Response to Letter to the Editor: “Gestational Gigantomastia Complicated by PTHrP-Mediated Hypercalcemia”

We would like to clarify that our conclusion was not “the placenta was the source of PTHrP” but that there may exist an underexplored placenta-breast axis mediated by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D, and/or possibly human placental lactogen.

Our colleagues propose that the presence of nephrolithiasis suggests hypercalcemia preceded pregnancy or occurred in prior pregnancies. The patient was in her early second trimester, not first, and this is a common time for development of nephrolithiasis, even in patients who are normocalcemic (1, 2). That the patient had a corrected calcium of 14 on admission and likely had elevated levels of serum and urinary calcium for the preceding months of her pregnancy would be completely consistent with de novo nephrolithiasis.

It is important to note that in both our case (3) and our colleagues’ case (4), serum levels of prolactin were low for pregnancy trimester (15.8 ng/mL and 57 ng/mL, respectively; second trimester normal 110 to 330 ng/mL). Our colleagues have illustrated this low prolactin in the context of normal pregnancy reference values in a poster presentation (5) that preceded the publication of their report in Journal of Clinical Endocrinology & Metabolism (4). Therefore, it seems unlikely that the effectiveness of bromocriptine seen in their case was a result of a reduction in prolactin. We discuss in our article why the proposed pathophysiology of breast tissue hypersensitivity to prolactin does not completely or adequately explain several other cases.

We also thank Professor David Haig (6) (Harvard University) who shared thoughts related to the possible role of paternal placental genotype in this pathophysiology, given that it did not occur in previous pregnancies. Whereas we have no information about the paternity history of the patient’s pregnancies and have been unsuccessful in contacting the patient, we encourage future clinicians who encounter similar cases to inquire regarding this possibly elucidating variable.

Acknowledgments

We thank our colleagues for their interest and perspective.

Additional Information

Disclosure Summary: The authors have nothing to disclose.