A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism.

OBJECTIVE: Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS: A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS: Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION: Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.

The Smarter Safer Homes Solution to Support Older People Living in Their Own Homes Through Enhanced Care Models: Protocol for a Stratified Randomized Controlled Trial.

BACKGROUND: An aging population, accompanied by the prevalence of age-related diseases, presents a significant burden to health systems. This is exacerbated by an increasing shortage of aged care staff due to the existing workforce entering their retirement and fewer young people being attracted to work in aged care. In line with consumer preferences and potential cost-efficiencies, government and aged care providers are increasingly seeking options to move care and support to the community or home as opposed to residential care facilities. However, compared to residential care, home environments may provide limited opportunity for monitoring patients' progression/decline in functioning and therefore limited opportunity to provide timely intervention. To address this, the Smarter Safer Homes (SSH) platform was designed to enable self-monitoring and/or management, and to provide aged care providers with support to deliver their services. The platform uses open Internet of Things communication protocols to easily incorporate commercially available sensors into the system. OBJECTIVE: Our research aims to detail the benefits of utilizing the SSH platform as a service in its own right as well as a complementary service to more traditional/historical service offerings in aged care. This work is anticipated to validate the capacity and benefits of the SSH platform to enable older people to self-manage and aged care service providers to support their clients to live functionally and independently in their own homes for as long as possible. METHODS: This study was designed as a single-blinded, stratified, 12-month randomized controlled trial with participants recruited from three aged care providers in Queensland, Australia. The study aimed to recruit 200 people, including 145 people from metropolitan areas and 55 from regional areas. Participants were randomized to the intervention group (having the SSH platform installed in their homes to assist age care service providers in monitoring and providing timely support) and the control group (receiving their usual aged care services from providers). Data on community care, health and social-related quality of life, health service utilization, caregiver burden, and user experience of both groups were collected at the start, middle (6 months), and end of the trial (12 months). RESULTS: The trial recruited its first participant in April 2019 and data collection of the last participant was completed in November 2020. The trial eventually recruited 195 participants, with 98 participants allocated to the intervention group and 97 participants allocated to the control group. The study also received participants' health service data from government data resources in June 2021. CONCLUSIONS: A crisis is looming to support the aging population. Digital solutions such as the SSH platform have the potential to address this crisis and support aged care in the home and community. The outcomes of this study could improve and support the delivery of aged care services and provide better quality of life to older Australians in various geographical locations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000829213; https://tinyurl.com/2n6a75em. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31970.

Tumor-Induced Osteomalacia Localized and Excised After Pregnancy.

OBJECTIVE: Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). CASE REPORT: A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level, <8 (18-72) pg/mL; (4) 24-hour urine phosphorus level, 0.5 (0.3-1.3) g; and (5) fibroblast growth factor 23 levels, 1241 (reference range, <180) RU/mL. The patient became pregnant, and at term, a cesarean delivery was performed. Ga-68 DOTATATE PET/MRI showed a 9-mm intracortical mass in the right fibular head and right femoral and bilateral calcaneal stress fractures. The fibular lesion was resected; pathology showed a 1.5-cm lesion with positive fibroblast growth factor receptor 1 staining. DISCUSSION: This patient with TIO had an uneventful pregnancy and delivery. TIO is typically caused by benign mesenchymal tumors. Ga-68 DOTATATE PET/computed tomography has been used for localizing tumors causing TIO, yet MRI has superior contrast resolution over computed tomography. Therefore, it is not surprising that Ga-68 PET/MRI successfully localized this patient's tumor to the intracortical space of the fibular head and distinguished it from insufficiency fractures. CONCLUSION: To our knowledge, this is the first report of phosphate treatment in a pregnant patient with TIO and the first report of a tumor-inducing TIO being localized by Ga-68 DOTATATE PET/MRI.

A Case Report: Euglycemic Diabetic Ketoacidosis Presenting as Chest Pain in a Patient on a Low Carbohydrate Diet.

INTRODUCTION: Sodium-glucose cotransporter-2 [SGLT2] inhibitors reduce cardiovascular events and mortality in patients with diabetes, particularly patients with established cardiovascular disease. Euglycemic diabetic ketoacidosis [euDKA], a complication of SGLT2 therapy, can be exacerbated by a low carbohydrate diet. CASE REPORT: A 61-year-old man with a history of type 2 diabetes, taking an SGLT2 inhibitor empagliflozin 10 mg orally daily, presented to the emergency room with a 2-day history of nausea and chest pain. A week prior to presentation, he had started a ketogenic diet. He was initially admitted with a diagnosis of acute coronary syndrome. On initial assessment in the emergency room, his cardiac enzymes were normal and there were no ischemic changes in his ECG. As there was concern for unstable angina, he underwent cardiac catheterization, which showed a known total occlusion with collaterals and arteries with a non-obstructive disease without any evidence of acute plaque rupture. His baseline laboratory assessments revealed an elevated anion gap of 17, increased urinary and plasma ketones, and metabolic acidosis. His plasma glucose level was 84 mg/dL. The diagnosis of euDKA was made, and treatment with intravenous fluids and insulin was initiated. His chest pain and nausea subsequently resolved. CONCLUSION: We present a case of euDKA triggered by a ketogenic diet while on SGLT2 inhibitor therapy presenting as chest pain. The recognition of euDKA is important in the context of increased SGLT2 use for the management of cardiovascular risk for patients with diabetes.

ATRAID regulates the action of nitrogen-containing bisphosphonates on bone.

