OBJECTIVE: The management of primary hyperparathyroidism (PHPT) during pregnancy may be surgical or conservative. This study compared adverse outcomes between surgical and non-surgical treatments. Additionally, the study investigated the correlation between serum calcium values and complication rates.
METHODS: A systematic review of retrospective studies, case series, and case reports. Biochemical parameters, interventions, and outcomes of each pregnancy were recorded. The study population comprised two groups: the non-surgical and surgical groups. Adverse outcomes were categorized as maternal, obstetric, or neonatal.
RESULTS: The surgical and non-surgical groups consisted of 163 and 185 patients, respectively. A positive correlation was observed between the mean maternal gestational calcium value and both maternal and obstetric complication. Neonatal complications were more prevalent in patients treated conservatively across all maternal calcium values (p < 0.001). No significant differences were observed in maternal outcomes and overall obstetric outcomes between the study groups, albeit a higher mean serum calcium value in the surgical group (12.3 mg/dL) compared with the non-surgical group (11.1 mg/dL).
CONCLUSIONS: Given the significantly lower neonatal adverse outcomes in the non-surgical group compared to the surgical group, along with non-inferior maternal and obstetric outcomes in the surgical group, the overall data of this study suggest that parathyroidectomy is favorable to non-surgical management even in cases of mild hypercalcemia.

UNASSIGNED: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild.
UNASSIGNED: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases.
UNASSIGNED: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively).
UNASSIGNED: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

BACKGROUND: Transient hypercalcaemia due to teriparatide occurs in up to 11% of patients though delayed hypercalcaemia (> 24 h post injection) is rare. We report the case of a female who developed significant delayed hypercalcaemia after teriparatide treatment for osteoporosis and review other cases in the literature to date.
METHODS: A 72-year-old female on teriparatide for the treatment of osteoporosis was found to have hypercalcaemia (3.30 mmol/l) on routine testing approximately 3 months after starting therapy. Serum calcium pretreatment was normal at 2.39 mmol/l. She was admitted to the hospital for investigations which identified a serum 25-hydroxyvitamin D of 94 nmol/l, a low parathyroid hormone of 6.0 pg/ml, and normal test results for 1,25 dihydroxyvitamin D (115 pmol/l), parathyroid hormone-related peptide (< 1.4 pmol/ml), serum electrophoresis and angiotensin-converting enzyme (39 IU/l). CT abdomen, pelvis, and thorax revealed no evidence of malignancy and an isotope bone scan ruled out skeletal metastases. Serum calcium normalised (2.34 mmol/l) several days after stopping teriparatide and calcium supplements and administering intravenous fluid. On restarting teriparatide, delayed hypercalcaemia reoccurred and treatment was switched to denosumab.
CONCLUSIONS: Delayed moderate to severe hypercalcaemia (serum calcium > 3.0 mmol/l) due to teriparatide is rare but may lead to therapy withdrawal. The underlying predisposing risk factors remain unclear and highlight the importance of a routine serum calcium assessment on therapy.

The infiltration of substances into the buttocks for esthetic purposes can cause local or systemic damage. These infiltrated substances, known as adjuvants, foreign substances, and polymers, often lack sufficient and frequently controversial evidence. To identify the systemic complications associated with substances locally infiltrated in the buttocks for treatment, we conducted a systematic review following the PRISMA criteria. Of 275 publications, 29 met the eligibility criteria: 3 systematic reviews, 6 case series, and 20 case reports. The study comprises 463 cases, mainly women (87%), with an average age of 39.94 years. The average time between infiltrations was 7.65 years. Infiltrated substances included silicone, oils, methyl methacrylate, guaiacol, sodium gadolinium, collagen, paraffin, and other unknown substances. The complications fell into three categories: local, systemic with inflammatory-immune response, and renal damage due to hypercalcemia induced by the granulomatosis caused by the substance. Treatment lacked uniformity, mainly focusing on the main effect. Surgical resection of affected tissue resulted in local and systemic improvement (renal, hypercalcemia, or inflammatory-immune) for most patients. Patients who received comprehensive treatment based on inflammatory-immune control, control of renal involvement, and resection of the tissue area that contained large amounts of the infiltrated substance had a better prognosis than those with diffuse infiltration and delayed treatment.

