Bone Density and Mineral Metabolism in Thyroidectomized Patients Treated with Long-Term l-Thyroxine

Abstract

1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone-suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group. 2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, post-menopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients. 3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma

“…Among premenopausal women, the effect does not appear to be significant (Marcocci et al 1994). Furthermore, individual studies reported both accelerated BMD loss (Kung et al 1993, McDermott et al 1995, increased risk of hip fractures (Quan et al 2002) and no effect (Franklyn et al 1992, Giannini et al 1994, Marcocci et al 1994, Muller et al 1995, Rosen et al 1998) in a similar number of reports. Thus, the quality of evidence on the strength of the association between serum TSH and BMD reported in the American Medical Association guidelines for diagnosis and management of subclinical thyroid disease was negative, or only fair in postmenopausal women with a history of overt hyperthyroidism (Surks et al 2004).…”

“…Some authors described decreased BMD in pre-and postmenopausal women with a significant negative correlation with T3 levels (Tauchmanova`et al 2004). In other reports only postmenopausal women were affected (Faber & Galloe 1994) or no diminution was observed (Franklyn et al 1992, Giannini et al 1994, Marcocci et al 1994, Muller et al 1995, Rosen et al 1998. With respect to hyperthyroidism due to suppressive LT4 treatment, some trials included premenopausal women with little or no change in BMD between controls and long-term treated patients (Franklyn et al 1992, Giannini et al 1994, Marcocci et al 1994, Muller et al 1995.…”

“…In other reports only postmenopausal women were affected (Faber & Galloe 1994) or no diminution was observed (Franklyn et al 1992, Giannini et al 1994, Marcocci et al 1994, Muller et al 1995, Rosen et al 1998. With respect to hyperthyroidism due to suppressive LT4 treatment, some trials included premenopausal women with little or no change in BMD between controls and long-term treated patients (Franklyn et al 1992, Giannini et al 1994, Marcocci et al 1994, Muller et al 1995. Studies performed in postmenopausal women showed decreased BMD in all measured sites in two trials (Diamon et al 1991, Kung & Yeung 1996 and no changes in another six (Franklyn et al 1992, Giannini , Hawkins et al 1994, Marcocci et al 1994, Muller et al 1995, Go¨rres et al 1996, Guo et al 1997.…”

“…In fact, the Clinical Practice Recommendations for the Management of Thyroid Carcinoma suggest a risk of accelerated bone turnover but do not express definitive recommendations for its monitoring (Thyroid Carcinoma Task Force 2001). Previous studies have been focused both on endogenous and drug-induced subclinical hyperthyroidism (Franklyn et al 1992, Kung et al 1993, Giannini et al 1994, Marcocci et al 1994, McDermott et al 1995, Muller et al 1995, Rosen et al 1998). In two studies, patients with nodular goitre and endogenous subclinical hyperthyroidism had lower BMD than comparable normal subjects (Mudde et al 1992, Foldes et al 1993, although in one trial significant reductions in BMD occurred only in postmenopausal and in sites rich in cortical bone (Foldes et al 1993).…”

“…Nevertheless, the effects of subclinical hyperthyroidism (undetectable TSH levels and total triiodothyronine (TT3) and/or free thyroxine (FT4) in normal range) on bone mineral density (BMD) are less well defined (Toft 2001). Despite publication in the last decade of several studies (Franklyn et al 1992, Kung et al 1993, Giannini et al 1994, Marcocci et al 1994, McDermott et al 1995, Muller et al 1995, Rosen et al 1998) and meta-analyses on this topic (Faber & Galloe 1994, Uzzan et al 1996, evidence that subclinical hyperthyroidism affects skeletal integrity and is therefore a risk factor for osteoporosis, is inconclusive (Greenspan & Greenspan 1999, Toft 2001, Quan et al 2002, Murphy & Williams 2004. The meta-analyses and systematic reviews reported either a decrease in bone mineral density during prolonged subclinical hyperthyroidism, mainly in postmenopausal women, or no changes (Faber & Galloe 1994, Uzzan et al 1996, Greenspan & Greenspan 1999, Lau et al 2001, Toft 2001, Quan et al 2002, Murphy & Williams 2004.…”