L-thyroxine Suppressive Therapy Research Articles

Mixed Medullary Papillary Thyroid Carcinoma in Hyperfunctioning Hot Nodule: A Case Report and Review of the Literature

Mixed medullary papillary carcinoma (MMPC) is a rare variant of papillary thyroid carcinoma, according to the WHO classification and it presents as a single lesion histologically composed of two distinct and intermingled neoplastic cell patterns. The histogenesis is still debatable. The lymph node metastases are usually present at the time of the diagnosis and distal metastases may appear late during follow-up. At least 13 similar lesions have been reported in the literature. We describe the case of a 61-year-old woman with a mixed medullary papillary carcinoma found in a hyperfunctioning thyroid nodule and negative pre-surgical serum calcitonin. After surgery, the patient started suppressive L-thyroxine therapy and underwent radioiodine ablation. The follow-up for both papillary and medullary components has shown no signs of persistence or recurrence of disease five years after surgery. However, the rarity of the MMPCs makes the management and the prognosis of these tumors still unclear.

Sternal Mass as First Presentation of Follicular Thyroid Carcinoma

Abstract Thyroid carcinoma is the commonest endocrine malignancy, although less than 1% of all cancers. Osseous metastases are more often associated with the follicular type of thyroid carcinoma. Fewer than 5% of patients present with distant metastases. We present a case of sternal metastasis being the first observed feature of follicular thyroid carcinoma. A 62-year old female developed a painless nodule over her sternum, which progressively enlarged over approximately two years. Patient was seen at another medical facility, where histology of the mass revealed metastatic follicular thyroid carcinoma. Subsequent left thyroid lobectomy confirmed follicular thyroid cancer on histology. She was treated with 100 mCi of radioiodine I-131 (RAI), and suppressive L-thyroxine therapy implemented thereafter. However, the sternal mass recurred seven months post-sternectomy. She patient was then referred to our facility. The mass was deemed inoperable. Thus, she was treated with 200 mCi of RAI under steroid cover. The RAI therapy scan showed intense uptake in the sternal mass as well as less prominent thyroid bed uptake. The patient has since been referred for external beam radiation therapy. The clinician is reminded of one of the modes of presentation of thyroid cancer. Thyroid cancer has been deemed an indolent tumour but may also exhibit aggressive behaviour as occurred in this patient. This case also buttresses the importance of early biopsy and diagnosis in the investigation of tumours.

A randomized equivalence trial to determine the optimum dose of iodine-131 for remnant ablation in differentiated thyroid cancer

We conducted a stratified randomized equivalence/noninferiority trial from January 2001 to December 2006 to determine whether lower administered activities are as effective as 3.7 GBq (100 mCi) of iodine-131 (I) for remnant ablation. The sample size was found to be 450 on the basis of 80% power (α=5%) and noninferiority margin (δ=0.15). We used an allocation ratio of 2 : 2 : 1 for the 0.93, 1.85, and 3.7 GBq (25, 50, and 100 mCi) groups, respectively. Randomization with concealment was followed for patient group allocation. All patients underwent preablation I whole-body scan, 48-h radioiodine neck uptake measurements and post-therapeutic scans. The patients were advised suppressive L-thyroxine therapy (2 µg/kg/day). Repeat evaluation was performed after 6 months, along with thyroglobulin and antibody assays. The criteria for ablation were as follows: major criterion - negative I whole-body scan; minor criteria - 48-h radioiodine neck uptake less than or equal to 0.2% and stimulated thyroglobulin less than or equal to 10 ng/ml. A total of 422 patients who fulfilled the inclusion criteria (360 papillary and 62 follicular) could be recruited. As per AJCC, 6th ed., we had 70, 11, and 19% of patients in stage I, II, and III, respectively. First-dose ablation was 81.5, 84.9, 88.5, and 84.2% in the 0.93, 1.85, and 3.7 GBq groups and overall, respectively. Histology had no effect on ablation rate. The equivalence testing of the hypothesis was conducted between the 0.93 and 3.7 GBq groups, the 1.85 and 3.7 GBq groups, and the 0.93 and 1.85 GBq groups. Results showed that, at a significance level of 5%, the null hypothesis was rejected for each pair. First-dose I ablation rates at 6 months with 0.93, 1.85, and 3.7 GBq of I are equivalent with the prespecified clinically acceptable noninferiority margin. We conclude that we are probably administering too much I for remnant ablation (trial registration number: CTRI/002291).

