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Osteoporosis is underrecognized and undertreated in men, even though up to 25% of fractures in patients over the age of 50 years occur in men. Men develop osteoporosis with normal aging and accumulation of comorbidities that cause bone loss. Secondary causes of bone loss may be found in up to 60% of men with osteoporosis. Mortality in men who experience major fragility fracture is greater than in women. Diagnosis of osteoporosis in men is similar to women, based on low-trauma or fragility fractures, and/or bone mineral density dual-energy X-ray absorptiometry (DXA) T-scores at or below -2.5. Because most clinical trials with osteoporosis drugs in men were based on bone density endpoints, not fracture reduction, the antifracture efficacy of approved treatments in men is not as well documented as that in women. Men at a high risk of fracture should be offered treatment to reduce future fractures.

Context Kidney complications may be considerably higher in patients with chronic hypoparathyroidism (hypoPT) treated with activated vitamin D and calcium supplementation. Objective We aimed to investigate the risk of chronic kidney disease (CKD), urolithiasis, and hospitalization in patients with chronic hypoPT. Methods In this population-based cohort study in Sweden, national registries (Swedish National Patient Register, Swedish Prescribed Drug Register, and Total Population Register, 1997–2018) were used to identify patients with chronic hypoPT and controls matched by sex, age, and county of residence. We determined time to CKD and urolithiasis diagnosis, and incidence rates of hospitalization. Results A total of 1562 patients with chronic hypoPT without preexisting CKD and 15 620 controls were included. The risk of developing CKD was higher in patients with chronic hypoPT compared with controls (hazard ratio [HR] 4.45; 95% CI, 3.66-5.41). In people without prior urolithiasis (n = 1810 chronic hypoPT and n = 18 100 controls), the risk of developing urolithiasis was higher in patients with chronic hypoPT (HR 3.55; 95% CI, 2.84-4.44) compared with controls. Patients with chronic hypoPT had higher incidence rates for all-cause hospitalization (49.59; 95% CI, 48.50-50.70, per 100 person-years vs 28.43; 95% CI, 28.15-28.71, respectively) and for CKD (3.46; 95% CI, 3.18-3.76, per 100 person-years vs 0.72; 95% CI, 0.68–0.77, respectively), compared with controls. Men with hypoPT appear to have a higher risk of CKD than women. Conclusion Patients with chronic hypoPT had an increased risk of CKD, urolithiasis, and hospitalization compared with controls.

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders in 2019 were discussed during two virtual workshops in 2021 and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosis of familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represents areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborn children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed at a broader clinical audience and were developed with the focus on endocrinologists in training.

Context There are scarce data on the management of chronic hypoparathyroidism (hypoPT) in pregnant women. Objective The aim of this study was to evaluate pregnancy outcome and total number of births in maternal chronic hypoPT. Methods The Swedish National Patient Register, The Swedish Prescribed Drug Register, Swedish Medical Birth Register, and the Total Population Register were used to identify 97 women with chronic hypoPT and 1030 age-matched controls who delivered 139 and 1577 singleton infants, respectively, following diagnosis between 1997 and 2017. Results Women in the chronic hypoPT group had more frequent diabetes (DM) and chronic kidney disease (CKD) compared with the control group (P = 0.043 and P < 0.001, respectively). After adjusting for DM, CKD, maternal age at delivery, and calendar year of delivery, chronic hypoPT cases were associated with increased risk of induction of labor (OR, 1.82; 95% CI, 1.13-2.94) and birth of infants with lower birth weight (β-coefficient −188 g; 95% CI, −312.2 to −63.8) compared with controls. No difference was found in infant length, small for gestational age, or head circumference after adjustments. Mean gestational age at delivery after controlling for DM, CKD, and pre-eclampsia was not significantly younger (P = 0.119). There was no difference in congenital malformations or perinatal death and no difference in the total number of infants born between groups (P = 0.518). Conclusion The majority of women with chronic hypoPT had normal pregnancy outcomes, and the overall risks appear low. Maternal chronic hypoPT is, however, associated with higher risk of induction of labor and slightly lower infant birth weight.

