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Gabija Germanaitė Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania

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Diana Šimonienė Department of Endocrinology, Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania

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Summary

Primary hyperparathyroidism (PHPT) is a common endocrinological pathology; nonetheless, it is rarely diagnosed in pregnancy. Primary hyperparathyroidism can present with clinically expressed hypercalcemia. High Ca levels in the blood may lead to a miscarriage. We present the case of a 39-year-old woman who visited our Endocrinology clinic in search of a cause of infertility. Blood work showed elevated Ca and parathyroid hormone (PTH) levels. Upper left parathyroid gland adenoma was found during a neck ultrasound. Parathyroid gland adenoma was likely the cause of PHPT and was treated with parathyroidectomy. Surgery was carried out, and the upper left parathyroid lobe adenoma was removed. High levels of Ca were found in all performed blood works since the first visit to the clinic, but following the surgery, Ca levels of the patient were in the normal range and the woman got pregnant for the third time, later delivering a healthy baby. In conclusion, we would like to put forward the idea that an evaluation of Ca level in the blood should be included in the protocol for treating patients with recurrent miscarriages. Early detection of hypercalcemia can improve the outcomes of disease that primary hyperparathyroidism can cause. Swift and accurate decrease of serum Ca correspondingly safeguards the woman from a possible pregnancy loss along with complications that arise from it.–

Learning points

  • Primary hyperparathyroidism (PHPT) is a common endocrinological pathology, nonetheless, it is rarely diagnosed in pregnancy.

  • Primary hyperparathyroidism can present with clinically expressed hypercalcemia, and high Ca levels in the blood may lead to a miscarriage.

  • Early detection of hypercalcemia can improve the outcomes of disease that primary hyperparathyroidism can cause.

  • Swift and accurate decrease of serum Ca correspondingly safeguards the woman from a possible pregnancy loss along with complications that arise from it.

  • All pregnant patients with hypercalcemia should be assessed for the presence of primary hyperparathyroidism as it is likely the cause.

Open access
Matthew J Verheyden Department of Diabetes, Metabolism and Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

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Natassia Rodrigo Department of Diabetes, Metabolism and Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
Department of Diabetes and Endocrinology, Nepean Hospital, Kingswood, New South Wales, Australia

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Anthony J Gill Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia

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Sarah J Glastras Department of Diabetes, Metabolism and Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

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Summary

Necrobiosis lipoidica (NL) is a rare and chronic disease characterised by yellow-brown, atrophic, telangiectatic plaques usually located on the lower extremities, with pathological features of collagen necrobiosis and dermal inflammation. Most cases are seen in those with diabetes mellitus, particularly type 1 diabetes (T1DM), and many without diabetes have evidence of abnormal glucose tolerance or family history of autoimmune disease. In this study, we describe four patients with NL and T1DM. A common theme is late identification and delay in diagnosis. Hence, we discuss the clinical features, need for clinicopathological correlation, and the management and prognostic implications for this distinctive entity. While most remain relatively asymptomatic, others progress to debilitating disease with pruritus, dysesthesia, and pain. Pain is often intense in the presence of ulcerated plaques, a morbid complication of NL. Diagnosis requires the integration of both clinical and histopathological findings. NL has proven a challenging condition to treat, and despite the numerous therapeutic modalities available, there is no standard of care. Hence, in this study, we provide an overview of current management strategies available for NL.

Learning points

  • Necrobiosis lipoidica (NL) is classically seen in patients with type 1 diabetes.

  • Koebner phenomenon, defined as the appearance of new skin lesions on previously unaffected skin secondary to trauma, is a well-recognised feature in NL.

  • Background skin phototype contributes to variable yellow appearance of lesions in NL.

  • Diagnosis of NL requires careful clinicopathological correlation.

  • NL is a chronic disease often refractory to treatment leading to significant morbidity for the patient and a management conundrum for the multidisciplinary healthcare team.

  • No standard therapeutic regimen has been established for the management of NL.

