Biomedical subjects

C Marcocci

Publications and source records attributed to C Marcocci.

At least 37 records · Page 2Linked to original sources

PubMed2002

GH secretion is impaired in patients with primary hyperparathyroidism.

The activity of the GH/IGF-I axis as a function of parathyroid activity and calcium metabolism in humans has never been assessed. To address this issue, we studied 18 patients (5 men, 13 women; age range, 23-76 yr; mean, 61 yr) with primary hyperparathyroidism (PHP) due to solitary parathyroid adenoma. GH secretion was evaluated by serum IGF-I levels, spontaneous mean GH secretion over two morning hours, and GH response to arginine (ARG) alone or combined with GHRH. In five patients, serum GH concentrations were measured every 20 min for 24 h, and deconvolution analysis was performed. A group of 35 age- and sex-matched normal subjects served as controls. Mean serum IGF-I levels in PHP were lower than in normal controls, and in six PHP patients individual serum IGF-I levels were below the age-related normal range. The mean (+/-SE) peak GH response to ARG alone in PHP patients was significantly lower than in normal subjects (4.0 +/- 1.0 vs. 22.0 +/- 1.3 microg/liter; P < 0.001). Likewise, the mean (+/-SE) peak GH response to ARG plus GHRH was reduced in PHP patients (9.9 +/- 0.9 vs. 38.0 +/- 3.5 microg/liter; P < 0.001). The mean GH concentration over two morning hours in PHP was lower (0.20 +/- 0.05 vs. 1.34 +/- 0.31 microg/liter; P < 0.001). The mean GH concentration over 24 h in five PHP patients was lower than in six normal controls (0.3 +/- 0.1 vs. 0.7+/- 0.1 microg/liter; P < 0.05); the deconvolution analysis showed that 24-h GH production rate (3.0 +/- 1.7 vs. 28.2 +/- 4.7 microg/liter.d; P < 0.05) and mean secretory burst mass (1.2 +/- 0.7 vs. 10.5 +/- 2.6 microg/liter; P < 0.05), but not pulse frequency, were lower in PHP patients than in normal controls. GH half-life and approximate entropy values of 24-h GH profiles were similar in PHP patients and normal controls. No correlation was found between serum-ionized calcium or PTH levels and spontaneous or stimulated GH levels in PHP patients. In conclusion, this study demonstrates that PHP patients have a reduction in both spontaneous and stimulated GH secretion. Accordingly, PHP should be mentioned as a further example of a metabolic condition in which GH secretion in adults is reduced.

Adult↗

PubMed2002

A quick intraoperative parathyroid hormone assay in the surgical management of patients with primary hyperparathyroidism: a study of 206 consecutive cases.

OBJECTIVE: The traditional surgical approach for patients with primary hyperparathyroidism (PHPT) consists of the identification of at least four glands and in the removal of all hyperfunctioning parathyroid tissue. DESIGN: To evaluate whether intraoperative parathyroid hormone (PTH) monitoring will allow a more limited surgical procedure by confirming complete removal of all hyperfunctioning tissue. METHODS: Plasma samples were obtained from 206 consecutive patients with sporadic PHPT before skin incision, during manipulation of a suspected adenoma, and 5 min (T-5) and 10 min after removal of abnormal parathyroid tissue. PTH was measured by a quick immunochemiluminescent assay (QPTH). The operative success was defined by a decrease of PTH greater than 50% of the highest pre-excision value. RESULTS: A >50% decrease of PTH occurred in 203 patients and was evident at T-5 in the majority of cases. All but three had normal serum calcium the day after surgery and afterwards. PTH concentration did not show a >50% decrease in the remaining three cases after completion of surgery. One patients had negative neck exploration and remained hypercalcemic; the other two had normal serum calcium at follow-up. Thus, the intraoperative QPTH correctly predicted the outcome of surgery in 201 patients (97.5%) (200 true positive and 1 true negative), and provided three false positive and two false negative results. CONCLUSIONS: The intraoperative QPTH measurement represents a useful tool to assist the surgeon during parathyroidectomy. It indicates whether all hyperfunctioning parathyroid tissue has been removed, limiting the procedure to a unilateral neck exploration in most cases.

