Critical Care Obstetrics part 45 ppsx

[43] reported a higher incidence of neonatal thyrotoxicosis in four infants of 44 mothers with Graves ’ disease; in all four cases, the mothers had TBII levels greater than 70%.. In pati

years after the diagnosis of Graves ’ disease, when the mother is either euthyroid or hypothyroid after radioactive thyroid abla-tion Thyroid disease in pregnancy has recently been reviewed by Glinoer [41]

Neonatal thyroid status may be affected transiently by either thionamides therapy or thyroid receptor antibodies The inci-dence of neonatal hyperthyroidism or hypothyroidism due to maternal passive transmission of thyroid receptor antibodies appears to be 1 – 3% [38] Mitsuda et al [42] reported overt thy-rotoxicosis in six neonates of 230 women with Graves ’ disease In four of the mothers, TBII levels were elevated In addition, tran-sient hypothyroidism was found in fi ve neonates with normal TBII levels and thionamides treatment Mortimer et al [43] reported a higher incidence of neonatal thyrotoxicosis in four infants of 44 mothers with Graves ’ disease; in all four cases, the mothers had TBII levels greater than 70% These investigators observed that the neonatal free T4 index correlated inversely with maternal thionamides dose In addition, women who had a free T4 index in the lower half of the reference range on thionamides were more likely to deliver a child with an elevated TSH than women with a free T4 index in the upper half of the reference range Similarly, Momotani et al [44] studied 43 women main-tained on thionamide therapy until delivery and 27 women in whom thionamides therapy was discontinued due to normaliza-tion of thyroid funcnormaliza-tion tests prior to delivery They found in women who took thionamides until delivery, a greater number had fetuses with increased TSH levels, lower T4 levels, and higher maternal TBII levels It is important to note that in both of these studies there was only evidence of mild chemical, not clinical, hypothyroidism However, taken together these data suggest that the minimal dose of thionamides therapy should be used to keep maternal thyroid function at the upper limits of normal Because TBII antibodies are positive although at lower levels in 50 – 80%

of women with Graves ’ disease [38,43,44] , their utility remains to

be further demonstrated In patients with Graves disease, the fetal heart rate may also be an indicator of fetal thyroid function and should be auscultated for a persistent fetal heart rate tachycardia

at each prenatal visit In 1 – 5% of cases, TSH receptor - stimulating antibodies may cross the placenta producing fetal/neonatal thy-rotoxicosis Findings suggestive of fetal thyrotoxicosis could include the presence of a persistent fetal heart rate tachycardia [45] , fetal goiter, or intrauterine growth impairment

Wing et al [28] found that only one infant of 185 women treated with propylthiouracil or methimazole had transient hypo-thyroidism at birth Similarly, Davis et al [27] found one neonate had transient hypothyroidism and a second was euthyroid with

an asymptomatic goiter among 43 mothers receiving propylthio-uracil Both were on high doses of propylthiouracil at the time of delivery This is consistent with a review of the literature by Mandel et al [46] in which the incidence of neonatal goiter in women exposed to antithyroid medications was 4% PTU may be concentrated in the fetal compartment since umbilical blood levels were higher than maternal serum samples in fi ve maternal – fetal pairs [47]

onset of pregnancy that the free T4 index was increased in the

fi rst trimester, fell in the second and third trimester, and was

again increased postpartum A fall in antimicrosomal antibodies

during pregnancy and an increase postpartum was also measured

in patients with Graves ’ disease or postpartum thyroiditis [34]

For further information, the reader is referred to a recent review

of postpartum thyroiditis, which occurs in 5 – 7% of patients [35]

The diagnosis of Graves ’ disease is suggested by the presence

of thyrotoxicosis, ophthalmopathy, a diffuse goiter, dermopathy,

and thyroid receptor antibodies The diagnosis is clinical and is

supported by thyroid function tests; thyroid receptor antibody

tests are often not necessary but levels of the antibodies at 36

weeks correlate with the risk of neonatal thyrotoxicosis [36]

