[The thyroid gland in Anothomia Mundini (1316)]. / Glandula thyreoidea i Anothomia Mundini (1316).

Andreas Vesalius described the human thyroid lobes very distinctly in his De humani corporis fabrica in 1543 calling them glandulae laryngis. Before him Leonardo da Vinci had depicted the human thyroid gland in his anatomical drawings. The first publication which could be called a textbook of human anatomy, because it was used as the basis for cathedral teaching in human anatomy for about two centuries, was the Anothomia of Mundinus Liucius, Mondino de'Liuzzi, published in 1316. In the chapter on the blood vessels of the neck he describes two glands, which he calls amigdalae, situated under the longitudinal muscles and below the larynx. Their function should be 1) to wet the trachea; 2) to fill the grove below the larynx because the neck was broader above due to the large larynx but much slender below because of the narrower trachea. And 3): they should function as a shield for the deep arteries and veins. Later anatomists at the beginning of the 15th and the 16th century, like Achillini, Massa and Zerbus, all used the text of Mundinus but obviously they tried to locate the glands of Mundinus to the tonsils apparently only because he used the denomination amigdalae. Berengario da Carpi, however, who was a much experienced anatomist, published a large treatise Commentaria super Anothomia Mundini in which he confirms the location of the glands of Mundini below the larynx. Obviously the two glands in the neck Mundinus mentions are the two thyroid lobes. According to his description they cannot be the tonsils because 1) of their location below the larynx, and 2) their function of adequating the appearance of the neck and 3) shielding, at least to some extent, the deep vessels in the neck. Before Mundini there is no similar description of the anatomy of the human neck in the literature, so what he describes must he based upon his own experience. Furthermore, he did the autopsies himself and did not use the assistance of a prosector as the professors after him used to do.

The value of visual evoked potentials in optic neuropathy of Graves' disease.

Visual evoked potentials (VEP) were tested in patients with ophthalmopathy (OP) of Graves' disease (GD) before treatment and half-a-year and 5-7 yr after orbital decompression (7 patients) or retrobulbar irradiation (3 patients). Five patients not requiring treatment for OP and 16 healthy subjects served as controls. Treatment of OP was given on clinical grounds including decreased visual acuity (VA) indicating optic neuropathy. Before treatment VA was decreased in 5 out of 19 eyes whereas VEP were abnormal in all. The mean latency at N60 both in the operated (83.1 +/- 21.6 ms) and in the irradiated groups (80.9 +/- 7.0 ms) was significantly different from that in the untreated group (62.6 +/- 8.2 ms; p < 0.001) and the healthy subjects (58.9 +/- 6.3; p < 0.001). At P120 only the latency of the operated group differed significantly from that of the other groups (p < 0.001). There was a relationship between the eye muscle changes seen on CT scans and the ophthalmopathy score (according to the classification of the American Thyroid Association) and the latency both at N60 and P120. A change from a V-shape to a W-shape of the waves occurred more often in the treated patients before therapy than in the other groups. Two patients had multiphase VEP in both eyes which improved after treatment. After adequate clinical response the visual acuity improved in one of the 5 patients with initially depressed VA. VEP, initially abnormal in all, improved in 7 of the 19 eyes (37%) but further deterioration was observed in 8 (42%).(ABSTRACT TRUNCATED AT 250 WORDS)

Endemic goitre--iodine deficiency disorders.

Endemic goitre occurs when the prevalence of thyroid enlargement in the population of an area exceeds 10%. With few exceptions its cause is iodine deficiency superimposed on other goitrogenic factors normally present and responsible for sporadic goitre. Iodine deficiency causes significant health problems and so, the term iodine deficiency disorders (IDD) has been introduced. The earliest sign of IDD is goitre, but these disorders also include cretinism, neonatal hypothyroidism and congenital defects, as well as retardation of mental and physical development etc. IDD are a worldwide problem: WHO estimates that substantially more than 800 million people are at risk and more than 190 millions suffer from IDD; over 3 million people have cretinism and in the largest and worst affected areas many millions suffer from mental and physical developmental defects. IDD can be totally eliminated by prophylaxis using iodine administered in salt, oil or some other vehicle. Problems over preventing iodine deficiency relate to difficulties in the handling and distribution of the iodized vehicle in some parts of the world and on the political will to introduce preventive schemes. In only a very few areas does the presence of goitrogenic agents in the environment cause endemic goitre despite adequate iodine supply. In a limited number of places excessive iodine from seaweed used as staple food results in endemic goitre.

Visual evoked potentials in Basedow's ophthalmopathy before and after orbital decompression or retrobulbar irradiation.

VEP are an objective and a more sensitive sign of optical neuropathy in Graves' ophthalmopathy than is visual acuity. A correlation exists between VEP and the changes in the external eye muscles as visualized on CT scans. VEP should always be registered if CT changes are present. Improvement of optic neuropathy as evaluated from VEP seems to be remarkably infrequent.