Pneumocystis jirovecii pneumonia (PJP) is a rare but serious complication of immunosuppression post-solid organ transplantation. We present a case of refractory, severe hypercalcaemia due to PJP in a renal transplant recipient. Treatment of PJP led to normalisation of the patient\'s calcium levels, and clinical improvement. To further explore the proposed calcitriol-driven mechanism leading to hypercalcaemia in PJP, we performed biochemical analysis on pre- and post-treatment serum and bronchoalveolar lavage sample at the time of PJP diagnosis. We confirmed high circulating and pulmonary levels of calcitriol in acute, untreated PJP with severe hypercalcaemia. PJP treatment led to reduction of circulating calcitriol to within normal range. We present this case, together with a literature review of similar reported cases, and the novel biochemical evidence supporting extra-renal production of calcitriol by activated pulmonary macrophages as the mechanism underpinning hypercalcaemia in PJP.

Hypercalcemia, defined as an abnormal elevation of serum calcium, is a common electrolyte anomaly in primary care, affecting almost 1% of the worldwide population. Clinical manifestations concern the neuromuscular, cardiovascular, gastrointestinal, renal and skeletal systems. Among the causes, the main ones are primary hyperparathyroidism, and malignancies. Le initial workup should include the measurement of parathyroid hormone (PTH), and the discontinuation of any medication likely to be involved in iatrogenic hypercalcemia. The chosen treatments and their speed of introduction depend mainly on the severity of hypercalcemia. They include intravenous rehydration, and antiresorptive agents such as bisphosphonates, denosumab or calcitonin.
L’hypercalcémie, définie comme une élévation anormale du taux de calcium sérique, est un trouble électrolytique courant en médecine de premier recours, touchant presque 1 % de la population mondiale. Les manifestations cliniques affectent les systèmes neuromusculaire, cardiovasculaire, gastrointestinal, rénal et ostéoarticulaire. Les causes les plus fréquentes sont l’hyperparathyroïdie primaire et l’hypercalcémie paranéoplasique. Le bilan diagnostique initial nécessite la mesure de l’hormone parathyroïdienne et l’exclusion de tout médicament susceptible d’induire une hypercalcémie. Les traitements choisis et leur rapidité d’introduction dépendent surtout de la sévérité de l’hypercalcémie et comprennent l’hydratation intraveineuse et les inhibiteurs de la résorption osseuse (biphosphonates, dénosumab, calcitonine, etc.).

In tuberculous patient, abnormal extrarenal production of 1.25-dihydroxyvitamin D3 by activated macrophages results in hypercalcemia. High calcium level associated with tuberculosis is frequent in adults with active pulmonary tuberculosis even though most patients are asymptomatic, while hypercalcemia in children due to disseminated tuberculosis is rare. Here, we described a case of a 5-year-old who presented with cough and right anterior chest swelling of two-month duration with an Erythrocyte Sedimentation Rate of 144mm/hour, and a high serum ionized calcium level of 1.46millimol/L. With the epidemiologically prevalence, clinical and radiological imaging findings the diagnosis of disseminated tuberculosis to lung, pleura, lymph node, liver and bone was made, and the child was started with the anti-tuberculosis treatment, hypercalcemia was attributed to the disseminated tuberculosis precipitated by high calcium meal intake and excessive sun exposure. Tuberculosis can be complicated with hypercalcemia; care must be taken in supplementing vitamin D and high calcium meals especially in high sun exposure geographic areas.

Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common paraneoplastic syndrome that is commonly observed in patients with malignancies but rarely encountered in patients with benign tumors. Thus far, not many cases of ameloblastoma with hypercalcemia have been reported, and the pathogenic mechanism has not been studied in depth. This paper presents a case report of a 26-year-old male diagnosed with giant ameloblastoma of the mandible, accompanied by rare hypercalcemia. Additionally, a review of the relevant literature is conducted. This patient initially underwent marsupialization, yet this treatment was not effective, which indicated that the selection of the appropriate operation is of prime importance for improving the prognosis of patients with ameloblastoma. The tumor not only failed to shrink but gradually increased in size, accompanied by multiple complications including hypercalcemia, renal dysfunction, anemia, and cachexia. Due to the contradiction between the necessity of tumor resection and the patient\'s poor systemic condition, we implemented a multi-disciplinary team (MDT) meeting to better evaluate this patient\'s condition and design an individualized treatment strategy. The patient subsequently received a variety of interventions to improve the general conditions until he could tolerate surgery, and finally underwent the successful resection of giant ameloblastoma and reconstruction with vascularized fibular flap. No tumor recurrence or distance metastasis was observed during 5 years of follow-up. Additionally, the absence of hypercalcemia recurrence was also noted.

Familial hypocalciuric hypercalcemia (FHH) is one of the conditions that should be considered in the differential diagnosis of hypercalcemia and normo-hypophosphatemia in childhood. Heterozygous Calcium-sensing receptor (CASR) gene mutations cause FHH, and homozygous CASR gene mutations cause neonatal severe primary hyperparathyroidism (NSHPT). Cinacalcet is an allosteric modulator of Calciumsensing receptor (CaSR), and has been used in the treatment of these clinical entities in recent years.
A 26-month-old boy was examined for a recurrent rash. During the evaluation, hypercalcemia (13.3 mg/ dL), hypophosphatemia (2.3 mg/dL) and inappropriately normal PTH level (67 pg/mL) were observed. Neck and renal ultrasonography were normal. The parathyroid scintigraphy was unremarkable. The patient`s family members were also evaluated, and hypocalciuria (fractional excretion of calcium were 0.01%, 0.04% on two separate tests) was detected concurrently with the patient`s hypercalcemia. The mother`s serum calcium was 10.2 mg/dL, the father`s was 10.6 mg/dL, and the brother`s was 12.8 mg/dL. CASR gene sequencing showed a novel homozygous mutation in exon 4 (c.1057G > A), which had generated a substitution of the amino acid glutamate to lysine at codon 353 (p.Glu353Lys). This mutation was homozygous in the children and heterozygous in the parents. Fluid hydration, furosemide, oral phosphorus, prednisolone, pamidronate and cinacalcet treatments were used in the management of hypercalcemia of the proband. A longer and more effective control was achieved with cinacalcet treatment.
FHH can be seen in heterozygous as well as homozygous CASR gene mutations. Different clinical findings may occur in different individuals from the same family. Cinacalcet therapy can be used successfully in the treatment of individuals with FHH.

OBJECTIVE: There is no specific recommendation for management in pregnant women: the aim of this review, based on a clinical case study, is to clarify its development, complications, risk factor and treatment.
METHODS: A review of the literature was performed by consulting the Pubmed, Cochrane Library, and Science Direct databases.
RESULTS: Primary hyperparathyroidism is defined as excessive production of parathyroid hormone resulting in hypercalcemia. The prevalence of primary hyperparathyroidism during pregnancy is not known. Indeed, the symptomatology, related to hypercalcemia, is not very specific and easily confused with the clinical manifestations of pregnancy. The physiological changes specific to the pregnant state frequently lead to a slight hypocalcemia which may complicate the diagnosis of primary hyperparathyroidism. Primary hyperparathyroidism results from a parathyroid adenoma in the majority of cases and is detected by ultrasound during pregnancy. Primary hyperparathyroidism in pregnancy causes significant risks to both mother and fetus. The maternal complication rate is 14-67%, however, the most serious complication is hypercalcemic crisis, which requires increased surveillance in the postpartum period. Obstetrical complications are also induced by primary hyperparathyroidism, such as acute polyhydramnios, or intrauterine growth retardation. The fetal complication rate can reach 45-80% of cases with neonatal hypocalcemia as the main complication. If medical treatment is based on hyperhydration, only surgical treatment is curative.
CONCLUSIONS: Surgery should be proposed to symptomatic patients or those with high blood calcium levels, discussed in interdisciplinary committee and should be organized ideally in the second trimester to avoid maternal and fetal complications.