Harsha A*, Sharma K**, Gupta AS***.
(* First Year Resident, ** Specialty Medical Officer, *** Professor, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)
Hyponatraemia is a common electrolyte imbalance disorder. Cases of hyponatremia in pregnancy are less common, but can have major consequences for both the mother and child. It is important to diagnose hyponatremia, recognize its symptoms and its causes and commence prompt treatment.
Hyponatremia in pregnancy can have serious ill effects on mother and fetus. It is important to measure plasma sodium concentration, plasma osmolality, urine sodium concentration and urine osmolality to distinguish between various pathophysiological causes of hyponatremia. In this article we present a case where hyponatremia caused convulsions in a primigravida in early pregnancy and how syndrome of inappropriate anti diuretic hormone secretion (SIADH) was diagnosed as the cause of hyponatremia.
A 26 year old, primigravida, married since 2 months, came to emergency with complaint of pain in abdomen since four days, which had increased gradually in intensity and frequency. She also had few episodes of vomiting. She had her last menstrual period 37 days prior to the day of presentation. Urine pregnancy test was done which was faintly positive. Ultrasound showed no evidence of any gestational sac like structure in the uterine cavity or the adnexa. She continued to have vomiting, non bilious, non blood stained. Her liver and renal function tests and serum electrolytes were normal with sodium levels of 137 mEq/L which was also within normal limits. Serum β HCG levels were 378.19 mIU/mL. She was kept on antiemetics and serum β HCG was being monitored to look for effective rise in β HCG levels. Her vomiting had stopped after admission. On day 4 of admission she had 2 episodes of generalized tonic clonic seizures involving all four limbs and frothing from the mouth. She did not regain consciousness in between two episodes of seizures. Each episode lasted for 30 seconds with an interval of 1 minute between the two seizures. She was drowsy after the episodes, responding only to deep painful stimuli. A sudden unexplained drop in her serum sodium levels from normal to 108 mEq/L was found indicating hyponatremia as the cause of seizures. There was no history of convulsions or any other central nervous system (CNS) disease in the past. She had a history of abdominal tuberculosis 4 years back which was completely treated. Her serum osmolality was 226 mOsmol/kg (normal: 275-295 mOsmol/kg) while urine osmolality was 282 mOsmol/kg (average value: 200 – 500 mOsmol/kg). Her urea levels were 6 mg/dl and creatinine was 0.9 mg/dl. The adrenocorticotropic hormone level in plasma was raised to a value of 68.4 pg/mL, with a normal serum cortisol level and normal thyroid hormone levels. Physician and nephrologist were consulted. She was managed in medical intensive care unit (MICU) for 13 days. In view of serum hypo osmolality, urine hyper osmolality with normal cortisol and thyroid levels a diagnosis of SIADH was made. Her MRI brain showed an old calcified granuloma in right parietal parafalcine lobe. A possibility was that it could be a sequelae of the old tuberculous infection. A contrast enhanced computerized tomography (CECT) would have further clarified the nature of the lesion in the CNS that could have been the cause of her SIADH. Her sodium levels, were corrected by infusion of 3% normal saline, following which her serum sodium levels returned to normal. Her sodium levels were monitored and remained within normal limits. The β HCG levels on the other hand kept showing an increasing trend, upto a level of 748.82 mIU/mL and 1110.62 mIU/ mL on day 4 and 6 of her admission (day 40 and 42 of her LMP). An intrauterine pregnancy of 6weeks 1day was confirmed on a repeat scan done on day 53 of her LMP (7 weeks, 4 days by dates). She was discharged on steroids with advise of follow up for two weekly serum electrolytes monitoring and was advised a post delivery CECT to look for any CNS cause of SIADH. She is following regularly for antenatal care. She presently of oral Prednisolone and has had no further episodes of hyponatremia induced symptoms till date.
