Ultrasound-guided microwave ablation for primary hyperparathyroidism in a pregnancy patient with medullary sponge kidney: a case description and literature analysis

Introduction

Primary hyperparathyroidism (PHPT) is a disorder caused by lesions in the parathyroid tissue, leading to excessive secretion of parathyroid hormone (PTH). Its signs and symptoms include hypercalcemia, increased renal calcium reabsorption, and increased bone resorption. Due to the similarity of PHPT symptoms during pregnancy to other conditions, diagnosis and treatment are often delayed. Notably, PHPT during pregnancy is associated with an increased risk of adverse pregnancy outcomes, including the most feared complication—acute pancreatitis, which can be life-threatening for both mother and fetus (1). For newborns, the risk of complications such as intrauterine growth restriction, hypoparathyroidism, and even death due to poor maternal disease control is also significantly increased (2). Thus, early intervention for PHPT during pregnancy is crucial for the well-being of the mother, fetus, and newborn.

Parathyroidectomy (PTX) is currently recognized as the definitive treatment for pregnancy complicated by PHPT, although its timing presents considerable limitations. Performing the procedure in the first trimester may pose significant risks to the fetus, including a higher likelihood of teratogenicity and postoperative complications. Chinese expert consensus recommends considering PTX at any stage of pregnancy when hypercalcemia poses a significant risk to the patient or fetus (3). A systematic review indicated that PTX was performed in 28.3% (108/382) of pregnant patients with PHPT (4). The procedure was most frequently conducted during the second trimester (67.7% of cases), with a complication rate of 4.48%. In contrast, surgery-related complications and/or mortality occurred in 25% of patients in the first trimester and 21.1% in the third trimester. Therefore, PTX should be reserved for the second trimester when intervention is necessary during pregnancy. Most experts also recommend PTX after delivery as an alternative option (5).

Minimally invasive thermal ablation, including ethanol and thermal ablation, has been reported as an effective treatment for PHPT. Bansal et al. (6) described a case of PHPT due to a cystic parathyroid adenoma, presenting as severe hypercalcemia with acute pancreatitis in the second trimester of pregnancy, that was successfully treated with ultrasound-guided ethanol ablation. Thermal ablation techniques, including microwave ablation (MWA) and radiofrequency ablation (RFA), have been more widely used in the treatment of PHPT. Our previous study demonstrated that PHPT can be effectively and safely managed using ultrasound-guided MWA, as evidenced by a reduction in serum PTH levels and a decrease in the size of parathyroid adenomas (7). Here, we report a case of a pregnant woman with PHPT treated with ultrasound-guided MWA according to standard methods.

Case presentation

A 31-year-old female patient presented to our facility on 8 April 2024 with complaints of fatigue, nausea, and vomiting that had persisted for 1 month. Her obstetric history included one previous pregnancy and delivery. She reported regular menstrual cycles, with her last menstruation having started on 29 January 2024. The patient confirmed her current pregnancy after a missed menstrual period of over 1 month at a local medical facility. On 8 March 2024, she experienced fatigue, nausea, vomiting, and a decrease in appetite, initially considered typical pregnancy symptoms. However, these symptoms worsened over time. Subsequent assessments at a local facility revealed elevated blood calcium levels and parathyroid hyperplasia. Although her serum calcium levels temporarily stabilized with salmon calcitonin treatment, they rose again after discontinuation. Persistent pain in the right side of her neck also failed to improve. Consequently, the patient sought further evaluation and advanced treatment at our institution. Outpatient parathyroid ultrasonography revealed a first-order echo nodule measuring 1.11 cm × 0.76 cm × 0.52 cm in the right upper parathyroid region, suggestive of parathyroid hyperplasia. No significant lesions were detected in the thyroid or peripheral lymph nodes, which exhibited normal vascular flow parameters (Figure 1A). Color Doppler ultrasonography revealed no detectable mass effect in either breast [classified as Breast Imaging Reporting and Data System Category 1 negative (BI-RADS 1)] or in the bilateral axillary lymph nodes. The patient was admitted to the Endocrine and Diabetes Center with a diagnosis of parathyroid hyperplasia and pregnancy. She reported various discomforts, including weakness, dizziness, limb joint pain, non-bilious nausea and vomiting, poor appetite, and severe constipation, although her urination remained normal. During the most recent 10 days, she had experienced a weight loss of approximately 2 kg.

