DISCUSSION
Diabetes insipidus (DI) is a form of polyuria–polydipsia syndrome and
is characterized by excessive hypotonic polyuria (>50 mL/kg
body weight/24 h) and polydipsia (>3
L/day)3. It is characterized by the body’s inability
to retain free water and typically presents with polyuria, insatiable
thirst and symptoms associated with dehydration. It is a rare disease
with a prevalence of ~1 in 25,000 individuals or about
0.004% of the global population with no gender
predilection4, 5.
DI may occur due to four fundamentally different defects in the
physiological control of water balance including impaired antidiuretic
hormone (ADH) secretion (central DI), impaired renal response to ADH
(nephrogenic DI), excessive fluid intake (primary polydipsia), or
increased metabolism of the ADH (gestational diabetes
insipidus)3. The diagnostic challenge for the
clinician is to confirm the presence of polyuria and distinguish between
the various disease processes. Reliable distinction between the
different etiologies of DI is imperative since treatment differs
substantially. In this case report, we focus on central DI (CDI) which
was diagnosed after TAH and BSO complicated by ureteral injury.
CDI is the most common type of DI. It results from inadequate synthesis
of ADH by the supraoptic or paraventricular nuclei in the hypothalamus
or impaired release of ADH from the posterior pituitary
gland3. Acquired factors such as iatrogenic post
neurosurgery (20%), hypothalamo-neurohypophyseal axis lesions (20%)
and head trauma (16%), account for the majority of cases of
CDI6. The inherited/familial causes account for 1% of
CDI cases. Additionally, a large proportion of the cases of CDI
(30-50%) is idiopathic and has been associated with destruction of the
hormone secreting cells in the hypothalamic nuclei due to an autoimmune
process7.
While most of the post-operative DI cases reported have been associated
with pituitary/cranial surgery, cases of DI after abdominal surgery are
very rare. The diagnosis of an isolated posterior pituitary dysfunction
was made after gynecological surgery in one case8,
whereas one patient was reported to have developed DI after liver
transplantation surgery9. The cause of DI in the
latter case has not been clearly delineated. Other causes reported
include cobalt induced DI from hip prosthesis and propofol induced
DI10, 11.
Our patient developed central DI, as evidenced by the MRI findings and
response to desmopressin, after surgery. The surgery itself was
prolonged and had a complicated course with extensive blood loss (more
than 2 liters) requiring multiple transfusions. The patient was having
heavy irregular menstrual bleeds for more than a year before surgery.
Coupled with this, the large amounts of blood loss during surgery could
have contributed to posterior pituitary ischemia leading to impaired
synthesis and release of ADH.
The presence of intraoperative ureteral injury with urological
intervention and following hydronephrosis created suspicion for
post-obstructive diuresis being the culprit of the patient’s polyuria.
Therefore, the key step in identifying DI in this case was the presence
of hypotonic urine (urine osmolarity of 90 mOSm/kg) which ruled out
osmotic diuresis.
The indirect water deprivation test has been documented as the gold
standard in literature for diagnosing DI. It involves depriving the
patient of fluids and regularly measuring the patient’s urinary
excretion, urine osmolality, plasma sodium, and plasma osmolality. The
fluid deprivation is continued for either seventeen hours maximum, until
plasma concentration is greater than or equal to 150 mmol/L, or a loss
of 3%-5% of the patient’s body weight has
occurred12. After exogenous administration of
synthetic ADH, or desmopressin (DDAVP), the patient’s urine osmolarity
is measured to compare to the osmolarity before DDAVP administration. At
the end of the test, the urine osmolarity for healthy individuals should
be above 800 mOsm/kg osmolarity with no increase in urine osmolarity
following DDAVP. Both nephrogenic and central DI will have urine
osmolarity below 300 mOsm/kg13. Although the indirect
water deprivation test was not officially done for this patient, after
fourteen hours of fasting, she was noted to have urine osmolarity of 93
mOsm/kg. The response to DDAVP differentiates nephrogenic and central
DI. After DDAVP, urine osmolality will increase >50% for
CDI and <50% for NDI. Our patient’s urine osmolarity
increased from 93 mOsm/kg to 315 mOsm/kg after administration of DDAVP
pointing to a diagnosis of CDI.
Further workup in patients with CDI includes biochemical evaluation of a
morning plasma measurement of pituitary hormones (growth hormone, ACTH,
TSH, FSH and LH) and hormones from their target organs. An MRI of the
sella and suprasellar regions with gadolinium would identify any
anatomical pituitary or hypothalamic disruptions (macroadenomas, empty
sella, infiltrative diseases). The normal posterior pituitary
demonstrates hyperintensity on T1 images (also known as the ‘bright
spot’), suggested to be due to phospholipid-rich granules storing AVP
and oxytocin14. As seen in this case, the absence of
this bright spot could indicate an absence of posterior pituitary
function (See Figure 1).
To avoid the main adverse effect of hyponatremia, the minimum
desmopressin dose required to control symptoms should be started. A
retrospective review has shown that 27% of central DI patients show
mild hyponatremia on routine electrolyte testing and 15% develop more
severe hyponatremia, over long-term follow-up15.
In conclusion, accurate diagnosis of DI and ascertaining the underlying
cause poses a challenge in present clinical practice. The appropriate
diagnosis is critical to ensure improved quality of life for the
patient. The first step in approaching patients with polyuria-polydipsia
syndrome is appropriate medical history and examination, baseline
laboratory assessment using serum electrolytes and urine osmolarity. The
indirect water deprivation test, although cumbersome, can provide a
diagnosis with increased accuracy. There is also promising potential
for the utility of copeptin levels in the future. Most ambulatory
patients remain eunatremic due to the compensatory thirst mechanism
associated with DI. However, desmopressin remains widely used in the
treatment of DI. It is recommended to start with the lowest dose to
achieve symptom control to avoid hyponatremia.