Value of repeated US-guided fine-needle aspiration (US-FNAB) in the follow-up of benign thyroid nodules: a real-life study based on the MoCyThy (Modena's Cytology of the Thyroid) DATABASE with a revision of the literature.

PURPOSE: The utility of repeating ultrasound-guided fine-needle aspiration (US-FNAB) in the follow-up of benign (THY2) thyroid nodules is still debated. The aim of this study was to retrospectively investigate the diagnostic value of re-biopsy of thyroid nodules following an initially benign result. METHODS: We retrospectively analyzed US-FNABs performed at the Unit of Endocrinology of Modena from 2006 to 2009. The firstly benign cytological result was compared with the cytological results of subsequent US-FNABs (2nd and/or 3rd) executed on the same nodule. RESULTS: Among 10449 US-FNABs, 6270 (60%) received a THY2 cytological categorization. Of them, 278 (4.43%) underwent a subsequent US-FNAB: 86.7% maintained the same cytology, 32 (11.5%) changed to THY3 (indeterminate) and 5 (1.8%) to THY4 (suspicious of malignancy). Among the 24 nodules addressed to surgery, 9 (37%) were histologically malignant, with an overall miss rate of 3.2%. Male patients had higher risk of discordant results at subsequent US-FNAB (p = 0.005, OR:3.59, 95%CI:1.453-7.769) while dimensional increase above 5 mm was predictive of concordant benign cytology (p = 0.036, OR:0.249, 95%CI:0.068-0.915). Age, suspicious US characteristics, and distance between US-FNABs resulted not predictive. CONCLUSIONS: Re-biopsy of benign nodules confirmed the benign nature in most cases. In case of discordant cytology, relocation in indeterminate category was the most common. The histological diagnosis of cancer occurred in one quarter of nodules surgically removed, with a low overall clinically significant miss rate. Thus, a small percentage of false negatives exists; males and subjects with US suspicious nodules should be carefully followed-up, considering case by case re-biopsy possibility.

Long-Term Use of Temozolomide as Safe and Effective Therapy for an Aggressive Corticotroph Adenoma in a Very Old Patient.

BACKGROUND: Temozolomide (TMZ) is safe and effective in the treatment of aggressive pituitary adenomas (PAs). However, the optimal duration of TMZ therapy is still unknown. Moreover, data about administration of TMZ in elderly (≥65 years) people to treat aggressive PAs are scarce. We report the case of the oldest female patient undergoing the longest TMZ protocol described so far to treat an aggressive, initially silent corticotroph PA. CASE REPORT: The patient initially underwent partial surgical removal of the PA. Subsequent treatment with cabergoline was applied, but it was unsuccessful in controlling the growth of the residual tumor. Pasireotide and external radiation also showed to be ineffective; therefore, treatment with TMZ was started at the standard dose of 200 mg/m2/day for 5 days every 4 weeks for a total of 47 cycles. At the time of treatment's beginning, the patient was 83 years old. Radiological follow-up documented a progressive, remarkable reduction of the adenoma and the last imaging, after 39 cycles of TMZ, showed an intrasellar lesion with large areas of cystic degeneration. The patient also developed adrenal deficiency managed with glucocorticoid replacement. No major side effects were observed throughout the treatment, with exception of nausea, well controlled with anti-emetic medication. TMZ therapy was discontinued after 47 cycles; hormonal and imaging follow-up investigations documented sustained functional and dimensional response. CONCLUSIONS: Our case supports the long-term use of TMZ, confirming its safety and efficacy also for elderly patients.

The Added Value of Operator's Judgement in Thyroid Nodule Ultrasound Classification Arising From Histologically Based Comparison of Different Risk Stratification Systems.

Objective: Several ultrasound classifications for thyroid nodules were proposed but their accuracy is still debated, since mainly estimated on cytology and not on histology. The aim of this study was to test the diagnostic accuracy and the inter-classification agreement of AACE/ACE-AME, American Thyroid Association (ATA), British Thyroid Association (BTA), and Modena Ultrasound Thyroid Classification (MUT) that stratifies malignancy risk considering also the clinician subjective impression. Methods: A prospective study collecting thyroid nodule features at ultrasound and histological diagnosis was conducted. Ultrasound features were collected following a preformed checklist in candidates for surgery because of indeterminate, suspicious, or malignant cytology. All the nodules, besides the cytologically suspicious one, were blinded analyzed. MUT score was applied prospectively, and the others retrospectively. Sensitivity, specificity, diagnostic cut-off value, and accuracy of each classification were calculated. The overall agreement between classifications was tested by Bland-Altman, and agreement between single nodule analysis by different classifications by Weighted Cohen's Kappa. Results: In classifying a total of 457 nodules, MUT has the highest accuracy (AUC 0.808) and specificity (89%), followed by ATA and BTA, and finally by AACE/ACE-AME. ATA, BTA, and MUT are highly interchangeable. Considering agreement between single nodule analyses, ATA and BTA had the best (κ = 0.723); AACE/ACE-AME showed slight agreement with BTA (κ = 0.177) and MUT (κ = 0.183), and fair agreement with ATA (κ = 0.282); MUT had fair agreement with both ATA (κ = 0.291) and BTA (κ = 0.271). Conclusion: Classifications have an acceptable overall diagnostic accuracy, improved using a less rigid system that takes into consideration operator subjective impression.