Figure 1 Preoperative ultrasonography demonstrated a hyperechoic nodule in the right upper parathyroid region and bilateral renal imaging findings consistent with medullary sponge kidney. (A) Ultrasonography of the parathyroid gland showed a first-class echogenic nodule in the right upper parathyroid region, suggesting the possibility of parathyroid hyperplasia. (B) Color Doppler ultrasound of the urinary system showed that both kidneys were consistent with the spongiform kidney.

The patient was diagnosed with medullary sponge kidney (MSK) at the age of 24 years. She also had a history of gestational hypertension but no family history of thyroid disorders. She had previously delivered a healthy son.

The physical examination revealed no significant abnormalities. Laboratory testing results were as follows: (I) blood routine examination: white blood cell count 7.89×10⁹/L; red blood cell count 3.90×10¹²/L; hemoglobin 112 g/L; platelet count 234.0×10⁹/L. (II) Biochemical detection: alanine aminotransferase 13.4 U/L; aspartate aminotransferase 11.0 U/L; total protein 60.7 g/L; albumin 41.8 g/L; creatine kinase 25 µmol/L; serum phosphorus 0.76 mmol/L (normal reference range, 0.81–1.45 mmol/L); serum sodium, potassium, and magnesium levels were normal (normal reference range of sodium: 137.0–147.0 mmol/L; normal reference range of potassium: 3.50–5.30 mmol/L; normal reference range of magnesium: 0.66–1.07 mmol/L). (III) Urinary calcium: 5.56 mmol/L over 24 hours (normal reference range, 2.50–7.50 mmol/24 h); 24-hour urinary phosphorus 23.76 mmol/L (normal reference range, 13.00–42.00 mmol/24 h). (IV) Thyroid function: thyrotropin 0.106 µIU/mL (normal reference range, 0.27–4.20 µIU/mL). (V) 25-hydroxyvitamin D: 14.4 ng/mL. (VI) Repeated blood calcium and PTH tests were abnormally elevated. Color Doppler ultrasound of the urinary system showed findings consistent with MSK, along with cysts in both kidneys. The left kidney exhibited wall calcification, and stones were detected in the right kidney. No significant abnormalities were observed in the bilateral ureters or bladder (Figure 1B). The chest radiograph showed no abnormalities.

The procedure was managed by a multi-disciplinary team comprising endocrinologists, interventional radiologists, anesthesiologists, and obstetricians. Ultrasound-guided MWA was employed to avoid ionizing radiation. Local anesthesia without sedatives minimized fetal risks. Perioperative hydration with normal saline was administered to reduce hypercalcemia risk. Postprocedural monitoring included serial measurements of calcium, PTH, vital signs, and fetal assessment. In addition, the patient was advised to adhere to a more stringent postoperative review schedule and were closely followed up, with serological parameters monitored at 2 weeks, 1 month, and 3 months after surgery.

The patient was treated with MWA after a thorough evaluation of the potential benefits and risks. As previously reported, MWA of the right upper parathyroid gland was performed under intraoperative ultrasound guidance. The MWA system (KY-2000) was produced by Canyon Medical Inc. (Nanjing, China). Briefly, a total of 54 mL of normal saline was injected and maintained around the parathyroid adenoma to create a barrier, preventing thermal damage to the trachea, esophagus, and recurrent laryngeal nerve. The microwave antenna was inserted into the parathyroid lesion along a previously determined path, and MWA was initiated at 35 W output power. The procedure continued until the entire gland appeared hyperechoic. Following ablation, color Doppler ultrasound showed no blood flow in the parathyroid lesions.

The MWA procedure lasted 75 seconds. The operative heart rate was 72 beats per minute, blood pressure was 147/99 mmHg, and blood oxygen saturation was 98%. The patient reported only mild pain. PTH levels dropped immediately postoperatively, falling below the normal range. After 20 minutes and 12 hours, PTH levels remained low, but they returned to normal at 36 hours postoperatively and stayed within normal limits for up to three months, indicating a complete remission of hyperparathyroidism (Figure 2). Three months after surgery, serum calcium and PTH levels remained normal, and no significant adverse events, such as hoarseness or bleeding, were reported.

