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  • Author: Pierre M Zelissen x
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Lisanne C C J Smans, Patrick C Souverein, Hubert G M Leufkens, Andy I M Hoepelman and Pierre M J Zelissen

Background

Previous studies have suggested that infections are an important cause of death in patients with Addison's disease, but epidemiological studies on the frequency of infections in this population are lacking.

Objective

To assess and compare the incidence risk of infections in patients with primary adrenal insufficiency with controls.

Design and setting

We conducted a cohort study, using data from the Dutch PHARMO record linkage system, that links patients' demographics and medication histories to hospital admissions.

Patients

From a cohort of oral glucocorticoid users, 390 patients with primary adrenal insufficiency were identified by assessing concurrent use of glucocorticoids and mineralocorticoids using pharmacy dispensing records. A reference cohort (n=1933) with the same age and sex distribution was sampled from patients not using glucocorticoids.

Outcome measure

Incidence rates and incidence rate ratios (IRR) were calculated of infections, defined by use of antimicrobial agents, as well as hospital admissions for infection.

Results

The incidence of infectious episodes, defined by usage of antimicrobial agents, among patients with primary adrenal insufficiency (incidence rate 59.2/100 person-years) was 1.5 times higher compared with controls, yielding a crude IRR of 1.61 (95% CI 1.51–1.72). The IRR decreased slightly to 1.58 (95% CI 1.47–1.70) after adjustment for co-medication and co-morbidity also associated with infection risk. Also with respect to hospital admissions for infection, the incidence rates observed for patients with primary adrenal insufficiency was higher compared with controls (3.8/100 vs 0.8/100 person-years): crude IRR 5.02 (3.66–6.87) and adjusted IRR 4.34 (95% CI 3.04–6.22).

Conclusion

Patients with primary adrenal insufficiency had an increased use of antimicrobial agents and hospital admissions related to infection.

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Frederik A Verburg, Bart de Keizer, Cornelis J M Lips, Pierre M J Zelissen and John M H de Klerk

Objectives: Currently, little is known about the prognostic significance of achieving successful ablation with the first dosage of I-131 in patients with differentiated thyroid cancer. This study aimed to assess the following: (i) whether successful or unsuccessful ablation at post-ablation follow-up has prognostic consequences; (ii) possible factors predicting success of ablation in a patient.

Methods: In order to do this, we retrospectively studied 180 patients with a median follow-up of 55 months. Ablation was considered to be successful if 1 year after the initial dosage of I-131 patients fulfilled all of the following criteria: not dead from thyroid cancer, no additional therapy needed for any kind for thyroid cancer within the first year, undetectable thyroglobulin (Tg) levels under TSH stimulation, and negative I-131 scintigraphy. Tg levels at the time of ablation (P < .001), lymph node metastasis (P = 0.04) and distant metastasis (P < .001) have a significant influence on the success of ablation. P values were calculated by Mann–Whitney U test and Chi-square test, respectively.

Results: Patients with successful ablation had a better prognosis than those with unsuccessful ablation: disease-free survival was 87% versus 49% after 10 years; additionally, thyroid-cancer related survival was 93% versus 78%.

Conclusion: We conclude that the extent of the remaining normal or neoplastic thyroid tissue influences the outcome of ablation, and that successful ablation leads to a better prognosis. It seems that it is very important to achieve complete ablation as soon as possible in order to ensure the best possible prognosis for a patient.

