The effects are due to the metabolic actions of excess thyroid hormones. Vitamin D deficiency is widely prevalent throughout the world including India. 1 Recently, Dhanwal et al. have reported hypovitaminosis D and its impact on bone mineral homeostasis and bone density.It is initiated by activation of osteoclast precursors that become mature osteoclasts by proliferation and differentiation. 8 The osteoclasts cause bone resorption until they have reached a final resorption depth. The osteoblasts then invade the area and begin bone formation.
9 The space corresponding to the amount of bone resorbed by osteoclasts but not formed by osteoblasts is the remodeling space. Activation frequency indicates how often a given site of the bone surface undergoes resorption and subsequent formation.The major form of thyroid hormone in the blood is thyroxine (T 4. help regulate long bone growth (synergy with growth hormone) and neural maturation.
In skin, ultraviolet light (wavelength of 290315 nm) converts 7-dehydrocholestrol, a precursor of cholesterol, to vitamin D3. Vitamin D3 is metabolized in the liver to 25(OH)D by 25-hydroxylase enzyme and then in kidneys to its active form 1,25(OH)2D by 1-hydroxylase enzyme.Till 1963, only 31 cases of thyrotoxic hypercalcemia were reported in literature. 13 In 1966, Baxter and Bondy reported hypercalcemia in 19 of the 77 patients (23) with hyperthyroidism. In another series, percentage of patients with hypercalcemia in thyrotoxic state varied between 5 and 27.
Experimental studies in mice lacking either the TR-alpha or TR-beta receptor suggest bone loss is mediated by TR-alpha 6. Thus, thyroid hormone may affect bone calcium metabolism either by a direct action on osteoclasts, or by acting on osteoblasts which in turn mediate osteoclastic bone resorption 7.In these selected patients the risk of bone loss is outweighed by beneficial effects on control of the cancer. Hence, it is important is to adjust the dose of thyroxine to achieve TSH levels that are appropriate for each individual patient.
B ONNERATABOLISMEOSTASIS IPERTHYROIDISM The first report of hyperthyroid bone disease was published in 1891 when von Recklinghausen described the worm eaten appearance of long bones of a young woman who died due to hyperthyroidism.Therefore careful selection of which elderly patients should be treated with thyroxine is critical. Thyroid hormone overtreatment of elderly patients is an avoidable problem. Individuals vary in their absorption of thyroxine, sometimes because of use of interfering medications, higher thyroxine doses may be required for some patients to achieve normal TSH levels.
10 Plummer gave similar description in 1920 and reported A 53 year old woman gave a history of hyperthyroidism. The patient died three hours after operation. The ribs showed multiple fractures, were very friable and could easily be crushed between the fingers.Excess thyroid hormone can increase the risk or heart rhythm problems and bone loss making the use of thyroxine for. thyroid cancer, thyroid hormone is.
2 Patients with Graves disease in India have steatorrhea and marked proximal muscle weakness due to skeletal muscle myopathy. 3 Majority of patients have increased skin pigmentation during thyrotoxic state. 4.Turner MR, Camacho X, Fischer HD, Austin PC, Anderson GM, Rochon PA, Lipscombe LL 2011 Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ 342:d2238 Syed FA, Ng AC 2010 The pathophysiology of the aging skeleton.
Increased serum interleukin-6 (IL-6) concentrations in hyperthyroid patients may also play a role in thyroid hormone-stimulated bone loss 9. IL-6 stimulates osteoclast production and may be an effector of the action of parathyroid hormone (PTH) on bone.The calvarium was found to be extremely thin, and was almost translucent when held up to the light. In early part of the century, emphasis of studies in thyrotoxicosis was on calciumphosphorus metabolism.
By contrast, adult TRß-/- mice with elevated TSH and thyroid hormone levels were osteoporotic with evidence of increased bone resorption, whereas juveniles had advanced ossification with increased bone mineral deposition. Analysis of T3 target gene expression revealed skeletal hypothyroidism in TR0/0 mice, but skeletal thyrotoxicosis in TRß-/- mice.The net effect of PTH is to raise serum Ca and 1,25(OH)2D while decreasing serum phosphorous levels. N ORMANMODELING Bone remodeling is a dynamic process and characterized by coupling between resorption and formation.
The mechanisms of thyroid hormone induced bone resorption include cAMP-mediated, increased sensitivity of beta adrenergic receptors to catecholamines, increased sensitivity of bone cells to PTH, osteoclast activator factor and interleukin-1 (IL-1) mediated increased bone resorption.Failure to recognize the relationship of age and thyroxine requirements will lead to over dosage if the dose of thyroxine is not titrated down as patients age. Unnecessary treatment of elderly patients adds to this danger.
The diagnosis of thyroid failure in the elderly needs to be carefully evaluated with the knowledge that the upper normal value for TSH in people over 80 yrs is 7.5 uU/ml, compared to 4.0 uU/ml in young adults ( 12 ).This problem has been found to be especially important in post menopausal women and older men ( 3 ) who are at increased risk for fractures from worsening osteoporosis when overtreated with thyroid hormones ( 4 ).
7 The net effect of 1,25(OH)2D is to raise serum calcium while decreasing PTH. Serum calcium and 1,25(OH)2D levels regulate PTH secretion from parathyroid gland. PTH stimulates bone turnover and renal phosphorous excretion by inhibiting phosphorous reabsorption in proximal and distal tubules and renal calcium reabsorption at distal tubule.Those patients taking higher doses of thyroxine were more likely to have had a fracture than those taking lower doses. Unfortunately serum TSH data were not available so it is not certain which patients were properly treated, but it is plausible that many patients were overtreated, especially those who received higher doses.