However, pretibial dermopathy is rarely present in pregnant

women, and active clinical ophthalmopathy is evident in only half

of patients with Graves ’ disease [37,38] Exophthalmos, weakness

of the extraocular muscles, chemosis, and impairment of

conver-gence are signs of infi ltrative ophthalmopathy and may remain

despite normalization of thyroid hormone levels

In pregnancy, the signs and symptoms of hyperthyroidism are

slightly more diffi cult to interpret due to the normal changes that

occur during gestation Heart rate and cardiac output increase,

and heat intolerance, nausea, and weight loss are common

Thyrotoxicosis is suggested by clinical fi ndings which include a

pulse rate persistently greater than 100 that fails to decrease with

Valsalva in the presence of a tremor, previously mentioned signs,

thyroid bruit, thyromegaly, and mild systolic hypertension The

cardiac effects of hyperthyroidism are summarized in Table 33.2

An elevated free T4 and low serum TSH confi rms the diagnosis

Clinical signs of thyrotoxicosis without elevated total or free T4

should suggest free T3 thyrotoxicosis or defi cient TBG states [39]

but these are much less common

“ Thyroid receptor antibodies ” is a generalized term that may

be used to include both thyroid - stimulating immunoglobulins

(TSIs) as well as thyrotropin - binding inhibitor immunoglobulins

(TBIIs) and may be a useful predictor of neonatal thyroid

dys-function [40] Consequently, neonatal thyroid effects may occur

Table 33.2 Cardiovascular changes in hyper - and hypothyroid states

Hyperthyroid Hypothyroid

Systemic vascular resistance ↑ ↓

↓ QT, ↑ PR interval Pleural effusion

ST elevation ↑ QT interval

↑ conduction abnormalities

lowed by a continuous infusion at 50 – 100 µ g/kg/min Labetalol has also been used successfully [55] Although β - adrenergic blockade may inhibit peripheral conversion of T4 to T3, this does not alter thyroid release and does not prevent thyroid storm [56,57] Because large increases in pulmonary diastolic pressure may be precipitated [58] and because congestive heart failure may

be a common presentation of thyroid crisis in pregnant women, propranolol and other β - blocking agents should be used with caution

Corticosteroids have been advocated for inhibiting peripheral conversion of T4 and to prevent adrenal insuffi ciency, but there are few data to support their use Fever should be treated with cooling blankets or acetaminophen to decrease cardiovascular demands A thorough search for underlying infection is necessary because pyelonephritis, endometritis, or sepsis are common pre-cipitating factors Because of the increased incidence of atrial arrhythmia and central nervous system emboli, thromboembolic disease should be considered in the patient with altered mental status that does not respond to the aforementioned therapy [59] Complications of propylthiouracil and methimazole include chemical hepatitis, rash or other drug reactions (5%) and rarely agranulocytosis (0.3%) [60] Because of the seriousness of the latter, patients with fever or sore throat should be instructed to discontinue mediation until a white cell count is checked Agranulocytosis, as defi ned by a total leukocyte count of < 1,000/

mm 3 or granulocyte count of less than 250/mm 3 , is generally seen

in older patients and within 2 months of the onset of therapy [60] Finally lactation may be continued if the total dose of pro-pylthiouracil does not exceed 450 mg/day and if methimazole dosage does not exceed 20 mg/day [61,62] See Table 33.3 for an overview of thyroid storm management in pregnancy

Hypothyroidism

Overt hypothyroidism during pregnancy is uncommon as many women with overt hypothyroidism are anovulatory The most common etiologies are prior surgical thyroidectomy, radioiodine, ablation, and autoimmune thyroiditis Clinical signs and symp-toms include delayed deep tendon refl exes, fatigue, weight gain, cold intolerance, hair loss, dry skin, brawny edema, thickened tongue, hoarse voice, hypertension, and bradycardia, some of which are more diffi cult to ascertain during pregnancy The hemodynamic changes of hypothyroidism are summarized in the table Hyponatremia, ascites, pericardial effusions, or psychosis are not commonly present but may herald myxedema coma Laboratory confi rmation of hypothyroidism can be established

by a low free T4 in the presence of an elevated TSH However, TSH levels may be suppressed in the fi rst trimester with less sensi-tive tests and undetectable in as many as 13% of women [63] More sensitive TSH assays are unlikely to return undetectable Although earlier studies of hypothyroidism suggested an increase in congenital anomalies, perinatal mortality, and infant neurologic dysfunction, more recent studies report better out-comes with adequate replacement [64] Leung et al [65] studied

