Carney Complex A Rare Cause of Cushing Syndrome in Pregnancy LT Alison Spaniol, MC, USN, Capt. Bethany M. Mulla, MC, USAF, LCDR Jason G. Daily, MC, USN, and CDR Christopher S. Ennen, MC, USN BACKGROUND: Carney complex is a rare, autosomaldominant, multisystem disorder characterized by endocrine overactivity, spotty skin pigmentation, and myxomas. CASE: We present the case of a 24-year-old primigravid woman with a pregnancy complicated by Carney complex. At 18 weeks of gestation, severe hypertension developed. Medical history was significant for chronic hypertension, nephrolithiasis, and an atrial myxoma excised in 2011. She had Cushingoid features, an elevated 24-hour urine free cortisol, and a cutaneous myxoma. At 26 weeks of gestation, superimposed preeclampsia developed. She underwent a primary classical cesarean delivery, delivering a live female weighing 650 g. CONCLUSION: Carney complex is a rare cause of hypercortisolism and hypertension during pregnancy. It should be considered when features of Cushing syndrome and severe hypertension are present. (Obstet Gynecol 2014;124:426–8) DOI: 10.1097/AOG.0000000000000340
C
arney complex is a rare multisystem disorder characterized by endocrine overactivity, abnormalities of skin pigmentation, and myxomas. Physical findings include lentigines, blue nevi, and myxomas in the heart, skin, and breast. Endocrine manifestations include acromegaly, thyroid disorders, and corticotropin-independent From the Departments of Obstetrics and Gynecology, Endocrinology, and Maternal Fetal Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia. The authors thank Constantine A. Stratakis, MD, D(Med)Sci, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, for his advice in managing this patient and for his editorial assistance. The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. Corresponding author: Bethany M. Mulla, MD, Department of Obstetrics and Gynecology, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
426
Spaniol et al
Carney Complex in Pregnancy
Cushing syndrome due to primary pigmented nodular adrenocortical disease. Cushing syndrome is a rare diagnosis during pregnancy, and primary pigmented nodular adrenocortical disease is an extremely rare cause of Cushing syndrome that has only been described outside of pregnancy. Management of Carney complex consists of regular screening for disease manifestations and surgical instead of medical treatment depending on the location and size of tumors and clinical signs of hormonal dysfunction. Cardiac myxomas require surgical removal. Bilateral adrenalectomy is the recommended treatment for Cushing syndrome because of primary pigmented nodular adrenocortical disease. We performed a PubMed search from January 1990 to July 2013 using the key words “Carney complex pregnancy” and “Carney’s complex pregnancy.” We found one case of Carney complex diagnosed during the puerperium1 and another case diagnosed 3 years before pregnancy.2 We found no reported cases of Carney complex diagnosed or managed during pregnancy. The purpose of this report is to describe our evaluation and management of a primigravid woman with hypercortisolism and worsening hypertension during the second trimester who met diagnostic criteria for Carney complex.
