Anesthesia for cesarean section in a patient with congenital adrenal hyperplasia: case report

Abstracts

JUSTIFICATIVA E OBJETIVOS: O objetivo deste relato de caso é ilustrar a conduta anestésica para cesariana em paciente portadora da forma não clássica de hiperplasia adrenal congênita (HAC) e revisar as manifestações clínicas e a conduta nas suas várias formas durante a gestação. RELATO DO CASO: Paciente primigrávida, 32 anos, portadora da forma não clássica de HAC foi admitida com quadro de retardo de crescimento intra-uterino, com 28 semanas de gestação. Suas características clínicas incluíam obesidade mórbida, hipertensão arterial leve e uso crônico de glicocorticóides. Com 29 semanas de gestação, a paciente foi submetida à cesariana de emergência sob raquianestesia, observando-se administração de esteróides no período peri-operatório. Mãe e recém-nascido apresentaram boa evolução. CONCLUSÕES: A conduta clínica em parturientes portadoras de HAC deve incluir no planejamento os efeitos da corticoterapia crônica, os sinais de insuficiência adrenal e a administração peri-operatória de esteróides. Em relação à anestesia é necessário considerar aspectos relacionados à obesidade e à hipertensão arterial. Uma abordagem multidisciplinar é necessária para garantir um bom resultado materno-fetal.

CIRURGIA; CIRURGIA; DOENÇAS; TÉCNICAS ANESTÉSICAS; TÉCNICAS ANESTÉSICAS

CLINICAL REPORT

Anesthesia for cesarean section in a patient with congenital adrenal hyperplasia. Case report^*

Anestesia para cesárea en paciente con hiperplasia adrenal congénita. Relato de caso

Mrinalini Balki, MD^I; José Carlos Almeida Carvalho, TSA, M.D.^II; Carmencita Castro, M.D.^III

^IClinical and Research Fellow in Obstetric Anesthesia, Mount Sinai Hospital

^IIAssociate Professor of Anesthesia and Obstetrics and Gynecology, University of Toronto; Director, Obstetric Anesthesia, Mount Sinai Hospital

^III Assistant Professor, Department of Anesthesia, University of Toronto; Staff Anesthesiologist, Mount Sinai Hospital

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: The purpose of this case report is to illustrate the anesthetic management of a Cesarean section in a patient with non-classic congenital adrenal hyperplasia (CAH) and to review the clinical features and management of various forms of CAH during pregnancy.

CASE REPORT: A 32-year-old primigravida, diagnosed with non-classic CAH, was admitted with intrauterine growth retardation at 28 weeks of gestation. Clinical features included morbid obesity, mild hypertension and chronic use of glucocorticoids. An emergency Cesarean section was performed at 29 weeks of gestation under uneventful spinal anesthesia with perioperative steroid coverage. Both mother and neonate had good outcome.

CONCLUSIONS: The management of patients with CAH presenting for labour or operative delivery should include the understanding of the effects of chronic steroid therapy, signs of adrenal insufficiency and perioperative steroid coverage. Anesthetic considerations should include issues related to obesity and hypertension. A multidisciplinary approach is required to ensure successful outcome.

Key Words: ANESTHETIC TECHNIQUES, Regional; spinal block; DISEASES, Endocrine; SURGERY, Obstetric: cesarean section

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: El objetivo de este relato de caso es ilustrar la conducta anestésica para cesárea en paciente portadora de la forma no clásica de hiperplasia adrenal congénita (HAC) y revisar las manifestaciones clínicas y la conducta en sus varias formas durante la gestación.

RELATO DEL CASO: Paciente primípara, 32 años, portadora de la forma no clásica de HAC fue admitida con cuadro de retardo de crecimiento intrauterino, con 28 semanas de gestación. Sus características clínicas incluían obesidad mórbida, hipertensión arterial leve y uso crónico de glucocorticóides. Con 29 semanas de gestación, la paciente fue sometida a cesárea de emergencia bajo raquianestesia, observándose administración de esteróides en el período peri-operatorio. Madre y recién nacido presentaron buena evolución.

