Maternal Death Due to Lymphocytic Hypophysitis: A Case Report
Article information
Abstract
Lymphocytic hypophysitis is a rare condition characterized by lymphocyte and plasma cell infiltration, leading to fibrosis and functional impairment of the pituitary gland. Although lymphocytic hypophysitis is associated with pregnancy, its diagnosis may be challenging in pregnant women owing to unclear symptoms of pituitary dysfunction. Lymphocytic hypophysitis can lead to serious complications, including a sudden death; however, no case of maternal death has been reported in Korea. This study presents a case of maternal death after childbirth. The deceased had a history of hypertension, obesity, hypothyroidism, and gestational diabetes and died suddenly the day after the emergency cesarean section. Notably, no other pregnancy-related complications were observed. Histopathological examination of the pituitary gland confirmed lymphocytic hypophysitis. This case report emphasizes the requirement of clinical awareness and underscores the significance of examining the pituitary gland during autopsy investigations of maternal deaths.
Introduction
Lymphocytic hypophysitis, an unusual inflammatory condition affecting the pituitary gland, is characterized by lymphocyte and plasma cell infiltration into the pituitary gland, leading to its functional impairment and fibrosis [1]. Lymphocytic hypophysitis occurs more frequently in women than in men, with an approximately 5-8 times higher prevalence in women. Furthermore, its occurrence has strongly been associated with pregnancy, with the most common occurrence in the late stages of pregnancy and within 6 months postpartum [2]. Lymphocytic hypophysitis may involve symptoms related to pituitary enlargement, including headaches and visual disturbances, and pituitary dysfunction [3]. However, these symptoms are often less apparent in women during pregnancy or immediately postpartum, thus making the diagnosis challenging.
Lymphocytic hypophysitis can lead to serious complications, such as acute mortality [4], underscoring the importance of awareness and early intervention. However, it is clinically rare and no case of maternal death has been reported in Korea.
This study presents a case of maternal death shortly after childbirth, where no significant findings related to lymphocytic hypophysitis were observed on autopsy, but severe lymphocytic hypophysitis was identified upon histopathological examination of the pituitary gland.
Case Report
The patient was a 42-year-old primipara woman with obesity who had a height of approximately 157 cm and a weight of about 70 kg. She was on medication for hypertension and hypothyroidism and had a history of gestational diabetes. She underwent an emergency cesarean section due to placental abruption at 37 weeks and 5 days of her gestation period. On admission, her blood pressure and heart rate were 160/100 mmHg and 120 beats/min, respectively. No other abnormal symptoms, such as headaches or fever, were reported on admission.
The patient delivered a healthy baby weighing 3.06 kg via cesarean section, with approximately 800 mL of blood loss during surgery. Notably, no significant issues were noted during or immediately after surgery. The following morning, the blood pressure and heart rate of the patient were 120/70 mmHg and 76 beats/ min, respectively, with no other abnormal symptoms. However, she was found unconscious in the bathroom that evening, with no pulse or breathing. Despite emergency resuscitation, the patient did not recover and died.
An autopsy was performed approximately 38 hours after the death. During autopsy, an external examination revealed a horizontal surgical scar measuring 14.5 cm in the lower abdomen, signs of cardiopulmonary resuscitation around the sternal area, and needle marks on both arms and the inguinal area. No other injury was observed. Internal examination did not reveal any damage other than rib fractures due to cardiopulmonary resuscitation, and no abnormalities such as bleeding or necrosis in the surgical area of the lower abdomen were observed. Uterine contractions progressed to a level below the umbilicus, and no retained placenta or perforation in the uterus was observed.
Heart examination revealed severe stenosis due to atherosclerosis in the left anterior descending coronary artery, narrowing by approximately 90% of its cross-section (Fig. 1). Histopathological examination of the myocardium revealed no other notable findings, such as infarction or fibrosis. Examination of the head revealed an enlarged pituitary gland, weighing approximately 1.2 g (0.5-0.9 g in normal adults), with a maximum diameter of approximately 2 cm (approximately 1.2 cm in normal peripartum women) (Fig. 2). No other visible abnormalities, such as tumors or bleeding, were observed. Histopathological examination revealed the infiltration of numerous lymphocytes into the parenchyma of the anterior pituitary gland (Fig. 3A), causing partial destruction of the glands (Fig. 3B). No other abnormalities, such as amniotic fluid embolism, were observed.
The cut surface of the left anterior descending coronary artery showing severe atherosclerosis.
The cross-section of the pituitary gland showing a maximum diameter of approximately 2 cm (approximately 1.2 cm in normal peripartum women).
(A) Severe lymphocytic inflammation of the parenchyma in the anterior pituitary gland (H&E, ×200). (B) Evident pituitary gland destruction due to inflammation at high magnification (H&E, ×400).
Analgesics and local anesthetics within therapeutic ranges were detected via toxicology testing, and postmortem blood tests revealed a C-reactive protein level of 1.64 mg/dL (lesser than a normal range of 1.00 mg/dL) and serum tryptase concentration of 10.5 μg/L (lesser than a normal range of 11 μg/L). No other significant factors contributing to death, such as systemic inflammation or drug hypersensitivity reactions, were observed.
Considering the severe inflammation of the pituitary gland, along with underlying endocrine abnormalities such as hypothyroidism, obesity, and hypertension, lymphocytic hypophysitis was considered the most likely cause of death.
Discussion
This study reports the first case of maternal death due to lymphocytic hypophysitis in Korea based on the autopsy findings, histopathological findings, medical records, and postmortem test results following a sudden cardiac arrest postpartum.