23 women with overt hypothyroidism and 45 women with

In thyroid crisis or storm, an acute increase in the signs and

symptoms of thyrotoxicosis may be life - threatening The overall

incidence of thyroid crisis in women who receive thionamides

treatment during pregnancy, some of whom remain thyrotoxic,

is about 2% [27] A clinical diagnosis must be established and

treatment initiated well before confi rmatory thyroid function

tests are available The classic signs of thyroid storm (altered

mental status, temperature above 41 ° C, hypertension, and

diar-rhea) are not necessarily present Postpartum congestive heart

failure, tachycardia, and severe hypertension should suggest the

diagnosis and prompt an evaluation for other signs of

thyrotoxi-cosis [48] Rarely loss of consciousness following cesarean section

[49] or seizures mimicking eclampsia [50] may complicate the

presentation of thyrotoxicosis

The risks appear to be related to metabolic status and to the

precipitating cause Pekonen et al [51] reported that two of seven

untreated thyrotoxic women in labor developed thyroid crisis

Similar results were described in eight untreated women in labor,

of whom fi ve developed heart failure, and four had stillbirths

[27] In that series, among 16 other women who had received

thionamides but were still thyrotoxic at the time of delivery, two

had stillbirths and one developed heart failure whereas there were

no complications in 36 women who were euthyroid In an

expanded review, Sheffi eld and Cunningham [52] found that

nearly 10% of thyrotoxic women developed reversible congestive

heart failure Kriplani et al [29] also reported three patients who

developed thyroid storm, including one maternal death, among

32 patients who were hyperthyroid during pregnancy Although

thyroid functions were not specifi cally detailed, thyroid storm

was associated with either emergent operative delivery or

infec-tion Thionamide therapy, even of short duration, is generally

effective in preventing storm Therefore, congestive heart failure

that occurs after administration of propylthiouracil should

suggest another precipitating event, such as underlying infection,

hypertension, or anemia

The treatment of thyroid storm is somewhat empiric and

con-sists of thionamides, iodide, and β - blockers Therapy differs from

the usual management of hyperthyroidism in the dose and choice

of thionamide Although propylthiouracil and methimazole are

equally effective in the treatment of hyperthyroidism in

preg-nancy [28] , in the setting of thyroid storm, propylthiouracil is

administrated by mouth and if necessary by nasogastric tube to

inhibit peripheral conversion of T4 to T3 Despite inhibition of

T4 synthesis, it may take 7 – 8 weeks of therapy to deplete thyroid

colloid stores and normalize thyroid function tests [27,28]

Clinical improvement commonly precedes resolution of the

tachycardia due to the long half - life of T4 Iodide inhibits thyroid

release rapidly [53,54] Iodide should be given only after

propyl-thiouracil is administered and should be discontinued when there

is clinical improvement to avoid the risk of congenital goiter if

the pregnancy continues Propranolol (1 mg IV every 5 minutes

and repeated as necessary) may be used to control autonomic

symptoms The fast - acting/short half - life β - blocker, esmolol, is

also a reasonable choice The loading dose is 250 – 500 µ g/kg

fol-measurement should be used to guide thyroid replacement therapy because of the advantage of treating subclinical thyroid disease [26,71]

The importance between the maternal and fetal thyroid axis has recently been examined A study using 25 216 second - trimes-ter matrimes-ternal serum α - fetoprotein samples [72] selected 62 women with TSH levels greater than the 98th percentile At 8 years of age, the children of women with elevated TSH levels had a mean IQ that was 4 points less than matched controls (p = 0.06) In 48 of the women who did not receive thyroid replacement during preg-nancy, the IQ was 7 points less than matched controls (p = 0.05) and these children scored lower on 8 of 15 neuropsychological tests Within 11 years, 64% of the untreated women and 4% of the match - control women had confi rmed hypothyroidism Similar differences have been found by Pop et al [73] A recent workshop was held to discuss the many issues surrounding hypo-thyroidism and pregnancy [74] Although universal thyroid screening is not currently recommended [21,45] , screening of women with a history of thyroid disorders and normalization of TSH levels would appear benefi cial in these women

Pheochromocytoma

Pheochromocytoma is a rare tumor of catecholamine - secreting chromaffi n cells Recent reviews have noted 43 cases associated with pregnancy between 1988 and 1997 [75 – 77] Compared to the period of 1980 – 1987, maternal mortality fell from 16 to 2%, fetal loss decreased from 26 to 11%, and cases diagnosed antena-tally increased from 52 to 83%

The most common signs are hypertension (90%), headache, excessive truncal sweating, and paroxysmal attacks in 40 – 50% of patients Pallor, fl ushing, anxiety, chest pain, nausea, and vomit-ing are less common The diagnosis should be considered in the differential with hyperthyroidism and pre - eclampsia as higher maternal mortality is increased with hypertensive crisis when the diagnosis is not established prior to delivery [75] Most (90%) pheochromocytomas occur sporadically and some 10% are asso-ciated with familial disorder including multiple endocrine neo-plasia (MEN) II syndromes, von Recklinghausen ’ s disease, or von Hippel – Lindau syndrome [78] Hypertension in the setting of caf é - au - lait spots and neurofi bromas should raise the suspicion

of pheochromocytoma Genetic screening may be warranted not only in familial syndromes [79] but also in sporadic cases [80] MEN 2A is an autosomal dominant syndrome in which medul-lary thyroid carcinoma is associated with pheochromocytoma and hyperparathyroidism A more extensive review of pheochro-mocytoma has been published by Prys - Roberts [78]

