Benign and malignant thyroid nodules with autoimmune thyroiditis

ABSTRACT Objective: The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. Materials and methods: This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. Results: The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. Conclusion: The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.

Benign and malignant thyroid nodules with autoimmune thyroiditis.

Objective: The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. Materials and methods: This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. Results: The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. Conclusion: The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.

Taller-than-wide Thyroid Nodules With Microcalcifications Are at High Risk of Malignancy.

BACKGROUND/AIM: Previous studies have shown that there may be a diversity in the ultrasonographic (US) features discriminating a malignant from a benign thyroid nodule. We determined the reliability of the specific nodule shape in combination with other US features in predicting thyroid carcinomas. PATIENTS AND METHODS: This was a retrospective single-center study investigating the association of the morphological characteristics of nodular goiters from preoperative US and color Doppler images with malignancy based on pathology. RESULTS: We evaluated 254 thyroid nodules (malignant, n=131) from 205 patients. Multivariable logistic regression analysis showed that taller-than-wide shape [odds ratio (OR)=25.3, 95% confidence interval (CI)=5.4-118.9; p<0.001], microcalcifications (OR=4.9, 95% CI=2.5-9.5; p<0.001), hypoechogenicity (OR=4.5; 95% CI=2-10.3; p<0.001) and size (OR=0.93; 95% CI=0.89-0.98; p=0.002) were independently associated with thyroid nodule malignancy. Additionally, we found a strong negative correlation between size and taller-than-wide shape of a thyroid nodule (r=-0.41, p<0.001). CONCLUSION: Among the important indicators of thyroid malignancy, taller-than-wide nodules with microcalcifications are most likely to be malignant.

Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of gestation.

BACKGROUND: Antenatal corticosteroid therapy recently has been considered for term and near-term infants, in addition to preterm infants, delivered by elective cesarean section, with the aim of preventing an adverse respiratory outcome. OBJECTIVES: The objective of this study was to investigate hormonal and metabolic effects of antenatal betamethasone when administered to term fetuses. METHODS: Cord blood levels of cortisol, C-peptide, insulin-like growth factor I and its binding protein 3, and 5 more analytes including glucose were measured in singleton newborns of over 35 weeks of gestational age. In anticipation of a cesarean delivery, the mother was either treated or not treated with 12 mg of intramuscularly administered antenatal betamethasone approximately 24 hours prior to birth. Babies of comparable gestational age, sex, and nutritional status who were not treated antenatally served as controls. RESULTS: Cord serum cortisol levels of the betamethasone-treated fetuses were suppressed to <10% of that of untreated controls (median levels of 11.6 nmol/L vs. 138.2 nmol/L, respectively), and their C-peptide and glucose levels were significantly higher (2.85 mcg/L vs. 1.19 mcg/L, respectively, p < 0.0001; and 62.5 mg/dL vs. 56.0 mg/dL, respectively, p = 0.01). CONCLUSIONS: Prophylactic betamethasone therapy causes immediate hormonal alterations, which might interfere with the metabolic adaptation of the newborn. This issue deserves thorough investigation.

Cytokines and insulin resistance after zoledronic acid-induced acute phase response.

Zoledronic acid is known to induce a transient acute phase response (APR). The aim of the study was to investigate whether an APR caused by zoledronic acid administration can induce insulin resistance in post-menopausal osteoporotic women and the potential involvement of different inflammatory markers, cytokines and adipokines to this response. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). APR symptoms appeared in 30 post-menopausal osteoporotic women within 24 h and attenuated on day 3 after zoledronic acid infusion. Twenty-eight age- and body mass index-matched, patients without an APR following zoledronic acid administration, served as a control group. In patients with APR, concurrently with a significant increase in serum high sensitive C-reactive protein (hsCRP), interleukin-6 (hsIL-6), tumour necrosis factor-alpha (hsTNF-α) and cortisol levels on days one and two, serum insulin was also significantly elevated, resulting in an increased HOMA-IR. Leptin and resistin significantly increased on day two in contrast to adiponectin which declined, though not statistically significant. The alterations in HOMA-IR were mainly associated to the increase of hsCRP and leptin. In conclusion, zoledronic acid induces an acute, short term insulin resistance, due to an APR, by altering the levels of various adipokines and cytokines.

