Follow up of thyroid hormone parameters in chronically ill geriatric patients: screening for thyroid disorders at hospital admission justified.

UNLABELLED: The objective of this study was to investigate if screening of chronically ill geriatric patients for thyroid dysfunction is justified just upon hospital admission. TSH was measured in 124 patients at hospital admission and 11-86 (Median 37) days afterwards. FT4 was measured in cases with subnormal, suppressed or elevated TSH (43 cases). Out of 81 patients with normal (0.5-3.6 mU/l) TSH, the control value was subnormal (0.1-<0.5 mU/l) in 6 and elevated (>3.6 mU/l) in one case, but in none of the patients became suppressed (<0.1 mU/l). In 13/30 patients with subnormal TSH the control value was normal but in none of the patients suppressed or elevated. On the contrary, all cases with suppressed (N=9) or elevated (N=4) TSH remained in the same ranges at follow up. Low (<13 pmol/l, N=3) or elevated (>27 pmol/l, N=5) initial FT4 levels did not change in the follow up as well. Out of 35 patients with normal FT4, one became low and another elevated. Improvement or worsening of the clinical state in the follow up did not correlate to changes of TSH. The prevalence of unsuspected thyroid dysfunctions were 11.3% (hyperthyroidism clinical: 4, subclinical: 5, hypothyroidism clinical: 3, subclinical: 2 cases). All cases except one with subclinical hypothyroidism were detected by the initial screening. Only one patient with clinical hyperthyroidism was initial misinterpreted as having subclinical disease. CONCLUSIONS: In chronically ill geriatric patients investigated at hospital admission, a measurable TSH practically excludes hyperthyroidism in the follow up. Suppressed TSH levels remain suppressed but subnormal levels should be controlled because their normalization frequently occur in the follow up. Screening upon hospital admission is sensitive enough to detect cases of thyroid dysfunction and justified by their high prevalence.

[Therapy of endemic goiter with iodide or l-thyroxine in older patients]. / Therapie der endemischen Struma mit Jodid oder L-Thyroxin bei älteren Patienten.

OBJECTIVE: To compare the efficacy of iodide (300 micrograms daily) with that of levothyroxine (1.5 micrograms/kg daily) in the treatment of endemic goitre in middle-aged and elderly persons. The possible occurrence of antibodies against thyroid peroxidase and thyroglobulin was also tested. PATIENTS AND METHODS: 67 patients (54 women, 13 men; aged over 40 years, average 53.5 years) with endemic goitre, excluding toxic goitre, were randomly treated with either iodine or thyroxine. Every 3 months for one year their thyroid volume was obtained by ultrasound and the activities of thyroid hormone (TH) and thyroid stimulating hormone (TSH) and the concentration of antibodies against peroxidase and thyroglobulin were measured. RESULTS: In patients on levothyroxine the thyroid volume had already markedly decreased after 3 months (P < 0.0001), diminishing by 15.4% at 12 months. Volume reduction in the group on iodine was 16.2% at one year. There was no significant difference between the two medications and no case of antibody production in the iodine group. CONCLUSIONS: Treatment of endemic goitre with iodine alone is efficacious even in middle-aged or elderly patients, toxic goitre having been excluded. There was no evidence of antibody production against thyroid antigens at the stated iodine dosage.

Thyroid autoantibodies in hospitalized chronic geriatric patients: prevalence, effects of age, nonthyroidal clinical state, and thyroid function.