Adult↗

PubMed2001

Increased prevalence of primary hyperparathyroidism in treated breast cancer.

UNLABELLED: Hypercalcemia occurring in patients with advanced breast cancer (BC) is generally due to osteolytic metastases or to the activity of circulating tumor-derived products. In these conditions, the production of endogenous PTH is reduced. The frequency of hypercalcemia due to primary hyperparathyroidism in breast cancer is unknown. We examined the occurrence of primary hyperparathyroidism in a large group of women with treated BC. A total of 100 consecutive women aged 28-80 years with treated breast cancer were enrolled. One hundred and two healthy age-matched women and 60 age-matched female patients with differentiated thyroid carcinoma examined before thyroidectomy were used as controls. Intact serum PTH and serum calcium were measured in all patients and controls. Hypercalcemia associated with elevated serum PTH concentration indicating primary hyperparathyroidism was found in 7 BC patients (7%) and in none of healthy women or patients with thyroid cancer. The pre-operative staging of BC patients with primary hyperparathyroidism was I in six and II in one of them, and no patient had evidence of distant metastases. A parathyroid adenoma was found in all 6 BC patients submitted to neck exploration, one patient refused surgery. Serum calcium and PTH concentrations returned to normal levels after surgery. Two BC patients had increased serum PTH and normal calcium concentrations. One of them had low serum 25-hydroxyvitamin D [25(OH)D]. One patient with spread bone metastases had neoplastic hypercalcemia with undetectable serum PTH concentration. All remaining 90 BC patients had serum calcium and PTH concentrations within normal limits, but their mean (+/-SD) values (9.6+/-0.5 mg/dl for serum calcium, 38.0+/-16.4 mg/dl for serum PTH ) were slightly but significantly greater than in normal controls (9.3+/-0.5 mg/dl, p=0.003 and 27.9+/-10.6 pg/ml, p=0.0001, respectively) and in patients with thyroid cancer (9.2+/-0.6 mg/dl, p=0.001 and 26.2+/-11.0 pg/ml, p=0.001), with no relationship with clinical staging or anti-tumor therapy. IN CONCLUSION: 1) an increased frequency of parathyroid adenoma was found in BC patients with mildly aggressive neoplastic disease; 2) in BC patients with no evidence of primary hyperparathyroidism mean serum PTH and calcium concentrations were significantly greater than in healthy controls and in patients with thyroid carcinoma; and 3) this finding was unrelated to clinical staging or anti-tumor therapy. Thus, primary hyperparathyroidism should be considered as a possible cause of hypercalcemia in patients with non-aggressive breast cancer. We suggest that serum PTH should be determined in all BC patients with increased serum calcium concentration, especially in those with no evidence of metastatic disease.

Adenoma↗

PubMed2001

A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder characterized by hypoparathyroidism, adrenal failure, chronic mucocutaneous candidiasis, and ectodermal dystrophies and other organ-specific autoimmune diseases. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is caused by mutations of the autoimmune regulator gene. We identified an Italian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and a pattern of inheritance suggestive of a dominant mechanism. Serological and clinical studies showed a high prevalence of hypothyroid autoimmune thyroiditis in affected members with classical autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Direct sequencing of the entire coding region of the autoimmune regulator gene revealed the presence in the proband of a novel missense (G228W) mutation in exon 6 in a heterozygous state. The same heterozygous mutation was identified in all family members with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and/or hypothyroid autoimmune thyroiditis. None of the unaffected family members and 50 unrelated Italian controls carried the mutation. In contrast with all other autoimmune regulator mutations reported in families, the novel G228W mutation acts in a dominant fashion in our family, as only one heterozygous mutation was found in the entire coding sequence of the autoimmune regulator gene in the proband. Moreover, analysis of the family tree showed direct transmission of the hypothyroid autoimmune thyroiditis/polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype to the offspring in each generation in the absence of consanguinity, further supporting a dominant inheritance. The G228W closely cosegregated with hypothyroid autoimmune thyroiditis in our family, whereas a low penetrance of the full autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype was observed. In conclusion, we report a novel mutation of the autoimmune regulator gene in a family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, closely cosegregating with hypothyroid autoimmune thyroiditis. The G228W mutation acts in a dominant fashion and may shed light on the structure-function relationship of the autoimmune regulator protein.

