Severe hypertriglyceridemia during pregnancy in a hypothyroid patient: A case report and literature review

Key clinical message

Severe hypertriglyceridemia in pregnancy, especially in hypothyroid patients, poses significant risks, including acute pancreatitis. This case underscores the importance of lipid monitoring and thyroid management in pregnant women. A multidisciplinary approach is crucial for reducing maternal and fetal risks, ensuring timely intervention, and optimizing outcomes in these high-risk pregnancies.

Introduction

Pregnancy is associated with significant alterations in lipid metabolism. While routine lipid panel screening is not a standard component of antenatal care in normal pregnancies, it is known that serum triglyceride (TG) levels progressively rise, though they typically stay below 300 mg/dL (3.4 mmol/L) in healthy women.^1,2 Acute pancreatitis is an uncommon but serious complication, with an estimated incidence of 1 in 1000 to 1 in 10,000 pregnancies.^3,4 In individuals with genetic or secondary lipid metabolism abnormalities, the physiological rise in TGs can lead to severe hypertriglyceridemia, which is responsible for up to 56% of all pancreatitis cases during gestation and has also been associated with an increased risk of preeclampsia.^3,4

All major lipoprotein fractions experience concentration changes during pregnancy. Compared to pre-conception levels, very-low-density lipoprotein (VLDL) cholesterol and triglycerides increase by approximately 2.5 times, while low-density lipoprotein (LDL) cholesterol rises by 1.6 times, reaching peak levels near term. ¹ High-density lipoprotein (HDL) cholesterol initially rises during mid-gestation but declines slightly towards term. While human studies on the exact mechanisms remain limited, evidence from animal research suggests increased hepatic VLDL production and reduced lipoprotein lipase activity in adipose tissue as contributing factors. ⁵ These changes are thought to be hormonally driven, with oestrogen and other sex hormones playing a central role in modulating lipid dynamics. ⁶

In this report, we present a case of a pregnant woman with recurrent episodes of hypertriglyceridemia-induced pancreatitis, including one episode necessitating plasmapheresis. A comprehensive review of related literature is also included to highlight relevant clinical considerations and management approaches.

Case presentation

Case history and examination

A 34-year-old Indian female, G2P1, at 32 weeks of gestation, presented to the Emergency Department with a 1-day history of severe, sharp, epigastric pain, accompanied by nausea and vomiting. The pain was non-radiating. Upon presentation, her vitals were stable except for episodes of tachycardia reaching up to 110 beats per minute. Physical examination revealed tenderness in the epigastric area without rebound tenderness. The fundal height corresponded to her gestational age, and fetal heart rate was positive with a cephalic presentation. Cardiotocography was category 1, indicating no fetal distress or contractions.

In reviewing her medical history, the patient had a diagnosis of type 2 diabetes, with a recent HbA1c of 7.8%, and hypothyroidism, with a TSH of 4.5 mIU/L on admission, managed with levothyroxine (LT4). Prior to this pregnancy, her lipid-lowering regimen consisted of Rosuvastatin 20 mg and Fenofibrate 200 mg. She had a history of recurrent triglyceride-induced pancreatitis, occurring four times since 2014. While no formal documentation was available, she reported a strong family history of hyperlipidaemia affecting several first-degree relatives, suggesting a probable hereditary component. In her previous pregnancy, she also experienced acute pancreatitis at 32 weeks of gestation, with TG levels reaching 35 mmol/L (Figure 1). Her treatment at the time included insulin infusion and dextrose, and she was subsequently discharged on Gemfibrozil 600 mg BID and Omega-3 Ethyl Esters 1000 mg BID.

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Figure 1.

Representing levels of TSH and T4, respectively, upon different presentations from (1 February 2017 till 1 June 2022).

