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Reference values of parathyroid hormone and vitamin D

Hormone by chemiluminescent automated assay

Valores de referencia de hormona paratiroidea y vitamina D por método quimioluminiscente automatizado en perros

Beatriz Martiarena,

1

Esp, Nadia Kogovsek,

5

Bioq, Helena Salerni,

5 Esp,

Víctor Castillo,

2

Ph.D, Georgina Brandi,3

MV, Mariela Regonat,

1 MV,

Andrea Visintini,

1

Esp, Héctor Quintana,

4

MV, P Otero,

5 Bioq.

Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Cátedra de Clínica Médica de Pequeños

Animales y Hospital Escuela de Medicina Veterinaria, 1

Servicios de Nefrología,

2Endocrinología y

3

Laboratorio,

4 Nutrición. Av. Chorroarrín 280, Ciudad Autónoma de Buenos Aires (CP1427) (C.A.B.A.),

Argentina.

5 Hospital General de Agudos "Carlos G.Durand" Servicio de Endocrinología, Av. Diaz Velez

5044 (CP 1405DCS) C.A.B.A. *Correspondencia: bmartiar@fvet.uba.ar

Received: July 2014; Accepted: January 2015.

ABSTRACT

Objective. Provide reference data for parathyroid hormone 1-84 (PTH 1-84) and 25OH Vitamin D (25OH D) using a new technique. Materials and methods. The hormones were evaluated, in serum,

using a third generation automated chemiluminescent method for PTH in a group of 60 adult dogs,

clinically healthy, grouped according to age in years in GA: 1 to 5, GB: 6 to 10 and GC:>10. Results.

Data expressed as average ± DS were for PTH (pg/ml): 9.3±2.3; 12±6.3; 12.2±3.7; and for 25OH

comparison with GA, showing no differences between GB and GC. A negative correlation between

25OH D and PTH was found (r= -0.28; p=0.015). Conclusions. Data contributed by this study

provide reference values for PTH 1-84 and 25OH D, evaluated using a third generation automated chemiluminescent method for PTH in local dogs. The results will facilitate monitoring diseases that alter the metabolism of calcium and phosphorus in dogs. Key Words: Calcium, phosphorus, parathyroid hormone, metabolism, vitamin D (Source: MeSH).

RESUMEN

Objetivo. Aportar datos de referencia, para hormona paratiroidea 1-84 (PTH 1-84) y 25OH Vitamina D (25OH D) con una nueva técnica. Materiales y métodos. Las hormonas fueron valoradas, en

suero, por un método quimioluminiscente automatizado, y de tercera generación para la PTH, en una

población de 60 perros adultos clínicamente sanos, agrupados según edad en años en GA: 1 a 5, GB: 6 a

10 y GC:>10. Resultados. Los datos expresados como media ± DS fueron para la PTH (pg/ml): 9.3±2.3;

12±6.3; 12.2±3.7; y para la 25OH D (ng/ml): 84.2±27.8; 68.2±16.0; 63.6±23.1, respectivamente. El

ORIGINAL

Rev.MVZ Córdoba 20(2):4581-4590, 2015. ISSN: 0122-0268 4582
en el GB (p<0.05) y en el GC (p<0.01) con respecto al GA, sin haber diferencias entre los GB y GC.

Se encontró una correlación negativa entre 25OH D y PTH (r= -0.28; p=0.015). Conclusiones. Los

datos aportados en este trabajo permiten disponer de valores de referencia de PTH 1-84 y de 25OH

D, valorados por un método quimioluminiscente automatizado y de tercera generación para la PTH, en

una población local de perros. Los resultados facilitarán el seguimiento de enfermedades que alteran

el metabolismo del calcio y fósforo en perros. Palabras clave: Calcio, fósforo, hormona paratiroidea, metabolismo, vitamina D (Fuente: MeSH).

INTRODUCTION

The parathyroid hormone (PTH) is the one

that controls the concentration of ionic calcium (iCa) in blood and extracellular liquid. Binding to membrane receptors on bone and kidney, it triggers a response that increases iCa; also, it stimulates the renal synthesis of 1.25 (OH) 2 D 3 (Calcitriol), the active form of Vitamin D. This (VDR) in the intestines; increasing the absorption of dietary calcium in bones and kidneys to induce

The resulting increased serum calcium and 1.25

(OH) 2 D 3 exert a negative control on PTH synthesis and secretion in parathyroid cells. The increased in the secretion of PTH (1,2). Dogs ineffectively photosynthesize Vitamin D through their skin, so that concentration depends on dietary intake and absorption through the intestines. Transported to the liver, it becomes 25-hydroxyvitamin D (25OH

D or Calcidiol), to be later hydroxylated in the

renal proximal tubule to calcitriol via stimulation by PTH (2.3).