Nodular goiter with multiple cystic and solid swellings

Thyroid nodules are very common in the general population, but only 5% are malignant. We report the case of a man presenting with nodular goiter, and multiple swellings over the scalp and arm, with pathological fractures. On evaluation by fine needle aspiration, these swellings were found to be metastases from follicular thyroid carcinoma. The patient underwent total thyroidectomy, radioiodine ablation, resection of the bone lesion, and L-thyroxine suppressive therapy, with no recurrence / metastasis over a five-year follow-up.

High Cathepsin K Levels in Men with Differentiated Thyroid Cancer on Suppressive l-Thyroxine Therapy

Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption. A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L). In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002). Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference.

BackgroundThe diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach.MethodsThe study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses.ResultsThere are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women.ConclusionIt seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

OPYT PRIMENENIYa PROFILAKTIChESKOY DOZY ALENDRONATA (FOSAMAKS 35 mg) DLYa LEChENIYa OSTEOPOROZA u zhenshchin v postmenopauzes subklinicheskim tireotoksikozom

The aim was to estimate the effects of treatment with alendronate (Fosomax 35 mg) in postmenopausal women with osteoporosis and subclinical hyperthyroidism. Thirty postmenopausal women (64 (60-69) years old) with osteoporosis (T-score ≤ -2,5) and subclinical hyperthyroidism (77% with endogenous subclinical hyperthyroidism and 23% on L-thyroxine suppres-sive therapy after thyroidectomy due to differentiated thyroid cancer) were randomly assigned into two groups: 1-14 women received Fosamax 35 mg a week in combination with 500 mg of calcium and 400 UI of Vitamin D3 (VD) daily; 2-16 women received 1000 mg of calcium and 800 UI of VD daily. Euthyroidism was achieved in all women with endogenous subclinical hyperthyroidism. An increase in physical activity was recommended to all patients and a hypolipidemic diet was given to those who had had high cholesterol level. Biochemical parameters (calcium (Ca), phosphorous (P), creatinine (Cre), alkaline phosphatase (ALP), cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG), cholesterol/HDL ratio) in fasting serum as well as calcium/creatinine ratio in fasting urine (U-Ca/U-Cre); biochemical markers of bone metabolism: osteocalcin (OC) and C-terminal telopeptide of type I collagen (b-CTx) serum ("ECLIA", Roche Elecsys 1010/2010), BMD (DXA; Prodigy, Lunar) at the lumbar spine (L1-L4), femoral neck (FN), total hip (TH) and radius total (RT) were measured at the baseline visit and after 1 year of treatment. At the baseline visit there were not found any differences between the 1 and the 2 groups. After 12 months of treatment the markers of bone metabolism as well as ALP decreased significantly in both groups, though the decreases were significantly greater (p

Radioiodine therapy in non-toxic multinodular goitre. The possibility of effect-amplification with recombinant human TSH (rhTSH)

