Thyroid Storm
Thyroid storm is a rare but life-threatening endocrine emergency occurring in 1% to 2% of pregnant women with hyperthyroidism. It typically has an acute onset and is associated with the following symptoms: fever, tachycardia, and central nervous system dysfunction (restlessness, altered mental status, and seizures). Untreated, it can lead to significant morbidity and mortality, including cardiac dysrhythmia, multiorgan failure, and even death. Case fatality rates range from 10% to 30% in the literature. Given the severity of the disease process, a high clinical suspicion, rapid recognition, intervention, and supportive care are needed to maximize both maternal and fetal outcome.
Although the exact triggering mechanism is unknown, most cases are due to poorly controlled hyperthyroidism. Events such as pre-eclampsia, trauma, ketoacidosis, surgery, and infection have been associated with storm. , A careful search for underlying associated etiologies should be performed concurrent with treatment.
A high clinical suspicion is needed as the presenting signs and symptoms may be nonspecific enough to be confused with any number of other conditions. Elevated blood pressure, headaches, abdominal pain, and even pulmonary edema or heart failure are features compatible with pre-eclampsia that may make the diagnosis of thyroid storm more difficult.
The physiologic changes of pregnancy result in a compensated respiratory alkalosis, thus consultation with an obstetrician or Maternal Fetal Medicine specialist is suggested. Metabolic changes can lead to fetal heart rate tracing abnormalities, including tachycardia, loss of variability, and late decelerations, ultimately resulting in increased fetal morbidity and mortality.
Laboratory analysis includes thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), complete blood count (CBC), and complete metabolic panel (CMP). TSH is typically undetectable in thyroid storm, although cautious interpretation is required in the first trimester, as human chorionic gonadotropin (hCG) can bind to the TSH receptors present in thyroid tissue and act like a weak form of TSH. There are no generally accepted levels of thyroid hormone in maternal serum at which the diagnosis of thyroid storm is assured. FT4 and FT3 are often well above the upper limits of normal in pregnancy. Total hormone levels are also usually elevated, thus there may be significant laboratory overlap with simple hyperthyroidism. There is typically an associated leukocytosis as well as evidence of hyperglycemia, hypercalcemia, elevated liver enzymes, and electrolyte disturbances on metabolic panel screening.
Given a high incidence of case fatality rates and the need for early recognition, Burch and Wartofsky have outlined a commonly cited clinical scoring system for the probability of thyroid storm. Points are allocated for elevation in temperature, maternal pulse, and a number of organ system dysfunctions indicating a high, medium, or low probability of the diagnosis. A score of 45 or more is highly indicative of thyroid storm, a score of 25 or less makes the diagnosis unlikely and scores between 25 and 45 are suggestive and rely strongly on the use of clinical context.
A diagnosis of thyroid storm requires prompt intervention for both mother and fetus, and treatment should not be delayed. A multidisciplinary approach to management is recommended, including Maternal Fetal Medicine, Endocrinology, Neonatology, and Critical Care specialists. In addition, preparation should be made for admission to an intensive care unit (ICU), with the availability of continuous fetal monitoring if the fetus has reached viability. Treating the underlying maternal metabolic derangement(s) is key to improving fetal status, thus it is important to exhaust all attempts to correct the underlying maternal abnormalities prior to intervening for the fetus. The presence of a persistent fetal bradycardia or the development of category III fetal heart rate tracing that is unresponsive to resuscitative measures may require expedited delivery.
Intravenous access should be obtained, and cooling measures performed. Fluid balance and vital signs, including continuous pulse oximetry, need to be carefully monitored. An initial electrocardiogram (ECG) and continuous telemetry are recommended to identify arrhythmias. In addition, some patients can have thyrotoxic heart failure due to the myocardial effects of excess FT4, thus any cardiorespiratory complaints should be thoroughly evaluated, including echocardiography. Treatment is generally the same for thyroid storm and thyrotoxic heart failure, even in pregnancy.
The treatment of thyroid storm involves the use of several medications to decrease the level of thyroid hormone. Propylthiouracil (PTU) and methimazole (MMI) are thionamides and act within the thyroid gland to inhibit follicular growth and development, as well as the packaging of iodothyronines into T4 and T3. PTU has the advantage of antithyroid effects within the thyroid gland as well as inhibiting the peripheral conversion at the tissue level, limiting the active form of thyroid hormone. However, there is a significant disadvantage of the use of PTU in that there have been rare cases of fulminate liver failure and death associated with its use, including instances in pregnancy. There is a Food and Drug Administration (FDA) “black box” warning for PTU concerning this link to hepatotoxicity. It is unclear how thyroid storm specifically affects this risk. MMI use in the first trimester of pregnancy has been linked to some teratogenic effects, specifically aplasia cutis and choanal atresia. In addition, rarely a life-threatening agranulocytosis may develop after MMI and PTU use. Given these conflicting risks, there is no clear recommendation for which thionamide to initiate in thyroid storm in pregnancy; however, MMI is generally avoided in the first trimester.
