Hypothyroidism and Double Mitral Lesion in Antiphospholipid Syndrome During Pregnancy: A Case Report

Introduction

Hypothyroidism is the most common thyroid pathology in the general population, as well as in pregnant women, and occurs in 0.3–2.5% of them [1,2]. It is a systemic disorder caused by a decrease in the function of the thyroid gland [3], whose most prominent function is hormonal regulation [4], and if left untreated, can cause serious adverse health effects on multiple organ systems, with the cardiovascular system being the most studied target [5].

Gestational hypothyroidism has been linked to a higher risk of premature delivery, intrauterine growth restriction (IUGR) fetuses, miscarriage, and risk of fetal death [6]. Adverse maternal-fetal outcomes of subclinical hypothyroidism during pregnancy include higher risk for pregnancy loss, placental abruption, premature rupture of membranes, neonatal death [7], gestational diabetes, gestational hypertension, preeclampsia [8], low birth weight, small size for gestational age, and low Apgar score [9]. Also, high thyroid-stimulating hormone (TSH) levels in pregnant women have been associated with an increased risk of neurocognitive deficit in the offspring [10], leading to a decline in the areas of learning and language [11], word discrimination, and Conners tests (attention disorders) [10], which are more common in children born to mothers with hypothyroidism than in children born to euthyroid mothers. Thyroid deficiencies at different stages of pregnancy impact diverse brain regions, including the neocortex, medial ganglionic eminence, cerebellum, hippocampus, and myelinated white matter tracts such as the corpus callosum and basal ganglia [12]. Autoimmune thyroid disease and APS are common in childbearing age women and can lead to recurrent miscarriages. APS is significantly more common in patients with autoimmune thyroid disease, especially Hashimoto’s thyroiditis [13]. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombosis and recurrent early pregnancy loss, all in the presence of positive antiphospholipid antibodies (aPL). Its prevalence in the general population ranges is 1–5%, while the prevalence of APS ranges is 40–50 cases per 100 000 people, being more common in women [14]. In pregnant women, APS can have significant impacts and lead to serious complications for both the mother and the fetus. One of the most common complications of APS during pregnancy is recurrent miscarriage. Often occurring in the second or third trimester, this is due to the formation of blood clots in the placenta, which can impair blood flow and nutrient exchange between the mother and the fetus [15]. Pregnant women with APS are at a higher risk of developing preeclampsia and, in severe cases, eclampsia, which can lead to seizures. Both conditions can endanger the lives of the mother and the baby. Poor blood supply to the placenta due to clot formation can lead to IUGR, meaning the fetus does not grow at the expected rate. This can result in preterm delivery or the need for early induction to protect the baby’s health [16]. Women with APS are at higher risk for deep vein thrombosis (DVT) and pulmonary embolism (PE), which can be life-threatening. The risk increases during pregnancy and the postpartum period due to physiological changes that make the blood more prone to clotting [17]. APS presents as an independent pathology known as primary APS, although it can also appear together with another autoimmune disorder, particularly systemic lupus erythematosus [18,19]. Some antibodies aPL reported include lupus anticoagulant, anticardiolipin (aCL), and anti-β2Glycoprotein I [20,21], which constitute an important cause of cardiovascular events in young people [22].

aPL can affect the heart, and valvular heart disease appears to be the most common clinical manifestation of this [23]. Although heart disease is not very common among pregnant women, its incidence is 0.4–2% and continues to be an important cause of maternal mortality [24,25]. The mitral valve is the most frequently affected (63%) [26], followed by the aortic (32%) [27] and tricuspid (8%) valves [28]. Young women may have asymptomatic mitral valve disease that manifests during the hemodynamic stress of pregnancy [29–31]. This report, unique in its documentation, describes a 34-year-old woman presenting simultaneously with hypothyroidism and antiphospholipid syndrome with mitral valve fibrosis at 26 weeks of pregnancy.

Case Report

TREATMENT IN INTENSIVE CARE:

The patient was admitted to intensive care, and treated with enoxaparin, bisoprolol, intravenous furosemide, and levothyroxine. A new transthoracic echocardiogram showed no significant differences (data not shown) compared with the first one. A new electrocardiogram was also performed with a ventricular rate of 92 bpm, PR interval of 120 ms, QRS duration of 100 ms, and sinus rhythm (Figure 1B). The patient underwent an abdominal and obstetric ultrasound: in relation to the liver, intra- and extrahepatic bile duct, and spleen without ultrasound alteration at the time of study. Both kidneys were of the usual shape, size, and location for the patient’s age, with no evidence at the time of the study of images suggestive of stones or masses. An ultrasound study in relation to the pregnancy at 25 weeks 5 days by fetometry was normal. She had grade II anterior placenta without evidence of abruption or hematoma at the time of the study, and amniotic fluid with ultrasound characteristics according to gestational age (data not shown).

