Primary Hyperparathyroidism in Pregnancy: Management and Diagnostic Pearls

Abstract

Background/Objective

Primary hyperparathyroidism in pregnancy is rare, representing <1% of cases, but carries substantial maternal and fetal risks, including nephrolithiasis, pancreatitis, pre-eclampsia, miscarriage, and neonatal hypocalcemia. Diagnosis is obscured by physiologic reductions in calcium and limited imaging options. The objective of this report is to describe 2 cases of primary hyperparathyroidism in pregnancy where unique imaging modalities were utilized.

Case Presentation

A 36-year-old G3P2 female presented in the first trimester with nausea, fatigue, hypercalcemia (11.1 mg/dL; reference 8.5–10.5), and hyperparathyroidism (108 pg/mL; reference 19–88). Biplanar ultrasound and 4D CT of the thyroid and parathyroid glands were unremarkable. Management included oral hydration and parathyroidectomy at 22 weeks, with normalization of calcium and parathyroid hormone postoperatively.

A 24-year-old G1P0 female presented in the first trimester with abdominal pain, hypercalcemia (12.2 mg/dL), and high-normal parathyroid hormone (70.5 pg/mL). Ultrasound of the thyroid/parathyroid glands was nondiagnostic and MRI suggested a lesion along the posterior-inferior aspect of the left thyroid lobe. Management included intravenous hydration and resection of a parathyroid adenoma at 23 weeks. Calcium and parathyroid hormone normalized postoperatively, and delivery was uncomplicated.

Discussion

Primary hyperparathyroidism in pregnancy is difficult to diagnose due to hemodilution, hypoalbuminemia, and increased renal calcium excretion, lowering measured serum calcium. Treatment options are limited and expedited as standard medications lack safety data and serious complications are possible. Hydration provides temporary stabilization, while second-trimester surgery is the definitive treatment.

Conclusion

These cases highlight the importance of clinical suspicion, prudent imaging, and timely surgery to optimize maternal and fetal outcomes.

Highlights

• •Primary hyperparathyroidism (PHPT) in pregnancy is often difficult to diagnose given physiologic hypocalcemia
• •Standard imaging modalities are limited due to fetal safety and radiation concern
• •Preoperative pharmacologic management is limited due to fetal safety concerns
• •Second-trimester parathyroidectomy is effective and first line management of PHPT in pregnancy
• •Early recognition and surgical intervention improve maternal and fetal outcomes

Clinical Relevance

The treatment of primary hyperparathyroidism in pregnancy is stricter compared to non-pregnant individuals given fetal and maternal risks, with lower calcium thresholds indicated for intervention. Timely diagnosis, judicious imaging, and second-trimester surgery optimize outcomes for pregnant patients with PHPT.

Introduction

Primary hyperparathyroidism (PHPT) in pregnancy is rare, accounting for less than 1% of all PHPT cases,¹ but clinically significant due to maternal and fetal complications from hypercalcemia, including hyperemesis, nephrolithiasis, pancreatitis, pre-eclampsia, neonatal hypoparathyroidism, hypocalcemia, intrauterine growth restriction, and miscarriage.² Hypertension and gestational diabetes mellitus may be nonclassical complications of PHPT.³ The pre-existence of these comorbidities can also complicate pregnancy and increase the maternal-fetal risk profile, lowering the threshold for PHPT management and surgical intervention.⁴ Early recognition and intervention are crucial to reduce morbidity and mortality.

PHPT in pregnancy can be difficult to diagnose because of reduced serum calcium from transplacental calcium transfer, hemodilution, and hypoalbuminemia.⁵ These physiological changes can mask hypercalcemia, and up to 80% of patients are asymptomatic.⁵ Symptoms are often nonspecific, contributing to underdiagnosis.² Pregnancy also increases urinary calcium excretion, complicating use of the calcium-creatinine-clearance-ratio to distinguish PHPT from familial hypocalciuric hypercalcemia. In pregnancy, this ratio may appear falsely elevated, limiting diagnostic reliability.^6,7

Given the rarity of PHPT in pregnancy, data on the workup and treatment of PHPT are limited, and standard management guidelines are lacking. Consensus favors second-trimester parathyroidectomy for definitive treatment. The following cases describe 2 patients diagnosed with PHPT in pregnancy, illustrating diagnostic challenges and management considerations.

