Von Basedow Research Articles

Iodine in the Therapy of Graves' Disease: A Century After Henry S. Plummer.

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By an anniversary of the birth of Carl Adolph von Basedow – 221 years

March 28 marked the 221st anniversary of the birth of Karl Adolph von Basedow - a versatile and attentive family doctor who made a great contribution to the development of endocrinology and medicine in general. He is best known in German-speaking countries and in Eastern Europe for the discovery in 1840 of a diffuse toxic goiter and the discovery of the Merseburg triad (exophthalmos, tachycardia, goiter). K. Bazedov also described most of the other main characteristics of immune hyperthyroidism and endocrine ophthalmopathy, reflecting on the pathophysiological causes of these disorders. We sincerely congratulate K. Bazedov on his solid anniversary and thank him for his great work and contribution to medicine.

The Historical Development of Immunoendocrine Concepts of Psychiatric Disorders and Their Therapy.

Relationships between the central nervous, immune and endocrine systems are a focus of psychiatric research, particularly in depression and schizophrenia. The field has long antecedents. Observed phenomena attributable to these relationships date back to the Neolithic era. Immunoendocrine theories in the broadest sense are recorded in antiquity. In the 19th century, Kraepelin and Wagner-Jauregg reported pioneering clinical observations in psychiatric patients. Von Basedow, Addison and Cushing described psychiatric symptoms in patients suffering from endocrine diseases. The 20th century opened with the identification of hormones, the first, adrenaline, chemically isolated independently by Aldrich und Takamine in 1901. Berson and Yalow developed the radioimmunoassay (RIA) technique in 1959 making it possible to measure levels of hormones and cytokines. These developments have enabled great strides in psychoimmunoendocrinology. Contemporary research is investigating diagnostic and therapeutic applications of these concepts, for example by identifying biomarkers within the endocrine and immune systems and by synthesizing and testing drugs that modulate these systems and show antidepressant or antipsychotic properties.

A Century of Hyperthyroidism at Mayo Clinic

From the Division of Endocrinology & Metabolism, Mayo Clinic, Jacksonville, FL (R.C.S.); and the Division of Endocrinology & Metabolism, Mayo Clinic, Rochester, MN (J.C.M.). H yperthyroidism was first described by Caleb Hillier Parry (1825), Robert Graves (1835), and Karl von Basedow (1840). At the beginning of the 20th century, the causes were poorly understood and treatment was limited to surgery because antithyroid drugs and radioactive iodine (RAI) were unavailable until the early 1940s. Because of high surgical mortality, treatment was often delayed until the condition was advanced, and a multistage procedure might be required. Initially, hot water was injected into the thyroid, then a thyroid artery was ligated, and subsequently one or both thyroid lobes were resected. Furthermore, critically ill patients who survived surgery risked postoperative death from thyroid storm. Understanding of the etiology, pathology, physiology, clinical manifestations, and management of hyperthyroidism has evolved over the past 100 years, and new insights continue to emerge. Mayo Clinic physicians and scientists, working across disciplines, have contributed importantly to understanding this illness. This review of the Mayo Clinic experience will highlight these achievements, including pathologic clarification of the most common forms of hyperthyroidism, isolation of a crystalline product of thyroid hormone, development of a basal metabolism laboratory, discovery of a method to reduce postoperative mortality, investigation of the kinetics of thyroid hormones using radioisotopes, development and/ or establishing the clinical utility of laboratory tests to diagnose and monitor therapy for hyperthyroidism, clinical characterization of extrathyroidal manifestations of Graves disease, surgical management of severe Graves ophthalmopathy, the role of orbital radiotherapy, and the pathogenesis of Graves ophthalmopathy.

Etiopathogenesis of Basedow's disease

SummaryBasedow's disease (BD) owes its name to the German physician Karl Adolph von Basedow, who described in 1840 the clinical picture of exophthalmic toxic goitre. More than one century after the seminal paper of Karl von Basedow, the ultimate cause of BD remains to be fully elucidated. In the last years, evidence was accumulated indicating that BD is a polygenic and multifactorial disease that develops as a result of a complex interplay between genetic susceptibility and environmental and endogenous factors, which leads to the loss of immune tolerance to thyroid antigens and in particular to the TSH receptor.Our aim is to review the current knowledge on the pathogenesis of BD. To this purpose, we will firstly focus our attention on the role of genetic factors (the HLA complex, the genes encoding for thyroglobulin, the TSH receptor, CD40, CTLA-4 and PTPN22), and of environmental factors (iodine, infections, psychological stress, gender, smoking, thyroid damage, vitamin D, selenium, immune modulating agents) as possible causes of BD. Taking advantage of the experimental animal models of BD, we will then focus on the immunological mechanisms leading to the loss of tolerance in BD. The pathogenic role played by the chemokine system will be also reviewed.