Markers of inflammation after zoledronic acid redosing.

The symptoms of acute phase response (APR) following the first infusion of zoledronic acid (ZA) are attenuated after re-administration. We investigated the reasons for this attenuation, focusing on the changes in several hormones, bone markers and markers of inflammation occurring after the second ZA injection in patients who had experienced a severe APR after their first ZA infusion. Twenty-two postmenopausal women with osteoporosis and severe symptoms of APR following the first ZA infusion were included in the study (group A1). A year later, the same women (possibly with a residual activity of ZA) were subjected to ZA re-administration (group A2). Urine NTx (uNTx), white blood cells, parathyroid hormone, serum calcium, phosphorus and several serum markers of inflammation were measured before (0) and at 1 and 2 days following the first as well as the second infusion. In group A1, the APR was associated with a significant increase in serum C-reactive protein (CRP), high-sensitive interleukin 6 (hsIL-6), high-sensitive tumor necrosis factor alpha (hsTNF-α) and cortisol within 24 h after the infusion. The majority of the patients in group A2 did not experience an APR and serum calcium, phosphorus, CRP, hsIL-6, hsTNF-α, and cortisol remained essentially unchanged throughout the study. In group A2, on day 0, the uNTx were significantly lower than in group A1. In group A1 the uNTx decreased by 69 and 78% from baseline on days 1 and 2, whereas in group A2, they decreased by 48 and 53% (p < 0.01), respectively. A positive correlation was found between the degree of uNTx decline from the baseline levels (Δ-uNTx) and hsTNF-α and between Δ-uNTx and CRP. The Δ-uNTx, reflecting the osteoclast-mediated bone resorption, may play some role in the APR appearance, although it must be excluded if the relationships of the changes between uNTx and hsTNF-α/CRP are coincidental effects and not causal.

Autoimmune thyroiditis in benign and malignant thyroid nodules: 16-year results.

BACKGROUND: It is controversial whether autoimmune thyroiditis is associated with higher frequency of papillary thyroid carcinoma (PTC). METHODS: This was a cross-sectional, retrospective study. PTCs were compared to benign nodules regarding the prevalence of autoimmune thyroiditis over 16 years. RESULTS: A similar proportion of autoimmune thyroiditis was observed in both benign and/or malignant nodules. Mean nodule size in cases with autoimmune thyroiditis was smaller than those without autoimmune thyroiditis. Multivariate analysis showed a negative association between the coexistence of autoimmune thyroiditis and lymph node and/or distant metastases. Lymph nodes involvement and distant metastases were lower in the PTC with autoimmune thyroiditis compared to those without autoimmune thyroiditis. Capsular invasion was a strong predictor for distant metastases attenuated by the presence of autoimmune thyroiditis. CONCLUSION: Thyroid nodules with autoimmune thyroiditis are not more likely to be malignant than those without autoimmune thyroiditis. The coexistent autoimmune thyroiditis may be beneficial as a decreased incidence of lymph nodes involvement and distant metastasis was seen in those patients.

Hormonal imbalance in relation to exercise intolerance and ventilatory inefficiency in chronic heart failure.

