Primary Hyperparathyroidism: Part One: Evaluation.

Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment.

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.

Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies.

Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasms. It also constitutes a summary of the current knowledge regarding the diagnosis of hypercalcemia and its management. Hypercalcemia of malignancy is estimated to affect over 40% of cancer patients and can be associated with both solid and blood cancers. Elevated calcium levels can be an indicator of developing cancer. The main mechanism of hypercalcemia development in tumors appears to be excessive production of parathyroid hormone-related peptides. Among the known treatment methods, bisphosphonates, calcitonin, steroids, and denosumab should be mentioned, but ongoing research promotes progress in pharmacotherapy. Given the rising global cancer prevalence, the problem of hypercalcemia is of high importance and requires attention.

Do large parathyroid adenomas increase the risk of severe hypercalcemia?

<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0-3.5 g are called "large" or "giant" adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm³ (control group). In both groups, the majority were women (81.5% - study group, 90.5% - control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3-0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>.

Operative management of primary hyperparathyroidism in Europe.

BACKGROUND: Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism. METHODS: Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up. RESULTS: A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5-93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries. CONCLUSION: This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes.

Congenital liquified subcutaneous fat necrosis in a newborn: an unusual case.

Subcutaneous fat necrosis of the newborn is a self-limited disorder of the panniculus that arises in the first six weeks of life. Some differential diagnoses may be difficult such as bacterial cellulitis or erysipelas. The prognosis is usually favorable but there are serious complications for which the patient must be regularly monitored, especially hypercalcemia. We report a case of a full-term newborn with a liquidated area of subcutaneous fat necrosis. A surgical incision was performed because of the discomfort and the lack of regression. Hypercalcemia and nephrocalcinosis appeared afterward. A set of clinical, biological, and histological arguments allows the diagnosis of subcutaneous fat necrosis. Follow-up to early detection and to manage such complications is necessary.

Too Much of a Good Thing: Severe Hypercalcemia Presenting with Lethargy and Kidney Failure.

INTRODUCTION: We present a case of a 58-year-old man with a history of laryngo-pharyngectomy including bilateral thyroidectomy due to hypopharyngeal cancer presenting with lethargy, acute kidney failure, and hypercalcemia. Milk alkali syndrome was diagnosed given the history of high-dose calcium / vitamin D supplementation after ruling out other causes of hypercalcemia. After initial treatment with normal saline, furosemide and denosumab, the patient developed severe symptomatic hypocalcemia as a rare adverse effect of denosumab.

Immunotherapy combined with targeted therapy in advanced small cell carcinoma of the ovary of hypercalcemic type: A case of overall survival lasting for over 5 years.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly aggressive ovarian malignant neoplasm lacking a unified clinical management process. Most patients are diagnosed at an advanced stage and have an extremely poor prognosis with an overall probability of survival less than 10 %. Here, we describe the case of a patient with advanced SCCOHT achieved a survival of over 5 years after receiving multiple cycles of immunotherapy combined with anti-angiogenic therapy or CDK4/6 inhibitors. At the same time, we also summarized the case reports and clinical trials of immunotherapy in SCCOHT.

Primary hyperparathyroidism in pregnancy: a case report highlighting uncommon complication.

Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyperemesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis. Further investigations revealed hypercalcemia and persistently elevated PTH levels, consistent with PHPT. After localization studies, the patient underwent an emergency parathyroidectomy with a diagnosis of parathyroid adenoma. During follow-up, intrauterine growth restriction and severe preeclampsia developed, necessitating an emergency cesarean section. Both the mother and neonate had favorable outcomes. PHPT is an infrequent condition in the pregnant population, and its diagnosis can be challenging due to the overlap of symptoms with normal physiological changes during pregnancy. The occurrence of uncommon complications, such as thrombotic phenomena, highlights the need for a comprehensive approach to ensure early detection and management. In most cases, parathyroidectomy is the treatment of choice.

El hiperparatiroidismo primario (HPTP) se caracteriza por niveles elevados de calcio y hormona paratiroidea (PTH). Sin embargo, la interpretación de pruebas diagnósticas, como los niveles de calcio sérico y PTH, es compleja en mujeres embarazadas. El objetivo de este reporte es presentar un caso de HPTP en una adolescente embarazada, con especial hincapié en una complicación infrecuente, así como en las estrategias diagnósticas y de tratamiento. Una mujer embarazada de 17 años presentó hiperémesis gravídica y síntomas neurológicos, lo que llevó al diagnóstico de trombosis venosa cerebral. Posteriores investigaciones revelaron hipercalcemia y niveles persistentemente elevados de PTH, consistentes con HPTP. Tras la realización de estudios de localización, la paciente fue sometida a una paratiroidectomía de emergencia con diagnóstico de adenoma de paratiroides. Durante el seguimiento, se desarrolló restricción del crecimiento intrauterino y preeclampsia grave, lo que resultó en la necesidad de realizar una cesárea de emergencia. Tanto la madre como el neonato evolucionaron favorablemente. El HPTP es una condición infrecuente en la población embarazada y su diagnóstico puede ser desafiante por la superposición de síntomas con los cambios fisiológicos normales del embarazo. La aparición de complicaciones infrecuentes, como fenómenos trombóticos, resalta la necesidad de un abordaje integral para garantizar la detección y el manejo temprano. En la mayoría de los casos, la paratiroidectomía es el tratamiento de elección.

