Primary hyperparathyroidism presenting as severe hypercalcemia with acute pancreatitis in pregnancy

Abstract

Primary hyperparathyroidism presenting first time with severe hypercalcemia is rare in pregnancy. We report a case of primary hyperparathyroidism due to a cystic parathyroid adenoma presenting as severe hypercalcemia with acute pancreatitis in second trimester of pregnancy. Acute pancreatitis was managed by conservative treatment. Hypercalcemia failed to respond to medical management and ultimately responded to ultrasound-guided ethanol ablation of parathyroid adenoma. The delivery was uneventful and patient continues to remain normocalcemic during follow up. As such, ethanol ablation of parathyroid adenoma may be considered during pregnancy in case of failure of response to medical management and when surgical removal of parathyroid adenoma is not safe.     

Pregnancy complicated by concurrent primary hyperparathyroidism and arrhythmia.

Primary hyperparathyroidism during pregnancy results in a high rate of fetal complications and maternal morbidity. Maternal hypercalcemia in pregnancy results in fetal hypercalcemia, which leads to suppression of fetal parathyroid function. Spontaneous abortion and stillbirth can occur, and the loss of maternal calcium after birth leads to neonatal hypocalcemia. It is essential to detect primary hyperparathyroidism during pregnancy because early diagnosis and management can decrease the rate of fetal and maternal complications. We present the case of a 27-year-old gravida 1, para 0 woman whose pregnancy was complicated by hyperparathyroidism and arrhythmia. The patient complained of dyspnea and palpitations in the seventh and 15th weeks of gestation. Electrocardiography showed ventricular premature contraction bigeminy and trigeminy in association with hypercalcemia (3.3 mmol/L). A parathyroidectomy in the second trimester revealed parathyroid adenoma. Hypercalcemia and arrhythmia resolved completely and the patient delivered a term baby without any maternal or fetal complications. The simultaneous occurrence of arrhythmia with ventricular premature contractions and hyperparathyroidism in pregnancy is rarely reported. Palpitations and dyspnea due to arrhythmia may be associated with primary hyperparathyroidism in pregnancy and should be considered in the differential diagnosis. In the management of symptomatic primary hyperparathyroidism during pregnancy, surgical intervention is preferable in the second trimester when organogenesis is completed and the risk of spontaneous abortion is low.     

Self-diagnosis of hyperparathyroidism during pregnancy resulting in parathyroidectomy and uncomplicated delivery

Primary hyperparathyroidism is a condition with hypercalcemia and elevated parathyroid hormone (PTH). Typically, treating patients with such disease does not pose a problem for doctors, unless the patient is pregnant. Firstly, pregnancy may mask signs of hypercalcemia. Secondly, treatment should be applied with special care for immature fetus. If undiagnosed and untreated, it is life-threatening for the mother and the baby. The main cause of primary hyperparathyroidism is parathyroid adenoma, which should be removed surgically in second trimester. If the patient is monitored by a multidisciplinary team, the risk of mortality and pregnancy loss is reduced.     

Recurrent pancreatitis induced by hyperparathyroidism in pregnancy

Introduction  

As primary hyperparathyroidism affects mainly middle-aged and elderly women, it is an infrequent finding during gestation and breastfeeding. To date, less than 200 pregnant patients with primary hyperparathyroidism diagnosed during pregnancy have been described. Like in other disorders of the parathyroid gland, the recognition of primary hyperparathyroidism during pregnancy and lactation may be difficult, as clinical symptoms are not specific, while laboratory findings may be masked by some typical pregnancy-induced changes in calcium and phosphate homeostasis. If remains untreated, the disease may result in serious clinical implications for the mother and fetus. Most authors consider surgery within the second trimester of pregnancy as the treatment of choice in this group of patients.     

