Frontal assessment battery scores and non-motor symptoms in parkinsonian disorders.

Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score ≤ 23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score ≤ 3.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p ≤ 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (ß ≤ -0.16) and age with all FAB items but prehension behavior (ß ≤ -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (ß = -0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients.

Reproductive factors and Parkinson's disease: a multicenter case-control study.

BACKGROUND: The objective of this study was to evaluate the possible association between endogenous and exogenous estrogens and Parkinson's disease (PD). METHODS: The FRAGAMP study is a large Italian multicenter case-control study. PD was diagnosed according to Gelb's criteria. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Adjusted ORs and 95% CIs were estimated using multivariate analysis (logistic regression). RESULTS: Two hundred PD women (mean age, 68.0 ± 9.5 years) and 299 control women (mean age, 61.8 ± 9.9 years) were enrolled in the study. Age at menarche, age at menopause, fertile life duration, cumulative duration of pregnancies, hormone replacement therapy, and surgical menopause were not significantly associated with PD. Multivariate analysis showed a significant positive association between use of oral contraceptives and PD, with an adjusted OR of 3.27 (95% CI, 1.24-8.59; P = .01). CONCLUSIONS: Our data suggest that oral contraceptives could increase the risk of PD.

Voluptuary habits and clinical subtypes of Parkinson's disease: the FRAGAMP case-control study.

We evaluated the possible association between smoking, coffee drinking, and alcohol consumption and Parkinson's disease (PD). The FRAGAMP study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Adjusted ORs were estimated using unconditional logistic regression. Smoking, coffee, and alcohol consumption were also considered as surrogate markers of lifestyle and analysis was carried out considering the presence of at least one, two, or three factors. This latter analysis was separately performed considering Tremor-Dominant (TD) and Akinetic-Rigid (AR) patients. Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. Multivariate analysis showed a significant negative association between PD and cigarette smoking (OR 0.51; 95%CI 0.36-0.72), coffee drinking (OR 0.61; 95%CI 0.43-0.87) and wine consumption (OR 0.62; 95%CI 0.44-0.86); a significant trend dose-effect (P < 0.05) has been found for all the factors studied. We have also found a trend dose-effect for the presence of at least one, two or three factors with a greater risk reduction (83%) for the presence of three factors. However, a different strength of association between TD and AR was found with a greater risk reduction for the AR patients. We found a significant inverse association between PD smoking, coffee, and alcohol consumption. When analysis was carried out considering the association of these factors as possible surrogate markers of a peculiar lifestyle the association was stronger for the AR phenotype.

Characterization of thyroglobulin epitopes in patients with autoimmune and non-autoimmune thyroid diseases using recombinant human monoclonal thyroglobulin autoantibodies.

CONTEXT: Thyroglobulin (Tg) epitopes of serum Tg autoantibodies (TgAb) have been characterized using inhibition of Tg binding by human monoclonal TgAb in autoimmune thyroid diseases (AITD) [Hashimoto's thyroiditis (HT) and Graves' disease (GD)] but not in non-AITD [nontoxic multinodular goiter (NTMG) and papillary thyroid carcinoma (PTC)]. OBJECTIVE: Our objective was to compare Tg epitopes of serum TgAb from patients with AITD, non-AITD, and PTC associated with histological thyroiditis (PTC-T) using inhibition of Tg binding by four recombinant human TgAb-Fab (epitopic regions A-D). DESIGN: Inhibition of Tg binding of 24 HT, 25 GD, 19 NTMG, 15 PTC, and 25 PTC-T TgAb-positive sera by each TgAb-Fab was evaluated in ELISA. Inhibition by the pool of the four TgAb-Fab was evaluated using labeled Tg. RESULTS: Levels of inhibition were different for TgAb-Fab regions A (P = 0.001), B (0.007), and D (0.011). Inhibition by region A TgAb-Fab was significantly higher in HT, GD, and PTC-T than in NTMG and PTC patients. Inhibition levels by region B TgAb-Fab were significantly higher in HT compared with NTMG and PTC patients and in GD compared with NTMG patients. Inhibition by D region TgAb-Fab was significantly lower in NTMG than in the other groups. Inhibition by the pool ranged from 44% (NTMG) to 72% (GD). CONCLUSIONS: The pattern of Tg recognition is similar when HT patients are compared to GD and NTMG to PTC patients and differs when AITD are compared with non-AITD patients. In PTC-T patients, it is similar to that of AITD patients.

