Femora of women with premature ovarian insufficiency exhibit reduced strength and misalignment with the transmitted vertical forces from the upper body.

BACKGROUND: Women with premature ovarian insufficiency (POI) lack oestrogen, which is a key determinant of bone growth, epiphyseal closure, and bone tissue organisation. Although dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the gold standard for fracture risk evaluation, it does not fully characterise the skeletal abnormalities present in these women. Hence, we aimed to assess hip/femur anatomy, strength, and geometry and femoral alignment using advanced hip analysis (AHA). METHODS: We conducted a cross-sectional, case-control study including 89 women with spontaneous normal karyotype POI (s-POI) or iatrogenic POI (i-POI), aged 20-50 years compared with 89 age- and body mass index (BMI)-matched population-based female controls. Hip anatomy, strength, geometrical parameters, and femur alignment were measured using hip DXA images and Lunar AHA software. Femoral orientation angle (FOA) was quantified as the overall orientation of the femur with respect to the axis of the forces transmitted from the upper body. RESULTS: The median age of POI diagnosis was 35 (18-40) years; the mean POI duration at the time of DXA was 2.07 (range 0-13) years, and 84% of POI women received oestrogen therapy. Areal BMD at all sites was significantly lower in the POI group (all P < .05). Indices of compressive and bending strength were lower in women with POI compared with controls, specifically the cross-sectional area (CSA, mm2) and section modulus (SM, mm3) (139.30 ± 29.08 vs 157.29 ± 22.26, P < .001 and 665.21 ± 129.54 vs 575.53 ± 150.88, P < .001, respectively). The FOA was smaller (124.99 ± 3.18) in women with POI as compared with controls (128.04 ± 3.80; P < .001) at baseline and after adjusting for height and femoral neck BMD. CONCLUSION: Alongside lower BMD at multiple sites, the femora of women with POI demonstrate reduced strength and a misalignment with forces transmitted from the upper body. Further research is needed to establish the role of these newly identified features and their role in fracture risk prediction in this population.

Usefulness of Functional Thyroid-Stimulating and Thyroid-Blocking Immunoglobulin Bioassays in an Atypical Presentation of Graves' Disease.

Background/Objective: Thyroid-stimulating hormone (TSH) receptor antibody (TRAb) is well recognized as the pathogenic antibody that causes the clinical manifestation of Graves' disease (GD). Although the majority of TRAb measured in GD is due to thyroid-stimulating immunoglobulin (TSI), there are other functional classes of TRAb, ie, thyroid-blocking immunoglobulin (TBI) and neutral antibodies, which can alter the clinical course of the disease. We present a case of a patient who demonstrated interesting coexistence of both the forms using Thyretain TSI and TBI Reporter BioAssays. Case Report: A 38-year-old woman presented with thyrotoxicosis (TSH level, 0.01 mIU/L, free thyroxine level, >7.8 ng/mL [>100 pmol/L], and free triiodothyronine level, >32.6 pg/mL [>50 pmol/L]) to her general practitioner. She was treated with 15-mg carbimazole twice daily before the dose was reduced to 10 mg. Four weeks later, she developed severe hypothyroidism, with a TSH level of 57.5 mIU/L, free thyroxine level of 0.5 ng/mL (6.7 pmol/L), and free triiodothyronine level of 2.6 pg/mL (4.0 pmol/L). Carbimazole was ceased; however, she remained severely hypothyroid, with a TRAb level of 35 IU/L. Both TSI (304% signal-to-reference ratio) and TBI (56% inhibition) were present, with predominance of the blocking form of thyroid receptor antibodies (54% inhibition). Thyroxine was commenced, and her thyroid functions remained steady and TSI became undetectable. Discussion: The results of the bioassays confirmed that both TSI and TBI can coexist in a patient and that its action changes within a short period of time. Conclusion: Clinicians and laboratory scientists should be aware of the usefulness of TSI and TBI bioassays in the interpretation of atypical presentations of GD.

Abnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement.

Background: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking. Objective: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI. Method: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years. Results: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm2 and 0.0070 (p<0.05), respectively. Conclusion: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes.

Musculoskeletal Health in Premature Ovarian Insufficiency. Part Two: Bone.

