Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

ABSTRACT Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

Vitamin d deficiency and paratohommonium increase in late postoperative gastric bypass in roux-en-y / Deficiência de vitamina d e elevação do paratohôrmonio no pós-operatório tardio de bypass gástrico em y-de- roux

ABSTRACT Background : Roux-en-Y gastric bypass patients can experience changes in calcium metabolism and hyperparathyroidism secondary to vitamin D deficiency. Aim : To evaluate nutritional deficiencies related to the calcium metabolism of patients undergoing gastric bypass with a 10-year follow-up. Method : This is a longitudinal retrospective study of patients submitted to Roux-en-Y gastric bypass at a multidisciplinary clinic located in the Brazilian southeast region. The study investigated the results of the following biochemical tests: serum calcium, ionized calcium, vitamin D, and parathormone (PTH). The generalized estimating equations (GEE) determined the nutritional deficiencies using a significance level of 5%. Results : Among the patients who finished the study (120 months), 82.86% (n=29) had vitamin D deficiency, and 41.94% (n=13) had high PTH. Postoperative time had a significant effect on PTH (p=0.0059). The percentages of patients with vitamin D, serum calcium, and ionized calcium deficiencies did not change significantly over time. Conclusion : One of the outcomes was vitamin D deficiency associated with secondary hyperparathyroidism. These findings reaffirm the importance of monitoring the bone metabolism of patients submitted to Roux-en-Y gastric bypass. HEADINGS: Calcium deficiency. Vitamin D deficiency. Secondary hyperparathyroidism.

Resumo Racional: Pacientes submetidos ao bypass gástrico em Y-de-Roux, podem apresentar alterações do metabolismo do cálcio e hiperparatireoidismo secundário à deficiência de vitamina D. Objetivo: Avaliar as deficiências nutricionais relacionadas ao metabolismo do cálcio de pacientes submetidos à bypass gástrico em Y-de-Roux, com seguimento de 10 anos. Método: Um estudo retrospectivo longitudinal foi conduzido com pacientes submetidos à bypass gástrico em Y-de-Roux, em uma Clínica Multidisciplinar no Sudeste do Brasil. Investigou-se a frequência do acompanhamento médico e nutricional e os exames bioquímicos de cálcio sérico, cálcio iônico, vitamina D e paratormônio (PTH). Para a análise das deficiências nutricionais, foram utilizadas as Equações de Estimativas Generalizadas (EEG), com nível de significância de 5%. Resultados: Dos pacientes que permaneceram no estudo até o final (120 meses), 82,86% (29), apresentaram níveis de deficiência de vitamina D e 41,94% (13) apresentaram PTH elevado. O efeito do tempo foi significativo para o PTH (p=0,0059). Para a vitamina D, cálcio sérico e cálcio iônico, o percentual de deficiência manteve-se constante ao longo do tempo, sem diferença significativa entre os tempos. Conclusão: A deficiência de vitamina D, associada ao hiperparatireoidismo secundário, foi um desfecho encontrado. Tais achados reafirmam a importância do cuidado com o metabolismo ósseo, em pacientes submetidos à bypass gástrico em Y-de-Roux.

Vitamin D (25(OH)D) in patients with chronic kidney disease stages 2-5 / Niveles de vitamina D (25(OH)D) en pacientes con enfermedad renal crónica estadios 2 a 5

Abstract Objective: To establish the impact the chronic kidney disease stage has in the native vitamin D levels in patients not undergoing dialysis treatment. Methods: A study performed in Manizales, Colombia, a city located 2,200 meters above sea level, without important stational variations. Patients with 18 years of age or more, with chronic kidney disease stages 2 to 5 and not undergoing dialysis treatment were recruited for this study. Demographic and anthropometric variations were evaluated as well as solar exposure, CKD etiology and laboratory variables related to bone and mineral diseases. For each CKD clinical stage, correlations were evaluated for vitamin D levels, laboratory results for bone and mineral diseases, solar exposure and ethnicity. Results: Three hundred thirty-three patients were evaluated with a median age of 71 years, most of them mestizo (71%), 173 were women. The main CKD etiology was hypertensive nephropathy (32.2%). 21.1% of patients had normal vitamin D levels, 70.1% were within insufficient range and 8.8% were in deficit. A negative correlation was found between the levels of vitamin 25 (OH) D and the values for: creatinine, phosphorous, calcium x phosphorous product, PTH, 24 hours urine protein and BMI. A positive relationship was found for calcium and albumin. Positive significant statistical correlation was found for vitamin 25(OH) D levels and solar exposure for stages 3b and 4 of CKD. Conclusions: It is common to find low levels of vitamin 25(OH) D in patients with CKD; these can contribute to the appearance of secondary hyperparathyroidism.