There is no consensus regarding the optimum treatment of benign non-toxic goitre. L-thyroxine suppressive therapy is widely used, but there is poor evidence of its efficacy, and it may have serious adverse effects on health. Surgery is first choice in large goitres or if malignancy is suspected. 131I therapy results in a one-year goitre reduction of around 40% in multinodular goitres, usually with a high degree of patient satisfaction and improvement of the inspiratory capacity. The effect is attenuated with increasing goitre size. The risk of hypothyroidism is 22–58% within 5–8 years. A sufficient thyroid 131I uptake is mandatory for 131I therapy to be feasible and pre-stimulation with recombinant human TSH (rhTSH) increases this considerably. This leads to an increased absorbed thyroid dose by approx.75%, mainly in those patients with the lowest thyroid 131I uptake, and a more homogeneous intrathyroidal isotope distribution. Pre-stimulation with even a small dose of rhTSH seems to allow a reduction of the 131I activity while still achieving a mean goitre reduction of approximately 40% within a year. A significantly lower extrathyroidal radiation is achieved by this approach. With an unchanged 131I activity, rhTSH pre-stimulation improves the goitre reduction by 30–50%. However, this is at the expense of a higher rate of hypothyroidism, cervical pain and transient thyrotoxicosis. Of particular concern is the observation made in healthy persons, that rhTSH results in a transient average thyroid volume increase of 35%. A similar goitre swelling may cause problems in susceptible patients during rhTSH-augmented 131I therapy. Thus, this concept still needs a closer evaluation before routine use.

Auswirkungen von Schilddrüsenfehlfunktionen auf den Knochen

Interactions between thyroid hormones and the bone are complex and are still not fully understood. During development, thyroid hormone is essential for the recruitment and maturation of bone cells. A deficit of thyroid hormone during pregnancy and in the newborn leads to retardation of the skeleton. Hypothyroidism during later life causes a relevant decrease of bone turnover. Excessive amounts of thyroid hormone induce increased activity of osteoblasts and osteoclasts leading to high bone turnover and a loss of BMD, as the activity of osteoclasts predominates over the activity of osteoblasts. In subclinical hyperthyroidism, premenopausal women show no significant BMD loss, whereas postmenopausal women face a significant BMD loss. Men seem to have a limited, but significant bone loss in subclinical hyperthyroidism. Therapeutic consequences focus on the normalization of thyroid function, which can lead to restoration of BMD and normalization of bone turnover. In particular, patients on long-term suppressive L-thyroxine therapy or anti-thyroid drug medication benefit from additional antiresorptive treatment. This article surveys the complex interactions between thyroid hormones and bone cells and their effects on bone turnover, BMD and fractures according to the different states of thyroid function.

Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma

Untreated hyperthyroidism and treatment with high doses of thyroid hormone are associated with osteoporosis. However, their effect on bone turnover, their contribution to bone mineral density (BMD) in the context of other clinical risk factors for osteoporosis and the prevalence of vertebral fractures is not well documented. Cross-sectional study. We studied 59 patients receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption was measured by C-telopeptides of type I collagen (ICTP) and bone formation by procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis were evaluated using a questionnaire. Z-scores of BMD were similar as the NHANES (National Health and Nutrition Examination Survey) III reference group in women and men, also after long-term (> 10 years) suppression therapy. Patients in the lowest and highest quartile of BMD showed significant differences in the presence of clinical risk factors. ICTP levels were significantly higher than in age-matched controls, PINP levels were not different. We found four patients with a prevalent vertebral fracture. We conclude that patients with well-differentiated thyroid carcinoma are not at increased risk of developing low bone mass nor have a higher prevalence of vertebral fracture at least when treated with relatively low doses of L-thyroxine.

Recombinant Human TSH Modulates In Vivo C-Telopeptides of Type-1 Collagen and Bone Alkaline Phosphatase, but Not Osteoprotegerin Production in Postmenopausal Women Monitored for Differentiated Thyroid Carcinoma