Accelerated bone loss and muscle loss coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This review describes estrogen signaling in bone and its role in skeletal health and disease. Possible mechanisms contributing to bone loss in different forms of POI and current evidence regarding the utility of available diagnostic tests and therapeutic options are also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In bone, loss of bone mineral density (BMD) and compromised bone quality result in increased fracture risk; however, tools to assess bone quality such as trabecular bone score (TBS) need to be validated in this population. Timely initiation of HRT is recommended to minimize the deleterious effects of estrogen deficiency on bone in the absence of contraindications; however, the ideal estrogen replacement regimen remains unknown. POI is associated with compromised bone health, regardless of the etiology. Ongoing research is warranted to refine our management strategies to preserve bone health in women with POI.

Musculoskeletal Health in Premature Ovarian Insufficiency. Part One: Muscle.

Accelerated bone loss and muscle decline coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This article is the first of a two-part review which describes estrogen signaling in muscle and its role in musculoskeletal health and disease. Current evidence regarding the utility of available diagnostic tests and therapeutic options is also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In addition to bone loss, muscle decay and dysfunction is now increasingly recognized. Nevertheless, there is a paucity of validated tools to assess muscle parameters. There is a growing need to acknowledge bone-muscle codependence to design new therapies which target both muscle and bone, resulting in improved physical performance and reduced morbidity and mortality. More high-quality research and international collaborations are needed to address the deficiencies in our understanding and management of musculoskeletal health in women with POI.

Anti-AMPA receptor encephalitis associated with Medullary thyroid cancer.

AMPA receptor (AMPAR) antibodies are a group of recently discovered antibodies which target the neuronal synaptic proteins causing B-cell (immune) mediated neuronal damage, resulting in various neurologic syndromes depending on the area of central nervous system involvement. These syndromes are mostly reversible if treated early. Tumour association has been reported in up to 60% of cases in the most recent case series with lung, breast, ovarian cancers and thymomas being the most commonly associated malignancies with these antibodies. We present here the first case of AMPAR encephalitis associated with medullary thyroid cancer. Our patient presented with cognitive dysfunction and behavioural changes over a period of 3 weeks, with a full recovery after starting immunotherapy, once the diagnosis of AMPAR limbic encephalitis was established. This case highlights the importance of early diagnosis and management of AMPAR encephalitis as these patients respond well to immunotherapy and can have an almost complete recovery.

Severe symptomatic hyponatremia associated with the use of polyethylene glycol-based bowel preparation.

SUMMARY: Colonoscopy is a useful tool in modern medicine and is increasingly employed for both diagnostic and treatment reasons. However, its effectiveness is highly reliant on the quality of bowel cleansing. Among different bowel-cleansing agents available, PEG (polyethylene glycol) is considered to be the safest cleansing agent, especially in relation to fluid and electrolyte problems. We present here a case of severe symptomatic hyponatremia that developed after the use of PEG for an elective colonoscopy. This case highlights that despite the use of PEG-based preparations, life-threatening fluid and electrolyte disturbances can still occur in patients with risk factors, such as old age, use of thiazide diuretics and SSRIs, chronic kidney disease, heart failure and a history of electrolyte problems. These patients should be closely monitored when undertaking bowel cleansing and should receive prompt care in the event of complications, to avoid permanent neurological sequelae and death. Rapid correction of sodium levels in patients requiring treatment of hyponatremia should be avoided to prevent complications such as osmotic demyelination syndrome. LEARNING POINTS: PEG is considered to be the safest bowel-cleansing agents among different options available, but it can still cause significant side effects in susceptible individuals.Those at risk of developing adverse events include elderly individuals, patients with chronic kidney disease, heart failure or previous history of electrolyte problems and those taking thiazide diuretics and SSRIs.All such patients should be closely monitored i.e. have their metabolic profile checked prior to the commencement of bowel cleansing and a low threshold should be kept for the initiation of investigations and treatment in case of development of symptoms.Medications with a potential of causing fluid and electrolytes such as thiazide diuretics and SSRIs should be withheld while patient is undertaking bowel preparation.Hyponatremia in a hospitalized patient can be multifactorial, and the treatment principles are based on duration of onset, presence of symptoms and patients volume status.Overzealous correction of sodium levels during treatment of hyponatremia can result in serious complications such as osmotic demyelination syndrome.