Figure 2 Changes in parathyroid hormone levels at different postoperative time points in patients. PTH, parathyroid hormone.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

PHPT is a disorder caused by lesions in the parathyroid tissue, leading to excessive secretion of PTH. Its signs and symptoms include hypercalcemia, increased renal calcium reabsorption, and increased bone resorption. During pregnancy, a series of physiological changes occur in the mother to meet the needs of fetal growth and development, particularly regarding calcium and phosphorus homeostasis, which is essential for both maternal and neonatal outcomes. Notably, there is no significant difference in albumin-corrected blood calcium or ionic calcium concentrations between pregnant and non-pregnant women (8). Thus, the diagnosis of PHPT in pregnancy should be based on medical history and clinical manifestations, with or without hypercalcemia. Hypercalcemia is diagnosed when albumin-corrected blood calcium or serum ionic calcium is elevated, and the serum PTH level is either increased or not suppressed (6). The physiological regulation of calcium and phosphorus metabolism during pregnancy involves the intestines, bones, and kidneys. PTH and PTH-related peptides also play key roles in maintaining calcium and phosphorus balance during pregnancy. This report describes a case of PHPT during pregnancy that was successfully treated with ultrasound-guided MWA. Three months after surgery, follow-up showed normal serum calcium and PTH levels, with no reported complications.

The treatment of PHPT during pregnancy primarily focuses on the removal of the parathyroid lesion, with surgery being the preferred option. Drug therapy is typically used only to create a safer preoperative environment for surgery. Conservative treatment may be considered for patients with mildly elevated serum calcium levels (up to 0.25 mmol/L above the upper limit of normal) or those without significant symptoms of PHPT during pregnancy. Conservative management usually involves oral and intravenous rehydration while avoiding high dietary calcium intake. Currently, medications considered safe for use during pregnancy include diuretics, phosphates, calcitonin, and vitamin D. However, these drugs do not reliably maintain serum calcium levels within the normal range throughout pregnancy (9). Many of these, including calcitonin, phosphate, and diuretics, fall into Class C or Class D of the Food and Drug Administration (FDA) pregnancy drug classification and are not recommended unless absolutely necessary. Compared to surgical treatment, conservative drug therapy is associated with a higher incidence of complications such as hypocalcemia and hand-foot convulsions in both mothers and newborns. Additionally, the rates of fetal loss, preeclampsia, and preterm birth are significantly increased in patients receiving drug therapy (10). Surgical treatment, specifically pathological PTX, is currently regarded as the definitive approach for managing PHPT during pregnancy. For sporadic cases of PHPT, minimally invasive PTX combined with intraoperative PTH monitoring is preferred. However, there is no universally accepted threshold for serum calcium levels that warrant surgical intervention during pregnancy. It is generally recommended that surgery be considered for patients with PHPT who have a history of miscarriage and serum calcium levels exceeding 2.75 mmol/L, or if total serum calcium continues to rise above 2.85 mmol/L after albumin correction (11,12). Surgery is also indicated when serum calcium levels exceed 2.75 mmol/L after albumin correction. Although the second trimester is considered the safest period for surgery, procedures have also been performed in both early and late pregnancy (5,10,13,14). According to the Chinese expert consensus on the management of PHPT during pregnancy, PTX may be considered at any stage of gestation if hypercalcemia poses a significant risk to the mother or fetus, particularly when acute pancreatitis is suspected or needs to be ruled out. This consensus emphasizes the importance of timely surgical intervention in preventing life-threatening complications such as pancreatitis, which is strongly associated with severe hypercalcemia (serum calcium >2.85–3.0 mmol/L) (1). Surgery in the early stages of pregnancy carries a higher risk of fetal teratogenesis and miscarriage. In contrast, late-pregnancy surgeries pose significant risks to the mother due to substantial physiological changes and uterine sensitivity, which increase the likelihood of premature delivery. Although PTX has generally been well-tolerated in recent years, potential complications include postoperative issues, complexity of the case, recurrent laryngeal nerve paralysis, and scarring at the incision site. In summary, there is no ideal diagnostic and treatment protocol for the early detection of PHPT during pregnancy, highlighting the need for new therapeutic approaches that ensure the safety of both mother and fetus.

