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E. Iversen and P. Laurberg

Abstract. Recently we found small amounts of TRH immunoreactivity in the thyroid gland of dogs and pigs. In the present study we investigated if exogenous TRH influences the release of T4, T3 and cAMP from the follicular cells, and calcitonin and somatostatin from the C-cells of perfused dog thyroid lobes.

10−5 mol/l TRH inhibited the TSH induced iodothyronine and cAMP release from the thyroid while 10−8 mol/l TRH had no effect. The relative proportions of T4 and T3 in thyroid secretion were not altered by TRH infusion. TRH did not influence the basal or the Ca++ induced release of somatostatin and calcitonin.

Hence TRH has a direct inhibitory effect on the hormone secretion from thyroidal follicular cells. This opens the possibility that TRH in the thyroid participate in the regulation of thyroid hormone secretion.

Even though the concentration of TRH found to be effective is high our results may indicate that TRH in the thyroid participates in the regulation of thyroid hormone secretion as an antagonist to TSH.

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P Kissmeyer-Nielsen, H Christensen and S Laurberg

Kissmeyer-Nielsen P, Christensen H, Laurberg S. Growth hormone treatment of rats with chronic diverting colostomy. Differential response on proximal functioning and distal atrophic colon. Eur I Endocrinol 1994;130:508–14. ISSN 0804–4643

Diversion of colon from the fecal stream leads to profound intestinal atrophy. After diverting colostomy for 4 weeks, female rats were treated with biosynthetic human growth hormone (b-hGH; 2.0 mg.kg−1 body wt.day−1) in order to investigate whether b-hGH could reverse atrophic changes in distal colon, with special reference to changes in morphometric composition, collagen content and biomechanical properties. Biosynthetic hGH treatment for 28 days stimulated growth of the muscularis propria of the defunctioned, atrophic colon (p < 0.05), whereas the mucosal atrophy was unaffected by the treatment. In colon proximal to the colostomy, however, b-hGH increased the colonic wet weight (p < 0.01), defatted dry weight (p < 0.005) and the collagen content (p < 0.05). Morphometric analysis showed that the growth increase was localized to the mucosa and the muscularis propria. In conclusion, fecal diversion alters the response of b-hGH treatment and indicates that the trophic effect of growth hormone on colonic mucosa is dependent on fecal bulk passage, whereas the trophic effect on muscularis propria is fully retained when colon is deprived of luminal nutrients.

Peter Kissmeyer-Nielsen, Surgical Research Unit, Department of Surgery L, Amtssygehuset, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark

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S Andersen, SB Petersen and P Laurberg

OBJECTIVE: The iodine intake level is important for the occurrence of thyroid disorders in a population. We have previously found that iodine in drinking water is related to iodine excretion but whether iodine is present as iodide or bound in other molecules remains unknown. DESIGN: We measured iodine in drinking water from 22 locations in Denmark. Six locations were selected by iodine content for further tap water analysis (Skagen 140 micro g/l, Samsoe 56 micro g/l, Nykoebing S. 50 micro g/l, Nakskov 40 micro g/l, Ringsted 38 micro g/l, Copenhagen 19 micro g/l). METHODS: HPLC size exclusion before (Skagen) and after (all sites) freeze drying and measurement of absorbance (280 nm) and iodine in fractions, and fluorescence spectroscopy of bulk organic matter in Skagen drinking water. RESULTS: Iodine content was unaltered after 3 Years (P=0.2). All samples contained organic molecules with characteristics similar to humic substances. Most iodine eluted with humic substances (Skagen 99%, Ringsted 98%, Nykoebing S. 90%, Copenhagen 90%, Samsoe 75%, Nakskov 40%). Changing pH and ionic strength and preincubation with iodide indicated that iodine was bound in humic substances. Humic substances may affect thyroid function but differ with geology. Geological and geochemical data agree with tap water humic substances having been released from marine deposits. Iodine is abundant in the marine environment and marine deposits are particularly rich in iodine. Correlation analysis (r=0.85, P=0.03) conform to iodine in drinking water, suggesting marine humic substances at the source rock. CONCLUSION: Iodine in Danish drinking water varied considerably. In drinking water with a high iodine content, the iodine mainly eluted with humic substances derived from marine source rock. We hypothesize that iodine in drinking water in general suggests coexisting humic substances of marine origin.