Advances in biochemical testing have improved the diagnosis Table 33.4 summarizes the sensitivity and specifi city of plasma and urine tests [79] If biochemical evaluation and the history suggest a pheochromocytoma, MRI can be safely performed in pregnancy to confi rm the presence of an adrenal mass, as 90% of pheochromocytomas arise in the adrenal glands After delivery,

clinical hypothyroidism (elevated TSH level with a normal T4

index) One stillbirth occurred in an untreated overtly

hypothy-roid patient who was also eclamptic Other than one infant with

clubfeet, neonatal outcomes were satisfactory Pre - eclampsia,

pregnancy - induced hypertension, and eclampsia were common

in women who were not yet euthyroid at delivery (9/30 subjects)

In another study of 16 pregnancies in overtly hypothyroid women

and 12 cases of subclinical hypothyroidism, complications were

more common in overtly hypothyroid women including

postpar-tum hemorrhage, anemia, pre - eclampsia, and placental

abrup-tion [66] Two women also had evidence of cardiac dysfuncabrup-tion,

one of whom developed congestive heart failure It is likely that

the etiology of the increase in abruption was secondary to the

higher incidence of chronic hypertension in hypothyroid patients

[67] Rarely hypothyroid patients may have prolonged bleeding

times that normalize with T4 replacement [68]

As previously mentioned, thyroid replacement requirements

may increase during pregnancy [64,69] Mandel et al [25] found

it necessary to increase the mean T4 dose from 102 to 147 µ g/day

in 9 of 12 patients in order to normalize TSH levels Another

group of investigators studied 35 pregnancies and noted that only

20% of women required an increase in T4 dosage [70] TSH

Table 33.3 Treatment of thyroid storm

Propylthiouracil 800 mg administered orally, then 150 – 200 mg every 4 – 6 hours

Starting 1 – 2 hours after propylthiouracil administration

Saturate solution of potassium iodide 2 – 5 drops orally every 8 hours, or

Sodium iodide 0.5 – 1.0 g IV every 8 hours

Dexametasone 2 mg IV every 6 hours for 4 doses

β - blockade to decrease hypermetabolic state

Propranolol 12 mg IV, repeated every 5 min, up to a total of 6 mg for extreme

tachycardia or

Esmolol 250 – 500 µ g/kg IV loading dose followed by 50 – 100 µ g /kg/min

continuous infusion

Treatment of anxiety/restlessness

Hydroxyzine 50 – 100 mg orally every 6 hours or

Lorazepam 1 – 2 mg orally every 6 – 8 hours or 20 – 25 µ g /kg IV every 6 hours

Phenobarbital 30 – 60 mg every 8 hours as needed for extreme restlessness

Search for precipitating event, in particular infection

Control temperature if hyperthermic

Acetaminophen 500 – 1000 mg every 4 – 6 hours, not to exceed 4000 mg/day

Cooling blanket

Critical tests

Free T4, TSH, urine culture

Evaluate for other autoimmune disorders

Chest X - ray if indicated

EKG (atrial fi brillation)

and the expanded extracellular fl uid volume result in an overall decrease in total serum calcium levels of 0.5 mg/dL [88] However, ionized calcium levels are not affected Pregnant women with primary hyperparathyroidism have biochemical parameters similar to those who are not pregnant [89] In normal gestation, PTH levels are stable or slightly lower in the second trimester, refuting earlier studies of elevated PTH levels [90 – 92] Thus, repeatedly elevated PTH levels in the presence of increase ionized calcium, or total calcium adjusted for albumin, must be consid-ered signifi cant

When hyperparathyroidism is diagnosed, a search for MEN is indicated [87] Most non - parathyroid causes of hypercalcemia are associated with suppression of PTH and urinary cAMP levels Non - parathyroid causes of hypercalcemia include malignancy (breast, melanoma, lymphoma), hypocalcuric hypercalcemia (familial, thiazides, lithium), granulomatous disease (sarcoidosis, tuberculosis), thyrotoxicosis, drug - induced causes (hypervita-minosis D or A, calcium, milk – alkali syndrome), adrenal

insuf-fi ciency, and immobilization Hypercalcemia secondary to PTH - related protein produced by breast tissue during pregnancy and lactation with normal PTH levels has also been reported [93]

A history should include the use of over - the - counter vitamin preparations and other medications

