International Journal of Clinical Medicine, 2011, 2, 278-280
doi:10.4236/ijcm.2011.23045 Published Online July 2011 (
Copyright © 2011 SciRes. IJCM
A Case of Central Diabetes Insipidus: Evaluation
in Pregnancy
Patrizia Gargiulo, Nicoletta Mecca, Valeria Mercuri, Tania D’Amico
Division of Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Received January 6th, 2011; revised March 2nd, 2011; accepted April 1st, 2011.
A 20 years old woman, admitted in our Centre at the 6th week of pregnancy, was affected by Central Diabetes Insipidus
and since the age of 10 years old she assumed desmopressin at a dose of 30 mg/nostril/day. She was primigravida , with
normal past medical history. Fasting blood levels were normal; specific gravity of the urine: 1006; no glucosuria or
proteinuria was present. Urinary and plasma osmolality were 245 and 287 mOsm/l; water intake about 2700 mL/day;
diuresis 2000 mL/day. On the basis o f the value of urine outpu t and osmolality the dose of desmop ressin was increased
at 40 mg/nostril/day. Patient was evaluated every month with fluid balance, urine volume, osmo lality, and serum elec-
trolytes. Daily dosage of desmopressin was 40 mg/nostril for all the duration of pregnancy according to a trend of an
adequate fluid and electrolytes balance and in absence of symptoms. Mean blood Pressure was 100/60 mmHg; coagu-
lation, liver, renal function were normal. Fetal monitoring with periodic ultrasound detected a normal intrauterine
growth. Patient had an uncomplicated labor of a healthy male baby at the 39th week. Because of an insufficient dilata-
tion of the cervical canal caesarian section was chosen. Despite a previous Central Diabetes Insipidus may worsen in a
pregnant with impaired reserve of Antidiuretic Hormone because of the changes in osmoregulatory system and in-
creased levels of vasopressinasis in middle and late pregnancy, our patient required a slightly higher dose of desmo-
pressin in the first trimester. Contrary to expectations the need of desmopressin did not increase during the weeks.
Keywords: Diabetes Insipidus, Pregnancy, Desmopressin
1. Introduction
Diabetes Insipidus is a rare complication in pregnancy
and its incidence in pregnant status is about 1 per 30,000
cases; three different subtypes of Diabetes Insipidus are
described: central, nephrogenic and transient. The first
one may predate the pregnancy or can be discovered
during pregnancy and it’s caused by an impaired pitui-
tary release of vasopressin; the second one is related to
the resistance of the kidney to circulating vasopressin.
Trans ient Diabet es Insip idus typ ically occurs in the th ird
trimester or at the end of pregnancy for an increase of
levels and activity of enzyme vasopressinase and can be
associated with preeclampsia, acute fatty liver and
HELLP Syndrome (Hemolytic anemia; Elevated Liver
enzymes and Low Platelet count)
We describe a case of a 20 years old woman, followed
in our Centre for Diabetes Insipidus, during pregnancy.
2. Case Report
A 20 years old woman was affected by Central Diabetes
Insipidus after a trauma of the skull during childhood,
and sinc e the age of 10 year s old she was in therapy with
desmopressin intranasally, at a dose of 30 mg for nostril/
day. Past medical history was normal; familial history
showed the presence of thyroid nodules, type 2 diabetes
mellitus and hypertension. She had menarche at the age
of 12 years, with regular menstrual cycles. At time of
observation she was primigravida at the 6th week of
pregnancy. She felt well, except for a slight breathless-
ness after moderate efforts. Her height was 153 cm;
weight 47 Kg and target gene according to Tanner 159
cm. Blood pressure was 110/70 mmHg; heart rate 88;
water intake about 2700 mL/day and diuresis 2000
mL/ d a y.
Fasting blood levels were: hematocrit: 36%, platelets:
363,000, glucose: 90 mg/dL, serum sodium: 143 mmol/L,
potassium: 4.02 mmol/L, and chloride: 105 mmol/L.
Liver and renal function tests were normal; AST:17
IU/L, ALT: 19 IU/L, total bilirubin: 0.30 mg/dL, serum
creatinine: 0.4 mg/dL, BUN: 20 mg/dL total protein: 6.9
A Case of Central Diabetes Insipidus: Evaluation in Pregnancy279
g/dL, and Albumin 3.0 g/dL. The specific gravity of the
urine was 1006 and no glucosuria or proteinuria was
present. Urinary and plasma osmolality were 245 and
287 mOsm/L, respectively.
Pituitary function and thyroid function were normal
(GH: 1.0 ng/mL; IGF1: 20 ng/mL; TSH: 2 IU/L; FT3:
2.8 pg/mL; FT4: 1.1 ng/dL;) and a MRI of the sellar
region detected a partial empty sella.
She was assuming desmopressin at a dose of 30mg/
nostril every day.
On the basis of the value of urine output and osmo-
lality the dose of desmopressin was increased at 40
During the course of pregnancy the patient was
evaluated every month with fluid balance, urine volume
and osmolality, serum electrolytes.
