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Hyperthyroidism - Bone Mineral Density and Fractures
Thyrotoxicosis is a clinical situation resulting from increased free T3 and T4 thyroid hormones in the blood; it is called hyperthyroidism if provoked by overactive tissue within the thyroid gland causing an overproduction of thyroid hormones. Accordingly, thyrotoxicosis can be provoked by causes external to the thyroid gland, such as iatrogenesis provoked by excess medication of thyroid hormones (Table 1); however, in clinical practice, the terms thyrotoxicosis and hyperthyroidism tend to be used indiscriminately.
In subclinical hyperthyroidism, free T3 and T4 are within the normal reference parameters, but the levels of circulating THS are low. In differentiated carcinomas of the thyroid, treatment with thyroid hormone is done by administering supraphysiological doses to suppress the endogenous secretion of TSH.
The prevalence of hyperthyroidism in women over 65 years of age is between 5% and 15%.
____________________________
Diffuse toxic goiter
Toxic multinodular goiter
Toxic adenoma
Thyrotoxic phase of subacute thyroiditis
Iodine-induced thyrotoxicosis
TSH producing hypophyseal tumours
Excessive human chorionic gonadotropin (hydatidiform mole / choriocarcinoma)
Hypophyseal resistance to thyroid hormones
Functioning metastases from differentiated carcinoma of the thyroid
Struma ovarii with thyrotoxicosis
____________________________
Table 1. Causes of Thyrotoxicosis and Hyperthyroidism.
Among the various complications caused by hyperthyroidism, those related to bone metabolism range from calcium and vitamin D anomalies to the effects of thyroid hormones and TSH on the bone. Studies have demonstrated changes in bone mineral density (BMD) and increased risk of fractures due to bone frailty in patients with subclinical hyperthyroidism.
In hyperthyroidism, calcium absorption is reduced as a result of changes in intestinal transit and vitamin D metabolism.
For that reason, hyperthyroidism has been considered to be one of the main causes of secondary osteoporosis, and is presumably one of the most important endocrine etiologies, after hypercortisolism and hypogonadism (Table 2).
____________________________
Low calcium and vitamin D intake
Prolonged corticotherapy
Hypogonadisms
Chronic alcoholism and smoking
Hyperthyroidism
Hyperparathyroidism
Malabsorption syndromes
Anorexia nervosa, weight loss
Sedentarianism, inactivity
Organ transplantation
Excessive caffeine consumption
Drugs (iatrogenesis)
____________________________
Table 2. Causes of Secondary Osteoporosis.
The mechanisms involved in the catabolic action of T4 and T3 on the bone are not yet fully clear. T3 appears to be important in regulating the integrity of bone tissue and bone formation, acting through receptors TR-alpha. Both hormones may stimulate gene expression on osteoblasts for the production of collagen, oestocalcin and growth factors, which are essential for bone apposition.
Osteoclasts contain T3 receptors, which may indirectly stimulate bone resorption. Excessive amounts in children and young persons may speed up growth, leading to premature epiphyseal closure and reducing peak bone mass. Subsequently, and at any stage of adult life, it may contribute to increased bone resorption and loss of bone capital. Bone remodelling is accelerated and the formation stage is reduced, leading to incomplete replacement of the resorbed bone.
TSH acts on bone remodelling, as it can inhibit the formation and survival of osteoclasts and osteoblasts differentiation, for which reason is has been recently theorised that low TSH levels may, on their own, prompt the emergence of osteoporosis and fractures.
Accordingly, there is progressive bone mass loss, the speed depending on the severity and duration of hyperthyroidism, subsequent BMD loss and, eventually, osteoporosis.
Hence, BMD loss has been detected in the lumbar spine, hip and distal radius. Several studies have shown bone mass loss between 10%and 20%. Osteoporosis and hyperthyroidism in elderly women are quite frequent pathologies linked to the risk of early death.
There is higher fracture risk in hyperthyroidism, mostly of the hip. Weight loss and changes in the intestinal transit may contribute to reduced muscle mass and to higher risk of osteoporosis-related fractures.
