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Pepijn van Houten, Romana Netea-Maier, Margreet Wagenmakers, Sean Roerink, Ad Hermus, and Annenienke Van de Ven

Objective: Cushing’s syndrome (CS) is associated with osteoporosis and high fracture risk. Besides males sex it is unknown which variables influence bone mineral density (BMD) at diagnosis and it is unclear to what extent BMD normalizes during long-term follow-up after treatment of CS. The aim of this study was to determine factors associated with BMD at diagnosis of CS and to determine the long-term course of BMD and fracture rate after successful treatment of CS.

Design: Retrospective cross-sectional and longitudinal cohort study.

Methods: Data were collected from 231 patients with CS who were treated at the Radboud University Medical Centre between 1968 and 2020.

Results: At diagnosis, male sex was associated with lower Z-scores at the lumbar spine (LS) compared with female sex: -0.97SD [-1.45 - -0.49] after correction for possible confounders. Shorter duration of symptoms and younger age were also associated with lower Z-scores at diagnosis, while etiology of CS, urinary cortisol excretion and gonadal status were not associated with Z-scores at diagnosis. Z-scores improved up to 20 years after treatment. Fifteen years after treatment, men showed larger improvements of Z-scores than women; +2.56 [1.82-3.30] increase in LS Z-score versus +1.48 [0.96-2.00] respectively. Fracture incidence was highest during the 2 years before diagnosis and decreased after treatment.

Conclusion: Male sex, younger age and shorter duration of symptoms are associated with lower BMD at diagnosis of CS. BMD continues to improve up to 20 years after treatment of CS. Fracture rate decreases after treatment of CS.

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Annenienke C van de Ven, Romana T Netea-Maier, Femmie de Vegt, H Alec Ross, Fred C G J Sweep, Lambertus A Kiemeney, Johannes W Smit, Ad R Hermus, and Martin den Heijer

Objective

The aim of this study was to investigate the influence of age on the association between thyroid function and mortality.

Design

The Nijmegen Biomedical Study is a population-based study, comprising 5816 randomly selected adults of all age groups without previously known thyroid disease.

Methods

TSH, free thyroxine (FT4) and peroxidase antibodies were measured in 2002–2003. The number of deaths were established in 2012 (median follow-up time 9.4 years).

Results

Subclinical thyrotoxicosis was associated with mortality in subjects aged <65 years (hazard ratio (HR) 2.5, 95% CI 1.1–5.7), but not in subjects aged >65 years. As for thyroid function within the normal range: in the 493 participants aged 80 years or older, an FT4 level in the high-normal range (18.5–22 pmol/l) was associated with a higher mortality in comparison with FT4 levels in the middle range (11.5–15.0 pmol/l): HR 1.7 (95% CI 1.0–2.9). In these elderly, TSH levels within the high-normal range (3.0–4.0 mIU/l) were also associated with a higher mortality in comparison with TSH levels within the middle range (1.0–2.0 mIU/l): HR 1.8 (95% CI 1.0–3.1).

Conclusions

The relationship between thyroid function and mortality differs according to age. This finding might (partially) explain the discrepant results of previous studies examining the relationship between thyroid function and mortality in different age groups.

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Annenienke C van de Ven, Romana T Netea-Maier, H Alec Ross, Teun A E van Herwaarden, Suzanne Holewijn, Jacqueline de Graaf, Bart L A Kiemeney, Doorlène van Tienoven, Jack F M Wetzels, Johannes W Smit, Fred C G J Sweep, Ad R M M Hermus, and Martin den Heijer

Objective

Several cross-sectional studies on populations with iodine deficiency showed that TSH-levels are negatively associated with age, while in populations with high iodine intake TSH is positively associated with age. The question is whether such an age-thyroid function relation is an ongoing process apparent also in longitudinal studies and whether it reflects an actual iodine deficiency or an iodine insufficiency in the past.

Methods

In an area with a borderline iodine status in the past, we studied 980 participants of the Nijmegen Biomedical Study. We measured serum TSH, free thyroxine (FT4), total triiodothyronine (T3), peroxidase antibodies, and the urine iodine and creatinine concentration 4 years after our initial survey of thyroid function, in which we reported a negative association between TSH and age.

Results

Within 4 years, TSH decreased by 5.4% (95% CI 2.5–8.3%) and FT4 increased by 3.7% (95% CI 2.9–4.6%). Median urinary iodine concentration was 130 μg/l. Estimated 24-h iodine excretion was not associated with TSH, T3, change of TSH, or FT4 over time or with the presence of antibodies against thyroid peroxidase. Only FT4 appeared to be somewhat higher at lower urine iodine levels: a 1.01% (95% CI 0.17–1.84%) higher FT4 for each lower iodine quintile.

Conclusions

In this longitudinal study, we found an ongoing decrease in TSH and increase in FT4 in a previously iodine insufficient population, despite the adequate iodine status at present. This suggests that low iodine intake at young age leads to thyroid autonomy (and a tendency to hyperthyroidism) that persists despite normal iodine intake later in life.