Re: FW: Re: Help!

[Guest guest]

Sheila,

You wrote:

>

> Chuck - will you post references to the studies you mention please.

I'll have to get the AACB paper later, but a quick search turned up about 350

abstracts. Here are the first few. - Chuck

Bone mineral density changes and bone turnover in thyroid carcinoma patients

treated with supraphysiologic doses of thyroxine. Karner, I.; Hrgovic, Z.;

Sijanovic, S.; Bukovic, D.; Klobucar, A.; Usadel, K. H.; Fassbender, W. J.

Department of Nuclear Medicine, Radiation Protection and Pathophysiology,

Clinical Hospital Osijek, Croatia. European Journal of Medical Research

(2005), 10(11), 480-488.

Abstract

The aim of this one-year prospective study was to det. whether longterm

thyroxine treatment is a risk factor for elevated bone turnover, loss of bone

mass and subsequent development of osteoporosis. Premenopausal women (N = 19),

and men (N = 9) suffering from differentiated thyroid gland carcinoma in the

mean age of 39.0 8.0 years and 41.8 10.0 years were investigated. All of them

had undergone a total thyroidectomy and subsequent thyroxine therapy. The

duration of the TSH-suppressive therapy prior to the the beginning of our study

was 9.4 6.4 years in the female and 8.1 6.0 years in the male group. The

prospective observation was performed by dual X-ray absorptiometry (DXA) at the

spine and the femoral neck and by single-photon absorptiometry (SPA) at the

distal radius. Lab. testings included thyroid hormones T3, T4 and TSH, serum

calcium, phosphate and PTH, and urinary calcium and phosphate from spontaneous

and 24-h urine samples. Markers of bone formation (osteocalcin, alk.

phosphatase and PICP) and resorption (Ca/Cr and ICTP) were detd. Statistically

significant loss of bone mass was obsd. only on the distal radius in males

(p<0.05). At the lumbar spine and femoral neck, only a minor bone loss was

registered in a small no. of patients. Almost 50 % of the females showed values

above the ref. range. In more than 30 % of the females, and smaller no. of male

patients, ICTP values ranged above the ref. range, corresponding to elevated

bone turnover. These two variables exhibited a slight correlation with bone d.

at the measured skeletal areas, mostly considering the male group. The results

are a proof that accelerated bone turnover and subsequent bone loss occurs

during TSH-suppressive thyroxine therapy. In future prospective studies a

prolonged time of observation will be necessary, as well as to increase the no.

of studied patients, in order to better assess the relative risk of osteoporosis

in patients undergoing TSH-suppressive treatment more precisely.

Treatment of benign nodular goiter with mildly suppressive doses of L-thyroxine:

effects on bone mineral density and on nodule size. Baldini, M.; Gallazzi,

M.; Orsatti, A.; Fossati, S.; Leonardi, P.; Cantalamessa, L. Department of

Internal Medicine, University of Milan, Milan, Italy. Journal of Internal

Medicine (2002), 251(5), 407-414.

Abstract

The aim was to evaluate (i) the demineralizing effect of L-thyroxine (LT4)

therapy at doses mildly inhibiting serum TSH (TSH) in patients with benign

nodular goiter; (ii) the efficacy of treatment on nodule size. Cross-sectional

study comparing euthyroid women with nodular goiter treated with LT4 for 2 yr

(52 32 mo, range 24-138, median 42) and a matched group with untreated goiter.

A total of 89 female outpatients (53.3 9 yr; 36 pre- and 53 postmenopausal), 43

treated and 46 untreated. Bone mineralization was measured with total body and

regional mineralometry [dual energy X-ray absorptiometry (DEXA)], and indirectly

evaluated with biochem. parameters (alk. phosphatase, osteocalcin). Efficacy of

LT4 therapy was assessed by measuring the nodule size during ultrasonog. The

adequacy of the treatment was evaluated on the basis of serum TSH levels. No

significant differences were found at DEXA for total body and regional

mineralization (P > 0.05 for all comparisons) in treated and untreated patients,

both in pre- and postmenopausal states. Evaluation of the nodule size during

the ultrasound scan showed a redn. of 30% in 11 of 43 treated patients (26%)

vs. none of the untreated, an unchanged size in 29 treated patients (67%) vs. 18

untreated, an increase of nodules and/or new nodule development in three treated

patients (7%) vs. 28 untreated (61%). L-thyroxine (LT4) treatment at doses

slightly suppressing TSH does not significantly affect bone mineralization, nor

does it represent a risk factor for osteoporosis, even in postmenopausal

patients. The efficacy of this therapeutic schedule on goiter size is

comparable with the effects previously reported with suppressive doses.

