OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

OBJECTIVE: To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family. METHODS: Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009). RESULTS: CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent. CONCLUSION This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Duplication/genetics* ; Male ; Pedigree ; DiGeorge Syndrome/diagnosis* ; Adult ; Chromosomes, Human, Pair 22/genetics* ; Abnormalities, Multiple

Parathyroid carcinoma is a rare endocrine malignancy with an indolent course but a high risk of recurrence. Diagnosis remains challenging, requiring integration of clinical, biochemical, radiologic, and histopathologic findings. We report a young patient presenting with primary hyperparathyroidism complicated by multiple pathologic fractures and chronic renal failure. Despite initial surgical and medical management, late aggressive recurrence occurred, resulting in significant systemic complications. This case highlights the need for vigilant long-term surveillance and improved diagnostic and therapeutic strategies.

Introduction: Parathyroidectomy is the definitive treatment for primary hyperparathyroidism (PHPT) due to parathyroid adenoma. However, surgery may be contraindicated in patients with significant comorbidities. Ultrasound-guided percutaneous ethanol ablation (PEA) is a minimally invasive alternative that induces biochemical remission through targeted destruction of hyperfunctioning tissue. We report a case of PHPT successfully managed with PEA in a patient unfit for surgery due to cardiac dysfunction. Case: In 2023, a 53-year-old female with stage IB breast carcinoma was found to have persistent hypercalcemia (2.68– 3.59 mmol/L) during chemotherapy and post-mastectomy follow-up. Evaluation excluded bone metastases. Biochemical assessment demonstrated elevated intact parathyroid hormone (iPTH) levels 38.6 pmol/L (Reference: 1.6–6.0 pmol/L), hypophosphatemia (0.42–0.80 mmol/L), and elevated alkaline phosphatase (ALP) 215–309 U/L (30–120 U/L)—consistent with PHPT. Tc-99 m sestamibi scintigraphy localized a 1.1 × 1.5 × 1.2 cm hyperfunctioning parathyroid adenoma. Initial management prioritized oncological therapy, including trastuzumab for 1 year. Hypercalcemia was intermittently controlled with intravenous hydration and zoledronic acid when calcium exceeded 3 mmol/L. Her disease was complicated with severe osteoporosis (DEXA T-score −3.3) with vertebral fractures, renal impairment requiring cessation of alendronate, and medullary nephrocalcinosis on computed tomography surveillance. Following completion of cancer therapy, she was evaluated for parathyroidectomy. Preoperative assessment revealed NYHA class II heart failure, with reduced ejection fraction (36%) and severe tricuspid regurgitation attributed to trastuzumab-related cardiomyopathy. Despite optimal medical therapy, she was deemed high-risk for surgery. Cinacalcet failed to achieve sustained calcium control with levels exceeding 3 mmol/L. She was therefore referred for PEA. Post-procedure, iPTH decreased 80% by Day 5 (54.9–10.6 pmol/L), with sustained normocalcemia (2.25 mmol/L) at 10 days without further need for cinacalcet. Conclusion This case illustrates that PEA can serve as definitive therapy for PHPT in patients unsuitable for surgery. It provides rapid and sustained biochemical control, while avoiding operative risk, supporting its role in individualized management.
Hyperparathyroidism, Primary ; Ethanol