Etiopathogenesis and diagnostics of autoimmune thyroid diseases

The pathogenesis of Graves-Basedow's disease is similar to that of Hashimoto’s disease (chronic autoimmune thyroiditis) and it is assumed that these two forms are the opposite poles of the same autoimmune disease. The name of the first disease derives from the surnames of two scientists who described it in the literature: Robert James Graves (1835) and Karl Adolf von Basedow (1840). The first description of the second disease was presented in 1912 by Hakaru Hashimoto. Genetic, environmental and endogenic factors are involved in the pathogenesis of autoimmune diseases. Genetic predisposition to an autoimmune disease depends on many genetic loci, of which three seem to be most important: alleles of the major histocompatibility system genes (human leukocyte antigen – HLA), mainly of class II HLA-DR3 and DR5; alleles of the gene encoding antigen-4 associated with the cytotoxic T lymphocyte (cytotoxic T lymphocyte associated antigen-4 – CTLA-4) and alleles of the gene encoding the lymphocytic tyrosine phosphatase (Protein Tyrosine Phosphatase Non Receptor – Type 22 - PTPN22). Epidemiological studies also confirm that genetic factors are responsible for autoimmune thyroid diseases with a high prevalence in patients’ relatives, especially among monozygotic twins. The environmental factors responsible for the presence of thyroid autoantigens on thyrocyte surface include viral infection, extreme stress, an excessive iodine content in diet, the action of some drugs (interferon α, amiodarone) and a huge number of chemical compounds in polluted surroundings. The most important endogenic factors include female sex and the phenomenon of foetal microchimerism in pregnant women. An organ-specific suppressor T lymphocyte defect develops in genetically predisposed people, which leads to an excessive stimulation of the T-helper lymphocytes. As a consequence, B lymphocytes experience excessive stimulation with subsequent production of plasma cells, which are responsible for the disproportionate production of antibodies against thyroid antigens – mainly the TSH receptor, thyroglobulin and thyroid peroxidase. In Graves-Basedow's disease, TSH receptor is the main autoantigen against which the antithyroid antibodies are directed. High titres of ATG and anti-TPO may suggest the coexistence of Hashimoto’s disease. In 80% cases of Graves-Basedow's disease, TSHR antibodies are stimulatory (thyroid stimulating immunoglobulins – TSI). In some cases, antibodies that inhibit thyrotropin binding to thyroid cells are produced (thyrotropin binding inhibiting immunoglobulins – TBII), which may lead to the development of hypothyroidism. In Hashimoto’s disease, cytotoxic lymphocytes, able to destroy thyroid follicular cells, receive considerable stimulation. Apart from cytotoxic lymphocytes, macrophages and the phenomenon of programmed cell death (apoptosis) also take part in the process of thyrocyte destruction. Clinical diagnosis of Graves-Basedow's disease is based on the detection of evenly enlarged thyroid gland with tactile fremitus and/or audible vascular murmur and the occurrence of the typical ophthalmic changes. Some patients also suffer from pretibial myxoedema and thyroid acropathy. Ultrasonography is a very useful imaging tool in the diagnosis of Graves-Basedow's disease – the thyroid gland is usually enlarged and has a homogenous, hypoechoic structure. Scintigraphy is not obligatory in each case of Graves-Basedow's disease, but it is very helpful in patients with the features of nodular structure and in the form without the goitre in which diagnostic difficulties occur. In the classical form of Hashimoto’s disease, a painless goitre of intensified cohesion presents with a butterfly-like shape because of the palpable pyramidal lobe. Patients complain of pressure and feeling of obstruction within the neck, and can report swallowing disorders and hoarseness. Chronic autoimmune thyroiditis can also occur in the atrophic, focal and juvenile form. Additionally, there are two variants of Hashimoto’s disease: postpartum thyroiditis and silent, painless thyroiditis. High anti-TPO antibody concentrations confirm the diagnosis of Hashimoto’s disease or any of its variants. The absence of antibodies in serum does not exclude lymphocytic thyroiditis as they are provided by intrathyroid lymphocyte infiltrations. Some authors attribute a special diagnostic significance to fine-needle aspiration biopsy in seronegative forms. Ultrasound thyroid examination is helpful in establishing correct diagnosis. Heterogeneous and distinctly hypoechoic structures of the thyroid gland are typical sonographic manifestations.

