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Biomedical subjects

P Laurberg

Publications and source records attributed to P Laurberg.

At least 55 records · Page 3Linked to original sources

Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test.

The insulin tolerance test (ITT) is regarded as the most reliable provocative test in the diagnosis of growth hormone (GH) deficiency in adults. In the present study the test was evaluated by investigating the range of GH responses in normal adult males and females and the intra-individual reproducibility of the test. Sixteen healthy non-obese adults, eight males (median age 31.5 years) and eight females (median age 31.8 years) were tested twice with the ITT, with a minimum of 72 h between each test. The females were tested between day 3 and day 10 of their menstrual cycles. Adequate hypoglycemia was achieved in all cases with a median nadir blood glucose of 1.3 mmol/l (range 0.8-2.0). Growth hormone in serum was measured by immunoradiometric assay and low values were confirmed by a different assay. Median peak GH concentration responses to the ITT were: in males 27.9 micrograms/l, range 5.0-71.1 (test 1) and 30.5 micrograms/l, range 7.9-69.5 (test 2); and in females 9.0 micrograms/l, range 4.1-17.9 (test 1) and 8.4 micrograms/l, range 0.09-42.4 (test 2). The rise in GH concentration during the ITT was higher in males than in females. In the males, all stimulated GH values were > or = 5.0 micrograms/l. In the females, four out of 16 tests gave values below 5.0 micrograms/l and in one test the GH value was around the detection limit of the assays. There was poor reproducibility during repeated testing, with no correlation between the results of the two tests. The results did not correlate to the magnitude of the hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical significance of changing from a second to a third generation thyroid stimulating hormone (TSH) assay].

In recent years new sensitive immunochemoluminiscentic methods to measure thyroid stimulating hormone, TSH have been introduced. In this investigation we have made a comparison between an older, less sensitive, second generation TSH assay and a new, sensitive, third generation TSH assay in order to evaluate if new information of clinical value is obtained. We found that 20% of all the sera that were sent to the laboratory for TSH measurement showed low values. In the sera with low TSH concentration a great variation was observed between the "correct" values found with the third generation assay and the values found with the less sensitive second generation assay. We conclude, that since many sera sent to a routine laboratory have low TSH concentrations, and since it is of clinical importance to know the correct TSH value in many different patient categories, a third generation TSH assay is recommended in the daily routine.

Evaluation Studies as Topic↗

Hypercalcaemic crisis after excessive topical use of a vitamin D derivative.

Topical application of the vitamin D analogue calcipotriol has been found to be of clinical value in the treatment of dermatological disorders. This is considered to be safe with respect to alterations in calcium homeostasis. We report a 17-year-old female patient who developed hypercalcaemic crisis after excessive use of calcipotriol for ichthyosis. The clinical condition and serum calcium improved after cessation of calciprotiol treatment and rehydration with intravenous fluids and electrolytes. The case emphasizes the importance of limiting the topical use of calcipotriol as recommended by the manufacturer.

Acitretin↗

Iodine status in neonates in Denmark: regional variations and dependency on maternal iodine supplementation.

Iodine status of 147 neonates born in five different regions of Denmark was evaluated in relation to the iodine content of breast milk and iodine supplementation taken by the mother. Approximately two-thirds of the women had not received iodine supplementation. They had low iodine concentrations in breast milk and urinary iodine concentrations of the neonates at day 5 were low. The median values (milk/urine) were 33.6/31.7 micrograms/l (Randers 22/26, Ringkøbing 29/16, Aalborg 36/31. Arhus 54/41 and Copenhagen 55/59 micrograms/l). Higher values were found in the group where tablets containing iodine had been taken (milk/urine: 57.0/61.0 micrograms/l). In general, the values are low compared with internationally recommended levels. We suggest that mothers without autoimmune thyroid disease should receive iodine supplementation in the form of vitamin/mineral tablets containing iodine (150 micrograms per tablet).

Denmark↗

Growth hormone and thyroid function: is secondary thyroid failure underdiagnosed in growth hormone deficient patients?

Thyroid hormones and the GH/IGF-1 system show considerable mutual interference which may have physiological, pathophysiological and clinical importance. GH therapy of children and adults may induce a fall in serum T4, which seems to be due to an effect on the deiodination of T4 to T3. Animal studies suggest that the alterations in thyroid hormones in tissue may be much more prominent than the changes observed in serum. It is possible that the GH deficiency seen in the majority of patients with pituitary/hypothalamic disorders may mask secondary hypothyroidism in some patients by giving a relatively high serum T4. GH therapy may then unmask the hypothyroidism. In accordance with such a mechanism GH deficient children evaluated thoroughly to exclude secondary thyroid failure before GH administration do not develop thyroid insufficiency during GH substitution therapy. It is suggested that thyroid insufficiency should be considered in GH deficient patients with low normal serum T4.