CASE We present the case of a 24-year-old primigravid woman admitted to our obstetrics antepartum service at 18 weeks of gestation with severe hypertension observed during the postoperative period after a ureteral stent replacement. The patient’s medical history was significant for chronic hypertension not requiring any antihypertensives, nephrolithiasis, and urolithiasis with a ureteral stent placed before pregnancy, and excision of a left atrial myxoma in 2011. Systolic blood pressure ranged from 122 to 154 mm Hg and diastolic blood pressure ranged from 80 to 100 mm Hg during the first trimester, and she was administered oral labetalol. Stent replacement was recommended every 4 weeks during pregnancy, with planned lithotripsy postpartum. At 18 weeks of gestation, after ureteral stent replacement, headaches and a persistent severe range of blood pressures (systolic blood pressure 160 mm Hg or greater or diastolic blood pressure 110 mm Hg or greater) developed, and the obstetrics antepartum service was consulted. Physical examination was notable for Cushingoid features, including obesity (body mass index [calculated as weight (kg)/[height (m)]2] 39), facial acne, moon facies, dorsocervical fat pads, and abdominal striae. The patient’s 24-hour urine protein level was elevated at 567 mg. She was initially treated with intravenous antihypertensives, which were transitioned to oral labetalol and nifedipine. Fetal anatomy ultrasonography was performed and was normal. Given the patient’s severe blood pressure measurements at such an early time of gestation, a comprehensive work-up for secondary hypertension was started. At 24 weeks of gestation, the results of her biochemical
OBSTETRICS & GYNECOLOGY
evaluation were consistent with corticotropin-independent Cushing syndrome. The 24-hour urinary free cortisol level was elevated at 871.3 micrograms/mL. Morning and evening serum cortisol levels were also elevated (range 21.1–27.3 micrograms/dL) and corticotropin measurements were in the low normal range (11–18 pg/mL). In pregnancy, the corticotropin may not be completely suppressed in corticotropinindependent Cushing syndrome. The patient underwent a high-dose dexamethasone suppression test in which her cortisol level showed an increase, which is diagnostic of primary pigmented nodular adrenocortical disease.3 Imaging of the adrenal glands was unremarkable. Carney complex, a rare cause of corticotropin-independent adrenal Cushing syndrome, was suspected because of the history of cardiac myxoma. A third diagnostic criterion of Carney complex, a cutaneous myxoma, was present in the external auditory canal. Medical therapy with twice-daily 250 mg metyrapone to limit cortisol secretion was initiated. The patient received a course of betamethasone for fetal lung maturity. At 25 weeks of gestation, superimposed preeclampsia was diagnosed by a persistent severe range of blood pressure measurements requiring intravenous antihypertensive therapy in addition to dual oral antihypertensive therapy, an increase in her 24-hour urine protein excretion to 1,584 mg, and new intrauterine fetal growth restriction with absent end-diastolic flow of the umbilical artery. She was treated with magnesium sulfate for seizure prophylaxis. She was administered an additional rescue dose of betamethasone and received daily fetal Doppler velocimetry. At 26 weeks of gestation, persistently elevated blood pressures refractory to intravenous antihypertensive therapy and persistent headaches developed, and she underwent a primary classical cesarean delivery. She delivered a viable female neonate weighing 650 g with Apgar scores of 2, 6, and 7 at 1, 5, and 10 minutes, respectively. Resolution of the severe range of blood pressure measurements was noted soon after delivery, and oral antihypertensive therapy was slowly titrated down. The metyrapone was discontinued 2 weeks after delivery. The patient was readmitted twice for pyelonephritis secondary to significant stone burden. She was referred to the National Institutes of Health for repeat testing. Four months postpartum, she underwent a bilateral adrenalectomy and was started on appropriate replacement with corticosteroid and mineralocorticoid replacement therapy. Pathology demonstrated primary pigmented nodular adrenocortical disease.