CONCLUSIONES: La conducta clínica en parturientas portadoras de HAC debe incluir en la planificación los efectos de la corticoterapia crónica, los señales de insuficiencia adrenal y la administración peri-operatoria de esteróides. Con relación a la anestesia, es necesario considerar aspectos relacionados a la obesidad y a la hipertensión arterial. Un abordaje multidisciplinar es necesario para garantizar un buen resultado materno-fetal.

INTRODUCTION

Although low fertility rates attributable to a variety of factors are reported in patients with classic or non classic form of congenital adrenal hyperplasia (CAH), a few cases of successful pregnancies have been described ¹. Pregnancy adds to the complex issues of anthropometric and endocrinologic features of CAH which can vary to a great extent depending on the type of CAH. The anthropometric features include obesity and short stature while the endocrinologic manifestations are related to the deficiency of glucocorticoids, mineralocorticoids or both. To our knowledge, this report represents the only case in the literature of anesthetic considerations for non classic CAH during pregnancy and operative delivery.

CASE REPORT

A 32-year-old primigravida was admitted to our hospital at 28 weeks of gestation with intrauterine growth retardation (IUGR) for delivery by cesarean section. She was diagnosed with CAH at the age of 20 years when she developed symptoms of weight gain, hirsutism and irregular menses. She was investigated and found to be a heterozygous carrier of 21-hydroxylase gene mutation. She was treated with dexamethasone 0.25 mg daily. She was started on birth control pills at the age of 27 years, which resulted in regular menses. She got pregnant as a result of natural conception one month after stopping birth control pills. At 12 weeks of gestation, the dose of dexamethasone was increased from 0.25 mg/day to 0.5 mg/day as her androgen levels were noted to rise during pregnancy. Fetal ultrasounds during pregnancy showed normal structural and functional characteristics except for symmetric IUGR. At 28 weeks of gestation, the estimated fetal weight was 770 grams. It was decided to perform an elective Cesarean section at 29 weeks due to progressive fetal growth retardation. The fetus was monitored for signs of distress by twice daily non-stress tests. Prior to the scheduled day of cesarean section, fetal decelerations developed with biophysical profile of 4/8 and an emergency Cesarean section was indicated.

Preoperative anesthesia assessment revealed a morbidly obese woman with body mass index of 48 (height 150 cm, weight 107 kg). She had centripetal distribution of fat and mild hypertension with blood pressure of 140/90 mmHg and heart rate of 85 bpm but no features of Cushing’s syndrome. Examination of her cardiovascular and respiratory system was normal. Her airway revealed Mallampati III classification with good range of neck movement and normal thyromental distance. Her spinous processes were difficult to palpate on deep palpation. Laboratory investigations revealed hemoglobin of 13.1 mg/dL, blood glucose of 113.4 mg/dL, normal electrolytes and coagulation profile.

She received 30 mL 0.3 M sodium citrate per os, and metoclopramide 10 mg intravenously (i.v.) as prophylaxis against aspiration on call to operating room. A stress dose of hydrocortisone 100 mg i.v. was administered. In the operating room, after application of routine monitors, the patient was preloaded with 1 L of lactated Ringer's solution. Spinal anesthesia was instituted in the sitting position using 1.4 mL of 0.75% hyperbaric bupivacaine and 150 µg of preservative free intrathecal morphine with a 27 gauge Whitacre needle. The patient was positioned supine, with left uterine displacement using a wedge under the right buttock. Supplemental oxygen was provided via nasal prongs at the rate of 4 L.min^-1. Sensory block to pinprick up to T₂ dermatomal level was achieved. Intraoperative hypotension was treated with a total of 500 µg of phenylephrine administered intravenously in the incremental boluses of 50 µg each. Larger doses were deemed unnecessary as adequate response could be obtained with 50 µg. Systolic blood pressure was maintained between 120 and 140 mmHg and heart rate between 80 and 100 bpm. A male baby weighing 730 grams was delivered, with an Apgar score of 5 and 8 at 1 minute and 5 minutes respectively. Oxytocin infusion of 20 international units in 1 L normal saline was started i.v. immediately after the delivery of baby. Hydrocortisone 100 mg was continued i.v. every 8 hours for 24 hours and then tapered to 50 mg i.v. every 8 hours for next 24 hours. This was followed by resumption of oral dexamethasone therapy. The patient was discharged from the hospital three days post partum. Pathological examination of the placenta and umbilical cord revealed placental weight less than 10^th percentile, excessive umbilical cord coiling and fetal thrombotic vasculopathy. The initial fetal cord blood gases showed a predicted fetal acidosis. Interestingly the fetal platelet count at delivery was 35,000/mm³, which was interpreted as a feature of early onset IUGR. The neonate required intubation and artificial ventilation for a week in NICU and was discharged from the hospital after two months.