The patient’s condition improved, leading to her discharge from the intensive care unit on May 27, 2023. She was discharged with enoxaparin and furosemide until August, avoiding contraindicated medications or medications with maternal-fetal risk (such as ACE inhibitors).

After discharge, the patient was managed on an outpatient basis by Cardiology, Endocrinology, and Obstetrics, presenting a normal pregnancy, with visits every 15 days, with intake of hematinics, folates, calcium, vitamin D, and natural micronized progesterone. The evaluation of the pregnancy was normal, with no obstetric or infectious complications. It was decided to terminate the pregnancy by abdominal route due to maternal pathology at 36.5 weeks of gestation on August 10, 2023, delivering a male neonate at 38 weeks of gestation by Capurro, weighing 2805 grams, and Apgar score 9/9.

After delivery, the patient presented a mediate and immediate puerperium without obstetric complications and without signs of orthopnea or chest pain. Only paracetamol and ceftriaxone were administered when the patient was discharged on the third day after cesarean section. Treatment at discharge consisted of acenocoumarol and bisoprolol, and diuretics were gradually reduced until discontinuation, in addition to hematinics and calcium plus vitamin D during the postpartum period.

Discussion

Every patient with APS and hypothyroidism should undergo a preconception cardiovascular assessment. If not performed beforehand, it should be conducted as soon as possible upon pregnancy diagnosis [32]. We described the case of a woman with double mitral lesion, hypothyroidism, and antiphospholipid syndrome during pregnancy. The surveillance of the patient was carried out between the obstetrician-gynecologist, internist, and cardiologist, with exhaustive prenatal control every 15 days, and every week if necessary, at any time. There is a recognized association between APS and autoimmune hypothyroidism. In our patient, the diagnosis (Sapporo/Sydney 2006 criteria) of APS was established in 2017 with positive titers of anti-β2-glycoprotein I and anticardiolipin IgG antibodies, while the diagnosis of thyroid disease was based on antiTPO and anti-thyroglobulin antibodies.

In a recently published study [33], a review of 70 pregnancies in 62 women presenting aPL was performed. The factors associated with a worse obstetric prognosis were triple positivity for aPL, and the presence of acquired risk factors, which were mainly cardiovascular, as well as manifestations associated with APS and systemic lupus erythematosus (SLE). Heart valve disease is the most common abnormality in patients with positive aPL [34] and is detected in more than 80% of the population through sensitive examinations such as transesophageal echocardiography [32]. Its prevalence is higher when it is associated with SLE [35].

The treatment of hypothyroidism in pregnant patients requires adjustment of the levothyroxine dosage, as requirements increase from the early weeks of gestation. Frequent monitoring of TSH levels is recommended, starting at the first prenatal visit and every 4 weeks thereafter, adjusting the dosage according to pregnancy-specific reference ranges. Patients with a TSH level greater than 2.5 mIU/L and positive antiTPO antibodies have a higher risk of complications such as preterm birth and pregnancy loss [36]. Studies have reported maternal-fetal outcomes in pregnant women suffering hypothyroidism, such as IUGR fetuses, miscarriage, risk of fetal death, [7] gestational diabetes, hypertension, and preeclampsia [9].

One of the many clinical manifestations in APS is valvular heart disease, which is defined by the presence of nodules or vegetations and valvular dysfunction in the absence of a history of rheumatic fever or endocarditis [22]. APS tends to affect the left heart valve, with a predilection for the mitral valve, and it can lead to valvular dysfunction. Although the pathophysiology is not yet fully understood, it is believed that APS forms immune complexes that injure the valvular endothelium, causing fibrotic changes in the valve [37].

Studies have shown a correlation between elevated aCL and mitral valve thickening, predominantly of the IgG type. Our patient previously presented positive titers of this antibody type, which are an associated risk factor for recurrent cardiac events [25,38,39], indicating that higher levels of these antibodies are associated with greater severity of valvular lesions [28,40].