Additionally, an iodide-containing medication to inhibit the further release of active thyroid hormone from the thyroid gland may be used. Oral potassium iodide, five drops every 8 hours, or intravenous sodium iodide 500 to 1000 mg every 8 to 12 hours may be used. It is important to be aware of the paradoxical release of thyroid hormone from the thyroid gland associated with iodide use; thus it is important to start iodine administration approximately 1 hour after the use of thionamides. Corticosteroids are also an important treatment of thyroid storm, as they decrease systemic inflammation, as well as having the peripheral effects of decreasing T4 to T3 conversion. Beta-blockers such as propranolol or metoprolol will also reduce peripheral conversion of T4 to T3, and lessen the complications of tachycardia, such as high-output cardiac failure. Long-term use of beta-blockers has been associated with fetal growth restriction, but is generally considered safe in a risk/benefit consideration with the exception of atenolol. Other supportive medications include antipyretics such as acetaminophen ( Table 22.1 ).
| Treatment | Dose | |
|---|---|---|
| MATERNAL | Supportive care IV access Consultation Cooling measures | LR bolus then IVF at 150–250 mL/hour Continuous pulse oximetry, serial BP ICU admission, Critical Care, Endocrine, Maternal Fetal Medicine Acetaminophen 500 mg q6 hour Cooling blankets |
| Testing Laboratory Ancillary | TSH, fT3/4, CBC diff, ABG, CMP ECG/telemetry, CXR, ECG Additional testing as needed (cultures, CT scan, etc.) | |
| Medications First-line Initial dose given 30–60 minutes after PTU Block T4→T3 conversion Heart rate control (goal< 120 bpm) a Therapies not recommended | Propylthiouracil (PTU) 300 mg PO or NG q6 hour Methimazole 20–25 mg PO q6–q8 hour (total daily dose 60–80 mg). Do not use methimazole during the first trimester Potassium iodide (SSKI) 5 drops PO/NG q8 hour Dexamethasone 2 mg IV q6 hour × 4 doses Propranolol 40–60 mg PO/NG q6 hour (IV alternative = propranolol prn or esmolol drip) Radioiodine (contraindicated) Thionamide and levothyroxine combination therapy (insufficient evidence) | |
| FETAL | ||
| Monitoring Fetal optimization | Consult Maternal Fetal Medicine Initiate fetal monitoring if viability achieved Maternal left lateral decubitus Maternal O 2 supplementation Stabilize maternal condition PRIOR to delivery |
a Ensure no evidence of heart failure or medical contraindication (e.g., asthma). ABG, Arterial blood gas; BP, blood pressure; bpm, beats per minute; CBC, complete blood count; CMP, complete metabolic panel; CT, computed tomography; CXR, chest X-ray; FT3/4, free T3/T4; ICU, intensive care unit; IVF, intravenous fluid; LR, lactated Ringer’s; NG, nasogastric; PO, by mouth; prn, as needed; q, every; TSH, thyroid-stimulating hormone.
Conventional treatments may fail after trials of medical management in the most severe cases. There also may be adverse reactions to the thionamides, which may require discontinuation. Emergency thyroidectomy, with or without plasmapheresis, has been described successfully in thyroid storm, but must be considered high-risk and last-line treatment and can be performed in pregnancy.
In summary, thyroid storm is a rare, life-threatening condition that requires early recognition, multidisciplinary care, and aggressive therapy.
Diabetic Ketoacidosis
Like thyroid storm, diabetic ketoacidosis (DKA) is a medical emergency, which can result in both maternal and fetal morbidity and mortality. With early recognition and aggressive multidisciplinary management, the overall incidence has decreased from approximately 10% to 20% in the late 1970s to approximately 1% to 2% in most recent reports, resulting in improved maternal and fetal mortality. Preterm birth, both from premature labor and from medical intervention, is a common occurrence after DKA.
The pathophysiology of DKA occurs due to the lack of insulin resulting in a perceived hypoglycemia at target cells. Glucagon is subsequently released, increasing serum glucose and leading to osmotic diuresis, which results in hypovolemia and electrolyte depletion.