Hypoparathyroidism in pregnancy

Pregnancy and lactation are associated with remarkable changes in calcium homeostasis, resulting from pregnancy-induced alterations in the production, metabolism and excretion of calcium and calcitropic hormones. Therefore, the clinical course of disorders affecting the parathyroid glands during pregnancy and lactation is often atypical. As the symptoms experienced by patients with parathyroid disorders are not specific, their diagnosis during gestation and breastfeeding may be sometimes very difficult. If left untreated, parathyroid disorders may pose a significant risk to the mother and fetus associated with increased perinatal and maternal morbidity and mortality. Hypoparathyroidism is a disorder rarely observed during pregnancy, resulting in most cases from surgical thyroidectomy. In our article, we present the case of a 32-year-old female with primary hypoparathyroidism diagnosed for the first time during pregnancy. We describe in details the treatment strategies undertaken in this patient and their impact on the outcome of pregnancy and lactation.     

Hyperparathyroidism in a pregnant woman with previous thyroid carcinoma. Case report and review of the literature

A 29 year old woman, primipara, at 26 weeks' gestation had been undergone, five years before, a total thyroidectomy owing to a mixed papillary-follicular carcinoma of thyroid. After thyroidectomy the patient was placed on suppressive thyroxine treatment. Since she was 22 years old she suffered from recurrent renal colics and cholelithiasis. For these reasons she underwent, at the age of 27, an operation to remove bilateral renal calculi and a cholecystectomy owing to gall-stones. During her pregnancy biochemical determinations revealed slight and persistent hypercalcemia, hypophosphatemia, elevated urine calcium besides elevated serum parathyroid hormone (PTH) levels. Thus a diagnosis of primary hyperparathyroidism was taken into consideration. It was considered, but temporarily delayed, the surgical exploration of the neck. A strict clinic overseeing of the patient, which allowed her to carry out the pregnancy happily, was undertaken. Any thyroid carcinoma repercussion on pregnancy was not noted. A left inferior parathyroid adenoma was removed five months after the woman's delivery. The child psychosomatic development, at one year of age, was absolutely normal. A review of the literature indicates that when a pregnancy is complicated by hyperparathyroidism its prognosis is improved by parathyroidectomy, if possible during the second trimester. In patients with asymptomatic hypercalcemia and/or in late pregnancy surgical treatment may be postponed until after delivery. It is also demonstrated that thyroid carcinoma is not aggravated by pregnancy and that the latter can develop without any worry for mother and fetus.     

Primary hyperparathyroidism in pregnancy

Gestational primary hyperparathyroidism presents with features which, from a physiological and prognostic viewpoint, entail great difficulty in diagnosis and a high risk of complications. These complications occur at rates of 67% and 80% in the mother and fetus, respectively, and can be reduced by up to four times by means of prompt application of effective therapeutic measures. We report a case involving a pregnant woman in the 16th week of gestation who presented with asymptomatic hypercalcemia secondary to a solitary parathyroid adenoma. When the patient did not improve after conservative therapeutic measures, it was decided to employ surgical treatment in the second trimester of pregnancy. The surgery was successful, and the follow-up period was without complications for the mother and neonate. We therefore agree with the growing evidence that surgery in the second trimester of pregnancy constitutes a safe and effective alternative to conservative treatment.     

Primary hyperparathyroidism in pregnancy.

Gestational primary hyperparathyroidism presents with features which, from a physiological and prognostic viewpoint, entail great difficulty in diagnosis and a high risk of complications. These complications occur at rates of 67% and 80% in the mother and fetus, respectively, and can be reduced by up to four times by means of prompt application of effective therapeutic measures. We report a case involving a pregnant woman in the 16th week of gestation who presented with asymptomatic hypercalcemia secondary to a solitary parathyroid adenoma. When the patient did not improve after conservative therapeutic measures, it was decided to employ surgical treatment in the second trimester of pregnancy. The surgery was successful, and the follow-up period was without complications for the mother and neonate. We therefore agree with the growing evidence that surgery in the second trimester of pregnancy constitutes a safe and effective alternative to conservative treatment.     

