SIMPOSIO

EMERGENCIAS Y
COMPLICACIONES
SEVERAS Endocrine emergencies
OBSTÉTRICAS Christopher G. Goodier, MD1

Assistant Professor, Maternal Fetal

1 Abstract
Medicine, Obstetrics & Gynecology Endocrine emergencies such as thyroid storm and diabetic ketoacidosis should be consid-
Department, Medical University of South ered life-threatening disease processes in the obstetric population. Diagnosis requires a high
Carolina, USA clinical suspicion with prompt initiation of treatment, supportive care and intervention. A mul-
tidisciplinary team of specialists, including maternal fetal medicine, endocrinology, medical
Conflict of interest: I have no conflict of intensivist, neonatologists and anesthesiology should be assembled to achieve the best out-
interest comes for mother and baby.
Keywords: Pregnancy; Diabetes; Diabetic Ketoacidosis; Thyroid Dysfunction; Hyperthyroid-
Recieved: August 20, 2016 ism; Thyroid Storm.
Accepted: September 29, 2016

Correspondence:
Emergencias endocrinas
Christopher G. Goodier, MD Resumen
96 Jonathan Lucas St, CSB 634 Las emergencias endocrinas, tales como la tormenta tiroidea y la cetoacidosis diabética, de-
MSC 619 ben ser consideradas como procesos mórbidos que ponen en riesgo la vida de la población
Charleston, SC 29425 obstétrica. El diagnóstico requiere gran sospecha clínica e inicio inmediato del tratamiento,
Tel 843 792 4500 soporte clínico e intervención. Se debe organizar un equipo multidisciplinario de especialistas
Fax 843 792 0533 que incluyan la medicina maternofetal, endocrinología, intensivista médico, neonatólogos y
anestesiólogos, de manera de lograr el mejor resultado para la madre y el bebe.
@ goodier@musc.edu Palabras clave: Embarazo; Diabetes; Diabetes, cetoacidosis; Tiroides, disfunción; Hipertiroi-
dismo; Tiroides, Tormenta.