As summarized in Table 1, in th e cou r s e of pregnancy
was observed an adequate fluid and electrolytes balance,
without evidence of changes in clinical situation during
the weeks.
According to the trend showed in Table 1, and in ab-
sence of symptoms, daily dosage of desmopressin was
40 mg/nostril for the duration of pregnancy.
Patient referred no particular symptoms, except a mild
back pain, and physical examination showed slight
edema of the legs since the 16th week.
Mean Blood Pressure during the weeks was 100/60
mmHg; coagulation, liver and renal function were nor-
mal; mild anemia occurred in the third trimester.
Fetal monitoring with periodic ultrasound detected a
norma l i n tr auterin e gro wth.
Patient had an uncomplicated labor at the 39th week.
Because of an insufficient dilatation of the cervical canal
was chos en cesa r ian s e ction.
She gave birth to a healthy male baby, with a weight
of 2900 g and Apgar index of 8.
3. Discussion
Pregnancy is hemodynamically characterized by a frame-
work of low blood pressure, low peripheral resistance
and high flow.
Systemic arterial vasodilatation in early pregnancy is
Table 1. Mean values of diuresis, urine specific gravity,
electrolytes, serum osmolality for trimester.
1 trimester 2 trimester 3 trimester
diuresis 2500 2600 2600
urine specific
gravity 1009 1012 1010
potassium 3, 8 3, 9 4, 1
sodium 138 136 136
osmolality 287 289 284
accompanied by a compensatory rise in cardiac output
and a decline in Blood Pressure. This relative arterial
underfilling in early pregnancy is coupled to stimulation
of the renin-angiotensin-aldosterone system and hypo-
tonicity. Arterial underfilling induces the non-osmotic
stimulation of arginine vasopressin and up-regulation of
aquaporin 2 followed by trafficking of th is water channel
to the apical membrane of principal cells along the col-
lecting ducts. Changes of osmoregulatory system in
pregnancy are also caused by HCG, that plays a role in
the reduction of the set point of the osmoregulatory sys-
tem because induce the reduction at a lower concentra-
tion of threshold of vasopressin release and a decrease of
threshold of thirst. Perception of thirst occurs at lower
serum osmolality and serum sodium, with the effect of
decreased plasma sodium concentration and osmolality.
In middle and late pregnancy, there is also a four-fold
increase in vasopressinase, a cystine aminopeptidase
produced by placental trophoblasts, which enhances the
metabolic clearance of vasopressin, oxytocin and other
small peptides. Levels of vasopressinase are related to
the weight of the palcenta and achieve maximal concen-
trations at 24th week. Women with impaired reserve of
antidiuretic hormone can develop symptoms as polyuria
and polydipsia, and also intolerance for oral water intake,
nausea, fatigue and weight loss. For these reasons during
pregnancy a previous central diabetes insipidus may
worsen or may be unmasked.
Nevertheless, Central Diabetes Insipidus does not re-
duce fertility.
Pregnants, in fact, can have delivery with appropriate
clinical observation, monitoring fluid balance, body
weight, renal function, and vital signs and fetal status.
Initial biochemical evaluation should include a complete
blood count, serum electrolytes, plasma and urine os-
molality, serum creatinine, bilirubines, total proteins and
liver enzymes. It’s necessary to have periodic measure-
ments of urine volume of 24 hours, serum osmolality
and urine osmolality. Urine volume more than 2.5l, se-
rum osmolality > 295 mOsm/Kg and urine osmolality <
300 mOsm/Kg are indicative of overt and uncontrolled
Diabetes Insipidus. An important finding to be taken
into account is the sodiemia: in pregnancy sodium val-
ues greater than or equal to 140 mEq/L should be con-
sidered as hypernatremia.
Is often required an adjustment in the dose of desmo-
pressin during the weeks. As described in literature, pa-
tients with a history and partial diabetes insipidus,
treated with low doses of desmopressin, can require an
increase in dosage since the start of pregnancy. Polyuria
and Polydipsia in central DI can be recurrent and can
occur from the early weeks of gestation, before the in-
crease of serum vasopressinase. In some pregnancies
Copyright © 2011 SciRes. IJCM
A Case of Central Diabetes Insipidus: Evaluation in Pregnancy
Copyright © 2011 SciRes. IJCM
there aren’t changes compared to previous situation and
it’s not necessary to adapt dosage of desmopressin. Our
patient, in fact, required a slightly higher dose of des-
mopressin in the first trimester. Contrary to expectation,
the need of desmopressin did not increase during the
weeks, allowing an easy management in the administra-
tion of the drugs.
The primary aim of the therapy is the control of nic-
turia, using the lowest dosage possible of desmopressin,
followed by a daytime dose for the control of daytime
diuresis. It’s also important to maintain water intake at
1000 mL for day.
Safety in administration of desmopressin in pregnancy
is nowadays testing because of lack of controlled studies
regarding pregnant women treated. Available studies
agree on the safety of the drugs for maternal and fetal
outcome and show an incidence of fetal malformations,
Down syndrome, intrauterin growth retardation, low
birth weight or neonatal death comparable to uncompli-
cated pregnancies. Preeclampsia has been documented
in few cases and there aren’t described severe cases of
hypertension of the pregnant. This finding confirms the
lack of effect of vasoconstriction of desmopressin. As
observed in our case, ossitocino-like effects of this drug,
which can lead to preterm delivery, are not reported.