Subsequent to euthyroidism, there seems to be a partial or total recovery of BMD to normal levels. However, the risk of osteoporosis facture appears to be higher in patients treated with radioactive iodine, and lower in those who received surgery.
In patients with differentiated carcinoma of the thyroid treated with supraphysiological doses of thyroid hormones, studies on BMD and on the prevalence of fractures show contradictory results.
In conclusion, both hyperthyroidism and osteoporosis and their most feared consequence – bone fracture – are very important issues in clinical practice, not only due to their high prevalence among the population (mostly female) but also because of the high morbidity and even mortality (the latter associated to hip fracture) they cause if not diagnosed and treated in time.
Ana Paula Barbosa
Endocrinology, Diabetes and Metabolism Unit, Santa Maria Hospital, CHLN-EPE,
Lisbon and Faculty of Medicine of the University of Lisbon
ana_pbarbosa@hotmail.com
____________________________
BIBLIOGRAPHY: -Heemstra KA et al. Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma. Eur J Endocrinol, 2008;159:69-76.
-Franklin JA et al. Long-term thyroxine treatment and bone mineral density. The Lancet, 1992;340:9-13.
-Abe E et al. TSH is a negative regulator of skeletal remodeling. Cell, 2003;115:151-162.
-Vestergaard P et al. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk. Calcif Tissue Int, 2005;77, 139-144.
-Panico A et al. Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate. Thyroid, 2009:19:437-42.
-Heijckmann AC et al. Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma. Eur J Endocrinol, 2005;153:23-9.
-Barbosa AP. Efeitos de fármacos na massa óssea: Bisfosfonatos e Neoplasias. Endocrinologia, Metabolismo e Nutrição, 2004:13 (Supl 2):155-6.
-Barbosa AP. Efeitos das neoplasias na massa óssea. Journal of the Faculty of Medicine of Lisbon, 2005;10 (supl. 1):23-4.
-Barbosa AP. Osteoporose secundária. Journal of the Faculty of Medicine of Lisbon, 2008; 13 (supl 1):21-6.
-Barbosa AP. Iatrogenia na osteoporose. Endocrinologia e Metabologia (Brasil), 2009;53 (supl 7):786.
-Barbosa AP et al. Hipertiroidismo em homens jovens: que impacto na massa óssea? Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo (Portuguese Journal of Endocrinology, Diabetes and Metabolism), 2010;5:174.
In subclinical hyperthyroidism, free T3 and T4 are within the normal reference parameters, but the levels of circulating THS are low. In differentiated carcinomas of the thyroid, treatment with thyroid hormone is done by administering supraphysiological doses to suppress the endogenous secretion of TSH.
The prevalence of hyperthyroidism in women over 65 years of age is between 5% and 15%.
____________________________
Diffuse toxic goiter
Toxic multinodular goiter
Toxic adenoma
Thyrotoxic phase of subacute thyroiditis
Iodine-induced thyrotoxicosis
TSH producing hypophyseal tumours
Excessive human chorionic gonadotropin (hydatidiform mole / choriocarcinoma)
Hypophyseal resistance to thyroid hormones
Functioning metastases from differentiated carcinoma of the thyroid
Struma ovarii with thyrotoxicosis
____________________________
Table 1. Causes of Thyrotoxicosis and Hyperthyroidism.
Among the various complications caused by hyperthyroidism, those related to bone metabolism range from calcium and vitamin D anomalies to the effects of thyroid hormones and TSH on the bone. Studies have demonstrated changes in bone mineral density (BMD) and increased risk of fractures due to bone frailty in patients with subclinical hyperthyroidism.
In hyperthyroidism, calcium absorption is reduced as a result of changes in intestinal transit and vitamin D metabolism.
For that reason, hyperthyroidism has been considered to be one of the main causes of secondary osteoporosis, and is presumably one of the most important endocrine etiologies, after hypercortisolism and hypogonadism (Table 2).
____________________________
Low calcium and vitamin D intake
Prolonged corticotherapy
Hypogonadisms
Chronic alcoholism and smoking
Hyperthyroidism
Hyperparathyroidism
Malabsorption syndromes
Anorexia nervosa, weight loss
Sedentarianism, inactivity
Organ transplantation
Excessive caffeine consumption
Drugs (iatrogenesis)
____________________________
Table 2. Causes of Secondary Osteoporosis.