Primary hyperparathyroidism may be due to parathyroid ade-nomas (89% of cases), parathyroid hyperplasia (9%), or parathy-roid cancer (2%) [94] The majority of patients with primary hyperparathyroidism are thought to be asymptomatic and are found to have elevated serum calcium levels on routine screening However, on closer questioning, nearly half of these patients may complain of weakness or fatigue [95] Approximately 20% of patients with hyperparathyroidism will have nephrolithiasis Other common signs and symptoms include nausea or vomiting, mental disturbances, pancreatitis, and bone pain [83,96,97] Hypercalcemic crisis is characterized by progressive hypercalce-mia with hypovolehypercalce-mia, renal insuffi ciency, altered mentation, and pancreatitis in the most severe cases Rarely, seizures from hypercalcemia may mimic eclampsia [98]

The only defi nitive treatment is surgical removal of the glands Since only 25% of asymptomatic patients will have progressive disease, which is usually in the form of a decrease in bone mass, the management of asymptomatic hyperparathyroidism is some-what controversial In non - pregnant patients with mild to mod-erate hyperparathyroidism that was left untreated, no increase in mortality was seen The only increase in mortality occurred in those patients with serum calcium levels in the uppermost quar-tile [99] Treatment during pregnancy, however, may be war-ranted in view of the risk of neonatal tetany as well as the increase

in perinatal complications including miscarriage and stillbirth seen in maternal hypercalcemia [100]

There is no satisfactory medical treatment for primary hyperparathyroidism in the pregnant or non - pregnant state Mithramycin and bisphosphonates are contraindicated during pregnancy Asymptomatic patients with mild hypercalcemia can

be followed closely through pregnancy, with surgery deferred

radioactive iodine - labeled metiodobenzylguanidine scintigraphy

offers greater than 95% specifi city in the detection [79] of a

pheochromocytome

The most frequently used treatment consists of non - specifi c

α- adrenergic blockade with phenoxybenzamine given by

mouth, 10 mg daily, increased by 0.5 – 1.0 mg/kg/daily [76,79]

Alternatively, the shorter - acting selective α 1 - blocker prazosin is

less likely to cause tachycardia The initial dosage is 1 mg three

times a day, increased to 2 – 5 mg three times a day Beta - blockers

should be used in conjunction only after adrenergic blockade is

initiated as unopposed α - adrenergic activity may lead to

vaso-constriction and a marked increase in blood pressure Commonly,

labetalol is used as it has both α - and β - adrenergic antagonist

properties As hypertension is the most common presenting

feature, pre - eclampsia will often be included in the differential

diagnosis Interestingly, magnesium sulfate given as a bolus

fol-lowed by a 2 - g infusion has been used in non - pregnant patients

for operative control during surgical removal of

pheochromocy-toma [81,82] The use of magnesium sulfate may therefore be

advantageous

Hyperparathyroidism

Primary hyperparathyroidism is more common in women than

men (3 : 1 ratio) Since the average age of diagnosis is 55 years,

the combination of hyperparathyroidism and pregnancy is

uncommon Approximately 145 cases of primary

hyperparathy-roidism have been reported during pregnancy, which is

propor-tionately less than the expected incidence of 8 new cases per

100 000 per year in women of childbearing age [83,84] The

dis-crepancy is in part due to the asymptomatic nature of most cases

of hyperparathyroidism Combining the results of two series

[85,86] , the majority of patients were diagnosed postpartum

fol-lowing the presentation of neonatal tetany A recent review

sum-marizes parathyroid disorders [87]

Whether in pregnancy or not, the diagnosis of

hyperparathy-roidism is suggested by elevated levels of ionized calcium in the

presence of inappropriately elevated parathyroid hormone

(PTH) The majority of calcium is bound to albumin The

reduced serum albumin levels in pregnancy, acquisition by the

fetus of 25 – 30 g of calcium, increase in glomerular fi ltration rate,

Table 33.4 Biochemical tests for pheochromocytoma

Test Sensitivity (%) Specifi city (%)

