# Beyond Malignancy: Clinical Insights from Three Cases of Severe Hypercalcemia

**Authors:** Shani Ben Dori, Noor Kabaha, Amer Abu Husseine, Eilam Rabina, Liat Barzilay Yoseph, Pnina Rotman-Pikielny, Martin H. Ellis, Osnat Jarchowsky Dolberg

PMC · DOI: 10.3390/jcm15062412 · 2026-03-21

## TL;DR

This paper presents three cases of severe hypercalcemia caused by non-cancerous conditions, emphasizing the importance of timely diagnosis and treatment.

## Contribution

The paper highlights non-malignant causes of severe hypercalcemia through detailed clinical cases and emphasizes PTH-based diagnostic stratification.

## Key findings

- Hypercalcemia resolved in a postpartum woman after stopping breastfeeding, suggesting lactation-associated hypercalcemia.
- A 30-year-old woman's hypercalcemia was linked to primary adrenal insufficiency, diagnosed through systematic evaluation.
- A parathyroid adenoma was identified as the cause of hypercalcemia in a 47-year-old man, confirmed by surgery and pathology.

## Abstract

Severe hypercalcemia is a life-threatening condition requiring immediate treatment alongside a systematic evaluation to identify the underlying cause. Although malignancy is a common etiology among hospitalized patients, alternative causes must be considered to guide targeted therapy, as illustrated in these cases. The first case involved a 31-year-old postpartum woman with corrected calcium levels of 14.5 mg/dL and suppressed PTH. Hypercalcemia resolved after tapering and temporary cessation of breastfeeding, consistent with lactation-associated hypercalcemia that is likely PTHrP-mediated. The second case describes a 30-year-old woman who presented with hypotension, hypercalcemia, hyperphosphatemia, and low PTH. A systematic evaluation revealed severe glucocorticoid deficiency consistent with primary adrenal insufficiency (Addison’s disease). The final case featured a 47-year-old man with severe symptomatic hypercalcemia (18.5 mg/dL) and markedly elevated PTH. Imaging revealed a 3 cm parathyroid tumor. Selective parathyroidectomy produced a rapid intraoperative PTH decline, and pathology supported parathyroid adenoma rather than carcinoma. Together, these cases highlight that symptomatic severe hypercalcemia is a medical emergency warranting prompt clinical intervention, followed by an early PTH-based stratification to direct a focused, stepwise diagnostic workup and definitive management.

## Linked entities

- **Proteins:** PTH (parathyroid hormone), PTHLH (parathyroid hormone like hormone)
- **Diseases:** hypercalcemia (MONDO:0001566), primary adrenal insufficiency (MONDO:0015128), Addison’s disease (MONDO:0100480), parathyroid adenoma (MONDO:0006890)

## Full-text entities

- **Genes:** PTHLH (parathyroid hormone like hormone) [NCBI Gene 5744] {aka BDE2, HHM, PLP, PTHR, PTHRP}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}
- **Diseases:** Malignancy (MESH:D009369), Hypercalcemia (MESH:D006934), parathyroid adenoma (MESH:D010282), glucocorticoid deficiency (MESH:C565974), hypotension (MESH:D007022), Addison's disease (MESH:D000224), hyperphosphatemia (MESH:D054559)
- **Chemicals:** calcium (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13026940/full.md

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Source: https://tomesphere.com/paper/PMC13026940