Parathyroid hormone-related peptide induced hypercalcemia of pregnancy due to mammary hyperplasia.

Maternal Parathyroid Hormone-related Protein (PTHrP) is involved in the placental transport of calcium. Autonomous overproduction of PTHrP is a rare cause of hypercalcemia in pregnancy. Prior cases of PTHrP-induced hypercalcemia in pregnancy have been managed with either dopamine agonists, fetal delivery, termination of pregnancy, or mastectomy. However, PTHrP level normalization following mastectomy has not previously been documented. Herein, we present a 39-year-old female hospitalized at 19 weeks of gestation for acute encephalopathy due to PTHrP induced hypercalcemic crisis (calcium 15.8 mg/dL, PTHrp 46.5 pmol/L [normal 0-3.4]). Mammary hyperplasia resulting in gigantomastia significantly impaired her ability to ambulate and perform activities of daily living. She remained hypercalcemic during hospitalization despite aggressive hydration, calcitonin, and 2 weeks of dopamine agonist treatment. Bisphosphonate therapy was not administered due to pregnancy and potential effects on the fetus. Our patient underwent bilateral mastectomy along with excision of a large axillary mass. The pathology of all three specimens revealed mammary stromal hyperplasia. PTHrP was undetectable on post-op day 2 and calcium normalized by post-op day 3. At discharge, she was able to ambulate independently. To our knowledge, this is the first reported case of PTHrP induced hypercalcemia related to gigantomastia, documenting resolution of hypercalcemia, and PTHrP levels following mastectomy. Mastectomy is a potential option in the second trimester for pregnant patients with PTHrP induced severe hypercalcemia due to gigantomastia, refractory to treatment with dopamine agonist therapy.

Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene.

CONTEXT: Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the Chloride Channel 7 gene (CLCN7) that cause disease by a dominant negative mechanism. Variants in the T-cell immune regulator 1 gene (TCIRG1) are commonly identified in autosomal recessive osteopetrosis but have only been reported in 1 patient with ADO. CASE DESCRIPTION: Here, we report 3 family members with a single heterozygous missense variant (p.Gly579Arg) in TCIRG1 who have a phenotype consistent with ADO. Three of 5 protein prediction programs suggest this variant likely inhibits the function of TCIRG1. CONCLUSION: This is the first description of adult presentation of ADO caused by a TCIRG1 variant. Similar to families with ADO from CLCN7 mutations, this variant in TCIRG1 results in marked phenotype variability, with 2 subjects having severe disease and the third having very mild disease. This family report implicates TCIRG1 missense mutations as a cause of ADO and demonstrates that the marked phenotypic variability in ADO may extend to disease caused by TCIRG1 missense mutations.

The Use of Inhaled Epoprostenol for Acute Respiratory Distress Syndrome Secondary Due To COVID-19: a Case Series.

Introduction: Inhaled epoprostenol (iEpo) is a pulmonary vasodilator used to treat refractory respiratory failure, including that caused by Coronavirus 2019 (COVID-19) pneumonia. Aim of Study: To describe the experience at three teaching hospitals using iEpo for severe respiratory failure due to COVID-19 and evaluate its efficacy in improving oxygenation. Methods: Fifteen patients were included who received iEpo, had confirmed COVID-19 and had an arterial blood gas measurement in the 12 hours before and 24 hours after iEpo initiation. Results: Eleven patients received prone ventilation before iEpo (73.3%), and six (40%) were paralyzed. The partial pressure of arterial oxygen to fraction of inspired oxygen (P/F ratio) improved from 95.7 mmHg to 118.9 mmHg (p=0.279) following iEpo initiation. In the nine patients with severe ARDS, the mean P/F ratio improved from 66.1 mmHg to 95.7 mmHg (p=0.317). Ultimately, four patients (26.7%) were extubated after an average of 9.9 days post-initiation. Conclusions: The findings demonstrated a trend towards improvement in oxygenation in critically ill COVID-19 patients. Although limited by the small sample size, the results of this case series portend further investigation into the role of iEpo for severe respiratory failure associated with COVID-19.