Chronic candidiasis, alopecia, vitiligo, and multiple endocri-nopathies should suggest the autoimmune polyendocrinopathy – candidiasis – ectodermal dystrophy syndrome [87,106] Perioral paresthesias, psychiatric disturbances, and Chvostek ’ s or Trousseau ’ s sign may be present Trousseau ’ s sign, also known as the “ obstetrician ’ s hand ” , or carpal spasm due to ulnar and median nerve ischemia, is elicited by infl ating a sphygmomanom-eter cuff around the arm to 20 mmHg above systolic pressures The thumb adducts and the fi ngers are extended, except at the metacarpophalangeal joints, within minutes, indicating latent tetany Cardiac changes of hypocalcemia are non - specifi c but include electrocardiogram Q – T prolongation, hypotension, and reversible congestive cardiomyopathy [104,107] Hypopharyngeal tetany may present as stridor and seizures and may be life - threat-ening Magnesium sulfate rarely has been implicated in hypocal-cemia and should be used cautiously when pre - eclampsia is superimposed on hypoparathyroidism [108] Dilantin may increase vitamin D metabolism In one case, decreased fetal heart rate variability was reported although there was no evidence of acidosis [109] Secondary fetal or neonatal hyperparathyroidism, bone demineralization, and skeletal and skull fracture have been reported

Medical treatment of hypocalcemia can be divided into long term and acute management Vitamin D (50 000 – 100 000 units/ day) or 1,25 - dihydroxyvitamin D (calcitriol 0.5 – 3.0 µ g/day) and

1 – 2 g/day of elemental calcium have been used successfully in pregnancy [88] Vitamin D 2 is the least expensive form of vitamin

D, but several weeks may be needed for its full effect Calcitriol has a faster onset of action (1 – 2 days) but requires more frequent monitoring to prevent hypercalcemia Requirements during pregnancy may increase in the latter half of pregnancy, presum-ably due to increased vitamin D - binding protein It is often nec-essary to reduce replacement doses in the postpartum period to avoid hypercalcemia, even in women who are breastfeeding [110] The latter require closer monitoring of calcium levels, because it may be diffi cult to predict calcium need during lacta-tion Of interest, in some species (cattle in particular), the onset

of lactation can result in hypocalcemia and parturient paresis [111]

Acute hypocalcemia or impending signs of tetany are treated by 10% calcium gluconate (10 mL diluted in 150 mL

of D5W given over 10 minutes), followed by continuous infusion of calcium (0.5 – 2.0 mg/kg/h) Serial calcium measure-ments should be measured initially every 2 – 4 hours to assess the adequacy of the administered dose and adjust the infusion rate accordingly [112] Laboratory evaluation in addition to ionized calcium should include magnesium, phosphorus, and PTH levels Hypoparathyroidism is diagnosed by normal serum magnesium concentration, low or inappropriately normal PTH level, and low ionized calcium High PTH and low phosphorus levels suggest vitamin D defi ciency, whereas high PTH and high phosphorus levels are consistent with the diagnosis of pseudohypoparathyroidism or renal insuffi ciency

until after delivery [85,101,102] Occasionally, a patient with

sig-nifi cant symptoms due to hypercalcemia but who is not a surgical

candidate has been controlled safely and effectively with oral

phosphate therapy (1.5 g/day in divided doses) throughout

gesta-tion [103] This therapy is only indicated in patients in whom the

initial serum phosphorus level is less than 3 mg/dL; phosphate

administration should be adjusted to maintain serum phosphate

below 4 mg/dL Furosemide increases the excretion of calcium in

the urine and can be given orally to help lower the serum calcium

levels on a chronic basis In contrast, patients with progressive

symptoms, signifi cant hypercalcemia ( > 12 mg/dL), or

deteriora-tion of renal funcdeteriora-tion should be treated surgically by an

experi-enced parathyroid surgeon [83,94] Neck exploration should not

be deferred in the symptomatic woman because of pregnancy,

unless delivery is imminent [83]

