Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level.

OBJECTIVE: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes. METHODS: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated. RESULTS: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC. CONCLUSION: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels. ABBREVIATIONS: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma.

IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

PURPOSE: To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. METHODS: We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. RESULTS: IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas. CONCLUSIONS: IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

Elevated white blood cell counts in Cushing's disease: association with hypercortisolism.

BACKGROUND: Glucocorticoid receptors are expressed in white blood cells (WBC's) and are known to play a role in cell adhesion and WBC's recruitment from bone marrow. In Cushing's disease leukocytosis is frequently mentioned as laboratory finding. However, there is no data on the prevalence of this finding among patients, or correlation with disease severity. PURPOSE: To investigate the prevalence of leukocytosis in patients with Cushing's disease, alterations in other blood count parameters and correlation with degree of hypercortisolism. METHODS: Data of 26 patients diagnosed and followed for Cushing's disease at our clinic was reviewed. Two patients had disease relapse after complete remission and were studied as 2 separate events. RESULTS: Of the 26 patients, 17 were women (71 %), with a mean age of 39.8 ± 12.7 years. Mean baseline WBC count was 10,500 ± 2,600 cells/µl and dropped to 8,400 ± 1,900 cells/µl (p < 0.05) after treatment, mean neutrophil count at baseline was 7,600 ± 2,600 cells/µl and dropped to 5,300 ± 1,700 cells/µl (p < 0.05), lymphocyte count was 2,000 ± 600 cells/µl and raised to 2,300 ± 600 cells/µl (p < 0.05), hemoglobin was 13.7 ± 1.2 g/dl and dropped to 12.8 ± 1.4 g/dl (p < 0.05), and platelet number did not change. Elevated WBC count was present in 11/28 cases (40 %). Those patients with normal baseline WBC (mean 9,000 ± 1,500 cells/µl) dropped also to 7,700 ± 1,300 cells/µl after treatment (p < 0. 05). There was a significant positive correlation between decrease in UFC secretion and change in WBC's following treatment (r = 0.67, p < 0.01). CONCLUSIONS: Patients with Cushing's disease present with leukocytosis in approximately 40 % of cases. In most cases, including those without elevated baseline count, the WBC's decreased with disease remission, demonstrating the effect of glucocorticoids on these blood cells.

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.

Anemia in a cohort of men with macroprolactinomas: increase in hemoglobin levels follows prolactin suppression.

Men with hypogonadism tend to have low hemoglobin (HGB) levels. We have investigated a cohort of 36 consecutive male patients with macroprolactinomas to evaluate HGB during presentation and following treatment with cabergoline to suppress prolactin (PRL). Patients' mean age at diagnosis was 48 years, the mean adenoma size measured 31 mm. The median PRL at baseline was 1,969 ng/ml; the mean testosterone level was low, 1.5 ng/ml. PRL had been successfully normalized in all but six men by using cabergoline. Mean baseline HGB at diagnosis was 13.1 gr%. Sixteen patients had HGB ≤ 13 gr%, including 4 men with HGB ≤ 11.5 gr%. In the subgroup of 15 men with very low testosterone (≤ 1 ng/ml), baseline HGB was 12.6 gr% compared with 13.5 gr% in patients with higher testosterone (P < 0.005). In 30 men in whom follow-up CBC data were available, mean baseline HGB increased from 13.2 to 13.9 gr% following PRL suppression by cabergoline. Baseline HGB levels inversely correlated with tumor size, reaching levels of 13.7 gr% in 10 men with macroprolactinomas of 10-20 mm in size, 13.0 gr% in 18 subjects with macroadenomas of 21-40 mm, and 12.4 gr% in 7 patients with giant prolactinomas (>40 mm). In 22 men with normal follow-up testosterone, current HGB levels measured 14.5 gr%, but only 12.8 gr% in 9 men with current low testosterone (P < 0.0005). In men with macroprolactinomas, anemia is common. It is associated with hypogonadism and tumor size, and improves following treatment that normalizes PRL and increases testosterone.

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.

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.