Guri Grimnes

Background: Pregnancy-related transient osteoporosis of the hip (PR-TOH) is an uncommon and frequently underdiagnosed condition that typically presents with acute hip pain during late pregnancy or the early postpartum period. Because its clinical presentation is nonspecific and overlaps with pregnancy-related pelvic girdle pain, the diagnosis is often delayed, and the initial management is suboptimal. Although bilateral involvement has been reported, comparative data on diagnostic work-up, multidisciplinary management, and follow-up remain limited. Case Presentation: We report a case of bilateral PR-TOH in a 35-year-old Caucasian primigravida (G1, P0) who presented at 31 + 6 weeks of gestation with progressively worsening bilateral hip pain that culminated in severe functional impairment and wheelchair dependence. Initial ultrasound, laboratory work-up, and rheumatological screening were inconclusive, and intra-articular corticosteroid injections failed to relieve symptoms and were temporally associated with deterioration of glycaemic control and a periorbital and palmar eczematous rash. Magnetic resonance imaging (MRI) demonstrated diffuse bone marrow oedema in both femoral heads with preserved articular cartilage and no evidence of avascular necrosis, supporting a diagnosis of bilateral PR-TOH. Postpartum dual-energy X-ray absorptiometry (DXA) confirmed reduced bone mineral density at both femoral necks (Z-scores below −2.0). Pregnancy was prolonged until 37 + 4 weeks, and delivery was by elective caesarean section. Postpartum care included analgesia, calcium and vitamin D supplementation, structured physiotherapy, and a graded weight-bearing rehabilitation programme. Bone mineral density improved markedly on follow-up DXA at six months, with complete clinical recovery and no further imaging abnormalities at 12, 24, and 30 months. Conclusions: PR-TOH should be considered in pregnant or postpartum women with persistent hip pain and progressive functional limitation. MRI is the key imaging modality for early diagnosis and for excluding alternative causes, whereas DXA remains the reference standard for quantifying bone mineral density and monitoring recovery. Bilateral presentations require a multidisciplinary, individualised approach that addresses both maternal and obstetric outcomes.

Background: Pregnancy-related transient osteoporosis of the hip (PR-TOH) is a rare and often underdiagnosed condition presenting with acute hip pain in late pregnancy or postpartum. Due to its nonspecific clinical presentation, it is frequently misinterpreted as common musculoskeletal or pelvic girdle pain, leading to delayed diagnosis and suboptimal management. Case Presentation: We report a rare case of bilateral PR-TOH in a 35-year-old primigravida diagnosed at 31+6 weeks of gestation. The patient presented with progressively worsening hip pain leading to severe mobility impairment. Initial investigations, including ultrasound and laboratory testing, were inconclusive. Definitive diagnosis was established by magnetic resonance imaging (MRI), demonstrating characteristic bone marrow oedema in both femoral heads. The patient was managed conservatively with analgesia, restricted weight bearing, and multidisciplinary care involving obstetrics, endocrinology, and orthopaedics. Pregnancy was successfully prolonged until 37+4 weeks, when caesarean section was performed due to clinical deterioration. Postpartum management included calcium and vitamin D supplementation and rehabilitation. Follow-up demonstrated significant improvement in bone mineral density on DEXA and complete clinical recovery at 12 months. Conclusions: PR-TOH should be considered in pregnant or postpartum women presenting with persistent hip pain and progressive functional limitation. Early use of MRI is essential for accurate diagnosis and differentiation from more common pregnancy-related conditions. Prompt recognition and multidisciplinary management are crucial to prevent complications and optimize maternal and obstetric outcomes.

Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare yet severe multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Classical APS-1 arises from biallelic recessive AIRE mutations, whereas dominant negative mutations cause a milder, nonclassical phenotype with variable clinical presentation. Due to its rarity, long-term, population-based data are limited, underscoring the need for extended follow-up to guide lifelong care and research. Objective: To characterize the clinical profiles of APS-1 and explore associations between disease manifestations, autoantibody profiles, and AIRE mutations over an extended follow-up (1996-2025). Patients: All known Norwegian patients with APS-1. Methods: We analyzed longitudinal clinical and laboratory data of 71 APS-1 patients (49 classical, 22 nonclassical) from the Norwegian Registry of Organ-specific Autoimmune Diseases. Data included clinical progression, autoantibody and cytokine profiles, and AIRE genotypes. Additionally, we compared age at diagnosis of primary adrenal insufficiency (PAI) in patients with and without (n = 999) APS-1. Results: In classical APS-1, the most frequent clinical manifestations were chronic mucocutaneous candidiasis, enamel hypoplasia, and PAI, while for nonclassical APS-1 vitiligo, hypothyroidism, and PAI were most common. A broad proinflammatory cytokine signature was observed in classical APS-1, along with increased levels of the soluble form of the interferon (IFN)-α/β receptor. Conclusion: APS-1 should be considered in patients diagnosed with PAI before age 20, and AIRE sequencing is recommended for diagnostic confirmation. The presence of IFN-ω autoantibodies, a proinflammatory cytokine profile, and increased soluble IFN receptor levels further support the role of dysregulated interferon responses in APS-1 pathogenesis.