As research on hyperparathyroidism progresses, ablation therapy has gained attention as a potential treatment option. Ablation methods include high-intensity focused ultrasound (HIFU), RFA, MWA, and laser ablation (LA). Previous studies have demonstrated that ablative therapy is an effective treatment for PHPT, with minimal complications in non-pregnant patients (15,16). For patients with poor cardiopulmonary function, or those who are not candidates for surgery or decline it, ultrasound-guided thermal ablation for parathyroid hyperplasia offers several advantages, including safety, ease of execution, quick recovery, and repeatability. A meta-analysis indicated that parathyroid ablation reduces the risk of hypocalcemia but increases the risk of persistent and recurrent hyperparathyroidism (17). Additionally, compared to PTX, thermal ablation offers benefits such as lower cost, lack of radiation exposure, better patient tolerance, fewer complications, and shorter hospital stays and recovery times. MWA has been shown to have a shorter operation time for a single lesion and a higher complete ablation rate for a large lesion than RFA (18), and can be safely applied during pregnancy. Due to the unique physiological conditions during pregnancy and the rarity of pregnancy complicated by hyperparathyroidism, clinical perspectives on the use of ablation therapy during pregnancy remain inconsistent. As of May 2024, a systematic literature search was conducted using China Next Generation Internet (CNGI), PubMed, Web of Science, and Embase, focusing on terms related to ablation of hyperparathyroidism during pregnancy. The number of relevant studies was fewer than five, most of which were case reports. Pal et al. (19) retrospectively analyzed one case of PHPT during pregnancy over the past decade. In this case, the patient presented blood calcium levels above 3.0 mmol/L at diagnosis, and clear qualitative and positional assessments were made before ablation. The follow-up pregnancy outcomes were favorable.

In this report, the patient opted to terminate the pregnancy after being informed of the risks the disease posed to the fetus. Her blood calcium levels returned to normal, and PTH levels dropped within 48 hours following ablation. During the three-month postoperative follow-up, both serum calcium and PTH levels remained within normal ranges. Genetic testing for multiple endocrine neoplasia type 1 (MEN1) and screening for other neuroendocrine tumors were not conducted due to financial constraints and the absence of a family history of parathyroid disease.

The patient had a history of MSK, necessitating a differential diagnosis between secondary hyperparathyroidism caused by MSK and pregnancy-associated PHPT. MSK is a congenital renal dysplasia characterized by fusiform dilation of the papillary ducts and cystic dilation of the collecting ducts in the renal medulla. MSK can lead to calcium metabolism disorders, with long-term hypercalciuria potentially causing hypocalcemia and secondary hyperparathyroidism, resulting in increased calcium absorption and synthesis. In this report, the patient had normal renal function and right kidney stones without a history of recurrent infections, and no signs of renal atrophy were observed. Therefore, secondary hyperparathyroidism caused by MSK was ruled out. Furthermore, the results matched the typical characteristics of PHPT, defined by “hypercalcemia and hypophosphatemia”. Consequently, one can exclude the diagnosis of secondary hyperparathyroidism associated with MSK. Thakker (20) recommends genetic counseling and germ-line mutation testing for patients with hyperparathyroidism suspected to have a genetic cause, especially those with early onset, multiple gland involvement, parathyroid carcinoma, or atypical parathyroid adenoma.

In conclusion, ultrasound-guided thermal ablation presents a promising, effective, and scalable alternative to PTX for pregnant women with PHPT caused by parathyroid adenoma. It is essential to fully evaluate each case, communicate thoroughly with the patient and their family, and develop individualized treatment plans that take the patient’s wishes and comprehensive health needs into account.

Conclusions

Ultrasound-guided MWA may be considered a treatment option for patients with PHPT in early pregnancy.

Acknowledgments

None.