COMMENT Carney complex is a rare multiple neoplasia syndrome characterized by endocrine overactivity, spotty skin pigmentation, and myxomas. Stratakis et al4 reported 338 known patients with Carney complex, of which 70% of cases are familial, inherited in an autosomaldominant pattern. Bertherat5 reported that approximately 500 cases have been registered in the United States and France. Germline loss of the PRKAR1A allele at 17q22-24 is suspected to play a role in pathogenesis.4,5
VOL. 124, NO. 2, PART 2, AUGUST 2014
Diagnostic criteria for Carney complex consist of 12 disease manifestations and two supplemental factors. Manifestations include spotty skin pigmentation, cutaneous and mucosal myxomas, cardiac myxoma, breast myxomatosis, primary pigmented nodular adrenocortical disease, acromegaly attributable to growth hormone–producing adenoma, large cell calcifying Sertoli cell tumor, thyroid tumor, melanotic schwannoma, and osteochondromyxoma. Supplemental criteria include affected first-degree relative and inactivating mutation of the PRKAR1A gene.4,5 To meet diagnostic criteria, an individual must have two disease manifestations or have one manifestation plus a supplemental factor. Our patient had a history of a cardiac myxoma and a cutaneous myxoma. Although the etiology of her Cushing syndrome was not confirmed at the time of presentation, it was suspected to be attributable to primary pigmented nodular adrenocortical disease. In primary pigmented nodular adrenocortical disease, hyperplastic pigmented adrenal cortical cells secrete cortisol independent from pituitary adrenocorticotropic hormone. Primary pigmented nodular adrenocortical disease is specific to Carney complex; however, only 20% to 30% of patients with Carney complex have primary pigmented nodular adrenocortical disease– associated Cushing syndrome.5 Cushing syndrome is a rare diagnosis during pregnancy, likely because of the associated menstrual abnormalities and ovulatory dysfunction.6 The most common etiology during pregnancy is an adrenal adenoma, with pituitary etiology as the second most common cause.6 Diagnosing Cushing syndrome during pregnancy may be challenging because classic signs including weight gain, striae, edema, and skin pigmentation can be found in normal pregnancies.6,7 Other associated signs such as hypertension, diabetes, and nephrolithiasis may also occur during pregnancy. Laboratory diagnosis of Cushing syndrome is complicated because physiologic changes that occur in pregnancy include increase in serum cortisol and urine free cortisol. An absent diurnal variation of cortisol and a markedly elevated 24-hour urinary free cortisol level in conjunction with imaging of the brain and adrenals may help establish a diagnosis.6,7 Cushing syndrome, regardless of etiology, is associated with high maternal and fetal morbidity.6,7 Maternal risks include uncontrolled hypertension and diabetes from high cortisol levels. Fetal risks include prematurity, intrauterine growth restriction, oligohydramnios, and intrauterine fetal demise.7 The recommended treatment for primary pigmented nodular adrenocortical disease is bilateral adrenalectomy attributable to the high recurrence risk after unilateral or partial adrenalectomy.2,5 Although surgery may have been successful in our
Spaniol et al
Carney Complex in Pregnancy 427
patient, we decided to treat her with metyrapone because of her gestational age and severe preeclampsia. Metyrapone, an 11-b-hydroxylase inhibitor, reduces serum cortisol levels in patients with Cushing syndrome and has been used safely during pregnancy. However, reduced cortisol levels stimulate corticotropin, which increases the production of mineralocorticoids, resulting in hypertension. Metyrapone has not been demonstrated to cause preeclampsia, but an association does exist.7 Oral antihypertensive therapy may be used to manage blood pressures; however, if superimposed severe preeclampsia is diagnosed and blood pressures become refractory to medication, delivery may be warranted. In patients with a history of bilateral adrenalectomy, mineralocorticoid and glucocorticoid replacement must be carefully monitored and stress dose steroids administered at the time of delivery. Screening the neonate for inherited disease is recommended because most cases are familial. Cardiac and cutaneous myxomas and primary pigmented nodular adrenocortical disease are the most common tumors during infancy,4 and an annual clinical work-up for all manifestations is recommended.4 Screening with baseline echocardiography is recommended by age 6 months and then annually.4,5 In families with a known PRKAR1A mutation, genetic testing can be performed to eliminate this screening for noncarriers. Genetic counseling is recommended in subsequent pregnancies and should
include discussion of autosomal-dominant inheritance and neonatal screening.4 It is important to recognize severe elevations of blood pressure and signs of hypercortisolism in pregnancy as abnormal. Although Carney complex is a rare cause of Cushing syndrome, and although Cushing syndrome is a rare diagnosis during pregnancy, it should be promptly identified so it can be treated to optimize maternal and fetal outcomes.
Cogan Syndrome in Pregnancy
known about whether it affects pregnancy or whether pregnancy affects the disease.
Christopher M. Tarney, MD, Karen Wilson, MD, and Mark F. Sewell, MD BACKGROUND: Cogan syndrome is a rare, multisystem, autoimmune disorder of unknown etiology. Little is From the Department of Obstetrics and Gynecology and Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Womack Army Medical Center, Fort Bragg, North Carolina. The opinions or assertions contained herein are the private views of the authors and are not to be construed as the official policy of the Department of the Army, Department of Defense, or the U.S. Government.