BACKGROUND: Skeletal muscle wasting is associated with altered catabolic/anabolic balance and poor prognosis in patients with chronic heart failure (CHF). This study evaluated catabolic and anabolic abnormalities in relation to disease severity in CHF patients. METHODS: Forty-two stable CHF patients (34 men; aged 56±12 years, body mass index, 27±5 kg/m2) receiving optimal medical treatment underwent incremental symptom-limited cardiopulmonary exercise testing on a cycle ergometer. Blood samples were drawn within 10 days to determine serum cortisol, plasma adrenocorticotropin (ACTH), and serum dehydroepiandrosterone sulfate, insulin-like growth factor 1, growth hormone, and total testosterone in men. RESULTS: Patients with higher cortisol levels presented with impaired peak oxygen uptake (Vo2 peak: 18.3±3.9 vs. 14.2±3.7 ml/kg/min, p<0.01), ventilatory (Ve) response to exercise (Ve/carbon dioxide output [Vco2] slope: 36±6 vs 30±5, p<0.01), and chronotropic reserve ([peak heart rate [HR]--resting HR/220--age--resting HR]×100%: 40±19 vs. 58±18, p=0.01) compared with those with lower serum cortisol. Cortisol was inversely correlated with Vo2 peak, (r = -0.57; p<0.01) and was correlated with Ve/Vco2 slope (r = 0.47; p<0.01) and chronotropic reserve (r = 0.44; p = 0.017). In multivariate regression analysis, cortisol was an independent predictor of Vo2peak (R2 = 0.365, F = 12.5, SE = 3.4; p≤0.001) and Ve/Vco2 slope (R2 = 0.154; F = 8.5; SE = 5.96; p = 0.006), after accounting for age, body mass index, sex, CHF etiology, creatinine, left ventricular ejection fraction, and ACTH in all patients. In men, cortisol and dehydroepiandrosterone levels were both independent predictors of Vo2peak (R2 = 0.595, F = 24.53, SE = 2.76; p<0.001) after accounting also for all measured hormones, whereas cortisol remained the only independent predictor of Ve/Vco2 slope (R2 = 0.133; F = 6.1; SE = 6.2; p = 0.02). CONCLUSIONS: Enhanced catabolic status is significantly associated with exercise intolerance, ventilatory inefficiency, and chronotropic incompetence in CHF patients, suggesting a significant contributing mechanism to their limited functional status.

Transient changes in thyroid functions tests after zoledronic acid infusion.

Zoledronic acid (ZA) induces an acute phase response in association with elevation of serum cytokines, which possibly alter the 3 types of iodothyronine deiodinase activity. We therefore studied the possible alteration in thyroid function tests by ZA. We investigated the acute changes in serum thyroid hormones, TSH, cortisol, white blood cells, CRP, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), before (0) and 1, 2 and 3 days after iv infusion of 5 mg ZA in 24 asymptomatic postmenopausal women with osteoporosis (ZA group) in comparison with a placebo group. In the majority of patients the ZA infusion was associated with acute phase response and fever within 24h after infusion which became attenuated on day three. Concurrently with increase in serum cortisol, CRP, IL-6 and TNF-α, on day 1 and 2, total serum T3 (TT3), free T3 (fT3), total T4 (TT4) and fT4 decreased with a nadir on day 2 in association with an increase in the fT4/fT3 ratio and reverse T3 (rT3) levels. All thyroid function changes returned to the baseline levels on day 3, with cytokines still at higher levels, although lower than those on day 2. Serum TSH remained essentially unchanged throughout the study. The changes in thyroid hormones were at least in part explained by the increased TNF-α, but not by IL-6. ZA induces short term changes in thyroid hormones, characteristic of nonthyroidal illness syndrome (NTIS), in association with an increase in TNF-α and IL-6.

Diagnostic markers in combination improve the identification of growth-restricted neonates.

BACKGROUND: The identification of growth-restricted neonates is hampered by the lack of an appropriate diagnostic tool. AIM: To determine the value of combining diagnostic markers in detecting growth-restricted neonates. METHODS: A set of anthropometric indices, nutritional status and placental weight were assessed in the study population soon after birth. Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) were assayed in cord blood. Babies having low values (≤25th centile for gestational age) in 0, 1 or more of four anthropometric indices were classified as Group(25)0, Group(25)1 and Group(25)2, respectively. For statistical evaluation the Mann-Whitney test and a multiple regression analysis were performed. RESULTS: One hundred-eighty (180) singleton babies of over 36 weeks of gestational age (GA) were studied. IGF-I, IGFBP-3 levels and placental weight were significantly lower in Group(25)2 than both Group(25)0 (P<0.0001) and Group(25)1 (p<0.0001 to p = 0.03). Group(25)1 and Group(25)0 did not differ significantly regarding IGF-I and IGFBP-3 levels (p values 0.09 and 0.13, respectively). The combination of anthropometric indices enhanced their ability to predict IGF-I, IGFBP-3 levels and placental weight; the nutritional status of the babies added power to all individual models in predicting the three outcome variables. Analogous results were obtained when the 10th (instead of the 25th) centile for GA was used for the anthropometric indices. CONCLUSION: The combination of simple diagnostic markers of growth restriction can define a reference test with enhanced diagnostic potential compared to the potential of the same markers in isolated use.

