A Case report of atypical preeclampsia with severity criteria for hydatidiform complete mole

doi:10.21203/rs.3.rs-2440071/v1

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Case Report

A Case report of atypical preeclampsia with severity criteria for hydatidiform complete mole

https://doi.org/10.21203/rs.3.rs-2440071/v1

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Background: Preeclampsia is defined as the elevation of blood pressure levels and any of the following severity criteria: proteinuria, thrombocytopenia, elevation of creatinine in the absence of another renal pathology, elevation of transaminases, pulmonary oedema or neurological symptoms. This after 20 weeks of gestation in a previously normotensive patient, however, cases of preeclampsia have been described in patients with less than 20 weeks of gestation associated with molar pregnancy.

Case description: A 26-year-old woman, with 14.1 weeks of gestation, is admitted with in the lower extremities, facial oedema, holocranial headache, nausea, epigastralgy, phosphenes and photophobia, with double-length uterine fundus for gestational age and ultrasound. obstetrician who showed image in snowflake, without foetus and annexes with multiple thecal-lutein cysts. Atypical preeclampsia was identified with severity data for complete hydatidiform mole.

Conclusion. Given the possibility of serious complications that may endanger the life of the maternal-foetal binomial, atypical forms of presentation of preeclampsia should be suspected.

Mola

pregnancy

preeclampsia

arterial hypertension

Traditionally preeclampsia has been defined as blood pressure over 140/90 mmHg after 20 weeks of gestation^1,2 in a previously normotensive patient and any of the following characteristics: proteinuria (more than 300 mg in a 24 h urine collection or a protein/creatinine index ≥0.3 mg/mg in a random sample or ≥ 1+ in a reactive urine strip), thrombocytopenia <100,000/ɥL, creatinine elevation >1.1 mg/dL or double over the basal measure in absence of any other renal pathology.

There are other severity criteria even in absence of proteinuria: transaminase elevation at least doubles the superior normal limit, pulmonary oedema and neurologic symptoms such as headache, phosphenes or blurred vision. However, it has been described as atypical preeclampsia in <20 weeks of gestation associated with molar pregnancy³.

On the other hand, the trophoblastic gestational disease comprehends a wide spectrum of pathologies originating in the placenta, such as the trophoblastic tumours of the placental vessels, epithelioid trophoblastic tumour, the choriocarcinoma, the invasive mole (chorioadenoma destruens) and the hydatidiform mole, partial or complete, being the last ones the most frequent form of presentation, almost 80% in the gestational trophoblastic disease⁴. These pathologies, although by separate conglomerates of different epidemiology, for example in a systematic review 4.6% of global pregnancies⁵ had a complication of preeclampsia type.

There are various theories about the physiopathology that provokes preeclampsia, the one that is more accepted refers to a wrong implantation of the placenta which produces that the spiral arteries lost their property of high blood flow, which produces placental ischemia which also produces production of inflammatory factors which finally produces a systemic response because of the peripheral vascular resistance, pro-thrombotic status and endothelial dysfunction⁶.

There are cases of preeclampsia before the 20 weeks of pregnancy, which is uncommon, but that has been reported in molar pregnancies⁷ or associated with antiphospholipid syndrome⁸, which makes the early recognition very important, even in the first trimester, making differential diagnosis with look-alike pathologies such as lupus nephritis, thrombocytopenic purpura and haemolytic uremic syndrome.^9,10

A 26-year-old woman, with 14.1 weeks of gestation, which more relevant clinical records were familiar history of hypertension in her mother and 2 sisters with repetitive abortions, without any other relevant personal risk factors.

She was admitted with 14.1 weeks of gestation by last date of menstruation, with 5-day evolutions symptoms of inferior limbs and facial oedema, headache and intense nausea reaching vomit in various occasions, epigastralgy, phosphenes and photophobia without any transvaginal secretions.

Her blood pressure at admission was 175/108 mmHg, hearth rate of 131 bpm, respiratory rate of 24 breaths per minute, temperature of 36.3°C, oxygen saturation of 94%, 1.55 cm of height and 54.5 kg of weight.

In the physical examination the patient was found conscious, with hyperreflexia and anasarca, cardiac sounds augmented in frequency, low intensity respiratory sounds in the basal areas, increased abdominal perimeter due to gestational uterus with a fundus at 22 cm (double of the expected according to the gestational age table by Fescina et al.), no foetal heart rate was found. Vaginal exploration found mild oedema of genitalia, euthermic cavity, with posterior cervix, large, semi-soft, close, without any secretion or bleeding, limbs with correct anatomy, presence of oedema reaching he knee.

Pelvic ultrasound was performed and a uterus of 24x18 cm with a “snowflake” image was found in the interior, as well as multiple hypoechoic images, without a foetus, also annexes were found with increased volume, with images suggestive of theca-lutein cysts, the right ovary with a cyst >3 cm.

Biochemistry at admission: Haemoglobin 9.7 g/dL, haematocrit 32.1%, platelets 100,000, leukocytes 6,570, neutrophils 3,800 (57.7%), glucose 84 mg/dL, blood ureic nitrogen 22 mg/dL, urea 47 mg/dL, creatinine 0.71 mg/ dL, total bilirubin 0.3 IU/L, direct bilirubin 0.1 IU/L, indirect bilirubin 0.2 IU/L, ALT 18 IU/L, AST 20 IU/L, alkaline phosphatase 65 IU/L, ureic acid 5.68 mg/dL, time of prothrombin 9.7 s, INR 0.91, aPTT 25.8 s, Group O Rh Positive. VDRL negative, HIV negative, total protein 5.3 g/dL, DHL 300 IU/L, Albumin 2.8 g/dL. Urine test showed proteins greater than 300 mg/dL. Human chorionic gonadotropin hormone (B-hCG) 130,000 IU/mL.