DISCUSSION

Congenital adrenal hyperplasia is inherited as an autosomal recessive disorder in which there is deficiency of one of the enzymatic activities necessary for cortisol synthesis. Ninety percent cases of CAH are due to 21-hydroxylase deficiency presenting in about 1 in 15,000 live births ^2,3. Insufficient cortisol synthesis in these patients leads to excessive secretion of the corticotrophin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by the hypothalamus and pituitary respectively. This results in adrenal hyperplasia and excess production of sex hormone precursors that do not require 21-hydroxylation. Most patients also have inadequate aldosterone synthesis affecting the sodium balance ^2,3.

Low fertility rates are observed among the women with CAH because of several factors such as anovulation, secondary ovarian hyperandrogenism and leuteal phase defects ⁴. Spontaneous first trimester abortion rates are also high (30%) when compared with the normal population (12% to 15%) ⁵. In some patients with the salt wasting form of CAH, the increases in androgen levels during pregnancy may be substantial. Increased corticotropic releasing hormone (CRH) and other factors such as non-adrenal or ovarian androgen production may contribute to the high androgen levels during late gestation ⁴.

Clinically two different forms of CAH due to 21-hydroxylase deficiency have been identified: Classic variant (salt wasting and simple virilizing) and non-classic variant (cryptic or late onset) ^2,3. In patients with classic CAH, excess adrenal androgen production that begins in early fetal life causes masculinization in girls and inappropriately early puberty leads to premature epiphyseal closure and short adult height. Lack of both cortisol and aldosterone predispose severely affected individuals to adrenal crisis, manifested as dehydration, hypotension, shock, acute abdomen, unexplained hypoglycemia, fever, hyponatremia, hyperkalemia, azotemia and hypercalcemia.

The non-classic form of CAH in which 21-hydroxylase deficiency is partial, manifests in later childhood or even young adult life with signs of androgen excess including acne, hirsutism, oligomenorrhea, signs of polycystic ovaries and also reduction in insulin sensitivity.^2,3 These patients do not have mineralocorticoid deficiency or serious developmental anomalies.

The medical treatment of CAH consists of administration of a glucocorticoid in order to decrease ACTH secretion, suppress the hyperplasic adrenal gland and stop the overproduction of adrenal androgens. In addition, salt wasters with aldosterone deficiency need mineralocorticoid and sodium chloride supplements. Genital reconstructive surgery may be required in classic form of CAH ^1-4.

Women with classic form of CAH may require higher doses of steroid to provide adequate coverage during labor and operative delivery analogous to the management of addisonian patient ⁴. Treatment of adrenal crisis requires administration of intravenous hydrocortisone, 0.9% normal saline and 5% dextrose, with monitoring of blood pressure, serum electrolytes, glucose, plasma cortisol and ACTH ^2-4. Hemodynamic monitoring in the form of an arterial line and central line is desirable for unstable patients.

For women with non-classic CAH who become pregnant without glucocorticoid treatment, the mild degree of hyperandrogenism generally does not warrant glucocorticoid treatment, owing to the large capacity for the placental aromatization of circulating maternal androgens. For those already receiving maintenance glucocorticoid treatment at the time of pregnancy, it is advisable to continue treatment and administer stress dose of steroids at the time of labour and delivery because of potential hypothalamo-pituitary axis suppression ⁴.