A Rare Ectopic Parathyroid Adenoma in the Prevertebral Space.

Ectopic parathyroid adenomas are an uncommon etiology of primary hyperparathyroidism. We present a case of a patient admitted to the hospital with severe hypercalcemia and elevated parathyroid hormone levels, in whom imaging revealed two distinct parathyroid masses in the prevertebral space, representing a rare and atypical location for parathyroid tissue. This case highlights the importance of considering ectopic parathyroid adenomas as a potential cause of hyperparathyroidism and discusses the diagnostic challenges and management strategies associated with such cases.

[Hypercalcaemia: intensive care or general ward]. / Die Hyperkalzämie ­ Intensivmedizin oder Normalstation.

Hypercalcaemia is a life-threatening electrolyte imbalance, which not only occurs in the context of an endocrinological disease but is also frequently associated with a tumour. Its severity is determined by the level of deviation from normal, acuity of occurrence, and severity of the symptoms. These are unspecific, can affect any organ system and ultimately result in a life-threatening hypercalcaemic crisis characterised by cardiac arrhythmia, metabolic acidosis, exsiccosis, fever, psychotic states and, ultimately, coma. Endocrinological disorders, drugs such as vitamin D3, vitamin A, checkpoint inhibitors, but also malignancies can be causative for the development of hypercalcaemia. Up to 30% of tumour patients are affected by hypercalcaemia. It is associated with a poor prognosis and a high tumour burden. Malignant hypercalcaemia is mainly caused by PTHrP (parathormone-related peptide), which is secreted by the tumour cells. In oncological patients, serum calcium (ionised calcium and non-ionised calcium) should be evaluated regularly. As the level of serum calcium depends on the albumin concentration, the latter should also be evaluated. Treatment consists of increasing the intravasal volume, increasing calcium excretion and inhibiting calcium reabsorption.

[Hypercalcemia: a practical review]. / Hypercalcémie : revue pratique.

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.).

An infant developing hypercalcemia and hypophosphatemia due to the use of exclusively almond milk.

OBJECTIVES: Plant-based milk alternatives are increasingly utilized in children with cow milk allergy, lactose intolerance, and personal preference. However, notable differences exist in mineral content between cow milk and plant-based alternatives. Almond milk, in particular, varies in mineral and caloric content across different brands. This case report highlights a toddler who developed hypercalcemia and hypophosphatemia attributed to almond milk consumption. CASE PRESENTATION: A fourteen-month-old girl with a history of biliary atresia underwent liver transplant at seven months of age. She was exclusively consuming almond milk for two months prior to presentation. She was admitted to the hospital for severe hypercalcemia (14.6 mg/dL) and hypophosphatemia (1.6 mg/dL). She had elevated random urine calcium to creatinine ratio (2.56 mg/g) and low urine phosphorus to creatinine ratio (<0.44 mg/g) were noted. Parathyroid hormone (PTH) level was appropriately suppressed (<6 pg/mL), while 1,25 dihydroxyvitamin D level was slightly elevated at 88 pg/mL. Initial management included intravenous fluids, followed by a switch to a formula with higher phosphorus and lower calcium concentrations. The patient was discharged after six days with normalized calcium and phosphorus levels, which remained within the normal range. CONCLUSIONS: Although plant-derived milk serves as a viable alternative to cow milk, careful consideration of mineral content, particularly in infants and toddlers, is imperative. Sole reliance on almond milk for nutritional needs in this population is not recommended. Caregivers should be informed about the potential risks associated with almond milk consumption in infants and toddlers.

Hypercalcaemia of malignancy: a case of vitamin-D-mediated hypercalcaemia in lymphoma.

Hypercalcaemia of malignancy (HCM) is a paraneoplastic syndrome that often portends a poor prognosis. We present an extremely rare (<1%) case of HCM due to extrarenal calcitriol (1,25-(OH)2D) production in a patient with splenic marginal zone lymphoma. A man in his 80s presented with a 3-week history of fatigue, unsteadiness and abdominal pain, and new findings of anaemia, kidney injury and hypercalcaemia. Laboratory evaluation, bone marrow biopsy and positron emission tomography/computed tomography (PET/CT) confirmed the diagnosis of splenic marginal zone lymphoma which produced calcitriol (1,25-(OH)2D3), causing the patient's hypercalcaemia.

Neonatal hypocalcaemic seizures unmasking asymptomatic maternal primary hyperparathyroidism.

Hypocalcaemia is a common cause of neonatal seizures. Here, we present a breastfed neonate with smooth perinatal transition and no family history of seizures presenting at 3 weeks with recurrent multifocal clonic seizures. On evaluation, the neonate was found to have low iCa and total calcium. 25-hydroxy vitamin D (25(OH)D) level was low and intact parathyroid hormone (iPTH) was inappropriately normal. The maternal evaluation revealed high calcium and low phosphate levels. iPTH was very high and 25(OH)D was very low in the mother. Sestamibi scan showed a left inferior parathyroid adenoma in the mother. Maternal primary hyperparathyroidism causing hypercalcaemia can suppress parathyroid activity in the fetus, resulting in inappropriate parathyroid response to hypocalcaemia after birth causing recurrent hypocalcaemic seizures. So neonatal hypocalcaemic seizures need careful evaluation of the neonate and the mother at times and can help both mother and neonate.