REFERENCES 1. Schulz S, Redlich A, Koppe I, Reschke K, Weise W. Carney complex—an unexpected finding during puerperium. Gynecol Obstet Invest 2001;51:211–3. 2. Kalelioglu I, Mert M, Has R, Kale T, Iyibozkurt C, Aral F. Carney’s complex: a successful pregnancy after bilateral adrenalectomy. Arch Med Sci 2012;8:175–7. 3. Stratakis CA, Sarlis N, Kirschner LS, Carney JA, Doppman JL, Nieman LK, et al. Paradoxical Response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999;131:585–91. 4. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and Recommendations for patient evaluation. J Clin Endocrinol Metab 2001;86:4041–6. 5. Bertherat J. Carney complex (CNC). Orphanet J Rare Dis 2006;I:21. 6. Nader S. Other endocrine disorders of pregnancy. In: Creasy and Resnik’s Maternal-fetal medicine. 6th ed. Philadelphia (PA): Saunders Elsevier; 2009. p. 1041–58. 7. Lim WH, Torpy DJ, Jeffies WS. The medical management of Cushing’s syndrome during pregnancy. Eur J Obstet Gyencol Reprod Biol 2013;168:1–6.
CASE: A 24-year-old primigravid woman with Cogan syndrome diagnosed 3 years before her pregnancy presented to our clinic for prenatal care. During pregnancy she experienced no worsening of symptoms of her disease but reported subjective improvement in vision and hearing. Cesarean delivery was performed at term because of nonreassuring fetal status. There were no obstetric or postpartum complications. CONCLUSION: Cogan syndrome requires close monitoring. If it worsens, then the disease process can be similar to both physiologic and pathologic changes of pregnancy. However, unlike the former, worsening Cogan syndrome can have irreversible maternal consequences.
Corresponding author: Christopher M. Tarney, MD, Womack Army Medical Center, Department of Obstetrics and Gynecology, 2817 Reilly Road, Fort Bragg, NC 28307; e-mail: [email protected].
(Obstet Gynecol 2014;124:428–31)
Financial Disclosure The authors did not report any potential conflicts of interest.
ogan syndrome was first described in 1934, with a later review of five cases by the ophthalmologist David Cogan who described this syndrome as a rare autoimmune disorder characterized by nonsyphilitic
© 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
428
Tarney et al
Cogan Syndrome During Pregnancy
DOI: 10.1097/AOG.0000000000000390
C
OBSTETRICS & GYNECOLOGY
C
arney complex is a rare multisystem disorder characterized by endocrine overactivity, abnormalities of skin pigmentation, and myxomas. Physical findings include lentigines, blue nevi, and myxomas in the heart, skin, and breast. Endocrine manifestations include acromegaly, thyroid disorders, and corticotropin-independent From the Departments of Obstetrics and Gynecology, Endocrinology, and Maternal Fetal Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia. The authors thank Constantine A. Stratakis, MD, D(Med)Sci, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, for his advice in managing this patient and for his editorial assistance. The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. Corresponding author: Bethany M. Mulla, MD, Department of Obstetrics and Gynecology, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
426
Spaniol et al
Carney Complex in Pregnancy
Cushing syndrome due to primary pigmented nodular adrenocortical disease. Cushing syndrome is a rare diagnosis during pregnancy, and primary pigmented nodular adrenocortical disease is an extremely rare cause of Cushing syndrome that has only been described outside of pregnancy. Management of Carney complex consists of regular screening for disease manifestations and surgical instead of medical treatment depending on the location and size of tumors and clinical signs of hormonal dysfunction. Cardiac myxomas require surgical removal. Bilateral adrenalectomy is the recommended treatment for Cushing syndrome because of primary pigmented nodular adrenocortical disease. We performed a PubMed search from January 1990 to July 2013 using the key words “Carney complex pregnancy” and “Carney’s complex pregnancy.” We found one case of Carney complex diagnosed during the puerperium1 and another case diagnosed 3 years before pregnancy.2 We found no reported cases of Carney complex diagnosed or managed during pregnancy. The purpose of this report is to describe our evaluation and management of a primigravid woman with hypercortisolism and worsening hypertension during the second trimester who met diagnostic criteria for Carney complex.