Concurrent Parathyroidectomy and Caesarean Section in the Third Trimester

BackgroundPrimary hyperparathyroidism is the most common cause of hypercalcemia in the general population. It is a rare complication of pregnancy that is difficult for clinicians to recognize, yet it can have important and devastating effects for both mother and baby.CaseA 27-year-old primigravida at 32 + 3 weeks’ gestation had a serum calcium level in excess of 2.75 mmol/L and evidence of HELLP syndrome. She underwent concurrent parathyroidectomy and Caesarean section. Neither the mother nor the neonate developed hypocalcemia postoperatively. The mother’s parathyroid tissue was pathologically atypical, and a left hemithyroidectomy was performed at three months postpartum.ConclusionWhen hyperparathyroidism is diagnosed in the third trimester, concurrent parathyroidectomy and Caesarean section is a safe and reasonable option for management. This should be performed by a multidisciplinary team with careful monitoring of the calcium levels of both mother and neonate after surgery.     

Primary hyperparathyroidism in pregnancy – report of 3 cases

Three cases of primary hyperparathyroidism in pregnancy are described. Patient 1 developed left thigh pain and lower abdominal pain at 34 weeks' gestation. Patient 2 had right flank pain and lower abdominal pain at 32 weeks' gestation. Both patients accepted medical therapy initially, which resulted in poor control of hypercalcemia. Patient 1 delayed her parathyroidectomy until the postpartum period; she had maternal hypercalcemia and neonatal hypocalcemia. Patient 2 accepted parathyroidectomy at 32 weeks' gestation with an uneventful outcome for both mother and baby. Patient 3 was asymptomatic; her hyperparathyroidism was diagnosed postpartum after neonatal hypocalcemia and agreed to parathyroidectomy. All 3 patients had a parathyroid adenoma. Accepted: 14 January 1998     

Impact of Perinatal Primary Hyperparathyroidism on Maternal and Fetal and Neonatal Outcomes: Retrospective Case Series

ObjectiveWe sought to describe the maternal, fetal, and neonatal outcomes of primary hyperparathyroidism in a contemporary setting through a retrospective case series conducted in a tertiary referral centre focused on women diagnosed with primary hyperparathyroidism prior to conception, in the antepartum period, or within 6 weeks postpartum.MethodsA retrospective chart review was conducted and data were abstracted to case report forms. Summary statistics are reported.ResultsFrom 2000 to 2017, 19 women (23 pregnancies) with primary hyperparathyroidism were identified. Most women (79%) were symptomatic at presentation, though often with non-specific manifestations. While 14% of pregnancies involved maternal/obstetric complications, fetal/neonatal complications were observed in 45%. Mild hypercalcemia was identified in 57% of women, with accompanying hypophosphatemia and hypomagnesemia in 46% and 36% of women, respectively. Surgical intervention was performed for 89% women, and no complications were encountered. Normal calcium levels achieved through treatment before conception did not fully eliminate adverse outcomes.ConclusionRates of perinatal complications in our series are more reassuring than the ubiquitously quoted rates from small and dated studies. The diagnosis of primary hyperparathyroidism may be easily missed during pregnancy, owing to its non-specific presentation. A high index of suspicion and measurement of ionized calcium levels is encouraged, especially for patients with excessive nausea and vomiting, nephrolithiasis, atypical presentations of hypertensive disorders, or isolated polyhydramnios. Mild degrees of calcium derangement do not preclude adverse perinatal outcomes. Surgery appears to be safe, even in the third trimester. The attenuated rate of complications noted in our series may have been the result of the high proportion of surgery, though this will require verification via meta-analysis or future prospective work.     