PTH is a peptide molecule with 84 amino acids,

synthesized in cells of the parathyroid gland as a precursor of 115 amino acids called pre-pro-

PTH. The pre and pro sequences are unfolded and

degraded during their transit through the cisterns of the endoplasmic reticulum, and the hormone is stored in two types of secretory vesicles: some contain the intact molecule with 84 amino acids (PTH 1-84) which it is the biologically active form, and the others contain proteases that degrade the molecule generating different carboxyl-terminal fragments (PTH Ct) (5,6).

According to the extracellular concentration

of iCa, parathyroid cells can secrete both PTH

1-84 and PTH Ct. iCa levels in the extracellular

sensor calcium receptor (Ca-SR) coupled to a G protein located in the membrane of parathyroid cells. Low concentrations of extracellular iCa stimulate the secretion of PTH 1-84, and high levels of iCa activate Ca-SR which initiates an intracellular signaling cascade that culminates in the inhibition of biologically active PTH secretion

INTRODUCCIÓN

La hormona paratiroidea (PTH) es la encargada

de controlar la concentración de calcio iónico (Cai) en sangre y líquido extracelular. Su unión a receptores de membrana, en el hueso y el riñón, desencadena una respuesta que aumenta el Cai; también, estimula la síntesis renal de 1.25 (OH) 2 D 3 (Calcitriol), la forma activa de vitamina D. Ésta vitamina D (VDR), en el intestino; aumentando la absorción del calcio dietario, y en el hueso y sangre. El consiguiente aumento del calcio sérico y de la 1.25 (OH) 2 D 3 ejercen un control negativo en la síntesis y secreción de PTH en las células paratiroideas. El aumento del fósforo en sangre produce importantes incrementos en la secreción de PTH (1,2). vitamina D en su piel, por lo que su concentración depende de su ingesta en la dieta y su absorción por el intestino. Transportada hasta el hígado se transforma en 25-hidroxivitamina D (25OH D o Calcidiol), para luego ser hidroxilada en el túbulo proximal renal a calcitriol, vía estimulación por la PTH (2,3).

La PTH es una molécula peptídica de 84

aminoácidos, sintetizada en las células de la glándula paratiroides como un precursor de 115 aminoácidos llamado pre-pro-PTH.

Las secuencias pre y pro son desdobladas y

degradadas, durante su tránsito a través de las cisternas del retículo endoplásmico, y la hormona es almacenada en dos tipos de vesículas secretorias: unas contienen la molécula intacta con sus 84 aminoácidos (PTH 1-84), que es la forma biológicamente activa, y las otras contienen proteasas que degradan la molécula generando distintos fragmentos carboxi- terminales (PTH Ct) (5,6). De acuerdo con la concentración extracelulares de Cai, las células paratiroideas son capaces de secretar tanto

PTH 1-84 como PTH Ct. Los niveles de Cai en el

líquido extracelular se mantienen dentro de la normalidad gracias a un receptor sensor de calcio (CaSR) acoplado a una proteína G localizada en la membrana de las células paratiroideas. Baja 4583
and increases PTH proteolysis. Accordingly, by increasing the concentration of extracellular iCa, the proportion of PTH Ct fragments secreted are increased (2,3-5). While it was believed that these fragments had no biological activity, it has been demonstrated in humans and animals that some PTH Ct fragments have an opposite effect on blood concentration of iCa (5-7). PTH in plasma circulates at very low concentrations and the presence of circulating peptide fragments presents a wide variability between methods of measurement. with radioimmunoassay, and the few sensitive form and their fragments. Second generation immunoassays, called intact PTH analysis, have the carboxyl terminal portion and one for the amino terminal portion of the molecule. Initially it was believed that these methods only detected

PTH 1-84. However, later studies showed that

there are circulating PTH fragments which, being degraded in the amino terminal portion of the molecule, do not possess amino acids 1-7 that are responsible for the biological activity of the hormone. This PTH 7-84 molecule and other long PTH Ct fragments can be detected by some second generation immunoassay with different specificity. This produces a great variation in the results obtained using different methodologies, especially in samples of patients with kidney disease, which have higher proportion of serum PTH Ct due to decreased renal clearance (1,2,5,7).

In recent years third generation immunoassays

they do not detect PTH 7-84 fragments since the antibodies used in their design are directed against amino acids 1-7 of the molecule, so they confer less variability in measuring biologically active PTH (1,2,5-7).

There are no previous reports of reference

values in dogs with automated chemiluminescent method for 25OH D and PTH, and the latter with new third generation technology. The aim of this study was to measure both hormones in a population of clinically healthy adult dogs toquotesdbs_dbs30.pdfusesText_36

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