Adult↗

Impaired growth hormone secretion in patients operated for pituitary adenomas.

The frequency of growth hormone (GH) deficiency in patients operated for pituitary neoplasms of various size and type was investigated using the insulin tolerance test. 45 patients were included in the study. 20 of the patients had a non-hormone secreting pituitary neoplasm, 9 had GH-, 6 ACTH-, 7 prolactin secreting adenomas and 3 had a craniopharyngeoma. Complete endocrinological examination was obtained in all patients after pituitary surgery. Apart from patients operated for GH secreting adenomas, GH deficiency was very common after pituitary surgery (92%), even in patients operated for small lesions. Among the 45 patients LH/FSH deficiency was found in 33%, ACTH in 33%, TSH in 18% and ADH deficiency in 9% of the patients. In this study, impaired GH secretion was found to be independent of the size of the tumors and was present in nearly all patients after pituitary surgery (with exception of GH secreting adenomas). Deficiencies of other pituitary hormones were predominantly observed after surgery for large tumors.

Adenoma↗

[Radioiodine therapy of recurrent hyperthyroidism in patients previously treated for diffuse toxic goiter with subtotal surgery].

Radioiodine therapy is often employed for treatment of patients with relapse of hyperthyroidism due to Graves' disease, after previous thyroid surgery. Little is known about the outcome of this treatment compared to patients with no previous surgery. A total of 20 patients, who had received surgical treatment for Graves' hyperthyroidism 1-46 years previously and with relapse of hyperthyroidism, and 25 patients with hyperthyroidism due to Graves' disease and no previous thyroid surgery were treated with radioiodine, following the same protocol. Early after treatment the previously operated patients showed a higher sensitivity to radioiodine, with more cases of early hypothyroidism than non-operated patients. However, after 50 months of follow-up the outcome was identical. The results indicate that frequent assessment is necessary after radioiodine treatment of patients with previous thyroid surgery, since some patients develop early hypothyroidism.

Adult↗

Persistent problems with the specificity of immunometric TSH assays.

Sensitive immunometric TSH assays have led to improved diagnosis of thyroid function abnormalities, and serum TSH is often used as the initial screening method for evaluation of thyroid function. Shortly after the marketing of the first of these assays, it was discovered that some sera contained heterophilic antibodies leading to spuriously high TSH values. This problem is considered to be solved by modifications of the assays. We have, however, found that these assays may still give nonspecific results. A panel of sera from 63 patients with untreated hyperthyroidism (51 Graves' disease, 12 Plummer's disease) were used for evaluation of 6 different TSH assays (BeriLux, Spectria, London, Amerlite, Delfia, Delfia Ultra). Several problems were encountered. Most importantly, although all 63 sera gave totally suppressed TSH values in at least one of the assays, many sera gave clearly and reproducibly measurable values in one or more assays. Eleven sera gave values of more than 0.10 mU/L (6 more than 0.40 mU/L) in at least one assay. The pattern of nonspecific values was different in all 6 assays. TRH stimulation did not alter the measured values. Addition of 10% mouse serum to the patient sera gave unpredictable alterations with lower TSH measurements in one assay, but unaffected values in other assays. Hence a measurable serum TSH alone does not always exclude primary hyperfunction of the thyroid. Nonspecific TSH values are the most common cause of nonsuppressed TSH in hyperthyroidism and should be considered before other causes, such as pituitary TSH producing neoplasms or pituitary resistance to thyroid hormone.

Adult↗

Amelioration of some pregnancy-associated variations in thyroid function by iodine supplementation.

Knowledge of the effect of differences in iodine intake levels on public health in areas with no endemic goiter is limited. Groups at risk when iodine intake is relatively low are pregnant and lactating women and their newborns. A prospective randomized study was performed to evaluate the effect of iodine supplementation in an area where the median daily iodine excretion in urine is around 50 micrograms. Fifty-four normal pregnant women were randomized to be controls or to receive 200 micrograms iodine/day from weeks 17-18 of pregnancy until 12 months after delivery. In the control group, serum TSH, serum thyroglobulin (Tg), and thyroid size showed significant increases during pregnancy. These variations were ameliorated by iodine supplementation. Iodine did not induce significant variations in serum T4, T3, or free T4. Cord blood Tg was much lower when the mother had received iodine, whereas TSH, T4, T3, and free T4 levels were unaltered. The results suggest that a relatively low iodine intake during pregnancy leads to thyroidal stress, with increases in Tg release and thyroid size. However, the thyroid gland is able to adapt and keep thyroid hormones in the mother and the child normal, at least under normal circumstances, as evaluated in the present study. It is not known whether this stress is sufficient to be of importance for late development of autonomous thyroid growth and function.