Open access
Tamaryn Fox Department of Internal Medicine, Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania, USA

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Hamza Akhtar Department of Cardiology, Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania, USA

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Nissa Blocher Department of Endocrinology and Metabolism, Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania, USA

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Catherine Anastasopoulou Department of Endocrinology and Metabolism, Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania, USA

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Summary

Graves’ disease can have multiple cardiac manifestations. A rare complication is that of severe mitral regurgitation secondary to mitral valve chordae rupture, due to both compromise of valve integrity by deposition of glycosaminoglycans and the hemodynamic stresses of thyrotoxicosis. Pregnancy, with its related hemodynamic changes, is another setting in which mitral valve chordae rupture has occasionally been documented. We present a unique case of a 36-year-old female with uncontrolled Graves’ disease who presented during pregnancy at 13 weeks gestation with atrial flutter and features of congestive heart failure. Echocardiogram found severe mitral regurgitation secondary to a ruptured mitral chord. She was treated conservatively with diuresis and ultimately delivered her baby without complication at 28 weeks when she had preterm premature rupture of membranes. She is currently on methimazole and propranolol and pending definitive management of her Graves’ disease. This represents not only a rare cardiac complication in a patient with Graves’ disease but also is the first in the literature, to our knowledge, which describes this complication in a pregnant patient with Graves’ disease.

Learning points

  • Thyroid disease can have multiple effects on the heart through hemodynamic and structural changes and can result in heart failure, arrhythmias, valvular disease, and pulmonary hypertension.

  • Graves’ disease can cause glycosaminoglycan deposition in valvular tissue resulting in fragile leaflets that can rupture with little stress.

  • Pregnancy and thyrotoxicosis have similar hemodynamic consequences with increased cardiac output and reduced systemic vascular resistance.

  • Be vigilant in those with hyperthyroidism with a new murmur or features of acute heart failure, as a ruptured valve chord can result in increased morbidity and mortality if not recognized and addressed quickly.

Open access
Melanie Nana Department of Obstetric Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

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Catherine Nelson-Piercy Department of Obstetric Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

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Summary

COVID-19 is associated with severe disease in pregnancy. Complications of the disease, or simultaneous diagnoses, may be missed if clinicians do not retain a large differential diagnosis when assessing such women. Starvation ketoacidosis is one such diagnosis which may complicate the disease and should not be missed. A 37-year-old woman, 33 weeks’ gestation presented with breathlessness. Clinical history, examination and investigations supported a diagnosis of starvation ketosis of pregnancy complicating COVID-19 pneumonitis. Prompt correction of the metabolic disturbance resulted in resolution, and preterm delivery was avoided at this time. Early recognition and prompt management of starvation ketosis of pregnancy in women with COVID-19 are important in reducing maternal and neonatal morbidity and mortality. Preterm delivery may be avoided with prompt resolution of the metabolic disturbance. Clinicians should keep a wide differential diagnosis when assessing women with breathlessness. A multidisciplinary team (MDT) approach is required to facilitate optimal care.

Learning points

  • Clinicians should maintain a wide differential when assessing women who are unwell with COVID-19 in pregnancy.

  • Complications such as starvation ketoacidosis are rare but life-threatening.

  • An awareness of such complications facilitates early identification of the condition, and involvement of appropriate specialists who can initiate optimal and timely management.

  • In the context of pregnancy, where ketoacidosis poses a threat to the mother or baby, prompt management and resolution may avoid preterm delivery.

  • Conditions that may increase the risk of developing starvation ketoacidosis include pregnancy, medication use such as corticosteroids or tocolytic therapies, previous gastric surgery, intercurrent illness and pregnancy-related conditions that might contribute towards a degree of chronic starvation.

  • Multidisciplinary input supports the delivery of best practice and care for the patients.