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 Christopher G. Goodier

Thyroid storm of thyroid storm is assured, and there may be

significant laboratory overlap with simple hy-
Hyperthyroidism occurs in 0.1-0.4% of all preg- perthyroidism. The white blood cell count (WBC)
nancies and usually the result of maternal may be variably elevated, especially if there is an
Grave’s disease, an autoimmune condition char- associated infection. There may also be evidence
acterized by the production of thyroid stimulat- of dehydration, acidosis, hyperglycemia, hyper-
ing immunoglobulin (TSI) and TSH binding in- calcemia, elevated liver enzymes and electrolyte
hibitory immunoglobulin(1). Early treatment and disturbances on metabolic panel screening.
normalization of maternal thyroid function im-
portant because poor control increases the risk While thyroid storm is primarily a clinical diagno-
of PTB, fetal morbidity and thyroid crisis. sis, Burch and Wartofsky have outlined a com-
monly cited clinical scoring system for the prob-
Thyroid storm is a potentially fatal endocrine ability of thyroid storm(5). Points are allocated for
emergency characterized by a severe hyper-met- elevation in temperature, maternal pulse and a
abolic state precipitated by high levels of endog- number of organ system dysfunctions. Scores
enous thyroid hormones. While the exact trig- can indicate a high, medium or low probability
gering mechanism is unknown, most cases are of the diagnosis of thyroid storm. Chest X-rays
a result of poorly controlled hyperthyroidism. It and CT scans can be useful when looking for
has been associated with preceding events such concomitant infections or pulmonary pathology
as infection, surgery, trauma, venous thrombo- such as edema or emboli.
embolism and diabetic ketoacidosis.
The maternal adaptations to pregnancy are also
Case fatality rates vary in different series, but factors that must be considered when making
range from 10-30%(2); however with treatment the diagnosis of thyroid storm. Mild tachycardia
incidence in pregnancy 2%(3). Rapid recognition, and leukocytosis are not unusual in pregnancy.
prompt supportive care and intervention likely Pre-eclampsia may present with hypertension,
maximizes maternal and fetal outcome. systemic symptoms, pulmonary edema and
even heart failure. Interpretation of maternal ac-
Presenting signs and symptoms can be vari- id-base status must take into consideration the
able, and may commonly include tachycardia, moderate compensated respiratory alkalosis
diaphoresis, anxiety or confusion, weakness, hy- that occurs in pregnancy.
perpyrexia and a widened pulse pressure(4). The
presentation may be nonspecific enough to be Fetal heart rate tracings may reflect maternal met-
confused with any number of other conditions, abolic changes, including fetal tachycardia (>160
leading to a delay in diagnosis and treatment. A beats per minute), loss of variability and in severe
prominent goiter, thyroid bruit or exopthalmos cases late decelerations, suggesting hypoxia and
may be discriminating physical signs that are acidosis. Fetal morbidity remains high with thyroid
more specific to thyroid dysfunction. storm, with significant incidences of preterm birth,
neonatal complications and even fetal death(6).
Laboratory analysis may be useful in making a
diagnosis, especially in patients who have no re- A diagnosis of thyroid storm requires prompt
ported history of thyroid dysfunction. Thyroid intervention for both mother and fetus. Multi-
stimulating hormone (TSH) is usually undetect- disciplinary care should include Maternal-Fetal
able, although in the first trimester this may be Medicine, Endocrinology and possibly Critical
due to the normal physiology of pregnancy due Care specialists, as ICU admission may be neces-
to the suppressive effects of human chorionic sary. Once viability is achieved, continuous fetal
gonadotropin (hCG). Free T4 (FT4) and free T3 monitoring should be available. The presence
(FT3) are often well above the upper limits of of a persistent fetal bradycardia or the devel-
normal in pregnancy. Total hormone levels are opment of Category III heart rate tracing that is
also usually elevated. Trimester and laboratory unresponsive to resuscitative measures may re-
specific reference ranges should be used; al- quire expedited delivery for a viable fetus. Gen-
though typically the goal FT4 is set at the upper erally speaking, the maternal condition should
limits of the normal range. However there are no be treated and stabilized; prior to intervening on
generally accepted levels at which the diagnosis behalf of the fetus(7).