Adult↗

Iodine deficiency in pregnancy in Denmark. Regional variations and frequency of individual iodine supplementation.

Iodine requirements are increased during pregnancy and lactation and adequate iodine intake is important for normal brain development of the fetus/newborn child. The aim of the present study was to evaluate the extent to which this increase in iodine requirement is met in pregnant women living in various regions of Denmark. One hundred and fifty-two healthy pregnant women admitted to five different Danish departments of obstetrics participated in the study. Iodine status was evaluated by measurement of iodine in spot urine at day five after delivery and by careful history of the intake of iodine containing vitamin/mineral tablets. Approximately one third of the women had received tablets containing iodine. In women who had not received iodine supplementation urinary iodine was low with a median value of 39.7 micrograms/g creatinine (Aalborg 28, Randers 33, Ringkøbing 34, Arhus 43 and Copenhagen 62 micrograms/g creatinine). These values are far below internationally recommended levels. The consequences remain to be evaluated and no firm recommendations can be given. It seems reasonable, however, to recommend a high intake of food containing iodine (e.g. milk products) during pregnancy and lactation. Since nearly all the women took some kind of vitamin/mineral supplementation it could be considered to advocate intake of vitamin/mineral tablets containing iodine.

Adolescent↗

Radioiodine treatment of recurrent hyperthyroidism in patients previously treated for Graves' disease by subtotal thyroidectomy.

Radioiodine therapy is often employed for treatment of patients with relapse of hyperthyroidism due to Graves' disease, after previous thyroid surgery. Little is known about the outcome of this treatment compared to patients with no previous surgery. A total of 20 patients who had received surgical treatment for Graves' hyperthyroidism 1-46 years previously and with relapse of the hyperthyroidism, and 25 patients with hyperthyroidism due to Graves' disease and no previous thyroid surgery were treated with radioiodine, following the same protocol. Early after treatment the previously operated patients showed a higher sensitivity to radioiodine, with more cases of early hypothyroidism, than non-operated patients. However, after 50 months of follow-up the outcome was identical. The results indicate that frequent assessment is necessary after radioiodine treatment of previously operated patients, since some patients develop early hypothyroidism.

Adult↗

Sensitive enzyme-linked immunosorbent assay for measurement of autoantibodies to human thyroid peroxidase.

The development of a sensitive assay for detection of autoantibodies against one of the major thyroid antigens, thyroid peroxidase (TPO), is described. TPO was purified from human thyroid tissue by: (1) isolation of thyroid microsomes using homogenization and differential centrifugation, (2) solubilization of membrane proteins by Zwittergent 3-14, and (3) anion exchange liquid chromatography on a FPLC Mono Q column. Autoantibodies against TPO (TPO-Ab) were measured using an enzyme-linked immunosorbent assay (ELISA) with serum samples diluted 1:100. Standards containing 70, 7, 0.7, 0.02 and 0 U ml-1 TPO-Ab were employed (reference standard code 66/387 NIBSC, London, UK). The detection limit was 0.02 U ml-1 corresponding to 2 U ml-1 in undiluted serum. The inter- and intra-assay coefficients of variation were 8.6% and 5.3%. In 109 healthy control subjects TPO-Ab was found in 9 (8.3%), while 43 (97.7%) out of 44 patients with newly diagnosed untreated Graves' disease had detectable TPO-Ab in serum. All of 16 patients with newly diagnosed spontaneously developing primary hypothyroidism had circulating TPO-Ab (range 16-7000 U ml-1). The new assay is a valuable tool for evaluation of thyroid autoimmunity in individual patients and for studying the epidemiology of thyroid autoimmunity.

Adolescent↗

High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland.

Little is known about the optimum level of iodine intake for iodine supplementation programmes, or about the effects of the high levels of iodine intake that are found in some countries. We compared the incidence of different types of hyperthyroidism in East-Jutland Denmark with a low average iodine intake but no endemic goitre, and the incidence in Iceland with a relatively high iodine intake. Hyperthyroidism was more common in East-Jutland than in Iceland, due to a much higher incidence of multinodular toxic goitre and also of single toxic adenoma. Most of the patients with these diseases were over 50 years of age. By contrast, the incidence of Graves' disease was significantly higher in Iceland than in East-Jutland. This difference was most marked in the younger age groups, in which hyperthyroidism was more than twice as common in Iceland as in East-Jutland. These results demonstrate that even mild iodine deficiency has a significant effect on population health, since it leads to a high incidence of autonomous thyroid nodules with hyperthyroidism in the elderly population. However, population iodine intake probably should not exceed a level much higher than that necessary to avoid iodine deficiency, otherwise Graves' disease may be induced in the young population.

