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[Function of the hypothalamo-hypophyseal-thyroid axis in patients with pulmonary malignancies].

The presented literature on the function of hypothalamo-hypophyseal-thyroid axis in patients with pulmonary malignancies is unequivocal. No clinical manifestations of thyroid dysfunction were observed, however, laboratory investigations have demonstrated significant impairment of the axis function. Most frequently a decrease of T3 concentration with normal TSH level occurred in the serum of patients. Attempts at explanation of the disturbances in hypothalamo-hypophyseal-thyroid axis function are still at hypothesis stage.

Female↗

Dual ectopic thyroid gland with Graves' disease and unilateral ophthalmopathy: a case report and review of the literature.

Ectopic thyroid gland (ETG) is a rare entity and can be seen anywhere in the route of descending gland. It is much rarer when encountered away from the midline. Dual ETG is such a rare entity that only a few have been reported in the literature. ETGs not only cause thyroid dysfunction, most commonly hypothyroidism and rarely hyperthyroidism, but also frequent local symptoms. Therapeutic options change according to patients' co-morbid diseases, age, size of goiter and presence of local symptoms. Graves' disease is very rarely detected in a patient with ectopic thyroid. There is no report in literature concerning ectopic thyroid presenting with Graves' disease and unilateral ophthalmopathy. We describe a case with dual ETG and Graves' disease and unilateral ophthalmopathy: it is the first reported in literature.

Choristoma↗

Evaluation of thyroid function in patients with rapid-cycling and non-rapid-cycling bipolar disorder.

The problem of whether rapid-cycling (RC) bipolar disorder is more frequently associated than non-rapid-cycling (NRC) bipolar disorders with thyroid dysfunction was investigated in two groups of 11 women matched for age and therapy. Seven patients in each group were under chronic lithium therapy. Both RC and NRC patients, as compared to euthyroid controls, showed a reduction in mean total and free thyroid hormone concentrations, subnormal values of free thyroxine being found in four RC and three NRC patients. No patient had supranormal baseline thyroid stimulating hormone (TSH) values, but an exaggerated TSH response to thyrotropin releasing hormone was found in three RC and two NRC patients: all these patients had been receiving lithium therapy for more than one year. No differences in the prevalence of goiter and thyroid-directed autoantibodies were observed in the two groups. These data confirm that bipolar disorder, especially during treatment with lithium, is associated with at least subclinical hypothyroidism, and suggest that RC patients do not differ from NRC patients in the prevalence of spontaneous or lithium-induced thyroid hypofunction. Lithium-induced hypothyroidism is likely to be related to the length of treatment.

Adult↗

Triiodothyronine rapidly lowers plasma lipoprotein (a) in hypothyroid subjects.

BACKGROUND: Increases in plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) are well known in primary hypothyroidism, but it is uncertain whether thyroid dysfunction is associated with elevated levels of the atherogenic lipoprotein (a) (Lp(a)). METHODS: The effect of short-term hypothyroidism on plasma Lp(a) was studied in 14 patients who had undergone a total thyroidectomy because of a well-differentiated thyroid carcinoma. They were studied 2 weeks after withdrawal of triiodothyronine (T3) therapy and 7 (5-9) weeks after resumption of T3 treatment (75-100 micrograms T3 daily). Fourteen euthyroid subjects served as controls. RESULTS: In the hypothyroid phase the athyreotic patients had higher levels of Lp(a) (105 [12-536] vs. 42 [1-321] mg/l, p < 0.05), apo-B (p < 0.001) and LDL cholesterol (p < 0.001) as compared with the euthyroid control subjects. T3 therapy lowered Lp(a) by 29% to 50 (12-535) mg/l, p < 0.01. Apo B and LDL cholesterol fell by 42% (p < 0.001) and by 53% (p < 0.001), respectively. After resumption of T3 therapy the levels of Lp(a), apo-B and LDL cholesterol were not different from those of the control subjects. The mean percentual decreases in Lp(a) and in apo-B were similar, although the individual changes in Lp(a) were more variable. CONCLUSIONS: Short-term hypothyroidism increases plasma Lp(a) and T3 therapy rapidly lowers Lp(a) together with apo-B and LDL cholesterol. Our findings support the hypothesis that thyroid hormone regulates plasma Lp(a) and apo-B in a parallel manner. Elevated concentrations of Lp(a) in combination with LDL cholesterol may be involved in the increased risk of cardiovascular disease assumed to be associated with hypothyroidism.