Footnote

Funding: This work was supported by Jiangsu Provincial Traditional Chinese Medicine Administration Bureau Science and Technology Project (No. MS2021023); Nanjing University of Chinese Medicine Natural Science Foundation Project (No. XZR2023011); and Nanjing Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Support Project (No. NJCC-ZJ-202349).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-100/coif). All authors report research grant support for this work from Jiangsu Provincial Traditional Chinese Medicine Administration Bureau Science and Technology Project (No. MS2021023); Nanjing University of Chinese Medicine Natural Science Foundation Project (No. XZR2023011); and Nanjing Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Support Project (No. NJCC-ZJ-202349). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Augustin G, Lai Q, Cigrovski Berkovic M. Primary hyperparathyroidism-induced acute pancreatitis in pregnancy: A systematic review with a diagnostic-treatment algorithm. World J Gastroenterol 2024;30:3755-65. [Crossref] [PubMed]
2. Arnez L, Lawrence V. Complex management decisions in a woman with concurrent primary hyperparathyroidism and metastatic papillary thyroid carcinoma, both presenting during pregnancy. Endocrinol Diabetes Metab Case Rep 2019;2019:19-0110. [Crossref] [PubMed]
3. Zhong H, Liao Q, Liu JSociety of Parathyroid and Metabolic Bone Diseases, Chinese Research Hospital Association. Chinese Society of Perinatal Medicine; Chinese Society of Osteoporosis and Bone Mineral Research. Expert consensus on multidisciplinary approach to the diagnosis and treatment of primary hyperparathyroidism in pregnancy in China. Endocrine 2023;82:282-95.
4. Sandler ML, Ho R, Xing MH, Gidumal S, Spitzer H, Levy JC, Chai RL. Primary Hyperparathyroidism During Pregnancy Treated With Parathyroidectomy: A Systematic Review. Laryngoscope 2021;131:1915-21. [Crossref] [PubMed]
5. Bilezikian JP, Khan AA, Silverberg SJ, Fuleihan GE, Marcocci C, Minisola S, Perrier N, Sitges-Serra A, Thakker RV, Guyatt G, Mannstadt M, Potts JT, Clarke BL, Brandi ML. International Workshop on Primary Hyperparathyroidism. Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop. J Bone Miner Res 2022;37:2293-314. [Crossref] [PubMed]
6. Bansal S, Kaushik RM, Kaushik R, Modi S, Raghuvanshi S, Kusum A. Primary hyperparathyroidism presenting as severe hypercalcemia with acute pancreatitis in pregnancy. Gynecol Endocrinol 2020;36:469-72. [Crossref] [PubMed]
7. Ni W, Yuan Y, Chu X, Chen G, Han X, Li J, Wu X, Wang J, Liu C, Xu S. Bone Turnover Markers in Response to Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism. Front Endocrinol (Lausanne) 2021;12:782050. [Crossref] [PubMed]
8. Dahlman T, Sjöberg HE, Bucht E. Calcium homeostasis in normal pregnancy and puerperium. A longitudinal study. Acta Obstet Gynecol Scand 1994;73:393-8. [Crossref] [PubMed]
9. Hui E, Osakwe O, Teoh TG, Tolley N, Robinson S. Three case reports of maternal primary hyperparathyroidism in each trimester and a review of optimal management in pregnancy. Obstet Med 2010;3:33-7. [Crossref] [PubMed]
10. Arshad MF, Arambewela MH, Bennet WM, Sterrenburg M, Balasubramanian SP. Primary hyperparathyroidism in pregnancy: experience of a tertiary centre. Surg Today 2023;53:470-5. [Crossref] [PubMed]
11. Jiao HN, Sun LH, Liu Y, Zhou JQ, Chen X, Liu JM, Zhong HP. Multidisciplinary team efforts to improve the pregnancy outcome of pregnancy complicated with primary hyperparathyroidism: case series from a single hospital. BMC Pregnancy Childbirth 2021;21:576. [Crossref] [PubMed]
12. Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, et al. European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders. Eur J Endocrinol 2022;186:R33-63. [Crossref] [PubMed]
13. Beck AJ, Reddy VM, Sulkin T, Browne D. Management of severe and symptomatic primary hyperparathyroidism in the first trimester of unplanned pregnancy. Endocrinol Diabetes Metab Case Rep 2022;2022:21-0203. [Crossref] [PubMed]
14. Sharma SG, Levine SN, Yatavelli RK, Shaha MA, Nathan CAO. Parathyroidectomy in First Trimester of Pregnancy. J Endocr Soc 2020;4:bvaa015. [Crossref] [PubMed]
15. Hussain I, Ahmad S, Aljammal J. Radiofrequency Ablation of Parathyroid Adenoma: A Novel Treatment Option for Primary Hyperparathyroidism. AACE Clin Case Rep 2021;7:195-9. [Crossref] [PubMed]
16. Zhang M, Gao Y, Zhang X, Ding Z, Wang X, Jiang W, Zhao C. Evaluation of efficacy of ultrasound-guided microwave ablation in primary hyperparathyroidism. J Clin Ultrasound 2022;50:227-35. [Crossref] [PubMed]
17. Gong L, Tang W, Lu J, Xu W. Thermal ablation versus parathyroidectomy for secondary hyperparathyroidism: A meta-analysis. Int J Surg 2019;70:13-8. [Crossref] [PubMed]
18. Xu W, Li S, Cheng F, Gong L, Tang W, Lu J, Li Y, Wang Z. Microwave ablation versus radiofrequency ablation for patients with primary and secondary hyperparathyroidism: a meta-analysis. Int Urol Nephrol 2023;55:2237-47. [Crossref] [PubMed]
19. Pal R, Bhadada SK, Gupta N, Behera A, Aggarwal N, Aggarwal A, Raviteja KV, Saikia UN, Kaur G, Arvindbhai SM, Walia R. Primary hyperparathyroidism in pregnancy: observations from the Indian PHPT registry. J Endocrinol Invest 2021;44:1425-35. [Crossref] [PubMed]
20. Thakker RV. Genetics of parathyroid tumours. J Intern Med 2016;280:574-83. [Crossref] [PubMed]