Resumen Objetivo: Establecer el impacto del estadio clínico en los niveles de vitamina D nativa en pacientes con enfermedad renal crónica (ERC) sin diálisis. Métodos: Estudio realizado en Manizales, Colombia, una ciudad tropical ubicada a 2,200 metros de altura sobre el nivel del mar, sin variaciones estacionales importantes a lo largo del año. Se incluyeron pacientes mayores de 18 años, con enfermedad renal crónica estadio 2 a 5 sin tratamiento dialítico. En ellos se evaluaron variables demográficas, antropométricas, grado de exposición solar, etiología de la enfermedad, y variables de laboratorio relacionadas con desórdenes óseos y minerales. Para cada estadío clínico se evaluó la correlación entre los niveles de vitamina D y los resultados de las pruebas de laboratorio relacionadas con desordenes óseos y minerales, exposición solar y etnia. Resultados: Se evaluaron 331 pacientes, con una edad media de 71 años, la mayoría mestizos (71%), 173 mujeres. La principal etiología de ERC fue nefropatía hipertensiva (33.2%). El 21.1% de los pacientes tenían niveles normales de vitamina D, fueron insuficientes en 70.1% y 8.8% en déficit. Se detectó correlación negativa, entre los niveles de vitamina 25(OH)D y los valores de creatinina, fósforo, producto calcio x fósforo, PTH, proteínas en orina de 24 horas e IMC. Correlación positiva para el calcio y la albumina. Se encontró significancia estadística positiva entre los niveles de vitamina 25(OH)D y la exposición solar para los estadios 3b y 4. Conclusiones: En pacientes con ERC es comun detectar bajos niveles de 25(OH)D, los cuales pueden contribuir a la generación de hiperparatiroidismo secundario.

The history of the parathyroid surgery / A história da cirurgia das paratireoides

ABSTRACT The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment.

RESUMO Os autores fizeram uma revisão dos principais aspectos históricos da progressão do conhecimento sobre o tratamento cirúrgico do hiperparatireoidismo. Por meio de revisão bibliográfica, foram analisados artigos selecionados sobre a história da evolução do conhecimento anatômico, fisiológico, patológico e cirúrgico das glândulas paratireoides. Devido às suas características anatômicas peculiares, as paratireoides foram as últimas das glândulas endócrinas a serem descobertas, o que dificultou sobremaneira seu tratamento adequado até as primeiras décadas do Século XX. A evolução tecnológica ocorrida nos últimos 30 anos facilitou sobremaneira a localização das glândulas e a cirurgia do hiperparatireoidismo. Contudo, um cirurgião experiente e dedicado ao tratamento dessa enfermidade ainda é fundamental para a excelência do tratamento.

Hiperparatiroidismo primario normocalcémico

Presentamos las características clínicas, bioquímicas y densitométricas de 35 pacientes con hiperparatiroidismo primario (HPP) normocalcémico, que se caracteriza por un nivel elevado de hormona paratiroidea intacta (PTHi) con el calcio sérico y iónico persistentemente normales, una vez descartadas posibles causas de hiperparatiroidismo secundario. Del total, 30 fueron mujeres (90%) y 5 varones (10%). Se seleccionó un grupo control de 55 pacientes con hiperparatiroidismo primario hipercalcémico: 51 mujeres (93%) y 4 varones (7%). El promedio de edad al diagnóstico de HPP normocalcémico fue de 61.4 ± 11.7 años y del HPP hipercalcémico de 56.4 ± 11.3 años. Además de las diferencias esperables de la calcemia, el calcio iónico, el fósforo y la calciuria de 24 horas, no encontramos cambios significativos en el resto de las variables bioquímicas. Tampoco encontramos diferencias en los valores densitométricos, la presencia de osteopenia u osteoporosis y el número de fracturas entre ambos tipos de HPP. Sí hubo una diferencia significativa en la presencia de litiasis renal entre el HPP normocalcémico (11.4%) vs el HPP clásico (49.1%), p < 0.0005, en parte vinculada a la presencia de hipercalciuria en el HPP clásico. Dos de los 35 pacientes con HPP normocalcémico evolucionaron al HPP hipercalcémico durante un seguimiento de 4 años. Nuestros resultados apoyan la hipótesis que el HPP normocalcémico podría ser una forma temprana del HPP clásico, teniendo ambos similares repercusiones clínicas a nivel renal y óseo.

This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

Concurrent Parathyroid Carcinoma and Hyperplasia in Hyperparathyroidism

No abstract available.

Parathyroid Carcinoma Presenting as a Hyperparathyroid Crisis

No abstract available.