Disorders of maternal calcium metabolism implicated by abnormal calcium metabolism in the neonate

Normal fetal and neonatal calcium homeostasis is dependent upon an adequate supply of calcium from maternal sources. Both maternal hypercalcemia and hypocalcemia can cause metabolic bone disease or disorders of calcium homeostasis in neonates. Maternal hypercalcemia can suppress fetal parathyroid function and cause neonatal hypocalcemia. Conversely, maternal hypocalcemia can stimulate fetal parathyroid tissue causing bone demineralization. We report two asymptomatic women, one with previously unrecognized hypoparathyroidism and the other with unrecognized familial benign hypercalcemia, who were diagnosed when their newborn infants presented with abnormalities of calcium metabolism. J.B. was born at 34 weeks' gestation with transient hyperbilirubinemia and thrombocytopenia. At 1 month of age he had severe bone demineralization, cortical irregularities, widening and cupping of the metaphyses, and lucent bands in the scapulae. The total serum calcium and phosphorus were normal with an ionized calcium of 5.4 mg/dL (4.6-5.4). His alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were all increased. P.B., mother of J.B., had no symptoms of hypocalcemia either prior to, or during this pregnancy. She had severe hypocalcemia and hyperphosphatemia, laboratory values typical of hypoparathyroidism. J.N. presented at 6 weeks of age with new onset of seizures and tetany secondary to severe hypocalcemia. The serum phosphorus, creatinine, alkaline phosphatase, and parathyroid hormone levels were normal. At 15 weeks of age his calcium was slightly elevated with a low fractional excretion of calcium. P.N., mother of J.N., had no symptoms of hypercalcemia either prior to, or during this pregnancy. Her serum calcium was 12.7 mg/dL and urine calcium was 66.5 mg/24 hr, with a low fractional excretion of calcium ranging from 0.0064 to 0.0073. P.N. has a brother who previously had parathyroid surgery. Both J.N. and P.N. meet the diagnostic criteria for familial benign hypercalcemia. These cases illustrate the important relationships between maternal serum calcium levels and neonatal calcium homeostasis. They emphasize the need to assess maternal calcium levels when infants are born with abnormal serum calcium levels or metabolic bone disease.     

Hipertensión arterial no controlable en el primer trimestre de la gestación. Hiperparatiroidismo primario,a propósito de un caso

Spontaneous dichorionic-diamniotic twin pregnancy. Patient is admitted at 9 weeks pregnant due to uncontrollable vomiting and is diagnosed with hyperemesis gravidarum. Blood pressure remains high. Study of hypertensive disease and treatment initiated without improvement. Blood tests showed a very high serum calcium and PTH with low phosphoremia. Study is completed with neck ultrasound revealing a lower hypoechoic lesion of the right thyroid lobe suggestive of parathyroid adenoma. Diagnosis of severe hypercalcemia secondary to primary hyperparathyroidism due to parathyroid adenoma was confirmed. It was decided to perform a parathyroidectomy in the second trimester after which a decrease in serum calcium, control blood pressure and other symptoms was found.Although it is the most common cause of hypercalcemia in the general population, it is a rare condition in women of childbearing age. Its approximate incidence during pregnancy is 8/10,000. During pregnancy, maternal calcium and phosphorus is transferred to the fetus, which results in suppression of fetal PTH secretion and increased fetal calcitonin values. It is associated with high maternal and fetal morbidity and mortality and risk of nephrolithiasis, hyperemesis, hypertension, high morbidity with increased risk of preeclampsia and kidney disease. In the fetus, there is an increased risk of spontaneous abortion, intrauterine growth retardation and preterm birth.Among conservative treatment measures, it is recommended to maintain good oral hydration, limit calcium intake and treat associated symptoms. Parathyroidectomy is the definitive treatment and should be performed in the second trimester.     