OBJECTIVE: To investigate the effect of age, clinical condition, and thyroid function on the prevalence of thyroid autoantibody positivity in hospitalized chronic geriatric patients. DESIGN: A screening study of hospitalized chronic geriatric patients. PARTICIPANTS: 249 non-selected, hospitalized, chronic geriatric patients more than 60 years of age and 81 20 to 40-year-old healthy persons. MEASUREMENTS: Thyrotropin (TSH); thyroxine (T4) and free thyroxine (FT4); and triiodothyronine (T3), thyroglobulin (Tg), antibodies against thyroid peroxidase (AbTPO) and antibodies against thyroglobulin (AbTg) estimation in a screening study. RESULTS: AbTPO positivity (AbTPO+) was found more often than AbTg positivity (AbTg+) (15.3% vs 9.2%, P = .04), one being positive (Ab+) in 19.3%. The occurrence was higher in females than males (Ab+:27.1% vs 7.1%, P < .001; AbTPO+:21.9% vs 5.1%, P < .001; AbTg+:13.2% vs 3.1%, P = .0052). Among the Ab+ patients, AbTPO was more often positive than AbTg (40/48 vs 21/48, P < .001). The sensitivity, specificity, and positive predictive value of Ab positivity to detect a thyroid disorder were 0.35, 0.85 and 0.38, respectively. Within the population of euthyroid geriatric patients, the occurrence of AbTg+ (chi 2(2) = 8.65, P = .013) and Ab+ (chi 2(2) = 8.02, P = .018) correlated positively with the age of the patients, and there was also a female predominance (AbTPO+ 18% vs 3.7% in the males; AbTg+ 13% vs 2.4%; Ab+ 25.8% vs 6.1%). When compared with 20 to 40-year-old subjects, only the euthyroid > or = 80-year-old patients showed a significantly higher occurrence of Ab+ (26.2% vs 9.9% chi 2(1) = 5.64, P = .017). In the euthyroid > or = 80-year-old females, AbTPO+ was 25%, AbTg:22.2%, and Ab+: 36.1%!. The nonthyroidal clinical state of the euthyroid patients did not correlate with the antibody prevalence. CONCLUSIONS: In hospitalized chronic geriatric patients, AbTg and especially AbTPO positivity is frequent, even in euthyroid patients without goiter. This aspecific Ab positivity in the euthyroid state correlates to the age, but not to the severity of the nonthyroidal clinical condition of the patients and explains why the Ab positivity is not predictive enough for thyroid dysfunction in this subpopulation. Thus, in hospitalized chronic geriatric patients the AbTg and AbTPO titers should be examined only in cases where thyroid screening (TSH) reveals abnormal results.

[Rational diagnosis of disorders of thyroid function]. / Rationelle Diagnostik von Schilddrüsenfunktionsstörungen.

A. A dysfunction of the thyroid gland can be safely excluded when the local finding of the thyroid gland, perhaps including an ultrasound, is normal and the TSH-levels are unchanged (between 0.4 and 4.0 microE/ml). B. A hyperthyreosis can be proven in 98% when TSH is suppressed (possibly a negative TSH-test) and the T3 levels and the FT3 levels, respectively, are elevated. Following examinations are necessary for the further diagnostics: When a Base-dow hyperthyreosis is suspected, T4, TR and TPO antibodies should be measured and an ultrasound obtained. When a focal or disseminated autonomy is suspected, a scintigraphy and suppression scintigraphy, respectively as well as an ultrasound should be undertaken. C. A hypothyreosis can be proven in 98% when TSH is elevated (possibly an overshooting TSH test), and the T4 levels are low. For further diagnostics, ultrasound and maybe scintigraphy should be undertaken in case of a congenital hypothyreosis. In case of an acquired hypothyreosis, TR and TPO antibodies should be measured, an ultrasound obtained, and a cytology might be taken to exclude a thyreoiditis De Quervain or a Hashimoto thyreoiditis.

[Pathogenesis, diagnosis and therapy of hyperthyroidism]. / Pathogenese, Diagnose und Therapie der Hyperthyreose.

Different forms of hyperthyreosis have to be distinguished: Frequent forms: Basedow's disease (Graves' disease, autoimmunogenic hyperthyreosis), Plummer's disease (focal or disseminated functional autonomy). Rare forms: Hyperthyreosis with thyreoiditis. This 'morphologic' hyperthyreosis is due to a destruction caused by an infection combined with a release of the thyroid hormones. This transitory hyperthyreosis can be observed particularly in the beginning of a thyreoiditis De Quervain. The treatment of the inflammation eliminates the hyperthyreosis. Sometimes, a hyperthyreosis may also be observed during a Hashimoto-thyreoiditis which, however, will turn into a hypothyreosis. An increased TSH stimulation (secondary hyperthyreosis) is a rare disease which, i.e., may be due to a genetically caused hormone resistance in the periphery followed by an overproduction of TSH. The even more rare hyperthyreosis caused by a TSH producing tumor of the pituitary gland should also be mentioned. A hyperthyreosis during struma ovarii, trophoblast tumors and recently during interferon treatment are similarly rare. A 'hyperthyreosis factitia' in correlation with a permanent application of an overdose of thyroid hormones is observed only rarely in Germany. However, a hyperthyreosis caused by physicians is more frequent: The application of contrast mediums or other substances containing iodine during a hidden functional autonomy of the thyroid gland is taken into account for the diagnosis and treatment of the Plummer's disease.

Serum thyroglobulin in hospitalized chronic geriatric patients: its relationship to age, non-thyroidal illness, goitre and thyroid dysfunction in a follow-up study.

