxedema. Indeed, Falta states that typical myxedema seems to be relatively rare in districts where goiter is endemic, and Dock mentions its infrequency in Derbyshire, the traditional home of goiter in England. Several American writers have stressed the fact that the disease is almost invariably incorrectly diagnosed and the patient passes through the hands of several consultants before myxedema is recognized. The experience of Anders, Plummer and the writers substantiate this. Moffitt many years ago collected 83 cases in California; many are never reported and many more are never recognized. The disease is probably scattered fairly evenly throughout the world, and impressions of preponderance in certain localities are apt to originate from the fact that a few physicians in these regions have been sufficiently alert to have collected many cases and placed them on r...