早期妊娠合并甲状旁腺功能亢进一例并文献复习

目的探讨妊娠合并甲状旁腺功能亢进疾病的临床特点，治疗方案、治疗时机及母儿结局。 方法根据南方医科大学附属小榄医院收治的1例及近5年文献报道47例妊娠合并甲状旁腺功能亢进患者的临床资料，对该病的临床特点、治疗方案、治疗时机及母儿结局进行分析。 结果本例患者33岁，妊娠6周因妊娠剧吐收住入院，经过治疗病情反复未能好转，发现血钙升高，进一步诊断妊娠合并甲状旁腺功能亢进，患者要求终止妊娠，3个月后行甲状旁腺切除手术，随访半年患者血钙及甲状旁腺素水平恢复正常。文献检索的47例妊娠合并原发性甲状旁腺功能亢进早孕期及中孕期行甲状旁腺切除术分别为4例和21例，总体母胎结局较好，其术前的血钙水平差异无统计学意义。 结论妊娠合并甲状旁腺功能亢进严重危害母胎安全，漏诊误诊风险高，患者结合临床实际可早孕期选择药物治疗，降低血钙水平，待中孕期后选择手术治疗，可有效减少母胎并发症发生。     

Variability of clinical presentations in three cases of parathyroid carcinoma.

Parathyroid carcinoma accounts for 0.5 to 4.0% of cases of primary hyperparathyroidism. The prognosis depends largely on the extent of successful resection at the time of initial operation. Therefore, early diagnosis before surgery is important. We report 3 cases of primary hyperparathyroidism. The first patient, a 20-year-old uremic female, had refractory hypercalcemia after 5 years of hemodialysis treatment. Hypercalcemia persisted despite repeated parathyroidectomy. Pathology revealed diffuse hyperplasia of the parathyroid glands with focal adenomatous changes. Multiple pulmonary metastases were found later. The second patient, a 45-year-old female with history of nephrolithiasis, presented with severe osteoporosis. She underwent repeated parathyroidectomy for local recurrence. Pathology disclosed typical features of parathyroid carcinoma with adjacent lymph node metastasis. The third patient, a 34-year-old male, had recurrent episodes of extremity fracture and hypercalcemia with palpable neck mass. He underwent resection of the parathyroid tumor. Vascular and capsular invasions were noted microscopically. All three patients were relatively young and had extremely high intact parathyroid hormone (iPTH) level (15 to 31 times the upper limit of normal). The first patient died of hypercalcemia and respiratory failure and the other 2 were treated successfully with surgical excision and, in case 2, combined chemotherapy and radiotherapy. The latter 2 patients had no recurrence during 18 months and 14 months of follow-up, respectively. Our experience with these cases suggests that the combination of the following characteristics are highly suggestive of parathyroid carcinoma: young age, palpable neck mass, concomitant renal and skeletal disease, and extremely high iPTH level in patients with PTH-dependent hypercalcemia.     

Acute pancreatitis secondary to primary hyperparathyroidism in a postpartum patient: A case report and literature review

ObjectivePrimary hyperparathyroidism (PHPT) is a rare clinical entity in reproductive women. Unusual hypercalcemia causing pancreatitis in the peripartum period carries significant morbidity to both the fetus and the mother.Case ReportA 38-year-old woman developed a morbid course of intractable intra-abdominal abscess by pancreatitis, hydronephrosis by renal lithiasis, and unusual neurological presentations soon after delivery. Serial serum calcium level and imaging studies lead to the final diagnosis of PHPT due to a parathyroid adenoma. Data on 14 patients who suffered from pancreatitis due to hyperparathyroidism were collected from a MEDLINE search. The reasons for delayed diagnosis and literature review of acute pancreatitis in PHPT are discussed.ConclusionHypercalcemia can be masked during pregnancy and in severe pancreatitis, as was detected in about half of the case series. Clinicians should have a high level of suspicion of parathyroid adenoma in cases with a profound pancreatitis. Timely diagnosis and early therapeutic intervention are important to resolve complications and improve the outcomes of mothers and fetuses.     