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P. Laurberg, J. Tørring and J. Weeke

Abstract. Two groups of patients with newly diagnosed thyrotoxicosis were treated with propylthiouracil (PTU) 400 mg every 6 h for 4 days followed by methimazol (MMI) 40 mg every 6 h for 4 days or by MMI for 4 days followed by PTU for 4 days. The shift from MMI to PTU induced a considerable decrease in serum T3 while shift from PTU to MMI led to an increase in serum T3. Serum T4 decreased gradually during the whole treatment period. The opposite variations in serum T3 were accompanied by similar opposite variations in basal metabolic rate (BMR) (P < 0.001). Hence the rapid variations in serum T3 which can be induced by PTU in thyrotoxic patients, are followed by rapid alterations in the thyrotoxic state as evaluated by BMR.

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S L Andersen, A Carlé, J Olsen and P Laurberg

Objective

Immunological changes in and after a pregnancy may influence the onset of autoimmune diseases. An increased incidence of hyperthyroidism has been observed both in early pregnancy and postpartum, but it remains to be studied if the incidence of hypothyroidism varies in a similar way.

Design

Population-based cohort study using Danish nationwide registers.

Method

All women who gave birth to a singleton live-born child in Denmark from 1999 to 2008 (n = 403 958) were identified, and data on hospital diagnosis of hypothyroidism and redeemed prescriptions of thyroid hormone were extracted. The overall incidence rate (IR) of hypothyroidism during 1997–2010 and the IR in three-month intervals before, during and after the woman’s first pregnancy in the study period were calculated and compared with the IR of hyperthyroidism.

Results

Altogether 5220 women were identified with onset of hypothyroidism from 1997 to 2010 (overall IR 92.3/100 000/year) and 1572 women developed hypothyroidism in the period from 2 years before to 2 years after birth of the first child in the study period. The incidence of hypothyroidism decreased during the pregnancy (incidence rate ratio (IRR) vs overall IR in the rest of the study period: first trimester: 0.89 (95% CI: 0.66–1.19), second trimester: 0.71 (0.52–0.97), third trimester: 0.29 (0.19–0.45)) and increased after birth with the highest level at 4–6 months postpartum (IRR 3.62 (2.85–4.60)).

Conclusion

These are the first population-based data on the incidence of hypothyroidism in and around pregnancy. The incidence declined during pregnancy followed by a sharp increase postpartum. Notably, hypothyroidism as opposed to hyperthyroidism showed no early pregnancy increase.

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M Rix, P Laurberg, A S Hoejberg and B Brock-Jacobsen

Objective: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour.

Design: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism.

Methods: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age.

Results: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being.

Conclusions: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

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KM Pedersen, P Laurberg, S Nohr, A Jorgensen and S Andersen

The iodine intake level of the population is of major importance for the occurrence of thyroid disorders in an area. The aim of the present study was to evaluate the importance of drinking water iodine content for the known regional differences in iodine intake in Denmark and for the iodine content of infant formulas. Iodine in tap water obtained from 55 different locations in Denmark varied from <1.0 to 139 microg/l. In general the iodine content was low in Jutland (median 4.1 microg/l) with higher values on Sealand (23 microg/l) and other islands. Preparation of coffee or tea did not reduce the iodine content of tap water with a high initial iodine concentration. A statistically significant correlation was found between tap water iodine content today and the urinary iodine excretion measured in 41 towns in 1967 (r=0.68, P<0.001). The correlation corresponded to a basic urinary iodine excretion in Denmark of 43 microg/24h excluding iodine in water and a daily water intake of 1.7 l. The iodine content of infant formulas prepared by addition of demineralized water varied from 37 to 138 microg/l (median 57 microg/l, n=18). Hence the final iodine content would depend heavily on the source of water used for preparation. We found that iodine in tap water was a major determinant of regional differences in iodine intake in Denmark. Changes in water supply and possibly water purification methods may influence the population iodine intake level and the occurrence of thyroid disorders.