Thyroid autoantibodies and thyroid function in subjects exposed to Chernobyl fallout during childhood: evidence for a transient radiation-induced elevation of serum thyroid antibodies without an increase in thyroid autoimmune disease.

CONTEXT: An increase in the prevalence of thyroid autoantibodies (ATAs) was reported 6-8 yr after the Chernobyl accident in radiation-exposed children and adolescents. OBJECTIVE: Our objective was to reassess the effects of childhood radiation exposure on ATAs and thyroid function 13-15 yr after the accident. DESIGN AND SETTING: We measured the antithyroglobulin (TgAbs) and antithyroperoxidase (TPOAbs) antibodies and TSH in 1433 sera collected between 1999 and 2001 from 13- to 17-yr-old adolescents born between January 1982 and October 1986 in paired contaminated and noncontaminated villages of Belarus, Ukraine, and Russia. A total of 1441 sera was collected from age- and sex-matched controls living in Denmark and Sardinia (Italy). Free T(4) and free T(3) were measured when TSH was abnormal. RESULTS: TPOAb prevalence was higher in contaminated than in noncontaminated Belarusian children (6.4 vs. 2.4%; P = 0.02) but lower than previously reported (11%) in a different contaminated Belarus village. No difference in TPOAb prevalence was found in Ukrainian and Russian villages. TgAbs showed no difference between contaminated and noncontaminated Belarus and Ukraine, whereas in Russia they showed a relative increase in the exposed subjects with respect to the unexposed, who showed an unexpectedly lower prevalence of TgAbs. Besides radiation exposure, female gender was the only variable significantly correlated with ATAs in all groups. ATA prevalence in nonexposed villages of Belarus, Ukraine, and Russian Federation did not differ from that found in Sardinia and Denmark. With few exceptions, thyroid function was normal in all study groups. CONCLUSIONS: TPOAb prevalence in adolescents exposed to radioactive fallout was still increased in Belarus 13-15 yr after the Chernobyl accident. This increase was less evident than previously reported and was not accompanied by thyroid dysfunction. Our data suggest that radioactive fallout elicited a transient autoimmune reaction, without triggering full-blown thyroid autoimmune disease. Longer observation periods are needed to exclude later effects.

Curcumin protects Leydig cells of mice from damage induced by chronic alcohol administration.

BACKGROUND: It is known that alcohol consumption inhibits testosterone production and causes testicular atrophy. Curcumin is a phytochemical characterized by anti-inflammatory and antioxidant properties. It was also observed that curcumin protects the liver, pancreas, and nervous system from the toxic effects of alcohol consumption. The goal of this study was to determine if curcumin protects the Leydig cells of mice from chronic alcohol administration. MATERIAL/METHODS: Fifteen mice were treated daily for four weeks with a 3.0 g/kg of a 25% solution of alcohol. Fifteen mice received curcumin (80 mg/kg) added to the same alcohol solution. Fifteen mice were treated with a solution of maltose dextrins isocaloric to ethanol. Fifteen untreated mice were used as controls. RESULTS: In the alcohol-fed mice, numerous Leydig cells showed cytoplasmic rarefaction and increased diameter of the mitochondria. Several mitochondria had diameters three or more times larger than that of mitochondria from control mice. Numerous necrotic Leydig cells were observed. Testosterone plasma levels significantly decreased in comparison with control mice. In alcohol plus curcumin-treated mice the number of necrotic Leydig cells was reduced compared with alcohol-fed mice; the diameters of the mitochondria were significantly decreased. Testosterone plasma levels were not significantly different from those of the controls. CONCLUSION: This study demonstrates that curcumin exerts efficacious protection against damages caused in the Leydig cells of mice by chronic alcohol ingestion and that the preservation of mitochondrial structure and size in Leydig cells is a specific effect of curcumin.

RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center.