In women monitored for thyroid carcinoma, short-term stimulation with rhTSH induced an acute decrease in serum C-telopeptides of type-1 collagen and an increase in serum BALP levels without any effect on OPG production. The inhibitory effect of TSH on bone resorption occurred only in postmenopausal women who showed low BMD and a high bone turnover rate as an effect of L-thyroxine suppressive therapy. It has been recently shown that thyrotropin (TSH) has an inhibitory activity on skeletal remodeling in in vitro conditions. Here, we have aimed at evaluating whether TSH has similar effects in vivo. For this purpose, we have evaluated the sequential profile of serum bone metabolism markers during acute stimulation with recombinant human TSH (rhTSH) in thyroidectomized women monitored for thyroid carcinoma. The study group included 66 thyroidectomized patients, of whom 38 were premenopausal and 28 postmenopausal, who underwent routine rhTSH-assisted whole body radioactive iodine scanning for differentiated thyroid carcinoma. The patients were sequentially evaluated for TSH, free triiodothyronine (FT3), free thyroxine (FT4), bone alkaline phosphatase (BALP), C-telopeptides of type-1 collagen (CrossLaps), and osteoprotegerin (OPG) levels during rhTSH stimulation. The samples were drawn just before and 2 and 7 days after the first administration of rhTSH. BMD was evaluated by ultrasonography at baseline. Seventy-one healthy women (41 premenopausal and 30 postmenopausal) acted as a control group. At study entry, all patients had subclinical thyrotoxicosis as effect of L-thyroxine (L-T4) treatment. The patients had higher serum CrossLaps and OPG levels and lower BMD than healthy subjects. Postmenopausal patients showed comparable serum FT4 and FT3 concentrations with those found in premenopausal patients. However, postmenopausal patients showed higher serum CrossLaps (p < 0.001), OPG (p = 0.03), and BALP (p < 0.001) levels and lower BMD (p < 0.001) than those measured in premenopausal patients. Two days after the first administration of rhTSH, all patients had serum TSH values >100 mUI/liter. At this time, serum CrossLaps levels decreased significantly (p < 0.001) and BALP values increased (p = 0.001) with respect to the baseline values in postmenopausal but not in premenopausal patients. rhTSH did not induce any significant change in serum OPG values either in premenopausal or in postmenopausal patients. One week after the first rhTSH administration, serum CrossLaps values decreased again to values comparable with those measured at baseline, whereas serum BALP values remained high. This study shows that subclinical thyrotoxicosis is accompanied by high bone turnover rate with an increase in serum OPG levels compared with euthyroid healthy subjects. Acute increase in serum TSH levels is accompanied by a reversible inhibition of bone resorption. This effect is characterized by a decrease in serum CrossLaps and an increase in BALP levels without any evident effect on OPG production. The activity of TSH occurs specifically in postmenopausal women in whom the negative effects of L-T4 suppressive therapy on bone mass and metabolism are more marked compared with premenopausal women.

Treatment of Goitre

No consensus exists regarding the optimum treatment of benign non-toxic goitre. L-thyroxine suppressive therapy is widely used for treatment of goitre, but there is poor evidence of its efficacy, and the suppression of serum TSH may have serious adverse effects on health. Iodine supplementation is no better than L-thyroxine in comparative trials. Surgery is first choice in large goitres or if malignancy is suspected. Post-surgery, risk of goitre recurrence is inversely correlated with the extent of the operation. 131I therapy results in a one-year goitre reduction of around 50 % in multinodular and 70 % in diffuse goitres, usually with a high degree of patient satisfaction and improvement of the inspiratory capacity. The effect is attenuated with increasing goitre size. The risk of hypothyroidism is 22-58 % within 5-8 years. A sufficient thyroid 131I uptake is mandatory for 131I therapy to be feasible. Prestimulation with recombinant human TSH (rhTSH) may increase the thyroid 131I uptake considerably. This leads to an increased absorbed thyroid dose by approx. 75 %, mainly in those patients with the lowest thyroid 131I uptake. In addition, rhTSH results in a more homogeneous intrathyroidal isotope distribution. Recent studies with rhTSH stimulation before 131I therapy are encouraging. Pre-stimulation with even a small dose of rhTSH allows a reduction of the 131I activity while still achieving a mean goitre reduction of approximately 40 % within the first 12 months. A significantly lower extrathyroidal radiation is achieved by this approach. With an unchanged 131I activity, rhTSH pre-stimulation seems to improve the goitre reduction by up to 50 %. However, this is at the expense of a higher rate of hypothyroidism in addition to other side effects like cervical pain and transient thyrotoxicosis. Of particular concern is the observation made in healthy persons, that rhTSH results in a transient average thyroid volume increase of 35 %. A similar goitre swelling may cause problems in susceptible patients during rhTSH-augmented 131I therapy. Thus, this concept still needs a closer evaluation before routine use.

