Polydipsia and Polyuria in a 12-year-old Girl.

Abstract

A 12-year-old girl presents to the endocrinology clinic with a chief complaint of polydipsia. She reports drinking five to eight 32-oz water bottles during the day and one 32-oz bottle overnight. Her fluid intake consists entirely of water without any juice or soda. She also reports polyuria and nocturia, typically waking to void 3 times per night. She reports increased thirst and dry mouth but denies orthostatic symptoms. The symptoms have been ongoing for 7 months without any significant changes over time. The patient has not attempted to restrict her fluid intake during this time. She does not have excessive salt intake or cravings, and her only medication is over-the-counter allergy medications as needed.Before the onset of her symptoms, she tripped forward and hit the frontal area of her head on a brick wall while playing ball at school. She developed a headache and dizziness, but never lost consciousness. In the emergency department she had normal neurologic examination findings and was diagnosed as having a concussion. Her concussion was managed with rest; she missed 2 days of school and then quickly returned to normal activities. She did not have lingering vestibular system deficits, cognitive deficits, or mood alteration. She began to exhibit polydipsia approximately 1 week after the concussion. There is no history of kidney disease, hypertension, diabetes insipidus (DI), or diabetes mellitus in the family.On presentation via telehealth during the coronavirus disease 2019 (COVID-19) pandemic her examination findings are normal. The patient is well-appearing with moist mucus membranes and no visible goiter, acanthosis nigricans, or edema. She denies blurry vision, heat or cold intolerance, constipation, and changes in her hair or skin. Menarche occurred approximately 3 months earlier, and she has had 1 additional cycle since. The patient reports being tired due to her nocturia but denies other excessive fatigue. Her height remained at the 50th percentile throughout the course. There was concern for some subjective weight loss early in her course, but her weight has since stabilized in the 65th percentile with a BMI in the 68th percentile. In private, she denies calorie restricting, body dysmorphism, and substance use.Laboratory values obtained at different time points in her clinical course are presented in the Table 1. Several months earlier, her primary care provider checked a urinalysis and found significant proteinuria (protein level, 26.1 mg/dL [0.26 g/L]) (reference range, 0–14 mg/dL [0–0.14 g/L]) without hypoalbuminemia or edema, prompting nephrology evaluation. Her glucose, potassium, blood urea nitrogen, creatinine, calcium, and albumin levels were all within normal limits. In addition, her glucose, calcium, and potassium levels were within normal limits on multiple studies. Random aldosterone and vasopressin levels obtained before endocrinology referral were undetectable; the urine sodium level was measured at the same time as the serum sodium level. Repeated first-morning urine studies without paired serum and urine studies showed a urine specific gravity of 1.010 and osmolality of 92 mOsm/kg (92 mmol/kg). Renal ultrasonography was also normal. She was presumed to have orthostatic proteinuria and was referred to endocrinology for further evaluation of the polyuria and polydipsia.Given the risk of dehydration and need for intensive laboratory monitoring, water deprivation tests are typically performed in the inpatient setting; however, due to the COVID-19 pandemic, the patient completed a 12-hour home water deprivation test (Table). Given these challenges, laboratory studies could not be obtained before the start of the water deprivation test and are available only on completion of the study.Polydipsia and polyuria in children are defined as greater than 2 L/m2 per day of fluid intake and urine output, respectively. (1) With a body surface area of 1.3 m2 and up to 8,640 mL of fluid intake, or 6.6 L/m2 per day, our patient had polydipsia. The differential diagnosis for polydipsia includes hyperglycemia, nephrogenic DI (NDI) or central DI (CDI), and psychogenic polydipsia, which is also sometimes referred to as primary polydipsia or habitual drinking.When serum glucose values exceed 180 mg/dL (>10 mmol/L), the resorptive capacity of the renal tubules is overwhelmed, resulting in glucosuria. (2) High levels of glucose in the urine draw water into the renal lumen, resulting in increased free water losses, increased thirst, and polydipsia. The patient was euglycemic on multiple studies, excluding hyperglycemia as the cause of her symptoms.DI is defined as an inability to appropriately concentrate the urine in the setting of elevated serum osmolality. Laboratory diagnostic criteria include a sodium level