The objectives were to determine whether the serum thyroglobulin (TG) level is influenced by age or by non-thyroidal illness (NTI) of the aged, to investigate the constancy of the TG level after 1- and 2-month intervals and to investigate if the TG level could help to differentiate whether a subnormal thyrotrophin (TSH) level in a geriatric patient is caused by autonomous thyroid function, by age or by NTI. Two-hundred and twenty-six non-selected, chronic hospitalized patients over 60 years old and 82 healthy adults (20-40 years) participated in the study, and TSH, thyroxine, free thyroxine, triiodothyronine and TG were estimated. In 122 euthyroid geriatric patients with normal TSH the mean TG was normal (12.18 micrograms/l), but elevated (> 45 micrograms/l) TG values occurred more often than in healthy control persons (15/122 vs 3/82; chi 2(1) = 4.54, p = 0.03). The severity of the clinical state of the euthyroid patients had no influence on the TG values. If TG was measured after 1 and/or 2 months, in only 3/123 non-selected geriatric patients was there a fluctuation between the normal and abnormal range (versus fluctuation of the corresponding TSH values in 19/123 cases; chi 2(1) = 12.78, p = 0.0012). In 28 patients with subnormal TSH, a normal TG value had a predictive value of 0.6 to exclude autonomous thyroid function. Age and NTI of the geriatric patients have no significant influence on their mean TG level but high TG levels occur more often, even in euthyroid patients. The predictive value of TG is not sufficiently high to allow a clear differentiation of whether a subnormal TSH is caused by autonomous thyroid function or by the age process or by NTI. Nevertheless, the advantage of TG estimation to be more constant than TSH could be of benefit in screening studies.

Surgical reintervention for differentiated thyroid cancer.

Reoperation was performed in 110 of 185 patients with a differentiated thyroid carcinoma. In 25 patients (23 per cent) the indication for reintervention was a large thyroid remnant and in the other 85 (77 per cent) persistent or recurrent cancer was suspected. In 32 (29 per cent) of the 110 patients undergoing reoperation no evidence of cancer tissue was found. Tumour tissue in 33 patients (30 per cent) was resectable. Of 45 patients (41 per cent) with residual tumour after operation 24 showed only occult thyroid carcinoma with a raised serum thyroglobulin level. Eight of 21 patients with macroscopically persistent tumour died from the disease during a mean follow-up of 2.3 years. In 13 of 38 patients the investigated recurrent tumours were histologically less differentiated than the primary lesions, stressing the importance of total tumour clearance. The treatment of choice for persistent and recurrent differentiated thyroid carcinoma is surgical reintervention, if feasible, before radioiodine and radiation therapy are considered.

Effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and iodide on the thyrotropin-releasing hormone-induced thyrotropin release from superfused rat pituitary fragments.

The effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and potassium iodide were investigated on basal and stimulated thyrotropin release in an in vitro experimental model. Rat pituitary fragments were superfused by Medium-199 with or without T3 (10(-7) mol/l), triiodothyroacetic acid (10(-8)-10(-6) mol/l), iopanoic acid (10(-7)-10(-5) mol/l) or potassium iodide (10(-7)-10(-4) mol/l). This was followed by a 6-min pulse of thyrotropin-releasing hormone (10(-8) mol/l). TSH was measured in 3-min fractions. The TRH-induced TSH release from the pituitary fragments was inhibited by T3 (10(-7) mol/l), by triiodothyroacetic acid (10(-7)-10(-6) mol/l), and by high concentrations of iodide (10(-4) or 10(-5) mol/l). Iopanoic acid had no significant effect at the concentrations tested. It is assumed that in vitro, and at similar concentrations, the inhibitory effect of triiodothyroacetic acid on the TRH-induced TSH secretion is comparable to that of T3, whereas iopanoic acid may have no direct detectable effect. In contrast, a direct inhibitory effect of inorganic iodide, at least in pharmacological concentrations in vivo, cannot be excluded.

Palliative therapy of an ectopic Cushing's syndrome due to a metastatic carcinoid tumor.

The case of a 39-year-old patient with ectopic Cushing's syndrome due to a metastatic carcinoid tumor is presented. Palliative therapy consisting of 800 mg ketoconazole and 0.3 mg SMS 201-995/die resulted in clinical remission and correction of hypokalemia and hypercortisoluria. Combined therapy was clearly superior to monotherapy with ketoconazole or SMS 201-995, respectively. Side effects were not observed, the tumor masses remained unchanged throughout the observation period of now 19 months.

Age-related decreases in the thyrotropin (TSH) responsiveness to thyrotropin-releasing-hormone (TRH) stimulation and to the inhibitory effect of triiodothyronine (T3); in vitro study on superfused rat pituitaries.

