case_images: PMC11032210_01
case_images: Clinical course of the patient. (a) Clinical course during the perinatal period. Around the end of 31 weeks of gestation, the patient suddenly presented with thirst, polydipsia, and polyuria and was referred to our endocrinology section at 34 weeks and one day of gestation. Although gestational diabetes insipidus was initially suspected, we closely monitored her clinical course without therapy. At 34 weeks and five days of gestation, because of the possible development of acute prerenal failure, an emergency cesarean section (CS) was performed, immediately followed by an initiation of intranasal administration of 1-desamino-8-D-arginine vasopressin (DDAVP). The patient's daily urine volume promptly decreased, along with an increase in specific gravity. (b) Clinical course after delivery. This patient was once discharged on the 8th day postpartum and readmitted to our hospital for pituitary function evaluation, including a hypertonic saline infusion test, on the 25th day postpartum. Thus, no data for daily urine volume and urine-specific gravity from the 8-25th day postpartum were available (dotted line). Although the intranasal administration of DDAVP was discontinued on the 30th day postpartum, the patient remained DI-related symptom-free thereafter. The dotted bar and solid line represent daily urine volume and urine-specific gravity, respectively. CS: cesarean section; DDAVP: 1-desamino-8-d-arginine vasopressin; DI: diabetes insipidus; GWs: gestational weeks; MRI: magnetic resonance imaging (hypothalamic-pituitary region).
case_images: CRIE2024-8687054.001.jpg
case_images: PMC11032210_01_CRIE2024-8687054.001.jpg
case_images: fig1
case_images: Around the end of 31 GWs, she suddenly developed thirst, polydipsia of about 5 L/day, and polyuria of about 5-6 L/day during hospitalization, for which she was referred to our endocrinology section at 34 weeks and one day of gestation (Figure 1(a)). Based on the suspicion of acute prerenal failure attributed to DI-related dehydration, intranasal administration of 1-desamino-8-D-arginine vasopressin (DDAVP, a starting dose of 2.5 microg/day) was initiated immediately after the delivery, and the patient's daily urine volume promptly decreased, along with an increase in its specific gravity (Figures 1(a) and 1(b)). After initiating intranasal administration of DDAVP on the day of delivery, the DI-related symptoms were quickly alleviated and eventually disappeared by the 14th day postpartum (Figure 1(b)). However, no symptom recurrence was observed thereafter (Figure 1(b)).
case_images: Fat-suppressed T1-weighted magnetic resonance imaging of the hypothalamic-pituitary area. (a) A magnetic resonance imaging (MRI) scan on the fourth day after the delivery showed no obvious abnormal findings in the hypothalamic-pituitary area, except for a loss of the normal bright spot in the posterior lobe (arrowhead). (b) An MRI on the 28th day after the delivery showed a partial reappearance of this bright spot (arrowhead). (c) An MRI on the 201st day after the delivery showed a clear bright spot in the posterior lobe (arrowhead).
case_images: CRIE2024-8687054.002.jpg
case_images: PMC11032210_01_CRIE2024-8687054.002.jpg
case_images: fig2
case_images: T1-weighted images with fat suppression, without thickening of the stalk and enlargement of the neurohypophysis (Figure 2(a)). The results of the patient's plasma AVP level measured four days before the delivery (i.e., at 34 weeks and one day of gestation) were then released and found to be inappropriately low (0.7 pg/mL) compared to her high serum sodium level and plasma osmolality (Table 1). Meanwhile, fat-suppressed T1-weighted MRI around the same time showed a partial reappearance of a physiological bright spot in the posterior pituitary (Figure 2(b)). MRI around six months after the delivery showed a clear bright spot in the posterior pituitary, suggesting the recovery of the posterior lobe function (Figure 2(c)). Meanwhile, pituitary MRI findings meeting the criteria for the diagnosis of LINH in Japan, e.g., enlargement of the pituitary gland or stalk on imaging, could not be observed during the clinical course.
case_images: Result of the hypertonic saline infusion test. The relationship between plasma arginine vasopressin (AVP) and serum sodium levels in a 5% hypertonic saline infusion test was performed at four weeks postpartum. Plasma AVP levels did not sufficiently increase in response to the gradual increase in serum sodium levels. Simple linear regression analysis revealed that the equation of the regression line was Y = 0.025X - 2.9. The slope (=0.025) was <0.1, and the estimated plasma AVP level (=0.825 pg/mL) at a serum sodium level of 149 mEq/mL was <1.0 pg/mL, thus fulfilling the diagnosis criteria for central diabetes insipidus. For reference, the normal range of plasma AVP levels based on the data measured by a former AVP-radioimmunoassay (RIA) kit (Mitsubishi Petrochemical Co. Ltd., Tokyo, Japan), which is now unavailable in Japan, is shown. It is reported that plasma AVP levels measured by the Yamasa RIA kit are significantly and positively correlated with those measured by the Mitsubishi RIA kit (Spearman's rank correlation coefficient (r) = 0.905, p < 0.001).
case_images: CRIE2024-8687054.003.jpg
case_images: PMC11032210_01_CRIE2024-8687054.003.jpg
case_images: fig3
case_images: The result of a hypertonic saline infusion test performed at four weeks (on the 27th day) postpartum fulfilled the diagnosis criteria for central DI (Figure 3), and the patient was positive for anti-rabphilin-3A antibodies, a highly sensitive and specific diagnostic marker for LINH (Figure 4).
case_images: Detection of anti-rabphilin-3A antibodies by western blotting. Recombinant full-length human rabphilin-3A expressed in HEK293FT cells (RPH3A + HEK293FT) or negative control (HEK293FT) were probed with serum from the present patient (patient), or from a patient who was diagnosed with LINH previously (positive control patient). The arrowhead indicates the presence of anti-rabphilin-3A antibodies. The dashed arrowhead indicates the absence of anti-rabphilin-3A antibodies.
case_images: CRIE2024-8687054.004.jpg
case_images: PMC11032210_01_CRIE2024-8687054.004.jpg
case_images: fig4
case_images: The result of a hypertonic saline infusion test performed at four weeks (on the 27th day) postpartum fulfilled the diagnosis criteria for central DI (Figure 3), and the patient was positive for anti-rabphilin-3A antibodies, a highly sensitive and specific diagnostic marker for LINH (Figure 4).