The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in ...calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.
X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization ...of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care.
Studies suggest that melatonin may promote cardiovascular protection. Previous trials have primarily been performed on co-morbid patients. Little information exist on the effect in postmenopausal ...women with general good health.
In a double-blinded placebo-controlled study, we randomized 41 postmenopausal women to either 10 mg melatonin per day or placebo for 3 months.
Outcomes of the trial was changes in blood pressure, pulse wave velocity (PWV), and quality of sleep evaluated by Pittsburgh Sleep Quality Index (PSQI).
Thirty-nine women completed the study. Mean age was 63 years (range 55–75 years). Over the 3 months of the trial, PWV did not differ between groups: Placebo 1.1% (IQR −2.1;9.9) vs. melatonin 0.0% (IQR-9.8;4.1), p = 0.43). The were no significant differences in blood pressure bewteen melatonin and placebo group. Both groups had a pour quality of sleep at baseline (placebo: PSQI 6.0 (IQR 3.3; 8.8) vs. melatonin PSQI 6.0 (IQR 3.0; 10.0), p = 0.94), which did not change in response to treatment.
In healthy postmenopausal women, supplementation with 10 mg melatonin was well-tolerated, but we did not observe any significant improvements in pulse wave velocity, blood pressure or quality of sleep compared with placebo.
•Randomized controlled trial on general healthy postmenopausal women.•Investigating the effect of melatonin on cardiovascular indices and quality of sleep.•Additional effect of melatonin on blood pressure and arterial stiffness was sparse in healthy women.
Summary
Objective
Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH, resulting ...in hypocalcaemia and hyperphosphataemia. Studies in patients with PHP are limited. We sought to identify all patients in Denmark with PHP and access their mortality data and risk of complications.
Design
Patients were identified through the Danish National Patient Registry and a prescription database, with subsequent validation by investigation of patient charts.
Methods
For each case, three age‐ (±2 years) and gender‐matched controls were randomly selected from the general background population. We identified a total of 60 cases, equal to a prevalence of 1·1/100 000 inhabitants. The average age at diagnosis was 13 years (range 1–62 years), and 42 were women. Only 14 patients had an identified mutation in the GNAS1 gene.
Results
Compared with controls, patients with PHP had an increased risk of neuropsychiatric disorders (P < 0·01), infections (P < 0·01), seizures (P < 0·01) and cataract (P < 0·01), whereas their risk of renal, cardiovascular, malignant disorders and fractures was compatible with the general background population. The same tendencies were found in a subgroup analysis in cases with genetically verified PHP.
Conclusion
Patients with PHP have an increased risk of neuropsychiatric disorders, infections, cataract and seizures, whereas mortality among PHP patients is compatible with that in the background population.
Context:
Renal complications in terms of hypercalciuria, nephrolithiasis, and nephrocalcinosis are well-known risks in primary hyperparathyroidism (PHPT) and may lead to impaired renal function.
...Evidence Acquisition:
We reviewed published evidence on the occurrence, pathophysiology, and consequences of renal complications in PHPT and highlighted areas of uncertainty that should be investigated further.
Evidence Synthesis:
In asymptomatic PHPT, renal stones are present in approximately 7% of the patients, which is a significantly higher prevalence than among patients without PHPT (1.6%). Also, before diagnosis of PHPT, risk of hospital admissions due to renal stones is increased compared with the background population, and the risk remains increased for at least 10 yr after surgical cure from PHPT. However, shortly after parathyroidectomy, risk of recurrent stone episodes is reduced to the recurrence rate among patients with idiopathic renal stone disease. In general, patients with PHPT who develop nephrolithiasis are of younger age and more often are males, compared with those who do not form renal calcifications. Although 24-h urinary calcium is decreased after parathyroidectomy, studies have shown a higher renal calcium excretion and lower serum phosphate levels in former PHPT patients compared with healthy controls, suggesting that these patients have some additional mineral disorder.
Conclusion:
All patients with a diagnosis of PHPT should initially be evaluated for renal calcifications by unenhanced helical computed tomography. If calcifications are present, parathyroidectomy is recommended. If symptoms develop after parathyroidectomy, patients should be evaluated and treated similar to other patients with renal stones.
A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on ...characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation.
We identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses.
Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels.
PDF