Introduction: Giant parathyroid adenomas (GPAs), defined as lesions >3.5 g, are rare. Their size, biochemical severity, and compressive features often mimic carcinoma, creating diagnostic and surgical challenges. Case: A 33-year-old female was incidentally found to have hypercalcemia during evaluation after her newborn developed severe hypocalcemic seizures requiring NICU admission. Maternal calcium was 2.95 mmol/L with hypophosphatemia. Subsequent reviews showed persistent hypercalcemia (3.15–3.3 mmol/L), hypophosphatemia (0.32– 0.51 mmol/L), and markedly elevated intact parathyroid hormone (85–96 pmol/L). She had vitamin D deficiency, very high alkaline phosphatase (1,329 U/L), and progressive bone pain with reduced mobility. Bone mineral density revealed Z scores of −2.9 (hip) and −3.3 (lumbar spine). Multiphase computed tomography demonstrated a multilobulated 6.9 cm mass extending from C5 to T2, compressing the esophagus and raising suspicion for carcinoma. Endoscopic evaluation excluded mucosal invasion. She underwent en bloc left inferior parathyroidectomy with hemithyroidectomy. Intraoperative parathyroid hormone fell from 41.7 to 13.4 pmol/L, confirming complete excision. The gland measured 65 × 20 × 15 mm and weighed 18.4 g. Histopathology revealed a hypercellular parathyroid tumor with endocrine atypia but no invasion, consistent with a giant adenoma. Postoperatively, calcium was initially stable (1.99 mmol/L at discharge) but fell to 1.68–1.82 mmol/L at 2 weeks despite high-dose supplementation. Hypocalcemia persisted for 6 weeks, consistent with delayed hungry bone syndrome, likely precipitated by preoperative vitamin D deficiency, markedly elevated alkaline phosphatase, and low bone mineral density. With intensive supplementation, calcium gradually stabilized, and symptoms improved. Conclusion GPAs can closely mimic carcinoma, with endocrine atypia complicating histopathological interpretation. This case illustrates both diagnostic overlap and the unusual, delayed onset of hungry bone syndrome, emphasizing the need for preoperative risk assessment, correction of metabolic deficiencies, and extended postoperative monitoring. Rare presentations such as delayed hungry bone syndrome refine management strategies and improve outcomes in primary hyperparathyroidism.
Parathyroid Neoplasms

Introduction: Primary hyperparathyroidism (PHPT) is a common disorder that typically leads to increased bone turnover and reduced bone mineral density (BMD). Osteopetrosis, in contrast, is a rare, inherited disorder of defective osteoclast function, resulting in diffusely sclerotic but structurally fragile bones. The coexistence of both conditions is rare and can significantly alter the expected skeletal phenotype of PHPT. Case: We report a 77-year-old female with a previous history of resected ovarian carcinoma in remission, chronic iron deficiency anemia, and hypothyroidism. During a hospital admission for a lacunar infarct, an incidental finding of sclerotic skull lesions on computed tomography (CT) brain prompted further investigation. She had no history of fractures, hearing impairment, or family history of parathyroid or bone disorders. Biochemistry revealed parathyroid-dependent hypercalcemia with normal renal function. Bone turnover markers showed a normal resorption marker (BCTx) but an elevated formation marker (P1NP), with a mildly raised alkaline phosphatase. A sestamibi scan localized a probable left upper parathyroid adenoma, despite a negative neck ultrasound. Skeletal survey unexpectedly revealed widespread osteosclerosis of the skull, spine, and long bones, with a markedly elevated BMD on densitometry. Review of prior imaging confirmed that these sclerotic changes predated her current presentation, having been present on CTs from over a decade ago. Recurrent malignancy was excluded with repeat imaging and tumor markers. A diagnosis of PHPT secondary to parathyroid adenoma, coexisting with underlying, previously unrecognized osteopetrosis, was made. The patient declined both recommended parathyroidectomy and genetic studies. Conclusion This case demonstrates a rare coexistence of two pathologies with opposing effects on bone metabolism. The underlying osteopetrosis, characterized by defective osteoclasts, likely rendered the patient’s osteoclasts resistant to the catabolic effects of elevated PTH. This resulted in an atypically normal bone resorption marker and an unexpectedly high BMD, despite the diagnosis of PHPT.
Bone Density' ; Hyperparathyroidism ; Primary Osteopetrosis