[Brown tumor of mandible in a patient with normocalcemic primary hyperparathyroidism]

Brown tumor or Osteitis Fibrosa Cystica [OFC] is a rare clinical entity complicating hyperparathyroidism. It may occur in the head and neck, with the mandible being the most frequent site. Primary hyperparathyroidism is usually associated with hypercalcemia. We report a 35 years old female with mandibular brown tumor secondary to primary hyperparathyroidism. In this case in spite of primary hyperparathyroidism and the bony lesion the serum calcium level was within normal limit. This case demonstrates that in osteolytic bony lesions a hyperparathyroidism complication can be expected even with normal serum calcium level. The presence of normocalcemia in hyperparathyroidism should prompt the physician to measurement of ionized calcium and look for vitamin D deficiency, magnesium deficiency, impaired renal function, use of interacting drugs and associated disorders. If there weren't these factors, normocalcemic primary hyperparathyroidism should be considered

Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario / Usefulness of intraoperative parathormone measurement to predict surgical cure in primary hyperparathyroidism

Background: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. Aim: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT Material and methods: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. Results: Eighty-eight operated patients, aged 58±15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6± 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98 percent) at 24 hours and 50 of 52 patients followed for six months (96 percent). The pathological study disclosed an adenoma in 69 (78 percent), and multiglandular disease in 16 (18 percent), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97 percent and 100 percent of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94 percent and 100 percent, respectively. Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

Vitamin D status and hyperparathyroisism in postmenopausal osteoporotic patients in Cipto Mangunkusumo hospital Jakarta.

AIM: to determine the profile of vitamin D and parathyroid hormone (PTH) and the proportion of vitamin D inadequacy in a population of postmenopausal osteoporotic patients from a rheumatologic outpatient clinic. METHODS: a cross sectional study was conducted between October and December 2006 in the Rheumatology Clinic, Cipto Mangunkusumo Hospital with osteoporosis confirmed by bone mineral densitometry (T score less than -2.5 at the lumbar spine or hip). Patients were excluded if there was a history of oral glucocorticoid treatment within 30 days, vitamin D supplementation, and have renal and/or liver function impairments. Forty-two postmenopausal osteoporotic patients aged 51-77 years old who had been postmenopausal for 5-28 years were included in this study. Vitamin D inadequacy was defined as the plasma levels of 25(OH)D less than 50 nmol/L whereas hyperparathyroidism was defined as the PTH level more than 69 pg/dL. RESULTS: vitamin D inadequacy was found in 61.9% of patients and 34.6% of them or 23.8% of total patients were also having high PTH level. There was an inverse correlation between 25(OH)D with PTH levels and positive correlation between duration of menopause and PTH level. Vitamin D inadequacy is common (61.9%) in postmenopausal osteoporotic patients who visited Rheumatology outpatient clinic of Cipto Mangunkusumo Hospital Jakarta. CONCLUSION: the low concentration of 25(OH)D was correlated with PTH level and duration of menopause. This finding should be confirmed in a larger epidemiological study, either hospital-or community-based to assess vitamin D status among postmenopausal women in Indonesia.

Primary hyperparathyroidism in North India: a description of 52 cases

Primary hyperparathyroidism [PHPT] has a variable clinical expression. Symptomatic PHPT is still the predominant form of the disease in many parts of the world, especially developing countries. Because the clinical profile of the disease has changed from that described in the past, we sought to improve our understanding of the disease in patients in north India. We summarized the clinical presentation, biochemical and radiological features, and operative findings from the case records from the last 13 years of 52 patients at a tertiary care centre in north India who had documented PHPT. The male: female ratio was 1: 3.3 with ages ranging from 6 to 60 years [mean +/- SD, 36.38 +/- 12.73]. Bone disease [46%], recurrent renal stones [21%] and body aches and pains [21%] were the most common modes of presentation. The lag time varied ranged from 1 month to 16 years. Common clinical manifestations included bone pain [67%], weakness/fatigue [56%], fracture of the long bones [48%], abdominal pain [39%], polyuria [37%] and psychiatric manifestations [23.1%]. Hypertension was observed in 42% and a palpable nodule in the neck in 19%. Biochemical features included hypercalcemia [86.5%], hypophosphatemia [65.4%] and hyperphosphatasia [67.3%]. Mean intact PTH [ +/- SD] was 809.0 +/- 696.3 ng/L with levels significantly lower in patients who had only kidney stone disease as compared with those with bone disease [P=0.017]. A single parathyroid adenoma was localized in 50 [98%] patients. Hungry bone disease was seen in 59% patients. PHPT in India continues to be a symptomatic disorder with skeletal and renal manifestations at a much younger age

Bone and renal stone disease in patients operated for primary hyperparathyroidism in Pakistan: is the pattern of disease different from the west?

