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An Unusual Cause of Postpartum Vomiting
M. Gina Glazier, MB, BCh;
Winifred M. Waldron, MD
Arch Fam Med. 2000;9:284-286.
ABSTRACT
We are presenting this case to emphasize that the symptoms of Addison disease are very similar to those of pregnancy and, although this disease is rare, the consequences can be catastrophic if it is overlooked, particularly in pregnancy.
INTRODUCTION
Addison disease has an incidence of about 1 in 10,000 people.1 It is associated with other autoimmune disorders, including type 1 diabetes, pernicious anemia, and both hyperthyroidism and hypothyroidism. When 2 or more of these disorders are found together, as in this patient, the term type II polyglandular autoimmune syndrome is often used. Addison disease is often associated with premature ovarian failure, and it is rare for a patient with untreated disease to become pregnant.2 In this case report, we describe a patient who became pregnant while already manifesting symptoms of Addison disease and presented with a crisis 7 days post partum.
REPORT OF A CASE
A 29-year-old woman presented to the emergency department 1 week following delivery of her first child by cesarean section. She reported severe vomiting for 10 hours, which was not related to food intake. The vomitus had become blood streaked, and this had worried her sufficiently to come to the hospital for evaluation. In addition, she reported feeling generally weak and dizzy. She denied other abdominal symptoms and did not report back pain, fever, dysuria, hematuria, or chills.
Her pregnancy had been significant for insulin-dependent gestational diabetes that developed early, at 19 weeks' gestation. She had complained of increasing thirst and urinary frequency, and a random glucose test result was 9.9 mmol/L (180 mg/dL). An oral glucose tolerance test confirmed the diagnosis. Her family history was significant for type 1 diabetes in her 25-year-old sister; her father had autoimmune hyperthyroidism.
Following delivery, her glucose level returned to normal within 24 hours and she did not require any further insulin. She was not breastfeeding, as her milk supply had ceased 2 days post partum. The baby was thriving and had no problems.
Physical examination revealed a thin woman who had already returned to her prepregnancy weight. She had pronounced melasma and darkly pigmented skin, in contrast to the rest of her family who were of western European origin. Vital signs revealed sinus tachycardia with a heart rate of 120/min, an increased respiratory rate of 18/min, and a blood pressure of 90/60 mm Hg supine, which decreased to 70/40 mm Hg on sitting. She was afebrile. The rest of her physical examination results were normal. Of note, there was no increased mucosal pigmentation; her abdomen was soft with no evidence of wound infection, endometritis, or rectal bleeding; and her neurological examination results were entirely normal except for lethargy.
Laboratory test results revealed hyperkalemia, hyponatremia, and metabolic acidosis (Table 1). Based on her presentation, family history, and initial laboratory results, a presumptive diagnosis of Addison disease was made. In view of the fact that the patient was post partum, the differential diagnosis included Sheehan syndrome and bilateral adrenal hemorrhage.
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Table 1. Initial and Subsequent Laboratory Values
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In addition to the routine laboratory tests outlined in Table 1, baseline cortisol, corticotropin (ACTH), aldosterone, plasma renin activity, thyroid function tests, thyroid autoantibodies, and an ACTH stimulation test were ordered. The patient received 100 mg of hydrocortisone intravenously, and an endocrinologist was consulted for further management.
Low serum cortisol levels combined with an elevated ACTH level are diagnostic of adrenal failure. The patient's baseline cortisol level was low at 124 nmol/L. Results of the ACTH stimulation test showed failure of cortisol levels to increase above baseline at 60 minutes, and an ACTH level was 282 pmol/L (normal range, 0-10 pmol/L), consistent with a diagnosis of Addison disease. Plasma renin activity was elevated at 48.1 nmol · L-1 · h-1(normal range, 1.0-3.0 nmol · L-1 · h-1). Renin activity increases in Addison disease secondary to hypoaldosteronism following hypofunction of the renin-angiotensin-aldosterone system. Antimicrosomal thyroid antibody levels were elevated at 158 IU/mL (normal range, 0-99 IU/mL), and antithyroglobulin antibody levels were slightly elevated at 103 IU/mL (normal range, 0-99 IU/mL). Her thyroid-stimulating hormone level was also elevated at 11.54 mIU/mL (normal range, 0.49-4.67 mIU/mL), her total thyroxine level was normal at 113 nmol/L (normal range, 58-154 nmol/L), and her total triiodothyronine uptake was decreased at 0.26 (normal range, 0.34-0.45). These findings are suggestive of subclinical hypothyroidism (Table 2).