BACKGROUND: Germline RET gene mutations are causative of multiple endocrine neoplasia (MEN) 2 and may be identified by genetic screening. Three different syndromes are distinguished: MEN 2A, when medullary thyroid carcinoma (MTC) is associated with pheochromocytoma and/or parathyroid adenomas; MEN 2B, when accompanied by a marfanoid habitus and/or pheochromocytoma; and familial medullary thyroid carcinoma (FMTC), when only MTC is present. PATIENTS AND METHODS: During the last 13 yr, we performed RET genetic screening in 807 subjects: 481 with apparently sporadic MTC, 37 with clinical evidence of MEN 2, and 289 relatives. Genomic DNA was extracted from the blood of all subjects, and exons 10, 11, 13, 14, 15, and 16 were analyzed by direct sequencing after PCR. RESULTS: We unexpectedly discovered a germline RET mutation in 35 of 481 (7.3%) apparently sporadic MTC patients. A germline RET mutation was also found in 36 of 37 patients with clinical evidence of hereditary MTC. The distribution of RET mutations in cysteine and noncysteine encoding codons was significantly different in the two groups of patients, with the prevalence of RET mutations in noncysteine codons being higher in MTC that presented as apparently sporadic (P < 0.0001). A total of 34 FMTCs (75.5% of all FMTC) arrived with apparent sporadic MTC, with no familial history of other MTC cases. According to genetic screening and clinical data, our 72 families were classified as follows: 45 FMTC (62.5%), 22 MEN 2A (30.5%), and five MEN 2B (7%). CONCLUSIONS: In this large series of MTC, hereditary forms, mainly FMTC, were clinically unsuspected in 7.3% of apparently sporadic cases. As a consequence, the prevalence of FMTC in our series is higher than that previously reported (60 vs. 10%). In these cases, RET mutations were more prevalently located in noncysteine codons. Data derived from our series helped elucidate the role of RET genetic screening for the identification of all forms of MEN 2, and especially for FMTC, which are frequently clinically misdiagnosed as nonheritable, sporadic cases.

Prevalence and functional significance of antipituitary antibodies in patients with autoimmune and non-autoimmune thyroid diseases.

BACKGROUND: Circulating antipituitary antibodies (APA) are markers of autoimmune hypophysitis, which may cause deficient pituitary function. The prevalence of APA in autoimmune thyroid disorders (AITD) is uncertain. OBJECTIVES: The aims of this study were 1) to evaluate APA prevalence in a large series of patients with AITD and non-AITD and 2) to investigate the functional significance of APA by assessing pituitary function in APA-positive patients. DESIGN AND SETTING: We conducted a health survey on consecutive AITD and non-AITD patients at a tertiary referral center (Department of Endocrinology, Pisa). PATIENTS: Subjects, including 1290 consecutive patients with thyroid disorders (961 AITD and 329 non-AITD) and 135 controls, were enrolled in the study. METHODS: APA (indirect immunofluorescence), free T(4), free T(3), TSH, and organ-specific autoantibodies were assayed in all patients. Functional pituitary evaluation was performed in most APA-positive patients. RESULTS: APA frequency was higher in AITD (11.4%) than in non-AITD (0.9%; P < 0.0001) patients; all control subjects had negative APA tests. APA were more frequently found in Hashimoto's thyroiditis (13%) than in Graves' disease (7.1%; P = 0.05). Of 110 APA-positive AITD patients, 20 (18.2%) had autoimmune polyglandular syndrome, whereas 90 (81.8%) had apparently isolated AITD. APA positivity increased percentage of autoimmune polyglandular syndrome in our series from 10.4 to 13.5%. Of 110 APA-positive patients, 102 were submitted to dynamic testing for functional pituitary assessment; 36 patients (35.2%) had mild or severe GH deficiency (GHD). No additional anterior pituitary hormone deficiencies were found; one patient had central diabetes insipidus. Pituitary abnormalities at magnetic resonance imaging were found in most APA-positive GHD patients. CONCLUSIONS: APA are frequently present in patients with AITD. Patients should be tested for APA because positive tests are associated with GHD.

The reduction of bone mineral density in postmenopausal women with primary hyperparathyroidism is higher in the presence of concomitant GH secretion impairment.

