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  • Author: Bruce H R Wolffenbuttel x
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A Caroline Heijckmann, Maya S P Huijberts, Piet Geusens, Jolanda de Vries, Paul P C A Menheere and Bruce H R Wolffenbuttel

Objective: Untreated hyperthyroidism and treatment with high doses of thyroid hormone are associated with osteoporosis. However, their effect on bone turnover, their contribution to bone mineral density (BMD) in the context of other clinical risk factors for osteoporosis and the prevalence of vertebral fractures is not well documented.

Design: Cross-sectional study.

Methods: We studied 59 patients receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption was measured by C-telopeptides of type I collagen (ICTP) and bone formation by procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis were evaluated using a questionnaire.

Results: Z-scores of BMD were similar as the NHANES (National Health and Nutrition Examination Survey) III reference group in women and men, also after long-term (>10 years) suppression therapy. Patients in the lowest and highest quartile of BMD showed significant differences in the presence of clinical risk factors. ICTP levels were significantly higher than in age-matched controls, PINP levels were not different. We found four patients with a prevalent vertebral fracture.

Conclusions: We conclude that patients with well-differentiated thyroid carcinoma are not at increased risk of developing low bone mass nor have a higher prevalence of vertebral fracture at least when treated with relatively low doses of l-thyroxine.

Free access

Mark R Postma, Romana T Netea-Maier, Gerrit van den Berg, Jens Homan, Wim J Sluiter, Margreet A Wagenmakers, Alfons C M van den Bergh, Bruce H R Wolffenbuttel, Ad R M M Hermus and André P van Beek

Objective

To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly.

Design

This is a cross-sectional study in two tertiary referral centers in The Netherlands.

Patients and methods

One hundred and eight patients with acromegaly, in whom transsphenoidal (n=101, 94%) or transcranial (n=7, 6%) surgery was performed. Subsequently, 46 (43%) received additional radiotherapy and 41 (38%) were on postoperative treatment with SSTA because of persistent or recurrent disease at the time of study. All subjects filled in standardized questionnaires measuring HR-QoL. Disease control at the time of study was assessed by local IGF1 SDS.

Results

IGF1 SDS were slightly higher in patients treated with SSTA in comparison with patients without use of SSTA (0.85±1.52 vs 0.25±1.21, P=0.026), but the percentage of patients with insufficient control (IGF1 SDS >2) was not different (17 vs 9%, P=0.208). Patients using SSTA reported poorer scores on most subscales of the RAND-36 and the acromegaly QoL and on all subscales of the multidimensional fatigue inventory-20. A subgroup analysis in patients with similar IGF1 levels (SSTA+, n=26, IGF1 SDS 0.44±0.72 vs SSTA−, n=44, IGF1 SDS 0.41±0.65) revealed worse scores on physical functioning, physical fatigue, reduced activity, vitality, and general health perception across all HR-QoL questionnaires in patients treated with SSTA.

Conclusion

QoL is impaired in association with the need for prolonged postoperative therapy by SSTA in patients with acromegaly despite similar IGF1 levels.

Free access

Pauline Brummelman, Margriet G A Sattler, Linda C Meiners, Martin F Elderson, Robin P F Dullaart, Gerrit van den Berg, Janneke Koerts, Oliver Tucha, Bruce H R Wolffenbuttel, Alfonsus C M van den Bergh and André P van Beek

Objective

The hippocampus and prefrontal cortex (PFC) are important for memory and executive functioning and are known to be sensitive to radiotherapy (RT). Radiation dosimetry relates radiation exposure to specific brain areas. The effects of various pituitary RT techniques were studied by relating detailed dosimetry of the hippocampus and PFC to cognitive performance.

Methods

In this cross-sectional design, 75 non-functioning pituitary macroadenoma (NFA) patients (61±10 years) participated and were divided into irradiated (RT+, n=30) and non-irradiated (RT−, n=45) groups. The RT+ group (who all received 25 fractions of 1.8 Gy; total dose: 45 Gy) consisted of three RT technique groups: three-field technique, n=10; four-field technique, n=15; and five-field technique, n=5. Memory and executive functioning were assessed by standardized neuropsychological tests. A reconstruction of the dose distributions for the three RT techniques was made. The RT doses on 30, 50, and 70% of the volume of the left and right hippocampus and PFC were calculated.