CASE We present the case of a 24-year-old primigravid woman admitted to our obstetrics antepartum service at 18 weeks of gestation with severe hypertension observed during the postoperative period after a ureteral stent replacement. The patient’s medical history was significant for chronic hypertension not requiring any antihypertensives, nephrolithiasis, and urolithiasis with a ureteral stent placed before pregnancy, and excision of a left atrial myxoma in 2011. Systolic blood pressure ranged from 122 to 154 mm Hg and diastolic blood pressure ranged from 80 to 100 mm Hg during the first trimester, and she was administered oral labetalol. Stent replacement was recommended every 4 weeks during pregnancy, with planned lithotripsy postpartum. At 18 weeks of gestation, after ureteral stent replacement, headaches and a persistent severe range of blood pressures (systolic blood pressure 160 mm Hg or greater or diastolic blood pressure 110 mm Hg or greater) developed, and the obstetrics antepartum service was consulted. Physical examination was notable for Cushingoid features, including obesity (body mass index [calculated as weight (kg)/[height (m)]2] 39), facial acne, moon facies, dorsocervical fat pads, and abdominal striae. The patient’s 24-hour urine protein level was elevated at 567 mg. She was initially treated with intravenous antihypertensives, which were transitioned to oral labetalol and nifedipine. Fetal anatomy ultrasonography was performed and was normal. Given the patient’s severe blood pressure measurements at such an early time of gestation, a comprehensive work-up for secondary hypertension was started. At 24 weeks of gestation, the results of her biochemical
OBSTETRICS & GYNECOLOGY
evaluation were consistent with corticotropin-independent Cushing syndrome. The 24-hour urinary free cortisol level was elevated at 871.3 micrograms/mL. Morning and evening serum cortisol levels were also elevated (range 21.1–27.3 micrograms/dL) and corticotropin measurements were in the low normal range (11–18 pg/mL). In pregnancy, the corticotropin may not be completely suppressed in corticotropinindependent Cushing syndrome. The patient underwent a high-dose dexamethasone suppression test in which her cortisol level showed an increase, which is diagnostic of primary pigmented nodular adrenocortical disease.3 Imaging of the adrenal glands was unremarkable. Carney complex, a rare cause of corticotropin-independent adrenal Cushing syndrome, was suspected because of the history of cardiac myxoma. A third diagnostic criterion of Carney complex, a cutaneous myxoma, was present in the external auditory canal. Medical therapy with twice-daily 250 mg metyrapone to limit cortisol secretion was initiated. The patient received a course of betamethasone for fetal lung maturity. At 25 weeks of gestation, superimposed preeclampsia was diagnosed by a persistent severe range of blood pressure measurements requiring intravenous antihypertensive therapy in addition to dual oral antihypertensive therapy, an increase in her 24-hour urine protein excretion to 1,584 mg, and new intrauterine fetal growth restriction with absent end-diastolic flow of the umbilical artery. She was treated with magnesium sulfate for seizure prophylaxis. She was administered an additional rescue dose of betamethasone and received daily fetal Doppler velocimetry. At 26 weeks of gestation, persistently elevated blood pressures refractory to intravenous antihypertensive therapy and persistent headaches developed, and she underwent a primary classical cesarean delivery. She delivered a viable female neonate weighing 650 g with Apgar scores of 2, 6, and 7 at 1, 5, and 10 minutes, respectively. Resolution of the severe range of blood pressure measurements was noted soon after delivery, and oral antihypertensive therapy was slowly titrated down. The metyrapone was discontinued 2 weeks after delivery. The patient was readmitted twice for pyelonephritis secondary to significant stone burden. She was referred to the National Institutes of Health for repeat testing. Four months postpartum, she underwent a bilateral adrenalectomy and was started on appropriate replacement with corticosteroid and mineralocorticoid replacement therapy. Pathology demonstrated primary pigmented nodular adrenocortical disease.
