Hormones and Aging: An Endocrine Society Scientific Statement.

Multiple changes occur across various endocrine systems as an individual ages. The understanding of the factors that cause age-related changes and how they should be managed clinically is evolving. This statement reviews the current state of research in the growth hormone, adrenal, ovarian, testicular, and thyroid axes, as well as in osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism, with a specific focus on older individuals. Each section describes the natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, key points, and scientific gaps. The goal of this statement is to inform future research that refines prevention and treatment strategies in age-associated endocrine conditions, with the goal of improving the health of older individuals.

Treatment Guidelines for Hyponatremia: Stay the Course.

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting the guidelines, and the validity of data challenging them, we conclude that current safeguards should not be abandoned. To do so would be akin to discarding your umbrella because you remained dry in a rainstorm. The authors of this review, who represent 20 medical centers in nine countries, have all contributed significantly to the literature on the subject. We urge clinicians to continue to treat severe hyponatremia cautiously and to wait for better evidence before adopting less stringent therapeutic limits.

Age-Associated Abnormalities of Water Homeostasis.

Deficits in renal function, thirst, and responses to osmotic and volume stimulation have been repeatedly demonstrated in older populations. The lessons learned over the past six decades serve to emphasize the fragile nature of water balance characteristic of aging. Older individuals are at increased risk for disturbances of water homeostasis due to both intrinsic disease and iatrogenic causes. These disturbances have real-life clinical implications in terms of neurocognitive effects, falls, hospital readmission and need for long-term care, incidence of bone fracture, osteoporosis, and mortality.

Advances in human oxytocin measurement: challenges and proposed solutions.

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies-including the design and study of hormone secretion and biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.

Changing the name of diabetes insipidus: a position statement of the working group to consider renaming diabetes insipidus

"What's in a name? That which we call a rose / By any other name would smell as sweet" (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and endocrine pediatric societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies This editorial provides both the historical context and the rational for this proposed name change.

Changing the Name of Diabetes Insipidus: A Position Statement of the Working Group for Renaming Diabetes Insipidus.

Recent data show that patients with a diagnosis of diabetes insipidus (DI) are coming to harm. Here we give the rationale for a name change to arginine vasopressin deficiency and resistance for central and nephrogenic DI, respectively.

Changing the name of diabetes insipidus: a position statement of The Working Group for Renaming Diabetes Insipidus.

'What's in a name? That which we call a rose/By any other name would smell as sweet.' (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rationale for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology, nephrology and pediatric societies now proposes changing the name of 'diabetes insipidus' to 'arginine vasopressin deficiency (AVP-D)' for central etiologies and 'arginine vasopressin resistance (AVP-R)' for nephrogenic etiologies. This editorial provides both the historical context and the rationale for this proposed name change.

Changing the name of diabetes insipidus: a position statement of The Working Group for Renaming Diabetes Insipidus.

"What's in a name? That which we call a rose/By any other name would smell as sweet." (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and pediatric endocrine societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies. This editorial provides both the historical context and the rational for this proposed name change.

Changing the name of diabetes insipidus: a position statement of The Working Group for Renaming Diabetes Insipidus.

'What's in a name? That which we call a rose/By any other name would smell as sweet' (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word, and it therefore represents a convention with no intrinsic meaning. While this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rationale for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology, and pediatric endocrine societies now proposes changing the name of 'diabetes insipidus' to 'arginine vasopressin deficiency (AVP-D)' for central etiologies, and 'arginine vasopressin resistance (AVP-R)' for nephrogenic etiologies. This article provides both the historical context and the rationale for this proposed name change.

Changing the name of diabetes insipidus: a position statement of the working group to consider renaming diabetes insipidus.

"What's in a name? That which we call a rose / By any other name would smell as sweet" (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and endocrine pediatric societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies This editorial provides both the historical context and the rational for this proposed name change.

Central diabetes insipidus from a patient's perspective: management, psychological co-morbidities, and renaming of the condition: results from an international web-based survey.

BACKGROUND: Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients' perspectives on their disease. METHODS: This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes). FINDINGS: Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6-15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34-54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23-0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39-0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10-0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61-0·67) participants reported lower quality of life, and 369 (36%; 0·33-0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77-0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83-0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency. INTERPRETATION: This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin. FUNDING: Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.

Hyponatremia elicits gene expression changes driving osteoclast differentiation and functions.

Growing evidence indicates that chronic hyponatremia represents a significant risk for bone loss, osteoporosis, and fractures in our aging population. Our prior studies on a rat model of the syndrome of inappropriate antidiuretic hormone secretion indicated that chronic hyponatremia causes osteoporosis by increasing osteoclastic bone resorption, thereby liberating stored sodium from bone. Moreover, studies in RAW264.7 pre-osteoclastic cells showed increased osteoclast formation and resorptive activity in response to low extracellular fluid sodium ion concentration (low [Na+]). These studies implicated a direct stimulatory effect of low [Na+] rather than the low osmolality on cultured osteoclastic cells. In the present cellular studies, we explored gene expression changes triggered by low [Na+] using RNA sequencing and gene ontology analysis. Results were confirmed by mouse whole genome microarray, and quantitative RT-PCR. Findings confirmed gene expression changes supporting osteoclast growth and differentiation through stimulation of receptor activator of nuclear factor kappa-B ligand (RANKL), and PI3K/Akt pathways, and revealed additional pathways. New findings on low [Na+]-induced upregulation of lysosomal genes, mitochondrial energy production, MMP-9 expression, and osteoclast motility have supported the significance of osteoclast transcriptomic responses. Functional assays demonstrated that RANL and low [Na+] independently enhance osteoclast functions. Understanding the molecular mechanisms of hyponatremia-induced osteoporosis provides the basis for future studies identifying sodium-sensing mechanisms in osteoclasts, and potentially other bone cells, and developing strategies for treatment of bone fragility in the vulnerable aging population most affected by both chronic hyponatremia and osteoporosis. ISSUE SECTIONS: Signaling Pathways; Parathyroid, Bone, and Mineral Metabolism.

