RESUMO
Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.
Assuntos
Barreira Hematoencefálica/fisiologia , Cálcio/líquido cefalorraquidiano , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Hiperparatireoidismo/fisiopatologia , Hipoxantinas/líquido cefalorraquidiano , Metoxi-Hidroxifenilglicol/líquido cefalorraquidiano , Transtornos Neurocognitivos/fisiopatologia , Hormônio Paratireóideo/líquido cefalorraquidiano , Xantinas/líquido cefalorraquidiano , Humanos , Hiperparatireoidismo/psicologia , Hipoxantina , Transtornos Neurocognitivos/psicologia , Glândulas Paratireoides/fisiopatologia , Albumina Sérica/líquido cefalorraquidiano , XantinaRESUMO
Immunoreactive parathyroid hormone-related protein (PTH-rP) was measured in simultaneously obtained cerebrospinal fluid (CSF) and plasma from 51 patients suspected of suffering from a prolapsed intervertebral disc. Endocrine or psychiatric diseases were excluded. In addition, immunoreactive parathyroid hormone (PTH) in the CSF samples was measured. Both, PTH-rP and PTH were assayed by immunoradiometric assay. The results indicate the presence of both, PTH-rP and PTH in CSF. The following concentrations (mean values +/- SD) were found: PTH-rP (pmol/l) in CSF without pleocytosis (n = 17) 0.432 +/- 0.157, with pleocytosis (n = 34) 0.654 +/- 0.675; in plasma (pmol/l) 54.1 +/- 14.632; PTH (nmol/l) in CSF without pleocytosis (n = 17) 0.454 +/- 0.099, with pleocytosis (n = 34) 0.437 +/- 0.140, and in plasma 4.272 +/- 0.794. The concentrations of both, PTH-rP and PTH, in CSF with and without pleocytosis were not significantly different. No correlation was found between PTH-rP and PTH values. The present study demonstrated PTH-rP as a normal constituent in human CSF.
Assuntos
Líquido Cefalorraquidiano/química , Proteínas/análise , Adolescente , Adulto , Idoso , Humanos , Disco Intervertebral , Pessoa de Meia-Idade , Hormônio Paratireóideo/líquido cefalorraquidiano , Proteína Relacionada ao Hormônio Paratireóideo , Prolapso , Valores de Referência , Doenças da Coluna Vertebral/líquido cefalorraquidianoRESUMO
There are reports that patients with renal failure have elevated circulating concentrations of parathyroid hormone (PTH), which is suspected to be a causal factor of the cerebral symptoms of these patients. A positive correlation between the circulating level of immunoreactive PTH and the extent of abnormality in the electroencephalogram (EEG) in humans has been reported. Moreover, in uremic dogs normalization of the EEG was observed after parathyroidectomy, and increased abnormality of the EEG was observed on infusion of PTH. If PTH is really a causal factor of uremic encephalopathy and abnormality of the EEG in patients with renal failure, the question arises as to whether PTH acts on the brain after penetrating through the blood-brain barrier or in some other way. In this work, we measured PTH by both C-terminal-specific RIA (C-PTH) and N-terminal-specific RIA (N-PTH) in the circulation and cerebrospinal fluid (CSF) of normal subjects and patients with renal failure. Blood and CSF samples were obtained from 7 normal volunteers (31 approximately 81 years old: 4 males and 3 females) and 22 patients with chronic renal failure (25 approximately 87 years old: 12 males and 10 females). No patients had a psychotic disease or endocrinopathy other than secondary hyperparathyroidism. Samples of venous blood were collected from the subjects after an overnight fast at the time of lumbar puncture for CSF sampling. C-terminal-specific RIA for measurement of the plasma and CSF concentrations of C-PTH was carried out using a commercially available RIA kit (Eiken Laboratory Inc., Tokyo, Japan).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Barreira Hematoencefálica , Falência Renal Crônica/fisiopatologia , Hormônio Paratireóideo/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/líquido cefalorraquidiano , RadioimunoensaioRESUMO
Cerebrospinal fluid (CSF) levels of immunoreactive parathyroid hormone (iPTH) and immunoreactive calcitonin (iCT) were measured by radioimmunoassay in 23 outpatient leukemic children on maintenance chemotherapy. These hormones were detectable in the CSF of all patients: iPTH 148 +/- 11 pg/ml (mean +/- SEM); iCT 14.3 +/- 0.8 pg/ml. iPTH and iCT were also measured in serum (iPTH 396 +/- 18 pg/ml; iCT 32.3 +/- 1.4 pg/ml). CSF values were significantly lower (p less than 0.001) than serum concentrations; no significant correlation between the two compartments was found. Our study indicates the presence of iPTH and iCT in the CSF of children.