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Table 2. Results of Additional Investigations
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The following morning, she felt considerably improved, her vomiting had ceased, and her appetite had returned. She was prescribed oral hydrocortisone, 20 mg at 8 AM and 10 mg at 4 PM. She remained mildly acidotic but her laboratory results had otherwise normalized (Table 1). Following treatment, further history revealed that the patient had had salt cravings and increased skin pigmentation for about 5 years prior to presentation, consistent with the diagnosis of Addison disease.
With treatment, her addisonian crisis resolved rapidly, and she was discharged 3 days following hospital admission. She received instruction on the need to increase the dose of hydrocortisone with intercurrent illness and to increase her sodium intake, particularly following exercise. Although her diabetes had resolved quickly following delivery, a follow-up visit 2 weeks later revealed that her glucose level had increased to 23.9 mmol/L (430 mg/dL), and a diagnosis of type 1 diabetes was confirmed. Addison disease is frequently associated with hypoglycemia, which may have masked her diabetes. Despite her elevated thyroid-stimulating hormone level, she remains clinically euthyroid.
COMMENT
Addison disease is a rare entity, with an estimated incidence of about 1 in 10,000. It is thought to affect about 1 in 12,000 pregnancies.3 The majority of these patients are already receiving steroid replacement prior to pregnancy. Addison disease rarely presents during pregnancy. It is slightly more common for it to present, as in this case, in the postpartum period. One theory is that adequate steroids are produced by the fetoplacental unit to mask the disease, and their level drops abruptly following delivery, unmasking the disease in a dramatic fashion. Only 8 cases of Addison disease presenting in the postpartum period have been reported since 1966.4-9
Addison disease is caused by progressive destruction of the adrenal glands. Its most common cause is thought to be autoimmune destruction, although granulomatous diseases have also been implicated. Tuberculosis is now an uncommon cause. Symptoms usually do not occur until more than 90% of the glands are destroyed. Although Addison disease is rare, its symptoms are indolent, and the consequences of a misdiagnosis can be catastrophic. Therefore, physicians need to keep a high level of vigilance for this condition. Currently, approximately 25% of patients present with an adrenal crisis, the mortality of which, if not recognized, is almost 100%, and remains high even if recognized and treated appropriately.
Recognition of early Addison disease is challenging. The symptoms are mostly nonspecific. The most common are fatigue (99%), skin pigmentation (98%), weight loss (97%), anorexia (90%), hypotension (87%), and pigmentation of mucous membranes (82%). Salt cravings and abdominal symptoms are only present about 20% of the time. This diagnostic challenge increases when a pregnant patient develops these symptoms. Pregnancy itself frequently produces all these common symptoms and, therefore, neither the physician nor the patient is likely to recognize them as symptoms of disease. In fact, the only helpful differentiating clinical factor may be the pigmented mucous membranes, which were absent in our patient.
The diagnosis is easily confirmed, as in this case, with an ACTH stimulation test. A random serum cortisol level may be lower than normal in Addison disease, but this is not diagnostic, particularly in pregnancy when baseline cortisol levels are high. Therefore, diagnosis by ACTH stimulation is essential. This test involves the measurement of plasma cortisol at baseline, and then 30 and 60 minutes after administering 250 µg of ACTH intramuscularly or intravenously. The failure of an increase in cortisol above 2 to 3 times the baseline is diagnostic. A random serum ACTH level should also be measured. An elevation above 44 pmol/L is highly suggestive of Addison disease, but it often takes some time to obtain the result; therefore, this test may not be helpful in an acute situation.