Adult↗

Thyroid hormone binding protein abnormalities in patients referred for thyroid disorders.

BACKGROUND & OBJECTIVES: Thyroid hormone binding protein (THBP) abnormalities are the major cause of discordance in commonly performed total thyroxine (T4) and thyrotropin (TSH) estimations, though these do not interfere with thyroid hormone action. Determination of such abnormalities in patients showing discordant thyroid function tests (TFTs) is diagnostically important as it eliminates equivocal assessment of thyroid function and treatment especially where proper methodology for free T4 (FT4) estimation is not available. This study was undertaken to analyse the THBP abnormalities in the population attending thyroid clinic. Family members of affected patients were also screened to study the inheritance of quantitative TBG abnormalities. METHODS: Blood samples of 15000 consecutive patients over a period of 4 years (1994-1997) were tested for thyroid function. THBP abnormalities were studied using polyacrylamide gel electrophoresis autoradiography. Serum thyroxine binding globulin (TBG), free and total T4, total tri-iodothyronine (TT3) were assayed by radioimmunoassay methods. RESULTS: In our screening of 15,000 thyroid patients over a four year period, we found the presence of complete and partial TBG deficiency and TBG excess to be 1:2,500, 1:200 and 1:15,000 respectively. Our study on the families of three affected patients revealed X-chromosome linked inheritance pattern of TBG deficiency in two families and TBG excess in one family. INTERPRETATION & CONCLUSION: Our study suggests that it would be beneficial to rule out THBP abnormalities before interpreting results of TFTs, particularly when there is large discrepancy between T4 and TSH levels. In case of inherited THBP abnormalities, the family members of the affected individual should also be screened to avoid misdiagnosis and erroneous treatment in case they develop thyroid dysfunction in future.

Autoradiography↗

Highly sensitive immunoenzymometric assay for human thyrotropin.

A sensitive assay procedure for immunoenzymometric assay of serum thyrotropin (TSH) was developed by making several modifications of the Enzymun-Test TSH kit (Boehringer, Mannheim GmbH). Serum samples were first incubated in plastic tubes precoated with monoclonal antibodies specific to the beta subunit of human TSH. After the tubes were washed, the TSH bound to the tubes was detected with peroxidase-conjugated polyclonal antibodies to TSH. The sensitivity of the assay was 0.2 milli-int. unit/L, and the intra-and interassay CVs were less than 10%. Analytical recovery was 96 to 106%. The normal basal range of TSH was 0.5 to 4.8 milli-int. units/L. The basal levels of TSH in all but one of 48 thyrotoxic patients with Graves' disease were less than 0.2 milli-int. unit/L, clearly different from those of normal subjects. Thyrotoxic patients in early normal pregnancy showed TSH concentrations of 1.7 to 2.9 milli-int. units/L by conventional double-antibody radioimmunoassay, possibly from cross reactivity with human choriogonadotropin, but undetectable TSH by this method. Measurement of basal TSH by this sensitive assay can be used as an initial screening test for thyroid dysfunction.

Adult↗

The one-step approach to thyroid function tests. The diagnostic thyroxine ratio (DTR)/serum thyroxine (T4) level combination.

