13 December 2021: Articles
Adipsic Diabetes Insipidus in Children: A Case Report and Practical Guide
Unusual setting of medical care, Rare coexistence of disease or pathologyAnas M. AlShoomi1ABCDEF*, Khalid I. Alkanhal1EF, Abdulhameed Y. Alsaheel1F
Am J Case Rep 2021; 22:e934193
BACKGROUND: Diabetes insipidus (DI) is a clinical syndrome characterized by polyuria and polydipsia that result from a deficiency of antidiuretic hormone (ADH), central DI, or resistance to ADH, nephrogenic DI. In otherwise healthy patients with DI, normal thirst mechanism, and free access to water, the thirst system can maintain plasma osmolality in the near-normal range. However, in cases where DI presents with adipsia, cognitive impairment, or restricted access to water, true hypernatremia may occur, leading to severe morbidity and mortality.
CASE REPORT: We report a case of a 2-year-old boy who had global developmental delay and post-brain debulking surgery involving the hypothalamic region, which resulted in central DI and thirst center dysfunction. We describe the clinical presentation, the current understanding of adipsic DI, and a new practical approach for management. The main guidelines of treatment include (1) fixed desmopressin dosing that allows minimal urinary breakthroughs in-between the doses; (2) timely diaper weight-based replacement of water; (3) bodyweight-based fluid correction 2 times a day, and (4) providing the nutritional and water requirements in a way similar to any healthy child but at fixed time intervals.
CONCLUSIONS: This plan of management showed good effectiveness in controlling plasma sodium level and volume status of a child with adipsic DI without interfering with his average growth. This home treatment method is practical and readily available, provided that the family remains very adherent.
Keywords: Diabetes insipidus, Thirst, Water-Electrolyte Balance, Child, Child, Preschool, Diabetes Insipidus, Nephrogenic, Diabetes Insipidus, Neurogenic, Diabetes Mellitus, Humans, Hypernatremia, Male
Normal cellular functions require adequately maintained tonicity of extracellular fluids within a very narrow range . Serum electrolyte and water homeostasis is kept within the normal range by a coordinated interaction between thirst, arginine vasopressin (AVP) [or antidiuretic hormone (ADH)] release and action, and renal systems response . Failure of any of these systems can result in an unfavorable environment for human cells, which, if not promptly recognized and treated, can cause life-threatening cellular dysfunction. Diabetes insipidus (DI) is a clinical syndrome characterized by polyuria, polydipsia, and, if not ameliorated by consuming enough water, hypernatremia. DI results from either impaired release of AVP, central DI, or resistance to the action of ADH, nephrogenic DI. Adipsia, a condition characterized by the lack of thirst sensation, usually occurs due to a central lesion that causes dysfunction of the thirst center in the hypothalamus . In otherwise healthy individuals with DI, the thirst system can maintain plasma osmolality in the near-normal range despite relative AVP deficiency or decreased action . In patients with DI who have normal cognition and free access to water, true hypernatremia (plasma sodium concentration >150 mmol/L) should not occur given that the initial water loss stimulates thirst, resulting in increased water consumption that matches urinary losses [5,6]. However, in cases where DI presents with adipsia, cognitive impairment, or restricted access to water, true hypernatremia can occur, leading to severe morbidity and mortality. Only around 100 cases of adipsic DI have been reported worldwide over the last 4 decades . As such, there is indeed very limited experience in the management of such patients, especially children.
This report describes the clinical presentation and management provided, as well as the current understanding regarding adipsic DI.
We used daily serum sodium levels, which normally lies between 135–145 mEq/L, as an indicator of successful management. Moreover, clinical indicators included daily clinical assessment of hydration status, fluid input and output, and twice-daily body weight monitoring. By utilizing the aforementioned method during his stay and the follow-up in day care unit for chemotherapy for more than 3 months, our patient no longer developed dehydration and had consistently normal serum urea levels, which means a good hydration status and, hence, a normal kidney function. Furthermore, the family was satisfied with this management approach. Although the follow-up to date is relatively short-term, he showed a normal growth pattern over the observation period. The patient was receiving weekly doses of chemotherapy. He also has been admitted 2 times for chest infections (Figure 1) when he was developing hypernatremia due to disturbance in his tight fluid management secondary to tachypnea and being on nil per os (NPO) state.
Maintaining plasma osmolality and intravascular volume requires a concerted effort between thirst, AVP, and kidney function, in addition to a recently discovered bioactive peptide, apelin, which has been isolated from bovine stomach extracts and is thought to play a key role in maintaining body fluids [2,10].
AVP is encoded by the AVP-neurophysin II gene (AVP-NPII) at the short arm of chromosome 20 (20p13) , while its secretion is regulated by osmotic and non-osmotic factors. Osmotic regulation of AVP release involves plasma osmolality sensing by the hypothalamic osmoreceptors, which are specialized neural osmoreceptors in the anterolateral hypothalamus responsible for AVP production and secretion. On the other hand, non-osmotic regulation of AVP release involves hemo-dynamic factors (ie, the renin-angiotensin-aldosterone and natriuretic peptide systems), nausea, and other regulators such as stress and drugs (eg, morphine, vincristine, cyclophosphamide, and glucocorticoids) .