Following her first pregnancy, she remained stable until delivery at 38 weeks, when an emergency caesarean section was performed due to failure to progress. She delivered a healthy 3130 g baby boy. She was prescribed Atorvastatin 20 mg postpartum, in addition to her previous medications, with a TG level of 5.7 mmol/L at discharge. However, she was not counselled that statins are contraindicated during lactation and continued to breastfeed. Statins are excreted into breast milk and carry a theoretical risk of disrupting infant cholesterol synthesis, which is vital for development, although no adverse effects were noted in her infant. Two months postpartum, her labs showed an elevated total cholesterol level of 9 mmol/L (normal range <5.2 mmol/L), and her primary care physician subsequently switched her from Gemfibrozil to Fenofibrate 200 mg and from Atorvastatin to Rosuvastatin 20 mg. She was later admitted with another episode of triglyceride-induced pancreatitis, with a TG level of 22 mmol/L, and treated with insulin infusion and dextrose.

Methods

Investigations

Laboratory tests on admission confirmed a diagnosis of acute pancreatitis. Key findings are summarized in Table 1. Abdominal ultrasound (Figure 2) showed a bulky and heterogeneous pancreas with a mild amount of free intraperitoneal fluid in the perihepatic, peri-splenic, and iliac regions. Additional lab results indicated no other significant abnormalities.

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Table 1.

Key laboratory investigations on admission.

Investigation	Result	Reference range
Triglycerides	33.8 mmol/L	<1.7 mmol/L
Serum amylase	450 U/L	30–110 U/L
Serum lipase	620 U/L	10–140 U/L
HbA1c	7.8%	<6.0%
Thyroid stimulating Hormone (TSH)	4.5 mIU/L	0.4–4.0 mIU/L

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Figure 2.

Abdominal ultrasound showed a bulky and heterogeneous pancreas with a mild amount of free intraperitoneal fluid in the perihepatic, perisplenic, and iliac regions.

Conclusion and results

A multidisciplinary team, including obstetricians, neonatologists, and anaesthesiologists, determined that the risk of another pancreatitis episode outweighed the risks associated with early delivery. At 35 weeks of gestation, an elective caesarean section with bilateral tubal ligation was performed, delivering a 2218 g baby boy. Postpartum, the patient’s TG levels stabilized at under 11 mmol/L, and both mother and baby had a stable postoperative course.

Discussion

While variations in glucose metabolism during pregnancy are fairly well established, changes in lipoprotein physiology are just now being thoroughly investigated, and it is unclear what physiological significance these changes have for fetal growth. ¹ It was first discovered by Virchow that pregnant plasma’s noticeable turbidity is lipidic in origin. Since then, multiple studies have demonstrated a two- to four-fold increase in plasma total triglycerides. ⁵

The same increases in LDL and HDL triglyceride/cholesterol ratio in oral contraceptive or oestrogen-treated subjects offered a first indication that the lipoprotein lipid alterations in pregnancy are sex hormone-induced. ⁶ A difference in mean ratio does not always signify a meaningful change in composition because the ratio of cholesterol to triglycerides in a lipoprotein fraction is a curvilinear function of the triglyceride concentration. ⁷

The main cause of severe hypertriglyceridemia is a genetic disease that causes impaired lipoprotein lipase activity. ⁸ Secondary causes of severe hypertriglyceridemia include poorly managed diabetes mellitus, medications, nephrotic syndrome, obesity, or excessive alcohol consumption. ⁹

Acute pancreatitis is more likely to occur in people with TG levels between 1000 and 2,000 mg/dL, and in some series, 27.5%–50% of instances of acute pancreatitis during pregnancy are linked to hypertriglyceridemia. ¹⁰ Chylomicronaemia syndrome, a form of hyperviscosity syndrome, is also brought on by severe hypertriglyceridemia. ¹¹ Chylomicronaemia syndrome is characterized by chylomicronaemia combined with localized neurological symptoms, eruptive xanthoma, lipemia retinalis, stomach symptoms, or severe pancreatitis. Rarely, encephalopathy or convulsions may appear, especially during the infant stage. ⁹