Medical management for stabilization in hypercalcemic crisis

includes hydration with normal saline (2 – 3 L over 3 – 6 hours),

correction of electrolyte abnormalities, furosemide, which

decreases distal tubular calcium reabsorption (10 – 40 mg IV every

2 – 4 hours) to maintain urine output at 200 mL/h, and calcium

restriction Hypercalcemia resistant to this regimen may be

allevi-ated with more potent agents, such as calcitonin (100 – 400 units/

day) Although effective initially, tachyphylaxis to calcitonin

gen-erally occurs in 4 – 6 days Glucocorticoids can be used to decrease

gastrointestinal calcium absorption The reader is referred to a

recent review [84] for greater detail

In hyperparathyroid mothers, neonatal hypocalcemia is

pre-dictable and can be prevented Transient neonatal tetany should

not be associated with long - term sequelae Management of

maternal hyperparathyroidism diagnosed during pregnancy

should be individualized, taking into consideration the patient ’ s

symptoms, the gestational age of the fetus, and the severity of the

disease

Hypoparathyroidism

Hypocalcemia caused by hypoparathyroidism is an extremely

rare disorder in pregnancy The most common cause of

hypo-parathyroidism is non - production of PTH because of excision

of the parathyroid gland, usually following thyroidectomy

Anywhere from 0.5 to 3.5% of thyroid surgeries result in

hypo-parathyroidism As mentioned earlier, although total calcium

concentration decreases in pregnancy, ionized calcium does not

[88,90] In response to hypocalcemia, PTH normally increases,

which in turn augments renal tubular calcium reabsorption and

phosphate excretion PTH also increases 25 - hydroxyvitamin D

transformation to the active hormone 1,25 - dihydroxyvitamin D,

which stimulates intestinal calcium and phosphate absorption as

well as osteoclastic bone reabsorption [87] Ineffective PTH

syn-dromes may be caused by failure to respond to increased PTH

(pseudohypoparathyroidism), defi cient vitamin D from

malab-sorption, or increased vitamin D metabolism seen with phenytoin

or other anticonvulsants [104,105]

However, abnormal ACTH testing measures physiologic reserve and does not necessarily predict whether adrenal crisis will develop following stress The risk of clinically apparent adrenal insuffi ciency developing in unsupplemented patients undergoing surgery is well recognized [117] In obstetric patients, chemical adrenal suppression has been noted in women receiving two courses of betamethasone for fetal lung maturation, yet neither

of these patients had clinical signs of adrenal insuffi ciency during pregnancy [118] One suggested regimen is to use hydrocortisone

100 mg every 8 hours for 24 hours if the patient has received more than 20 mg of prednisone daily for more than 3 weeks within the previous year [114]

For chronic replacement in patients with primary adrenocorti-cal insuffi ciency, doses are similar to those in the non - pregnant patient: hydrocortisone 20 mg each morning and 10 mg each evening Since this dosage of hydrocortisone does not replace the adrenal mineralocorticoid component, mineralocorticoid sup-plementation is usually needed This is accomplished by the administration of 0.05 – 0.2 mg/day fl uorocortisone by mouth Patients should also be instructed to maintain an ample intake of sodium (3 – 4 g/day) During conditions of increased sweating, exercise, nausea and vomiting, these doses may need to be increased

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Adrenal c risis

Adrenal insuffi ciency may be primary or secondary The most

common cause of primary adrenal insuffi ciency (Addison ’ s

disease) is idiopathic or autoimmune adenitis Less frequently,

tuberculosis, sarcoidosis, AIDS, or bilateral hemorrhage

(antiphospholipid syndrome or anticoagulation) may be the

cause Autoimmune adenitis may be associated with gonadal

failure, hypothyroidism, hyperthyroidism, Hashimoto ’ s

thyroid-itis, vitiligo, hypoparathyroidism, and pernicious anemia

(poly-glandular failure type I or II) For further details, the reader is

referred to the review of Williams and Dluhy [113] Except for

those patients on corticosteroid therapy for other medical reasons,

secondary adrenal insuffi ciency is rare in pregnancy

Adrenal insuffi ciency is more commonly diagnosed during the

puerperium than earlier in pregnancy, in part due to the similar

symptoms of pregnancy, including nausea, fatigue, diffuse tan or

bronze darkening of the elbows or creases of the hands, and

bluish - black patches that may appear on the mucous membranes

Axillary and pubic hair may be reduced as adrenal androgens are

diminished The diagnosis may not be suspected until adrenal

crisis develops, with potentially serious sequelae Pregnancy may

be well tolerated until stresses such as infection, trauma, surgery,

labor, or dehydration from vomiting or diarrhea precipitate

adrenal crisis The clinical features of acute primary

adrenocorti-cal insuffi ciency include hypotension and shock (cardiovascular

collapse), weakness, apathy, nausea, vomiting, anorexia,

abdomi-nal or fl ank pain, and hyperthermia Electrolyte abnormalities

include hyponatremia, hyperkalemia, mild azotemia, and

metabolic acidosis Hypoglycemia and mild hypercalcemia may

also be seen Importantly, secondary adrenal insuffi ciency may

present similarly but without electrolyte changes (normal renin –

aldosterone response) and should be considered in patients

previously on corticosteroids

Treatment of acute adrenal insuffi ciency includes

hydrocorti-sone 100 mg IV every 6 hours for 24 hours This dose can be

reduced to 50 mg every 6 hours if the patient is improving, and

tapered to an oral maintenance dose in 4 – 5 days Doses of

hydro-cortisone in the range of 100 – 200 mg maximize

mineralocorti-coid effects and therefore supplementary mineralocortimineralocorti-coid is not

necessary [113] Additional therapy includes intravenous saline

and glucose and correction of precipitating factors (infection)

and electrolyte abnormalities Volume replacement is critical in

improving cardiovascular status Patients with cardiovascular

collapse may not respond well to pressor agents until

hydrocor-tisone is given

Patients on chronic corticosteroid therapy should receive stress

doses for infections, surgery, labor, and delivery Adrenal

sup-pression is unlikely to occur when corticosteroids are used for less

than 3 weeks [114] Following withdrawal of prolonged

cortico-steroids, approximately 70% of patients will have normal

func-tion within a month but in some individuals up to 9 months may

be necessary for restoration of normal function [115,116]

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Critical Care Obstetrics, 5th edition Edited by M Belfort, G Saade,

M Foley, J Phelan and G Dildy © 2010 Blackwell Publishing Ltd.

