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Biomedical subjects

G Beckett

Publications and source records attributed to G Beckett.

10 recordsLinked to original sources
PubMed2002

Can we measure serum thyroglobulin?

Measurement of serum thyroglobulin (Tg) by immunoassay is used to monitor the treatment of differentiated thyroid cancer. An understanding of the disease process and the biochemistry of Tg allows the laboratory to determine the characteristics of suitable Tg assays. There are a number of key analytical issues: standardization, long-term assay stability, minimum detection limit, working range and the effect of endogenous Tg antibodies (TgAb). There are significant limitations to the methods used to determine TgAb interference. Clinicians should be aware of the limitations of immunoassays for this tumour marker.

Antibodies↗
PubMed2001

Autoimmune hypothyroidism coexisting with a pituitary adenoma secreting thyroid-stimulating hormone, prolactin and alpha-subunit.

A 44-year-old woman presented to her GP with excessive tiredness. She had positive thyroid microsomal and thyroglobulin autoantibodies and was found to have an elevated serum thyroid-stimulating hormone (TSH) concentration of 8.37 (normal = 0.15-3.5)mU/L and a low normal total thyroxine (T4) of 86 (reference range 60-145)nmol/L. She was rendered symptom free on a dose of 150 microg of thyroxine per day. However, her TSH failed to return to normal, and following a further increase in her thyroxine dose she was referred to the endocrine clinic for further assessment. Her TSH at this stage was 14mU/L, free T4 (fT4) 28 (normal = 10-27)pmol/L and free T3 (fF3) 10 (normal = 4.3-7.6)pmol/L. She denied any problems with adherence to her medication. Her serum prolactin was elevated at 861 (normal = 60-390)mU/L. A pituitary tumour was suspected and an MRI scan showed a macroadenoma of the right lobe of the pituitary, extending into the suprasellar cistern. The tumour was resected trans-sphenoidally. Electron microscopy showed a dual population of neoplastic cells compatible with a thyrotroph cell and prolactin-secreting adenoma. Immunocytochemistry and cell culture studies confirmed the secretion of TSH, prolactin and alpha-subunit. Postoperative combined anterior pituitary function tests did not demonstrate any deficiency of anterior pituitary hormones. A repeat MRI scan showed no significant residual tumour; however, her serum TSH and prolactin levels remained high and she was given a course of pituitary irradiation. This case illustrates the difficulty of diagnosing a TSHoma when it coexists with autoimmune hypothyroidism. We believe the combination of pathologies reported here is unique.

Adrenocorticotropic Hormone↗
PubMed2000

Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?

There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves' disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves' disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves' disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.

Antithyroid Agents↗
PubMed1996

Lack of effect of thyroxine in patients with Graves' hyperthyroidism who are treated with an antithyroid drug.

BACKGROUND: Antithyroid drugs are effective in patients with hyperthyroidism due to Graves' disease, but the rate of recurrence after treatment is high. In a recent Japanese study, adjunctive treatment with thyroxine (T4) was associated with a recurrence rate 20 times lower than that among patients who received only an antithyroid drug. If these results are confirmed, combined therapy with an antithyroid drug and T4 might become the treatment of choice for all patients with Graves' hyperthyroidism. METHODS: We treated 111 patients (89 women and 22 men) who had Graves' hyperthyroidism. All patients initially received 40 mg of carbimazole daily for one month. Then one group received carbimazole alone for 17 months (52 patients), and the other group received carbimazole plus T4 for 17 months and T4 alone for 18 months (59 patients). In the carbimazole group, the dose was adjusted after one month to maintain a normal serum thyrotropin concentration. In the carbimazole-T4 group, the dose of carbimazole was not changed, but 100 micrograms of T4 per day was added to the regimen and the dose was adjusted to maintain an undetectable serum thyrotropin concentration (< 0.04 microU per milliliter). RESULTS: At the time of our analysis, 53 of the 111 patients had completed at least 3 months of follow-up (median, 12 months) after carbimazole was withdrawn. Hyperthyroidism recurred in eight patients in each group after a mean (+/- SD) of 6 +/- 4 months in the carbimazole group and 7 +/- 4 months in the carbimazole-T4 group. There was no difference between the recurrence rates in the two groups, despite the fact that serum thyrotropin concentrations were undetectable in 73 percent of patients in the carbimazole-T4 group on at least 75 percent of their visits. CONCLUSIONS: The administration of T4 to patients with Graves' disease during carbimazole treatment and after its withdrawal neither delays nor prevents the recurrence of hyperthyroidism.

Adult↗
PubMed1994

Bone mineral density and metabolism in premenopausal women taking L-thyroxine replacement therapy.