Regarding pharmacotherapy, fibrates are generally not recommended during pregnancy. Fenofibrate is classified as FDA Pregnancy Category C, as animal studies have shown embryocidal and teratogenic effects at high doses, and there is a lack of well-controlled studies in pregnant women. ¹² Its use is therefore reserved for cases where the potential benefit to the mother is deemed to outweigh the potential risk to the fetus. Omega-3 fatty acids, which have a moderate triglyceride-lowering effect, are considered safe. For severe cases unresponsive to conservative management, therapeutic apheresis (plasmapheresis) is an effective intervention to rapidly lower triglyceride levels and prevent complications. ¹³ A summary of such cases from the literature is presented in Table 2. ³

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Table 2.

Summary of case reports on apheresis for gestational hypertriglyceridemia-induced pancreatitis.

Author	Gestational week at onset	Peak TG (mmol/L)	Apheresis sessions	Maternal/fetal outcome
Huang et al.23	31	60.2	1	Emergency C-section at 32 weeks; healthy infant
Safi et al.30	27	113.0	3	C-section at 36 weeks; healthy infant
Zsíros et al.31	35	41.0	1	Vaginal delivery at 40 weeks; healthy infant
Djelmis et al.32	25	45.0	5	C-section at 36 weeks; healthy infant
Joglekar et al.33	29	55.0	2	Preterm delivery at 30 weeks; the infant required NICU

TG: triglyceride.

Recent studies have highlighted that severe hypertriglyceridemia in pregnancy is associated with a higher risk of complications, including pancreatitis, preeclampsia, and metabolic disturbances. ¹⁴ In addition to these well-known complications, emerging evidence suggests that systemic vascular dysfunction plays a critical role in the progression of disease severity, potentially exacerbating maternal cardiovascular outcomes. ¹⁵ The interplay between endocrine and metabolic pathways during pregnancy necessitates close monitoring and intervention to mitigate these risks. ¹⁶

Our case aligns with prior reports of gestational hypertriglyceridemia-induced pancreatitis (GHIP) requiring plasmapheresis. For example, Huang et al. reported similar cases requiring urgent delivery due to fetal distress, with TPE used for TG control. However, unlike many cases necessitating early caesarean, our patient remained stable until 35 weeks, reflecting the potential benefit of multidisciplinary coordination and early lipid-lowering interventions. Furthermore, while genetic hyperlipidaemias are commonly implicated, our patient’s case demonstrates additive risk from coexisting hypothyroidism and diabetes.

Six cases of GHIP treated with apheresis have been documented in the literature. ¹⁷ TPE alone and in conjunction with LDL apheresis were the different apheresis regimens used in these patients; however, all but one needed an emergent or semi-emergent caesarean section (C/sec) due to fetal distress or reduced umbilical blood flow. ¹ One instance, where C/sec was not necessary, led to the delivery of a premature baby. Only two case reports of the preventive use of apheresis to regulate maternal triglyceride levels and prevent GHIP exist, despite these disastrous effects. ¹⁸

In the present instance, we describe a patient who experienced frequent incidents of hypertriglyceride-induced pancreatitis during several pregnancies, one of which necessitated plasmapheresis.

Furthermore, the role of multidisciplinary teams in managing complex metabolic conditions, such as hypertriglyceridemia in pregnancy, cannot be overstated. ¹⁹ Obstetric medicine, a subspecialty of internal medicine, has been increasingly recognized as a crucial component of care, particularly for high-risk pregnancies involving endocrine and metabolic disorders. ²⁰ A structured, team-based approach involving endocrinologists, obstetricians, neonatologists, and nutritionists has been shown to improve maternal and fetal outcomes, emphasizing the importance of collaborative management strategies. ²¹

In conclusion, pregnancy impacts lipid metabolism, posing severe risks for patients with genetic predispositions. Our patient, with diabetes and hypothyroidism, experienced hypertriglyceridemia-induced pancreatitis managed by medications, insulin, plasmapheresis, and early delivery. Regular monitoring and appropriate management are crucial for mitigating risks to both mother and fetus during pregnancy.