Adolescent↗

PubMed2001

Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study.

Eighty-two consecutive patients with moderate-to-severe and active Graves' ophthalmopathy were randomly treated with orbital radiotherapy combined with either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, gender, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine therapy shortly before treatment for Graves' ophthalmopathy. Follow-up lasted for 12 months. A significant reduction in proptosis (from 23.2 +/- 3.0 to 21.6 +/- 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 +/- 1.8 to 21.7 +/- 1.8 mm in oral glucocorticoid group, P < 0.0001) and in lid width (from 13.3 +/- 2.5 to 11.8 +/- 2.2 mm, and from 13.6 +/- 2.0 to 11.5 +/- 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of amelioration of diplopia did not significantly differ between the two groups (P = 0.82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) and only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 +/- 1.2 to 1.7 +/- 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 +/- 1.1 to 2.2 +/- 1.2 (P < 0.0001) in the oral glucocorticoid group; final Clinical Activity Score was significantly lower in iv glucocorticoid than in oral glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorticoid treatment was better tolerated than oral glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv glucocorticoid and 35 (85.4%) oral glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocorticoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associated with orbital radiotherapy) are effective in the management of severe Graves' ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects.

Administration, Oral↗

PubMed2000

Effects of hormonal replacement treatment on bone mineral density and metabolism in hypogonadal patients.

We investigated 22 male patients affected by prepubertal hypogonadism with a mean age of 34.3+/-5.2. A significant reduction of bone mineral density (BMD) at both the lumbar spine (L2-L4, -14%, 1.039+/-0.11 vs. 1.217+/-0.16 g/cm(2), P=0.005) and femoral neck (-11%; 0.927+/-0.09 vs. 1.034+/-0.16 g/cm(2), P=0.01) was found in patients compared to age-matched controls. The mean Z score was -1. 55 for vertebrae and -1.33 for femur. Eleven and nine patients, respectively, had a lumbar and femoral BMD at least 1 S.D. below the normal mean; 8 and 4, respectively, 2 S.D. below. There was a strong positive correlation between BMD and duration of hormone replacement treatment (HRT) for both sites: respectively, r=0.71, P<0.005 for the vertebrae, and r=0.60, P<0.01 for the femur. A weak correlation was also present between onset of HRT and BMD: r=0.6, P<0.01 at the lumbar level, and r=0.47, P<0.05 at the femoral neck.

Adult↗

PubMed2000

Six novel MEN1 gene mutations in sporadic parathyroid tumors.

We report nine mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in sporadic parathyroid adenomas. Six of them have not previously been described: E60X, P32R, 261delA, 934+2T-->G, S443P, and 1593insC. The tissue samples were initially submitted to LOH analysis at 11q13 followed by SSCP screening of LOH-positive samples. Mutations were identified by direct sequencing and subcloning. Three (E60X, P32R, and 261delA) were in exon 2, one (934+2bp) in the splice junction of exon 5, one (S443P) in exon 9, and one (1593insC) in exon 10. The 3 mutations in exon 2 were associated with loss and/or creation of a restriction site. The corresponding germline sequence of the MEN1 gene was normal. Most mutations would likely result in a nonfunctional menin protein, and therefore in the loss of a tumor suppressor protein.

Adenoma↗

PubMed2000

Soluble interleukin-1 receptor antagonist concentration in patients with Graves' ophthalmopathy is neither related to cigarette smoking nor predictive of subsequent response to glucocorticoids.

