Radioiodine therapy in voluminous multinodular non-toxic goitre

Large doses of radioiodine were administered since 1969 to 15 euthyroid patients with compressive voluminous goitres. A decrease in goitre size was observed in all patients (between 15 and 63%, average 39%). Maximal effect on goitre size was attained rapidly, partially already after less than one year and was almost maximal after 24 to 30 months. No significant local adverse reactions were observed; no patient required steroid administration. Hypothyroidism followed radioiodine administration in 30% of the patients after 2 years; after 8 years, all those who had survived were hypothyroid, requiring substitution therapy. In all patients there was a marked improvement in compression symptoms. The use of radioactive iodine therapy constitutes an alternative to surgery in selected patients with large compressive goitres in whom surgery is contraindicated because of age or other medical conditions.     

Peripheral bone density in patients with rheumatoid arthritis

Bone loss in patients with rheumatoid arthritis (RA) varies at different skeletal sites. The aim of the study was to evaluate whether bone mineral density (BMD) of the forearm is significantly different in patients with RA and controls and may correlate to BMD or other parameters of inflammation or bone resorption. We included 421 patients (357 women: mean age 58.4 ± 12.87 years and 64 men: mean age 56.11 ± 12.80 years) with RA in the study. BMD values of the ultradistal forearm (0.381 ± 0.052 g/cm²) and middistal forearm (0.519 ± 0.091 g/cm²) were significantly (p < 0.01) lower in women with RA than controls (0.395 ± 0.043 and 0.535 ± 0.052 g/cm², respectively). In contrast, there was no difference in bone density at the lumbar spine (women 0.921 ± 0.l570 g/cm², men 0.941 ± 0.144 g/cm²) or hip (women 08.11 ± 0.140 g/cm², men 0.895 ± 0.143 g/cm²) in patients with RA in comparison to controls (lumbar spine: women 0.930 ± 0.146 g/cm²; men 0.960 ± 0.146 g/cm²; hip: women 0.820 ± 0.122 g/cm²; men 0.899 ± 0.144/cm²). Patients with increased inflammatory activity (elevated C-reactive protein) presented with significantly lower BMD of the hip (0.7533 ± 0.144 versus 0.825 ± 0.138 g/cm²) and ultradistal forearm (0.366 ± 0.09 versus 0.390 ± 0.07 g/cm²). This was not the case for the lumbar spine. BMD of the forearm is precise and, in contrast to BMD of the lumbar spine, significantly lower in patients with RA. It is related to inflammatory activity, grip strength, and treatment with glucocorticoids in patients with RA.     

Predictive factors of thyroid carcinoma in non-toxic multinodular goitre

The management of nontoxic multinodular goitre (NMNG) remains controversial. The challenge for the clinician is to identify the small proportion of NMNG patients with associated thyroid carcinoma who would thus benefit from surgery. We studied retrospectively the medical records of 80 patients with NMNG and coexisting thyroid carcinoma who underwent total thyroidectomy. Eighty total thyroidectomy patients with NMNG whose histology was benign were then randomnly chosen as controls. In univariate analysis, the following parameters were significantly more frequent in the carcinoma group: rapid growth of the goitre (p = 0.002), presence of microcalcifications (p = 0.01), hypoechogenicity (p = 0.02), firm consistency of a nodule (p = 0.03), and presence of a dominant cold nodule on scintigraphy (p = 0.03). In the multiple regression analysis, the variables significantly associated with carcinoma were rapid growth (Odds ratio (OR) = 4.13, 95% confidence interval(CI): 1.72-9.89), hypo-echogenicity (OR = 3.11, 95% CI: 1.13-8.51) and the presence of a dominant nodule (OR = 2.26, 95% CI: 1.06-4.79)). In the cancer group, tumour size was positively correlated with compression signs (p = 0.01), age (p = 0.02), the presence of a dominant nodule on scintigraphy (p = 0.02), and with rapid growth (p = 0.04). Concerning nodule size estimated on US (ultrasound), the majority (65%) of patients without carcinoma had nodules < 3 cm, whereas 73% of patients with clinical thyroid carcinoma (> or = 1 cm on histology) had nodules with a diameter of > or = 3 cm on US (p = 0.02). In conclusion, our study suggests that surgical treatment of NMNG should be proposed in the presence of rapid nodular growth, compression signs, dominant nodule on scintigraphy, nodule size > or 3 cm and hypo-echogenicity.     