Blood lymphocyte blastogenesis in patients with thyroid dysfunction: ex vivo response to mitogen activation and cyclosporin A.

OBJECTIVE: To evaluate lymphocyte activation following mitogen and cyclosporin A (CsA) administration in peripheral blood of hyperthyroxinaemic and hypothyroid patients. MATERIALS AND METHODS: Lymphocyte activation was evaluated by determining blastogenesis in 48 h cultured blood lymphocytes obtained from eight hyperthyroxinaemic and eight hypothyroid patients, following phytohaemagglutinin (PHA)-induced stimulation in the absence or presence of CsA. Twelve healthy volunteers served as controls. RESULTS AND CONCLUSIONS: Lymphocytes from hypothyroid patients exhibited reduced response to PHA and lower sensitivity to CsA compared with control, which could be attributed to their reduced activation capability coexisting with hypothyroidism. In hyperthyroxinaemic samples, the actions of high CsA concentrations were mostly targeted toward activated lymphoblasts. Considering the cellular targets that thyroid hormones and CsA may share, the therapeutic implications of their cross-talk need careful consideration.

Changes in risk factors and Tumor Node Metastasis stage of sporadic medullary thyroid carcinoma over 41 years, before and after the routine measurements of serum calcitonin.

The measurement of serum calcitonin (CT) in all thyroid nodules for the detection of medullary thyroid carcinoma (MTC) is controversial. We compare several prognostic factors, Tumor Node Metastasis (TNM) stage, and survival in sporadic MTC patients operated on before and after the use of routine measurements of serum CT in combination with thyroid ultrasonography (US). Thirty-seven patients had been operated on between 1969 and 1989 (group I), before the use of routine measurements of serum CT and the routine use of thyroid US, and 39 (group II) had been operated on between 1990 and 2009, after the introduction of routine use of serum CT and thyroid US. There were no between-group differences concerning age and sex. Group I had larger tumors at the time of operation (P < .001) and higher postoperative serum CT levels (P < .001). Cervical lymph node and distant metastases were found more frequently in group I in comparison with group II. The cases with TNM stage I were significantly higher in group II than in group I, in contrast with the cases with TNM stage IV that were significantly higher in group I. Univariate analysis revealed a significantly higher 15-year survival rate in group II than in group I (P = .002). The postoperative CT levels were positively correlated with tumor size (P < .001). During the last 2 decades, the diagnosis of sporadic MTC at an earlier stage has been made possible by the routine use of serum CT in combination with thyroid US. The significant increase of the 15-year survival rate shows better outcome in these patients.

The effects of recombinant human TSH on bone turnover in patients after thyroidectomy.

Thyrotropin receptors are expressed in several extrathyroidal tissues including bone. We investigated whether the increase of thyroid-stimulating hormone (TSH) levels, under stable thyroid hormone levels, affects the bone markers. Thirty-two postmenopausal women, with papillary thyroid carcinoma, previously treated with near-total thyroidectomy and I131 remnant ablation underwent routine evaluation for residual disease by using injections of recombinant human TSH (rhTSH) without withdrawal from thyroxine therapy. Changes in TSH levels and various serum and urine markers of bone metabolism were followed before and 1, 2, 5, and 7 days after the rhTSH injections. A transient, significant decrease in serum calcium and urinary excretion of C- and N-terminal telopeptides of type I collagen was observed after the injections of rhTSH. Serum parathyroid hormone (PTH) started to rise along with TSH, but a significant increase of PTH was only reached on Day 5 when the TSH concentration had fallen more than 80% of the peak value. Bone alkaline phosphatase and osteocalcin did not show any significant change over time. There was no significant correlation between TSH concentration and the various parameters we measured. The study provides evidence that rhTSH produces a transient inhibition of bone resorption, as well as an attenuation of osteoblast response in spite of the PTH activation. Additional studies are needed to resolve the mechanisms by which TSH alters the response of the bone cells.

Helicobacter pylori infection and endocrine disorders: is there a link?