[1] M. C. Hime and J. C. Richardson, “Diabetes Insipidus
and Pregnancy: Case Report, Incidence and Review of
Literature,” Obstetrical Gynecological Survey, Vol. 33,
No. 6, 1978, pp. 375-379.
[2] M. D. Sonia Ananthakrishnan, “Diabetes Insipidus in
Pregnancy: Etiology, Evaluation and Management,”
American Association of Clinical Endocrinologists, Vol.
15, 2009, pp. 377-382.
[3] R. W. Schrier, “Systemic Arterial Vasodilatation, Vaso-
pressin, and Vasopresinase in Pregnancy,” Journal of
American Society of Nephrology, Vol. 21, No. 4, 2010, pp.
[4] J. M. Davison, E. A. Sheills, P. R. Phillips and M. D.
Lindheimer, “Serial Evaluation of Vasopressin Release
and Thirst in Human Pregnancy. Role of Human Chori-
onic Gonadotrophin in the Osmoregulatory Changes of
Gestation,” The Journal of Clinical Investigation, Vol. 81,
No. 3, 1988, pp. 798-806. doi:10.1172/JCI113386
[5] J. M. Davison, E. A. Gilmore, J. Dürr, G. L. Robertson
and M. D. Lindheimer, “Altered Osmotic Thresholds for
Vasopressin Secretion and Thirst in Human Pregnancy,”
American Journal of Physiology, Vol. 246, No. 1, 1984,
pp. F105-F109.
[6] M. D. Lindheimer, W. M. Barron and J. M. Davison,
“Osmoregulation of Thirst and Vasopressin Release in
Pregnancy,” American Journal of Physiology, Vol. 257,
No. 2, 1989, pp. F159-F169
[7] M. D. Lindheimer, “Polyuria and Pregnancy: Its Cause,
Its Danger,” Obstetrics & Gynecology, Vol. 105, No. 5,
2005, pp. 1171-1172.
[8] J. M. Davison, E. A. Sheills, P. R. Philips, W. M. Barron
and M. D. Lindheimer, “Metabolic Clearance of Vaso-
pressin and an Analogue Resistant to Vasopressinase in
Human Pregnancy,” American Journal of Physiology,
Vol. 264, No. 2, 1993, pp. F348-F353.
[9] Y. Iwasaki, Y. Oiso, K. Kondo, et al., “Aggravation of
Subclinical Diabetes Insipidus during Pregnancy,” New
England Journal of Medicine, Vol. 324, No. 8, 1991, pp.
522-526. doi:10.1056/NEJM199102213240803
[10] Y. Hamai, T. Fujuu, H. Nishina, S. Kozuma, H. Yoshi-
kawa and Y. Taketani, “Differential Clinical Course of
Pregnancies Complicated by Diabetes Insipidus Which
Does, or Does Not Pre-date the Pregnancy,” Human Re-
production, Vol. 2, No. 8, 1997, pp. 1816-1818.
[11] J. A Dürr, “Diabetes Insipidus in Pregnancy,” American
Journal of Kidney Diseases, Vol. 9, No. 4, 1987, pp.
[12] U. C. Brewster and J. P. Hayslett, “Diabetes Insipidus in
the Third Trimester of Pregnancy,” Obstetrics & Gyne-
cology, Vol. 105, No. 5, 2005, pp. 1173-1176.
[13] B. A. Källén, S. S. Carlsson and B. K. Bengtsson, “Dia-
betes Insipidus and Use of Desmopressin (Minirin) during
Pregnancy,” European Journal Endocrinology, Vol. 132,
No. 2, 1995, pp. 144-146.
[14] J. G. Ray, “DDAVP Use during Pregnancy: An Analysis
of Its Safety for Mother and Child,” Obstetrical & Gyne-
cological Survey, Vol. 53, No. 7, 1998, pp. 450-455.
[15] S. Hjartardottir, B. G. Leifsson, R. T. Geirsso and V.
Steinthorsdottir, “Paternity Change and the Recurrence
Risk in Familial Hypertensive Disorder in Pregnancy,”
Hypertens Pregnancy, Vol. 23, No. 2, 2004, pp. 219-225.
[16] Y. Yamanaka, K. Takeuchi, E. Konda, T. Samoto, A.
Satou, M. Mizudori and T. Maruo, “Transient Postpartum
Diabetes Insipidus in Twin Pregnancy Associated with
HELLP Syndrome,” Journal of Perinatal Medicine, Vol.
30, No. 3, 2002, pp. 273-275. doi:10.1515/JPM.2002.039
[17] I. Kalelioglu, A. Kubat Uzum, A. Yildirim and T. Okzam,
“Transient Gestational Diabetes Insipidus Diagnosed in
Successive Pregnancies: Review of Pathophysiology,
Diagnosis, Treatment, and Management of Delivery,” Pi-
tuitary, Vol. 10, No. 1, 2007, pp. 87-93.