The impact of 25 years of iodine prophylaxis on the adult thyroid weight in Finland.

The effect of iodine prophylaxis on endemic goiter was studied in an adult Finnish population by comparing autopsy records from 1959 and 1984. In the 1950's the iodine intake calculated both from urinary excretion of stable iodine and from food analysis data was 50-70 micrograms per day the intake being lower in the main endemic area in the eastern part of the country. The use of iodized salt raised these figures only by 15 micrograms per day. At the beginning of the 1980's the iodine intake calculated in the same way was around 300 micrograms per day all over the country. Initially 696 records from 1959 and 525 from 1984 were analyzed. Excluded were cases with primary or secondary malignant thyroid tumors, autopsies with incompletely recorded thyroid weight, and autopsies from patients submitted to pituitary or thyroid surgery or radiation therapy. Finally, 318 cases from 1959 and 478 from 1984 were accepted. A significant decrease in thyroid weight from a mean of 44 to a mean of 34 g was observed. The difference between the two populations was most marked in the age groups below 45 yr. In these age groups the mean thyroid weight was about 20-27 g which can be regarded as normal. In the age groups over 75 years there were no significant differences. These data indicate that the iodine prophylaxis gradually eradicates the endemic goiter in Finland but that it requires still some 25-35 yr before it has disappeared also in the oldest age groups.

Differentiated follicle-derived thyroid carcinoma in children.

Fifteen patients, 11 females and 4 males, aged 4-16 years with follicle-derived differentiated thyroid carcinoma treated at the Helsinki University Central Hospital during 1953 through 1984 are reported. Histologically 13 carcinomata were papillary, 1 follicular and 1 was suspected to be follicular carcinoma (atypic adenoma). Eleven (73%) had cervical lymphnode metastases and 4 (25%) pulmonary metastases as well. All patients were initially operated on; total thyroidectomy was performed in 11 and subtotal in 4 patients. In 5 patients there was invasion into the thyroid capsule, perithyroid tissues and blood vessels; 4 patients with pulmonary metastases belonged to this group. Postoperatively 5 patients received radioactive iodine, 4 patients external irradiation to the neck and 6 were given both types of radiation. Pulmonary metastases were treated with radioactive iodine. The patients have been given suppressive doses of thyroxine. The follow-up ranged from 3.5 to 33 years. One patient with extensive pulmonary metastases died 6 years after the initial treatment, all others are still alive. Twelve patients have been followed for 9 to 33 years, in 10 serum thyroglobulin was determined. Tg was undetectable in 9 patients when measured during thyroxin therapy; in 1 patient followed for 33 years, the dose was not suppressive, and there were no signs of disease and Tg in the normal range. In 2 patients Tg could not be determined but they had no signs of disease 18 and 22 years after initial treatment. It is, therefore, presumed that these patients, forming 80% of the material, are cured. Two patients followed for 3.5 years are still under treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptors for epidermal growth factor and thyrotropin in thyroid carcinoma.

The EGF and TSH receptor properties in malignant thyroid tumours and adjacent normal thyroid tissues were characterized using radioreceptor assays. Ten patients with papillary, 4 with medullary, 1 with Hürthle cell type follicular carcinoma, and 2 with anaplastic thyroid carcinoma were studied. In 10 out of 12 patients with papillary and anaplastic thyroid carcinomas, more EGF receptors were found in the neoplastic tissue than in the adjacent normal tissue (P less than 0.01). The affinity of the EGF receptors varied between patients (from 0.5 X 10(9) l/mol to 1.9 X 10(9) l/mol), but was in each patient the same in the neoplastic and in the normal tissue. In medullary carcinomas and a follicular Hürthle thyroid carcinoma, the EGF receptor content was very low. The receptor number was unaltered or decreased in papillary carcinomas when compared with adjacent normal tissue. In anaplastic medullary and follicular (Hürthle cell) carcinomas, the neoplastic tissue had very few high affinity TSH receptor sites. The alterations in TSH receptor characteristics when thyroid neoplastic tissue was compared with adjacent normal tissue did not correlate to changes in EGF receptor characteristics. Our results demonstrate that the amount of EGF receptors in papillary and anaplastic thyroid carcinomas differ significantly from that in follicular and medullary carcinomas and that alterations in EGF receptor content in malignant thyroid tissues are independent of TSH receptor content.

Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy.

