Giovanni Lupoli

Familial papillary thyroid microcarcinoma: a new clinical entity

BACKGROUNDnFamilial, non-medullary thyroid carcinoma is clinically more aggressive than the sporadic form. We wanted to find out whether papillary thyroid microcarcinoma also occurs in a familial pattern, and, if so, to identify specific clinical and prognostic features.nnnMETHODSnWe reviewed the clinical records of 119 patients with papillary thyroid microcarcinoma. Familial occurrence, together with clinical presentation, surgical treatment, pathological characteristics, and follow-up were recorded.nnnFINDINGSnWe identified a family history of thyroid carcinoma in seven patients. The tumour was multifocal in five patients, bilateral in three, and vascular invasion occurred in three of the seven patients. Lymph-node metastases were found in four patients. Three patients had a recurrence and one patient with pulmonary metastases died within 11 months.nnnINTERPRETATIONnWe identified familial occurrence in 5.9% of cases of papillary thyroid microcarcinoma. The unfavourable behaviour in the familial form of papillary thyroid microcarcinoma suggests that radical treatment and careful follow-up are warranted.

Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer

Skeletal metastases from thyroid cancer are poorly responsive to medical or radioiodine treatment. Bone destruction in skeletal metastases results from osteoclast-induced bone resorption. Therefore, a new approach in the therapy of bone metastases consists in using aminobisphosphonates, such as pamidronate, which are potent inhibitors of osteoclastic activity. In the present study, 10 thyroid cancer patients with painful osteolytic bone metastases were administered pamidronate (90u2009mg, as a 2 hour intravenous infusion) monthly for 12 consecutive cycles. Bone pain, quality of life, performance status, analgesic consumption and disease staging were evaluated before and during the trial. The patients who had been administered pamidronate showed a significant decrease in bone pain (P = 0.0052). Performance status improved nearly significantly (P = 0.051), while the quality of life showed a remarkable amelioration. However, no significant decrease in analgesic consumption was recorded. Partial radiographic response of bone lesions was observed in 2/10 patients. The side effects of pamidronate were mild and transient. In conclusion, monthly infusion of pamidronate is a well-tolerated treatment that induces significant relief from bone pain and improves the quality of life of thyroid cancer patients with symptomatic and osteolytic bone metastases.

Percutaneous Ethanol Injection Efficacy in the Treatment of Large Symptomatic Thyroid Cystic Nodules: Ten-Year Follow-Up of a Large Series

We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment of a large series of symptomatic thyroid cystic nodules (STCN). Ninety-eight patients (72 females and 26 males) were treated. The mean basal volume of the STCN was 35.3 mL. In 92 of 98 patients PEI treatment induced a greater than 50% nodule shrinkage, only 6 of 92 responder patients relapsed at a follow-up of 9 years. Moreover, all the patients had a significant clinical benefit because a significant reduction of the cyst-associated symptoms was recorded. Furthermore, a limited number of sessions was required for the treatment of cysts larger than 40 mL (mean +/- standard deviation [SD]: 2.7 +/- 0.75) demonstrating the feasibility of the procedure also in the treatment of large cysts. In conclusion, PEI is an effective and inexpensive procedure with a high patient compliance and long-lasting effects in the treatment of cysts larger than 40 mL.

Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy

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

Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas

Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.

Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: A longitudinal study

Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce thyroid alterations. In this longitudinal study the thyroid function was investigated during lithium treatment over a period of 12 months in 12 euthymic bipolar patients with a normal thyroid function and absence of thyroid antibodies. Nine of the 12 patients were further studied on the 15th month, 5 of these 9 on the 18th month and 4 of the last-mentioned 5 on the 24th month. The mean basal and TRH-stimulated TSH values during lithium therapy were significantly higher as compared to those at the beginning of the treatment. More particularly, during lithium therapy, a significant increase of basal TSH over the normal range was found in 10 out of the 12 patients. A rise of TRH-stimulated TSH was found in 11 out of the 12 patients. The impairment of the hypothalamic-pituitary-thyroid (HPT) axis was transitory in the majority of cases. Two patients developed a nodular goiter during the treatment. Plasma T3, T4, FT3 and FT4 levels did not change during the treatment. Thyroid antibodies remained undetectable. The conclusions of the study are twofold: 1) Subclinical hypothyroidism during lithium therapy is much more frequent than previous cross-sectional studies suggest; 2) Thyroxine replacement in lithium-treated patients is advisable in order to prevent subclinical hypothyroidism and the risk of a subsequent goiter.

Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment.