OBJECTIVE: The aim of the present study was to evaluate serum soluble interleukin-1 receptor antagonist (sIL-1RA) concentration and its relationship with the degree of cigarette smoking in patients with Graves' ophthalmopathy (GO). DESIGN AND SUBJECTS: Twenty-two consecutive GO patients (20 women, two men; age range 25-68 years, mean 48 years; 12 smokers, 10 non-smokers) submitted to IV glucocorticoid pulses over a 3-month period. MEASUREMENTS: sIL-1RA levels were measured by an immunoenzymatic assay (sensitivity, 4 ng/l; normal range, 50-290 ng/l) before glucocorticoid treatment, after two months of therapy, and 3 months after drug withdrawal. RESULTS: Thirteen patients responded to treatment (59%; five smokers and eight non-smokers), nine were non-responders (41%; seven smokers and two non-smokers). Baseline median sIL-1RA concentration did not differ in smokers and non-smokers (222 and 173 ng/l, respectively; P = 0.69). Likewise, no significant differences were found between the two groups during treatment (537 and 389 ng/l, respectively; P = 0.28); sIL-1RA concentration after treatment was higher in smokers (258 vs. 94 ng/l; P = 0.02). There was no correlation between basal sIL-1RA levels and the degree of cigarette smoking. Likewise, there was no difference in sIL-1RA levels in responders and non-responders, either at baseline (186 vs. 216 ng/l; P = 0.83), during or after treatment. CONCLUSION: Our study suggests that circulating soluble interleukin-1 receptor antagonist levels, both at baseline and during glucocorticoid treatment, are neither influenced by cigarette smoking nor predictive of subsequent response to glucocorticoid treatment.

Adult↗

PubMed2000

Contrast-enhanced color Doppler ultrasonography in suspected parathyroid lesions.

PURPOSE: To assess the usefulness of US contrast media in the evaluation of patients with primary hyperparathyroidism, with a nodule showing US features of a primary parathyroid lesion but lacking the color Doppler US appearance of a parathyroid mass. MATERIAL AND METHODS: Thirteen patients (7 female, 6 male; age range 51-79 years) were examined with US before and after administration of a stabilized galactose-based microbubble contrast agent. Ten patients underwent surgery and the final histological examination demonstrated parathyroid adenoma in 9 cases and a mesenchymal benign nodule in 1 case. Three nodules were proved to be of thyroid origin at fine-needle aspiration biopsy. RESULTS AND CONCLUSION: The use of a US contrast agent resulted in a diagnostic gain compared to unenhanced studies in 12/13 cases. Color Doppler findings characteristic of parathyroid lesions were observed in 7/13 cases, of thyroid nodules in 4/13 cases, and nonspecific patterns in 2/13 cases. Contrast-enhanced color Doppler US can be proposed in selected patients in whom unenhanced color Doppler provides uncertain findings. Its ideal application should be the evaluation of cervical lesions without detectable intranodular flow at unenhanced Doppler studies. In these cases, the contrast agent helps in visualizing typical color Doppler signals of the parathyroid lesions ("vascular pole" and "mixed pattern").

Adenoma↗

PubMed2000

Management of Graves' ophthalmopathy: reality and perspectives.

Graves' ophthalmopathy is an debilitating disease impairing the quality of life of affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not satisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal taping of the eyes, prisms) can control symptoms and signs. In severe forms of the disease (3-5%), aggressive measures are required. If the disease is active, high-dose glucocorticoids and/or orbital radiotherapy, or orbital decompression represent the mainstay of treatment. If the disease is severe but inactive, orbital decompression is preferred. Novel treatments such as somatostatin analogs or intravenous immunoglobulins are under evaluation. Rehabilitative (extraocular muscle or eyelid) surgery is often needed after treatment and inactivation of eye disease. Correction of both hyper- and hypothyroidism is crucial for the ophthalmopathy. Antithyroid drugs and thyroidectomy do not influence the course of the ophthalmopathy, whereas radioiodine treatment may cause the progression of preexisting ophthalmopathy, especially in smokers. The exacerbation, however, is prevented by glucocorticoids. In addition, thyroid ablation may prove beneficial for the ophthalmopathy in view of the pathogenetic model relating eye disease to autoimmune reactions directed against antigens shared by the thyroid and the orbit.