Oxytocin levels in response to pituitary provocation tests in healthy volunteers.

OBJECTIVE: Oxytocin, secreted into circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism; however, diagnostic testing for oxytocin deficiency has not been developed. The aim of this study was to investigate known pituitary provocation tests to stimulate plasma oxytocin. DESIGN: Sixty-five healthy volunteers underwent either the hypertonic saline or arginine infusion test, known to stimulate copeptin, or the oral macimorelin test, known to stimulate growth hormone. Plasma oxytocin was measured before and once plasma sodium level ≥ 150 mmol/L for the hypertonic saline, after 60 min for the arginine infusion, and after 45 min for the oral macimorelin test (expected peak of copeptin and growth hormone levels, respectively). Primary outcome was a change from basal to stimulated oxytocin levels using paired t-tests. RESULTS: As expected, copeptin increased in response to hypertonic saline and arginine infusion (P < 0.001), and growth hormone increased to oral macimorelin (P < 0.001). Oxytocin increased in response to hypertonic saline infusion from 0.4 (0.2) to 0.6 pg/mL (0.3) (P = 0.003) but with a high variance. There was no change to arginine infusion (P = 0.4), and a trend to lower stimulated levels to oral macimorelin (P = 0.05). CONCLUSION: Neither the arginine infusion nor the oral macimorelin test stimulates plasma oxytocin levels, whereas there was an increase with high variance upon hypertonic saline infusion. As a predictable rise in most participants is required for a reliable pituitary provocation test, none of the investigated pituitary provocation tests can be recommended diagnostically to identify patients with an oxytocin deficiency.

First voided volume: A novel approach to characterize nocturia.

AIMS: Nocturnal polyuria syndrome (NPS) denotes nocturnal polyuria (NP) in the absence of identifiable contributory factors. The trajectory of nocturnal urine production (NUP; typically expressed as ml/hour) may be useful in delineating between NP patients with versus without NPS, but changes in absolute urine volume, the directly measured substrate for behavioral and pharmacologic interventions targeting nocturnal urine production, have not been well characterized. This study compares the ratio of the first nocturnal voided volume (FNVV) to the nocturnal average voided volume (NAVV) in patients with versus without NPS. METHODS: Secondary analysis of 24-h voiding diaries from male patients greater than or equal to 18 years of age with two or more nocturnal voids and NP using two different criteria for NP: NUP greater than or equal to 90 ml/h and nocturnal polyuria index (NPi) greater than or equal to 0.33. Patients with diabetes insipidus and CPAP-adherent obstructive sleep apnea (OSA) were excluded. Patients were divided into 2 groups: secondary NP (OSA, congestive heart failure, and chronic kidney disease) and NPS (absence of edema, diuretic use, and the aforementioned comorbidities). FNVV was defined as the volume of urine accompanying the first nocturic episode. NAVV was defined as nocturnal urine volume/(number of nocturnal voids + 1). The nocturnal urine trajectory ratio (NUTR) was defined as FNVV/NAVV. RESULTS: At NUP greater than or equal to 90 ml/h, NUTR was significantly greater in patients with (n = 73) versus without (n = 28) NPS (1.10 [0.89-1.33] vs. 0.91 [0.55-1.15], p = .012). At NPi greater than or equal to 0.33, NUTR was likewise significantly greater in patients with (n = 92) versus without (n = 32) NPS (1.09 [0.90-1.33] vs. 0.91 [0.57-1.17], p = .010). CONCLUSIONS: The volume of urine produced in the early hours of sleep is central to identification of NPS in patients with nocturia.

Lower Oxytocin Levels Are Associated with Lower Bone Mineral Density and Less Favorable Hip Geometry in Hypopituitary Men.

INTRODUCTION: Hypopituitary patients are at risk for bone loss. Hypothalamic-posterior pituitary hormones oxytocin and vasopressin are anabolic and catabolic, respectively, to the skeleton. Patients with hypopituitarism may be at risk for oxytocin deficiency. Whether oxytocin and/or vasopressin contribute to impaired bone homeostasis in hypopituitarism is unknown. OBJECTIVES: To determine the relationship between plasma oxytocin and vasopressin levels and bone characteristics (bone mineral density [BMD] and hip structural analysis [HSA]) in patients who have anterior pituitary deficiencies only (APD group) or with central diabetes insipidus (CDI group). METHODS: This is a cross-sectional study. Subjects included 37 men (17 CDI and 20 APD), aged 20-60 years. Main outcome measures were fasting plasma oxytocin and vasopressin levels, and BMD and HSA using dual X-ray absorptiometry. RESULTS: Mean BMD and HSA variables did not differ between the CDI and APD groups. Mean BMD Z-scores at most sites were lower in those participants who had fasting oxytocin levels below, rather than above, the median. There were positive associations between fasting oxytocin levels and (1) BMD Z-scores at the spine, femoral neck, total hip, and subtotal body and (2) favorable hip geometry and strength variables at the intertrochanteric region in CDI, but not APD, participants. No associations between vasopressin levels and bone variables were observed in the CDI or ADP groups. CONCLUSIONS: This study provides evidence for a relationship between oxytocin levels and BMD and estimated hip geometry and strength in hypopituitarism with CDI. Future studies will be important to determine whether oxytocin could be used therapeutically to optimize bone health in patients with hypopituitarism.