Cardiac and metabolic effects in patients who present with a multinodular goitre

Twenty-six consecutive patients who presented with clinically euthyroid multinodular goitre were studied for an overnight fasting serum lipid profile and 24 h Holter monitoring. Mean serum TSH was 0.6 +/- 0.4 vs 2.4 +/- 1.3 mU/l (p < 0.0001) and mean TT3 2.4 +/- 0.4 vs 2.0 +/- 0.5 nmol/l (p = 0.009) in patients vs controls (n = 15) while mean FT4 was not different from controls. Total serum HDL, LDL cholesterol and triglycerides were lower in patients but creatinine, ferritin and SHBG levels did not differ between patients and controls. The 24-hour ambulatory continuous ECG recordings did not demonstrate significant differences in mean, minimal and maximal heart rate between the study and the control group. Nocturnal heart rate, measured between 23.00 and 06.00 hours, also showed no differences between the two groups. Atrial fibrillation was absent in both the study and the control group. Premature atrial and ventricular complexes occurred equally frequently in both groups. Comparison of patients with a serum TSH below 0.4 mU/l (n = 11) and patients with a TSH above 0.4 mU/l revealed no differences. In conclusion, in consecutive patients who present with multinodular goitre, effects were found on the lipid profile, but not on the heart. It is argued that in this type of patients, cardiac effects depend on the degree of subclinical hyperthyroidism.     

Is there a relationship between thyroid function and serum osteocalcin in women with multinodular goitre? A preliminary report

The relationship between thyroid function and serum osteocalcin was studied in a population of 27 women with multinodular goitre and normal serum concentrations of thyroid hormones. Seven patients were found to have suppressed TSH levels (less than 0.1 mU/l) as measured by an immunoradiometric assay. Osteocalcin was statistically significantly correlated with serum free thyroxine (FT4), both in the total population and in the subpopulation of patients with TSH greater than or equal to 0.1 mU/l (r = 0.61; P less than 0.001, resp. r = 0.51; P less than 0.05). Mean (+/- SEM) serum osteocalcin and FT4 were higher in the patients with suppressed TSH than in those with TSH greater than or equal to 0.1 mU/l (10.6 +/- 1.9 vs. 7.1 +/- 0.6 micrograms/l; P less than 0.05, resp. 16.3 +/- 1.4 vs. 13.3 +/- 0.5 pmol/l; P less than 0.02). This study suggests that women with multinodular goitre who proceed to autonomous function are at risk of developing osteoporosis even when thyroid hormone concentrations are in the normal range.     

Utility of fine-needle aspiration for diagnosis of carcinoma associated with multinodular goitre

BACKGROUND: Fine-needle aspiration (FNA) is a useful method for evaluating a solitary thyroid nodule; however, this is not an agreed method for a multinodular goitre (MNG). The aim of this study was to assess the utility of preoperative FNA for detecting malignancy in MNG. PATIENTS AND METHOD: We analysed operated MNGs in which FNA had been performed. Puncture was carried out on the dominant nodule and any other nodules with features suggesting malignancy. The diagnosis was classed as colloid, follicular or Hurthle proliferation, suggestive of malignancy, haematic and inadequate. The thyroid FNA results, grouped into suggestive of malignancy (positive result) and other diagnoses (negative result), were compared to those of the final histological study in order to calculate the value of the test in diagnosing malignancy. RESULTS: FNA was performed in 432 MNGs, of which 42 (9.7%) were associated with carcinoma. Overall, the results of the test were poor, revealing a sensitivity of 17%, specificity of 96% and diagnostic accuracy of 88%, with a positive predictive value of 32% and negative predictive value of 88%. When the values were recalculated with the exclusion of microcarcinomas--considering their minor clinical importance--there was a slight improvement in the results: the sensitivity increased to 26%, diagnostic accuracy to 93% and negative predictive value to 96%. However, the specificity remained at 96%, and the positive predictive value fell from 32% to 25%. The results of the test improved in multifocal carcinomas. CONCLUSIONS: Thyroid fine needle aspiration is not useful for differentiating MNG with malignant degeneration from benign MNG, as more than 80% of carcinomas go unnoticed; it provides a sensitivity of 17% for detecting carcinomas, rising to 26% if microcarcinomas are excluded. We therefore suggest that clinical criteria should prevail over FNA.     

