Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population.

BACKGROUND: Long-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. METHODS: Patients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. RESULTS: A total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1-11.4), and mean parathyroid hormone was 272 pg/mL (range 108-622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. CONCLUSIONS: Screening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.

The Safety Profile of Vitamin D Supplements Using Real-World Data from 445,493 Participants of the UK Biobank: Slightly Higher Hypercalcemia Prevalence but Neither Increased Risks of Kidney Stones nor Atherosclerosis.

Background: Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32-1.62] and 1.11 [1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as "transient post-transplant hypercalcemia" (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Hipercalcemia e hipofosfatemia en prematuros que reciben nutrición parenteral agresiva / Hypercalcemia and hypophosphatemia among preterm infants receiving aggressive parenteral nutrition

Introducción. La nutrición parenteral agresiva constituye un estándar de cuidado en prematuros de muy bajo peso. Sin embargo, investigaciones recientes evaluaron su impacto en los resultados a corto plazo, como la homeostasis mineral y electrolítica. El objetivo fue comparar la prevalencia de hipercalcemia e hipofosfatemia en prematuros que recibían nutrición parenteral agresiva o estándar. Métodos. Estudio observacional retrospectivo que comparó a un grupo de prematuros menores de 1250 gramos que recibían nutrición parenteral agresiva con un grupo control histórico. Se calculó la prevalencia de hipercalcemia y se buscó la asociación con nutrición parenteral agresiva ajustando por confundidores. Se estimó la media de fosfatemia del grupo control mediante regresión lineal y se la comparó con el otro grupo. Resultados. Se incluyeron 40 pacientes por grupo. La prevalencia de hipercalcemia fue mayor en el grupo de nutrición parenteral agresiva (87,5% vs. 35%, p= 0,001). La nutrición parenteral agresiva se asoció con hipercalcemia al ajustar por peso al nacer, restricción del crecimiento intrauterino, aporte de aminoácidos y calorías (ORa 21,8; IC 95%: 3,7-128). La media de calcemia fue diferente entre ambos grupos (p= 0,002). El grupo de nutrición parenteral agresiva presentó más sepsis sin alcanzar significancia estadística y su fosfatemia media resultó menor que la estimada para el grupo control (p= 0,04). La prevalencia de hipofosfatemia en este grupo fue de 90% (IC 95%: 76-97%). Conclusiones. Nuestros datos muestran una asociación entre hipercalcemia/hipofosfatemia y nutrición parenteral agresiva. Se recomienda monitorizar la calcemia y la fosfatemia frecuentemente, ya que pueden estar asociadas con resultados clínicos adversos.

Introduction. Aggressive parenteral nutrition is the standard of care among very-low-birth weight preterm infants. However, in recent studies, its impact on short-term outcomes, has been evaluated. The objective was to compare the prevalence of hypercalcemia and hypophosphatemia among preterm infants receiving aggressive or standard parenteral nutrition. Methods. Observational, retrospective study comparing a group of preterm infants weighing less than 1250 grams who received aggressive parenteral nutrition with a historical control group. The prevalence of hypercalcemia was estimated and its association with aggressive parenteral nutrition was searched adjusting by confounders. The mean phosphate level was estimated for the control group by linear regression and was compared to the value in the other group. Results. Forty patients per group were included. The prevalence of hypercalcemia was higher in the group who received aggressive parenteral nutrition (87.5% versus 35%, p= 0.001). Aggressive parenteral nutrition was associated with hypercalcemia when adjusting by birth weight, intrauterine growth restriction, amino acid, and calorie intake (adjusted odds ratio: 21.8, 95% confidence interval -amp;#91;CI-amp;#93;: 3.7-128). The mean calcium level was different between both groups (p= 0.002). Infants who received aggressive parenteral nutrition had more sepsis without reaching statistical significance and the mean phosphate level was lower than that estimated for the control group (p= 0.04). The prevalence of hypophosphatemia in this group was 90% (95% CI: 76-97%). Conclusions. Our data show an association between hypercalcemia/hypophosphatemia and aggressive parenteral nutrition. It is recommended to frequently monitor calcium and phosphate levels since they might be associated with adverse clinical outcomes.