OBJECTIVE: To investigate, in a large group of postmenopausal primary hyperparathyroidism (PHP) women, whether the concomitance of GH deficiency (GHD) may contribute to the development of changes in bone mineral density (BMD). DESIGN: GH secretion, bone status and metabolism were investigated in 50 postmenopausal women with PHP and in a control group of 60 women with no evidence of PHP, matched for age, age at menopause and body mass index (BMI). METHODS: GH response to growth hormone-releasing hormone (GHRH)+arginine (Arg), femoral neck BMD (g/cm2) by dual energy X-ray absorptiometry, BMI, serum-ionized calcium, parathyroid hormone (PTH) and markers of bone remodelling were evaluated in all patients and controls. RESULTS: Among PHP patients, GH secretion was reduced (8.8 +/- 4.2 microg/l, range 1.1-16.5 microg/l) in 34 patients and normal (28.7 +/- 11.8 microg/l, range 17.9-55.7 microg/l) in the remaining 16 (P < 0.05), no women in the control group had GHD (peak GH 33.8 +/- 10.9 microg/l, range 21.7 +/- 63.2 microg/l). Osteoporosis (T-score < - 2.5) and osteopenia (T-score > -2.5 and < -1) were found in 73.5 and 17.6% of GHD patients, in 37.5 and 43.7% of patients with normal GH secretion and 3.1 and 27% of controls. T-score and BMD were not correlated with ionized calcium, age, age at menopause, BMI, GH peak and IGF-I but were correlated with serum PTH levels in both groups. T-score was correlated with serum levels of markers of bone remodelling only in PHP patients with GHD. CONCLUSIONS: Concomitant impairment of GH secretion may play a pathogenetic role in the occurrence of changes in bone mass observed in PHP and contribute to make them more severe.

Influence of human body composition on serum peak thyrotropin (TSH) after recombinant human TSH administration in patients with differentiated thyroid carcinoma.

OBJECTIVES: In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. PATIENTS: We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. RESULTS: The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. CONCLUSIONS: With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.

Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.

BACKGROUND: The development of antibodies to thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone (TSH) receptor is a main feature of autoimmune thyroid diseases. OBJECTIVE: To investigate whether complete removal of thyroid antigens results in the abatement of humoral thyroid autoimmunity. DESIGN: Retrospective chart review study of patients treated and monitored with a standard prospective protocol. SETTING: University hospital in Pisa, Italy, between 1976 and 1994. PATIENTS: 182 patients with differentiated thyroid carcinoma and serum antibodies to thyroid peroxidase, thyroglobulin, or TSH receptor due to coexistent clinical Hashimoto thyroiditis, Graves disease, or focal autoimmune thyroiditis. INTERVENTION: Total thyroidectomy and radioiodine treatment to ablate residual or metastatic thyroid tissue. Regular follow-up with iodine-131 whole-body scanning and serum thyroglobulin measurement. Mean follow-up (+/-SD) was 10.1 +/- 4.1 years (range, 4 to 20 years). MEASUREMENTS: Serum antibodies to thyroid peroxidase, thyroglobulin, and TSH receptor. RESULTS: Thyroid peroxidase, thyroglobulin, and TSH-receptor antibodies progressively disappeared after the initial treatment. The median disappearance time was 6.3 years for thyroid peroxidase antibodies and 3.0 years for thyroglobulin antibodies. There was a statistically significant correlation between the disappearance of thyroid tissue and that of thyroid antibodies. The coexistence of Hashimoto thyroiditis or Graves disease with thyroid cancer did not modify the pattern of disappearance of thyroid antibody compared with patients with focal autoimmune thyroiditis. CONCLUSIONS: Complete ablation of thyroid tissue with its antigenic components results in the disappearance of antibodies to all major thyroid antigens, thus supporting the concept that continued antibody production depends on the persistence of autoantigen in the body.

Low specificity of blood thyroglobulin messenger ribonucleic acid assay prevents its use in the follow-up of differentiated thyroid cancer patients.