In view of the high mortality rate, treatment of an adrenal crisis with hydrocortisone should be accomplished as soon as possible. If there will be a delay in obtaining the ACTH suppression test, the patient should be treated with dexamethasone, which treats the condition but will not interfere with test results.
Once diagnosed, patients require hydrocortisone supplementation. It is usually given in 2 doses, with two thirds of the daily dose in the morning to simulate physiological diurnal variation. The hydrocortisone has a weak mineralocorticoid effect, and fludrocortisone is frequently added to the regimen to provide this. In our patient, the weak mineralocorticoid effect of the hydrocortisone seemed adequate, as judged by her normal blood pressure and electrolyte values while receiving hydrocortisone alone.
Few cases of Addison disease associated with pregnancy were reported prior to 1965. However, there was one large series of 40 patients reported by Brent in 1950, prior to the availability of steroids for the treatment of adrenal failure.10 Of these, 18 mothers died while pregnant, and 7 of 12 patients who developed a crisis in the postpartum period also died, resulting in a mortality rate of more than 63%. A MEDLINE search from 1965 to 1998 reveals 39 cases of pregnancy with associated Addison disease. The majority of these patients (29 of 39) were already receiving cortisol replacement prior to becoming pregnant. There were no maternal deaths reported but there was 1 fetal death,10 and 1 infant died shortly after delivery of cardiac disease.11 These deaths occurred in 1967 and 1972; there are no recent reports of fetal deaths.
Untreated Addison disease is often associated with infertility and, prior to the advent of steroid therapy, pregnancy in these patients was rare. For the patient with known Addison disease who is followed up carefully during the pregnancy, and carefully educated about infection and other stressors, the outcomes have been good. Most reports note that the demand for both hydrocortisone and fludrocortisone did not increase during gestation, and an increase in dosage was not necessary. During labor, the patients should receive 100 mg of hydrocortisone every 6 to 8 hours, and this is continued post partum for 24 hours before returning to the prepregnancy regimen.12 In 1962, Osler13 noted in a retrospective study that infants born to mothers with Addison disease had a birth weight about 500 g less than average.13 This study was carried out before ultrasound was readily available for accurate dating. Although there are isolated reports of low birth weight, the subject of birth weight has not been addressed in a large study, and therefore remains controversial.14-15
New-onset adrenal insufficiency has been reported in only 2 patients during pregnancy. One of these presented with an adrenal crisis at 8 weeks' gestation,16 which was successfully treated, and the other presented with an adrenal crisis at 34 weeks' gestation, following a placental abruption, and the infant died in utero.17
Eight cases of Addison disease presenting in the postpartum period have been described. One patient developed a crisis shortly after delivery and died shortly thereafter.9 One presented with a crisis 10 days after cesarean section8 and the other 5 presented, as our patient did, between 6 days and 2 weeks post partum. There were no other deaths.4-7,18-19 About 1 to 2 weeks after delivery, there seems to be a critical period in which cortisol drops to prepregnancy levels and precipitates the crisis.
Primary care physicians are in a unique position to identify these patients, who may present with nonspecific complaints even prior to pregnancy. A high index of suspicion will aid in the timely diagnosis. Indeed, our patient had consulted a physician at the request of her family 2 years prior to pregnancy, as they were worried about her significant weight loss and feared she might have anorexia nervosa. A family history of other autoimmune disorders should increase suspicion of adrenal failure. Checking electrolyte levels and performing an ACTH stimulation test in these patients may yield a diagnosis and prevent further complications and even death.
AUTHOR INFORMATION
Accepted for publication July 16, 1999.
Corresponding author: M. Gina Glazier, MB, BCh, Department of Family Practice and Community Medicine, HUP, Second Floor Gates Bldg, 3400 Spruce St, Philadelphia, PA 19104 (e-mail: glazier{at}mail.med.upenn.edu).
From the Department of Family Practice and Community Medicine, University of Pennsylvania, Philadelphia (Dr Glazier); and the Somerset Family Practice Residency Program, Somerville, NJ (Dr Waldron).
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