*4.1.1. Mineral metabolism in hypothyroidism*

256 Thyroid Hormone

seems to be also affected by a hypothyroid status during childhood. In one cross-sectional study, BMD was reported to be lower in prepubertal children with congenital

Treatment with thyroxine results in a period of rapid catch-up growth, although predicted final height based on midparental height calculations may not be achieved, particularly when hypothyroidism is prolonged (Rivkees et al, 1988). The LT4 replacement for 8 years in children with congenital hypothyroidism did not have a negative effect on BMD for the lumbar spine and the femoral site and on biochemical markers of bone turnover (Leger et al, 1997). The results showed normal serum levels of calcium, phosphate, alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D and did not demonstrate any relationship between BMD and L-T4 dosage or biochemical markers of bone formation. These findings were confirmed by other studies reporting no alterations of bone mass in adolescents and young adults with congenital hypothyroidism, treated from the neonatal period (Salerno et

On the other hand, thyroid hormone excess results in accelerated skeletal maturation, premature closure of the EGPs and subsequent decrease in longitudinal bone growth with a compromised final adult height (Allain & McGregor, 1993; O'Shea et al, 1993; Harvey et al, 2002). In severe cases, hyperthyroidism during early childhood may also cause craniosynostosis due to premature fusion of the sutures of the skull (Segni et al 1999). Low bone density values and high bone resorption rates were demonstrated at diagnosis of hyperthyroidism in children and adolescents (Mora et al, 1999). Successful treatment of hyperthyroidism was shown to increase BMD in children and improve the conditions for

Consequences of syndrome of resistance to thyroid hormone (RTH) on the skeletal development have been described in literature. RTH results from dominant negative mutations in the carboxyl terminus of the thyroid hormone receptor β gene. The mutant receptors are transcriptionally impaired and inhibit thyroid hormone receptor action. RTH is characterized by phenotypic variability including skeletal manifestations (Weiss et Refetoff, 2000). Our current understanding is based mainly on the published case reports. Involvement of the skeleton can cause a short stature, advanced or delayed bone age, increased bone turnover, osteoporosis, fractures, craniofacial abnormalities and craniosynostosis. The clinical variability might be secondary to functional properties of mutant proteins and heterogeneity of cofactors mediating action of TR (Kvistad et al, 2004).

**4. Effects of thyroid dysfunction on bone turnover in adult bone** 

Reduced bone turnover in hypothyroidism impairs bone formation and mineralization (Eriksen et al, 1986). Results of population studies indicate an increased fracture risk in hypothyroid individuals (Ahmed et al, 2006; Vestegaard et al 2002, 2005). The association between subclinical hypothyroidism and decreased BMD with increased fracture risk has

hypothyroidism than in controls (Demartini et al, 2007).

al, 2004, Demeester-Mirkine et al, 1990).

**4.1. Hypothyroidism** 

the best obtainable peak bone mass (Mora et al, 1999).

Slight perturbations in some parameters of bone and mineral metabolism have been reported in hypothyroid patients. Minor abnormalities of calcium metabolism may exist with slightly elevated serum calcium, PTH and 1,25(OH)2 vitamin D, decreased level of alkaline phosphatase, decreased urinary calcium excretion and glomerular filtration rate. The exchangeable pool of calcium and its rate of turnover may be reduced, reflecting decreased bone formation and resorption. However, these changes seem not to be different, even during the treatment, in hypothyroid patients compared to euthyroid controls (Sabuncu et al, 2001).