Bone mineral density in male patients with L-thyroxine suppressive therapy and Graves disease.

Little is known about the effects of thyroid hormone excess in male patients. Our aim was to evaluate bone mineral density (BMD), bone turnover markers, and thyroid function in male patients with treated thyroid cancer on long-term suppressive L-T4 therapy (TC) and in male patients with Graves' disease (GD). We studied 49 male patients (aged 45+/-12 years), 17 with TC (29-288 months on L-T4 suppressive therapy; free T4: 1.9+/-0.6 ng/dl [normal< or =2.0]; TSH: 0.2+/-0.3 microU/ml [Normal 0.5-5.0]) and 32 with recent onset GD (<12 weeks, free T4: 2.0+/-1.4 ng/dl; TSH: 1.07+/-1.8 microU/ml; TSHRAb 53+/-45% [normal < 15]). BMD was measured by dual X-ray absorptiometry (DXA, Hologic QDR1000w) at the lumbar spine (L2-L4, LS), femoral neck (FN), and Ward's triangle (WT). Results were expressed as Z-score (SD compared to national controls). Total alkaline phosphatase (ALP), osteocalcin (BGP), iPTH, serum phosphorus, serum, and 24 h urine calcium were measured as bone markers. Age, weight, and body mass index were comparable in both groups. Patients with TC and with GD showed reduced axial BMD (95% confidence interval: LS: TC (-1.27-0.01)(P = 0.046), GD (-1.06 to-0.38)(P < 0.001); FN: TC (-0.82 to-0.16)(P = 0.007), GD (-0.95 to-0.15)(P = 0.008); WT: TC (-0.82 to -0.18)(P = 0.004), GD (-0.97 to -0.08)(P = 0.024). No significant differences in BMD were found between the groups. Among bone markers, total ALP and osteocalcin levels showed higher levels in Graves' disease (ALP: 139+/-76 vs. 88+/-34, P < 0.01; BGP: 7.5+/-3.7 vs. 4.6+/-1.6; P < 0.001). Our data suggest a mild deleterious effect of thyroid hormone excess in the axial bone mass from male subjects. A skeletal status assessed by BMD in male patients with chronic TSH suppression by L-T4 or history of hyperthyroidism is recommended.

Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH.

This study tested the hypothesis that administration of human recombinant thyroid-stimulating hormone (rhTSH: Thyrogen, thyrotropin alpha) could promote iodine-131 ((131)I) uptake in the therapy for metastatic or locally invasive differentiated thyroid cancer (DTC), obviating L-thyroxine suppressive therapy (L-T4) withdrawal and hypothyroidism in patients with advanced disease. Twelve totally (or almost completely) thyroidectomized adults, nine of whom had received earlier therapy after L-T4 withdrawal, underwent (131)I treatment while euthyroid on L-T4, after rhTSH administration. Nine underwent diagnostic whole-body scanning (WBS) after two consecutive daily i.m. injections (0.9 mg) of rhTSH. They then received an identical second course of rhTSH to promote therapeutic (131)I uptake. Post-therapy WBS was performed one week later. Three patients received only rhTSH (131)I therapy. Administration of rhTSH promoted (131)I uptake in all patients, as demonstrated by post-therapy WBS. Administration of rhTSH also promoted a significant increase in serum thyroglobulin (Tg) concentrations. According to the most recent measurements, 3-12 months after therapy, serum Tg levels fell in four, and stabilized in two out of eleven patients. Upon additional rhTSH-WBS 8 months post-study, a reduction in one metastatic site was noted in one patient. The rhTSH was well tolerated, with mild, transient fever and/or nausea occurring in only a minority of patients. Individuals with bone metastases experienced degrees of peritumoral pain and swelling that were similar (though more short-lived) to those seen in the same or other patients after L-T4 withdrawal. Administration of rhTSH is a safe, successful tool for inducing (131)I uptake in local and metastatic DTC lesions, and avoids L-T4 withdrawal, preserving metabolic homeostasis and preventing the debilitating effects of hypothyroidism.