428 Revista Peruana de Ginecología y Obstetricia

 Endocrine emergencies

Treatment should include 1) adequate intra- Corticosteroids can also be administered which
venous access; 2) replacement of fluids; 3) in- have the effect of decreasing systemic inflam-
terpretation of heart rhythm; and, 4) ensuring mation as well as peripheral effects of de-
oxygenation. EKG, continuous monitoring with creasing T4 to T3 conversion. Other supportive
telemetry if possible and pulse oximeter should medications again include antipyretics such as
be placed. Laboratory evaluation should include acetaminophen and beta-blockade.
TSH, FT3/4, liver and kidney function as well as
electrolytes and blood count with differential. Beta blockade is a critical adjunct to treatment
Respiratory failure is a late finding, but intuba- of thyroid storm and tachycardia leading to high
tion and mechanical ventilation is sometimes output cardiac failure is one of the leading caus-
necessary. es of mortality in a thyroid storm. Propranalol
may be used for rate control and has the advan-
Definitive treatment of thyroid storm also in- tage of reduces peripheral T4 to T3 conversion.
volves the use of several medications in addi- Long-term use of beta-blockers has been asso-
tion to supportive care. First-line treatment of ciated with fetal growth restriction, but is gen-
hyperthyroidism is the thionamides, specifically erally considered safe in a risk/benefit consider-
propylthiourocil (PTU) and methimazole (MMI) ation. Atenolol is generally avoided (Category D).
(8)
. Both agents act within the thyroid gland to
inhibit follicular growth and development. One If conventional treatments fail to generate an
advantage of PTU is that it also works outside adequate response, emergency thyroidectomy,
the thyroid gland to inhibit peripheral conver- with or without plasmaphoresis has been de-
sion at the tissue level of T4 to T3. PTU how- scribed successfully in thyroid storm, but must
ever is not typically first line given that there be considered a high-risk undertaking(10).
have been rare cases of fulminate liver failure
and death associated with its use, including in- Diabetic ketoacidosis
stances in pregnancy. There is a FDA “black box”
warning for PTU concerning this link to hepato- Diabetic ketoacidosis (DKA) is a medical emer-
toxicity. It is unclear how thyroid storm specifi- gency and can result in both maternal and fetal
cally affects this risk. morbidity and mortality with and overall inci-
dence, which has decreased, from approximate-
Methimazole use in pregnancy has been linked ly 10 to 20% in the late 1970s to approximately 1
to some teratogenic effects including aplasia cu- to 2% in most recent reports(11-13). The improve-
tis(9). This association is not particularly strong in ment has been attributed to early recognition
the literature so its use is generally considered and aggressive multi-disciplinary management.
to be acceptable, especially outside the time of As a result both maternal and fetal mortality
organogenesis. In addition, rarely a life-threat- have significantly improved. Preterm birth, both
ening agranulocytosis may develop after MMI from premature labor and from medical inter-
use. Given these conflicting risks there is no vention, is a common sequalae from severe DKA.
clear recommendation for which thionamide to
initiate in a thyroid storm. The pathophysiology of DKA is the result of a
complex interplay in which inadequate insulin
In addition to PTU or MMI to treat thyroid storm, action results in perceived hypoglycemia at the
it is also recommended to use iodide-contain- cellular level of target cells such as those in the
ing medication to inhibit the further release of liver, adipose and muscle tissues. The body re-
active thyroid hormone from the thyroid gland. sponds by releasing glucagon, which worsens
Oral potassium iodide, 5 drops every 8 hours, or the level of hyperglycemia in the serum causing
IV sodium iodide 1 000 mg every 12 hours may osmotic diuresis and resultant hypovolemia and
be used. The use of iodines should not be ad- electrolyte depletion.
ministered prior to the use of thionamides due
to their initial action, which releases thyroid hor- The lack of insulin and production of counter-reg-
mones from the thyroid, prior to suppressing ulatory hormones in the adipose tissue activates
it. The general time frame is recommended to hormone sensitive lipase, which causes the re-
be 30-60 minutes after the initiation of thion- lease of free fatty acids into the circulation. The
amides(8). free fatty acids are then oxidized to ketone bod-