Helicobacter pylori (H pylori) infection is a leading world-wide infectious disease as it affects more than half of the world population and causes chronic gastritis, peptic ulcer disease and gastric malignancies. The infection elicits a chronic cellular inflammatory response in the gastric mucosa. However, the effects of this local inflammation may not be confined solely to the digestive tract but may spread to involve extra-intestinal tissues and/or organs. Indeed, H pylori infection has been epidemiologically linked to extra-digestive conditions and diseases. In this context, it has been speculated that H pylori infection may be responsible for various endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus, dyslipidemia, obesity, osteoporosis and primary hyperparathyroidism. This is a review of the relationship between H pylori infection and these endocrine disorders.

Arterial stiffness but not intima-media thickness is increased in euthyroid patients with Hashimoto's thyroiditis: The effect of menopausal status.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disorder associated with increased cardiovascular risk, mainly as a result of accelerated atherosclerosis. The aim of this study was to determine the effect of HT on carotid atherosclerosis and arterial stiffness, as possible mediators of this vascular impairment. Menopausal status was also considered in this setting since HT is mainly prevalent in women. METHODS: Fifty-four women with HT and normal thyroid function (thyrotropin [TSH] < 4.5 mU/L) and 72 healthy controls with comparable age and risk factor prevalence were examined in this cross-sectional study. Intima-media thickness (IMT) in the carotid arteries averaged from six sites and carotid-femoral pulse wave velocity (PWV) were measured. RESULTS: Although both groups had TSH levels within normal limits, TSH was higher in HT patients (2.1 +/- 1.16 vs. 1.5 +/- 0.8 mU/L, p = 0.001). PWV (7.95 +/- 2.02 vs. 7.21 +/- 1.24 m/s, p = 0.021), but not IMT (0.644 +/- 0.144 vs. 0.651 +/- 0.169 mm, p = 0.798), was significantly higher in HT patients compared to controls. When the women were divided according to menopausal status, only premenopausal women without HT had significantly lower PWV when compared with the three other subgroups (6.51 +/- 1.09 m/s premenopausal controls vs. 7.64 +/- 2.05 m/s premenopausal HT vs. 7.69 +/- 1.11 m/s postmenopausal controls vs. 8.3 +/- 1.97 m/s postmenopausal HT, p < 0.001). By multivariate analysis PWV independently correlated with age (p = 0.042), the presence of HT (p = 0.002), TSH (p = 0.003), and menopause (p < 0.001) in the whole population while HT was an independent determinant of PWV only in premenopausal women. CONCLUSIONS: HT is associated with increased PWV independent of arterial atheromatosis, indicating a direct impact of this disorder on arterial stiffening. This effect may be masked in postmenopausal women possibly due to their heavier cardiovascular risk profile.

Vitamin D deficiency in the elderly in Athens, Greece.

Vitamin D deficiency characterized by low 25-hydroxyvitamin D [25(OH)D] levels has been found to be prevalent among the elderly in many regions of the world. To investigate the vitamin status in elderly community-living persons in Athens, we measured 25(OH)D and parathyroid hormone (PTH) in elderly persons and young blood donors during the winter and summer. The changes in these parameters in a subgroup of the elderly were studied longitudinally. The blood donors had mean 25(OH)D levels similar in winter and summer and twice as high in winter compared to the elderly. At the end of the winter, about 20% of the elderly had severe vitamin D deficiency, with 25(OH)D below 25 nmol/l, and only 6.5% could be judged as vitamin D sufficient with values above 80 nmol/l. The situation improved during summer, although 64.8% of the elderly continued to have levels below 80 nmol/l. Mean plasma PTH in the elderly in summer was not different from that of blood donors; however, it was doubled during the winter. Regression of PTH on 25(OH)D demonstrated that PTH starts to rise when 25(OH)D falls below approximately 80 nmol/l. We conclude that severe vitamin deficiency associated with secondary hyperparathyroidism is not uncommon in the elderly in Athens during the winter; it subsides during summer, although only one-third of the elderly population attain vitamin D sufficiency during summer. We found that a threshold value of 25(OH)D exists at approximately 80 nmol/l, below which secondary hyperparathyroidism ensues, as described previously.

Bone mineral density in hyperthyroidism.