Parry and Parry’s Disease

THE MANIn 1778 the Charter of Incorporation was granted by George Ill to the presidents and associates of the Medical Society of Edinburgh, confirming Robert Freer, James Melliar, Andrew Wardrop and Caleb Parry in their office as Presidents. Caleb Parry, whose name appears here, became a highly esteemed practitioner at Bath and like Heberden acquired a lifelong habit of taking notes. He described the first recorded case of facial hemiatrophy in 1814, of congenital idiopathic dilatation of the colon in 1825, and in 1786 he left an account of exophthalmic goitre so complete and original that it more justly entitles him to the honour of its discovery than either Flajani in 1800, Graves in 1835, or von Basedow in 1840.Caleb Hillier Parry was born on October 21st 1755, at Cirencester, near Gloucester, where his father Joshua was a non-conformist minister. His early education was at the grammar school in Cirencester, where he met Edward Jenner: and the latter dedicated his epochal Inquiry in the Causes and Effects of the Variolae Vaccinae" to "C. H. Parry, M.D., at Bath, My Dear Friend." At the age of 18, Parry became a student of medicine at Edinburgh, in the days when William Cullen dominated the scene. Parry spent two of his undergraduate years in London, but when he returned in 1777, he was elected a president of the Medical Society of Edinburgh. And it was during his term of office that the Royal Charter was achieved, an honour which remains unique for an undergraduate society.

Antithyroid Drug Treatment of von Basedow's Disease: Results from a Multicenter Study

Antithyroid Drug Treatment of von Basedow's Disease: Results from a Multicenter Study

Endokrinologische Befunde bei der endokrinen Orbitopathie

Carl-Adolph von Basedow described the typical clinical features of immune-mediated hyperthyroidism (tachycardia, proptosis, goiter) in 1840 and termed it the "Merseburg trias". Graves' disease is an autoimmune disease with thyroidal and extra-thyroidal manifestations such as endocrine orbitopathy, which is caused by a dense lymphocytic infiltrate. A genetic predisposition combined with so far unidentified environmental factors and a complex immunological process seem to be important for its pathophysiology. The pathognomonic histopathophysiological picture is characterised by the typical lymphocytic infiltration of the ocular muscles and retrobulbar connective and adipose tissues leading to the classical exophthalmus. No specific therapy is available. The goal of therapy is therefore the correction of the hyperthyroidism and inhibition of the immune-mediated orbital inflammation which can be achieved by early interdisciplinary team work of endocrinologists, ophthalmologists and radiation therapy.

Forum

In 2004 we commemorate the 150th day of death of Carl Adolph von Basedow, who takes a lasting place in the history of medicine for his description of the Merseburg triad (exophthalmos, goitre, tachycardia) with hyperthyroidism. There has been a long-lasting dispute over who first described these diagnostic features. In Germany, the dermatologically-relevant features of hyperthyroidism are known as Basedow disease. In the Anglo-American literature the name "Graves' disease" is predominately used, but also authors such as Parry or Flajani are also recognised. More than 60 other publications concerning arsenic poisoning, gonorrhoeal arthritis, anthrax, thrombophlebitis as well as a variety of surgical and gynaecological problems reflect the vast field of activity and broad scientific interests of the family doctor Basedow, who reached brilliant and lasting achievements on his own and without considerable resources.

A Tribute to Carl Adolph von Basedow: To commemorate 150 years since his death

A Tribute to Carl Adolph von Basedow: To commemorate 150 years since his death

Ophthalmic Eponyms From the Mayo Clinic

Ophthalmic Eponyms From the Mayo Clinic

Disturbances of menstruation in thyroid disease.

Both hyper- and hypothyroidism may result in menstrual disturbances. In hyperthyroidism, amenorrhea was described as early as 1840 by von Basedow. The most common manifestation is simple oligomenorrhea (decreased menstrual flow). Anovulatory cycles are very common. Increased bleeding may occur, but is rare in hyperthyroidism. Nowadays hyperthyroidism is diagnosed earlier than it once was, and so the clinical picture is generally milder. So, menstrual disorders are less common than in previous series. In a recent paper, 21.5% of 214 patients had disturbances in their cycle, compared to 50% in some older series. In hypothyroidism, on the contrary, polymenorrhea (increased menstrual bleeding) is more common. Defects in hemostasis may contribute to this. Anovulation may be represent. Fertility is reduced in both hyper- and hypothyroidism, and the outcome of pregnancy is more often abnormal than in euthyroid women. It is of interest that in juvenile hypothyroidism precocious puberty has been described. This is probably due to a "spillover" effect of the glucoprotein hormones: TSH, which is markedly increased in hypothyroidism, has a small FSH- and LH-like effect. Galactorrhea may also be present in hypothyroidism, possibly because TSH, the hypophyseal TSH-releasing hormone, increases the secretion of both TSH and PRL.

Graves' ophthalmopathy. Is it really thyroid disease?

