[Current diagnosis and differential diagnosis of thyroid diseases].
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Biomedical subjects
Publications and source records attributed to D Reinwein.
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The effect of a single dose of 2 mg L-thyroxine on central and peripheral parameters of the hypophyseal-thyroid axis was studied on ten euthyroid and ten hypothyroid patients, and ten with euthyroid goitre. Without the occurrence of hyperthyroid symptoms, the T4 serum level was raised for five days in the euthyroid group, for 11 days in the hypothyroid ones. During this time the T3 serum level did not alter. Suppression of iodine uptake by the thyroid and TSH secretion of the hypophysis persisted longer, both for basal and TRH-stimulated liberation, than the substitution effect. Even when the T4 bolus has to be at a higher total T4 dose for the same therapeutic effect than with daily small single doses, it is a comparable alternative to present-day forms of treatment. It is of particular advantage where there are medical reasons for widely spaced drug intake or rapid normalisation of the T4 serum level is deemed desirable.
In a 49 years old patient with alcaptonuria we studied the question whether disturbances of the endocrine organs by deposition of products of homogenistic acid could be detected analogous to disturbances of connective tissue. The function of the hypothalamus and the pituitary gland were shown to be normal. The only defect of the endocrine organs was a hypergonadotropic hypogonadism with a serum testosterone of 5.4 and 9.4 mumol/l respectively (155 and 270 ng/dl rsp.) at elevated LH and FSH values. A sufficient stimulation of the testosterone in serum by chorionic gonadotropin (Primogonyl) could be demonstrated, thus supporting the diagnosis of a compensated insuffiency of the Leydig cells. This disorder might be a late endocrine defect due to the basic metabolic disturbance of the disease.
Binding of 125I-LH-RH and its analogue, 125I-6-D-Leu-10-Des-Gly-Ethylamide-LH-RH (6-D-LH-RH) in male serum was studied in 10 healthy males and in 11 patients with idiopathic gonadotropin deficiency (IGD) before and during treatment with 6-D-LH-RH. Using either equilibrium dialysis (A) or ethanol precipitation (B) 13.57 +/- 0.69% (A) or 19.32 +/- 1.73% (B) of LH-RH and 7.12 +/- 0.86% (A) or 14.56 +/- 1.06% (B) of the analogue were in the bound form, without difference between normal subjects and IGD. Capacity of this binding was high (greater than 9 less than 18 mu-Mol LH-RH/0.06 mMol of protein), affinity very low, and the binding almost completely disappeared following removal of albumins by affinity chromatography. Chronic treatment with 6-D-LH-RH did not alter these binding characteristics. These observations suggest non specific albumin binding of LH-RH in male serum and stress the role of this decapeptide as a rapid modulating regulator of gonadotropin secreting system.
Serum somatomedin B was measured by radioimmunoassay in forty-seven normal subjects, twenty-nine patients with acromegaly before and twenty-four after treatment, and eighteen patients with Turner's syndrome. Somatomedin B levels were significantly elevated in untreated acromegaly and in Turner's syndrome compared with the control group; they decreased following treatment of acromegaly. Because of the overlap between the groups, little information could be obtained from single somatomedin B estimations, which could, therefore, not replace dynamic tests of growth hormone secretion. No correlation between growth hormone and somatomedin B in acromegaly was detected; however, somatomedin B appeared to be related to the insulin response during the oral glucose tolerance test. In Turner's syndrome, no relationship between somatomedin B and insulin production, urinary oestrogen excretion, growth hormone secretion, gonadotrophin levels, age or height was found. The reason for the raised somatomedin B levels in Turner's syndrome remains at present unknown.
Sera of 7 patients with active acromegaly were fractionated by Sephadex G-100 chromatography and the effects of bromocriptine on the concentrations of total growth hormone (hGH) and its different molecular forms studied. Three immunoreactive peaks were observed, corresponding to molecular weights of about 20,000 ('little hGH'), 40,000 ('big hGH'), and more than 100,000 ('big big hGH') Following bromocriptine administration, there was significantly more reduction of 'little hGH' than of 'big big hGH'. Careful interpretation of these changes is required in view of the possible influences of sample storage and handling on hGH heterogeneity. We suggest that either bromocriptine acts differentially on the release of 'little' and 'big big hGH', or that these components differ in their metabolic half-life. However, even the suppression of 'little hGH' is insufficient to explain the clinical response of the disease to bromocriptine.
The syndrome of pure gonadal dysgenesis (PGD) cannot always easily be distinguished from other disorders of gonadal development. Relations are evident with Turner's syndrome, females with hypoplastic ovaries, male pseudohermaphroditism, mixed gonadal dysgenesis and the vanishing testes syndrome. The case is reported of a 40 year old female with primary amenorrhea, alopecia, eunuchoid features, XY karyotype with normal breast development and sexual hair after estrogen therapy. On laparotomy streak ovaries were found at ovarian site. Pathohistological examination revealed on the left side wolffian duct remnants such as ductuli deferentes and epididymis besides sparse Leydig-(hilus-)cells and on the right side only a rudimentary fallopian tube with subendothelial accumulation of hyperplastic Leydig-(hilus-)cells. Serum-testosterone elevation above the normal female range (630 ng/dl) persisted following gonadectomy (151 ng/dl). Ectopic Leydig-(hilus-)cells were regarded responsible for the continuing testosterone production. The present case lies on borderline between PGD and mixed gonadal dysgenesis because remnants of wolffian duct derivatives suggest unilateral fetal testicular activity; classification as PGD however was justified in purely female body features and lacking evidence of testicular tissue.
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Patients with toxic nodular goiter have only a slight chance for spontaneous remission. The same is true for hyperthyroid decompensated autonomous adenomas and iodine-induced thyrotoxicosis (jodbasedow). We therefore recommend antithyroid drugs only for preoperative preparation or for the therapy administered between fractionated 131I doses. The latter is indicated in patients over 40 years of age with a small goiter. The risk of hypothyroidism is less than 1% according to the experiences of eight thyroid centers. Experiences with euthyroid autonomous adenomas suggest no specific therapy. These patients may be managed under most circumstances by periodic follow-up evaluations.
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We may recapitulate: Chemotherapy, first of all with adriamycin, has proved successful in thyroid cancer even after exhaustion of the therapeutic measures used so far. The combination of adriamycin with bleomycin and Velbe, corresponding to our preliminary experiences, seems to be superior to a monotherapy with adriamycin. The side effects remain absolutely tolerable. Hence follows concerning further procedure that chemotherapy has to be applied earlier than practiced up to now, i.e. as soon as criteria for metastasition are observed and/or if the primary treatment--operation and irradiation--does not satisfy. Cytostatic therapy apparently is the optimal treatment technique in medullar carcinoma. But it is necessary, moreover, to search for other effective combinations of chemotherapeutic agents, especially in the case of anaplastic carcinoma. Chemotherapy, assisted by thyroid hormone treatment, can certainly be improved further by a more severe assessment of the indication, by early application and, last not least, by better coordination with surgical and radiotherapeutical action.
The effectiveness of combined cytostatic treatment with doxorubicin and bleomycin was analysed in 21 patients with metastasising thyroid carcinoma which had progressed despite both surgical and radiotherapy. Tumour histology (anaplastic carcinoma in 50%), age and general condition of all patients pointed to a poor prognosis. Significant success (full or partial remission) occurred in eight patients. It is possible that these results can be improved if chemotherapy is started earlier and other cytostatic drugs are used in case of failure of treatment.
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