Counterregulatory hormones release free fatty acids into the circulation, which are then oxidized to ketone bodies leading to a metabolic acidosis, which manifests as an anion gap. Ketoacids bind sodium and potassium, which are excreted in the urine, further worsening the electrolyte balance. If untreated, patients can experience cardiac dysfunction, decreased tissue perfusion, and worsened real function leading to shock, coma, and death. ,
The normal physiologic changes of pregnancy increase the susceptibility to DKA. Insulin resistance, primarily due to human placental lactogen, cause insulin requirements to increase with advancing gestation. Respiratory adaptations during pregnancy result in a compensated maternal respiratory alkalosis. The associated decrease in serum bicarbonate reduces the body’s normal buffering capacity, thus predisposing the patient to DKA. , ,
Although DKA more commonly affects those with type 1 diabetes, it can also be seen in patients with type 2 diabetes, ketosis prone diabetes, and latent autoimmune diabetes of adulthood (also known as LADA or “type 1.5”). Patients who are in DKA generally present with abdominal pain, malaise, persistent vomiting, increased thirst, hyperventilation, tachycardia, dehydration, and polyuria. Mental status changes can be seen as the level of acidosis worsens. The diagnosis is confirmed with documentation of hyperglycemia, acidosis, and ketonuria. Other laboratory findings include anion gap, ketonemia, renal dysfunction, and electrolyte abnormalities. , Typically, patients present with severely elevated serum glucose levels; however, DKA can occur with levels less than 200 mg/dL in pregnancy. Euglycemic DKA (euDKA) and has been described in susceptible patient populations such as those with poor oral intake (prolonged period of fasting), pregnant patients, and nonpregnant patients who are treated with sodium-glucose cotransporter 2 (SGLT-2) inhibitors.
Precipitating factors in pregnancy include emesis, infection, beta-sympathomimetic tocolytic agents, corticosteroids, poor compliance, and medical errors. , Although beta-sympathomimetics (e.g., terbutaline) are not routinely used for prolonged (greater than 48 hours) tocolysis due to the FDA safety communication in 2011, it is important to remember that they should be used very cautiously, if ever, for patients with diabetes.
Although the mechanism is not clearly understood, DKA presents a significant risk to overall fetal well-being. The likely mechanism is related to maternal ketoacids that cross the placenta and lead to decreased fetal tissue perfusion and oxygenation. The fetus has a limited ability to buffer significant acidemia, and therefore is quite sensitive to maternal acidosis. This often results in alterations of the fetal heart rate tracing, including decreased variability and/or late decelerations, which reflect fetal hypoxemia and acidosis. It is important to exhaust all attempts to correct the underlying maternal abnormalities prior to intervening for the fetus, as once maternal status stabilizes, the fetal status will generally follow. ,
Like thyroid storm, DKA is considered a medical emergency and a multidisciplinary team, including Maternal Fetal Medicine, Endocrinology, Neonatology, and Critical Care, should be assembled. In addition, strong consideration should be made for admission to an ICU.
Treatment includes adequate intravenous access and placement of an indwelling urinary catheter. Significant fluid deficits should be anticipated and corrected. Insulin should be started and electrolyte abnormalities corrected. Fluid balance and vital signs need to be carefully monitored and documented.
A CMP with magnesium and phosphorous, CBC with differential, urinalysis, fingerstick blood glucose, arterial blood gas, and serum ketones should be collected. Additional testing (urine culture, blood culture, chest X-ray, etc.) should be performed based on clinical suspicion and any potential underlying processes. Initially, serum ketones, electrolytes, and maternal acid/base status should be monitored every 2 hours until ketosis and acidosis resolved. Blood sugars should be collected hourly during this time to titrate insulin. , ,
Once viability is confirmed, fetal monitoring should be initiated. As noted, the fetal heart tracing will likely appear concerning during the initial phase of metabolic compromise. Maternal oxygen supplementation and left lateral decubitus positioning should be used to increase blood flow to fetus and improve oxygenation. Adequate hydration and correction of acid/base derangements must be started. Delivery is generally postponed until after the maternal metabolic condition is stabilized, as this will usually correct the fetal heart tracing abnormality. There are exceptions, including severely prolonged bradycardia or a persistent category III tracing.
Table 22.2 illustrates a general algorithm for the treatment of diabetic ketoacidosis in pregnancy, including rehydration, reduction of hyperglycemia, and correction of acid-base and electrolyte imbalance, while searching for and treating the underlying etiology. , ,
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