Hyperparathyroid crisis presenting with hyperemesis gravidarum

Purpose

Primary hyperparathyroidism during pregnancy is a rare condition, and the diagnosis may be confounded by pregnancy related conditions. Since the appropriate management reduces the maternal and fetal complications; differential diagnosis becomes quite crucial.

Method

Clinical course of a patient with hyperparathyroid crisis will be discussed with the review of the literature. A 22-year- old, (gravida 2, para 1) woman was presented with hyperparathyroid crisis at the 11th weeks' gestation. She was hospitalized twice due to hyperemesis gravidarum. When she was admitted to the hospital for the third time due to increased vomiting and weight-loss, serum biochemistry panel was performed and it revealed severe hypercalcemia that serum Ca was 17.59 mg/dl, and she was referred to our hospital as parathyroid crisis. Maternal hypercalcemia was resolved after urgent parathyroidectomy. She was diagnosed as preeclampsia at the 30 weeks' gestation and delivered a male infant weighing 1,090 g at 33 weeks' gestation with APGAR scores 6 at 1 min, and 7 at min 5, without evidence of neonatal hypocalcemia or tetany.

Results

Urgent parathyroidectomy is the definite treatment in symptomatic patients with hyperparathyroidism during pregnancy. Resolving maternal hypercalcemia prevents neonatal tetany and hypocalcemia.

Conclusion

Hyperemesis may lead to hypercalcemic crisis in patients with hyperparathyroidism, so serum Ca level should be checked in patients with hyperemesis gravidarum especially who detoriate rapidly. Although they share some common pathogenetic mechanisms, there is not enough evidence for attributing preeclampsia to primary hyperparathyroidism.     

Neonatal convulsion revealing maternal hyperparathyroidism: an unusual case of late neonatal hypoparathyroidism

Neonatal convulsion is a very alarming manifestation of underlying sinister problem. As an important cause, neonatal hypocalcemia usually occurs soon after birth and reflects abnormal maternal calcium regulation. We report an unusual case of late neonatal hypocalcemia presented with intractable seizures after two-month-old. Further investigations revealed maternal hyperparathyroidism secondary to parathyroid adenoma, which was missed during antenatal checkup. High index of suspicion is necessary in early detection and prompt treatment of neonatal hypocalcemia. Screening of maternal calcium level is mandatory in unexplained late neonatal hypocalcemia as mother with primary hyperparathyroidism could be asymptomatic and first manifest as late-onset neonatal convulsion. Early detection and appropriate intervention could avoid serious maternal and fetal morbidity.     

Primary hyperparathyroidism during the third trimester of pregnancy.

Primary hyperparathyroidism during pregnancy has been reported in 36 women; 1 new case is reported here. Screening by determining serum calcium levels is a valuable method of diagnosing the disease. Radioimmunoassay of serum parathyroid hormone (PTH) greatly aids in the diagnosis. Amniotic fluid PTH values are discussed. Hyperparathyroidism has a high association with progressive renal insufficiency, renal calculi, hypertension, and bone disease. During pregnancy, there is an increased incidence of stillborns, premature labor, and neonatal tetany. Acute hyperparathyroid crisis may result in maternal death. This is the first reported case surgically treated during the third trimester of pregnancy. Surgery should be considered when the diagnosis is made late in pregnancy, as this may protect the infant from neonatal tetany.     

Hyperparathyroidism and pregnancy. Review of the literature

This review of the literature includes 92 cases of hyperparathyroidism associated with pregnancy since 1930. Hyperparathyroidism is rare during pregnancy and often remains asymptomatic. Thus, a fetal death or an episode of neonatal tetany may reveal a maternal hyperparathyroidism. Determination of the calcium blood levels at the slighest maternal symptom, or a posteriori, in view of complications of pregnancy or in the neonatal period, must enable to entertain the diagnosis of this disease. If the diagnosis is made during pregnancy, the surgical treatment of choice is easier during the second trimester. Most frequently, the excision of a parathyroid adenoma responsible for the symptoms, prevents maternal and neonatal complications.