The mechanisms involved in the catabolic action of T4 and T3 on the bone are not yet fully clear. T3 appears to be important in regulating the integrity of bone tissue and bone formation, acting through receptors TR-alpha. Both hormones may stimulate gene expression on osteoblasts for the production of collagen, oestocalcin and growth factors, which are essential for bone apposition.
Osteoclasts contain T3 receptors, which may indirectly stimulate bone resorption. Excessive amounts in children and young persons may speed up growth, leading to premature epiphyseal closure and reducing peak bone mass. Subsequently, and at any stage of adult life, it may contribute to increased bone resorption and loss of bone capital. Bone remodelling is accelerated and the formation stage is reduced, leading to incomplete replacement of the resorbed bone.
TSH acts on bone remodelling, as it can inhibit the formation and survival of osteoclasts and osteoblasts differentiation, for which reason is has been recently theorised that low TSH levels may, on their own, prompt the emergence of osteoporosis and fractures.
Accordingly, there is progressive bone mass loss, the speed depending on the severity and duration of hyperthyroidism, subsequent BMD loss and, eventually, osteoporosis.
Hence, BMD loss has been detected in the lumbar spine, hip and distal radius. Several studies have shown bone mass loss between 10%and 20%. Osteoporosis and hyperthyroidism in elderly women are quite frequent pathologies linked to the risk of early death.
There is higher fracture risk in hyperthyroidism, mostly of the hip. Weight loss and changes in the intestinal transit may contribute to reduced muscle mass and to higher risk of osteoporosis-related fractures.
Subsequent to euthyroidism, there seems to be a partial or total recovery of BMD to normal levels. However, the risk of osteoporosis facture appears to be higher in patients treated with radioactive iodine, and lower in those who received surgery.
In patients with differentiated carcinoma of the thyroid treated with supraphysiological doses of thyroid hormones, studies on BMD and on the prevalence of fractures show contradictory results.
In conclusion, both hyperthyroidism and osteoporosis and their most feared consequence – bone fracture – are very important issues in clinical practice, not only due to their high prevalence among the population (mostly female) but also because of the high morbidity and even mortality (the latter associated to hip fracture) they cause if not diagnosed and treated in time.
Ana Paula Barbosa
Endocrinology, Diabetes and Metabolism Unit, Santa Maria Hospital, CHLN-EPE,
Lisbon and Faculty of Medicine of the University of Lisbon
ana_pbarbosa@hotmail.com
____________________________
BIBLIOGRAPHY: -Heemstra KA et al. Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma. Eur J Endocrinol, 2008;159:69-76.
-Franklin JA et al. Long-term thyroxine treatment and bone mineral density. The Lancet, 1992;340:9-13.
-Abe E et al. TSH is a negative regulator of skeletal remodeling. Cell, 2003;115:151-162.
-Vestergaard P et al. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk. Calcif Tissue Int, 2005;77, 139-144.
-Panico A et al. Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate. Thyroid, 2009:19:437-42.
-Heijckmann AC et al. Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma. Eur J Endocrinol, 2005;153:23-9.
-Barbosa AP. Efeitos de fármacos na massa óssea: Bisfosfonatos e Neoplasias. Endocrinologia, Metabolismo e Nutrição, 2004:13 (Supl 2):155-6.
-Barbosa AP. Efeitos das neoplasias na massa óssea. Journal of the Faculty of Medicine of Lisbon, 2005;10 (supl. 1):23-4.
-Barbosa AP. Osteoporose secundária. Journal of the Faculty of Medicine of Lisbon, 2008; 13 (supl 1):21-6.
-Barbosa AP. Iatrogenia na osteoporose. Endocrinologia e Metabologia (Brasil), 2009;53 (supl 7):786.
-Barbosa AP et al. Hipertiroidismo em homens jovens: que impacto na massa óssea? Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo (Portuguese Journal of Endocrinology, Diabetes and Metabolism), 2010;5:174.