Use of surgical gamma probe for the detection of lymph node metastases in differentiated thyroid cancer.

Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131I therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical reintervention when the nodal lesions persist after two 131I treatments. Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131I doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.

Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy

Osteoporosis is a well-known complication of thyrotoxicosis. Prolonged subclinical hyperthyroidism due to L-thyroxine treatment has been associated with reduced bone mass and thus with the potential risk of premature development of osteoporosis.The aim of this study was to assess the effect of a chronic L-thyroxine suppressive treatment on bone mineral density (BMD) in agroup of premenopausal women. Forty consecutive patients (mean age ± SE = 40.95 ± 1.56 years) affected by non-toxic goiter underwent bone mineral densitometry (dual energy X-ray absorptiometry; DEXA) of the lumbar spine (L1-L4) and right femoral neck. At the time of the study the patients had been under thyroid stimulating hormone (TSH) suppressive therapy for 74.95 ± 10.34 months (range 17-168 months). Baseline levels of free thyroxine (fT4), free triiodothyronine (fT3), TSH, calcium and phosphorus were measured and correlated with BMD. The age of starting, duration of treatment, main daily dose, cumulative dose of treatment and body mass index (BMI) were also correlated with BMD. Statistical analysis was performed by multiple linear regression. BMD among female patients was not significantly different from that of the general population matched for age and sex. With the use of the regression model, no significant correlation was found between BMD and the variables considered.In conclusion, our data suggest that L-thyroxine suppressive therapy, if carefully carried out and monitored, has no significant effect on bone mass.

L-thyroxine suppressive therapy and bone density in postmenopausal women—The effect of calcium supplementation and intranasal calcitonin

L-thyroxine suppressive therapy and bone density in postmenopausal women—The effect of calcium supplementation and intranasal calcitonin

TSH suppressive L-thyroxine therapy decreases bone density in the rat; Effect of hypogonadism and calcitonin

TSH suppressive L-thyroxine therapy decreases bone density in the rat; Effect of hypogonadism and calcitonin

Serum TSH measurements by a sensitive enzyme immunoassay discriminate euthyroid from hyperthyroid subjects and avoid the need for TRH test during suppressive therapy with L-thyroxine

Serum TSH was determined photometrically by a recently developed enzyme immunoassay (EIA) based on the use of a monoclonal antihuman TSH-beta antibody and a polyclonal antiTSH antibody coupled to horseradish peroxidase. The results obtained in patients with various thyroid disorders and in normal controls were compared with those achieved by conventional double antibody radioimmunoassay (RIA). In normal subjects, serum TSH was detectable in all cases by EIA (values ranging from 0.27 to 5.1 mU/L), but only in 76% by RIA. Ninety-two percent of hyperthyroids had undetectable serum TSH by EIA and the remaining 8% had values between 0.2 and 0.4 mU/L. In clinically euthyroid patients with nontoxic goiter, 9% had undetectable serum TSH by EIA, suggesting the presence of autonomously functioning areas within the thyroid. Serum TSH under basal conditions and after TRH stimulation was measured in 45 patients on L-thyroxine suppressive therapy. Undetectable basal serum TSH by EIA was associated with a lack of TSH response to TRH in 95% of cases. Conversely, 37.5% of patients with undetectable basal serum TSH by RIA had a normal or blunted response to TRH. Detectable basal values were predictive of a normal response to TRH by both methods. These data indicate that basal serum TSH measurement by EIA allows an almost complete differentiation of normal from thyrotoxic patients and can avoid the need of the TRH stimulation test.