Case Presentation

Case A

A 36-year-old G3P2 female at 16 weeks gestation was evaluated for PHPT after first-trimester labs revealed hypercalcemia, hyperparathyroidism, and hypovitaminosis D. Symptoms included fatigue and constipation. Her medical history included essential hypertension and prior pre-eclampsia. She had no personal history of GDM, or family history of parathyroid/thyroid disease, multiple endocrine neoplasia (MEN), or other endocrine pathologies.

Initial laboratory workup included serum/urine calcium, intact parathyroid hormone (PTH), and 25-OH-vitamin D (Table 1).

Table 1.

Laboratory Studies Before Pregnancy, During the First Trimester, and During the Second Trimester of Pregnancy in Patient A

Serum study	Patient prepregnancy value	Patient first trimester value	Patient second trimester value	Reference range
Serum calcium	10.3	11.1	11.9	8.5 - 10.5 mg/dL
Calculated calcium	−	−	12.3	8.5 - 10.5 mg/dL
Ionized calcium	−	−	1.39	1.14 - 1.35 mmol/L
Serum albumin	4.7	−	−	3.2 - 4.8 g/dL
PTH intact	−	108	105	19 - 88 pg/mL
Serum 25OH Vit D	−	12	15	30 - 100 ng/mL
24-h urine calcium	−	198	396	100 - 300 mg/24h

Abbreviation: PTH = parathyroid hormone.

Diagnostic workup included biplanar ultrasound and 4D CT of the neck. Point of care ultrasound revealed a normal right thyroid lobe and parathyroid glands without nodularity. The left thyroid lobe was also normal size without nodularity, but a subtle area of hypo-echogenicity in the left inferior lobe was visualized, potentially representing a small left parathyroid adenoma. This finding was partially obscured by vessels and difficult to measure, so supplementary imaging was pursued. A 4D CT was obtained following risk/benefit discussion with the patient and radiology to further localize the culprit parathyroid adenoma before proceeding with surgery. The 4D CT did not reveal any evidence of parathyroid adenoma or abnormalities corresponding to the area of hypo-echogenicity on ultrasound.

She was referred for an exploratory parathyroidectomy given persistent hypercalcemia above 11 mg/dL. In addition to preoperative management with oral hydration, vitamin D supplementation was encouraged. She proceeded with parathyroidectomy at 22 weeks gestation, where a presumed left inferior parathyroid adenoma was identified and resected. Pathology confirmed a parathyroid adenoma. Surgery was uncomplicated and intraoperative PTH decreased appropriately. Her postoperative course was uncomplicated, with normalization of serum calcium and PTH, with her PTH becoming undetectable and within normal limits for pregnancy (Table 2). Postoperatively, she was advised to supplement with vitamin D3 2000 IU daily according to available recommendations on vitamin D supplementation during pregnancy.8, 9, 10 Two months postoperatively, she developed severe-range hypertension and pre-eclampsia without severe features, and was treated with high-dose antihypertensives. She is currently 34 weeks pregnant without further complications, and fetal stress testing remains reassuring. She was referred for genetic testing to evaluate the etiology of her PHPT.

Table 2.

Laboratory Studies Before, During, and After Parathyroidectomy in the Second Trimester of Pregnancy in Patient A

Serum study	Preoperative lab values	Intraoperative lab values	POD 0 lab values	POD 1 lab values	POD 3 lab values	Reference range
Serum calcium	11	−	10.2	9.4	−	8.5 - 10.5 mg/dL
Calculated calcium	12.3	−	−	−	9.9	8.5 - 10.5 mg/dL
Serum albumin	−	−	−	−	−	3.4 - 4.9 g/dL
PTH intact	105	100 → 11	−	<6	−	19 - 88 pg/mL

Abbreviations: POD = postoperative day; PTH = parathyroid hormone.

Case B

A 24-year-old G1P0 female at 18 weeks gestation presented for endocrine evaluation after lab work was concerning for PHPT. Symptoms included abdominal pain, fatigue, and nausea. Medical history included self-reported hypercalcemia since adolescence, 2 episodes of nephrolithiasis, and polycystic ovarian syndrome. She had no personal history of hypertension or diabetes mellitus. Family history included Type 1 diabetes in her father, Type 2 diabetes in her mother, a grandmother with thyroid/parathyroid disease (details unknown), and 2 first cousins with diabetes and possible parathyroid disease. She had no family history of MEN or additional endocrine, thyroid, or parathyroid pathologies.