A one-step approach to thyroid function tests is reported, using Tetralute kits (Ames). Two parameters are obtained simultaneously--namely, the serum thyroxine (T4) level and the diagnostic thyroxine ratio (DTR), which correlates well with the free thyroxine index (FTI) as determined by two separate tests-the T4 level and the triiodothyronine resin uptake ((T3U)) estimations. Data presented from patients with a variety of thyroid states prove that the DTR, particularly in combination with the T4 level, is adequate for the assessment of thyroid dysfunction in almost all circumstances.

Adolescent↗

Multidisciplinary examination of patients with illness attributed to dental fillings.

OBJECTIVE AND METHODS: In 1993, a special Amalgam Clinic was established at Huddinge University Hospital. Residents in the Stockholm County area with morbidity attributed to dental fillings ('amalgam disease'), were referred to this clinic. Patients were examined by a dentist (n 428), a physician (n 379), and a psychologist (n 360). Sixty-nine per cent were women and 31% men; the mean patient age was 46 years. RESULTS: Oral symptoms included tender or aching teeth (60%), metallic taste (54%), sore mouth (43%) and dry mouth (43%). Signs of moderate or severe temporomandibular joint dysfunction were found in 81 cases, glossitis in 30 and oral lichen in 26 cases. Common general symptoms included diffuse pain (78%), general weakness (75%), extreme fatigue (68%) and dizziness (68%). Seven per cent of the patients suffered from previously undiagnosed medical conditions (thyroid dysfunction, anaemia, cardiopathy, renal disease, cancer). In 26 subjects, skin patch testing revealed allergy to mercury, gold or palladium. The median concentration of mercury was 10 nmol L-1 in whole blood, 3 nmol L-1 in plasma and 10 nmol L-1 in urine, i.e. normal levels. Earlier mental trauma was common, and in the psychological questionnaire SCL-90, clear tendencies to somatization were found. Only a few cases of severe psychiatric illness were observed. No positive correlation was found between the amount of amalgam and somatic symptoms or psychological effect parameters. CONCLUSIONS: The results do not support the hypothesis that release of mercury from amalgam fillings is the cause of 'amalgam disease', but suggest that there may be various explanations for the patient's complaints.

Acute Disease↗

A sensitive thyroid stimulating hormone assay for screening of thyroid functional disorder in elderly Japanese.

The use of a screening test for thyroid functional disorder by sensitive thyroid stimulating hormone assay in the elderly was investigated. The basal thyroid stimulating hormone levels predicted the response of thyroid stimulating hormone to thyrotropin releasing hormone; it was suppressed in 99 (99.0%) of 100 hyperthyroid patients. Therefore, not only primary hypothyroidism but also hyperthyroidism can be excluded when the serum thyroid stimulating hormone levels are normal. An epidemiological study was then performed on 2,421 (76.7%) of the Japanese general population aged 40 or over recruited from the residents in Hisayama town and also in 122 residents between 20 and 40 years of age. Additional free T4 measurement was necessary in about 10% of the residents with abnormal TSH levels to confirm the diagnosis of hyperthyroidism or distinguish latent from overt hypothyroidism. There was a significant correlation between age and serum thyroid stimulating hormone levels after logarithmic conversion (r = 0.1533, P less than .001). The prevalence of thyroid dysfunction found in 1,026 males and in 1,395 females aged 40 or over was, respectively: hyperthyroidism, less than 0.1% and 0.2%, latent (subclinical) hypothyroidism, 3.2% and 5.5%, and overt hypothyroidism, 0.4% and 0.7%. We conclude that the screening with this sensitive thyroid stimulating hormone assay and additional free T4 measurement is useful for detection of patients with thyroid functional disorder.

Adult↗

Management of the nontoxic multinodular goiter: a North American survey.