Introduction: Parathyroid carcinoma is a rare endocrine malignancy found in 1–5% of patients with primary hyperparathyroidism. It commonly presents with severe hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. We report a challenging case of parathyroid carcinoma presenting with refractory hypercalcemia with incidental papillary thyroid microcarcinoma. Case: A 63-year-old female with hypertension, diabetes mellitus, dyslipidemia, and ischemic heart disease had been followed for primary hyperparathyroidism since 2014 (PTH5.5 pmol/L, calcium range 2.3–4.7 mmol/L). Initial neck ultrasound was suggestive of parathyroid adenoma over left side, but parathyroid scintigraphy failed to localize a lesion. She refused surgical intervention initially until April 2025, then she later agreed. Re-evaluation prior to operation revealed PTH level 76 pmol/L, and repeated parathyroid scintigraphy showed mild sestamibi avid uptake on left thyroid nodule. While awaiting surgery, she was admitted with a hypercalcemic crisis (serum calcium 3.7–5.38 mmol/L), complicated with acute kidney injury. Repeated ultrasound neck revealed extrathyroidal lesion adjacent to inferior pole of left thyroid (1.6 × 1.7 × 1.2 cm). She required aggressive intravenous hydration, intravenous pamidronate, calcitonin, and Denosumab to optimize her calcium level peri-operatively. She underwent left neck exploration with en-bloc left inferior parathyroidectomy, left hemithyroidectomy, and central neck dissection in November 2025. Histopathological examination confirmed parathyroid carcinoma (pT3N1) with nodal metastasis (1/4 lymph nodes positive) and an incidental papillary thyroid microcarcinoma measuring 1 mm (pT1a). Conclusion This case highlights the challenges of perioperative hypercalcemia management in parathyroid carcinoma. Effective preoperative control often requires multiple treatment modalities. Severe refractory hypercalcemia and high PTH level should raise a high index of suspicion for malignancy. Early complete resection is the cornerstone of treatment and is associated with optimal outcomes.
Papillary Thyroid Microcarcinoma ; Calcium ; Parathyroid Neoplasms

Introduction: Primary hyperparathyroidism (PHPT) is frequently asymptomatic or detected incidentally; however, delayed diagnosis may lead to severe skeletal complications. Early recognition is essential, as timely identification and management of parathyroid disease can prevent significant morbidity, although diagnosis may be challenging when clinical and imaging findings are inconclusive. Case: A 46-year-old female with severe bilateral hearing impairment presented to the orthopedic clinic with 3 years’ history of bilateral knee pain and was found to have a right intertrochanteric femur fracture following minimal trauma. She was referred for evaluation of suspected secondary osteoporosis. She has had intermittent constipation and long-standing oligomenorrhea since menarche. There was no history of childhood fractures or use of medications affecting bone metabolism. Examination revealed bilateral knee bowing. Initial evaluation considered metabolic bone disease, including Paget’s disease; however, skeletal survey showed no features suggestive of Paget’s disease or multiple myeloma. Biochemical investigations demonstrated persistent hypercalcemia (2.65–3.1 mmol/L) with inappropriately elevated intact parathyroid hormone (peak 7.62 pmol/L), consistent with PHPT. Serum phosphate was low-normal. Concomitant vitamin D deficiency (25-OH vitamin D 34.46 nmol/L) improved following replacement. Bone mineral density confirmed severe osteoporosis (lumbar spine T-score −5, z-score -4.1); (forearm −6.7, z-score -6.1) reflecting prolonged untreated disease. Neck ultrasound demonstrated a mixed solid-cystic lesion posterior to the right thyroid lobe, suggestive of a parathyroid adenoma. The TC-99 m Sestamibi scan showed no definite focal uptake. However, subsequent SPECT-CT revealed focal tracer uptake at the posterior right thyroid gland, consistent with a hyperfunctioning parathyroid gland. Parathyroidectomy was done. Postoperatively, the calcium level normalized. Conclusion Severe osteoporosis and fragility fracture occur, reflecting prolonged exposure to excess parathyroid hormone and significant skeletal morbidity. Early biochemical evaluation in unexplained severe osteoporosis is essential, as timely diagnosis and definitive management of parathyroid disease are critical to halt ongoing bone loss and prevent irreversible complications.
Hyperparathyroidism, Primary ; Osteoporosis

