ADIPSIC DIABETES INSIPIDUS AFTER SECOND RESECTION OF A HYPOTHAMIC ASTROCYTOMA

Abstract

Objective:

We report a case of adipsic diabetes insipidus (ADI) post-astrocytoma resection.

Methods:

Clinical and laboratory data are presented.

Results:

A 16-year-old female with a history of incompletely resected hypothalamic astrocytoma was admitted with a headache. Head magnetic resonance imaging showed an interval increase in a suprasellar lesion with extension to the third ventricle. Following a second stage resection, she developed an increased urine output with diluted urine resulting in a negative fluid balance; however, she was unable to sense thirst. Blood tests showed a serum sodium of 155 mEq/dL (normal, 136 to 145 mEq/dL), serum osmolality at 321 mOs/kg (normal, 285 to 295 mOs/kg) and a urine osmolality of 128 mOsm/kg (normal, 300 to 1,600 mOsm/kg). Serum creatinine and potassium were normal. Pituitary hormone profiles were found to be normal: growth hormone 0.171 ng/mL (normal, 0.123 to 8.05 ng/mL), luteinizing hormone 3.44 mIU/mL (normal, 7.59 to 89.08 mIU/mL), follicle-stimulating hormone 5.60 mIU/mL (normal, 2.55 to 16.69 mIU/mL), thyroid-stimulating hormone 2.9 mIU/mL (normal, 0.35 to 4.94 mIU/mL), free thyroxine 0.92 ng/dL (normal, 0.7 to 1.48 ng/dL), adrenocorticotropic hormone 19.56 pg/mL (normal, 7.2 to 63.3 pg/mL), and prolactin 7.25 ng/mL (normal, 5.18 to 26.53 ng/mL). The patient was treated with desmopressin acetate 120 μg tablets twice daily with a fixed fluid intake of 1.5 to 2.0 L/day with close monitoring of fluid intake, output, and body weight. The response was good with a gradual reduction of serum sodium level of around 7 to 9 mEq/L/day.

Conclusion:

ADI is a rare entity of central diabetes insipidus, where the absence of polydipsia can be challenging in diagnosing and managing the condition. Cases of ADI are likely under reported and clinicians need to be aware of this condition.

INTRODUCTION

Diabetes insipidus can occur following neurosurgery, either transiently or permanently. The common classic presenting symptoms of central diabetes insipidus (CDI) are polyuria, and compensatory polydipsia. Adipsic diabetes insipidus (ADI) is a rare disorder triggered by injury to the hypothalamus impairing thirst osmoreceptors and the synthesis of antidiuretic hormone, leading to the absence of thirst (1,2). Here, we report a rare case of ADI post-astrocytoma resection who presented with severe hypernatremia postoperatively.

CASE REPORT

In January 2018, a 16-year-old female was admitted to the hospital with a 1 week history of progressive headache; she was known to have a hypothalamic pilocytic astrocytoma for which she had an incomplete resection in 2014. Clinical examination was unremarkable with no focal neurologic deficit. A head magnetic resonance imaging scan with contrast showed an interval increase in a suprasellar lesion with extension to the third ventricle. The pituitary hormone profile and renal functions were normal. She underwent a second stage resection. Several hours postoperatively, she developed an increased urine output resulting in a negative fluid balance. The patient was fully conscious; however, she did not complain of thirst despite a significant increase in serum osmolality and serum sodium. The thirst scale was not used.

Blood tests showed significant hypernatremia with serum sodium reaching 155 mEq/dL with a high serum osmolality at 363 mOs/kg, while her urine was diluted with a urine osmolality of 128 mOsm/kg. Over the next few days, sodium continued to increase reaching up to 173 mEq/dL. Refer to Table 1 for a summary of renal function tests and a urine workup. A brain magnetic resonance imaging was done postoperatively to confirm the extent of remnant tumor (Figs. 1 and 2).

Table 1.

Summary of Renal Function Tests and Urine Workup

Tests	Value	Reference range	Interpretation
Creat	0.77 mg/dL	0.6–1 mg/dL	Normal
Na	173 mEq/dL	136–145 mEq/dL	High
K	3.3 mEq/dL	3.5–5.1 mEq/dL	Low
Cl	134 mEq/dL	98–107 mEq/dL	High
Serum osmolality	363 mOs/kg	285–295 mOs/kg	High
Urine osmolality	128 mOs/kg	300–1,600 mOs/kg	Low
Urine Na	29 mEq/L	20–110 mEq/L	Normal
Urine volume	1,900 mL	800–2,000 mL	Normal

Abbreviations: Cl = chloride; Creat = creatinine; K = potassium; Na = sodium.