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 Christopher G. Goodier

ies. Acidosis occurs secondary to ketone body Maternal DKA presents a significant risk to over-
formation, which can overwhelm the buffering all fetal well being. The mechanism is not clear-
capacity of the body leading to a metabolic aci- ly understood; however appears to be related
dosis manifested as an anion gap. Ketoacids bind to ketoacid production, which readily cross the
sodium and potassium, which are excreted in the placenta, decreasing fetal tissue perfusion and
urine, further worsening the electrolyte balance. reducing oxygenation in the fetus. In addition
The final common pathway if this process is left these ketoacids can dissociate into anions and
untreated can lead to cardiac dysfunction, de- result in fetal metabolic acidosis(16). The fetus
creased tissue perfusion and worsened real func- has a limited ability to buffer significant acide-
tion leading to shock, coma and death(11,16). mia, and therefore is quite sensitive to maternal
acidosis.
The normal physiologic changes of pregnancy in-
crease the susceptibility of the gravid parturient This often results in a fetal heart tracing that may
to DKA. Pregnancy related physiology results in include decreased variability or late decelera-
increased insulin resistance primarily due to the tions. Interpretation can be difficult; however,
action of human placental lactogen. Thus, nor- it is likely that maternal acidosis, hyperglycemia
mal exogenous insulin requirements increase and hypovolemia all contribute to a potential
with advancing gestation. threat to fetal well-being(12). Initially, the primary
effort should focus on correcting the maternal
In addition, respiratory adaptations of normal acidosis, which should improve the underlying
pregnancy produce a compensated maternal re- fetal status. It is important to exhaust all at-
spiratory alkalosis. The compensatory decrease tempts to correct the underlying maternal ab-
in serum bicarbonate reduces the body’s normal normalities prior to intervening for the fetus(13,16).
buffering capacity, thus predisposing the patient
to DKA(11,12,16). Like thyroid storm, DKA is considered a medical
emergency and a multidisciplinary team should
Patients generally present with abdominal pain, be assembled, including Maternal-Fetal-Med-
malaise, persistent vomiting, polydypsia, hyper- icine, Neonatology and Critical Care, as soon
ventilation, tachycardia, dehydration and poly- as possible. In addition, strong consideration
uria. As the level of acidosis increases patient will should be made for admission to an intensive
often have altered mental status and sometimes care unit.
present obtunded. The diagnosis is confirmed
with documentation of hyperglycemia, acidosis Treatment includes adequate IV access and
and ketonuria. Other laboratory findings include placement of an indwelling urinary catheter. Sig-
anion gap, ketonemia, renal dysfunction as well nificant fluid deficits should be anticipated and
as possible electrolyte abnormalities(12,16). corrected, insulin should be started and electro-
lyte abnormalities corrected. Fluid balance and
Typically patient presents with serum glucose vital signs need to be carefully monitored and
levels greater than 300 mg/dL; however this documented.
threshold is much lower in pregnancy and DKA
can occur with levels <200 mg/dL(13). Basic labs, including a complete metabolic pan-
el with magnesium and phosphorous, complete
Precipitating factors for diabetic ketoacidosis in- blood count with differential, urinalysis, fin-
clude emesis, infection, previously undiagnosed gerstick blood glucose, arterial blood gas and
diabetes, beta-sympathomimetic tocolytic serum ketones should be collected. Additional
agents, corticosteroids, poor compliance, pump testing (urine culture, blood culture, chest X ray,
malfunctions and medical errors(14,15). While be- etc.) should be performed based on clinical sus-
ta-sympathomimetics (eg. terbutaline) are not picion and any potential underlying processes.
routinely used for prolonged (>48 hrs) tocolysis Initially, urine/serum ketones, electrolytes and
due to the FDA safety communication in 2011 maternal acid/base status should be monitored
warning potential for serious maternal heart every 2 hours until ketosis and acidosis resolved.
problems and death, it is important to remem- Blood sugars should be collected hourly during
ber that they should be used very cautiously, if this time to titrate appropriate insulin doses (11,12
ever, for patients with diabetes (11). 16-18)
.

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 Endocrine emergencies

Once viability is confirmed, fetal monitoring line) should be avoided initially as they can cause
should be initiated. As noted, the fetal heart a rapid decline in plasma osmolarity leading to
tracing will likely appear concerning during the cerebral edema. Blood glucose values should
initial insult. Maternal oxygen supplementation be monitored hourly as they will decrease with
and favorable maternal positioning should be initial hydration alone. Once the serum glucose
employed to increase blood flow to fetus and reaches <250 mg/dL fluids should be switched to
improve oxygenation. Adequate hydration and D5-0.45% normal saline.
correction of acid/base derangements must be
started. Delivery should usually be postponed Intravenous insulin administration should be
until after maternal metabolic condition is sta- undertaken immediately to aid in lowering blood
bilized, as this will usually correct the fetal heart glucose levels associated with lipolysis and ke-
tracing abnormality. There are exceptions, in- togenesis. Subcutaneous and intramuscular
cluding intractable bradycardia or persistent are typically avoided due to the slower onset of
Category III tracings. action, which is worsened in DKA 12. The initial
blood glucose target is 150-200 mg/dL in order
Figure 1 illustrates the goals of treatment for to avoid rapid correction and resulting compli-
any patient with diabetic ketoacidosis, including cations.
rehydration, reduction of hyperglycemia, cor-
rection of acid-base and electrolyte imbalance It is important to continue the insulin infusion
while searching for and treating the underlying until the anion gap is closed and acidosis re-
etiology(11,12,16-18). solved. This can take significantly longer than
correcting the hypoglycemia and typically takes
The fluid deficit leading to the profound intra- 12-24 hours.
vascular depletion is estimated at 100 mL/kg of
total body weight and is typically 4-10 liters(19). It is important to remember that insulin require-
Initially, aggressive intravenous replacement ments can be significant and most protocols sug-
with isotonic normal saline should be started gest an initial bolus dose of 10-20 units of regu-
with the goal to replace approximately 75% of lar insulin, followed by an infusion rate of 5-10
the overall deficit within the first 24 hours. Hy- units/hour. This amount should be increased if
potonic fluids (e.g. lactated ringers and 0.45% sa- the blood glucose values do not fall 25-20% over
two hours. Once it is deemed safe to transition
Figure 1. Diabetic ketoacidosis algorithm. to subcutaneous insulin, the first dose should be
given prior to the discontinuation of the intrave-
Maternal nous infusion to decrease the risk of recurrent
ketoacidosis.