Background Patients with hypoparathyroidism are at risk of both hypocalcemic and hypercalcemic crisis. Patients report that health professionals do not always respond adequately in an acute situation. The extent and handling of severe hypo- and hypercalcemia in hypoparathyroidism is unknown. Aims To outline the need for a medical emergency card for primary hypoparathyroidism. Method Postal survey amongst Norwegian and Swedish patients with chronic hypoparathyroidism of all causes. Altogether 455 invitations were sent (333 from Norway and 122 from Sweden). Results Three hundred and thirty-six of 455 (74%) patients responded (253 from Norway and 83 from Sweden). The majority were women (79%), and the main cause was postsurgical hypoparathyroidism (66%). Overall 44% and 16% had been hospitalized at least once for hypo- or hypercalcemia, respectively. Eighty-seven per cent felt that an emergency card would be highly needed or useful. Amongst those hospitalized for hypocalcemia, 95% felt a card was needed compared to 90% amongst those hospitalized for hypercalcemia. Five per cent believed that a card would not be useful. Conclusions The majority answered that an acute card is highly needed or useful. Hospitalization for acute hypocalcemia was more common (44%) than for acute hypercalcemia (16%). As a result of this survey, an emergency card will be distributed in three European countries to test its utility.

SummaryContext Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). Objective The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. Design and setting An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Patients Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Intervention Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. Main outcome measure We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Results Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Conclusion Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD.

Context: Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison’s disease. Objective: The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortisone (OHC) replacement therapy. Design, Patients, and Interventions: This was a prospective crossover, randomized, multicenter clinical trial comparing 3 months of treatment with thrice-daily OHC vs CSHI. From Norway and Sweden, 33 patients were enrolled from registries and clinics. All patients were assessed at baseline and after 8 and 12 weeks in each treatment arm. Main Outcome Measures: The morning ACTH level was the primary outcome measure. Secondary outcome measures were effects on metabolism, health-related quality of life (HRQoL), sleep, and safety. Results: CSHI yielded normalization of morning ACTH and cortisol levels, and 24-hour salivary cortisol curves resembled the normal circadian variation. Urinary concentrations of glucocorticoid metabolites displayed a normal pattern with CSHI but were clearly altered with OHC. Several HRQoLindices in the vitality domain improved over time with CSHI.Nobenefit was found for either treatments for any subjective (Pittsburgh Sleep Quality Index questionnaire) or objective (actigraphy) sleep parameters. Conclusion: CSHI safely brought ACTH and cortisol toward normal circadian levels without adversely affecting glucocorticoid metabolism in the way that OHC did. Positive effects on HRQoL were noted with CSHI, indicating that physiological glucocorticoid replacement therapy may be beneficial and that CSHI might become a treatment option for patients poorly controlled on conventional therapy. publishedVersion

Objectives: The results of studies of bone mineral density (BMD) in Addison's disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study we compare hip fracture risk in adults with and without AD. Design: A population-based cohort study. Methods: Through the Swedish National Patient Register and the Total Population Register, we identified 3,219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964-2006, and 31,557 age- and sex-matched controls. Time to hip fracture was measured. Results: We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture (hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6-2.1; p < 0.001). This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95% CI, 1.6-4.5). We found a positive association between hip fracture and undiagnosed AD (odds ratio (OR) = 2.4; 95% CI, 2.1- 3.0) with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95% CI, 1.8-4.2). Conclusion: Both clinically undiagnosed and diagnosed AD were associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age.

Autoimmune Addison's disease (AAD) tends to affect young and middle-aged women. It is not known whether the existence of undiagnosed or diagnosed AAD influences the outcome of pregnancy.The aim of the study was to compare the number of children and pregnancy outcomes in individuals with AAD and controls.We conducted a population-based historical cohort study in Sweden.Through the Swedish National Patient Register and the Total Population Register, we identified 1,188 women with AAD and 11,879 age-matched controls who delivered infants between 1973 and 2006.We measured parity and pregnancy outcome.Adjusted odds ratios (ORs) for infants born to mothers with deliveries 3 yr or less before the diagnosis of AAD were 2.40 [95% confidence interval (CI), 1.27-4.53] for preterm birth (≤37 wk), 3.50 (95% CI, 1.83-6.67) for low birth weight (2500 g), and 1.74 (95% CI, 1.02-2.96) for cesarean section. Compared to controls, women who gave birth after their AAD diagnosis were at increased risk of both cesarean delivery (adjusted OR, 2.35; 95% CI, 1.68-3.27) and preterm delivery (adjusted OR, 2.61; 95% CI, 1.69-4.05). Stratifying by isolated AAD and concomitant type 1 diabetes and/or autoimmune thyroid disease in the mother did not essentially influence these risks. There were no differences in risks of congenital malformations or infant death. Women with AAD had a reduced overall parity compared to controls (P0.001).Clinically undiagnosed and diagnosed AAD both entail increased risks of unfavorable pregnancy outcomes. AAD also influences the number of childbirths.