Open access
Nynne Emilie Hummelshøj Department of Hepatology and Gastroenterology, Aarhus University, Aarhus, Denmark

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Gitte Dam Department of Hepatology and Gastroenterology, Aarhus University, Aarhus, Denmark

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Lars Henning Pedersen Department of Obstetrics and Gynecology, Aarhus University, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Biomedicine, Aarhus University, Aarhus, Denmark

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Astrid Hjelholt Department of Endocrinology and Internal Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Pharmacology, Aarhus University, Aarhus, Denmark

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Gerda Elisabeth Villadsen Department of Hepatology and Gastroenterology, Aarhus University, Aarhus, Denmark

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Summary

This rare case describes the course of a pregnancy in a patient with a disseminated small intestinal neuroendocrine tumor. The patient received treatment with first-generation somatostatin ligand receptor (SLR) every 4 weeks and had stable disease for several years before her pregnancy. First-generation SLR treatment was initially paused after detection of the pregnancy. During pregnancy, the patient experienced moderate gastro-intestinal discomfort and fatigue, which was considered predominantly pregnancy related. However, since symptoms could be linked to the patient’s cancer, treatment was resumed after the first trimester. Chromogranin-A measurements remained stable throughout pregnancy and was paralleled by the absence of diarrhea and only minor flushing. She gave birth by elective caesarean section in week 37 to a healthy baby. Subsequent follow up imaging immediately after and 10 months postpartum showed no disease progression. The safety profile of SLR treatment during pregnancy in the context of disseminated neuroendocrine tumors (NET) is discussed.

Learning points

  • Neuroendocrine neoplasms (NEN) are rare cancers often occurring in the gastro-intestinal tract or lungs.

  • Many patients with NEN live for several years with disseminated disease.

  • SLR treatment has been given to pregnant patients before; often patients with acromegaly. Pregnancies are reported uneventful.

  • This patient completed an uneventful pregnancy while receiving SLR treatment for disseminated neuroendocrine disease and gave birth to a healthy baby.

  • More research regarding long term effects and safety signals of SLR treatment during pregnancy are much needed.

Open access
Ulla Kampmann Steno Diabetes Center Aarhus, Aarhus University Hospital, Hedeager, Aarhus N, Denmark

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Per Glud Ovesen Department of Obstetrics and Gynecology, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark

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Niels Møller Medical Research Laboratories, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark

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Jens Fuglsang Department of Obstetrics and Gynecology, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark

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Summary

During pregnancy, maternal tissues become increasingly insensitive to insulin in order to liberate nutritional supply to the growing fetus, but occasionally insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme insulin resistance with daily insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a hemoglobin A1c (HbA1c) at 59 mmol/mol. Insulin treatment was initiated immediately using Novomix 30, and the doses were progressively increased, peaking at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in insulin requirements, but with no signs of placental insufficiency. At week 36 + 1 a, healthy baby with no hypoglycemia was delivered by cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme insulin resistance and showed high levels of C-peptide, proinsulin, insulin-like growth factor (IGF-1), mannan-binding-lectin (MBL) and leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal. Insulin antibodies were undetectable, and no mutations in the insulin receptor (INSR) gene were found. The explanation for the severe insulin resistance, in this case, can be ascribed to PCOS, obesity, profound weight gain, hyperleptinemia and inactivity. This is the first case of extreme insulin resistance during pregnancy, with insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists.

Learning points

  • This is the first case of extreme insulin resistance during pregnancy, with insulin requirements of up to 1420 IU/day with a successful outcome without significant fetal macrosomia and hypoglycemia.

  • Obesity, PCOS, T2D and high levels of leptin and IGF-1 are predictors of severe insulin resistance in pregnancy.

  • A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.