greater than 145 mEq/L (>145 mmol/L), serum osmolality greater than 300 mOsm/kg (>300 mmol/kg), and urine osmolality less than 300 mOsm/kg (<300 mmol/kg). (1) This can result from an inability to appropriately secrete vasopressin, also known as antidiuretic hormone (ADH), from the hypothalamus or from an inability to respond to ADH at the level of the kidney. (3) Decreased or absent ADH secretion is referred to as CDI, whereas an inability to concentrate urine at the level of the kidney is called NDI or vasopressin-resistant DI.NDI can be differentiated from CDI during a water deprivation test. Access to fluid is withheld until a patient meets these laboratory diagnostic criteria for DI, as defined by hypernatremia, hyperosmolality, and inappropriately dilute urine. The patient is subsequently given vasopressin, with close monitoring of urine osmolality and urine output thereafter. (4) A twofold increase in urine osmolality after vasopressin administration with a concomitant reduction in urine output indicates an appropriate vasopressin response and confirms CDI rather than NDI. NDI in children most often results from an X-linked inherited defect but can also be caused by medications (most notably lithium and demeclocycline) and electrolyte abnormalities (hypercalcemia and hypokalemia).Psychogenic or primary polydipsia is characterized by excessive, habitual fluid intake in the absence of dehydration or renal concentrating defects. It often presents in patients with a coexisting psychiatric diagnosis. (4) Prolonged periods of excessive fluid intake, as with primary polydipsia, can result in acquired NDI due to decreased osmolality of the renal interstitium, which impairs the ability to concentrate urine. (4)A water deprivation test (Table) confirms a diagnosis of DI but does not specify whether it is central or nephrogenic. Typically conducted in an inpatient setting, subcutaneous vasopressin is used to differentiate between the 2 causes of DI. However, because of the COVID-19 pandemic restrictions, this test was completed at home and the patient was prescribed oral desmopressin acetate (ddAVP®; sanofi-aventis U.S. LLC, Bridgewater, NJ), a synthetic form of oral vasopressin that has a longer half-life than the subcutaneous vasopressin typically used during water deprivation tests. The patient was instructed not to eat or drink anything for 4 hours. During this time, she voided 1,150 mL (6.6 mL/kg per hour), and her weight decreased by 1.1 kg. After administering the desmopressin she did not void for 8 hours, consistent with the typical duration of effect of desmopressin. When she did void, the urine color changed from clear to dark yellow. Although we could not confirm a 2-fold increase in urine osmolality, the change in color and marked decrease in urine output strongly support a diagnosis of CDI.A brain magnetic resonance image (MRI) revealed a small but otherwise normal pituitary bright spot without any masses or thickening of the pituitary stalk (Fig, A). There were no healed fractures to suggest significant head trauma from the concussion that preceded the symptoms. On a normal T1-weighted brain MRI, the posterior lobe of the pituitary gland is hyperintense, creating the “pituitary bright spot.” (5) The pituitary bright spot is hyperintense due to the presence of neurosecretory vesicles containing vasopressin and other pituitary hormones. (5)(6) The characteristic MRI finding associated with CDI is the absence of a normal posterior pituitary bright spot (PPBS). An absent PPBS typically indicates a loss of function of the posterior pituitary gland and, therefore, disruption of the hypothalamic-pituitary axis. (5) The absence of a PPBS supports the diagnosis of CDI, but it is not diagnostic for CDI because the PPBS is absent in 20% to 30% of adults and up to 7% of children without CDI. (5) Its presence does not exclude CDI.Another goal of brain MRI in this patient with suspected CDI was to assess for a pituitary tumor. Germinoma accounts for 3% to 4% of primary pediatric and adolescent central nervous system tumors and commonly presents with CDI due to involvement of the hypothalamus, pituitary stalk, and gland. (5) Imaging in patients with germinomas often reveals a thickened pituitary stalk or a mass in this region that is typically well circumscribed, solid, and isointense or hypointense on T1-weighted sequences (Fig, B). (5) Early germinomas can be too small to visualize on MRI, and, therefore, follow-up imaging is crucial if the diagnosis is suspected. (5)Results of all other laboratory assessments of pituitary hormone function, including follicle-stimulating hormone/luteinizing hormone, estradiol, insulin-like growth factor (IGF)-1, IGF-BP3, cortisol, prolactin, and thyrotropin, were normal. Importantly, because central hypothyroidism can present with an inappropriately