Case Report: Hyperreactio luteinalis associated with chronic renal failure

M. Al-Ramahi1,2 and A. Leader1,3

Division of Reproductive Medicine, Department of Obstetrics and Gynecology, University of Ottawa, Ottawa Hospital,1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Hyperreactio luteinalis is a rare benign condition characterized by bilateral ovarian enlargement associated with pregnancies where high concentrations of maternal serum human chorionic gonadotrophins are present. This condition may mimic the ovarian hyperstimulation syndrome. We report a case of a 34 year old woman with a history of chronic renal failure on haemodialysis who presented at 10 weeks' gestational age with hyperreactio luteinalis which was treated conservatively. Because of chronic renal failure, the presentation and course of the disease was different from that which has been previously reported.

Key words: chronic renal failure/haemodialysis/hyperreactio luteinalis


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Hyperreactio luteinalis is an uncommon condition associated with bilateral and rarely unilateral ovarian enlargement due to theca lutein cyst formation. In some cases it may present with a fluid shift leading to ascites, hydrothorax (Foulk et al., 1997Go) or even anasarca (Lambers and Rosenn, 1996Go). Patients can be asymptomatic and the condition may be discovered accidentally at a routine pelvic ultrasound or at Caesarean section. Symptomatic patients may present with abdominal discomfort, dyspnoea, or abdominal pain as a result of ovarian torsion or haemorrhage. This condition usually complicates those pregnancies in which higher concentrations of maternal serum human chorionic gonadotrophin (HCG) are found, such as gestational trophoblastic disease, hyperplacentation in multiple pregnancies or rhesus isoimmunization. It may occur when the ovaries are exposed for a prolonged period to HCG.


    Case report
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 34 year old primigravida with a 5 year history of chronic renal failure who was on haemodialysis three times per week presented to the emergency department. She complained of abdominal distension, which had been slowly increasing and had become worse in the 3 days prior to her emergency visit. Her gynaecological history revealed that menarche occurred at age 14 years and she had regular menstrual cycles. Her past history was negative for induction of ovulation or diabetes. On examination her pulse was 84/min, respiratory rate was 20/min and her blood pressure was 150/92 mm Hg. Her chest was clear. Her abdomen was distended and tense with an irregular mass occupying the lower quadrants. Ascites was present.

A transabdominal pelvic ultrasound showed a single viable intrauterine pregnancy of 10 weeks' gestational age. There was a bilateral ovarian enlargement with multilocular cysts. Massive ascites extending to the diaphragm was noted. Her complete blood count revealed: haemoglobin 122 g/l, haematocrit 0.366, white blood cell concentration 8.2 x 109/l, and platelet concentration 196 x 109/l. Her electrolyte concentrations were: sodium 129 mmol/l, potassium 4.2 mmol/l, urea 13.4 mmol/l, creatinine 794 µmol/l, albumin 34 g/l.

The patient was admitted for conservative treatment. There was concern about thrombosis; therefore she was started on prophylactic heparin 5000 IU s.c. every 12 h, and continued on dialysis. Results of blood tests performed on the day after admission are shown in Table IGo. Four days later, she had vaginal spotting that was associated with lower abdominal pain. This was followed by the passage of tissue. Subsequently the patient underwent a dilatation and curettage for an incomplete abortion. The pathology report confirmed the presence of products of conception.


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Table I. Analysis of blood sample taken from patient on the day after admission
 
The day following surgery, the patient experienced abdominal discomfort with increasing distension and required paracentesis. About 600 ml of serosanguineous fluid was removed. The woman was discharged 2 days after this paracentesis. Four days later she returned to the emergency department with abdominal discomfort and nausea. Her ß-HCG was 84 986 IU/l. Ultrasound examination revealed massive amounts of ascites and a second paracentesis removed 4 l of serosanguineous fluid. Samples sent to cytology on both occasions were negative for malignancy. The patient was discharged 2 days after her paracentesis. The same complaints initiated another visit to the emergency department 1 week after this discharge. Her ß-HCG at that time was 14 948 IU/l, and a pelvic ultrasound revealed a large amount of ascites for which she was treated conservatively and discharged. Follow-up occurred weekly for 2 weeks, and then biweekly until she had a normal pelvic ultrasound showing normal ovaries with no ascites. This was achieved 10 weeks after her first admission. At this stage all blood values were normal except her prolactin (85 µg/l) and ß-HCG which remained at 111 IU/l. Her ß-HCG became negative 6 weeks later.


    Discussion
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
This is a unique presentation of hyperreactio luteinalis. Chronic renal failure is often associated with infertility due to oligomenorrhoea. Pregnancy in these patients is often diagnosed late because of menstrual irregularities associated with this condition. Fertility may be restored with dialysis but the fetal prognosis is poor (Cunningham et al., 1993Go). Pregnancy complications associated with dialysis may include spontaneous abortion, hypertension leading to pre-eclampsia and abruptio placenta, and preterm labour. Hou (1994) reviewed the pregnancy outcome in 60 pregnant patients undergoing dialysis. The incidence of spontaneous abortion was 40% and only 40% of pregnancies had a surviving infant. The patient in this case report was aware that she may have difficulty achieving pregnancy and that once achieved, the prognosis for a good outcome would be poor.