OBJECTIVE: To document the clinical presentation of primary hyperparathyroidism [PHPT] in a developing country and note differences from the West. SETTING: A tertiary care teaching hospital. METHOD: The records of 37 patients operated for PHPT between January 1986 and December 1997 were reviewed. Symptoms, laboratory parameters and histopathology results were analyzed. Surgery for PHPT accounted for 0.055% of 67,566 operative procedures performed in the Department of Surgery during the 12 year period. The mean age of our patients was 38.4 +/- 13.2 years [range 17 to 73 years]. Ninety% of patients were less than 60 years old and 51% less than 40 years. At presentation, the mean serum parathyroid hormone [sPTH] level was 618 +/- 741% above the upper limit of normal [range 0-2900% using a variety of assays]. A solitary adenoma was present in 86.5%, hyperplasia in 5.4% and carcinoma in 5.4% of patients. There was one [2.7%] negative exploration. Thirty-five% of patients had renal stone disease [StD], 32.4% had bone disease alone [BD] and 27% had both bone abnormality and stones [BStD]. There were neither bone disease nor stones in 5.4% of patients. BD was associated with a statistically non-significantly [p = 0.08] higher alkaline phosphatase level [sALP] as compared to the StD and BStD groups. The mean urinary calcium [Ca] was higher in the BD group [482 +/- 340 mg/24 hours] as compared to StD group [265 +/- 89 mg/24 hours] [p = 0.013]. The post-operative hospital stay was longer in the BD group [14.4 +/- 16 days] as compared to the StD group [6.7 +/- 3.7 days] [p = 0.001]. As compared to reports from the Western world, PHPT is less commonly diagnosed in our country and occurs at a younger age. In the absence of a screening programme, symptomatic disease and bone involvement occur more frequently. The high levels of PTH may indicate long-standing disease in our population, which may account for higher proportion of patients with symptoms. Unexpectedly, patients with bone disease had higher levels of urinary calcium than patients with stone disease

Primary hyperparathyroidism--an Indian study.

Twenty eight patients of sporadic primary hyperparathyroidism seen over a period of 10 years were studied. There were 18 females and 10 males with a mean age of 35.9 years. Bone involvement was the commonest clinical presentation (90%) followed by renal involvement (65%) and more than half the patients (54%) had involvement of both the skeletal and renal systems. The tumor was clinically palapable in six patients. Thalliumtechnetium subtraction scan had a sensitivity of 87% followed by computerised tomography (70%), and ultrasound (65%) in diagnosing parathyroid pathology. All the patients underwent surgical excision of the abnormal gland (S). Adenomas constituted the single largest group (90%). Histologically, only 32% of the patients had chief cell morphology. Clear cell (32%) mixed cell, and oxyphil cell (7.2%) types accounted for the remaining adenomas. Majority of the patients (82%) had symptomatic postoperative hypocalcemia requiring intravenous calcium with or without vitamin D supplementation. In contrast to western reports most of our patients were young, presented late with florid bone and renal disease and had large palpable tumors.

Primary hyperparathyroidism of the mandible. A case report.

Primary hyperparathyroidism is due to benign or malignant neoplasia of one or more parathyroid glands, causing a wide spread osteoclastic resorption of bone with fibrous tissue replacement. A case of primary hyperparathyroidism involving mandible of a 16 year old Saudi female is being reported. The patient was terated by surgical intervention. This case supports the opinion that negative laboratory tests viz., calcium and phosphorus levels do not exclude the existence of hyperparathyroidism (normocalcaemic type).

Primary hyperparathyroidism.

11 cases of primary hyperparathyroidism were seen during 1975-1988. Follow up has varied from 1-10 years. Renal disease in the form of renal calculi and nephro-calcinosis was observed in nine cases (81.8%). Two presented in chronic renal failure and required dialysis. Bone disease was found radiologically in six patients (54.5%); two had bone cysts in multiple bones while all six had subperiosteal bone erosion. Hypertension was found in three patients (27.3%). Proximal myopathy was observed in two cases (18.1%). One patient each presented with hypercalcaemic crisis, chondrocalcinosis and acute pancreatitis. The calcification of blood vessels and cornea was seen in two cases.

Circulating molecular forms of parathyroid hormone in primary and secondary hyperparathyroidism

To study the circulating forms of parathyroid hormone (PTH), sera from 5 patients with primary hyperparathyroidism (PHP) and 12 patients with secondary hyperparthyroidism due the chronic renal failure (SHP) were submitted to gel filtration chromatography. The eluent samples were analyzed using two sequence-specific radioimmunoassays (RIA), one amino-terminal (NH2), the other carboxyl-terminal (COOH). The results obtained with the NH2RIA showed a single molecular form in both groups co-eluting with the intact hormone. The COOH assay identified several molecular forms with a broader distribution in the SHP patients. These results confirm the diagnostic superiority of the NH2 assay under both conditions