Assuntos
Calcitonina/líquido cefalorraquidiano , Hormônio Paratireóideo/líquido cefalorraquidiano , Adolescente , Calcitonina/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia/sangue , Leucemia/líquido cefalorraquidiano , Masculino , Hormônio Paratireóideo/sangue , RadioimunoensaioRESUMO
In order to examine whether parathyroid hormone (PTH) enters the cerebrospinal fluid (CSF), the blood levels of the hormone were acutely elevated either by infusion of parathyroid extract or by stimulation of the parathyroid glands by hypocalcemia. Despite marked elevations in the blood levels of the hormone, PTH could not be detected in the CSF. The data indicate the intact PTH or its carboxyterminal fragment do not cross the blood-CSF interface of the blood-brain barrier. The results, therefore, suggest that the action of PTH on brain must be mediated by an effect on the blood-brain interface of the blood-brain barrier.
Assuntos
Hormônio Paratireóideo/líquido cefalorraquidiano , Animais , Cálcio/sangue , Cães , Ácido Edético/farmacologia , Feminino , Cinética , Glândulas Paratireoides/fisiologia , Hormônio Paratireóideo/sangue , Extratos de Tecidos/metabolismoRESUMO
Parathyroid hormone is reported to be a possible causal factor of abnormalities of electroencephalograms of patients with renal failure. In this study, the parathyroid hormone levels were compared in the circulation and cerebrospinal fluid of seven normal subjects and 22 patients with renal failure including those who showed abnormal electroencephalograms. The circulating levels of both C-terminal and N-terminal parathyroid hormone in the subjects studied showed a positive correlation (C-terminal, r = 0.58, P less than 0.01; N-terminal, r = 0.61, P less than 0.01) with the grade of abnormality of the electroencephalogram. However, the levels of C-terminal and N-terminal parathyroid hormone in the cerebrospinal fluid of both normal subjects and patients with renal failure were below the detectable limit (C-terminal, less than 0.1 ng/ml; N-terminal, less than 2.3 pg/ml). These data suggest that in patients with renal failure, the effect of parathyroid hormone on the central nervous system is mediated in some other way than via the cerebrospinal fluid.
Assuntos
Barreira Hematoencefálica , Falência Renal Crônica/metabolismo , Hormônio Paratireóideo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Creatinina/sangue , Creatinina/líquido cefalorraquidiano , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/líquido cefalorraquidiano , Fosfatos/sangue , Potássio/sangue , Valores de Referência , Ureia/líquido cefalorraquidianoRESUMO
Parathyroid hormone (PTH) was measured radioimmunologically in simultaneous plasma and cerebrospinal fluid (CSF) samples obtained from 72 patients aged 20 to 80 years without endocrine or psychiatric diseases and from 2 patients aged 40 and 70 years with secondary hyperparathyroidism due to renal insufficiency. They underwent routine diagnostic lumbar puncture because of suspected prolapse of a disc. Total calcium (Ca) and magnesium (Mg) were also determined in these samples by complexometry . The following findings were obtained (ng/ml, median, range in brackets): Plasma PTH 1.7 (0.7-6.6); CSF PTH 0.8 (0.5-2.3), respectively. No correlation was found between PTH concentrations in plasma and CSF in all 74 samples. The Ca concentrations in plasma, with a median of 2.3 mmol/l (2.1-2.6) were significantly higher than the Ca concentrations in CSF (median 1.1 mmol/l, range 0.4-1.3). The correlation between PTH and calcium levels in CSF was only weak (r = 0.284 P less than 0.05). The Mg levels in CSF (median 1.1 mmol/l, range 0.7-1.6) were higher than Mg concentrations in plasma (median 0.9 mmol/l, range 0.6-1.1). No correlation was found between PTH and Mg in CSF. Our study demonstrated that in man PTH is a normal constituent of CSF.