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S Andersen, G Mulvad, HS Pedersen and P Laurberg

OBJECTIVE: To establish an Inuit body mass index (BMI) norm from a healthy, not malnourished, pure Inuit population and to investigate the development of overweight in the Inuit in Greenland. DESIGN:Longitudinal study with 35 years follow-up on overweight among Inuit in Greenland. METHODS: The heights and weights of 97% of all inhabitants in Eastgreenland in 1963 (n=1852) were recovered recently and BMI calculated. We obtained similar data in 96% of the 50-69-year-old population in Eastgreenland in 1998 and in a random sample of 25% of individuals aged 50-69 years in the capital Nuuk (n=535). RESULTS: Overweight or obesity, as defined by the World Health Organization (WHO), was found in 30% of all men and 22% of all women in Eastgreenland in 1963, and in 31% of young Inuit hunters in 1963. Such high rates were incompatible with a hunter's way of living. Inuit-specific BMI norms from data on healthy Inuit aged 20-29 years in 1963 were computed: men, 20.2-27.9; women, 17.9-27.7. These differed from the WHO classification (P<0.001). Using the Inuit-specific BMI norm for the classification of 50-69-year-old Inuit in 1963 and 1998, the fraction of overweight men increased by over six times (4.0 to 25.6%; P<0.001), and overweight increased with Westernization (P=0.001). The fraction of overweight women by the Inuit BMI norm doubled from 1963 to 1998 (14.0 to 30.7%; P<0.001) while median BMI remained unaltered (P=0.22) because the fraction of slim women more than doubled (3.5 to 9.0%; P<0.001). CONCLUSION: A steep increase in the fraction of overweight Inuit men and women calls for intervention. Westernization predicted increased BMI. In women the increased number of obese people was accompanied by an increased fraction of slim people. This illustrates that transition can be modified and indicates that monitoring of populations in transition should observe gender differences. Finally, the historical data argue against the global applicability of the WHO delineation of normal BMI.

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S Andersen, KM Pedersen, IB Pedersen and P Laurberg

OBJECTIVE: The iodine intake level in a population is determined in cross-sectional studies. A fraction of samples with iodine content below a certain level, e.g. 25 microg/l, may suggest iodine deficiency in part of the population. However, urinary iodine varies considerably from day to day and the fraction of low samples caused by dispersion remains unsettled. DESIGN: A longitudinal study of 16 healthy men living in an area of mild to moderate iodine deficiency. METHODS: We measured urinary iodine and creatinine concentrations, and serum TSH, total thyroxine (T4), free T4 index and total tri-iodothyronine (T3) in samples collected monthly for 1 year. RESULTS: Average urinary iodine excretion was 57.0 microg/l (49.1 microg/24 h (corrected for creatinine excretion)) and varied from 29 to 81 microg/l (28 to 81 microg/24 h) between participants. Individual samples varied between 10 and 260 microg/l, and the variation around the mean was 2.4 times larger when calculated for the 180 individual samples compared with the 15 average annual values (1.7 times larger for estimated 24 h iodine excretion values). The fraction of individual samples below 25 microg/l was 6.7% (7.2% < 25 microg/24 h), whereas none of the participants had average iodine excretion below 25 microg/l or 25 microg/24 h. Participants with average annual iodine excretion below 50 microg/24 h had a negative correlation between iodine excretion and TSH, whereas a positive correlation was observed when average annual iodine excretion was above this level. CONCLUSIONS: Seven per cent of individual urine samples indicated severe iodine deficiency without this being present in the group studied. Dispersion was reduced by 24% when using estimated 24 h urinary iodine excretion rather than urinary iodine concentration. Participants with moderate iodine deficiency (average annual urinary iodine excretion 25-50 microg/24 h) showed clear signs of substrate deficiency for thyroid hormone synthesis while participants with mild iodine deficiency (50-100 microg/24 h) did not.