Summary Examining fracture dynamics by socioeconomic status may inform healthcare and prevention. We found a higher risk of hip fracture in men and women with lower educational level in Norway. However, by age 90 + years, the cumulative incidence was higher in those with higher education, due to their higher life expectancy. Purpose Socioeconomic gradients are seen for several health outcomes in high-income countries. We aimed to examine possible educational gradients in risk of hip fracture in Norway and to describe the cumulative incidence of hip fracture by educational level. Methods In a population-wide cohort of Norwegians aged ≥ 50 years, information on attained education from Statistics Norway was linked to hospital-treated hip fractures and deaths during 2002–2019. We estimated relative fracture risk by educational level (primary, secondary or tertiary) in Cox proportional hazards regression. We also examined the cumulative incidence over attained age by gender and educational level in competing risk regression. Results The population included N = 1,389,858 individuals with 135,938 incident hip fractures. Compared with men who had attained tertiary education, hazard ratios (95% confidence intervals) for hip fracture were 1.44 (1.40, 1.49) in men with primary education only and 1.26 (1.22, 1.29) in men with secondary education. In women, the corresponding estimates were 1.28 (1.25, 1.31) and 1.16 (1.13, 1.19). In the age range 50 to 90 years, the highest cumulative incidence of hip fracture was seen in those with primary education. The gradient gradually diminished with advancing age and was reversed in the oldest (> 90 years) in both genders. Conclusions There was a clear educational gradient in hip fracture incidence in both men and women in Norway, with a higher risk in people with lower education. Despite this, the cumulative incidence of hip fracture in old age was highest among people with higher education, due to their higher life expectancy.

Context: Longitudinal data regarding vitamin D status in adolescence is scarce. This study presents population-based data from an Arctic adolescent population (n = 589) at 16 and 18 years.Objective: The aims of this study were to investigate changes in vitamin D status during 2 years in adolescence, and whether lifestyle changes were associated with serum 25-hydroxyvitamin D (s-25(OH)D) at follow-up.Methods: Fit Futures is a longitudinal study at 69°N in Norway. Participants had their s-25(OH)D levels analyzed in their first and third year of upper secondary school (median age 16 and 18 years), in Fit Futures 1 (FF1) and Fit Futures 2 (FF2), respectively. Self-reported lifestyle habits were registered through questionnaires. The association between lifestyle changes and s-25(OH)D levels at follow-up were calculated by regression analyses, controlling for baseline s-25(OH)D levels.Results: Longitudinal data were available for 309 girls and 280 boys. The proportion of adolescents with s-25(OH)D <50 nmol/L were 73.7% in FF1 and 77.1% in FF2, while the proportion <30 nmol/L constituted 35.7% in FF1 and 40.9% in FF2. Of those with s-25(OH)D <30 nmol/L (severe vitamin D deficiency) in FF1, 73.3% remained severely deficient in FF2. Among boys, an increase in UV exposure was significantly associated with higher s-25(OH)D levels in FF2 (beta; CI [nmol/L] 12.9; 9.1, 16.7). In girls, decreased vitamin/mineral supplement intake was significantly associated with lower s-25(OH)D at FF2 (−6.7; −10.2, −3.1), while increased UV (10.8; 7.0, 14.7) and combined hormonal contraceptive exposure (12.1; 6.0, 18.1) in FF2 was significantly associated with higher s-25(OH)D levels in FF2.Conclusion: Severe vitamin D deficiency was prevalent throughout adolescence. Lifestyle changes may alter s-25(OH)D levels in this age group.

Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood. Design: Cross-sectional study. Methods: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH. Results: Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = −0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (−0.15 normalized protein expression [NPX], P = .0001, and −0.25 NPX, P = .0003, respectively). Conclusions: We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.

Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison’s disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. Methods: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). Results: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. Conclusion: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.