To assess approaches to the diagnosis and therapy of patients with nontoxic multinodular goiter, a questionnaire was circulated to all members of the American Thyroid Association (ATA). An index case report was presented (42-yr-old woman with an irregular, nontender, bilaterally enlarged thyroid of 50-80 g and no clinical suspicion of malignancy or thyroid dysfunction), and 11 variations were proposed to evaluate how each alteration would affect management. One hundred and forty responses were retained (approximately 50% of clinically active ATA members). For the index case, a TSH determination was the routine choice of 100%, and serum thyroid autoantibodies were measured by 74%. Simultaneous use of serum TSH, a thyroid hormone assay, and antithyroid peroxidase was employed by 49%. Only 4% included a calcitonin assay. The median number of blood tests ordered was 3 (range, 1-7). Ultrasound was used by 59%, thyroid scintigraphy by 24%, and both imaging modalities by 11%. Fine needle aspiration biopsy (FNAB) was performed by 74%. If scintigraphy showed inhomogeneous tracer distribution or a dominant hypofunctioning region, FNAB was performed by 15% and 97%, respectively. L-T4 treatment was preferred by 56%, radioiodine by 1%, surgery by 6%, and 36% would recommend no treatment. A large goiter, a history of external radiation, or rapid growth increased the preference for surgery. In case of a suppressed serum TSH level, radioiodine was used by 56%. In conclusion, in the work-up of patients with nontoxic multinodular goiter, ATA clinicians employ determinations of TSH often combined with a T4 and/or T3 assay and antithyroid peroxidase antibodies. Thyroid imaging, primarily ultrasound, is performed by more than two thirds, and FNAB by three fourths. This diagnostic evaluation is significantly less extensive than that of the European Thyroid Association members, but the distribution of treatment choices is quite similar. In accordance with their European colleagues, the majority of ATA members prefer the use of L-T4 therapy. There is, however, still a wide variation in the perceived optimal management of this condition among members of both organizations.

Autoantibodies↗

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.

Adolescent↗

Thyrotoxic periodic paralysis in caucasians. Report of 8 cases.

BACKGROUND: Periodic paralysis is a well known complication of thytotoxicosis in Chinese and Japanese patients, but has been considered extremely rare in caucasians. PATIENTS AND METHODS: Between 1991 and 1996, we admitted 8 caucasian patients to our Hospital due to thyrotoxic periodic paralysis. We retrospectively analysed their clinical manifestations. RESULTS: All the patients were males. Their attacks started at night or early after awakening, frequently triggered by a high carbohydrate diet and physical exertion. Myalgias and flaccid weakness predominated over proximal leg muscles, sparing bulbar and respiratory musculature. Reflexes were brisk at the onset of the attack and reduced or absent during the course of the episode. Prior to diagnosis patients presented 1-5 attacks of thyrotoxic periodic paralysis each lasting 1-96 hours. Hypokalemia was documented in 6 patients. The episodes of periodic paralysis led to the diagnosis of a previously unsuspected thyrotoxicosis in 6 patients. In the other 2 patients the diagnosis of the thyroid dysfunction preceded the periodic paralysis. Attacks resolved after treatment of the hyperthyroid state. CONCLUSIONS: Thyrotoxic periodic paralysis is an under-diagnosed but probably frequent complication of hyperthyroidism in caucasians. Early recognition of the attacks is essential to investigate and treat the underlying thyroid dysfucntion whose symptoms are usually mild. The episodes of periodic paralysis resolve with the correction of the hyperthyroidism.

Adult↗

Long-term follow-up of ophthalmic Graves' disease.

Sixteen patients with ophthalmic Graves' disease (clinically euthyroid with ophthalmopathy or exophthalmos) were followed up for 4.3 to 14.3 (mean 9.1) years to determine whether thyroid dysfunction developed and whether their ophthalmopathy progressed, regressed or remained stable. Five patients (31%) manifested hyperthyroidism or hypothyroidism, all before the end of the fifth year of follow-up. The ophthalmopathy was mild, and none of the patients required specific treatment. The thyroid function of patients with ophthalmic Graves' disease should be periodically monitored for at least 5 years.

Adolescent↗

Reference intervals for serum thyrotropin: dependence on the population investigated.