Animals↗

PubMed2000

Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with primary hyperparathyroidism.

A reduced expression of calcium-sensing receptor (CaR) messenger ribonucleic acid and protein accompanied by abnormalities in parathyroid cell proliferation and PTH secretion are present in primary hyperparathyroidism. We studied the expression of CaR protein by immunohistochemistry in 36 sporadic parathyroid adenomas and investigated the relationship between CaR expression and several preoperative clinical parameters, including the set-point of Ca(2+)-regulated PTH secretion (measured in vivo). The adenomas were classified in 4 categories according to the intensity of immunohistochemical staining: 5 (14%) showed a CaR staining intensity similar to that of normal parathyroid ( ), 10 (27%) showed moderate staining (++), 16 (45%) showed weak staining (+), and 5 (14%) were negative (-). The intensity of CaR staining was not related to preoperative serum Ca(2+), PTH levels or adenoma volume. Twenty-nine patients underwent preoperatively the calcium infusion test to evaluate the PTH-Ca(2+) set-point. Individual values of PTH-Ca(2+) set-point ranged from 1.38-1.93 mmol/L and were significantly correlated with basal Ca(2+) levels (r = 0.96; P: = 0. 0001) and adenoma volume (r = 0.5; P: = 0.01). The mean PTH-Ca(2+) set-point values were significantly different in the 4 groups of patients classified according to immunohistochemical staining intensity of their adenoma (P: = 0.025; F = 3.78); the mean PTH-Ca(2+) set-point was significantly higher in the groups classified as negative than in those classified as weak or moderate. No correlation was observed between the PTH-Ca(2+) set-point and basal PTH levels or between the percent maximal PTH inhibition and adenoma volume and basal PTH or Ca(2+) levels. In summary, our data suggest that there is a relationship between apparent CaR protein expression and PTH-Ca(2+) set-point abnormality, suggesting that a reduced receptor content might have an important role in the pathogenesis of primary hyperparathyroidism.

Adenoma↗

PubMed1999

Minimally invasive surgery for thyroid small nodules: preliminary report.

Cytological assessment of cold thyroid nodules cannot exclude malignancy in case of follicular tumors. Many follicular nodules undergo surgery although most of them later on prove to be benign. We report a new minimally invasive video-assisted approach (MIVA) for the treatment of thyroid lesions with a diameter minor than 3 cm. Ten females and 2 males (mean age: 37 yr) with a cold thyroid nodule and a cytological diagnosis of microfollicular tumor were selected for MIVA hemythyroidectomy. The procedure was carried out through a 15 mm incision with needlescopic instruments and a 30 infinity 5-mm endoscope. Mean operative time was 87 min (range 60-120). No complications were registered. Cosmetical result was excellent in all patients. MIVA hemythyroidectomy is safe and effective; indications and limits of this new procedure require further studies.

Adult↗

PubMed1999

[Video-assisted parathyroidectomy: a series of 85 cases].

AIM OF THE STUDY: To verify the feasibility of video-assisted parathyroidectomy, set up the indications and report the results in a series of 85 patients. MATERIAL AND METHODS: From 1997 to 1999, 85 patients affected by primary hyperparathyroidism due to single gland disease, with an adenoma smaller than 35 mm as demonstrated by preoperative imaging, were referred for video-assisted parathyroidectomy. There were 62 females and 23 males. Mean age was 53 years, (range 23-82). Video-assisted parathyroidectomy was associated with intra-operative PTH quick-assay. Calcium testing was controlled before leaving the hospital, 1 month and 3 months later, and postoperative laryngoscopy was performed in all patients. RESULTS: There were five conversions to open cervicotomy: three due to a contra-lateral second adenoma, two because of an intrathyroidal adenoma. The mean operative time for video-assisted procedure was 59 minutes (range: 25-180). Circulating PTH levels 10 minutes after the removal of the affected gland(s) always dropped significantly, and pathological report confirmed the parathyroid nature of the specimens (mean diameter 13 mm, range 7-35). Morbidity consisted of five cases of transient hypocalcemia and one permanent laryngeal nerve paralysis. We registered no persistent or recurrent disease (mean follow-up 12.8 months, range 1-28). CONCLUSIONS: Video-assisted parathyroidectomy is feasible, and its results are similar to those of traditional procedure, while it seems superior as regards postoperative course and aesthetic results. It also allows different strategical decisions even during operation (i.e. bilateral exploration or thyroid lobectomy) by the same approach.