After prolonged treatment (76.4±10 and 70.1±12.3 months, respectively) (mean± SE) with testosterone enanthate (250 mg im every 3 weeks), bone mineral density (BMD) and bone metabolism were evaluated in 12 patients (aged 29.3±1.4 yr) affected by idiopathic hypogonadotropic hypogonadism (IHH), in 8 patients (29.6±2.6 yr) affected by Klinefelter’s syndrome (KS), and in 10 healthy men (30.6±1.7 yr) matched according to age and BMI. Spinal BMD in IHH was significantly lower than in controls (0.804±0.04 vs 1.080±0.01 g/cm2; p<0.001), while there was no difference in neck BMD (0.850±0.01 vs 0.948±0.02 g/cm2). Neither spinal (0.978±0.05 g/cm2) nor neck (0.892±0.03 g/cm2) BMD in KS were significantly different from controls. Six IHH and one KS subjects were osteoporotic, while 6 IHH and 2 KS subjects were osteopenic. A significant inverse correlation was found between spinal BMD and age at the treatment onset in IHH (r=−0.726, p=0.007). In IHH there were significant increases in bone formation (alkaline phosphatase=318.3±33.9 vs 205.4±20.0 IU/l; osteocalcin=13.44±1.44 vs 8.57±0.94 ng/ml; p<0.05) and in bone resorption (urinary cross-linked N-telopeptides of type I collagen= 149.1± 32.3 vs 47.07±8.4 nmol bone collagen equivalents/mmol creatinine; p<0.05) compared to controls, while such differences were not present in KS. Our results outline the importance of BMD evaluation in all hypogonadal males. Nevertheless, bone loss is a minor characteristic of KS, while it is a distinctive feature of IHH. Therefore, early diagnosis and age-related replacement therapy coupled with a specific treatment for osteoporosis could be useful in preventing future severe bone loss and associated skeletal morbidity.

Cardiovascular Complications in Acromegaly: Methods of Assessment

Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy, dilation and diastolic filling abnormalities has been widely reported in literature. Generally, ventricular hypertrophy is revealed by echocardiography but early data referred increased cardiac size by standard X-ray. Besides, echocardiography investigates cardiac function and value disease. There are new technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non-invasive ultrasound tool which extends Doppler applications beyond the analysis of intra-cardiac flow velocities until the quantitative assessment of the regional myocardial left ventricular wall motion, measuring directly velocities and time intervals of myocardium. The radionuclide techniques permit to study better the cardiac performance. In fact, diastolic as well as systolic function can be assessed at rest and at peak exercise by equilibrium radionuclide angiography. This method has a main advantage of providing direct evaluation of ventricular function, being operator independent. Coronary artery disease has been poorly studied mainly because of the necessity to perform invasive procedures. Only a few cases have been reported with heart failure study by coronarography and having alterations of perfusion which ameliorated after somatostatin analog treatment. More recently, a few data have been presented using perfusional scintigraphy in acromegaly, even if coronary artery disease does not seem very frequent in acromegaly. Doppler analysis of carotid arteries can be also performed to investigate atherosclerosis: however, patients with active acromegaly have endothelial dysfunction more than clear-cut atherosclerotic plaques. In conclusion, careful assessments of cardiac function, morphology and activity need in patients with acromegaly.

Evaluation, by Noninvasive Methods, of the Effects of Acute Loss of Thyroid Hormones on the Heart

To evaluate the effects of the acute loss of thyroid hormones on the heart the authors studied 11 women with acute hypothyroidism. The cardiac study was performed by means of electrocardiography (ECG), radionuclide ventriculog raphy (RNV) at rest and under effort, and monodimensional echocardiography (MD-echo) and was repeated with ECG and MD-echo after six months of thyrox ine suppressive therapy. The ECG showed a significant prolongation of QT in terval and flattening and inversion of T wave with normal heart rate. The MD-echo revealed left ventricular function in the normal range and normal left ventricular dimensions. RNV showed the ejection fraction in the lower normal range at rest, which increased to a smaller extent under effort in comparison with a control group. The ECG performed during suppressive therapy with L- thyroxine yielded normal findings with an increase of heart rate and of R wave amplitude, and the MD-echo showed no significant variations of cardiac func tion due to the increase of heart rate.

Prevalence of Thyroid Autoimmunity in Patients with Spondyloarthropathies

Objective. To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto’s thyroiditis (HT) in a group of patients with spondyloarthritis (SpA). Methods. We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated. Results. Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration > 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05). Conclusion. Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.