Thyroglobulin (Tg) is a glycoprotein specifically synthesized by follicular thyroid epithelium. After thyroidectomy and remnant (131)I ablation, serum Tg is a specific and sensitive marker for the presence of thyroid cancer tissue, and its measurement is fundamental in the follow-up of patients affected by differentiated thyroid carcinomas (DTCs), being even more sensitive than diagnostic whole-body scan. Unfortunately, serum Tg measurement becomes useless in approximately 15-25% of DTC cases who are positive for anti-Tg antibodies that interfere with the Tg measurement. In these cases, Tg mRNA measurement has been proposed as an alternative to serum Tg determination. The aim of this study was to verify the sensitivity and specificity of Tg mRNA measurement, performed by quantitative real-time RT-PCR, in a series of 100 subjects (80 DTC patients and 20 controls). From our data, the sensitivity and the specificity of the blood Tg mRNA measurement are 82.3 and 24.2%, respectively, with a positive predictive value and a negative predictive value of 65.6 and 43.7%, respectively. The comparison of the Tg mRNA with the serum Tg, measured by both chemiluminescent and ultrasensitive ELISA methods, confirmed the low specificity of the Tg mRNA assay. The hypothesis that Tg mRNA detectable levels could be predictive of future recurrences is not supported by the long follow-up (median, 7 yr; range, 3-29 yr) of our disease-free patients, who did not develop any recurrences in their clinical history. Moreover, nine disease-free patients, who showed positive levels of Tg mRNA (11.8-336 pg equivalents/ micro g RNA), were confirmed to be serum Tg free, both in basal conditions and after recombinant human TSH stimulation, 4 yr after the Tg mRNA detection. In conclusion, we demonstrated that the Tg mRNA assay is of poor utility in the follow-up of DTC patients. On the contrary, serum Tg measurement is a very sensitive and specific thyroid tumor marker, and we recommend that the follow-up of patients affected by DTC must be performed using serum Tg rather than blood Tg mRNA measurement.

Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders.

The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules.

Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study.

Amiodarone-induced thyrotoxicosis (AIT) may occur either in the presence of underlying thyroid disease (type I AIT) or in apparently normal thyroid glands (type II AIT). Type II AIT, a destructive thyroiditis, often favorably responds to glucocorticoids. Iopanoic acid (IopAc) is an iodinated cholecystographic agent that inhibits deiodinase activity and reduces the conversion of T(4) toT(3). It has recently been reported that cholecystographic agents restore euthyroidism in patients with type II AIT. We describe the results of a prospective randomized study conducted in 12 patients with type II AIT treated with either iopanoic acid (group A, n = 6) or glucocorticoids (group B, n = 6). Serum free T(3) levels normalized rapidly in both groups after 7 d, from 0.75 +/- 0.20 ng/dl (11.5 +/- 3.1 pmol/liter) to 0.46 +/- 0.10 ng/d (7.1 +/- 1.7 pmol/liter), P < 0.01, and from 0.58 +/- 0.10 ng/dl (9.0 +/- 1.2 pmol/liter) to 0.34 +/- 0.03 ng/dl (5.2 +/- 0.5 pmol/liter), P < 0.003, in groups A and B, respectively (P = NS). Serum free T(4) levels reduced at 6 months in group B [from 2.70 +/- 0.32 ng/dl (35.1 +/- 4.1 pmol/liter) to 1.0 +/- 0.04 ng/dl (13.4 +/- 0.6 pmol/liter), P < 0.0001] but not in group A (from 2.90 +/- 0.6 ng/dl (38.0 +/- 7.5 pmol/liter) to 2.30 +/- 0.4 ng/dl (35.6 +/- 6.1 pmol/liter, P = 0.39; P = 0.005 group B vs. group A). All patients in both groups became euthyroid and had their amiodarone-induced destructive thyroiditis cured as defined by normalization of both serum free T(4) and free T(3) levels, during both drugs therapy. However, patients in group B were cured more rapidly than patients in group A (43 +/- 34 d vs. 221 +/- 111 d, respectively, P < 0.002). This study shows that, albeit both drugs are effective, glucocorticoids are probably the drug of choice for more rapidly curing type II AIT.

Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism.