The thirst sensation is triggered by peripheral osmoreceptor neurons in the upper regions of the gastrointestinal tract (GIT) and in blood vessels that collect nutrients absorbed from the GIT, as well as the central osmoreceptor located in the organum vasculosum of the lamina terminalis in the brain. Signals derived from peripheral osmoreceptors reach the brain through fibers that ascend the vagus nerve and spinal cord. Signals derived from both sources are then integrated in several brain areas .
Extracellular fluid osmolality is typically maintained at between 280 and 295 mOsm/kg H2O in the general population , below which serum AVP levels are low or undetectable. Any increase in plasma osmolality above the 283 mOsm/kg H2O threshold stimulates the release of AVP, which can also be released in response to other AVP regulators, namely, the renin-angiotensin-aldosterone system, the natriuretic peptide system, and nausea . However, the continued increase in plasma osmolality above 293 mOsm/kg H2O despite AVP secretion triggers thirst, which in turn stimulates water ingestion to restore plasma volume , although this osmolar threshold for thirst varies among individuals .
In patients with DI (either central or nephrogenic), the absence or resistance to AVP action makes the thirst mechanism the first layer of protection against high plasma tonicity (thirst is first!). However, this mechanism by itself can maintain plasma osmolality at near-normal levels. The kidneys can accommodate up to 5 to 10 L/m2 of water ingested under thirst drive during complete or relative AVP deficiency or resistance . For this reason, most otherwise healthy individuals with DI are eunatremic and need a water deprivation test for diagnosis. On the other hand, patients with DI who have adipsia, cognitive impairment (eg, during a sedated state following surgery), or restricted access to water are at high risk for developing hypernatremia and, hence, life-threatening abnormalities in plasma osmolality unless they are closely monitored and promptly treated. The management of patients with adipsic DI is exceptionally challenging considering their inability to sense rising osmolality and their rapid, wide swings in plasma sodium and volume status. Treatment success, therefore, requires close observation, frequent reassessment of water balance, and an adherent family. Regarding the timely urine output measurements; the 4-h timing may be appropriate for admitted young patients, but should be spaced longer if the patient is old enough to withstand longer fasting, outside the hospital, and can consume solid foods.
To date, no practical guideline has been available for the treatment of cases with adipsic DI. Expert opinion, mainly for adult patients, suggests fixed doses of DDAVP to achieve a daily urine output between 1.5 and 2 L, daily water intake based on adjustments for daily weight changes on a 1 kg=1 L basis, and weekly monitoring of sodium levels . These recommendations, however, are not suitable for pediatric patients considering their different physiological needs and relatively greater total body water content compared to adults, making them more sensitive to changes in extracellular compartment volume . Furthermore, as children grow, their target weight can change over time.
Some pediatric endocrinologists have prescribed a home sodium monitoring device for patients with adipsic DI in combination with a sliding-scale fluid prescription plan, with an 84% success rate in maintaining plasma sodium at the reference range . Unfortunately, this device is not always available. Moreover, the 84% success rate achieved in the aforementioned study is subject to many issues regarding accuracy, frequent blood sampling, and availability of consumables, while still being lower than our goal of 100% control. Pabich et al managed a 16-year-old patient with fixed daily doses of sub-cutaneous DDAVP combined with daily modulation of fluid in-take based on daily serum sodium measurement, which led to a reduction in hospitalizations resulting from the serum sodium dysregulation . Again, the daily sodium measurement is not an available choice at all times and is not always practical, especially in young children. This led us to devise an easier and more practical way to manage the condition based on the physiology of the body fluids, having known the difficulties and limitations of the other modalities of management and trying to avoid daily blood sampling.
We present a new method for the management of adipsic DI in a pediatric patient. Overall, the main guidelines include (1) fixed DDAVP dosing that allows minimal urinary breakthroughs; (2) timely diaper weight-based replacement; (3) bodyweight-based fluid correction twice daily, and (4) nutritional and water requirements similar to those of any healthy child, but at fixed time intervals. This plan showed good effectiveness in controlling the plasma sodium level and volume status of a child with adipsic DI without interfering with his average growth throughout follow-up for 3 months. The main limitations were the absence of practical guidelines in the literature for the management of such cases, and difficulties regarding frequent fluids and weight measurements for the parents. As it does not require daily serum sodium measurements, this method of treatment is more practical and available, provided that the family remains very adherent. However, this proposed method still needs data on more patients before it can become standard of care.
FiguresFigure 1.. Plasma sodium during the observation time: Plasma sodium levels for 4 months. The shaded area indicates days of hospital admissions. Figure 2.. Guidelines of fluid management: Upper part: this table was designed for the parents. Lower part: guidelines on how to use each cell. The body weight should be measured twice daily at fixed times. The dose of desmopressin is not shown in the table, as it should be given in fixed time intervals with doses that allow minimal urinary breakthroughs.
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