Gary A Dildy III 1 & Michael A Belfort 2

1 Maternal - Fetal Medicine, Mountain Star Division, Hospital Corporation of America, Salt Lake City, UT and Department of

Obstetrics and Gynecology, LSU Health Sciences Center, School of Medicine in New Orleans, New Orleans, LA, USA

2 Department of Obstetrics and Gynecology, Division of Maternal - Fetal Medicine, University of Utah School of Medicine, Salt

Lake City, UT and HCA Healthcare, Nashville, TN, USA

Introduction

Hypertensive disorders complicate 6 – 8% of pregnancies and

remain signifi cant contributors to maternal and perinatal

mor-bidity and mortality [1] Classifi cation systems of hypertensive

diseases during pregnancy tend to be confusing A National

Institutes of Health (NIH) sponsored working group proposed a

modifi ed classifi cation system (Table 34.1 ) for the purpose of

providing clinical guidance in managing hypertensive patients

during pregnancy Chronic hypertension is defi ned as

hyperten-sion that is present before pregnancy or diagnosed before the 20th

week of gestation Pre - eclampsia is defi ned as the appearance of

hypertension plus proteinuria, usually occurring after 20 weeks

of gestation Chronic hypertension may be complicated by

super-imposed pre - eclampsia or eclampsia In this classifi cation system,

gestational hypertension is reassigned retrospectively following

the puerperium as transient hypertension of pregnancy or chronic

hypertension

In the United States, pre - eclampsia is one of the top three

causes of maternal mortality in advanced gestations [2 – 5]

Substandard care is often an underlying factor leading to

mater-nal mortality and severe morbidity [6 – 9]

Pathologic changes commonly affect the maternal

cardiovas-cular, renal, hematologic, neurologic, and hepatic systems (Table

34.2 ) Equally important are the adverse effects on the

uteropla-cental unit, resulting in fetal and neonatal complications [10 –

12] ) Our goal is to help guide the clinician in managing potentially

severe complications of pre - eclampsia Therapy for pregnant

women with chronic hypertension will not be addressed in this

chapter [13,14]

Etiology of p re - eclampsia

Pre - eclampsia has been a recognized pathologic entity since the time of the ancient Greeks [15,16] The inciting factor remains unknown, however, and an empty shield located on a portico at the Chicago Lying - In Hospital awaits inscription of the name of the person who discovers the etiology of the disease [17] A sig-nifi cant amount of investigation has been undertaken during recent decades to elucidate the cause and improve the treatment

of this disease During the past 40 years of medical research, the number of published articles has grown in a geometric manner Numerous risk factors are associated with the development of pre - eclampsia (Table 34.3 ), allowing for antenatal recognition of potential problems in some cases Multiple interrelated patho-physiologic processes have been proposed as etiologic in the development of this disease [18 – 20] , including prostaglandin imbalance [21 – 25] , immunologic mechanisms [26 – 30] , hyperdy-namic increase in cardiac output [31] , and subclinical blood coagulation changes [32] Endothelial involvement and the role

of tumor necrosis factor, β - carotene, and reduced antithrombin III have also been investigated, but remain incompletely under-stood [33 – 38]

Increased vascular reactivity to vasoactive agents was demonstrated by Dieckmann and Michel in 1937 [39] In 1961, Abdul Karim and Assali [40] found that normal pregnant women were less responsive to angiotensin II than non - pregnant women Gant

et al [41] published data that demonstrated an early loss of refractoriness to angiotensin II in those patients who later were

to develop pre - eclampsia Although clinical improvement may follow hospitalization and bed rest, vascular sensitivity to angio-tensin II does not decrease until after delivery of the fetus [42]

A molecular variant of the angiotensinogen gene (T235), found

to be associated with essential hypertension, also has been associ-ated with pre - eclampsia [43] It is postulassoci-ated that increased con-centrations of plasma or tissue angiotensinogen could lead to increased baseline or reactive production of angiotensin II,