Pituitary growth hormone (GH) secretion is partially rescued in HIV-infected patients with GH deficiency (GHD) compared to hypopituitary patients.

Biochemical growth hormone deficiency is prevalent among human immunodeficiency virus-infected patients, but if this condition is clinically relevant remains challenging. The aim is to prospectively compare the growth hormone deficiency/insulin-like growth factor-1 status of 71 human immunodeficiency virus-infected patients with impaired growth hormone response to growth hormone releasing hormone + Arginine with that of 65 hypopituitary patients affected by a true growth hormone deficiency secondary to pituitary disease. The main outcomes were: basal serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein 3, growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine test, body mass index, waist and hip circumference, and body composition by dual energy X-ray absorptiometry. Insulin-like growth factor-1 binding protein 3, basal growth hormone (p < 0.005), growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine, waist to hip ratio, insulin-like growth factor-1, fasting glucose, insulin, and triglycerides (p < 0.0001) were lower in hypopituitary than human immunodeficiency virus-infected patients. Total and trunk fat mass by dual energy X-ray absorptiometry were higher in hypopituitary than in human immunodeficiency virus-infected patients (p < 0.0001). In all the patients total body fat was associated with both growth hormone peak and area under the curve at stepwise linear regression analysis. The degree of growth hormone deficiency is more severe in hypopituitary than in human immunodeficiency virus-infected patients, suggesting that the function of growth hormone/insulin-like growth factor-1 axis is partially rescued in the latter thanks to a preserved pituitary secretory reserve. Data from the current study suggest that human immunodeficiency virus-infected patients with peak growth hormone < 9 mg/L may have partial growth hormone deficiency and clinicians should be cautious before prescribing recombinant human growth hormone replacement treatment to patients living with human immunodeficiency virus.

Thyroid Ultrasound Pitfalls: Esophageal Fibrovascular Polyp Mimicking Thyroid Nodule.

Background. Ultrasound (US) is the most accurate tool in the diagnosis of thyroid nodules if performed by expert physician. Misdiagnosis due to extrathyroidal lesions mimicking thyroid nodules is reported in literature. We describe the first case of an esophageal fibrovascular polyp misdiagnosed as a thyroid nodule on US examination. Patient Findings. A 54-year-old woman presented to emergency department for headache and underwent carotid Doppler extended to neck ultrasound with incidental finding of a nodule in the posterior side of the left thyroid lobe. A following thyroid US performed by an endocrinologist allowed the characterization of the lesion as an esophageal pathology, considering the extrathyroidal position, the typical peripheral hyperechoic spots and hypoechoic rim, the connection to the esophagus, and the swallowing connected movement. The patient was addressed to further investigations and finally to anterior pharyngotomy with histological diagnosis of esophageal fibrovascular polyp. Summary. Differential diagnosis between thyroid nodules and other neck lesions is important to prevent an unnecessary fine needle aspiration biopsy and to treat the extrathyroidal pathology. In this case, an US performed by an expert endocrinologist allowed detecting an esophageal fibrovascular polyp requiring surgical removal. In conclusion, the possibility of an esophageal pathology, and even fibrovascular polyp, should be considered during US thyroid examination.

Gender differences in GH response to GHRH+ARG in lipodystrophic patients with HIV: a key role for body fat distribution.

OBJECTIVE: Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. DESIGN AND METHODS: To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRH+Arg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRH+Arg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). RESULTS: Men had lower GH peak and AUC than women (P<0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak <7.5 µg/l). VAT-to-SAT ratio was higher in men than in women with GHD (P<0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P<0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. CONCLUSIONS: These data demonstrate that GH response to GHRH+Arg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH-IGF1 status in these patients.