OBJECTIVE: To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis. DESIGN AND PATIENTS: In this cross-sectional study, 164 women with untreated or previously treated overt and symptomatic hyperthyroidism were examined 0-31 years after the initial episode of hyperthyroidism and its treatment, and were compared with a control group of 79 age-matched women without previous history of hyperthyroidism. Subjects with current or previous metabolic bone disease, any antiresorptive treatment for osteoporosis or treatments and habits known to affect bone metabolism were excluded. MEASUREMENTS: The age of the first manifestation of the disease, the age at the measurement of bone mineral density (BMD) at the spine and femoral neck and the interval between diagnosis and treatment of hyperthyroidism and BMD measurement were recorded and the Z-scores and T-scores of BMD were analysed. RESULTS: Untreated hyperthyroidism and hyperthyroidism up to 3 years after its diagnosis and treatment were associated with decreased BMD. Three or more years after the first episode of the disease the mean Z-score at both skeletal sites was near zero and not different from the controls. The age at which hyperthyroidism was manifested for the first time had no effect on the final outcome. Women affected at a young age (13-30 years) had a more pronounced loss of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD significantly above zero if examined later (> 3 years). Older women (aged 51-70 years) showed a similar pattern, although the differences were not significant. Middle-aged subjects (31-50 years) had the smallest loss of BMD during the first 3 years. Analysis of T-scores of former hyperthyroid women aged > or = 51 years showed no significantly different relative risk (RR) for osteoporosis in comparison with the controls. However, the study was not powered enough to give meaningful RR results. CONCLUSIONS: Overt symptomatic hyperthyroidism is associated with decreased BMD during the first 3 years after diagnosis and treatment of the disease. After this interval, former hyperthyroid women have a Z-score near zero and not different from women without a history of the disease, apparently because of recovery of the bone density lost early during the course of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long-lasting osteoporosis, and the age of the patient during the first episode is irrelevant.

L-thyroxine therapy attenuates the decline in serum triiodothyronine in nonthyroidal illness induced by hysterectomy.

It is controversial whether the administration of thyroid hormone to patients with nonthyroidal illness has any beneficial effect. Two groups of patients undergoing abdominal hysterectomy under the same general anesthesia were studied. Group A consisted of 15 women taking chronically l-thyroxine therapy (1.8 mug/kg daily), and group B (control) consisted of 16 apparently healthy euthyroid women taking placebo. Thyroid hormones, cortisol, and interleukin (IL)-6 were measured 1 day before and 1, 2, 3, and 6 days after surgery. Total triiodothyronine (TT(3)) decreased to a significantly greater degree (P <.05) and for a longer period of time in group B than in group A. The significant increase of reverse T(3) (rT(3)) noted early in group B failed to reach the baseline levels until the end of the study, whereas in group A, rT(3) returned to the preoperative values by day 2. Both groups had similar free thyroxine (FT(4)) at baseline. FT(4) increased significantly at day 1 and remained significantly elevated throughout the postoperative period in group B only. Serum TT(4), thyroid-stimulating hormone (TSH), and cortisol did not change significantly in either group. In all patients, IL-6 increased significantly to a peak value at day 1, showing a slow decrease thereafter. A stronger negative correlation was found between T(3) and IL-6 in group B than in group A (r = -.66, P <.0001 v r = -.38, P <.001, respectively) and a strong positive correlation was observed between rT(3) and IL-6 in group B only (r =.57, P <.001). The long-term treatment with T(4) seems to attenuate the decrease of serum T(3), which occurs during the development of nonthyroidal illness postoperatively. The elevation of IL-6 accounted for a greater proportion of the variations of the T(3) and rT(3) in the control group B than in the T(4)-treated group A.

Hypercalcemia due to sun exposure in a patient with multiple myeloma and elevated parathyroid hormone-related protein.

A patient with multiple myeloma who developed hypercalcemia during three different stages of his disease, with a different hypercalcemic agent elevated in his serum on each occasion, is described. The initial episode of hypercalcemia was associated with high serum interleukin-6 (IL-6). After treatment for myeloma normocalcemia was achieved. Subsequently, a relapse of hypercalcemia occurred, this time characterized by frankly elevated plasma parathyroid hormone-related protein (PTHrP) but normal IL-6. Monotherapy with pamidronate infusions resulted in remission of the hypercalcemia and a significant fall in PTHrP levels. A third spell of hypercalcemia characterized by an acute rise in serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to abnormally high levels occurred during the summer season after prolonged and intense exposure to the sun.