Laboratory workup included serum/urine calcium, PTH, and 25-OH-vitamin D (Table 3).

Table 3.

Laboratory Studies During the First and Second Trimester of Pregnancy in Patient B

Serum study	Patient first trimester value	Patient second trimester value	Reference range
Serum calcium	12.2 (8.6 – 10.0 mg/dL)a	11.3	8.5 - 10.5 mg/dL
Ionized calcium	1.51 (1.12 – 1.4 mmol/L)a	1.41	1.14 - 1.35 mmol/L
Serum albumin	4.5 (3.5 – 5.2 g/dL)a	4.0	3.4 - 4.9 g/dL
PTH intact	75.8 (15.0 – 65.9 pg/mL)a	89	19 - 88 pg/mL
Serum 25OH Vit D	18.7 ( ≥ 30 ng/mL)a	21	30 - 100 ng/mL
24-h urine calcium	443	−	100 - 300 mg/24hh

Abbreviation: PTH = parathyroid hormone.

^aReferences ranges adjusted for different laboratories.

Diagnostic workup included biplanar ultrasound and neck MRI. Her neck ultrasound did not reveal obvious parathyroid adenomas but suggested minimal bilateral inferior parathyroid enlargement. MRI of the neck, obtained in an effort to further localize a parathyroid adenoma, revealed hyperintensity along the posterior-inferior left thyroid lobe, possibly representing a parathyroid adenoma.

She underwent exploratory parathyroidectomy at 23 weeks gestation given persistent hypercalcemia above 11 mg/dL. She received IV hydration twice weekly preoperatively and was also encouraged to supplement with vitamin D. Surgery revealed abnormal enlargement of her right inferior parathyroid gland, which was resected and confirmed a parathyroid adenoma on pathology. Her intraoperative PTH decreased appropriately, and her surgical and postoperative course were uncomplicated, with normalization of her serum calcium and PTH postoperatively and PTH levels becoming undetectable and within normal limits of pregnancy (Table 4). Postoperatively, she was advised to supplement with vitamin D3 2000 IU daily according to available recommendations on vitamin D supplementation during pregnancy.8, 9, 10 Her vitamin D intake was decreased to 1000 IU daily 3 weeks postoperatively as her vitamin D levels improved on repeat examination and her serum phosphorus became elevated. She was induced at 38w1d for fetal growth restriction and delivered a healthy girl via vaginal birth. Her postpartum course was uncomplicated. She underwent genetic testing with the Invitae Multi-Center Panel, which was negative for parathyroid and endocrine diseases, including MEN 1.

Table 4.

Laboratory Studies Before, During, and After Parathyroidectomy in the Second Trimester of Pregnancy in Patient B

Serum study	Preoperative lab values	Intraoperative lab values	POD 0 lab values	POD 1 lab values	Reference range
Serum calcium	11.2	−	10.7	9.1	8.5 - 10.5 mg/dL
Ionized calcium	1.40	−	−	1.15	1.14 – 1.35 mmol/L
Serum albumin	4	−	−	−	3.4 - 4.9 g/dL
PTH intact	89	98 → 80	<6	<6	19 - 88 pg/mL

Abbreviations: PTH = parathyroid hormone; POD, postoperative day.

Discussion

These cases contribute to the limited data on PHPT in pregnancy, highlighting diagnostic and management challenges. While studies in nonpregnant patients suggest the use of ultrasound and sestamibi scintigraphy for localizing a parathyroid adenoma, with the addition of 4D CT for improved accuracy,¹¹ ultrasound is the preferred imaging modality during pregnancy given its safety profile.¹² Sestamibi scintigraphy and 4D CT are generally avoided in pregnancy as they involve ionizing radiation.¹³ MRI can be used for additional localization in elective settings.