Persistent disorders of mineral metabolism after one year of kidney transplantation / Alterações do metabolismo mineral e ósseo após um ano de transplante renal

Abstract Introduction: The persistence of mineral metabolism disorders after renal transplant (RT) appears to possess a negative impact over graft and patient's survival. Objectives: To evaluate the parameters of mineral metabolism and the persistence of hyperparathyroidism (HPT) in transplanted patients for a 12-month period after the procedure. Methods: Retrospective analysis of 41 transplants (18 women- 44%, mean age of 39 ± 15 years) performed in a University Hospital, evaluating changes of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) and the prevalence of persistent HPT. The patients were divided into two groups accordingly to PTH levels prior to Tx: Group 1 with PTH ≤ 300 pg/mL (n = 21) and Group 2 with PTH > 300 pg/mL (n = 20). The persistency of HPT after transplant was defined as PTH ≥ 100 pg/mL. The evolution of biochemical parameters and the persistency of HPT were analyzed in each group after 1 year of transplant. Results: After a one-year of follow up, 5% of the patients presented hypophosphatemia (p < 2.7 mg/dL), 24% hypercalcemia (Ca > 10.2 mg/dL) and 48% persistency of HPT (PTH ≥ 100 pg/mL). There was a positive correlation between the PTH pre and post Tx (r = 0.42/p = 0.006) and a negative correlation between PTH and Ca pre-Tx (r = -0.45/p = 0.002). However, there was no significant difference among groups 1 and 2 regarding PTH levels pre and post Tx. Conclusion: The findings in this article suggest that mineral metabolism alterations and the persistency of HPT may occur after one year of renal Tx, mainly in patients which present high PTH levels prior toTx.

Resumo Introdução: A persistência de distúrbios do metabolismo mineral ósseo após o transplante renal (Tx) parece possuir um impacto negativo sobre a sobrevida do enxerto e do paciente. Objetivos: avaliar os parâmetros do metabolismo mineral e a persistência de hiperparatiroidismo (pHPT) 12 meses após o Tx. Métodos: Análise retrospectiva de 41 transplantes (18 mulheres- 44%, idade de 39 ± 15 anos) realizados em um Hospital Universitário, avaliando cálcio (Ca), fósforo (P), hormônio da paratireóide (PTH) e a prevalência de pHPT. Pacientes foram divididos em dois grupos de acordo com os níveis de PTH pré Tx: Grupo 1: PTH ≤ 300 pg/ml (n = 21) e Grupo 2: PTH > 300 pg/ml (n = 20). pHPT foi definida como PTH ≥ 100pg/mL após o Tx. A evolução dos parâmetros bioquímicos e a pHPT foram analisadas após 1 ano de Tx. Resultados: após um ano, 5% dos pacientes apresentaram hipofosfatemia (p < 2,7mg/dL), 24% hipercalcemia (Ca > 10,2 mg/dL) e 48% persistência de HPT (PTH ≥ 100 pg/mL ). Houve correlação positiva entre PTH pré e pós Tx (r = 0,42/p = 0,006) e correlação negativa entre PTH e Ca pré-Tx (r = -0,45/p = 0,002). Entretanto, não houve diferença significativa entre os grupos 1 e 2 em relação aos níveis de PTH pré e pós-Tx. Conclusão: Os resultados sugerem que alterações do metabolismo mineral e a pHPT podem ocorrer após um ano do Tx, principalmente em pacientes com níveis elevados de PTH pré-Tx.