Which thyroid-stimulating hormone level should be sought in hypothyroid patients

under L-thyroxine replacement therapy? Gursoy, A.; Cin, M. Ozduman; Kamel,

N.; Gullu, S. Department of Endocrinology and Metabolic Diseases, School of

Medicine, Ankara University, Ankara, Turk. International Journal of

Clinical Practice (2006), 60(6), 655-659.

Abstract

We sought to det. whether relationships exist between level of TSH (TSH)

suppression and cardiovascular risk parameters such as plasma homocysteine,

C-reactive protein (CRP), fibrinogen, D-dimer and serum cholesterol in patients

taking L-thyroxine-replacement therapy (LT4-RT). Four hundred and two

hypothyroid patients under LT4-RT were cross-sectionally evaluated. Patients

were grouped according to their achieved TSH (mIU/l) levels under LT4-RT on an

arbitrary manner. Those patients having a TSH value 0.4-2 were defined as group

1 (n = 154), a TSH level of 2 to less than 5.5 were defined as group 2 (n = 176)

and a TSH level of 5.5 to less than 20 with a normal free T3 and free T4 level

were defined as group 3 (n = 72). The three groups of patients were also

compared with overt hypothyroid patients (n = 71) and healthy controls (n = 97).

Homocysteine levels (.mu.mol/l) were significantly different between the three

groups (10.4 4 for group 1, 11.3 3.7 for group 2 and 13.5 4.7 for group 3; p

< 0.01 for all groups). Significant differences in CRP (mg/l) levels were

present between the three groups (2.6 2.6 for group 1, 3.3 2.9 for group 2 and

4.8 4.1 for group 3; p < 0.01 for all groups). Univariate anal. showed that

both homocysteine and CRP levels significantly correlated with free T4 and TSH

level (p < 0.01 for both groups). No statistically significant differences were

noticed in respect to fibrinogen and D-dimer levels between three groups. In

examg. the effect of LT4-RT on lipid parameters, a tendency towards beneficial

effects without achieving statistical significance was obsd. Practically

speaking, a target TSH level of less than 2 might be advisable to lower CRP

levels and homocysteine levels, and possibly lipid parameters.

L-thyroxine therapy in differentiated thyroid carcinoma: criteria for evaluation

of TSH suppression. Kowalczyk P; Roskosz J; Jurecka-Tuleja B; Gubala E;

Czernik E; Jarzab B Zakladu Medycyny Nuklearnej i Endokrynologii

Onkologicznej Centrum Onkologii, Instytut im. Marii Sklodowskiej-Curie Oddzial w

Gliwicach Wiadomosci lekarskie (Warsaw, Poland : 1960) (2001), 54(5-6),

268-76.

Abstract

Life-time L-thyroxine therapy is obligatory in patients treated for

differentiated thyroid carcinoma (DTC) in order to suppress serum TSH. The

rationale for that is the TSH stimulation of follicular cells' growth and the

presence of TSH receptors on DTC cells. Nevertheless, the exact criteria for

TSH suppression in DTC are not specified and are a matter of discussion,

stimulated by the recent progress in the evaluation of thyroxine side effects on

bone and heart. The aim of the study was the optimalization of the reference

range for TSH suppression in DTC patients in order to minimalize the risk of

iatrogenic thyrotoxicosis. One hundred and twenty nine patients were randomly

chosen among patients treated radically for DTC (116 females and 13 males).

Basal and TRH stimulated TSH level, FT4 and FT3 serum level were estimated by

microimmunoenzymatic method, while SHBG was estimated by immunofluorimetry.

Full suppression (basal TSH < 0.05) was obtained in 64 patients (49%),

submaximal suppression (TSH between 0.1 and 0.3 mU/l) was observed in 21

patients (16%). In 29 patients (22%) no suppression was obtained by the applied

dose of thyroxine. The risk of iatrogenic hyperthyreosis, as judged by the

increase of FT3 or SHBG, was found to be 38% in patients with full suppression

and only 5% in patients with submaximal suppression (p < 0.05). CONCLUSION: 1.

Suppression of TSH secretion was achieved in 80% of patients with differentiated

thyroid carcinoma. The control of TSH level must be controlled every 3 months

in 5 first years of therapy. 2. The optimal serum TSH level for L-thyroxine

therapy in asymptomatic patients after radical treatment of differentiated

thyroid carcinoma ranges between 0.1 to 0.3 mU/L. This range ensures the

expected suppression of TSH with only minimal risk of iatrogenic hyperthyreosis.