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X-Linked Congenital Nephrogenic Diabetes Insipidus Mimicking Central Diabetes Insipidus: A Diagnostic Challenge in the Absence of the Posterior Pituitary Bright Spot
Corresponding author: Raiz Ahmad Misgar, Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India. E-mail: drreyaz2017@gmail.com
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How to cite this article: Qadir A, Misgar RA, Sofi JA. X-Linked Congenital Nephrogenic Diabetes Insipidus Mimicking Central Diabetes Insipidus: A Diagnostic Challenge in the Absence of the Posterior Pituitary Bright Spot. Indian J Nephrol. 2025;35:810-1. doi: 10.25259/IJN_515_2025
Dear Editor,
Nephrogenic diabetes insipidus (NDI), reclassified in 2022 as ‘arginine vasopressin resistance (AVR),’1 is a rare inherited disorder. We report a case of congenital NDI (CNDI) initially misdiagnosed as central diabetes insipidus (CDI).
A 4.5-year-old male child, first in birth order of a non-consanguineous union, presented with a history of sepsis, hypernatremic dehydration (serum Na 190, 178, and 168 mEq/L), and severe metabolic acidosis at 6 months of age. A contrast-enhanced magnetic resonance imaging (CEMRI) of the pituitary revealed an absent posterior pituitary bright spot (PPBS), as shown in Figure 1. He was empirically started on oral desmopressin (50 µg/day) but did not experience symptomatic improvement. At 2 years, he was referred to Pediatric Endocrinology services for persistent polyuria and polydipsia. Anthropometry showed severe short stature (Height: 77 cm, SDS: –3.6) and underweight (Weight: 9.7 kg, SDS: –2). Investigations, including renal ultrasonography, were unremarkable except for persistent hypernatremia, as shown in Table 1. A vasopressin challenge (0.5 units subcutaneously, at a dose of 1 U/m2)2 showed a minimal rise in urine osmolality (91 to 95 mOsm/kg; 4% increase), suggesting NDI. Clinical exome sequencing by next-generation sequencing identified a hemizygous pathogenic missense variant, c.500C>T (p.Ser167Leu), in exon 3 of the AVPR2 gene, confirming X-linked NDI. Management included a low-sodium diet, hydrochlorothiazide (HCTZ, up to 37.5 mg/day), and amiloride (7.5 mg/day), leading to a 28.5% reduction in urine output (from 3.5 to 2.5 L/day). Over a 2.5-year follow-up, the child exhibited a 13 cm increase in height and a 5 kg weight gain.
- Shows the absence of a posterior pituitary bright spot on the T1-weighted MRI sequence (red arrow).
| Biochemical characteristics | Value | Reference range |
|---|---|---|
| Hemoglobin (g/dL) | 12.1 | 12-16 |
| Total leucocyte count (x1000/µL) | 8.1 | 4-11 |
| Platelet count (lac/µL) | 1.36 | 1.5-3 |
| Urea (mg/dL) | 25 | 10-45 |
| Creatinine (mg/dL) | 0.30 | 0.5-1.50 |
| Calcium (mg/dL) | 9.9 | 8.8-10.80 |
| Phosphorus (mg/dL) | 5.07 | 3.5-4.5 |
| Albumin (g/dL) | 3.90 | 3.50-5.20 |
| Alkaline Phosphate (U/L) | 217 | 30-141 |
| iPTH (pg/mL) | 15 | 12-88 |
| 25(OH) vitamin D | 53 | 30-100 |
| TSH (µIU/mL) | 4.2 | 0.5-6.50 |
| FT4 (ng/dL) | 1.09 | 0.92-1.99 |
| 8AM cortisol (µg/dL) | 18 | 10-25 |
| pH | 7.38 | 7.35-7.45 |
| Sodium, Na (meq/L) | 148/145 | 135-145 |
| Potassium, K (meq/L) | 4.4/3.6 | 3.5-5 |
| IGF1 (ng/mL) | 50 | 30-60 |
| IGFBP3 (µg/mL) | 2.5 | 2-4 |
IGF1: Insulin-like growth factor, IGFBP3: Insulin-like growth factor binding protein, iPTH: Intact parathyroid hormone, TSH: Thyroid stimulating hormone, FT4: Free thyroxine
Although PPBS is absent in 60-100% of CDI cases,3 its absence is not pathognomonic. In NDI, chronic hypernatremia and arginine vasopressin (AVP) depletion may also result in an absent PPBS.4 Our case highlights the importance of completing the diagnostic workup before applying a NDI diagnostic label.
Conflicts of interest
There are no conflicts of interest.
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