Doença celíaca é super-representada em pacientes com constipação / Celiac disease is overrepresented in patients with constipation

OBJETIVO: Tem sido sugerido que pacientes com constipação sejam triados para doença celíaca. Da mesma forma, recomenda-se a investigação desses pacientes para hipotiroidismo e hipercalcemia. Contudo, nenhuma evidência para essas recomendações está disponível até o momento. Assim, propusemos-nos determinar a prevalência de doença celíaca, hipotiroidismo e hipercalcemia em crianças com constipação. MÉTODOS: Estudo de coorte prospectivo com 370 pacientes consecutivos que preencheram os critérios de Roma III para constipação. Esses pacientes foram encaminhados por um clínico geral a um pediatra devido ao fracasso no tratamento com laxantes. RESULTADOS: A biópsia comprovou doença celíaca em sete desses pacientes. Isso é significativamente mais alto (p < 0,001) do que a prevalência de 1:198 de doença celíaca nos Países Baixos. Dois pacientes tinham tiroidite autoimune. Nenhum paciente tinha hipercalcemia. CONCLUSÕES: Conclui-se que a doença celíaca é significativamente super-representada em pacientes com constipação encaminhados por um clínico geral a um pediatra devido ao fracasso no tratamento com laxantes. Todos esses pacientes devem, portanto, ser triados para doença celíaca.

OBJECTIVE: It is suggested that patients with constipation should be screened for celiac disease. Similarly, it is recommended to investigate these patients for hypothyroidism and hypercalcemia. However, no evidence for these recommendations is available so far. We therefore set out to determine the prevalence of celiac disease, hypothyroidism, and hypercalcemia in children with constipation. METHODS: Prospective cohort study of 370 consecutive patients who met the Rome III criteria for constipation. These patients were referred by a general practitioner to a pediatrician because of failure of laxative treatment. RESULTS: Seven of these patients had biopsy-proven celiac disease. This is significantly higher (p < 0.001) than the 1:198 prevalence of celiac disease in the Netherlands. Two patients had auto-immune thyroiditis. No patient had hypercalcemia. CONCLUSIONS: We conclude that celiac disease is significantly overrepresented in patients with constipation who are referred by a general practitioner to a pediatrician because of failure of laxative treatment. All such patients should, therefore, be screened for celiac disease.

Hipercalciuria idiopática y compromiso óseo en niños / Idiopathic hypercalciuria and bone injury in children

Introducción: la Hipercalciuria Idiopática (HI), entidad considerada tradicionalmente benigna y asociada a hematuria o urolitiasis, es uno de los trastornos del metabolismo de calcio y fósforo más frecuente en pediatría. En los últimos años se ha asociado a desmineralización ósea tanto en niños como en adultos. Objetivo: determinar el impacto de la Hipercalciuria Idiopática en el contenido mineral óseo en pacientes pediátricos chilenos. Métodos: estudio de corte transversal; se evaluaron 11 pacientes portadores de Hipercalciuria Idiopática. Se midió calcio en orina de 24 horas y en muestra aislada, calcemia, fosfemia, electrolitos plasmáticos, paratohormona plasmática (PTH) y densitometría ósea (DEXA) de columna lumbar y fémur. Para definir la relación entre la calciuria y las demás variables se utilizó un análisis de correlación simple para variables continuas. Se consideró estadísticamente significativo un p < 0,05. Resultados: se estudiaron 11 pacientes, 6 varones, 8,2 ± 2,7 años. El promedio de calcio en orina 24 h fue 9,1 ± 1,37 mg/kg/día, PTH 40 ± 15 pg/ml y el DEXA columna lumbar (Z score) fue de y -2,1 ± 0,29. El análisis estadístico mostró una correlación negativa entre calciuria de 24 h y densidad mineral ósea de columna lumbar (p < 0,05, r = -0,65), y entre Hipercalciuria vs niveles de PTH (p < 0,05, r = -0,58). Conclusión: la Hipercalciuria Idiopática en pediatría representa un riesgo de compromiso óseo que debe ser considerado al evaluar el manejo de cada paciente.

Hipercalcemia de la malignidad / Malignancy hypercalcemia

La hipercalcemia de la malignidad constituye la emergencia metabólica más frecuente en el área oncológica, pudiendo afectar hasta un 10-20 por ciento de los pacientes. La hipercalcemia afecta profundamente la calidad de vida del paciente con cáncer y compromete multiples sistemas orgánicos provocando alteraciones potencialmente letales a nivel neuromuscular, gastrointestinal, renal y cardiovascular. En la presente revisión se enfocan aspectois epidemiológicos, se analizan los mecanismos de producción de hipercalcemia en las diferentes neoplasias, se discuten las dificultades en el diagnóstico preciso de esta entidad y las causas desencadenantes del mismo y finalmente se plantean los diferentes tratamientos actuales así como los temas de controversia e investigación en el cuidado de los pacientes con cáncer.