Open access
Natassia Rodrigo Department of Diabetes and Endocrinology, Royal North Shore Hospital, Sydney, Australia
Northern Clinical School, Department of Medicine, University of Sydney, Australia
Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia

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Diana Learoyd Department of Diabetes and Endocrinology, Royal North Shore Hospital, Sydney, Australia
Northern Clinical School, Department of Medicine, University of Sydney, Australia
Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia

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Sarah J Glastras Department of Diabetes and Endocrinology, Royal North Shore Hospital, Sydney, Australia
Northern Clinical School, Department of Medicine, University of Sydney, Australia
Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia

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Summary

Hypercalcaemia in pregnancy is uncommon, with associated adverse obstetric and perinatal outcomes for both the mother and the fetus. Determination of causality is central to its management. Diagnostic imaging techniques are limited during pregnancy and the diagnosis is made more complex by physiological changes in calcium and vitamin D homeostasis in pregnancy. Further, therapeutic options are limited due to safety considerations for the pregnant woman and the developing foetus. Three cases of hypercalcaemia in pregnancy will be presented, highlighting the distinct aetiologies and management strategies for hypercalcaemia in pregnancy and the importance of early measurement of serum calcium in pregnancy screening.

Learning points

  • There are complex physiological changes in calcium balance in pregnancy, including increased calcium intestinal absorption and renal excretion.

  • Hypercalcaemia in pregnancy is uncommon but has important potential maternal and foetal complications, making a compelling argument for routine antenatal, calcium screening.

  • Identifying the cause of hypercalcaemia in pregnancy can be challenging due to the complex placental interplay in biochemical test interpretation and due to safety constraints restricting imaging and surgery.

  • Acute medical management of hypercalcaemia must be considered in the context of both maternal and foetal well-being, along with gestational age and specific consideration for the safety of the developing fetus in late gestation.

Open access
Sarah Ying Tse Tan Department of Endocrinology, Singapore General Hospital, Singapore

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Swee Ping Teh Department of Renal Medicine, Singapore General Hospital, Singapore

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Manish Kaushik Department of Renal Medicine, Singapore General Hospital, Singapore

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Tze Tein Yong Department of Obstetrics and Gynaecology, Singapore General Hospital, Singapore

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Shivani Durai Department of Obstetrics and Gynaecology, Singapore General Hospital, Singapore

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Claudia Jong-Chie Tien Department of Anaesthesiology and Surgical Intensive Care, Singapore General Hospital, Singapore

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Daphne Su-Lyn Gardner Department of Endocrinology, Singapore General Hospital, Singapore

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Summary

Gestational hypertriglyceridemia-induced pancreatitis is associated with significant maternal and fetal morbidity and mortality. We report a case of gestational hypertriglyceridemia-induced pancreatitis in a primigravida at 31-weeks gestation, complicated by impending preterm labor and metabolic acidosis requiring hemodialysis. This was successfully managed with therapeutic plasma exchange (TPE), followed by i.v. insulin, low-fat diet, and omega-3. Triglyceride levels stabilized after TPE and the patient underwent an uncomplicated term delivery. In pregnancy, elevated estrogen and insulin resistance exacerbate hypertriglyceridemia. Management is challenging as risks and benefits of treatment options need to be weighed against fetal wellbeing. We discuss management options including a review of previous case reports detailing TPE use, dietary optimization, and delivery timing. This case emphasizes the importance of multidisciplinary care to optimize maternal and fetal outcomes.

Learning points

  • Gestational hypertriglyceridemia-induced pancreatitis has high morbidity.

  • A multidisciplinary team approach is a key as maternal and fetal needs must be addressed.

  • Rapid lowering of triglycerides is crucial and can be achieved successfully and safely with plasma exchange.

  • A low-fat diet while ensuring adequate nutrition in pregnancy is important.

  • Timing of delivery requires consideration of fetal maturity and risk of recurrent pancreatitis.