COMMENT Carney complex is a rare multiple neoplasia syndrome characterized by endocrine overactivity, spotty skin pigmentation, and myxomas. Stratakis et al4 reported 338 known patients with Carney complex, of which 70% of cases are familial, inherited in an autosomaldominant pattern. Bertherat5 reported that approximately 500 cases have been registered in the United States and France. Germline loss of the PRKAR1A allele at 17q22-24 is suspected to play a role in pathogenesis.4,5
VOL. 124, NO. 2, PART 2, AUGUST 2014
Diagnostic criteria for Carney complex consist of 12 disease manifestations and two supplemental factors. Manifestations include spotty skin pigmentation, cutaneous and mucosal myxomas, cardiac myxoma, breast myxomatosis, primary pigmented nodular adrenocortical disease, acromegaly attributable to growth hormone–producing adenoma, large cell calcifying Sertoli cell tumor, thyroid tumor, melanotic schwannoma, and osteochondromyxoma. Supplemental criteria include affected first-degree relative and inactivating mutation of the PRKAR1A gene.4,5 To meet diagnostic criteria, an individual must have two disease manifestations or have one manifestation plus a supplemental factor. Our patient had a history of a cardiac myxoma and a cutaneous myxoma. Although the etiology of her Cushing syndrome was not confirmed at the time of presentation, it was suspected to be attributable to primary pigmented nodular adrenocortical disease. In primary pigmented nodular adrenocortical disease, hyperplastic pigmented adrenal cortical cells secrete cortisol independent from pituitary adrenocorticotropic hormone. Primary pigmented nodular adrenocortical disease is specific to Carney complex; however, only 20% to 30% of patients with Carney complex have primary pigmented nodular adrenocortical disease– associated Cushing syndrome.5 Cushing syndrome is a rare diagnosis during pregnancy, likely because of the associated menstrual abnormalities and ovulatory dysfunction.6 The most common etiology during pregnancy is an adrenal adenoma, with pituitary etiology as the second most common cause.6 Diagnosing Cushing syndrome during pregnancy may be challenging because classic signs including weight gain, striae, edema, and skin pigmentation can be found in normal pregnancies.6,7 Other associated signs such as hypertension, diabetes, and nephrolithiasis may also occur during pregnancy. Laboratory diagnosis of Cushing syndrome is complicated because physiologic changes that occur in pregnancy include increase in serum cortisol and urine free cortisol. An absent diurnal variation of cortisol and a markedly elevated 24-hour urinary free cortisol level in conjunction with imaging of the brain and adrenals may help establish a diagnosis.6,7 Cushing syndrome, regardless of etiology, is associated with high maternal and fetal morbidity.6,7 Maternal risks include uncontrolled hypertension and diabetes from high cortisol levels. Fetal risks include prematurity, intrauterine growth restriction, oligohydramnios, and intrauterine fetal demise.7 The recommended treatment for primary pigmented nodular adrenocortical disease is bilateral adrenalectomy attributable to the high recurrence risk after unilateral or partial adrenalectomy.2,5 Although surgery may have been successful in our
Spaniol et al
Carney Complex in Pregnancy 427
patient, we decided to treat her with metyrapone because of her gestational age and severe preeclampsia. Metyrapone, an 11-b-hydroxylase inhibitor, reduces serum cortisol levels in patients with Cushing syndrome and has been used safely during pregnancy. However, reduced cortisol levels stimulate corticotropin, which increases the production of mineralocorticoids, resulting in hypertension. Metyrapone has not been demonstrated to cause preeclampsia, but an association does exist.7 Oral antihypertensive therapy may be used to manage blood pressures; however, if superimposed severe preeclampsia is diagnosed and blood pressures become refractory to medication, delivery may be warranted. In patients with a history of bilateral adrenalectomy, mineralocorticoid and glucocorticoid replacement must be carefully monitored and stress dose steroids administered at the time of delivery. Screening the neonate for inherited disease is recommended because most cases are familial. Cardiac and cutaneous myxomas and primary pigmented nodular adrenocortical disease are the most common tumors during infancy,4 and an annual clinical work-up for all manifestations is recommended.4 Screening with baseline echocardiography is recommended by age 6 months and then annually.4,5 In families with a known PRKAR1A mutation, genetic testing can be performed to eliminate this screening for noncarriers. Genetic counseling is recommended in subsequent pregnancies and should
include discussion of autosomal-dominant inheritance and neonatal screening.4 It is important to recognize severe elevations of blood pressure and signs of hypercortisolism in pregnancy as abnormal. Although Carney complex is a rare cause of Cushing syndrome, and although Cushing syndrome is a rare diagnosis during pregnancy, it should be promptly identified so it can be treated to optimize maternal and fetal outcomes.