The triad of hyperthyroidism, diffuse goiter, and ophthalmopathy was identified as a disease entity by Parry, 1 Graves, 2 and von Basedow 3 in the first part of the 19th century. Although there is a strong temporal relationship between the onset of hyperthyroidism and eye symptoms, 4 many patients with hyperthyroidism do not experience clinical eye findings, and some patients with ophthalmopathy fail to manifest overt or subclinical signs of thyroid dysfunction. 5-9 The absence of a consistent linkage between the thyroid disease and the eye disease has been an impediment to the identification of a common causal agent and to agreement on the optimal clinical management of the ophthalmopathy. See also p 1098. Graves' disease is considered to be autoimmune in origin. Thyroid-stimulating immunoglobulins stimulate the thyroid-stimulating—hormone receptor on the thyroid cell membrane. 10 Some thyroid-stimulating immunoglobulins were once thought to cause ophthalmopathy, but that belief is no longer

Graves' Ophthalmopathy

The triad of hyperthyroidism, diffuse goiter, and ophthalmopathy was identified as a disease entity by Parry,¹Graves,²and von Basedow³in the first part of the 19th century. Although there is a strong temporal relationship between the onset of hyperthyroidism and eye symptoms,⁴many patients with hyperthyroidism do not experience clinical eye findings, and some patients with ophthalmopathy fail to manifest overt or subclinical signs of thyroid dysfunction.^5-9The absence of a consistent linkage between the thyroid disease and the eye disease has been an impediment to the identification of a common causal agent and to agreement on the optimal clinical management of the ophthalmopathy. See also p 1098. Graves' disease is considered to be autoimmune in origin. Thyroid-stimulating immunoglobulins stimulate the thyroid-stimulating—hormone receptor on the thyroid cell membrane.¹⁰Some thyroid-stimulating immunoglobulins were once thought to cause ophthalmopathy, but that belief is no longer

Von Basedow Research Prize Thyroid

Von Basedow Research Prize Thyroid

Endocrine ophthalmopathy: current ideas concerning etiology, pathogenesis, and treatment.

ALTHOUGH the association of exophthalmos with goiter was recognized as early as the twelfth century (1), the modern focus on the constellation of hyperthyroidism, diffuse goiter, and endocrine ophthalmopathy is best attributed to the work of Caleb Parry (1825) (2), Robert Graves (1835) (3), and Carl von Basedow (1840) (4). Since their early descriptions a plethora of reports have been published detailing the clinical and histologic features of endocrine ophthalmopathy and coining a variety of colorful synonyms and eponyms (5, 6). There remained, however, a number of important unanswered questions. These deal with the nature of the inciting factor, the pathogenesis of the disease, the unique and often asymmetric involvement of extraocular muscles, the relationship between the eye disease and the thyroid abnormality, and the most rational and efficacious methods of treatment. We will review the clinical, anatomic, histologic, and immunologic features of endocrine ophthalmopathy particularly as they apply to these issues.

Laser Iridotomy-Reply

In Reply. —In Dr Belcher's letter, a few points were raised that are of historical interest, and I am grateful for these astute amendments. Indeed, Dr Meyer-Schwickerath performed photocoagulation and the laser was not invented until 1960. It seems that Dr Zaret has, to some extent, suffered the same fate as Carl Adolph von Basedow and Caleb Hiller Parry with respect to Graves' disease, as his contributions tend to escape most of us. With regard to the relative contraindications to elective laser iridotomy of anticoagulation, uveitis, and rubeosis, I was merely citing the beliefs of others, but I must agree that laser surgery provides us with a mechanism for dealing with these problems in what, in my mind, at this time is a far safer fashion than conventional open-eye surgery. Whether it is necessary to gently precoagulate the area to be penetrated has yet to be clearly determined, but in

The pathogenesis of Graves' disease and Hashimoto's thyroiditis.

It is about 150 years since the publication of the original descriptions of the disorder now termed Graves' disease (toxic diffuse goitre, exophthalmic goitre, Von Basedow's disease) (Parry, 1825; Graves, 1835; Von Basedow, 1840) and over 60 years since Hashimoto's thyroiditis (struma lymphomatosa) was first described (Hashimoto, 1912). However, until the past 15 years, there was little understanding of possible pathogenic mechanisms in these disorders. At the present time, notwithstanding several persistent points of contention and gaps in our knowledge, it appears that Grave's disease and Hashimoto's thyroiditis are most probably closely related primary immunological disorders.

Karl von Basedow

<h3>To the Editor:—</h3> May I enter a minor correction to the note about von Basedow? (<b>208</b>:523, 1969). His birthplace correctly is Dessau, and Merseburg, where he lived and practiced, is a substantial city, the center of a huge industrial complex in East Germany, especially in the field of chemistry. The three main signs of hyperthyroidism, namely exophthalmos, goiter, and tachycardia are still called the Merseburg triad in German medicine.