Subclinical hypothyroidism of chronic autoimmune thyroiditis must be distinguished from the rare condition of thyroid resistance to TSH in which variable degrees of congenital insensitivity of the thyroid to a biologically active TSH molecule are present. We studied 42 subjects with slight to moderate elevations of circulating TSH and normal free thyroid hormone levels in whom the diagnosis of autoimmune thyroid disease had been excluded using the best of the currently available laboratory and instrumental techniques. In three families (A, B, and C), which included 8 of the 42 cases, other members besides the propositus were found to have isolated hyperthyrotropinemia. The entire coding regions of the TSH receptor (TSHr) gene were sequenced, and TSHr mutations were found in five subjects from families A and B. No mutations were identified in the two members of family C, in one member of family A, and in the 34 remaining cases of isolated hyperthyrotropinemia. A previously described P162A mutation was found in the proband (homozygous state), the son, and the mother of family A (both in the heterozygous state). A new inactivating heterozygous mutation was found in the proband and the mother of family B and consisted of the substitution of a leucine in place of a highly conserved proline at position 252 (L252P) in the extracellular portion of the TSHr. After transfection in COS-7 cells, the mutant L252P displayed a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production. A structural defect of the mutant TSHr protein was probably responsible for the poor routing of the receptor to the cell membrane. In conclusion, in two of three families, but in none of 34 sporadic cases of isolated hyperthyrotropinemia, inactivating mutations of the TSHr were identified. The question of whether the latter cases represent subtle forms of autoimmune thyroiditis or might bear as yet unidentified genetic defects remains a matter of future studies.

Improvement of growth hormone deficiency in patients with primary hyperparathyroidism after parathyroidectomy: results of a prospective study.

GH secretion is impaired in most patients with primary hyperparathyroidism (PHP), although the secretion of the other anterior pituitary hormones is unaffected. However, whether restoration of euparathyroidism is associated with reversal of GH deficiency in PHP patients is not known. To address this issue, we studied 30 consecutive patients with PHP due to a single parathyroid adenoma before and after parathyroidectomy. GH secretion was evaluated by peak serum GH after the maximal GHRH + arginine (Arg) stimulation test. A group of 35 age- and sex-matched normal subjects served as controls. Serum IGF-I concentration was below the normal age- corrected values in six of 30 patients before surgery and in four of 30 patients after parathyroidectomy (P = not significant). Mean serum peak GH values after the GHRH + Arg test were 17.5 +/- 2.8 micro g/liter before surgery and 23.8 +/- 2.5 micro g /liter after surgery (P = 0.0008). The GH response to the GHRH + Arg test was reduced in 20 (67%) and normal in 10 (33%) of 30 PHP patients at baseline; after surgery, 22 of 30 (73%) PHP patients had a normal GH response to the GHRH + Arg test, and only eight (27%) had an impaired GH secretion (P < 0.02). In conclusion, this study confirms that GH secretion is impaired in PHP patients and indicates that it is reversed in many patients after parathyroidectomy. Accordingly, GH deficiency in PHP patients must be considered a functional phenomenon for which GH therapy is not recommended.

Usefulness of salivary cortisol in the diagnosis of hypercortisolism: comparison with serum and urinary cortisol.

OBJECTIVE: Several tests have been proposed to diagnose patients with Cushing's syndrome (CS). The aims of the study were: i) to evaluate the performance of salivary cortisol (SC) in hypercortisolism and ii) to compare SC with serum cortisol (SeC) and urinary cortisol. DESIGN AND PATIENTS: This was a diagnostic study. Twenty-seven patients with untreated Cushing's disease (CD untr), 21 women consuming oral contraceptive pill (OCP), 18 pregnant women, and 89 healthy subjects (controls) were enrolled. METHODS: SC and SeC at baseline and after the low-dose dexamethasone suppression test (LDDST) and urinary free cortisol (UFC) were measured. RESULTS: Midnight SC had a sensitivity of 100% in the CD untr group and a specificity of 97.7% in the controls. Specificity remained high (95.2%) in women taking OCP, while in pregnant women, it decreased to 83.3%. SC after the LDDST showed a sensitivity of 96.3% in the CD untr group; specificity was 97.7% in the controls and 90.5% in OCP women. Midnight SeC had a sensitivity of 100% in the CD untr group. SeC after the LDDST had a sensitivity of 100% in the CD untr group while specificity was 97.7% in the controls and 61.9% in women taking OCP. For UFC, sensitivity was 92.6% in the CD untr group while specificity was 97.7% in the controls and 100% in the OCP group. CONCLUSIONS: SC is a reliable parameter for the diagnosis of severe hypercortisolism, with high sensitivity and specificity. In women during pregnancy or taking OCP, the measurement of SC, identifying the free fraction, could be helpful to exclude CS.

