Diabetes insipidus (DI) is characterized by polydipsia and polyuria with a dilute urine having a specific gravity less than 1.010, hypernatremia, and dehydration. It results either from a deficiency of arginine vasopressin (AVP), termed central DI (CDI), or from renal resistance to the action of AVP, called nephrogenic DI (NDI). The prevalence of DI is 1:25,000, with fewer than 10% of cases from hereditary forms. Intact thirst protects selfsufficient patients against severe hypernatremic dehydration, putting infants and neurologically compromised patients more at risk for clinically significant dehydration.Water balance is tightly regulated by AVP, which stimulates both water reabsorption by the kidneys and the ingestion of water in response to thirst. AVP is principally synthesized in the hypothalamic paraventricular, and supraoptic nuclei, and then is stored in the posterior pituitary before it is secreted into the systemic circulation in response to increasing plasma osmolality. In the kidneys, AVP, through binding to the vasopressin V2 receptor in the basolateral membrane of the collecting ducts, activates a series of reactions that allows water to move freely across an osmotic gradient back from a relatively dilute urine into the systemic circulation in response to the plasma's rising osmolality.Decreased production or release of AVP results in CDI, which can present at any age. Underlying mechanisms of CDI include mutations in the AVP gene, anatomical hypothalamic or pituitary defects, trauma, neoplasms, infections, autoimmune disease, or infiltrative processes affecting the AVP neurons or fiber tracts (Table 1). Familial, autosomal dominant CDI results from any of multiple different mutations in the coding region of the AVP gene, with variable severity within a family, and it usually presents after the first year after birth. Another cause of genetically acquired CDI is Wolfram syndrome, a rare autosomal dominant disorder characterized by diabetes mellitus, CDI, optic nerve atrophy, and sensorineural hearing loss. CDI may also manifest as a component of septo-optic dysplasia, which includes optic nerve hypoplasia, an abnormal septum pellucidum, and pituitary hormone deficiencies. CDI associated with septo-optic dysplasia puts patients at particular risk for dehydration due to dysfunction of the osmo-regulated thirst mechanism. Slightly more than half of patients with a craniopharyngioma have accompanying CDI, either before or, particularly, after resection. Typically, a triphasic response follows neurosurgery, with CDI first manifesting 1 to 2 days postoperatively, giving way to the syndrome of inappropriate antidiuretic hormone 2 to 10 days postoperatively, and then converting back to CDI, either transiently or permanently.AUTHOR DISCLOSURE Drs Weiner and Vuguin have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Summary 25‐hydroxy vitamin D (25 OHD) deficiency and secondary hyperparathyroidism have been seen after metabolic and bariatric surgery, but data are lacking on the bone health outcomes of adolescent sleeve gastrectomy (SG). The purpose of this study was to examine bone‐related nutrition after SG, compared to laparoscopic adjustable gastric band (LAGB), and trend bone turnover markers following SG. This is an observational study of 197 adolescents who underwent LAGB (n = 98) or SG (n = 99). Bone health labs were collected at baseline and 6 and/or 12 months after LAGB or SG, with additional analysis of bone turnover markers in the SG group. Calcium and 25 OHD levels increased at 6 and 12 months after LAGB and SG, with no difference between the surgeries. Parathyroid hormone levels decreased only in the SG group. SG patients had increased osteocalcin and carboxy‐terminal cross‐linking telopeptide of type 1 collagen (CTX) at 6 and 12 months post‐SG, although CTX decreased between 6 and 12 months. Excess weight loss at 6 months predicted the rise in CTX, but the changes in osteocalcin and CTX could not be attributed to 25 OHD deficiency, hypocalcemia or hyperparathyroidism. Patients had improved 25 OHD levels post‐surgery, which may be secondary to stringent vitamin supplementation guidelines. However, there were marked increases in bone turnover markers following SG. More studies are needed to evaluate the effects of SG on adolescent bone health and to correlate the early changes in bone turnover with bone mineral density and fracture risk.

Congenital hypothyroidism (CH) is one of the most common preventable causes of intellectual disability. Thyroid hormone is required for normal brain development, but neonates with CH typically appear healthy at birth, which leads to delays in diagnosis and treatment. In developed countries, newborn screening programs have led to earlier diagnosis and treatment of CH, resulting in improved neurodevelopmental outcomes. Neonates with an abnormal newborn screen require prompt confirmatory serum thyroid function tests and treatment with thyroid hormone. Further evaluation for the etiology of CH should not delay treatment decisions.

No abstract

Tirzepatide is a novel "twincretin" with glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist activity, which was recently approved by the Food and Drug Administration for the treatment of type 2 diabetes mellitus. In this review, we discuss preclinical and mechanistic human studies, which demonstrate improvements in insulin sensitivity and beta-cell function with the use of tirzepatide, as compared to placebo and glucagon-like peptide 1 receptor agonists. We then discuss SURPASS trials 1-5, which evaluated the safety and efficacy of tirzepatide for type 2 diabetes mellitus as either monotherapy or combination therapy with other antidiabetic agents. The magnitude of tirzepatide's effects and the efficacy relative to other anti-diabetes medications on weight, glycemic control, and beta-cell function may prove beneficial for the treatment of early type 2 diabetes mellitus. Further studies, including data on cardiovascular outcomes and long-term safety, will continue to elucidate the role of tirzepatide in the treatment algorithm of type 2 diabetes mellitus.