Lymphocytic hypophysitis is a rare condition characterized by inflammation and fibrosis of the pituitary gland, resulting in its destruction and dysfunction [1], involving T and B lymphocyte infiltration into the pituitary gland [5]. The incidence of pituitary dysfunction due to hypophysitis has been increasing, with an average age of 44.7 and 34 years in men and women, respectively [6].
Hypophysitis can be classified as primary or secondary, depending on the cause [5]. Primary hypophysitis can be further classified histologically as lymphocytic, granulomatous, xanthomatous, IgG4-related, or mixed, and anatomically as lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis, or lymphocytic panhypophysitis [3]. Notably, lymphocytic adenohypophysitis, neurohypophysitis, and panhypophysitis affect the anterior lobe, posterior lobe, and both lobes of the pituitary gland, respectively [5].
Primary hypophysitis involves inflammation of the pituitary gland, whereas secondary hypophysitis involves pituitary gland inflammation due to diseases such as lymphocytic hypophysitis associated with conditions such as sarcoidosis, hemochromatosis, amyloidosis, vasculitis, tuberculosis, syphilis, and immune-modulating drugs including immune checkpoint inhibitors such as cytotoxic T-lymphocyte antigen 4 and programmed cell death 1 inhibitors [3].
Adenohypophysitis, first reported by Goudie and Pinkerton in 1962, is associated with pituitary dysfunction [4]. This condition occurs primarily in women, often in late pregnancy or during the postpartum period, with an approximately 50% maternal mortality rate [2]. Autoimmunity is recognized as a significant factor in adenohypophysitis, with 20%-50% of cases being associated with other autoimmune disorders [3]. The most common manifestation is adrenocorticotropic hormone deficiency due to pituitary dysfunction, although deficiencies of thyroid-stimulating hormone and gonadotropins can also occur along with conditions such as thyroid dysfunction, diabetes mellitus, adrenal insufficiency, and central obesity [2,3]. Moreover, symptoms related to pituitary enlargement, such as headaches or visual disturbances, may occur, although these clinical signs are often not prominent in pregnant women, making its diagnosis challenging [7].
Histological evaluation often reveals T and B lymphocyte and plasma cell infiltration into the anterior pituitary gland, and T and B lymphocytes that infiltrate the pituitary gland can form perivascular lymphoid follicles [5]. Histological staining can also be used to identify inflammatory cells and classify the degree of lymphocytic infiltration [3].
The degree of lymphocytic infiltration corresponds to the degree of pituitary gland enlargement, resulting in mass-effect symptoms of asymptomatic pituitary gland dysfunction by exerting pressure on adjacent structures. Notably, the asymptomatic pituitary gland dysfunction can be resolved until the pituitary gland tissue is not completely destroyed. Furthermore, pituitary tissue fibrosis may also occur as the disease progresses [2]. Moreover, extensive lymphocytic infiltration leading to pituitary gland tissue destruction results in the replacement of the normal tissue with fibrotic tissue, causing partial or complete hypopituitarism.
In the present case, the deceased had an enlarged and heavier-than-normal pituitary gland with marked infiltration of inflammatory cells into the pituitary parenchyma, with no other conditions, such as Sheehan's syndrome, affecting the pituitary gland. In addition, the presence of endocrine disorders, such as obesity, thyroid dysfunction, and gestational diabetes, raised the suspicion of hypopituitarism and the possibility that pituitary dysfunction may be exacerbated by pregnancy and childbirth.
Lymphocytic hypophysitis, which results in death owing to pituitary dysfunction, can manifest in various forms. Gonzalez-Cuyar et al. [4] described a case of a 23-year-old woman diagnosed with lymphocytic hypophysitis during an autopsy. She experienced a sudden and unexpected death, accompanied by inflammation of the thyroid and adrenal glands, without any other apparent cause. In another rare case, individuals who died suddenly exhibited lymphocytic hypophysitis with inflammation in the posterior pituitary lobe accompanied by diabetes insipidus [8]. An autopsy revealed lymphoplasmacytic cell infiltration in the posterior pituitary lobe and a pattern of hypernatremia based on electrolyte testing.
Additionally, the occurrence of acute central hypoadrenalism, persistent hypopituitarism, or inflammation that affects the peripheral neurological structures due to lymphocytic hypophysitis can lead to death [9]. Individuals with compromised pituitary function have a higher mortality rate than age-matched individuals without pituitary dysfunction, primarily because of increased cardiovascular complications. Risk factors such as hypertension, elevated low-density lipoprotein cholesterol, and impaired glucose metabolism contribute to atherosclerosis, which is associated with heart function decline, abnormal electrocardiograms, and occasionally fatal arrhythmias [10].
In this case, a thorough autopsy revealed severe coronary atherosclerosis in the patient; however, no microscopic abnormalities, such as myocardial infarction, ischemia, or fibrosis, which could directly cause acute death, were found. Therefore, coronary atherosclerosis was not the direct cause of death in the present case. Considering the circumstances outlined underlying sudden death in the present case, coronary atherosclerosis may have accelerated the process of death due to lymphocytic hypophysitis.
Reports of maternal deaths after childbirth due to lymphocytic hypophysitis are rare worldwide. Lymphocytic hypophysitis is typically diagnosed postmortem, as it is challenging to diagnose it radiologically, and its clinical symptoms are also nonspecific. In conclusion, this study presents the first report of maternal death due to lymphocytic hypophysitis in Korea and highlights the importance of clinical awareness, serving as foundational data for the early prevention of maternal deaths. Additionally, it underscores the significance of examining the pituitary gland during autopsy investigations of maternal death cases.
Notes
Conflicts of Interest
No potential conflict of interest relevant to this article was reported.