BACKGROUND AND OBJECTIVE: Excess endogenous thyroxine causes bone loss, but the effects of exogenous thyroxine are disputed. We report on bone mass and metabolism in women taking L-thyroxine therapy. DESIGN: Cross-sectional and longitudinal studies. PATIENTS: Cross-sectional study: 40 healthy premenopausal women with autoimmune thyroiditis taking either physiological (serum TSH usually normal, 0.35-3.3 mU/l) or suppressive (serum TSH usually < 0.35 mU/l) doses of L-thyroxine; patients were also compared with previously acquired age and weight matched premenopausal volunteers with no history of thyroid dysfunction. Longitudinal study: 28 patients were followed-up > or = 1 year later. MEASUREMENTS: In all subjects bone mineral density (BMD) was measured at the anteroposterior lumbar spine and left hip (femoral neck, greater trochanter and Ward's area) using dual-energy X-ray absorptiometry, and physical activity assessed using the Framingham physical activity index. Serum osteocalcin (OC), PTH and vitamin D, and urinary pyridinoline and deoxypyridinoline excretion were measured in patients. RESULTS: Cross-sectional study: The patient groups were well matched for disease duration and physical activity although the suppressed group were slightly younger (mean 38.1 (SD 7.5) vs 43.3 (3.9) years, P < 0.05). BMD, serum OC, PTH and vitamin D, and urinary cross-link excretion did not differ significantly between the two groups. Multivariate analysis of the whole group suggested that BMD at the femoral neck and greater trochanter was related positively to weight and physical activity and negatively to thyroxine dose (microgram/kg/day) and patient age. At the lumbar spine BMD was reduced non-specifically in the presence of thyroid disease and treatment, but this effect appeared to decline with increasing duration of therapy. A similar analysis of the patient group suggested that urinary cross-link excretion correlated positively with thyroxine dose, and negatively with duration of treatment. Longitudinal study: Annualized changes in BMD were inversely related to thyroxine dose (microgram/kg/day) at all sites but achieved statistical significance only at the femoral neck and Ward's area. CONCLUSION: We did not find any effect of persistent historical TSH suppression on current bone mass, and this might relate to the relative insensitivity of older TSH assays. However, the cross-sectional and longitudinal data suggest that high daily doses of thyroxine in relation to patient body weight might adversely affect bone mass, particularly at the hip. These findings support the contention that excess exogenous thyroxine might predominantly deplete skeletal sites, such as the femoral neck, rich in cortical bone.

Absorptiometry, Photon↗
PubMed1993

Causes of death among persons reported with AIDS.

OBJECTIVES: This study describes causes of death in persons with acquired immunodeficiency syndrome (AIDS) and assesses the completeness of reporting of human immunodeficiency virus (HIV) infection or AIDS on death certificates of persons with AIDS. METHODS: AIDS case reports were linked with death certificates in 11 local/state health departments; underlying and associated causes of death were available for 32,513 persons with AIDS who died. RESULTS: HIV/AIDS was designated as the underlying cause of death for 46% of persons with AIDS who died between 1983 and 1986 and 81% of persons with AIDS who died since 1987 (the year specific coding procedures were implemented for HIV/AIDS). Most other underlying causes of death were conditions within the AIDS case definition (notably Pneumocystis carinii pneumonia), pneumonia, infections outside the AIDS case definition, and drug abuse. Unintentional injuries, suicide, and homicide were less common. HIV/AIDS was listed as underlying or associated on 88% of death certificates from 1987 to 1989; reporting varied primarily by HIV exposure category and time between diagnosis and death. CONCLUSIONS: Physicians and other health care professionals should realize their critical role in accurately documenting HIV-related mortality on death certificates. Such data can ultimately influence the allocation of health care resources for HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Diagnosis of hyperthyroidism: the newer biochemical tests.

Investigation of suspected hyperthyroidism is conventionally based on measurement of total or free T4 as the initial test, followed in equivocal cases by total or free T3, and the TRH test. Recent developments in techniques for measuring free hormones and TSH promise to change this approach. Free T4 and free T3 can now be rapidly and simply quantitated in whole serum using labelled analogue radioimmunoassays. Specific and highly sensitive assays using labelled monoclonal antibodies are now available for serum TSH that permit the suppressed levels found in most cases of hyperthyroidism to be distinguished from euthyroid levels. These newer assays are available at a cost per test that is often similar to that of the more established tests. Available evidence indicates that measurement of basal serum TSH by a sensitive labelled antibody method can serve as a first line test, at least in uncomplicated cases of suspected hyperthyroidism. In patients with a suppressed TSH, a serum free T4, and in equivocal cases free T3, will distinguish the clinical and subclinical forms of hyperthyroidism. Such an approach would obviate the need for the TRH test. It must be emphasized, however, that experience with this new approach is limited. Caution is advised in the interpretation of low TSH and free hormone levels when there are associated complicating features, such as severe non-thyroidal illness, or pregnancy. These developments mark a trend in thyroid function testing away from measurement of circulating total hormone levels. The newer tests provide an assessment of end organ (thyrotroph) response, and an assessment of biologically active (free) hormone to which the tissues are exposed. These complementary approaches have the potential to identify relatively minor degrees of thyroid dysfunction.

Diagnosis, Differential↗