Endocrine emergencies in pregnancy

Thyroid storm

Thyroid storm during pregnancy is very rare, and may occur with untreated or inadequately treated thyrotoxicosis during pregnancy. It may be masked by the physiological erythema and tachycardia of pregnancy, and may manifest as cardiac failure, especially at parturition. The exact pathophysiology is not well understood, but the labor process induces high emotional and physical stress, and in some the need of a Caesarean section may exacerbate adrenergic activity . Early recognition and initiation of appropriate therapy is important. There may be presence of high fever, disproportionate tachycardia and agitation or confusion. The diagnosis of thyroid storm is a clinical one, taking together the constellation of clinical symptoms and signs, and exclusion of infection and other causes. The elevated level of circulating thyroid hormone values is helpful but is not distinguishable from those seen in patients with uncomplicated hyperthyroidism. A scoring system using precise clinical criteria has been developed to facilitate the identification of thyroid storm .

The treatment of thyroid storm does not differ from non-pregnant women, and should be managed by a team consisting of an endocrinologist and maternal-fetal specialist in an intensive care unit. The management is directed at a rapid inhibition of thyroid hormone synthesis and its peripheral conversion, aggressive management of the systemic disturbances and identification and treatment of the precipitating cause . Aggressive treatment of the cardiac failure is essential with diuretics. Glucocorticoids are also essential: dexamethasone, 8 mg/day can be administered and blocks the deiodination of T4 to T3 (while assisting also with fetal lung maturation). PTU is the preferred anti-thyroid medication as it can additionally block the peripheral conversion of thyroxine (T4) to tri-iodothyronine (T3). PTU can be administered orally, by nasogastric tube, and in the event that the oral route is contraindicated, rectally. PTU is given at a dose of 200–250 mg every 6 hours. Iodide can be administered 1 hour after PTU to inhibit the release of preformed thyroid hormone. Iodide can be given orally (Lugol’s solution or saturated solution of potassium iodide, 4–8 drops every 6–8 hours; radiographic contrast media: iopanoic acid or sodium ipodate – 2 gm loading dose followed by 1 gm daily) or intravenously (sodium iodide 1 gm in 250–500 mL normal saline, infused twice daily).

Management of hyperpyrexia, treatment of precipitating factors and control of hyperadrenergic activity should be instituted simultaneously. Propranolol should be administered orally (40–80 mg every 6–8 hours) or intravenously (0.5–1 mg over 10 minutes, followed by 1–3 mg every few hours). The short-acting β ₁ -selective antagonist, esmolol can also be used intravenously (0.25–0.5 μg/kg loading dose, followed by an infusion of 0.05–0.1 μg/kg/min). The use of β-blocker is essential to survival from thyroid storm but need close monitoring. Plasma exchange has been tried in rare instances where aggressive conventional therapy fails to bring about discernible clinical improvement .

Careful monitoring of the fetus is also critical. However, prompt delivery of the fetus is currently not recommended during thyroid storm, unless indicated . If the fetus is exposed to recent high-dose maternal thionamides (e.g. PTU), close monitoring of the newborn thyroid status is important as thionamides may cross the placenta and inhibit fetal thyroid hormone synthesis and secretion.

Thyroid storm

Thyroid storm during pregnancy is very rare, and may occur with untreated or inadequately treated thyrotoxicosis during pregnancy. It may be masked by the physiological erythema and tachycardia of pregnancy, and may manifest as cardiac failure, especially at parturition. The exact pathophysiology is not well understood, but the labor process induces high emotional and physical stress, and in some the need of a Caesarean section may exacerbate adrenergic activity . Early recognition and initiation of appropriate therapy is important. There may be presence of high fever, disproportionate tachycardia and agitation or confusion. The diagnosis of thyroid storm is a clinical one, taking together the constellation of clinical symptoms and signs, and exclusion of infection and other causes. The elevated level of circulating thyroid hormone values is helpful but is not distinguishable from those seen in patients with uncomplicated hyperthyroidism. A scoring system using precise clinical criteria has been developed to facilitate the identification of thyroid storm .

The treatment of thyroid storm does not differ from non-pregnant women, and should be managed by a team consisting of an endocrinologist and maternal-fetal specialist in an intensive care unit. The management is directed at a rapid inhibition of thyroid hormone synthesis and its peripheral conversion, aggressive management of the systemic disturbances and identification and treatment of the precipitating cause . Aggressive treatment of the cardiac failure is essential with diuretics. Glucocorticoids are also essential: dexamethasone, 8 mg/day can be administered and blocks the deiodination of T4 to T3 (while assisting also with fetal lung maturation). PTU is the preferred anti-thyroid medication as it can additionally block the peripheral conversion of thyroxine (T4) to tri-iodothyronine (T3). PTU can be administered orally, by nasogastric tube, and in the event that the oral route is contraindicated, rectally. PTU is given at a dose of 200–250 mg every 6 hours. Iodide can be administered 1 hour after PTU to inhibit the release of preformed thyroid hormone. Iodide can be given orally (Lugol’s solution or saturated solution of potassium iodide, 4–8 drops every 6–8 hours; radiographic contrast media: iopanoic acid or sodium ipodate – 2 gm loading dose followed by 1 gm daily) or intravenously (sodium iodide 1 gm in 250–500 mL normal saline, infused twice daily).