Results

Cognitive test performance was not different between the four groups, despite differences in radiation doses applied to the hippocampi and PFC. Age at RT, time since RT, and the use of thyroid hormone varied significantly between the groups; however, they were not related to cognitive performance.

Conclusion

This study showed that there were no significant differences on cognitive performance between the three-, four-, and five-field RT groups and the non-irradiated patient group. A dose–response relationship could not be established, even with a radiation dose that was higher on most of the volume of the hippocampus and PFC in case of a four-field RT technique compared with the three- and five-field RT techniques.

Free access

Ha T T Phan, Pieter L Jager, Jacqueline E van der Wal, Wim J Sluiter, John T M Plukker, Rudi A J O Dierckx, Bruce H R Wolffenbuttel and Thera P Links

Objective

This retrospective study describes the role of serum thyroglobulin (Tg) in relation to tumor characteristics in the prediction of persistent/recurrent disease in patients with differentiated thyroid cancer (DTC) with negative Tg at the time of ablation.

Design

Between 1989 and 2006, 94 out of 346 (27%) patients with DTC had undetectable Tg at the time of 131I ablation and were included in this evaluation. The group of 94 patients consisted of 15 males and 79 females in the age range of 16–89 years with a median follow-up of 8 years (range 1–17). All medical records and follow-up parameters of the 94 patients were evaluated for the occurrence of persistent/recurrent disease. In patients with persistent/recurrent disease hematoxylin-eosin-stained slides of the primary tumors and/or metastatic lesions were also reviewed for histological features including immunostains for Tg.

Results

During follow-up, 8 out of 94 (8.5%) patients showed persistent/recurrent disease: in the course of the disease two patients showed Tg positivity, three showed Tg antibody (TgAb) positivity, and the other three showed persistently undetectable Tg and TgAb. Patients who developed Tg and/or TgAb positivity during follow-up had a significantly shorter disease-free survival period when compared with patients with persistently undetectable Tg and TgAb (P<0.006). Histological features were not able to predict the recurrent status.

Conclusions

Follow-up of Tg and TgAb in patients with initially negative Tg and TgAb is useful since a number of patients had shown detectable Tg or TgAb during follow-up indicative for persistent/recurrent disease. Tg and TgAb negativity at the time of ablation is not a predictive determinant for future recurrent status.

Restricted access

Mark R Postma, Thalijn L C Wolters, Gerrit van den Berg, Antonius E van Herwaarden, Anneke C Muller Kobold, Wim J Sluiter, Margreet A Wagenmakers, Alfons C M van den Bergh, Bruce H R Wolffenbuttel, Ad R M M Hermus, Romana T Netea-Maier and André P van Beek

Objective

To assess the effect of somatostatin analogs (SSAs) on mortality in relation to disease control of acromegaly after pituitary surgery.

Design

A retrospective study in two large tertiary referral centers in The Netherlands.

Methods

Overall, 319 patients with acromegaly in whom pituitary surgery was performed as primary therapy between January 1980 and July 2017 were included. Postoperative treatment with SSA was prescribed to 174 (55%) patients because of persistent or recurrent disease. Disease control at last visit was assessed by IGF1 standard deviation score (SDS). Adequate disease control was defined as IGF1 SDS ≤2. Univariate determinants of mortality and standardized mortality ratios (SMRs) were calculated for groups with and without SSA at any moment postoperatively and at last visit.

Results

In total, 27 deaths were observed. In univariate analysis, determinants of mortality were inadequate disease control (relative risk (RR): 3.41, P = 0.005), surgery by craniotomy (RR: 3.53, P = 0.013) and glucocorticoid substitution (RR: 2.11, P = 0.047). There was a strong trend toward increased mortality for patients who used SSA (RR: 2.01, P = 0.067) and/or dopamine agonists (RR: 2.54, P = 0.052) at last visit. The SMR of patients with adequate disease control who used SSA at any moment postoperatively (1.07, P = 0.785) and at last visit (1.19; P = 0.600) was not increased. Insufficiently controlled patients had a significantly raised SMR (3.92, P = 0.006).

Conclusions

Postoperative use of SSA is not associated with increased mortality in patients with acromegaly who attain adequate disease control. In contrast, inadequate disease control, primary surgery by craniotomy and glucocorticoid substitution are associated with increased mortality.