natriuretic-peptide--c-type and Hyperthyroidism

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnostic Techniques, Endocrine; Heart Failure; Humans; Hypertension; Hyperthyroidism; Immunoradiometric Assay; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Reference Values; Specimen Handling; Tachycardia, Supraventricular

C-type natriuretic peptide (CNP) and thyroid hormone (TH) are essential for normal skeletal growth. Plasma CNP peptides correlate with growth velocity, but the relationship between thyroid status and CNP production is unknown. This study examined the impact of restoring normal TH levels on CNP and height velocity (HV) in children with acquired hypo- and hyperthyroidism.. We performed a prospective, observational study in prepubertal children with acquired hypothyroidism (n = 15) and hyperthyroidism (n = 12).. Blood levels of CNP, amino-terminal proCNP (NTproCNP), bone-specific alkaline phosphatase (BSAP), IGF-I and TH levels were measured before and during the first 6 months of standard treatment for hypo- and hyperthyroidism, and correlations were determined.. At baseline, HV, CNP, NTproCNP and BSAP were significantly higher in hyper- than in hypothyroid subjects. Changes in TH after treatment were closely coupled to change in CNP and NTproCNP in hyperthyroid, but not in hypothyroid, children. In addition, a positive association of HV with CNP peptides was found during treatment of hyperthyroidism. Normalizing TH did not correlate with changes in BSAP or IGF-I in either group.. Plasma CNP peptides are higher in children with hyperthyroidism than in those with hypothyroidism at diagnosis and, in hyperthyroid children, change concordantly with TH and HV during treatment. Differential responses of CNP in the two groups suggest CNP production is dependent on growth plate activity and not a direct effect of TH on CNP gene expression. Our findings suggest novel mechanisms underlying changes in skeletal response during treatment in children with acquired thyroid disease.

Topics: Alkaline Phosphatase; Bone Development; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Natriuretic Peptide, C-Type; Prospective Studies; Puberty; Thyroid Diseases

Plasma C-type natriuretic peptide (CNP) forms correlate with linear growth velocity in juveniles. In hyperthyroid children, plasma CNP products fall in parallel with height velocity and thyroid hormones (TH) as euthyroidism is restored. The effect of TH on CNP forms after completion of endochondral growth is unknown.. To determine the effect of restoring euthyroidism on plasma CNP forms and bone turnover markers (BTMs) in hyperthyroid adults.. We performed a prospective observational study in 20 adults (19 women) with acquired hyperthyroidism before and during carbimazole treatment. INTERVENTION AND MAIN OUTCOMES: Blood levels of CNP, amino-terminal propeptide of CNP (NTproCNP), TH and BTMs - bone-specific alkaline phosphatase, osteocalcin, procollagen type 1 amino-terminal propeptide and type 1 collagen C-telopeptide (CTx) - were measured before and during the first 6 months of carbimazole treatment and correlations determined.. Both CNP and NTproCNP were significantly correlated with TH at baseline. As in children, decreases in CNP forms were closely associated with fall in TH. Significant associations were found between CNP forms and CTx.. CNP production from tissues other than endochondral cartilage is responsive to TH. Strong temporal links with markers of bone resorption suggest that CNP may also participate in bone remodelling in the adult skeleton.

Topics: Adult; Aged; Alkaline Phosphatase; Bone and Bones; Carbimazole; Collagen Type I; Female; Humans; Hyperthyroidism; Male; Middle Aged; Natriuretic Peptide, C-Type; Osteocalcin; Prospective Studies; Thyroid Hormones; Young Adult

The role of C-type natriuretic peptide (CNP) in the pathophysiology of atrial function in hyperthyroidism has not been defined. This study was to define the role of CNP-activated particulate (p) guanylyl cyclase (GC)-cGMP-phosphodiesterase (PDE)3 signaling in the regulation of cAMP levels and contractile and secretory functions in the atria from hyperthyroid rabbits. Experiments were performed in perfused beating rabbit atria. CNP was used to activate pGC. In euthyroid atria from sham-treated rabbits, CNP (100 nM) increased cGMP and cAMP efflux by 176.7+/-17.7 and 55.3+/-10.0%, respectively. CNP decreased stroke volume and pulse pressure and ANP release by 51+/-7 and 41+/-2 and 60.4+/-3.2%, respectively. Pretreatment with milrinone blocked the CNP-induced increase of cAMP but without significant changes in decrease of atrial dynamics and ANP release. In hyperthyroid atria, CNP-induced increase of cGMP levels was accentuated, while CNP-induced increase of cAMP was attenuated. The gain of cAMP, i.e., change in cAMP efflux concentration in terms of cGMP was attenuated in the hyperthyroid compared to euthyroid atria. CNP rather increased atrial dynamics in hyperthyroid atria instead of decrease. CNP-induced decrease in atrial ANP release was attenuated. Pretreatment with milrinone blocked the CNP-induced increase of cAMP levels concomitantly with a decrease of atrial dynamics. The present study demonstrates that altered role of CNP-activated pGC-cGMP-PDE3-cAMP signaling is involved in the pathophysiology of hyperthyroid heart.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Atrial Natriuretic Factor; Cyclic AMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 3; Enzyme Activation; Guanylate Cyclase; Heart Atria; Hyperthyroidism; In Vitro Techniques; Myocardium; Natriuretic Peptide, C-Type; Rabbits; Signal Transduction