Correspondence

Case 36-2006: A Pregnant Woman with New Hypertension

N Engl J Med 2007; 356:966-968March 1, 2007

Article

To the Editor:

The Case Record discussion by Klibanski et al. (Nov. 23 issue),1 concerning a woman with hypertension due to a cortisol-producing adrenal adenoma, illustrates that serious forms of secondary hypertension (e.g., pheochromocytoma and Cushing's syndrome) can present in an unorthodox fashion in gestation. However, the normal ranges in Table 1 of the article appear to be for nonpregnant populations. For example, a serum sodium level of 145 mmol per liter is hypernatremia during pregnancy. Increases in glomerular filtration rates and creatinine levels above 0.9 mg per deciliter are suspect; the published upper limits of 1.5 mg per deciliter for creatinine and 25 mg per deciliter for urea nitrogen are too high for pregnant women. Gestational changes in protein filtration increase normal amounts of protein excreted into the urine to a limit of 300 mg per 24 hours. In Table 2 of the article, normal production, secretion, and circulating levels related to the renin–aldosterone axis change in pregnancy; this patient's renin level (twice the upper limit for a nonpregnant person) is normal for pregnancy. Similarly, there is conflicting information regarding biologically active circulating cortisol and other variables in the pituitary–adrenal axis2; only recently have attempts to set rigid criteria to diagnose adrenal disease in gestation been published.3

Marshall D. Lindheimer, M.D.
University of Chicago, Chicago, IL 60637
mlindhei@medicine.bsd.uchicago.edu

3 References

1
Case Records of the Massachusetts General Hospital (Case 36-2006). N Engl J Med 2006;355:2237-2245
Full Text | Web of Science | Medline

2
Molitch ME. Pituitary, thyroid, adrenal, and parathyroid disorders. In: Barron WM, Lindheimer MD, eds. Medical disorders during pregnancy. 3rd ed. St. Louis: Mosby, 2000:101-46.

3
Suri D, Moran J, Hibbard JU, Kasza A, Weiss RE. Assessment of adrenal reserve in pregnancy: defining the normal response to the adrenocorticotropin stimulation test. J Clin Endocrinol Metab 2006;91:3866-3872
CrossRef | Web of Science | Medline

To the Editor:

We disagree with the choice of glyburide as initial treatment for gestational diabetes mellitus in the patient discussed by Klibanski et al. Glyburide has been shown to be effective and safe in treating gestational diabetes1 and is increasingly being used by physicians as an alternative to insulin. However, data do not support the use of glyburide in all patients with gestational diabetes. The degree of hyperglycemia, based on the fasting blood glucose level and the 1-hour postprandial blood glucose level, has been shown to be predictive of the failure or success of treatment with glyburide.2-4 Other significant predictors of glyburide failure include advanced maternal age (34 years vs. 29 years, P=0.001) and earlier diagnosis of gestational diabetes (at 23 weeks vs. 28 weeks, P=0.002).2 Glyburide treatment is 8.3 times as likely to fail in women in whom gestational diabetes was diagnosed at less than 25 weeks of gestation as in those in whom the diagnosis was made at or after 25 weeks.2 Gestational diabetes diagnosed at 16 weeks and 6 days in a 35-year-old patient with a 1-hour postprandial blood glucose level of 346 mg per deciliter suggests a high risk of glyburide failure.

Aman Khurana, M.D.
Namita Vinayek, M.D.
Sioux Valley Hospital University of South Dakota Medical Center, Sioux Falls, SD 57117
akhurana@usd.edu

4 References

1
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-1138
Full Text | Web of Science | Medline

2
Kahn BF, Davies JK, Lynch AM, Reybolds RM, Barbour LA. Predictors of glyburide failure in the treatment of gestational diabetes. Obstet Gynecol 2006;107:1303-1309
CrossRef | Web of Science | Medline

3
Rochon M, Rand L, Roth L, Gaddipati S. Glyburide for the management of gestational diabetes: risk factors predictive of failure and associated pregnancy outcomes. Am J Obstet Gynecol 2006;195:1090-1094
CrossRef | Web of Science | Medline

4
Chmait R, Dinise T, Moore T. Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus. J Perinatol 2004;24:617-622
CrossRef | Medline

To the Editor:

In the case discussed by Klibanski et al., Dr. Utz states that “after the operation, glucocorticoid replacement with dexamethasone was begun” and then says that “prednisone (5 mg twice daily) was continued throughout the pregnancy.” The otherwise excellent discussion that follows does not touch on glucocorticoid coverage during pregnancy. Dexamethasone would have been a poor choice for replacement of this mother's glucocorticoid needs because it readily passes the placenta as a result of its low affinity to maternal corticosteroid-binding globulin and lack of metabolism by placental steroid-metabolizing enzymes (mainly 11β-hydroxysteroid dehydrogenase).1 Prednisone is a better choice, despite its long half-life2; it is also preferable when endogenous cortisol levels need to be monitored, although this depends on the assay.3 We have used hydrocortisone, a substrate for 11β-hydroxysteroid dehydrogenase, at the usual dose of 12 to 15 mg per square meter of body-surface area without maternal or fetal complications in pregnant patients at our institution,4 and we recommend its use for glucocorticoid replacement in pregnant women with primary or secondary adrenocortical insufficiency.

Constantine A. Stratakis, M.D.
National Institutes of Health, Bethesda, MD 20892
stratakc@mail.nih.gov

4 References

1
Diederich S, Hanke B, Burkhardt P, et al. Metabolism of synthetic corticosteroids by 11 beta-hydroxysteroid-dehydrogenases in man. Steroids 1998;63:271-277
CrossRef | Web of Science | Medline

2
Malchoff CD, Carey RM. Adrenal insufficiency. Curr Ther Endocrinol Metab 1997;6:142-147
Medline

3
Pujos E, Flament-Waton MM, Paisse O, Grenier-Loustalot MF. Comparison of the analysis of corticosteroids using different techniques. Anal Bioanal Chem 2005;381:244-254
CrossRef | Web of Science | Medline

4
Lindsay JR, Jonklaas J, Oldfield EH, Nieman LK. Cushing's syndrome during pregnancy: personal experience and review of the literature. J Clin Endocrinol Metab 2005;90:3077-3083
CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Lindheimer that the normal values for several laboratory tests reported in Tables 1 and 2 of the Case Record do not apply to pregnant women. However, our laboratory, like others, reports normal ranges established in the laboratory from samples from nonpregnant persons. Although normal ranges have been reported for some of these tests at various gestational ages, these ranges are not reported by most clinical laboratories, including ours. It is the responsibility of the physician caring for the patient to know whether the patient is pregnant, the gestational age of the fetus, and the expected values for that stage.

We agree with Khurana and Vinayek that in patients with more severe degrees of hyperglycemia early in pregnancy, treatment with glyburide is more likely to fail to achieve adequate metabolic control. This was true in the patient under discussion, which is why we started to give her insulin as soon as we saw her.

We agree with Stratakis regarding glucocorticoid replacement during pregnancy. In this patient, dexamethasone was started postoperatively, as is routinely done to assess cure of Cushing's syndrome, before the use of prednisone replacement for the remainder of the pregnancy at the doses stated in the text. As Stratakis notes, hydrocortisone is also recommended.

Anne Klibanski, M.D.
Michael F. Greene, M.D.
Massachusetts General Hospital, Boston, MA 02114

Citing Articles (1)

Citing Articles

1
(2008) Reference values for clinical chemistry tests during normal pregnancy. BJOG: An International Journal of Obstetrics & Gynaecology 115:13, 1716-1716
CrossRef