Open access
Chi-Hong Ng Department of Medicine, University of Hong Kong, Hong Kong SAR, China

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Wing-Sun Chow Department of Medicine, University of Hong Kong, Hong Kong SAR, China

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Karen Siu-Ling Lam Department of Medicine, University of Hong Kong, Hong Kong SAR, China

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Chi-Ho Lee Department of Medicine, University of Hong Kong, Hong Kong SAR, China

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Summary

Thyroid stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is an uncommon cause of thyrotoxicosis, and is even rarer when found during pregnancy. Our patient presented with thyrotoxicosis accompanied by an inappropriately normal TSH level at 10 weeks of gestation during work-up of surgical termination of pregnancy (STOP). Subsequent investigations performed after STOP confirmed the presence of a TSH-secreting pituitary macroadenoma. She was initially treated with anti-thyroid drugs for biochemical control, followed by trans-sphenoidal surgery after STOP had been performed. Her thyroid function completely normalized after the trans-sphenoidal surgery. Our case illustrated the importance of recognizing the syndrome of inappropriate TSH secretion and highlighted several pregnancy-related aspects in the diagnosis and management of TSHoma during pregnancy.

Learning points:

  • This case report illustrates the need to raise awareness in recognizing the syndrome of inappropriate TSH secretion.

  • Illustrate the different hormone tests available for reaching the diagnosis of TSH-secreting pituitary adenoma.

  • Highlight the physiological changes in the thyroid status during pregnancy and the importance of using trimester-specific reference ranges for assessment of thyroid function during pregnancy.

  • Describe the challenges in the management of TSH-secreting pituitary adenoma during pregnancy.

Open access
Dalal Ali St. Vincent’s University Hospital, Dublin, Ireland

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Patrick Divilly St. Vincent’s University Hospital, Dublin, Ireland

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Ruth Prichard St. Vincent’s University Hospital, Dublin, Ireland

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Dermot O’Toole St. Vincent’s University Hospital, Dublin, Ireland
St. James’s University Hospital, Dublin, Ireland
Trinity College, Dublin, Ireland

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Donal O’Shea St. Vincent’s University Hospital, Dublin, Ireland
University College Dublin, Dublin, Ireland

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Rachel K Crowley St. Vincent’s University Hospital, Dublin, Ireland
University College Dublin, Dublin, Ireland

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Summary

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrine disorder with a high rate of penetrance. The incidence of MEN1 is 1/30,000 in the general population; however, it is quite rare for a patient to present for medical attention with MEN1 for the first time in pregnancy. Primary hyperparathyroidism (PHPT) is one of the most common features of MEN1. The incidence of PHPT occurring in pregnancy is 1%. Despite advances in the medical, surgical and obstetric care over the years, management of this condition during pregnancy may be challenging. It can be difficult to identify pregnant women with PHPT requiring intervention and to monitor safely. Hypercalcemia can result in significant maternal and fetal adverse outcomes including: miscarriage, intrauterine growth restriction, preterm delivery, neonatal hypocalcaemia, pre-eclampsia and maternal nephrolithiasis. Herein, we present a case study of a lady with a strong family history of MEN1, who was biochemically proven to have PHPT and evidence of Zollinger Ellison Syndrome (ZE) on endoscopy. This patient delayed her assisted pregnancy plans for in vitro fertilization (IVF) until completion of the MEN1 workup; nevertheless, she spontaneously achieved an unplanned pregnancy. As a result, she required intervention with parathyroidectomy in the second trimester of her pregnancy as her calcium level continued to rise. This case study highlights the workup, follow up and management of MEN1 presenting with PHPT and ZE in pregnancy.

Learning points

  • Women of childbearing age who are suspected to have a diagnosis of primary hyperparathyroidism ideally should have genetic testing and avoid pregnancy until definitive plans are in place.

  • Zollinger Ellison syndrome in pregnancy means off-label use of high dose of proton pump inhibitors (PPI). Use of PPI in pregnancy is considered to be safe based on retrospective studies. Omeprazole, however, is FDA class C drug because of lack of large prospective studies or large case series during pregnancy.

  • Calcium supplements in the form of calcium carbonate must be converted to calcium chloride by gastric acid in order to be absorbed, however, patients rendered achlorhydric as a result of PPI use will have impaired absorption of calcium. Therefore, use of calcium citrate might be considered a better option in this case.

Open access