Fig. 1.

Brain MRI, preoperative 2018. MRI = magnetic resonance imaging.

Fig. 2.

Brain MRI, postoperative 2018. MRI = magnetic resonance imaging.

The patient was treated with desmopressin acetate 120 μg tablets twice daily with a fixed fluid intake and a strict fluid balance with close monitoring of fluid intake, output, and body weight. All other pituitary hormones were normal postoperatively and on subsequent follow-up in the clinic. Refer to Table 2 for a summary of pituitary hormones.

Table 2.

Pituitary Hormone

Tests	Value	Reference range
Growth hormone	0.171 ng/mL	0.123–8.05 ng/mL
FSH	5.60 mIU/mL	2.55–16.69 mIU/mL
TSH	2.997 mIU/mL	0.35–4.94 mIU/mL
LH	3.44 mIU/mL	7.59–89.08 mIU/mL
ACTH	19.56 pg/mL	7.2–63.3 pg/mL
Prolactin	7.25 ng/mL	5.18–26.53 ng/mL

Abbreviations: ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; LH = luteinizing hormone; TSH = thyroid-stimulating hormone.

The patient was fine upon discharge and was functioning well at home with no recurrence of hypernatremian episodes, until she unfortunately passed away 3 months later on May 2018 most likely due to the natural progression of her astrocytoma. Thromboembolism as a complication of her fluid balance disturbance could also be the cause of death.

DISCUSSION

Our patient being reported was known to have a hypothalamic pilocytic astrocytoma for which she underwent an incomplete resection in 2014. In 2018, she complained of a headache and imaging revealed an increased tumor size suggestive of recurrence. She underwent a second resection. Postoperatively, she was found to have a high sodium level alongside of polyuria in the absence of thirst.

Diabetes insipidus (DI) is a frequent consequence following neurosurgery. Most patients with CDI have a preserved thirst sensation. As a result, the common classic presenting symptoms of CDI are polyuria, and compensatory polydipsia. The sense of thirst, which is triggered by increased concentrations of plasma sodium, is sufficient to alert the body to increase fluids intake (1).

ADI is a rare disorder. It is triggered by injury to the hypothalamus impairing thirst osmoreceptors and antidiuretic hormone-synthesizing neurons, leading to the failure to generate the sensation of thirst in response to hypernatremia. It can occur following surgical excision of a tumor, such as a craniopharyngioma, or subsequent to the rupture of saccular aneurysms of the anterior communicating artery. It has been linked to a significant risk of morbidity and mortality (2). Multiple etiologies which are linked to play a role in the development of CDI have been reported to occur with diminished or absent thirst responses (adipsia) to hypernatremia.

Adipsia indicates damage to the anterior hypothalamus specifically to the circumventricular organs where the thirst osmoreceptors are located. Due to a lack of perception of osmotic dehydration, patients do not increase their fluid intake when needed, rendering them susceptible to the development of hypernatremia (3). In addition to the susceptibility to hypernatremia, patients with ADI are also candidates to develop hyponatremia due to their inability to appreciate fluid overload (4).

The prevalence of ADI is unknown. However, according to a study done in 2014 by Gonzalez Briceno et al (5), including 159 patients who were treated for suprasellar tumors, classical CDI had the highest rate of occurrence including 80 out of 159 patients which persisted more than 1 month after surgical intervention. On the other hand, only 2 out of 159 patients were diagnosed as ADI (5). In the medical literature, there were 100 cases reporting adipsia combining DI. To the best of our knowledge, there were only 3 case reports documenting adipsic diabetes insipidus with an astrocytoma tumor (6–8) and our case is the fourth one. Table 3 summarizes similarities and differences between the cases.

Table 3.

Published Cases of Adipsia with Astrocytoma and Comparison with our Case

Reference/year	Age at diagnosis (years)	Sex	Serum sodium (mEq/L)	Other complications	Age at death (years)
Ramells et al (6)	63	Male	188	Not known	Not known
Modawai et al (5)	20	Male	180	Steroid-associated diabetes mellitus	21
Janus et al (7)	17	Male	163	Epilepsy, left-sided paresis & DVT	Not known
Elamin et al (our case)	12	Female	173	Seizer, obesity	17

Abbreviation: DVT = deep vein thrombosis.