Free thyroxine (FT4) and free triiodothyronine (FT3) concentrations in serum were measured by direct equilibrium dialysis methods in patients receiving thyroxine replacement or suppression therapy. Four of 50 hypothyroid patients euthyroid on replacement therapy (mean thyroxine dose 120 micrograms/day) had supranormal FT4 concentrations, whereas the FT3 concentrations were normal in all. Forty-one of 56 operated thyroid carcinoma patients on suppressive therapy (mean thyroxine dose 214 micrograms/day) had raised FT4 concentrations, whereas the FT3 concentrations was elevated in only one patient. There was a large difference in mean FT4 values for hypothyroid and thyroid carcinoma patients (17.2 vs 29.5 pmol/l), whereas the difference in mean FT3 values was small (5.0 vs 6.1 pmol/l), suggesting a decreased peripheral conversion of T4 to T3 with increasing concentrations of FT4. Serum TSH concentrations, as determined by an immunoradiometric assay, varied from less than 0.02 to 11.9 mU/l in treated hypothyroid patients; 21 patients (42%) had values outside the reference limits. As a single test, serum TSH is therefore not very useful for the assessment of adequate thyroxine dosage in patients with primary hypothyroidism. In thyroid carcinoma patients, the TSH concentrations were less than 0.18 mU/l; 45 patients had values less than 0.02 mU/l indicating sufficient suppression of TSH secretion in the majority of cases. On the basis of these results we recommend the combination of FT3 and TSH tests for monitoring thyroxine replacement and suppression therapy. FT4 appears less useful than FT3 for this purpose even if special reference values values were adopted for each patient group.

Low TSH-response to TRH in a former endemic goiter area.

During 30 yr of iodine prophylaxis endemic goiter in school children had disappeared in the Savonlinna area which has been the location of continuous surveillance in the East of Finland. In adults goiter is still found to some extent especially in older people. The iodine intake has increased from about 50 to 300 micrograms per day during these yr and the thyroidal uptake of radioactive iodine has decreased from over 60% to between 20 and 30%. However, there is a significant difference in this regard between nongoitrous individuals and goiter patients. In the present study comprising only goiter patients it was found that the thyroidal uptake was significantly higher in the group of patients with a subnormal response to TRH. These patients also had larger goiters and more palpable thyroid nodules than those with a normal response to TRH. The mean age was significantly higher (60.3 yr) as compared to that in the group which had a TSH-response to TRH of greater than 20 mU/l, smaller glands and less thyroid nodules (45.1 yr). The data fit well with the reports on increasing autonomy with increasing age in nontoxic goiter.

Assessment of thyroxine suppression in thyroid carcinoma patients with a sensitive immunoradiometric TSH assay.

Serum TSH was determined with a sensitive radioimmunometric method (TSH IRMA) in 57 patients on suppression therapy with T4 after operation for differentiated thyroid carcinoma. When using a conventional RIA technique basal TSH was not detectable and remained so even after stimulation with TRH. With the TSH IRMA method 46 patients had a basal TSH below the detection limit (0.02 mU/l) (81%) and in seven patients the values were between 0.02 and 0.05 mU/l (12%). In 23 of these patients there was a small increment of 0.01-0.15 mU/l. In two patients the basal TSH was 0.08 and 0.09 mU/l, and the increment after TRH was less than 0.7 mU/l. In two other patients with basal values close to 0.2 mU/l the increment after TRH was more than 1.0 mU/l. An undetectable basal TSH value did not thus predict an absent response to TRH. The responses were, however, in all but two cases, so small that they could be regarded as clinically insignificant. Therefore, the authors conclude that a basal TSH of 0.1 mU/l, as measured with a TSH IRMA method with a detection limit of 0.05, is a sufficient indication of TSH suppression in carcinoma patients on T4 therapy and that further testing with the TRH-stimulation test is unnecessary.

Endemic goitre in Finland and changes during 30 years of iodine prophylaxis.

Endemic goitre of moderate severity was mainly found in the East of Finland still in the 1950s but the whole country was moderately iodine deficient. The daily iodine intake determined both from food consumption and from the urinary excretion in population samples was 50-70 micrograms being lower in the East. The main iodine sources were milk products, about 50% of the daily intake being derived from these. Iodized salt was available but its use was very low and the iodine content insufficient so that only about 20% came from this source. In the late 1950s iodine prophylaxis was activated and since then only salt containing 25 mg KI/kg has been imported. However, during the last decades the consumption of salt has declined from 7-8 g to less than 4 g per day. Today the iodine intake in Finland is about 300 micrograms per day, the highest in Europe. The main sources are milk products and eggs which provide about 2/3 of the daily iodine intake due to an active iodine prophylaxis of house animals and only 20% comes from iodized salt. The origin of endemic goitre in Finland has obviously been multifactorial autoimmunity, natural goitrogens and possibly genetic factors being superimposed upon the basic iodine deficiency. The iodine supply is now adequate and there is no more goitre in neonates and no endemic goitre in school children in whom the prevalence is usually below 1%. Concomitantly, the nosology of hyperthyroidism has changed. Whereas more than 80% of hyperthyroid patients in the 1950s had nodular goitre the main type of hyperthyroidism today is Graves' disease proper with a small or normal-sized thyroid gland without nodules obviously due to disappearance of the endemic nodular goitre.