Carlos Benbassat

Effectiveness of long-term cabergoline treatment for giant prolactinoma : study of 12 men

OBJECTIVE To review our experience with cabergoline, a D2-selective dopamine agonist, for the treatment of giant prolactinomas. DESIGN A retrospective case series; descriptive statistics. METHODS The study group included 12 men aged 24-52 years (mean 39.2 years) treated for giant prolactinoma at our centers from 1997 to 2006. Cabergoline was started at a dose of 0.5 mg/three times a week and progressively increased as necessary to up to 7 mg/week. Patients were followed by hormone measurements, sellar magnetic resonance imaging, and visual examinations. RESULTS In ten patients, cabergoline served as first-line therapy. The other two patients had previously undergone transsphenoidal partial tumor resection because of visual deterioration. Mean serum prolactin level before treatment was 14,393 +/- 14,579 ng/ml (range 2047-55,033 ng/ml; normal 5-17 ng/ml). Following treatment, levels normalized in ten men within 1-84 months (mean, 25.3 months) and decreased in the other two to 2-3 times of normal. Tumor diameter, which measured 40-70 mm at diagnosis, showed a mean maximal decrease of 47 +/- 21%; response was first noted about 6 months after the onset of treatment. Nine patients had visual field defects at diagnosis; vision returned to normal in three of them and improved in five. Testosterone levels, initially low in all patients, normalized in eight. There were no side effects of treatment. CONCLUSION Cabergoline therapy appears to be effective and safe in men with giant prolactinomas. These findings suggest that cabergoline should be the first-line therapy for aggressive prolactinomas, even in patients with visual field defects.

Clinical Characteristics and Outcome of Familial Nonmedullary Thyroid Cancer: A Retrospective Controlled Study

BACKGROUND Familial nonmedullary thyroid cancer (FNMTC) is a disease defined by clustering of thyroid cancers of follicular cell origin, and it is estimated to account for 5% of all thyroid cancers. Several studies found FNMTC to be more aggressive than sporadic disease, whereas others found them to have a similar course and outcome. The purpose of this study was to determine whether FNMTC is more aggressive than sporadic thyroid cancer. METHODS A retrospective controlled study of FNMTC versus sporadic nonmedullary thyroid cancers was conducted using a registry of patients with thyroid cancer. Data on disease severity at presentation, treatment modalities, and outcome were collected. RESULTS Sixty-seven patients with FNMTC and 375 controls with sporadic disease were included. Follow-up period was 8.6 ± 10 years for patients with FNMTC and 8.4 ± 9.1 years for sporadic cases. Patients with FNMTC had comparable disease severity at diagnosis as sporadic patients, underwent similar surgical and radioiodine treatments, and had similar long-term disease-free survival. Long-term outcome in families with three or more affected relatives was similar to families with only two affected relatives. CONCLUSIONS Our results suggest that FNMTC is not more aggressive than sporadic thyroid cancer within our studied population. After a similar therapeutic strategy, FNMTC and sporadic cases had comparable prognosis, including in families with three or more affected members.

Impact of Pregnancy on Outcome and Prognosis of Survivors of Papillary Thyroid Cancer

BACKGROUND Papillary thyroid cancer (PTC) commonly affects women of child-bearing age. During normal pregnancy, several factors may have a stimulatory effect on normal and nodular thyroid growth. The aim of the study was to determine whether pregnancy in thyroid-cancer survivors poses a risk of progression or recurrence of the disease. METHODS The files of 63 consecutive women who were followed at the Endocrine Institute for PTC in 1992-2009 and had given birth at least once after receiving treatment were reviewed for clinical, biochemical, and imaging data. Thyroglobulin levels and neck ultrasound findings were compared before and after pregnancy. Demographic and disease-related characteristics and levels of thyroid-stimulating hormone (TSH) during pregnancy were correlated with disease persistence before conception and disease progression during pregnancy using Pearsons analysis. RESULTS Mean time to the first delivery after completion of thyroid-cancer treatment was 5.08 ± 4.39 years; mean duration of follow up after the first delivery was 4.84 ± 3.80 years. Twenty-three women had more than one pregnancy, for a total of 90 births. Six women had evidence of thyroid cancer progression during the first pregnancy; one of them also showed disease progression during a second pregnancy. Another two patients had evidence of disease progression only during their second pregnancy. Mean TSH level during pregnancy was 2.65 ± 4.14 mIU/L. There was no correlation of disease progression during pregnancy with pathological staging, interval from diagnosis to pregnancy, TSH level during pregnancy, or thyroglobulin level before conception. There was a positive correlation of cancer progression with persistence of thyroid cancer before pregnancy and before total I-131 dose was administered. CONCLUSIONS Pregnancy does not cause thyroid cancer recurrence in PTC survivors who have no structural or biochemical evidence of disease persistence at the time of conception. However, in the presence of such evidence, disease progression may occur during pregnancy, yet not necessarily as a consequence of pregnancy. The finding that a nonsuppressed TSH level during pregnancy does not stimulate disease progression suggests that it may be an acceptable therapeutic goal in this setting.

Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly compared with younger age groups.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) are the most common type of pituitary adenomas diagnosed in older patients. However, there are insufficient data regarding the clinical course, risk of regrowth, and long-term prognosis in elderly versus younger patients. METHODS This retrospective cohort study observed 105 adult patients with NFPAs diagnosed between 1995 and 2012. Patients were stratified into 3 age groups: 18 to 44 years (29 patients), 45 to 64 years (38 patients), and 65 years and over (38 patients). The impact of age on presenting symptoms, disease course, and outcome was analyzed. RESULTS Adenoma size was larger in patients <45 years (mean, 2.9 ± 1.2 cm) compared to patients aged 45 to 64 years and those ≥65 years old (2.3 ± 0.9 and 2.5 ± 0.8 cm, respectively; P = .05), with transsphenoidal surgery being the treatment of choice in all 3 groups (83, 92, and 84%, not significant). After a mean follow-up of 6 years, there were higher recovery rates from hypopituitarism in patients <45 years old (58% vs. 27% and 24%; P = .04). Visual fields improved in most affected patients in each group following surgery (74, 94, and 86%), with a trend toward more full normalization in the youngest age group (58% vs. 44% and 41%; P = .09). There were no significant differences in the risk of remnant growth (29 to 39%), rates of radiation therapy, or need for repeated surgeries. There was no disease-related mortality. CONCLUSION Elderly patients with NFPA have lower rates of recovery from hypopituitarism after treatment compared to younger patients, but the rates of regrowth and need for salvage surgery are similar.

Well-differentiated thyroid carcinoma: comparison of microscopic and macroscopic disease.

BACKGROUND The rapid increase in the incidence of well-differentiated thyroid cancer in recent years is the result of smaller thyroid tumors (1 cm or less) being diagnosed more frequently. Few studies are available regarding the appropriate approach to this previously known postmortem incidental finding, and their results remain controversial. METHODS In 2005, our center started a registry of all patients with nonmedullary thyroid carcinoma who were followed at our institute. In the present study, data on the background, clinical, and outcome characteristics were collected from the registry for 225 patients with microscopic disease and 543 patients with macroscopic disease. RESULTS Patients with microscopic disease were slightly older (51 vs. 47.5 years, p = 0.003), had a higher female to male ratio (189:37 vs. 419:123; p = 0.06), and were affected more by papillary carcinoma (98.2% vs. 85.5%; p < 0.001). Multifocal disease was documented in 50.2% of the patients with microscopic disease and 46.8% of the patients with macroscopic disease (NS), and bilateral disease, in 42.6% and 36.8%, respectively (NS). Corresponding rates for the two groups for other tumor-related factors were as follows: lymph node involvement at initial treatment, 25.7% and 30% (NS); distant metastases, 2.4% and 5.1% (p = 0.16); persistent/recurrent disease, 11% and 32% (p < 0.001); and new distant metastases, 2.65% and 6.5% (p = 0.07). At a median follow-up of 5 years, 96% of the microscopic carcinoma group were disease free compared to 77% of the macroscopic group (p < 0.001). CONCLUSION The differences between patients with microscopic and macroscopic well-differentiated thyroid carcinoma may not justify a different therapeutic approach.

Clinically silent chromaffin-cell tumors: Tumor characteristics and long-term prognosis in patients with incidentally discovered pheochromocytomas

Background: Chromaffin-cell tumors (CCT), a rare group of catecholamine producing endocrine neoplasms, are traditionally suspected and diagnosed in patients presenting with episodic hypertension, together with the classic triad of headache, sweating, and tachycardia. Asymptomatic CCT are increasingly diagnosed, frequently as “incidentalomas”. We have conducted a multicenter retrospective study, to assess the characteristics of a group of patients with clinically silent CCT, compared with a group of patients with typical CCT. Methods: Forty-three consecutive patients with CCT (24 with silent and 19 with typical tumors) have been retrospectively studied for a period of up to 20 yr (between 1989 and 2009); clinical picture, biochemical tests, as well as topographic and functional assessment were analyzed at diagnosis and periodically following treatment. Surgical samples were reviewed for neuroendocrine markers and for signs of invasiveness. Results: Patients with clinically silent CCT were significantly older than the typical ones (56.3±3.4 vs 48.0±4.8 yr; p<0.05); 15 of them (63%) were completely asymptomatic, and 9 patients (37%) complained of non-specific abdominal symptoms. Hypertension was present in only 6 silent CCT patients (25%), it was well controlled [mean blood pressure (BP) 134/84 mmHg], and persisted after surgery in only 2 patients. Fourteen out of twenty-four silent CCT patients (58%) were managed pre-operatively with prophylactic combination of α and β blockade, despite normal BP values. Clinically silent CCT were larger than typical CCT (mean diameter of 5.2±2.3 cm vs 4.6±1.5 cm, p<0.05) and secreted higher amounts of normetanephrines. All clinically silent CCT patients were defined as “cured” after surgery. Conclusion: Clinically silent CCT are more prevalent than previously reported. With an adequate pre-surgical diagnosis and patient preparation, the prognosis of silent tumors is usually excellent.