Whether the extensive surgical resection had led to an impairment in the sensory circumventricular organs or if the primary astrocytoma itself has contributed to this damage is difficult to know. Discovering the primary cause might not play an essential role in the process of diagnosis and management plan of ADI , but might help as a predictor of longevity of the disease. In other 3 reported cases where ADI had been concomitant with the presence of astrocytoma, 1 patient was diagnosed with hypernatremia and adpisia and then was found to have an astrocytoma with no prior history of intracranial surgery or head trauma proceeding the presentation (7); while the other 2 cases had a history of repeated surgical intervention for recurrence of the tumor like the case of our patient.

According to Seckl and Dunger (9) postoperative diabetes insipidus is diagnosed based on polyuria (2 mL/kg/hour) with an increased plasma osmolality (>300 mOsm/kg). Adipsia is usually diagnosed clinically by the absence of thirst during hypernatremia (4). Measurement of arginine vasopressin and thirst responses to a water deprivation test or a hypertonic saline infusion are also used to diagnose ADI (4). Our patient presented postoperatively with CDI detected by routine lab investigation as hypernatremia during her hospital stay, resulting from deficient antidiuretic hormone secretion. She denied any thirst sensation despite the presence of hypernatremia.

Adipsic disorders have been classified into 4 main categories: (1), Type A adipsia: this is known as essential hypernatremia. It is related to decreased sensitivity of the osmoreceptors which leads to partial DI with subnormal thirst sensation, thus patients are protected from the extremes of hypernatremia. It is characterized by having normal vasopressin responses to hypotension and hypoglycemia, while preserving the plasma osmolality but at an abnormally high level, which may be over 300 mOsm/kg (10); (2), Type B adipsia: this is described as subnormal thirst and vasopressin responses to osmotic stimuli. Despite the fact that these patients have a normal osmoregulatory point, the thirst and vasopressin responses are insufficient to a hyperosmolar challenge (11); (3), Type C adipsia: a complete absence of vasopressin release and thirst response in the presence of an osmotic stimulus due to extensive central destruction. The most common cause of this type is clipping of aneurysms of the anterior communicating artery which is supplying the osmoreceptors (12); (4), Type D adipsia: it is a condition where the osmoregulation of vasopressin release is intact, but thirst response is absent. A single case was reported since 1986 (13). According to this classification our patient is type A ADI. The management of ADI is challenging.

The main goal of the treatment is to maintain eunatremia (14). The principles of management are regular desmopressin therapy (DDAVP) (4), at least twice daily as 100 to 250 μg orally or 3 to 10 μg intranasally (14); in addition, fixed fluid intake around 1.5 to 2 L per day with daily body weight measurement. There is a need for the establishment of a target body weight at which the patient is considered to be euvolemic, and normonatremic. Measurement of plasma sodium is recommended to be taken on a weekly basis. Education of the patients and their families about the principles and goals of the treatment is essential; the importance of maintaining water balance by fixed daily water intake despite the adipsia (14). The most common complication of ADI is hypernatremia, sleep apnea, venous thromboembolism, and obesity (4).

The patient reported in this case had started to gain weight after her first operation and subsequent to her developing ADI, she developed obesity with a body mass index of 35 kg/m². Several factors contributing to the development of obesity in ADI include injury to the arcuate nucleus of the hypothalamus, affecting the satiety center and possibly leading to overeating and failure to control appetite in response to hormones such as leptin (4,15). Mavrakis (16), in his review of the literature, found that: 23 patients (33%) with hypothalamic dysfunction had appetite disturbances. Physical inactivity contributes to obesity in ADI patients (15); immobility, paralysis, and cognitive and visual impairments are also factors leading to reduced activity level (4).

Taking into consideration the fact that our patient unfortunately passed away around 3 months after developing ADI, we reviewed the literature looking for reported mortalities in ADI; 14 deaths were reported, occurring at a median age of 20.58 years (range, 2.9 to 42 years). ADI is not the main cause of death per say, but a study conducted by Arima et al (17) concluded that patients with ADI are at a higher risk of premature death compared to patients with classic CDI.

CONCLUSION

Astrocytoma is rarely linked with the development of CDI and even less with adipsia. The absence of polydipsia and polyuria can be challenging. In long-term therapy, the benefits of vasopressin and fluid therapy should be considered against the risk of brain edema/herniation. Monitoring of body weight and electrolytes is essential and should be maintained along with strict fluid intake. Despite strict input and output monitoring and the use of vasopressin with regular follow-up of sodium levels, it is difficult to achieve an optimal physiologic pattern. Long term hyperosmolality holds an increased risk for future morbidity and mortality. Although rare, cases of ADI are likely under-reported and clinicians need to be aware of this condition.

Abbreviations

ADI

adipsic diabetes insipidus

CDI

central diabetes insipidus

DI

diabetes insipidus