Hipercalcemia no câncer de pulmäo: consideraçöes sobre prevalência, diagnóstico e etiopatogenia / Hypercalcemia in the lung cancer: considerations about prevalence, diagnosis and etiopathogeny

Hipercalcemia é uma complicaçao freqüente em pacientes portadores de câncer de pulmao. O diagnóstico e tratamento precoces da hipercalcemia melhoram o prognóstico destes pacientes. Estudamos 79 pacientes ambulatoriais (59 homens e 20 mulheres) com idades variando entre 30 e 84 anos (mediana de 63 anos), todos com diagnóstico histológico de câncer de pulmao (46,8 por cento carcinoma espinocelular, 37,9 por cento adenocarcinoma e 12 por cento com outros tipos celulares). Dez pacientes (12,6 por cento) encontravam-se hipercalcêmicos (Ca++ maior que 1,29 mmol/L), com variaçao de 1,30 a 1,59 mmol/L. Dois deles (25 por cento) apresentavam níveis elevados de PTHrp (porçao média, RIA) e AMPc, com PTH suprimido; um apresentou associaçao com hiperparatiroidismo primário e quatro tiveram cintilografia positiva para metástases ósseas. Em três pacientes hipercalcêmicos o mecanismo patogênico da hipercalcemia nao foi associado com a presença de metástases ósseas, aumento dos níveis de PTHrp ou PTH. Concluímos que hipercalcemia é uma complicaçao freqüente em pacientes com câncer de pulmao, sendo sua fisiopatogenia heterogênea.

Prevalência de hipercalcemia em pacientes portadores de câncer de pulmäo / Prevalence of hypercalcemia in patients carriers of lung neoplasm

A hipercalcemia é uma das maiores freqüentes manifestaçöes paraneoplásicas, principalmente dentre as neoplasias malignas de pulmäo, mas ainda pouco valorizada em nosso meio. Neste trabalho estudamos a prevalência de hipercalcemia em uma populaçäo de pacientes portadores de tumor de pulmäo que freqüentaram o ambulatório específico da Escola Paulista de Medicina no Hospital Säo Paulo. Foram investigadso 90 pacientes assim distribuídos: 35 carcinomas espinocelulares (CEC), 30 adenocarcinomas (AdenoCa), 11 carcinomas indiferenciados de pequenas células (CIPC), 2 tumores de grandes células (RGC), 1 carcinóide, 1 mesotelioma, 2 indiferenciados, 1 adenoescamoso, 1 carcinoma in situ e 3 tumores metastáticos de origens diversas. Em todos estes pacientes foi dosado Ca ionizado (Ca-i) em amostras de sangue total. Nos pacientes em que se constataram níveis de Ca-i acima do limite de normalidade )>1,29 mmol/L), foram realizadas dosagens de paratormônio (PTH) sérico e AMP cíclico urinário para se afastar um possível hiperparatiroidismo como causa da hipercalcemia. Encontramos níveis de Ca-i elevados (variando de 1,3 a 2,0 mmol/L em 18 destes pacientes (20//), sendo: 12 CEC (66,7//), 3 AdenoCa (16,7//), 2 CIPC (11,1//) e 1 TGC (5,6//). O PTH estava baixo ou suprimido em todos os pacientes hipercalcêmicos, afastando, desta forma, um hiperparatiroidismo. A dosagem de AMP cíclico urinário näo se mostrou útil no diagnóstico diferencial, estando elevada em 6 dos 12 pacientes avaliados. Concluímos ser hipercalcemia um achado bastante comum em pacientes portadores de tumores de pulmäo, principalmente dentre os carcinomas espinocelulares, sendo seu diagnóstico sindrômico e etiológico de grande interesse para melhor tratamento desses pacientes