The effect of age on the thyrotropic function was investigated in vitro by superfusing pituitary fragments obtained from 2-3-month- and 24-month-old male Wistar rats with medium 199 (GIBCO) and by measuring basal TSH secretion and TSH response to a 6-min pulse of TRH (10 nM): a/ in the absence and b/ in the presence of T3 (100 nM). TSH was measured by RIA in 3-min fractions with rat TSH materials from the NIADDK. The TRH-induced TSH release elicited by pituitary fragments from the old rats was decreased in comparison to that found in young animals. Addition of T3 to the superfusion medium did not alter basal TSH release but significantly decreased the TSH secretory response to TRH in the young rats. This response was not modified in the old animals. Our results suggest that aging induces not only a TSH hyporesponsiveness to TRH stimulation but also a decrease of this responsiveness to the inhibitory effect of T3 which could be related to a decreased TSH synthesis and to an age-related impairment of T3 action on the thyrotrophs.

[Subtotal thyroid gland resection as therapy for thyrotoxic crises]. / Subtotale Schilddrüsenresektion als Therapiekonzept bei thyreotoxischer Krise.

Thyrotoxic crises occurred in six patients (four women aged 51, 63, 72 and 76 years; two men aged 52 and 63 years). In four patients the crisis was triggered by a contrast medium containing iodine, and in one by amiodarone. The cause of the crisis in the 51-year-old woman remained uncertain. After a latent period of up to two months, T3 and T4 concentrations rose in all the patients, and abnormal findings such as tachycardia, increased blood pressure, dehydration, tremor, restlessness, hallucinations and coma ensued. Because of ineffective conservative treatment, five patients underwent subtotal thyroidectomy. In all five the symptoms and signs of hyperthyroidism were promptly relieved, and the postoperative course was uneventful. The 76-year-old woman was considered unfit for surgery because of her cardiac condition, and she died of left ventricular failure resistant to therapy.

[Results of fractionated radioiodine therapy in 696 patients with hyperthyroidism and 690 patients with non-toxic goiter]. / Ergebnisse der fraktionierten Radiojodtherapie bei 696 Hyperthyreosen und 690 blanden Strumen.

During the course of twenty years 696 patients with hyperthyroidism and 690 cases of non-toxic goitre were treated with 131I in fractionated activities and controlled on an average 4,4 (1-18) years later. Treatment strategy included three special features: a. the first and any further activity amounted to not more than 1.85 MBq per g estimated thyroid weight; b. each therapeutic activity was accompanied by oral prednisone or prednisolone for 2-6 weeks; and c. after completion of radiotherapy each patient was put on thyroid medication which was not interrupted for purposes of control. Therefore, the rate of post-irradiation hypothyroidism could not be determined. All patients were found to be permanently euthyroid and none of the former hyperthyroid patients had relapsed. 84% of the hyperthyroid goitres and 78% of the non-toxic goitres had disappeared completely, 14% and 21%, respectively, were markedly reduced. Complete disappearance of the goitre was achieved with the first 131I activity in 35% of the patients with hyperthyroidism and in 48% of the non-toxic goitres, whereas 34% of the first and 35% of the second group required a second activity; the rest received three or more activities. The mean total activities of 131I necessary for complete reduction of the goitres depended on their size and amounted to 292, 507 and 1136 MBq, respectively, in euthyroid goitres with sizes, I, II and III. The corresponding figures in hyperthyroid goitres were 403, 577 and 1129 MBq, respectively. 314 patients had endocrine ophthalmopathy which was cured in 54% and significantly improved in 37%.

[Subtotal thyroidectomy as a superior therapeutic principle in the treatment of endocrine ophthalmopathy: a comparison with retrobulbar irradiation and thyrostatic therapy alone]. / Subtotale Thyreoidektomie als überlegenes Therapieprinzip bei der Behandlung der endokrinen Ophthalmopathie: Ein Vergleich mit Retrobulbärbestrahlung bzw. alleiniger thyreostatischer Therapie.

In order to investigate the influence of near total thyroidectomy on the course of endocrine ophthalmopathy (E.O.) in patients with Graves' disease, 29 patients with goitre and E.O. were classified before and after (up to 18 months) operation by use of a special ophthalmopathy index. 14 patients without goitre served as controls; they get only antithyroid drug treatment (ADT) (E.O. I and II, n = 7) or additional retoorbital irradiation (E.O. III and IV, n = 7, linear accelerator, 20 Gray). 20 out of 29 operated patients showed an improvement in the E.O., 4 a deterioration, 5 were unchanged. 3 out of 7 not operated patients with mild E.O. showed an amelioration during ADT, 4 no change. Additional radiotherapy in 7 patients with severe E.O. caused an improvement in the clinical condition of 3 patients, 3 patients deteriorated and 1 patient showed no change. It is concluded that adequate near total thyroidectomy has a positive effect on the clinical course of E.O. in patients with Graves' disease and E.O.