Adenoma↗

PubMed1999

The course of Graves' ophthalmopathy is not influenced by near total thyroidectomy: a case-control study.

OBJECTIVE: The relationship between the method of treatment of hyperthyroidism due to Graves' disease and the course of Graves' ophthalmopathy is debated. Antithyroid drug therapy is associated with no change, or even amelioration, of ophthalmopathy. Although controversial, radioiodine may be followed by progression of eye disease, preventable by glucocorticoid administration. Whether thyroidectomy affects the course of ophthalmopathy is uncertain. DESIGN: In a case control study, the course of non-severe Graves' ophthalmopathy after thyroidectomy was investigated and the results compared with those observed in patients treated with methimazole. PATIENTS: Thirty patients with Graves' hyperthyroidism and non-severe/absent ophthalmopathy were treated with near-total thyroidectomy (Group 1, Tx), after achievement of euthyroidism with methimazole. After surgery, all patients started levothyroxine replacement therapy. Sixty patients treated with methimazole, matched for age, sex, duration of hyperthyroidism, degree of ocular involvement and smoking habits, were used as controls (Group 2, MMI). MEASUREMENTS: Patients were seen every 1-2 months for 12 months for thyroid tests and ocular evaluation. RESULTS: In Group 1, ocular parameters did not change in 17 of 18 patients with pre-existing ophthalmopathy, and in 12 patients without ophthalmopathy. Eye manifestations worsened only in one (3.3%) patient with pre-existing ophthalmopathy. In Group 2, ocular parameters did not change in 58 patients (33 with, and 25 without ophthalmopathy), while new ophthalmopathy occurred in two without pre-existing eye disease. One of the 30 patients treated by surgery (3.3%) had permanent hypoparathyroidism. CONCLUSIONS: Treatment of Graves' hyperthyroidism with near-total thyroidectomy in patients with non-severe or absent pre-existing ophthalmopathy is not associated in the short term with significant effects on the course of ophthalmopathy.

Adult↗

PubMed1999

Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study.

BACKGROUND: Several studies demonstrated the feasibility of minimally invasive parathyroidectomy as a treatment for primary hyperparathyroidism. We compared its results with those of traditional surgery in a prospective randomized study. METHODS: From March to November 1998, 38 patients eligible for video-assisted parathyroidectomy (VAP) were referred to us. They were randomly divided into 2 groups: patients of group A underwent a conventional cervicotomy with bilateral exploration and frozen section of the removed adenoma; patients of group B underwent VAP with intraoperative measurement of parathyroid hormone. Operative time, postoperative pain, fever and hypocalcemia, cosmetic result, and costs were compared. Two cases of VAP were performed with locoregional anesthesia. RESULTS: Groups A (18 patients) and B (20 patients) were statistically balanced. Operative time was significantly shorter in group B (57 vs 70 minutes). Cosmetic result was significantly better in group B, which also experienced less postoperative pain (P < .05). No cases of persistent primary hyperparathyroidism were present in either group, but recurrent laryngeal nerve palsy occurred in 1 patient in group B. CONCLUSIONS: Compared with conventional surgery, VAP is associated with a shorter operative time, a better cosmetic result, and a less painful postoperative course.

Adult↗

PubMed1999

No evidence for mutations in the calcium-sensing receptor gene in sporadic parathyroid adenomas.