The aetiology of hyperreactio luteinalis is unknown, but it is believed that the production of high concentrations of HCG and increased ovarian sensitivity to prolonged exposure to HCG (Bradshaw et al., 1986Go) may be manifested as an exaggerated ovarian response leading to theca lutein cyst formation. This may be associated with gestational trophoblastic disease in 30–50% of cases (Clement, 1993Go) or hyperplacentation as is seen in multiple pregnancy, diabetes, and rhesus isoimmunization. This patient had a prolonged exposure to high concentrations of HCG because of the decreased clearance of HCG due to anuria resulting from her chronic renal failure.

There was improvement of her symptoms 6 weeks after the spontaneous abortion; however, the ß-HCG did not become negative until 16 weeks after the miscarriage. Because of chronic renal failure, the resolution of symptoms and ß-HCG was very slow.

Hyperreactio luteinalis can mimic ovarian hyperstimulation syndrome (OHSS). Patients with OHSS usually have a history of induction of ovulation. Although it is rare, OHSS may be spontaneous (Zalel et al., 1992Go; Ayhan et al., 1996Go). OHSS is usually manifested in the early first trimester with a rapid increase in ovarian size and fluid shift leading to ascites or hydrothorax in some cases. Patients usually present with a history of rapid weight gain, bloating and abdominal discomfort, and gastro-intestinal symptoms. In severe cases they may present with thrombo-embolic disorders or renal failure. Patients may require admission, hydration and prophylactic heparinization. They may undergo paracentesis or thoracocentesis as needed. OHSS usually resolves spontaneously although resolution may be delayed by up to 3 weeks in pregnant patients.

Hyperreactio luteinalis is usually asymptomatic. It may be discovered during a routine pelvic ultrasound for pregnancy, during Caesarean section or sometimes post partum. In symptomatic cases, patients may present with abdominal bloating or cyst complications, such as torsion and haemorrhage. In some cases it may be associated with fluid shift. Lambers and Rosenn (1996) described a case of hyperreactio luteinalis associated with normal singleton pregnancy where pregnancy termination was carried out for maternal respiratory decompensation secondary to pleural effusion and ascites. O'Loughlin and Brookes (1987) reported a 16 weeks pregnant patient who presented with dyspnoea and abdominal discomfort secondary to massive ascites and pleural effusion and underwent exploratory laparotomy with partial ovarian resection.

In this report, the woman presented with a spontaneous severe OHSS-like picture. Knowing that the patient was on haemodialysis, we were not expecting the usual haemoconcentration and electrolyte imbalance associated with severe OHSS. Subsequent to her abortion, it might have been expected that she would achieve a rapid resolution of her symptoms; however, in this case the ß-HCG concentrations remained high and her symptoms persisted. The pathology report confirmed an intrauterine conception without trophoblastic changes. The most likely diagnosis of this condition is therefore hyperreactio luteinalis which did not resolve subsequent to termination of pregnancy due to the persistence of high concentrations of ß-HCG in circulation. During this period of time, free testosterone was also elevated confirming the hyperandrogenic state that may be associated with hyperreactio luteinalis. Once the hyperreactio luteinalis had resolved, this patient's free testosterone did return to normal values. Hyperprolactinaemia is ongoing in this patient and is associated with chronic renal failure and dialysis (Hochstetler et al., 1994Go).

Although infrequent, pregnancy can occur in women with chronic renal failure when they undergo haemodialysis. The prognosis for a live birth delivery is poor. These patients may develop hyperreactio luteinalis due to the decreased clearance of ß-HCG.


    Notes
 
2 Present address: Department of Obstetrics and Gynecology,Jordan University Hospital, Amman, Jordan Back

3 To whom correspondence should be addressed Back


    References
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Ayhan, A., Tuncer, Z.S. and Aksu, A.T. (1996) Ovarian hyperstimulation syndrome associated with spontaneous pregnancy. Hum. Reprod., 11, 1600–1601.[Abstract]

Bradshaw, K.D., Santos-Ramos, R., Rawlins, S.C. et al. (1986) Endocrine studies in a pregnancy complicated by ovarian theca lutein cysts and hyperreactio luteinalis. Obstet. Gynecol., 67, 66–69.

Clement, P.B. (1993) Tumor-like lesions of the ovary associated with pregnancy. Int. J. Gyencol. Pathol., 12, 108–115.

Cunningham, F.G., MacDonald, P.C., Gant, N.F. et al. (eds) (1993) Williams obstetrics. Appleton and Lange, Norwalk, pp. 1139–1140.

Foulk, R.A., Martin, M.C., Jenkins, G.L. et al. (1997) Hyperreactio luteinalis differentiated from severe ovarian hyperstimulation syndrome in a spontaneously conceived pregnancy. Am. J. Obstet. Gynecol., 176, 1300–1304.[ISI][Medline]

Hochstetler, L.A., Flanigan, M.J. and Lim, V.S. (1994) Abnormal endocrine tests in a haemodialysis patient. J. Am. Soc. Nephrol., 4, 1774–1779.

Hou, S. (1994) Frequency and outcome of pregnancy in women on dialysis. Am. J. Kidney Dis., 23, 60.[ISI][Medline]

Lambers, D.S. and Rosenn, B. (1996) Hyperreactio luteinalis complicating a normal singleton pregnancy. Am. J. Perinatol., 8, 491–493.

O'Loughlin, J. and Brookes, C.M. (1987) Massive multiple theca lutein cysts complicating nonmolar pregnancy. Aust. N.Z. J. Obstet. Gynecol., 27, 166–168.[ISI][Medline]

Zalel, Y., Katz, Z., Caspi, B. et al. (1992) Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a women with polycystic ovary disease. Am. J. Obstet. Gynecol., 167, 122–124.[ISI][Medline]

Submitted on May 12, 1998; accepted on November 4, 1998.