Abstract
Introduction
We report a case of Cushing’s syndrome (CS) in pregnancy. CS occurs due to abnormal exposure to excess glucocorticoids for a prolonged duration which leads to significant consequences if not treated. Fortunately, it is rare in pregnancy because of the menstrual disturbances and infertility with which it is associated. 1 Its rarity leads to a low degree of clinical suspicion, often delaying diagnosis more or less completely. When it does occur, a high rate of miscarriage or preterm delivery and even sudden intrauterine death may be expected. Maternal morbidity includes hypertension, preeclampsia, wound breakdown, diabetes, fracture and opportunistic infections.2,3
Case Report
A 30-year-old multigravida patient, unbooked at 27 weeks of pregnancy, was admitted to the Emergency Department of Era’s Lucknow Medical College with chief complaints of generalised weakness and breathlessness for the previous 1 month. She was apparently asymptomatic until she experienced progressive increase in her body weight, raised blood pressure, deranged blood sugars and proteinuria. There were no similar complaints in the family. There was no past history of hypertension, diabetes, asthma and coagulopathy, intake of exogenous hormonal intake or steroid intake. On general examination, the patient was breathless, conscious and oriented, febrile, hypertensive (170/110 mmHg), tachycardic (130/min) and tachypnoeic (35/min). She had a BMI of 29.5 kg/m2, a moon face, hirsutism, purple striations all over the body, easy bruising, truncal obesity, severe pedal oedema and hyper pigmentation: in short, a classic appearance of CS. Investigations revealed an anaemia (Hb 95 g/L), fasting blood sugar was 11.9 mmol/L and post prandial was 16.09 mmol/L. Serum total proteins were 54 g/L, albumin was 28 g/L, HBA1C was 8.1%, LDH was 1632 (normal range, 105–333 IU/L), 24 h urinary protein 2.40 g (normal, <0.15 g), 24-h urine-free cortisol (UFC) 3467 nmol/24 h (normal range, 9.6–124 nmol/24 h). Ultrasonography revealed a 23-week gestation with oligohydramnios and absent fetal cardiac activity. Maternal MRI revealed a normal sella turcica. Antihypertensives and insulin were used but the patient’s condition deteriorated resulting in the decision to terminate the pregnancy. Post-delivery contrast-enhanced computed tomography (CT) abdominal scan revealed a well-defined hypoechoic space occupying lesion in the left adrenal gland of 3.8 × 3.9 cm suggestive of adrenal adenoma (Figure 1). An adrenalectomy for a histologically proven benign adenoma was performed. On discharge, 15 mg prednisolone daily was advised for 2 months. The patient remained asymptomatic.
Contrast-enhanced CT scan of the abdomen showing left-sided adrenal adenoma.
Discussion
Hyperandrogenism and hypercortisolism associated with CS suppress gonadotrophins, so pregnancy is uncommon in these women. 3 This also leads to oligomenorrhoea and amenorrhoea which are reported in approximately 75% of women of reproductive age diagnosed with CS. In patients with CS due to an adrenal adenoma (purely cortsol-producing tumours), ovulatory functions remains unaffected 4 so they are able to conceive. During pregnancy there is an increase in serum cortisol, UFC and plasma ACTH levels, which complicates the screening process for CS. 5 Whereas UFC excretion is normal in the first trimester, it increases up to three-fold by term significantly overlapping with the values seen in pregnant women with CS. 6 Therefore in order to label a case as that of CS, only UFC values in the second and third trimester greater than 3 times the upper limit of normal are considered as diagnostic. In CS there is 10–12-fold rise in serum cortisol levels. Pregnancy prominently affects the hypothalamic pituitary adrenal axis and the endogenous secretion of cortisol and ACTH but it has no effect on the circadian rhythm of cortisol and ACTH secretion 6 which is not the case with CS. These changes are attributed to the high levels of placental corticotrophin releasing hormone (CRH) in plasma during the latter half of pregnancy. Similarly, the measurement of plasma ACTH, the 8-mg high-dose dexamethasone suppression test (HDST), CRH stimulation test and bilateral inferior petrosal sinus sampling (IPSS) are various tests done for the differential diagnosis of CS in pregnancy but they have not been evaluated systematically in pregnancy.
Conclusion
CS in pregnancy is a rare entity. Its management can be best achieved by a multidisciplinary approach consisting of endrocrinologist, obstetrician, anaesthesiologist and endocrine surgeon. No specific guidelines are yet available for its diagnosis in pregnancy. The treatment plan in each case is dependent upon the clinician’s experience and the patient’s general condition.
Footnotes
Acknowledgements
We thank the patient and her attendants for their cooperation.
Competing interests
All the authors have seen the manuscript and approve it for submission. The authors have no competing interest in the publication of the manuscript to declare.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.