It was decided to terminate the pregnancy with manual intrauterine aspiration. Substantial trophoblastic tissue was extracted with grape bunches shape (Fig 1). Afterwards, the patients started with pain and abdominal distention and a second abdominal ultrasound was performed. Approximately 2 L of free-liquid in the paracolic sulc and right subphrenic space was found, with a right annexal image (probably a plastron) and endometrial echography in the medium line of 5 mm (fig 2). This made us think in a broken ectopic pregnancy and exploratory laparotomy was performed in which only abundant serous liquid in the right annex was found, which correspond with a bigger theca lutein cyst reported in USG, but without any alteration in any of the ovaries.

A pulmonary USG was also performed which found bilateral pleural infusion (Fig 3). Follow up continued in the intensive care unit to continue with haemodynamic monitorization and assessment. Rheumatology routine was performed which includes complement levels, anti-DNA antibodies, antinuclear antibodies and lupus anticoagulant, as well as thyroid hormones which resulted normal, this was performed in order to find a specific ethiology and in this case due to the suspicion of atypical preeclampsia^{16, 17}.

Blood pressure control was achieved with nifedipine, hydralazine and alfa-metildopa which were decrease gradually until withdrawn of this last two. Finally, the patient was discharge to receive follow up in out-patient care of gynaecology every 2 weeks to monitor levels of B-hCG to document the hormonal clearance and dismiss any malignant cause that remain them elevated.

The complications in the third trimester of pregnancy, although are well describe, can be fatal and any abnormality requires a integral assessment, especially with first appearance of hypertension, being associated or not to proteinuria¹.

The ultrasonographic exam of the uterus in the 1st trimester and in particular the colour Doppler vaginal echography has made it possible to detect anomalies in the early pregnancy like the hydatidiform mole, that even when the diagnosis is made mostly by this technique, the histologic exam of the evacuated material (Fig. 4) is vital to confirm the diagnosis¹¹. This disease has to be considered always as pre-malignant, because it has been described that 15–20% of the complete mole and 1% of the incomplete can generate malignant degradation of the invasive mole type, choriocarcinoma and in rare cases trophoblastic tumours of the placenta vessels.

After the evacuation of the mole, the patients should be under close monitoring with the quantification of the B-hCG at least every 2 weeks, until non detectable measures are obtained. After this, normal values should persist and being evaluated monthly for a minimum of 6 months¹².

In 10–20% of the patients in which the B-hCG levels remain high, various courses of chemotherapy could be required, depending on the FIGO and WHO stratification for gestational trophoblastic neoplasia¹³. In general, the patients are no longer required to receive prophylactic chemotherapy in the diagnosis of mole, this produces an unnecessary exposure in 80% of the cases and it should only be offered in patients which would not receive the appropriate follow-up¹².

The complications of a molar pregnancy are another topic that should be considered as well and not only the risk of neoplasia evolution. Firstly, one of the most relevant are the hyperthyroidism (because of the similarities between the α subunits of HCG and the TSH) in which a beta-adrenergic blockade could be required to prevent and revert metabolic and cardiovascular complications of a thyroid storm¹⁴.

Secondly, the thecal-lutein ovarian cysts, secondary to the ovarian hyperstimulation, which could be twisted or spontaneously broken (this actually might have been the cause of the abdominal syndrome that the patient presented posterior to the evacuation of the mole; however this was not evidenced in the moment of rupture with the laparotomy). Lastly, the cardiopulmonary symptoms that are associated to the trophoblastic emboly¹³.

All the aforementioned have a general trend of resolution according to the diminish of the B-hCG levels. The patients that present hyperemesis related to pregnancy in 8–28% generally in earlier stages of gestation and with more severity because of the high levels of this hormones related to different isoforms or mutations in the receptors of this hormone⁷.

The total levels of hCG are crucial for the follow up of the patients with gestational trophoblastic disorder. The chemical exams should measure all the portions of the molecule in particular the free- beta subunit, the hCG hyperglycosylated, hCG “nicked” and the hCG without the terminal carboxyl segment, because these segments in particular are higher in neoplasia than the total hCG.

Other clinical entity, although not very frequent that clinicians should also considered is the ghost hCG where the patients contain heterophilic antibodies that react with antibodies of certain analysis kits which generates a false positive result of hCG¹⁵,

In general, the patients with history of molar pregnancy either partial or complete can have other reproductive successful attempts, they only posses a higher risk of recurrence between 1-1.9% and after 2 or more molar pregnancies it increases to 15-17.5%¹⁶.

Lastly, it can result fatal not to maintain a suspicious of preeclampsia in an early pregnancy before 20 weeks in a clinical context that results relevant, although the prevalence is low, like it could have been in the case of this patients that coursed with severity criteria preeclampsia.

When treating a pregnant woman, we need to always consider, independently of the gestational stage, the possibility of severe complications that can threatened the life of the binomial. Is vital to know the updated definitions according to the latest guidelines of any disease that we are treating, although we also need to take in count atypical cases that could not match entirely with the definitions and that make us think in differential diagnosis or look after atypical forms of presentation of a disease, like it was the case of this patient.

Ethics approval and consent to participate

Consent for publication

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient have given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

Not applicable

Authors' contributions

OP, CH,KP,RF, JU, JA analyzed and interpreted the patient data, and conception of the work

OP, CH,KP,RF, JU, JA,MP, EZ,ED write the manuscript

All authors read and approved the final manuscript

Acknowledgements

Authors give thanks to a Kenia González-Perales, José Roberto Gallardo-Soberanis for their assistance during the assessment and treatment of this case.

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No competing interests reported.

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A Case report of atypical preeclampsia with severity criteria for hydatidiform complete mole

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