Podcast Summary: Endocrine Feedback Loop

Episode EFL062 – Primary Hyperparathyroidism in Pregnancy

Date: June 26, 2025
Host: Dr. Chase Hendrickson (Vanderbilt University Medical Center)
Guest Panelists: Dr. Allison Myers (Albert Einstein College of Medicine/Montefiore Medical Center) & Dr. Shoni Silverberg (Columbia University)

Episode Overview

This episode dives into a recent Journal of Clinical Endocrinology & Metabolism study on the impact of primary hyperparathyroidism (PHPT) on fertility and pregnancy outcomes, analyzing data from a large insured population in the US. The discussion explores the rarity of PHPT in pregnancy, management challenges due to limited evidence, historical context, observed complications, and the study's implications for clinical practice.

Key Discussion Points & Insights

1. Clinical and Historical Context of PHPT in Pregnancy

• Rare but challenging: PHPT affects about 0.05% of reproductive-age women, but is impactful due to its potential complications during pregnancy (02:41).
• Symptoms & evolving phenotype: The clinical presentation has shifted over decades from severe, symptomatic cases to milder, often asymptomatic disease due to improved detection (05:28).
• Complications:
  • Maternal: Nonspecific symptoms (nausea, vomiting, malaise), kidney stones, pancreatitis, rare postpartum crises (05:28–08:33).
  • Fetal/Neonatal: Historically high risk of miscarriage, stillbirth, and neonatal tetany—now likely much lower, especially with milder hypercalcemia (<11 mg/dL); severe complications more linked to higher maternal calcium (08:33–11:05).

“Many of the studies that made up what we call the literature on primary hyperparathyroidism in pregnancy actually describe a different disease.” —Dr. Shoni Silverberg [05:38]

2. Timing and Rationale for Parathyroidectomy

• Surgical intervention: Second trimester is the optimal window for surgery if needed, avoiding first-trimester risks and the third trimester’s crucial fetal parathyroid development (11:41–13:24).
• Historical literature and evolving understanding highlight decreasing complications as more cases are milder.

“The second trimester is the sweet spot—there are clear studies having nothing to do with hyperpara that there are deleterious effects of anesthesia on organogenesis in the first trimester… But why not wait till the third? The reason… is that the fetal parathyroid development occurs mainly in the third trimester.” —Dr. Shoni Silverberg [11:41–13:24]

3. Study Design & Approach

• Retrospective cohort methodology using the Kaiser Permanente Southern California database (14:31).
  • Inclusion: Women aged 18–44, data from 2005–2020.
  • PHPT definition: PTH >65 pg/mL within 6 months of calcium >10.5 mg/dL.
  • Matching: Three controls per case based solely on age (limitations for comparability).
  • Key outcomes: Rate of pregnancy, pregnancy/neonatal complications, and effect of parathyroid surgery timing (16:52–21:33).
  • Sensitivity analyses: Excluded women who underwent parathyroidectomy to examine impact.

“Their criteria may have missed some cases of primary hyperparathyroidism, but I do feel confident that those that they identified actually were likely to have had the disease.” —Dr. Shoni Silverberg [16:52]

4. Results Breakdown

a. Demographics & Baseline Characteristics

• Sample size: 386 women with PHPT; 1,158 age-matched controls (24:37).
• Minimal clinically significant differences in age, BMI, or ethnicity.
• Slightly higher prevalence of hypertension, CKD, and smoking history among PHPT group.

b. Pregnancy Outcomes

• Rates of pregnancy: Similar between groups.
• Blood loss at delivery: Slight statistical differences, not clinically meaningful (28:57).
• Mode of delivery: Higher C-section rate in PHPT group, likely reflecting closer monitoring and intervention rather than disease effect (29:54).

“There are findings, but attributing the findings to the underlying category, in this case primary hyperparathyroidism, is [hard]... Could have been because people were more worried about them, they checked them more commonly.” —Dr. Shoni Silverberg [29:54]

c. Neonatal Outcomes

• No significant differences: Birth weight, APGARs, hypocalcemia, need for calcium supplementation, NICU stays were all similar (31:56).
• Hypocalcemia: Only occurred in the control group.

d. Impact of Parathyroidectomy Timing

• Most patients had mild elevations in calcium and low rates of adverse outcomes, regardless of surgery timing.
• Numbers too small for strong conclusions about surgery during pregnancy (especially second trimester) (31:56–34:51).

5. Implications for Clinical Practice

• Recommendation from study authors: Parathyroidectomy before pregnancy is optimal; if diagnosed during pregnancy, consider surgery in second trimester if substantial hypercalcemia (>11 mg/dL).
• Skepticism about strength of study’s basis for recommendation: Panel agrees this recommendation is sensible, but not strongly supported by the data due to very few second-trimester surgeries.
• Practical considerations: Easier localization and operability outside pregnancy, prevention of potential acute complications, and skeletal implications for breastfeeding.

“Surgery in pregnancy is always more complicated… If you have a person in front of you who has known primary hyperparathyroid and you ask them about their plans for pregnancy… they should very strongly consider parathyroidectomy.” —Dr. Shoni Silverberg [36:55]

• Need for observation: Mildly elevated calcium (<11 mg/dL) and asymptomatic patients may be observed through pregnancy by a multidisciplinary team.

“Observation through pregnancy is associated with excellent maternal and fetal outcomes… But observation [means] a multidisciplinary team is warranted.” —Dr. Shoni Silverberg [42:45]

6. Study Limitations

• Retrospective design: Observational/coding bias, missing data, lack of randomized controls, residual confounders.
• Small sample for pregnancy/post-op outcomes: Especially for intervention groups (parathyroid surgery during pregnancy).
• Possible detection/observation bias: Increased surveillance in PHPT group may partially explain some outcome trends.

Notable Quotes & Memorable Moments

• “Even though this is not common… I’ve seen two [cases] and I even had a colleague… who had a case… that severe enough that she ended up having to terminate her pregnancy at about 14 weeks.”
  —Dr. Allison Myers [02:41]

• “None of us think that primary hyperparathyroidism causes pregnancy and causes a higher live birth rate. [But] these are individuals known to have primary hyperparathyroidism and therefore… were observed more carefully.” —Dr. Shoni Silverberg [29:54]

• “If you know that you want to breastfeed… doing the surgery upfront would definitely help prevent some of the compromise that can happen to the bones.”
  —Dr. Allison Myers [39:36]

Timestamps for Key Segments

• Historical context & complications: 05:28–11:05
• Second trimester surgery rationale: 11:41–13:24
• Study design & methods: 14:31–21:33
• Results and analysis: 24:37–34:51
• Recommendations discussion: 36:55–44:54
• Practice impact & limitations: 44:54–47:15

Conclusion & Clinical Takeaways

• Women with PHPT have similar fertility and pregnancy outcomes to controls; neonatal complications are not increased, especially in mild/asymptomatic cases.
• Parathyroidectomy is recommended pre-pregnancy if possible, or in the second trimester if moderate to severe hypercalcemia occurs.
• Observation is warranted in mild cases, but requires careful coordination between endocrinology, obstetrics, and neonatology.
• Future research: Need for larger, prospective studies to refine risk stratification and gather more data on medical management.

Useful for clinicians: This episode synthesizes evolving evidence to support cautious optimism for women with PHPT contemplating pregnancy, stressing individualized risk assessment, interprofessional collaboration, and up-to-date reference to contemporary data instead of relying solely on historic case reports.