Volumen Potassium is the most common electrolyte

Cause Hyperglycemia abnormality in DKA. The levels are often
Repletion
Thorough History and Estimate Fluid deficit Begin Insulin therapy normal at the time of initial DKA diagnosis;
Physical (~100 mL/kg) FSBG hourly however the actual deficit is estimated at
Rule out infection Place foley catheter Treat initially with Regular
(UA/Urine Cx, CXRAY) Monitor Ins/Outs 5-10meq/kg and replacement should begin
Insuin via IV (either
Treat underlying cause Correct 75% total deficit in continuous drip or hourly after fluid and insulin therapy has begun, as
1st 24hrs bolus) well as adequate renal function established
Start with isotonic fluid
(eg 0.9% NS)
Continue until AG closed, (i.e. do not start until you ensure appropriate
ketosis cleared
Labs Convert to D5 0.45NS urine output). The goal is to maintain potassi-
Start SQ insulin therapy
when FSBG <250mg/dL um levels between 4-5mmol/L and is not be-
prior to stopping IV
BMP, Mag/Phos every Replete electrolytes
Stop fluids once estimated insulin gun until the serum potassium falls below 5.
2-4 hours
Replete K+ once deficit corrected Potassium chloride is typically used and can
<5mmol/L (ensure either be added to the maintenance IV fluids
normal renal function). Fetal of repleted separately. Serum potassium lev-
ABG every 2 hours Initiate fetal monitoring els should be checked every 2-4 hours as sig-
Serum/Urine ketones Left lateral decubitus, oxygen to improve fetal nificant hypokalemia can precipitate a cardiac
every 2 hours (until environment
resolved) Stabilize maternal condition PRIOR to considering arrhythmia.
delivery

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 Christopher G. Goodier

Replacement of low serum bicarbonate levels re- ciation of Clinical Endocrinologists. Endocr Pract. 2011 May-
main a source of controversy and replacement is Jun;17(3):456-520.
generally agreed upon if the patients pH is <7.0.
Some studies have shown that routine replace- 9. Gianantonio E, Schaefer C, Mastroiacovo P. Adverse fe-
ment of low serum levels of bicarbonate have tal effects of prenatal methimazole exposure. Teratology.
not proven beneficial in DKA and may cause un- 2001;64(5):262-6. DOI: 10.1002/tera.1072.
necessary maternal and fetal complications. Re-
placement can delay the correction of ketoacids 10. Vyas AA, Vyas P, Fillipon NL, Vijayakrishnan R, Trivedi N. Suc-
in the maternal bloodstream and, if corrected to cessful treatment of thyroid storm with plasmaphoresis in
rapidly, elevate fetal PCO2 impairing fetal ability a patient with MMI-induced agranulocytosis. Endocr Pract.
to maintain adequate O2 transfer (11,18). 2010 Jul-Aug;16(4):673-6. DOI:10.4158/EP09265.CR.

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