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Yvonne EM Snel, Manorath E Doerga, Robert-Jan M Brummer, Pierre MJ Zelissen, Maria L Zonderland and Hans PF Koppeschaar

Snel YEM, Doerga ME, Brummer R-JM, Zelissen PMJ, Zonderland ML, Koppeschaar HPF. Resting metabolic rate, body composition and related hormonal parameters in growth hormone-deficient adults before and after growth hormone replacement therapy. Eur J Endocrinol 1995;133:445–50. ISSN 0804–4643

The resting metabolic rate (RMR), and body composition were assessed in 30 growth hormone-deficient (GHD) adults before and after 3 and 6 months of replacement therapy with recombinant human growth hormone (rhGH). In addition, insulin-like growth factor I (IGF-I), IGF binding proteins (IGFBPs) and plasma insulin were measured at baseline and at 6 months in relation to RMR. During 6 months of rhGH replacement therapy, body fat decreased from 18.2 ± 1.5 (mean±sem) to 14.3 ± 1.6 kg (p < 0.0001), whereas fat-free mass (FFM) increased from 53.5 ± 3.3 to 56.3 ± 3.6 kg (p < 0.0001), RMR increased from 1246 ± 92 to 1539 ± 102 kcal/24 h (p < 0.0001) and RMR per kilogram of FFM increased from 23.2 ± 0.6 to 27.4 ± 0.5 (p < 0.0001). When RMR data were adjusted for the differences in FFM, it appeared that apart from the increase in FFM, other factors may play a role in the increase in RMR. During rhGH replacement therapy, IGF-I (p < 0.0001) and IGFBP-3 (p = 0.003) levels increased, whereas IGFBP-1 levels decreased significantly (p = 0.004). The FFM explained for about 80% of the variance in RMR. In addition, waist/hip ratio and plasma IGF-I contributed significantly to the explained variance of RMR. This study shows that in GHD adults FFM is the main determinant of RMR and that, next to the increase in FFM, changes in metabolic and hormonal parameters contribute to the increase in RMR during rhGH replacement therapy.

HPF Koppeschaar, Department of Endocrinology, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands

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Corné A Roelen, Hans P Koppeschaar, Wouter R de Vries, Pierre M Zelissen, Yvonne E Snel, Manorath E Doerga, Jos H Thijssen and Rien A Blankenstein

Roelen CA, Koppeschaar HP, de Vries WR, Zelissen PM, Snel YE, Doerga ME, Thijssen JH, Blankenstein RA. High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency. Eur J Endocrinol 1996;135:82–6. ISSN 0804–4643

The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements.

HPF Koppeschaar, Department of Endocrinology, University Hospital Utrecht, HPL00.407, PO Box 85500, 3508 GA Utrecht, The Netherlands

Free access

Agatha A van der Klaauw, Nienke R Biermasz, Pierre M J Zelissen, Alberto M Pereira, Eef G W M Lentjes, Johannes W A Smit, Sjoerd W van Thiel, Johannes A Romijn and Ferdinand Roelfsema

Objective

GH-deficient women using oral estradiol treatment require higher doses of recombinant human GH (rhGH) to achieve similar IGF-I levels when compared with men and women on transdermal estradiol replacement. The aim of this study was to evaluate the effects of oral versus transdermal estrogen administration at similar plasma estradiol levels on IGF-I, IGF-binding protein-3, and sex hormone-binding globulin (SHBG) concentrations.

Design

Parallel crossover study in which two groups of hypogonadal and GH-deficient women with fixed and stable rhGH replacement passed through four different estradiol treatment schemes (2 and 4 mg oral, and 50 and 100 μg transdermal estradiol) with a duration of four cycles each to ensure a new steady state. Group I (18 patients using oral estradiol prior to the study) was treated with oral followed by transdermal estradiol and group II (five patients with transdermal estradiol prior to inclusion) with transdermal followed by oral estradiol.

Results

Estradiol concentrations were lowest during 50 μg transdermal and highest during 4 mg oral estradiol treatment. Estradiol concentrations did not differ during 100 μg transdermal and 2 mg oral treatment. Nevertheless, IGF-I levels were significantly higher during 100 μg transdermal when compared with 2 mg oral treatment (P=0.005 in group I and 0.02 in group II), while SHBG levels were significantly lower (P=0.002 in group I and P=0.004 in group II). SHBG and IGF-I concentrations were negatively correlated (R=−0.41, P=0.0001).

Conclusion

During fixed GH replacement, the route of estrogen administration is a determinant of IGF-I levels in hypogonadal GH-deficient women.