Because hypercalcemia increases risks of pancreatitis, nephrolithiasis, pre-eclampsia, and miscarriage, surgical parathyroidectomy is recommended in the second trimester when calcium exceeds 2.85 mmol/L (11.4 mg/dl), is greater than 0.25 mmol/L (1 mg/dl) above the upper limit of normal, or if an ionized calcium exceeds 1.45 mmol/L (5.8 mg/dl), even without evidence of adenoma on imaging.¹⁴ The risk of miscarriage is linearly related to the degree of hypercalcemia and is more common after exceeding 2.85 mmol/L (11.4 mg/dl); acute pancreatitis, although rare, is another serious complication.¹⁵ A 2024 review of 54 cases of primary hyperparathyroidism-induced acute pancreatitis by Augustin et al found that pancreatitis typically developed around mid-gestation, with median onset at approximately 20 weeks and maternal death occurring at a mean gestational age of 28 weeks. The median serum calcium among affected patients was 3.5 mmol/L (14 mg/dl), and maternal and fetal outcomes worsened significantly when calcium exceeded this threshold, typically from the second trimester onward. Maternal mortality was 9.3%, and fetal/neonatal loss and rate of complex deliveries occurred more frequently when calcium levels reached approximately 4.1 mmol/L (16.4 mg/dl) compared with 3.3 mmol/L (13.2 mg/dl) in survivors. Elevated maternal PTH (mean 1914 pg/mL in fetal/child death cases) and lipase at diagnosis also correlated with worse outcomes, including increased complex deliveries, abortions, and fetal and maternal mortality, respectively. Based on this review, semi-urgent parathyroidectomy is recommended when a patient is symptomatic or calcium exceeds 2.75 mmol/L (11 mg/dl), a slightly more conservative approach than the European consensus guidelines above. This data clarifies the timing and risks associated with maternal hypercalcemia in pregnancy and supports early surgical intervention in the second trimester to avoid such complications.¹⁵

Notably, both patients in these cases obtained multimodal imaging, with one getting an MRI and the other a 4D CT. Although CT is generally avoided due to potential fetal exposure to ionizing radiation, studies show that fetal radiation exposure from a maternal neck CT is negligible.^16,17 Though MRI does not use ionizing radiation, it is less sensitive for localizing parathyroid lesions. In both patients, further imaging failed to localize the adenoma, emphasizing that surgical exploration remains the most definitive diagnostic tool.¹⁸ In case A, the subtle abnormality on neck ultrasound, which was not visualized on CT, was confirmed to be a parathyroid adenoma in surgery, highlighting why surgery remains the gold standard.

Medical management of PHPT in pregnancy differs considerably from nonpregnant patients, as medications like bisphosphonates and cinacalcet are generally avoided due to potential teratogenicity and limited safety data.¹⁹ While case reports have shown safe use of cinacalcet for management of PHPT during pregnancy, these studies recommended reservation of cinacalcet for severe or symptomatic hypercalcemia, and only as a bridge until surgery or delivery are safe.²⁰ Efficacious strategies include oral or intravenous hydration, and less commonly, conservative use of calcitonin, though cost may be limiting.²¹ These treatments may be used for temporary management, but are often insufficient as long-term strategies. Given the fetal and maternal risks, the surgical threshold in pregnancy is lower than in non-pregnant individuals, where surgery may be deferred for mild or asymptomatic disease. Parathyroidectomy is generally advised for symptomatic patients or persistent calcium levels >11.4 mg/dL.¹⁴ Further studies have recommended an even lower threshold of >11 mg/dL to lower the risk of miscarriage.² These differences are based on scarce data and case reports, highlighting management challenges given limited guidelines. Surgery is generally recommended in the second trimester when anesthesia and surgery carry the lowest risk to the fetus.^2,22 One limitation of this report is incomplete maternal and fetal outcome data for Patient A, who remains pregnant.

Conclusion

These cases highlight the importance of high clinical suspicion and careful management strategies in pregnant patients with suspected PHPT. A multidisciplinary team, including endocrinology, maternal-fetal-medicine, and otolaryngology or endocrine surgeons, is essential to balance maternal benefit with fetal safety. Definitive treatment involves second-trimester parathyroidectomy, which has been associated with better neonatal outcomes than medical management.²³

Patient Consent

Complete written informed consent was obtained from the patient for the publication of this study and accompanying images.

Disclosure

The authors have no conflicts of interest to disclose.