Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

Spontaneous remission of acromegaly and Cushing's disease following pituitary apoplexy: Two case reports.

In this double case report, we present two special cases of pituitary apoplexy. First, we describe a patient with growth hormone deficiency despite clinical suspicion of acromegaly. Imaging showed evidence of a recent pituitary apoplexy, which might have caused spontaneous remission of the acromegaly before presentation at our outpatient clinic. Second, we describe a patient who presented with spontaneous remission of Cushing's disease after pituitary apoplexy, followed by a spontaneous remission of a relapse of the Cushing's disease due to a second pituitary apoplexy. These cases show that patients in spontaneous remission of hormonally active pituitary adenomas should be suspected of a pituitary apoplexy. Furthermore, even after spontaneous remission following pituitary apoplexy, careful long-term follow-up of these patients is mandatory, as relapses of hormonal hypersecretion can occur.

Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression.

OBJECTIVE: The aim of this study was to investigate whether thyroid function and thyroid peroxidase antibodies (TPOAb) are associated with depression, when using both state and trait parameters of depression. METHOD: In 1125 participants of the Nijmegen Biomedical Study, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and TPOAb were measured twice. The Beck Depression Inventory (BDI), a self-reported lifetime diagnosis of depression, and the neuroticism scale of the Eysenck Personality Questionnaire Revised Short Scale (EPQ-RSS) were used to evaluate the presence of state and trait features of depression. RESULTS: We found no association between TSH and FT4 levels and BDI score, current depression, lifetime diagnosis of depression, and EPQ-RSS neuroticism score. Subjects with TPOAb had higher EPQ-RSS neuroticism scores in comparison with subjects without TPOAb, mean score 4.1 vs. 3.2 (regression coefficient 0.70; 95% CI 0.1-1.3; P-value 0.02 after adjustment for confounders). The prevalence of a lifetime diagnosis of depression was higher in subjects with positive TPOAb in comparison with participants without TPOAb: 24.2% vs. 16.7% (relative risk 1.4; 95% CI 1.0-2.1; P-value 0.04 after adjustment for confounders). CONCLUSION: Thyroid peroxidase antibodies are positively associated with trait markers of depression. The presence of TPOAb may be a vulnerability marker for depression.

Changes of bone mineral density, quantitative ultrasound parameters and markers of bone turnover during treatment of hyperthyroidism.

BACKGROUND: The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment is not clear. METHODS: The bone density measured by dual X-ray absorptiometry (DXA), the parameters of quantitative ultrasound (QUS) and biochemical markers of bone turnover of 22 patients were measured before and after one year of treatment with thiamazole and levothyroxine. RESULTS: The mean BMD of lumbar spine, femoral neck, Ward triangle and total hip bone density increased by 5.9, 3.8, 3.0 and 6.7%, respectively, after one year of treatment, all significant increases except the increase in Ward triangle bone mass density. There was no significant change in QUS parameters, although the increase in broadband ultrasound attenuation (BUA) of the left and right calcaneus of 5.2 and 4.2%, respectively, suggests reversibility in the long term. Urinary pyridinoline cross-links declined significantly and normalised after treatment. Bone-specific alkaline phosphatase declined after an initial rise, not (yet) reaching normal values after one year of treatment. CONCLUSION: The decline in BMD in hyperthyroid patients measured by DXA seems to be reversible after treatment of hyperthyroidism, whereas a change in the QUS parameters, probably also an indicator of bone elasticity and architecture, could not be found.

The StethoDop: a Doppler stethoscope attachment for investigation of arterial and venous insufficiency of the lower extremities.

BACKGROUND: The aim of the current study was to investigate whether the StethoDop can serve as a valid and reproducible instrument for measuring the ankle-brachial index (ABI) and assessing venous reflux, even when used by inexperienced investigators, in comparison with the classic Doppler. METHODS: I) During four weeks, four ankle-brachial index (ABI) measurements were performed on 44 patients: one measurement with the classic Doppler by an experienced investigator, one with the classic Doppler by an inexperienced investigator and two measurements with the StethoDop by the inexperienced investigator. II) 36 patients were screened for venous insufficiency by detecting venous reflux with the StethoDop and classic Doppler at the saphenofemoral and saphenopoplitial junctions by an inexperienced investigator. The results were compared with the results of the duplex as gold standard and with the results of the examination by an experienced dermatologist with the classic Doppler. RESULTS: I) The confidence interval of ABI measurement for both the classic Doppler and the StethoDop by the inexperienced investigator was within an acceptable +/- 0.21 interval of significant change. II) For venous reflux determination, the overall sensitivity and specificity of the StethoDop were comparable with the sensitivity and specificity of the classic Doppler: sensitivity 76.0 and 75.0%, specificity 94.8 and 94.2%, respectively. The positive predictive value of the StethoDop, compared with the duplex, was 87.5%; the negative predictive value was 90.0%. CONCLUSION: I) For ABI measurement, the StethoDop is a valid instrument with reproducible results, even when used by inexperienced investigators. II) For venous reflux determination, the StethoDop is a valid screening instrument for venous insufficiency. However, as with determination with the classic Doppler, the reflux assessment by StethoDop gives no information about the deep veins and may miss up to 24% of apparent reflux.