In order to elucidate possible differences of reference intervals in various populations, serum basal thyrotropin (TSH) was measured in euthyroid healthy volunteers (N = 170), in thyroid out-patients (N = 215), in geriatric (N = 354) and in seriously ill (N = 32) patients. The results, except in the healthy control subjects, were compared to the TSH responses (delta TSH) in the Thyrotropin Releasing Hormone test. Normal ranges calculated from the basal TSH of the euthyroid groups of different age were similar. There was a significant positive correlation of basal to delta TSH in all groups but the regression equations expressing the qualitative connection of basal and delta TSH were rather different. The basal TSH cut off point predicting a positive TRH-test (i.e. euthyroidism) with more than 95% probability was higher in the geriatric groups (greater than 0.7 mU/l versus greater than 0.4 mU/l in the other groups). In thyroid out-patients and geriatric patients a measurable (greater than 0.1 mU/l) basal TSH indicated measurable delta TSH (thus excluding clinical hyperthyroidism), while in seriously ill patients only a basal TSH greater than 0.2 mU/l was reliably predictive in this respect. Thus, various populations have different reference intervals for TSH. This fact must be considered when the sensitive TSH is used in different populations as the primary screening parameter for thyroid dysfunctions.

Adolescent↗

Inappropriate thyroid gland ablation in patients with generalized resistance to thyroid hormone. A common sequela of a rare disorder.

Generalized resistance to thyroid hormone is one of several rare disorders of thyroid metabolism that can be associated with confusing symptoms and signs. Five cases of generalized resistance to thyroid hormone that were misdiagnosed with thyrotoxicosis, leading to unnecessary thyroid gland ablation and iatrogenic hypothyroidism, are reviewed herein. These cases illustrate the point that a careful review of the history, physical examination, and laboratory data, as well as an understanding of hormonal feedback relationships, will greatly benefit the practitioner in evaluating the patients with thyroid dysfunction. Consultation with an endocrinologist may be helpful to establish the correct diagnosis and avoid unnecessary treatments.

Adult↗

Prevalence of thyroid hormone abnormalities in elderly patients with symptoms of organic brain disease.

Analysis of the serum concentrations of free thyroid hormones (fT3, fT4) and thyrotropin (TSH) in 173 psychogeriatric patients (94 females and 79 males, mean age 79 +/- 8 years) disclosed that the hormone levels were related to sex, psychiatric diagnosis, medication and the presence of nonthyroid illness (NTI). Subnormal concentrations of thyroid hormones and/or TSH were found in 25% of the patients. In addition, fT3 and fT4 concentrations were significantly lower (p < 0.05 and p < 0.001, respectively) in demented males compared with demented females although the levels were within the reference limits. Strongly negative correlations between fT3 and age (p < 0.001), and between fT3 and the sedimentation rate (SR) (p < 0.01) were found in demented but not in non-demented patients. These correlations were most pronounced in (age) or restricted to (SR) demented males. In addition, the correlation between fT3 and Hb was strongly positive (p < 0.001) in demented as well as in nondemented patients, particularly in males. The concentration of fT4 was positively correlated to Hb in demented males (p < 0.001), whereas TSH concentration was positively correlated to Hb in demented females (p < 0.05). The results show that TSH is not sufficient as the sole screening assay for evaluation of possible thyroid dysfunction in psychogeriatric patients. In addition, central (hypothalamic?) hypothyroidism may be present in a substantial amount of psychogeriatric patients, as we found an adequate TSH response to exogenous thyrotropin-releasing hormone (TRH) also in patients with decreased fT3/fT4 and no signs of non thyroid diseases. Furthermore, there was an apparent lack of correlation between thyroid hormone levels and dementia (or subgroups of dementia), even though thyroid hormone abnormalities seemed to be rather common in frontotemporal dementia (38%) and non specified dementia (36%).

Age Distribution↗