Iodine fortification of vegetables improves human iodine nutrition: in vivo evidence for a new model of iodine prophylaxis.

BACKGROUND: Iodine deficiency is the result of insufficient intake of dietary iodine and as a consequence causes multiple adverse effects. About 2 billion individuals in the world are affected by iodine deficiency. It has been found that the most effective way to control iodine deficiency is through the universal salt iodization. However, salt iodization alone may not be sufficient to assure adequate iodine nutrition. In most industrialized countries, excess consumption of salt has become recognized as a health risk. Therefore, biofortification of vegetables with iodine offers an excellent opportunity to increase iodine intake. AIM AND METHODS: The aim of this study was to test the efficiency of a new model of iodine prophylaxis in a group of 50 healthy volunteers through the intake of vegetables (potatoes, cherry tomatoes, carrots, and green salad) fortified with iodine. Each serving of vegetables consisted of 100 g of potatoes, carrots, tomatoes, or salad containing 45 mg of iodine (30% of the Recommended Daily Allowance), and the volunteers consumed a single serving of vegetables, as preferred, each day for 2 weeks. Urinary iodine (UI) excretion was measured before and after intake of vegetables. RESULTS: The UI concentration measured in volunteers before the intake of vegetables was 98.3 mg/L (basal value), increasing to 117.5 mg/L during the intake of vegetables. Seven days after the discontinuation of vegetable intake, UI was 85 mg/L. UI concentration increment was 19.6% compared with the basal value; therefore, the difference was statistically significant (P = .035). CONCLUSIONS: Biofortification of vegetables with iodine provides a mild but significative increase in UI concentration and, together with the habitual use of iodized salt, may contribute to improve the iodine nutritional status of the population without risks of iodine excess.

Thyroglobulin autoantibodies in patients with papillary thyroid carcinoma: comparison of different assays and evaluation of causes of discrepancies.

CONTEXT: Thyroglobulin autoantibodies (TgAb) have been proposed as a surrogate marker of thyroglobulin in the follow-up of differentiated thyroid carcinoma. Commercially available TgAb assays are often discordant. We investigated the causes of discrepancy. DESIGN: TgAb were measured by three noncompetitive immunometric assays and three competitive RIA in 72 patients with papillary thyroid carcinoma and associated lymphocytic thyroiditis (PTC-T), 105 with papillary thyroid carcinoma and no lymphocytic thyroiditis (PTC), 160 with Hashimoto's thyroiditis, and in 150 normal subjects. The results of the six assays were correlated. TgAb epitope pattern, evaluated by inhibition of serum TgAb binding to thyroglobulin by TgAb-Fab regions A, B, C, and D, were compared in sera which were positive in all six assays (concordant sera) and positive in only one to five assays (discordant sera) were compared. TgAb International Reference Preparation (IRP) was measured in 2007 and 2009. RESULTS: The correlations of the six assays ranged from -0.01 to 0.93 and were higher in PTC-T and Hashimoto's thyroiditis than in PTC and normal subjects. Two uncorrelated components, one including the three immunometric assays, the other the three RIA, explained 40 and 37% of the total variance of the results of the six assays. The levels of inhibition were higher in concordant sera than in discordant sera by TgAb-Fab region B (27.0%, 21.2-34.0 vs. 6.0%, and 2.7-12.7%) and region C (30.5%, 21.3-37.7 vs. 4.0%, and 1.0-6.5%); thus, the epitope pattern was more homogeneous in concordant sera than in discordant sera. TgAb IRP ranged from 157 to 1088 (expected 1000) IU/ml in 2009; results in 2007 were similar in all but two assays. CONCLUSIONS: TgAb assays are highly discordant. Discrepancy is lower when comparing assays with similar methodology. Results of TgAb from PTC-T are more concordant than those from PTC because their epitope pattern is more restricted. The internal standardization of TgAb is generally, but not completely, satisfactory.