Inactivating mutations of the calcium-sensing receptor gene (CaR) might explain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A protection assay, no mutations were identified in a series of parathyroid specimens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and directly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change (Ala826Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrelated subjects. Loss of heterozygosity studies were also performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated. In conclusion, our results extend previous observation and suggest that clonal somatic mutations of the CaR gene and allelic loss at the CaR locus on chromosome 3q do not play a major role in the pathogenesis of sporadic parathyroid tumors.

Adenoma↗

PubMed1999

A new mutation of the MEN1 gene in an italian kindred with multiple endocrine neoplasia type 1.

OBJECTIVE: To report a new mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in an Italian kindred. DESIGN: The study included the female proband, aged 50 years, affected by primary hyperparathyroidism, insulinoma and prolactinoma, and ten relatives. Blood samples were obtained for biochemical and genetic analyses. Clinical screening tests included serum glucose, ionized calcium, intact parathyroid hormone, GH, insulin and prolactin. The coding sequence, including nine coding exons and 16 splice sites, was amplified by PCR and directly sequenced. RESULTS: Two additional cases of primary hyperparathyroidism were identified among the paternal family members. The sequence analysis showed a heterozygous T to C transition at codon 444 in exon 9, resulting in a leucine to proline substitution (L444P) in the patient and in the two paternal family members with primary hyperparathyroidism. The L444P amino acid change was absent in 50 normal subjects. The mutation determined the loss of a BlnI restriction site of the wild-type sequence and the creation of a new restriction EcoRII site. The patient, but not her paternal affected relatives, also had a common heterozygous polymorphism (D418D) in exon 9. CONCLUSIONS: A new MEN1 mutation (L444P) in exon 9 has been identified; this substitution caused the loss of a BlnI restriction site and the creation of a new EcoRII site.

Antisense Elements (Genetics)↗

PubMed1999

Graves' ophthalmopathy and 131I therapy.

Graves' ophthalmopathy is an autoimmune process initiated and maintained by antigen(s) shared by the thyroid and the orbit. A matter of argument concerns the choice of the method of treatment for Graves' hyperthyroidism when clinically evident ophthalmopathy is present. Restoration of euthyroidism appears to be beneficial for ophthalmopathy. On the other hand the continuing disease activity associated with the recurrence of hyperthyroidism appears to adversely affect the course of ophthalmopathy. For these reasons it is our opinion that in patients with Graves' hyperthyroidism and ophthalmopathy the permanent control of thyroid hyperfunction by ablation of thyroid tissue should be obtained by radioiodine therapy or thyroidectomy. The rationale for an ablative strategy is the following: i) permanent control of hyperthyroidism avoids exacerbations of eye disease associated with recurrence of hyperthyroidism; ii) hypothyroidism, which follows thyroid tissue ablation, should be regarded as a therapeutic end point rather than as an undesirable result; iii) ablation of thyroid tissue may result in the removal of both the thyroid-orbit cross-reacting antigen(s) and the major source of thyroid-autoreactive lymphocytes. The relationship between radioiodine therapy and the course of GO is a matter of controversy, and some authors have suggested that radioiodine administration may be associated with a worsening of preexisting ophthalmopathy. This was not observed when radioiodine treatment was associated with a 3-month oral course of prednisone. The development or progression of GO after radioiodine therapy might be due to the release of thyroid antigens following radiation injury and to subsequent exacerbations of autoimmune reactions directed towards antigens shared by the thyroid and the orbit. The view that radioiodine therapy may be associated with a progression of ophthalmopathy is not shared by some authors who claim that the apparent link between progression of ophthalmopathy and radioiodine therapy might simply be coincidental, reflecting the natural history of the disease. The radioiodine-associated exacerbation of eye disease might be used as an argument against the use of radioiodine therapy in patients with ophthalmopathy. We do not share this view, since the outward effects of radioiodine on eye disease can easily be prevented by concomitant administration of glucocorticoids. Glucocorticoid treatment should be limited, in our opinion, to patients with clinically evident eye disease and to those without ophthalmopathy but with other known risk factors, such as smoking.

Graves Disease↗