Androgens and bone density in women with hypopituitarism

Hypopituitarism is associated with osteopenia and a reduction in lean body mass. We have recently demonstrated markedly reduced serum androgen levels in women with hypopituitarism. We hypothesized that serum androgen levels and lean body mass are important determinants of bone mineral density (BMD) in women with hypopituitarism. In addition, because IGF-I may stimulate androgen secretion in women, we investigated whether GH administration results in an increase in serum androgen levels. Sixteen women with a history of pituitary disease of adult-onset and serum GH levels less than 5 ng/ml on stimulation testing underwent BMD and body composition testing by dual-energy x-ray absorptiometry. Univariate regression analysis revealed strong correlations between androgen levels and BMD [lateral spine BMD and dehydroepiandrosterone sulfate (DHEAS) (r = 0.68, P = 0.03), total hip BMD and free T (r = 0.60, P = 0.01), Ward's triangle BMD and DHEAS (r = 0.68, P = 0.004), Ward's triangle BMD and free T (r = 0.54, P = 0.03), femoral neck BMD and free T (r = 0.52, P = 0.04), and femoral neck BMD and DHEAS (r = 0.51, P = 0.04)]. When adjusted for age using Z scores, correlations at the femoral neck no longer reach significance. Correlations between androgens and BMD at other sites, including anterior-posterior spine and total body, were not significant, and neither total T nor androstenedione correlated with BMD at any site. Lean body mass strongly correlated with BMD [total hip (r = 0.80, P = 0.0002), total body (r = 0.78, P = 0.0003), trochanter (r = 0.74, P = 0.001), Ward's triangle (r = 0.56, P = 0.02), femoral neck (r = 0.53, P = 0.04), and anterior-posterior spine (r = 0.52, P = 0.04)]. In stepwise regression models, DHEAS determined 47% of the variation in Ward's triangle BMD (R(2) = 0.47, P = 0.004) and 46% of lateral spine BMD (R(2) = 0.46, P = 0.03). Lean body mass determined 64% of the variation in total hip BMD (R(2) = 0.64, P = 0.0002), 62% of total body (R(2) = 0.62, P = 0.0003), and 55% of trochanter BMD (R(2) = 0.55, P = 0.001). Subjects were then randomized to receive GH at a dose of 12.5 microg/kg per day or placebo for 12 months in a double-blind protocol. Serum androgen levels were obtained at baseline, 1, 3, 6, 9, and 12 months after initiation of GH. Androgen levels did not increase in the women receiving GH for 12 months, compared with those receiving placebo. Stimulation of androgen secretion is therefore unlikely to be a mechanism underlying the improvement in BMD, body composition, or quality of life observed with GH administration. In conclusion, androgen levels and lean body mass may be important determinants of BMD in women with hypopituitarism. It remains to be determined whether androgen replacement therapy itself or an increase in lean body mass achieved as a result of androgen administration will result in an improvement in BMD in this population.     

Decreased bone mineral density in pre-menopause women with prolactinoma

Tumoral hyperprolactinemia and consequent hypogonadism have been associated with osteoporosis. Bone mineral density (BMD) was measured by dual-energy RX absorptiometry in 24 patients with prolactinoma (15 macro and 9 micro adenomas; age range = 18 to 49 years). Student unpaired t or Mann-Whitney tests were used to compare groups, and Spearman test studied correlations. Lumbar spine (LS) was the most affected, as LS Z-score was < -2 SD in 20.83% of the patients. No difference was found in densitometric parameters for the comparison between macro and microprolactinoma, or those with normal prolactin versus hyperprolactinemia. LS BMD and LS Z-score were higher in the patients with > 8 menstrual cycles in the preceding year then in those with oligoamenorrhea (p = 0.030). The number of cycles was correlated to LS BMD (r = 0.515, p = 0.017) and body mass index to femoral neck BMD (r = 0.563, p = 0.006) and total femur BMD (r = 0.529, p = 0.011). CONCLUSIONS: Decreased bone mineral density was detected in 20.83% of our young patients with prolactinoma. The great involvement of trabecular bone skeletal regions, such as vertebrae, suggests the participation of hypogonadism in the pathogenesis of bone disease. Irrespective of prolactin levels, return to normal menses seems the best index of good control.     