Cogan Syndrome in Pregnancy
known about whether it affects pregnancy or whether pregnancy affects the disease.
Christopher M. Tarney, MD, Karen Wilson, MD, and Mark F. Sewell, MD BACKGROUND: Cogan syndrome is a rare, multisystem, autoimmune disorder of unknown etiology. Little is From the Department of Obstetrics and Gynecology and Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Womack Army Medical Center, Fort Bragg, North Carolina. The opinions or assertions contained herein are the private views of the authors and are not to be construed as the official policy of the Department of the Army, Department of Defense, or the U.S. Government.
REFERENCES 1. Schulz S, Redlich A, Koppe I, Reschke K, Weise W. Carney complex—an unexpected finding during puerperium. Gynecol Obstet Invest 2001;51:211–3. 2. Kalelioglu I, Mert M, Has R, Kale T, Iyibozkurt C, Aral F. Carney’s complex: a successful pregnancy after bilateral adrenalectomy. Arch Med Sci 2012;8:175–7. 3. Stratakis CA, Sarlis N, Kirschner LS, Carney JA, Doppman JL, Nieman LK, et al. Paradoxical Response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999;131:585–91. 4. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and Recommendations for patient evaluation. J Clin Endocrinol Metab 2001;86:4041–6. 5. Bertherat J. Carney complex (CNC). Orphanet J Rare Dis 2006;I:21. 6. Nader S. Other endocrine disorders of pregnancy. In: Creasy and Resnik’s Maternal-fetal medicine. 6th ed. Philadelphia (PA): Saunders Elsevier; 2009. p. 1041–58. 7. Lim WH, Torpy DJ, Jeffies WS. The medical management of Cushing’s syndrome during pregnancy. Eur J Obstet Gyencol Reprod Biol 2013;168:1–6.
CASE: A 24-year-old primigravid woman with Cogan syndrome diagnosed 3 years before her pregnancy presented to our clinic for prenatal care. During pregnancy she experienced no worsening of symptoms of her disease but reported subjective improvement in vision and hearing. Cesarean delivery was performed at term because of nonreassuring fetal status. There were no obstetric or postpartum complications. CONCLUSION: Cogan syndrome requires close monitoring. If it worsens, then the disease process can be similar to both physiologic and pathologic changes of pregnancy. However, unlike the former, worsening Cogan syndrome can have irreversible maternal consequences.
Corresponding author: Christopher M. Tarney, MD, Womack Army Medical Center, Department of Obstetrics and Gynecology, 2817 Reilly Road, Fort Bragg, NC 28307; e-mail: [email protected].
(Obstet Gynecol 2014;124:428–31)
Financial Disclosure The authors did not report any potential conflicts of interest.
ogan syndrome was first described in 1934, with a later review of five cases by the ophthalmologist David Cogan who described this syndrome as a rare autoimmune disorder characterized by nonsyphilitic
© 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
428
Tarney et al
Cogan Syndrome During Pregnancy
DOI: 10.1097/AOG.0000000000000390
C
OBSTETRICS & GYNECOLOGY
