Patil S*, Dhokia T**, Chauhan AR***.
(* Ex Fourth Year Resident, ** Third Year Resident, *** Professor, Department of Obstetrics and Gynecology, Seth GS Medical College and KEM. Hospital, Mumbai, India.)
Addison’s disease or primary adrenal insufficiency is one of the rare endocrine disorders in which the adrenal glands are unable to produce enough steroid hormones. Addison’s disease in pregnancy is even more rare. Addisonian crisis can occur following stressful conditions such as labor, surgery, infections and puerperium. We present a case of Addison’s disease with pregnancy and its successful outcome by multidisciplinary approach.
Primary adrenocortical insufficiency or Addison’s disease is an endocrine disorder; majority of cases are due to autoimmune adrenalitis. Untreated primary adrenocortical insufficiency results in subfertility. Addisonian crisis is a rare and life-threatening event in pregnant women, and occurs due to stressful conditions such as hyperemesis gravidarum, labor, puerperium, infection or surgical interventions. Patients with this disease in pregnancy can have symptoms such as weakness, fatigability, weight loss, myalgia, fever, anorexia, nausea, vomiting and mental irritability. While complications of Addison’s disease in pregnancy include postural hypotension, hyponatremia, hyperkalemia, pigmentary changes, these are seen less frequently due to the availability of steroid therapy. Addison’s disease was associated with a high maternal mortality rate before steroid treatment was available; the mortality has decreased from 45% in 1930, to 7% during 1948-1955, to 0.7% by the year 2000. Serious fetal complications such as intrauterine death are also reported.
Mrs. NS, 25 years old primigravida with 33 weeks of gestation, a diagnosed case of Addison’s disease was referred to us for tertiary care. Patient presented with complaints of headache and blurring of vision since one week and pain in abdomen since last 2 days. Patient had history of irregular use of steroids. In 2010, she was prescribed topical steroids for a skin lesion which she used for 6 months. However the treatment did not help and her skin lesions increased, for which she was investigated; serum cortisol level was less than 0.2 µg/ dl (normal range 5 - 25 µg/ dl). Subsequent testing of serum cortisol was done in 2012, 2013, 2015; all levels reported were less than 0.2 µ/ dl. Thus a diagnosis of Addison’s disease was made. Thereafter patient was put on tablet prednisolone 5 mg daily. In 2013, during a course of treatment with steroids, patient developed cushingoid features such as striae all over the body, humped back, generalized anasarca and weight gain. At this time, she stopped treatment on her own. In 2015, she developed Bell’s palsy and was diagnosed to have raised intracranial tension and papilledema. Patient was managed conservatively and restarted on tablet prednisolone 5 mg. While on treatment with prednisolone she conceived in January 2016 and again discontinued her steroidal treatment.
On presentation to us, she had raised blood pressure (150/ 100 mm Hg) and urine albumin 3 + by dipstick method. Patient was started on tablet labetelol 200 mg twice daily and tablet nifedepine 10 mg three times a day. Ophthalmology and endocrinology references were taken. There was no abnormality found on fundoscopy. Endocrinologist advised fresh 8 am serum cortisol, which was 17.21 µg/ dl, hence steroids were not required. Other investigations and fetal surveillance were normal. Meanwhile patient complained of persistent headache and blurring of vision; in view of associated persistent hypertension and albuminuria despite about a week of treatment, decision to terminate pregnancy in view of preeclampsia was taken. Induction of labor was done at 34 weeks with PGE2 gel. She delivered vaginally a healthy baby of 2.274 kg. Peri delivery steroids were not given. She did not develop adrenal crisis during intrapartum and postpartum period. Mother and baby were discharged after a week of observation.
In 1950, Brent studied 39 cases of Addison’s disease with pregnancy. He stated that symptoms of Addison’s disease may mask those of pregnancy and vice versa. Patients require constant observation, careful supervision, need for hospitalization especially in first trimester of pregnancy. Spontaneous delivery at term has best results. Trainer PJ in 2002 stated that adrenal insufficiency can be difficult to diagnose during pregnancy, however once the diagnosis is made there is usually a successful outcome with careful monitoring, steroidal dose adjustment and parenteral steroidal cover during labor. Quinkler et al in 2012 observed that pregnant women with Addison’s disease mostly do not need to adjust the dose of glucocorticoids in first and second trimester but dose needs to be increased in third trimester due to increased free cortisol during this period. The mineralo-corticoid dose also needs to increase during third trimester due to anti mineralocorticoid action of progesterone.
Early morning plasma cortisol levels < 3 µ/ dL confirm adrenal insufficiency while a cortisol > 19 µ/dL excludes the diagnosis in stable pregnant patients. The patient in this case report had cortisol of 17.21 µ/ dL hence adrenal insufficiency cannot be excluded in spite of normal serum cortisol levels.[8, 9] Plasma cortisol level may fall in the normal range during pregnancy due to increase in cortisol binding globulin concentration in second and third trimester as probably happened in our patient.
The stress of pain, physical exertion, hemorrhage and surgical intervention in labor, the physiological diuresis and withdrawal of adrenal hormones from the fetal adrenals in puerperium can lead to an Addisonian crisis. To prevent this, parenteral cortisone should be administered during labor. Thus, careful monitoring and treatment with steroids in patients with Addison’s disease and pregnancy especially during first trimester, labor and in first week of puerperium results in successful outcome of pregnancy.
Pregnancy with Addison’s disease may present with normal serum cortisol levels; however these cases should be carefully observed for Addison’s crisis during labor and other stress conditions.
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Patil S, Dhokia T, Chauhan AR. Pregnancy with Addison’s Disease. JPGO 2016. Volume 3 No. 10. Available from: http://www.jpgo.org/2016/11/pregnancy-with-addisons-disease.html