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase, resulting in defects in protein prenylation. Yet, it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Last, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare nonsynonymous coding variants in patients with ONJ or an AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.

Functional magnetic resonance imaging in primary hyperparathyroidism.

OBJECTIVE: The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and the brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional MRI (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post-parathyroidectomy (PTX). DESIGN: This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. RESULTS: There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation vs controls (max Z = 4.02, all P < 0.01) during matrix reasoning in brain regions involved in executive function (left frontal lobe (k = 57) and right medial frontal gyrus (k = 72)) and motor function (right precentral gyrus (k = 51)). During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k = 65, P < 0.01). Greater activation in this region bilaterally correlated with higher PTH (k = 96, P < 0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. CONCLUSIONS: PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT.

Chinese Women in Both the United States and Hong Kong Have Cortical Microstructural Advantages and More Trabecular Plates Compared With White Women.

We cross-sectionally compared racial differences in bone quality between Chinese women in the United States (US) and Hong Kong (HK) with white women. A total of 514 women were included. We measured bone geometry, mass, microstructure, and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT), individual trabecula segmentation (ITS), and microfinite element analysis (µFEA). After adjustment for age and body mass index (BMI), premenopausal Chinese women in the US and HK had smaller bone area but greater radial cortical (Ct.) thickness and Ct. and trabecular (Tb.) volumetric bone mineral density (vBMD) versus white women but did not differ from each other. At the radius, Tb. number was lower and spacing greater in Chinese women from HK and the US versus white women, whereas Chinese women did not differ from each other. Tb. thickness was highest in Chinese women from HK, intermediate in Chinese-Americans, and lowest in white women. Chinese women had more trabecular plates versus white women, leading to greater age- and BMI-adjusted stiffness for premenopausal Chinese women in HK and the US (both p < 0.05) versus white women. Tibial differences were similar in premenopausal women; analogous trends in microstructure were present in postmenopausal women at the tibia, although stiffness did not differ. In contrast, at the radius, cortical, plate-to-rod ratio, and stiffness were similar between postmenopausal HK and white women. Adjusting for age, weight, and height rather than age and BMI tended to reduce differences in bone size and Tb. parameters but accentuate cortical differences such that Chinese premenopausal women in both locations and postmenopausal women from HK had higher stiffness at both skeletal sites compared with white women. Compared with white women, Chinese women in the US and HK have vBMD and microstructural advantages leading to higher or similar mechanical competence in pre- and postmenopausal women, respectively, despite smaller bone size.

Pitfall in the Diagnosis of Diabetes Insipidus and Pregnancy.

Diabetes insipidus (DI) during pregnancy and the perinatal period is an uncommon medical problem characterized by polyuria and excessive thirst. Diagnosis of DI may be overlooked in the setting of pregnancy, a time when increased water intake and urine output are commonly reported. We report two cases: one of transient DI in a young woman during her third trimester of twin pregnancy in association with acute fatty liver and hypertension and one of postpartum DI secondary to Sheehan syndrome from rupture of a splenic artery aneurysm. These cases illustrate the spectrum with which DI related to pregnancy and delivery can present and highlight the difficulty in making the diagnosis since the symptoms are often initially overlooked.

Is there a role for early chemotherapy in the management of pituitary adenomas?

Pituitary adenomas are benign intracranial neoplasms that are frequently well-controlled with standard treatments that include surgical resection, radiotherapy, and agents that modulate hormonal excess. Unfortunately, a subset of patients remains uncontrolled or develops complications from these interventions. For these patients, chemotherapy is an additional treatment option that could improve outcomes. Temozolomide is an oral chemotherapy with a favorable side-effect profile that has shown activity against pituitary adenomas. Its non-overlapping toxicity and ability to induce rapid tumor regression renders it a potentially important adjunctive treatment. In patients with tumors that cannot be optimally addressed with standard treatments, there may be a role for early initiation of temozolomide.

Bone mineral density accrual determines energy expenditure with refeeding in anorexia nervosa and supersedes return of menses.

Osteopenia and osteoporosis are major complications of anorexia nervosa (AN). Since bone is a tissue requiring large amounts of energy, we examined the disproportionate increase in resting energy expenditure (REE) that occurs with refeeding of AN patients to determine if it was related to bone accretion. Thirty-seven AN patients aged 23.4 ± 4.8 years underwent a behavioral weight-gain protocol lasting a median of 66 days; 27 remained amenorrheic, and 10 regained menses. Sixteen controls aged 25.1 ± 4.7 years were age- and % IBW matched with patients. REE was measured using a respiratory chamber-indirect calorimeter. Significant correlations were found between REE and changes in spine (r = 0.48, P < 0.02) and leg (r = 0.43, P < 0.05) BMDs in AN patients. Further subgroup analysis of the amenorrheics revealed significant correlation between REE and change in spine BMD (r = 0.59, P < 0.02) and higher IGF-1 after weight gain compared to controls. Amenorrheics also had lower BMDs. These findings were absent in the regained menses group. The increase in REE seen in women with AN during nutritional rehabilitation may be related to active bone formation, which is not as prominent when menses have returned.

Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome.

The purpose of this study was to compare the hormonal/clinical profiles and markers of bone health of women with hypothalamic amenorrhea (HA) to women with suspected HA and underlying polycystic ovary syndrome (PCOS). The results indicate that compared to women with HA, women with HA and underlying PCOS exhibit higher body mass index (BMI), bone mineral densities, and incidence of hyperandrogenism, that they may exhibit increased hyperandrogenism and irregular menses with weight gain, and that they remain at similar risk for osteopenia and osteoporosis.