The recommendation is that hydrocortisone 100 mg is administered i.v. every 8 hours, at the start of active labor with continuation until after delivery, followed by a rapid taper to previous maintenance doses ^1,4,5. Hydrocortisone 100 mg should be administered perioperatively for cesarean section. Hydrocortisone, cortisone acetate, prednisone, prednisolone and methylprednisolone are metabolized by the placenta, minimizing placental transfer and fetal adrenal suppression. In contrast, dexamethasone, which provides longer and more effective suppression of adrenal androgen production is transferred across placenta and can suppress the fetal adrenal gland ⁴. Obviously the treatment considerations differ in pregnancies in which the fetus is at risk for CAH, in which case suppression of the abnormal fetal adrenal gland is the goal of prenatal therapy.

Short term concerns of steroid therapy include possible reduced resistance to infection for both the mother and infant, impaired glucose tolerance, suppression of fetal and maternal adrenal function, and alteration of the fetal biophysical profile. Long term use of steroids may result in spontaneous abortion, fetal demise during late pregnancy, intrauterine growth retardation, liver steatosis, hydrocephalus and fetal virilization ^1,4,6,7. Excess glucocorticoid and mineralocorticoid doses may be associated with maternal risk of fluid overload, weight gain, hypertension, glucose intolerance, hypokalemia or cushingoid features ^1,4. Preeclampsia has been described in some patients, but the relationship of preeclampsia to the underlying adrenal disorder or steroid therapy has not been established ^1,4. Postpartum eclampsia can also occur ⁵. Severe or malignant phase hypertension may be associated with cardiac failure and necessitates invasive monitoring ⁸. Control of blood pressure with hydralazine and labetalol may be required. Diabetes produced by steroid administration may require insulin treatment.

Regional and general anesthesia are appropriate in these patients once the anesthesiologist recognizes the obesity-related problems, such as difficult intravenous access, difficult airway, sub-optimal landmarks for regional techniques or enhanced spread of local anesthetic solutions. In addition, these patients may behave in a similar fashion as severe pregnancy induced hypertension. Considering these factors, the dose of local anesthetic for spinal anesthesia was reduced in our patient. An even more appropriate anesthetic option for this case would have been a titrated epidural or combined spinal-epidural anesthesia, since the spread of the block and the hemodynamic changes with these techniques are more predictable. Hypotension occurring as a result of regional anesthesia should be cautiously treated as these patients may require smaller doses of vasopressors due to increased sensitivity to pressor agents. If unexplained intraoperative hypotension occurs, adequate infusion of hydrocortisone may be necessary ⁸.

In conclusion, the key issues in the management of patients with CAH presenting for labour or operative delivery include the understanding of the effects of chronic steroid therapy, signs of adrenal insufficiency and perioperative steroid coverage. Anesthetic considerations include issues related to obesity and hypertension. A multidisciplinary approach is required to ensure successful outcome.

REFERENCES

Submitted for publication February 18, 2004

Accepted for publication August 16, 2004

• 01. Lo JC, Schwitzgebel VM, Tyrrell JB et al - Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab, 1999;84:930-936.
• 02. Speiser PW - Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Endocrinol Metab Clin North Am, 2001;30:31-59.
• 03. Levine LS - Congenital adrenal hyperplasia. Pediatr Rev, 2000;21:159-170.
• 04. Lo JC, Grumbach MM - Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia. Endocrinol Metab Clin North Am, 2001;30:207-229.
• 05. Garner PR - Congenital adrenal hyperplasia in pregnancy. Semin Perinat, 1998;22:446-456.
• 06. Gabbe SG, Niebyl JR, Simpson JL - Obstetrics - Normal and Problem Pregnancies, em: Iams JD. Preterm Birth, 4^th Ed, Philadelphia: Churchill Livingston, 2002;755-826.
• 07. Lajic S, Wedell A, Bui TH et al - Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia. J Clin Endocrinol Metab, 1998;83:3872-3880.
• 08. Datta S - Endocrine Disorders, em: Wallace DH, Gilstrap LC - Anesthetic and Obstetric Management of High Risk Pregnancy, 2^nd Ed, St. Louis: Mosby, 1996;272-295.

*

Received from Department of Anesthesia, Mount Sinai Hospital, University of Toronto, Ontario, Canada

Publication Dates

• Publication in this collection
  26 Jan 2005
• Date of issue
  Dec 2004

History

• Received
  18 Feb 2004
• Accepted
  16 Aug 2004