Management of hyperpyrexia, treatment of precipitating factors and control of hyperadrenergic activity should be instituted simultaneously. Propranolol should be administered orally (40–80 mg every 6–8 hours) or intravenously (0.5–1 mg over 10 minutes, followed by 1–3 mg every few hours). The short-acting β ₁ -selective antagonist, esmolol can also be used intravenously (0.25–0.5 μg/kg loading dose, followed by an infusion of 0.05–0.1 μg/kg/min). The use of β-blocker is essential to survival from thyroid storm but need close monitoring. Plasma exchange has been tried in rare instances where aggressive conventional therapy fails to bring about discernible clinical improvement .

Careful monitoring of the fetus is also critical. However, prompt delivery of the fetus is currently not recommended during thyroid storm, unless indicated . If the fetus is exposed to recent high-dose maternal thionamides (e.g. PTU), close monitoring of the newborn thyroid status is important as thionamides may cross the placenta and inhibit fetal thyroid hormone synthesis and secretion.

Acute diabetic complications in pregnancy

Pregnancy in women with type 1 diabetes is associated with a higher risk of maternal and perinatal complications than in the non-diabetic population . Studies have shown that increasing levels of first-trimester glycosylated haemoglobin (HbA1C) starting from values slightly below 7% show a dose-dependent association with the risk of adverse pregnancy outcome . The Diabetes Control and Complications Trial showed that timely institution of intensive therapy was associated with rates of spontaneous abortion and congenital malformation similar to those in the non-diabetic population . However, several studies reported that near optimal glycaemic control did not obviate these complications considerably . In addition, specificity and sensitivity of HbA1C was relatively low in predicting adverse outcome in the individual pregnancy, making HbA1C measurements a less useful and reliable tool in diabetic pregnancies .

The incidence of diabetic ketoacidosis (DKA) during pregnancy ranges between 2 to 3%, and carries a 10–20% risk of fetal death . The majority of DKA occur in the second and third trimesters of pregnancy. During second and third trimester, there is a significant decrease in the maternal insulin sensitivity which renders the need to increase the insulin requirement by an average of 50% . Other precipitating factors include infection, non-compliance to insulin therapy, insulin pump failure, and the use of sympathomimetic drugs or corticosteroids. DKA during pregnancy may occur at lower glycaemic levels or even at euglycaemic state due to enhanced ketogenesis, in particular towards the end of gestation . In addition, pregnant women have a respiratory alkalosis from increased alveolar ventilation. The development of respiratory alkalosis is followed by a compensatory decrease in serum bicarbonate concentration which reduces the capacity to buffer hydrogen ions . Women with type 1 diabetes with unexplained hyperglycaemia (blood glucose >11.1 mmol/L) during pregnancy should alert their physician immediately to exclude DKA. In oriental women (predominantly) recent reports of ‘fulminant diabetes’ have been described. This is an abrupt and rapidly developing severe diabetes during pregnancy or within 2 weeks of delivery . Fulminant diabetes mellitus often rapidly progresses to DKA and is characterized by absence of diabetes-related autoantibodies and a very low C-peptide level during presentation. The pathophysiology of fulminant diabetes is still not clear, but accumulating evidence suggest acute viral related immune destruction of the pancreatic β-cells .

The acute management of DKA during pregnancy is similar to that of non-pregnant and has been reviewed elsewhere . Briefly, DKA should be treated in a high dependency unit under combined medical and obstetric care. Treatment includes aggressive volume replacement, insulin infusion, careful attention to electrolytes, and a search for and correction of precipitating factors. About 1–1.5 L of isotonic saline (0.9% NaCl) is given during the 1st hour. Subsequent choice for fluid replacement depends on the state of hydration, serum electrolyte levels, and urinary output. Potassium supplementation is usually added when renal function is adequate. Continuous infusion of regular insulin therapy is necessary to reduce ketogenesis. A fixed-rate intravenous insulin infusion calculated on 0.1 units/kg is recommended, aims for (i) reduction of the blood ketone concentration by at least 0.5 mmol/L/hr; (ii) in the absence of blood ketone monitoring, the venous bicarbonate should rise by 3 mmol/L/hr and capillary blood glucose fall by 3 mmol/L/hr . If these targets are not achieved, the rate of the insulin infusion should be increased. If the initial blood glucose level is low (<14 mmol/L) or when the blood glucose falls below 14 mmol/L, infusion of dextrose (5% or 10%) solution should commence simultaneously in order to avoid hypoglycaemia. Ketonemia typically takes longer to clear than hyperglycaemia, and direct measurement of serum β-hydroxybutyrate may be helpful. Regular (recommended 2 to 4 hourly) monitoring of serum electrolytes, glucose, urea, creatinine, and venous pH should be performed to assess the efficacy of treatment. Bicarbonate and phosphate replacement is only indicated in specific situations and thus should be individualized.

Continuous fetal monitoring is of paramount importance. Some degree of fetal distress may be present as placental transfer of ketoacids may cause fetus to become acidotic. However, fetal distress improves with stabilization of maternal hyperglycaemia and acidosis, thus immediate fetus delivery is reserved for persistence fetal compromise after maternal resuscitation .

Although there is an increasing number of women with type 2 diabetes mellitus who now becoming pregnant, the incidence of hyperosmolar hyperglycaemic nonketotic syndrome in pregnancy is rare. The increase tendency of enhanced ketogenesis and lower buffer capacity for acidosis during pregnancy predispose them to ketoacidosis.