Pituitary and bilateral adrenal enlargement: an unusual presentation of hepatocellular carcinoma.

Pituitary metastases account for about 1% of operated pituitary lesions. Most derive from primaries in the breast or lung. Pituitary metastases from hepatocellular carcinoma (HCC) have rarely been reported. We describe a patient in whom headache and left external ophthalmoplegia were the only presenting signs of a clinically silent and radiographically undetectable HCC, that had metastasized to the pituitary and both adrenal glands. Pituitary histology and adrenal needle biopsy failed to establish the final diagnosis, which was reached only after surgical exploration of the abdomen. This case illustrates the difficulties encountered in the histopathological diagnosis of pituitary metastasis and the need for good clinical judgment when confronting pituitary tumors with atypical features.

Total versus hemithyroidectomy for small unilateral papillary thyroid carcinoma

The correct approach to treat low-risk intrathyroidal papillary thyroid carcinoma (PTC) is controversial. Specific authors advocate unilateral thyroidectomy to minimize perioperative morbidity. The purpose of the present study was to determine an effective treatment strategy for patients with small unilateral papillary thyroid. This was a retrospective comparative analysis of 161 patients with PTC treated between 2001–2010; 60 consecutive patients following hemithyroidectomy and 101 patients following total thyroidectomy. Only patients with preoperatively-predicted localized unilateral disease were included. No between-group difference was identified in the rate of permanent surgical complications. In total, 36 hemithyroidectomy patients (60%) exhibited benign thyroid nodules in the contralateral lobe on preoperative ultrasound; this factor was found to positively correlate with the performance of ≥1 fine needle aspirations (FNAs) during follow-up. In addition, 47 hemithyroidectomy patients (78.3%) were prescribed thyroxine postoperatively. The hemithyroidectomy patients visited the endocrine clinic significantly less frequently than the total thyroidectomy patients (P=0.01), but were referred more often for neck ultrasound (P=0.03) and FNA (P<0.001). In addition, an increased number of patients in the hemithyroidectomy group were reoperated for suspected recurrent/persistent disease (P=0.06). Results of this retrospective study indicate that hemithyroidectomy for small unilateral PTC is associated with a significant follow-up burden and provides no clear patient benefit.

Amiodarone-Induced Thyrotoxicosis Type 2: A Case Report and Review of the Literature

Amiodarone-induced thyrotoxicosis (AIT) is not an uncommon complication in countries with low iodine intake. Two types of AIT have been described. Type 1 is associated with an underlying disorder of the gland that becomes clinically evident because of the high intrathyroidal iodine content, which acts as a trigger for hyperthyroidism. Type 2 is characterized by an ongoing inflammatory process of the thyroid, with derangement of the parenchyma causing the release of thyroid hormones into the circulation. Yet, there are no definitive tools for the differential diagnosis of these two entities, and the therapeutic approach is still a subject of controversy. A case of AIT type 2 successfully treated with steroids is described followed by a review of the literature.

SHORT-TERM DECLINE IN PROLACTIN CONCENTRATIONS CAN PREDICT FUTURE PROLACTIN NORMALIZATION, TUMOR SHRINKAGE, AND TIME TO REMISSION IN MEN WITH MACROPROLACTINOMAS

OBJECTIVE To identify early follow-up measures that will predict the dynamics of prolactin (PRL) decrease and adenoma shrinkage in men harboring macroprolactinomas. METHODS A single-center historical prospective study including a consecutive group of 71 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (PRL >7 times the upper limit of normal [ULN]) treated medically with cabergoline. Comparisons of PRL normalization rates were performed according to PRL levels achieved at 6 months, maximal adenoma shrinkage during follow-up, and other patient characteristics. Correlations were analyzed to identify characteristics of PRL suppression dynamics. RESULTS PRL levels after 6 months of treatment correlated positively with current PRL levels (r = 0.74; P<.001), with time to PRL normalization (r = 0.75; P<.001), and with adenoma diameter following treatment (r = 0.38; P = .01). Adenoma shrinkage depicted by first magnetic resonance imaging on treatment correlated with maximal adenoma shrinkage during follow-up (r = 0.56; P = .006). Five patients had nadir PRL levels ≥3 times the ULN (51 ng/mL) and showed slower response to cabergoline treatment, with consistently higher PRL levels compared with responding patients throughout follow-up (mean 6-month PRL levels, 519 ± 403 ng/mL versus 59 ± 118 ng/mL; P<.001). CONCLUSION Six-month PRL level might serve as a surrogate marker for PRL normalization and adenoma shrinkage dynamics among men harboring macroprolactinomas.