Hyponatremia is a condition in which sodium levels in blood are less than normal ( <135mEq/l ). Symptoms of mild hyponatremia are headaches, nausea, confusion and poor balance. Severe hyponatremia when the sodium level is below 120 mEq/L causes intracerebral osmotic fluid shifts and brain edema which leads to convulsions and coma. Hyponatremia can be classified based on volume status into hypovolemic, euvolemic and hypervolemic. While vomiting, diarrhea and excess use of diuretics can cause hypovolemic hyponatremia; hypervolemic hyponatremia may be caused by heart failure, cirrhosis and renal failure. Glucocorticoid deficiency, hypothyroidism and the condition of our interest; SIADH are causes of euvolemic hyponatremia. Our patient had severe hyponatremia with normal cardiac, renal and liver parameters. Though she had vomiting, the hyponatremia presented long after the vomiting had ceased and no signs of dehydration were present. Our patient was thus a case of euvolemic hyponatremia. It is necessary to rule out renal disease and insufficiency of thyroid, pituitary, and adrenal glands, before attributing the hyponatremia to SIADH in euvolemic states. This was done in our case. Thus SIADH is mostly a diagnosis of exclusion. SIADH is defined by inappropriate secretion and function of anti diuretic hormone which reduces water excretion excessively despite a normal or increased plasma volume resulting in hyponatremia and hypo osmolality. During pregnancy, physiologic changes occur in intravascular volume and osmoregulation that aggravate the problem of SIADH. Mean plasma osmolality reduces by 5-10 mmol, and serum sodium levels reduce by 5mmol/l in a normal pregnancy. This drop in plasma osmolality is caused by a ‘reset osmostat’ phenomenon: that is ADH-release and a thirst stimulus start at a comparatively lower serum osmolality level in pregnancy. As early as 6 weeks of pregnancy there is vasodilation resulting in a decrease in effective circulating volume subsequently decreasing blood pressure which trigger non-osmotic arginine vasopressin release. Common causes of SIADH are neurological and pulmonary disorders and certain psychiatric medication. However pregnant women experience pain, anxiety and nausea very frequently and these become more common causes of increased ADH production in pregnancy. Bartter and Schwartz in 1967 laid down criteria to define SIADH which are valid till today. The criteria includes serum hyponatremia with corresponding hypoosmolality, urinary hyperosmolality, an absence of features of volume depletion (normal skin turgor, normal blood pressure), absence of other causes of hyponatremia (adrenal insufficiency, hypothyroidism, cardiac failure, renal disease with salt wastage, hepatic disease, and drugs) and correction of hyponatremia by fluid restriction. Hyponatremia (serum Na+ <135 mEq/L), serum hypo osmolality (serum osmolality <280 mOsm/kg) and high urine osmolality characterizes SIADH. ADH secretion is suppressed in serum hypoosmolality to permit the excess water to be excreted in urine causing urine osmolality to be less than 100 mOsm/kg. Therefore, in a case of plasma hypoosmolality if urinary osmolality is more than 100 mOsm/kg, ADH excess is confirmed. In our case hyponatremia of 108 mEq/L, low serum osmolality of 226 mosm/kg and high urine osmolality of 282 mosmol/Kg suggested SIADH. In SIADH total body water increases in which blood urea gets diluted resulting in lower levels of blood urea nitrogen (BUN), usually below 10 mg/dl. In our case urea levels were always < 6 mg/dl. In SIADH, serum potassium concentration generally remains unchanged because potassium moves from intra cellular to extra cellular space which prevents its dilution. In our case potassium was 3.4 mEq/L. During second trimester and delivery, it can be difficult to differentiate between hyponatraemia and impending eclampsia as both present with symptoms of headache, nausea, dizziness, drowsiness, coma and seizures. Aggressive treatment of hyponatremia is indicated in patients who have severe symptoms (like convulsions, stupor, coma) and who have an acute episode of moderate to severe hyponatremia of a duration of less than 48 hours. In our case correction with 3% hypertonic saline was given which caused sodium levels to return to normal. Sodium levels were then serially monitored which remained normal without any further treatment. Hyponatremia correction rate was monitored as too aggressive correction can cause central pontine myelinolysis (CMP). In pregnancy and lactation, vaptans (ADH receptor antagonists) are contraindicated as these are category C drugs. Diuretics are also avoided as there is a risk of IUGR. Hypertonic saline and fluid restriction are main modalities of treatment in pregnancy. During labor, use of oxytocin should be avoided and if used sodium levels should be monitored. Case has been reported of patients with SIADH developing hyponatremia due to oxytocin use in labor. Oxytocin has a structure and function similar to ADH and causes water reabsorbtion and hyponatremia. Chances of developing hyponatremia are less when oxytocin is dissolved in NaCl 0.9 % or Ringers Lactate and chances are more if oxytocin is used with Glucose 5%. Hyponatraemia in pregnancy is a significant problem as it can cause severe symptoms and even mortality. Hyponatremia in mother can cause low sodium levels in the child both in utero and during immediate postpartum because sodium exchanges take place in the placenta. Thus sodium levels need to be maintained in normal range for benefit of both mother and fetus. SIADH ,which is an important cause accounting for almost one third cases of hyponatremia in pregnancy, should be promptly diagnosed and treated.
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Harsha A, Sharma K, Gupta AS. A Case Of Syndrome Of Inappropriate Anti diuretic Hormone Secretion In Pregnancy. JPGO 2017. Volume 4 No.3. Available from: http://www.jpgo.org/2017/03/a-case-of-syndrome-of-inappropriate.html