Although heart disease in pregnancy is rare (0.4–2%), it remains a significant cause of maternal mortality. This is due to the hemodynamic changes that occur during pregnancy, which may be well tolerated by healthy women, but carry a significant risk for those with preexisting heart disease [24]. Vascular thrombosis and pregnancy ending in stillbirth are among the vascular manifestations of APS caused by aPL, and is a criterion of the Sapporo classification. Proper treatment is essential to improve the condition [23].

In patients with APS, valvular lesions can be as sources of emboli, increasing the risk of thromboembolic events such as systemic or cerebral embolisms. This has important clinical implications, as patients with APS and mitral lesions are at higher risk for strokes or transient ischemic attacks. Valvular lesions can progress to significant fibrosis, resulting in clinically relevant mitral stenosis. This condition may require more invasive interventions, such as valve replacement in severe cases [41].

Immunopathological studies of valves from patients with antiphospholipid or SLE-associated syndrome have shown deposits of aCL and complement components in the subendocardium of affected valves [42,43], suggesting a possible pathogenic role [44] of the antibodies in valvular disease [45].

The association between APS and valvular pathology is a key factor in the predisposition to thrombotic events and cardiac structural alterations. The evolution of valvular lesions reinforces the importance of echocardiographic monitoring and anticoagulant management in patients with APS [41].

In general, most patients with heart disease who can successfully carry a pregnancy to term [46], with adequate obstetric follow-up [47], are asymptomatic and without hemodynamic repercussions [48,49]. The risk of adverse events during pregnancy for women with preexisting cardiovascular disease is determined by their ability to adapt to the physiological changes of pregnancy [50], by the nature of the heart disease, and by the hemodynamic impact [51,52]. Mitral prolapse is the most common cause of regurgitation [53] in young women during pregnancy [54,55], which is characterized by allowing blood from the left ventricle to return to the left atrium during systole [56,57].

For the diagnosis, anamnesis and clinical examination are very important [58], and auscultatory signs can suggest the diagnosis [59]. Another complementary test used is the electrocardiogram [60]. During pregnancy, QRS axis deviation, small Q wave, inverted T wave in DIII, sinus tachycardia, and changes in the ST segment and T wave can occur, as well as atrial and ventricular premature beats [61,62].

Because an electrocardiogram in the early stages of double mitral injury is not a sensitive method, an echocardiogram was used; echocardiograms [63,64] allow the mechanism of mitral regurgitation to be determined and quantified [65,66]. If it is inconclusive, three-dimensional echocardiography, magnetic resonance imaging [67,68], and stress echocardiography [61] are useful in the diagnosis. Complete laboratory tests should be requested, including coagulation tests [69], and liver and kidney function. The change in pharmacological treatment was based on protection of the mother and fetus [70]. The most commonly used cardiovascular drugs are shown in Table 4 [69].

The patient showed a good response to medical treatment during acute decompensation and maintained stable, allowing the pregnancy to be carried to term successfully. A cesarean section was performed without complications, with preventive measures appropriate for her history. She required control and monitoring of her valvular disease and hypercoagulability, with a low-sodium diet and control of oral fluids, relative rest, vitamin and nutritional supplements, and biophysical profiling of the fetus [69,70], along with a cardiotocography test without stress [71]. Her decompensated mitral valve disease was successfully managed during pregnancy by the timely intervention of specialists and monitoring of both the baby and the mother during and after delivery.

The treatment for pregnant women with APS has 2 main objectives: to protect the mother from thrombotic phenomena and to minimize fetal morbidity. Drugs such as glucocorticoids, oral anticoagulants, acetylsalicylic acid, heparin, and intravenous immunoglobulins can be used [72].

This case is of special interest due to the challenging clinical management. Valvular heart disease in patients with APS is associated with a higher risk for strokes or transient ischemic attacks; therefore, in pregnant women with APS, valvular disease should always be ruled out.

Conclusions

The symptoms presented by the patient during pregnancy were characterized by acute precordial pain that increased in intensity, in addition to orthopnea. Early and accurate detection, as well as timely treatment of valvular disease, in patients with APS is crucial. Based on these case report findings, and the risk of valvular disease, we recommend a cardiac evaluation during or before pregnancy for patients with a history of hypothyroidism, APS, and prior fetal loss.

Based on the results of this patient, it can be concluded that although such patients may tolerate pregnancy well, gestational cardiovascular changes can generate severe decompensation; therefore, a timely diagnosis must be made to ensure a successful full-term pregnancy.