Introduction: Parathyroid carcinoma (PC) is an exceedingly rare malignancy. Definitive surgical management with en bloc resection is crucial for cure, but the post-operative course can be complicated by profound metabolic derangements, most notably hungry bone syndrome (HBS). We report a case of PC in a 15-year-old female to highlight the challenges in perioperative management. Case: A 15-year-old female presented with a painless, palpable neck mass. There is no family history of note. Investigations revealed severe primary hyperparathyroidism (PHPT) with a corrected calcium of 3.4 mmol/L and an elevated intact parathyroid hormone level of 118.6 pg/mL. Alkaline phosphatase was markedly elevated at 1,168 U/L. Ultrasound, computed tomography neck, and a sestamibi scan identified a large, lobulated 4.7-cm mass posterior to the right thyroid lobe, suspicious of malignancy. Bone mineral density of the forearm was severely diminished, with a Z-score of -6.6. The patient underwent right hemithyroidectomy and parathyroidectomy with intraoperative neural monitoring. Intraoperative parathyroid hormone levels dropped from a pre-excision level of 120.1–16.5 pg/mL 5 minutes post-excision, confirming complete resection of the hyperfunctioning tissue. Histopathological examination confirmed the diagnosis of PC, demonstrating lymphovascular invasion and clear resection margins. The Ki-67 proliferation index was 5%. Post-operatively, the patient developed hypocalcemia, with corrected calcium dropping to a nadir of 1.95 mmol/L. This was managed with intensive calcium and activated vitamin D supplementation. At 10 months post-surgery, the patient continues to require supplementation for persistent hypocalcemia. Surveillance ultrasound at 3 months showed no evidence of recurrence, and she is planned for ongoing annual monitoring. Conclusion This case illustrates the need for a high index of suspicion for PC in young patients with severe PHPT. The postoperative course highlights the challenges in managing HBS, hypoparathyroidism, and long-term surveillance.
Adolescent ; Humans ; Parathyroid Neoplasms

Introduction: Hypocalcemia in patients with advanced malignancy is usually attributed to bone metastases, vitamin D deficiency, renal impairment, or antiresorptive therapy. Paclitaxel, a taxane-based chemotherapy agent widely used for breast cancer, is not commonly associated with calcium disturbances. Proposed mechanism includes renal tubular dysfunction, renal salt wasting, and disruptions in bone metabolism. In patients with underlying disorders of calcium homeostasis such as hypoparathyroidism, taxanebased chemotherapy such as Docetaxel and Paclitaxel may exacerbate calcium imbalance. We reported a case of recurrent hypocalcemia associated with paclitaxel therapy in a patient with metastatic breast cancer. Case: A 42-year-old female with metastatic breast cancer, involving the liver and bones, had previously undergone neoadjuvant chemotherapy, mastectomy, and adjuvant radiotherapy. Following the disease progression, she was commenced on weekly intravenous paclitaxel at a 20% dose reduction due to prior complications and underlying metabolic risk. She had a history of post-thyroidectomy hypoparathyroidism and had previously been intolerant to docetaxel during the neoadjuvant chemotherapy, which was complicated by hypocalcemia, likely secondary to renal salt wasting. During paclitaxel treatment, she developed recurrent symptomatic hypocalcemia, requiring multiple hospital admissions and repeated intravenous calcium gluconate infusions despite ongoing oral calcium and calcitriol supplementation, which were temporarily increased during the chemotherapy. These episodes occurred intermittently in temporal association with paclitaxel administration, with other causes of hypocalcemia were considered less likely. Conclusion Hypocalcemia associated with paclitaxel is rarely described in literature. This case highlights the importance of monitoring calcium level in patients receiving paclitaxel, particularly in those with pre-existing hypoparathyroidism.
Hypocalcemia ; Hypoparathyroidism ; Breast Diseases ; Paclitaxel