RANKL:osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

OBJECTIVE: To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL:osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease. METHODS: Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects. RESULTS: At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL:OPG ratio compared with that in healthy children (mean +/- SD 2.19 +/- 3.03 and 0.13 +/- 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of -1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than -1.5 (P = 0.038). Lumbar spine BMD Z scores (mean +/- SD -0.13 +/- 1.19 [range -2.10 to 2.85]) were inversely associated with the duration of untreated disease (R = -0.50, P = 0.003). CONCLUSION: Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.     

Calcaneus bone mineral density in Japanese women with rheumatoid arthritis

Objectives The aim of this study was to investigate the relationships among bone mineral densities (BMD) in the calcaneus and leg activity of daily living (L-ADL) in rheumatoid arthritis (RA) patients.Methods We measured and compared calcaneus BMD using single X-ray absorptiometry and lumbar spine and femoral neck BMD using dual X-ray absorptiometry in 158 Japanese female outpatients with RA and 358 normal controls (NC).Results Regardless of whether the women were premenopausal or postmenopausal, calcaneus and femoral neck BMDs in the RA group were significantly lower than in the NC group. Calcaneus BMD correlated with the modified health assessment questionnaire, L-ADL score, and 10-m walking time, regardless of whether the patients were premenopausal or postmenopausal (P<0.01).Conclusions We conclude that calcaneus BMD reflects the L-ADL of RA patients very well and allows us to perform the same level of BMD evaluation as that with current BMD measurement methods.     

Peripheral bone density in patients with rheumatoid arthritis and factors which influence it

INTRODUCTION: Patients with rheumatoid arthritis (RA) frequently possess a number of risk factors for osteoporosis. Additionally, oral steroids are often used to control active rheumatoid disease and may further potentiate bone loss. We wished to establish the degree of peripheral bone loss in RA and to assess the influence of oral steroids and other risk factors. METHODS: We measured bone mineral density (BMD) in the non-dominant forearm using a DTX 200 osteometer in 191 RA patients who were receiving oral prednisone in a dose of at least 5 mg daily for over 3 months. We compared the results with those of two other groups: 165 RA patients who had never received oral prednisone and 242 normal controls without RA or any history of steroid therapy. Forward stepwise multiple regression analysis was used to determine the effects of age, disease variables and steroids on BMD. RESULTS: Age (P<0.001), RA (P<0.02) and steroid therapy (P<0.05) were all associated with reduced BMD using multiple regression analysis. Duration of RA was also associated with reduced BMD (P<0.05), but activity of disease was not. By WHO criteria (BMD T score<-2.5 S.D.), 95 (50%) of the RA steroid-treated patients (RAS) had osteoporosis, while 48 (25%) of the RA patients not exposed to steroids (RAN) were osteoporotic. Among the normal controls (NC), 48 (20%) had osteoporosis. The mean (S.D.) BMD Z scores for the three groups were -0.8 (1.3) for RAS, -0.4 (1.3) for RAN and 0.0 (1.0) for NC (P<0.01 for all differences). The percentages of patients with a Z score of -1 or less were 51% for RAS, 29% for RAN and 14% for NC. These differences were also significant (P<0.01). Male sex was associated with reduced BMD when compared to female sex (Z<-1) in the RAS (57 vs. 49%; P<0.05) but not in the RAN (25 vs. 31%) groups. For men with RA, the mean (S.D.) BMD Z scores were -1.3 (1.3) for RAS compared to -0.5 (1.3) for RAN (P<0.005), while for women the differences were less marked at -0.7 (1.3) for RAS compared to -0.4 (1.3) for RAN (P<0.05). CONCLUSIONS: In general, patients with RA have a significantly reduced forearm BMD, which correlates with increasing disease duration. Exposure to oral steroids increases bone loss, notably in male patients. Patients with RA on oral steroids need BMD measurements with a view to prophylactic therapy in those with a low result. Previous fractures and a daily dose of 15 mg or more of prednisone are also important factors in determining when prophylaxis is indicated.