Adolescent↗

Relations between diurnal variations in serum osteocalcin, cortisol, parathyroid hormone, and ionized calcium in normal individuals.

Serum osteocalcin varies in a diurnal rhythm, with peak values during the night and minimum levels before noon, but the factors controlling this rhythm are unknown. In this study, we evaluated the temporal relations between the osteocalcin rhythm and variations in serum concentrations of cortisol, intact parathyroid hormone (PTH(1-84)), and ionized calcium (Ca2+) in 15 normal volunteers, aged 22-46 years. Serum cortisol varied in a typical way preceding inverse changes in serum osteocalcin by about 4 h (r = 0.78, p less than 0.0001). Changes in serum osteocalcin following the early morning increase in serum cortisol were statistically indistinguishable from the changes seen after oral administration of 2.5 or 10 mg of prednisone. Serum PTH (1-84) showed a diurnal rhythm (p less than 0.01) with peak values (4.06 +/- 0.42 pmol/l) at 20.30 h and nadir (2.81 +/- 0.10 pmol/l) around 10.30 h, preceding changes in serum osteocalcin in the same direction by 5 h (r = 0.55, p less than 0.02). Prednisone at a dose of 10 mg did not change the time course significantly. Serum Ca2+ varied in an almost bi-phasic pattern (p less than 0.01) with maximal mean levels around 16.30 and 09.30 h and minimal levels around 05.30 and 14.30 h. Serum Ca2+ correlated inversely with PTH (1-84) (r = 0.53, p less than 0.01), and serum osteocalcin was inversely related to Ca2+ at concurrent time points (r = 0.59, p less than 0.005). Prednisone caused a 2-3 h lasting increase in serum Ca2+ 3-5 h after ingestion (p less than 0.001). In conclusion, our results suggest that cortisol is strongly associated to the diurnal rhythm in serum osteocalcin. The biological relevance of the reported relation between serum osteocalcin and PTH (1-84) and serum Ca2+ is uncertain.

Administration, Oral↗

Hyperfunctioning thyroid nodules.

The authors describe the principal clinical and pathological aspects of the solitary hyperfunctioning adenoma or the multifocal hyperfunction of a multinodular goitre. Successively they report the incidence of these conditions in countries with different iodine intake as well as the age distribution of the examined patients. In the area with low iodine intake the incidence of hyperthyroidism caused by multinodular goitre is 10 times higher than in the high iodine intake area. Finally, the role of the laboratory in the diagnosis of hyperthyroidism and in identifying the type of hyperthyroidism is discussed; an up-todate flow-sheme is also reported.

Adenoma↗

Turnover of thyrotropin-releasing hormone in patients with chronic renal failure and chronic alcoholic liver disease.

Homogenates of liver and kidney tissues are efficient in degrading TRH, but the liver contains only membrane-bound pyroglutamyl aminopeptidase, active in degrading TRH at the extracellular side of cell membranes. In the present study the effect of liver and kidney failure on the degradation of infused TRH was investigated in man. In 7 uremic patients (group I) and 7 patients with chronic alcoholic liver disease (group II) plasma clearance rate, half-time of disappearance (t1/2) and half time of disappearance of TRH in serum in vitro (t1/2p) was determined. The plasma clearance rate, t1/2 and t1/2p were, respectively, 19.8 +/- 6.2 ml.kg-1.min-1, 6.6 +/- 1.5 min and 16.4 +/- 6.2 min in group I versus 28.2 +/- 4.8 ml.kg-1.min-1, 9.3 +/- 2.6 min and 25.3 +/- 15 min (mean +/- SD) in group II. The volume of distribution of TRH was 19.3% of the body weight in group I and 36.5% in group II. The calculated half-time in the extravascular tissue compartment (t1/2) was 5.4 +/- 1.4 min in group I and 9.2 +/- 2.7 min in group II patients (mean +/- SD). TRH metabolism in the uremic patients was almost identical to that previously reported in normal subjects. In the patients with chronic liver disease plasma clearance rate was significantly greater than in normal subjects, indicating an increased TRH-degrading enzyme activity in the tissue compartment. However, owing to the very large expansion of this compartment, the t1/2 and t1/2t were significantly prolonged. Hence, half-time determination of TRH is no reliable indicator of overall TRH degradation in patients with liver disease.

Adult↗