Evaluation and follow-up of patients diagnosed with hypophysitis: a cohort study.

OBJECTIVE: Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis. DESIGN: A retrospective observational study. METHODS: The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed. RESULTS: One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%. CONCLUSION: The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases.

Clinicopathological Correlates of PIT1 and SF1-Multilineage Pituitary Neuroendocrine Tumors and the Diagnostic Utility of NKX2.2 Immunohistochemistry in Pituitary Pathology.

CONTEXT.­: PIT1 and SF1-multilineage pituitary neuroendocrine tumors (PitNETs) have been defined since the classification of adenohypophysial tumors based on the PIT1, SF1, and TPIT transcription factors. OBJECTIVE.­: To describe the clinicopathologic features of PIT1 and SF1-multilineage PitNETs and to contribute to the pituitary pathology practice by questioning the expression of NKX2.2 in PitNETs. DESIGN.­: We reviewed 345 PitNETs and described the clinicopathologic features of 8 PIT1 and SF1-multilineage tumors. NKX2.2 positivity and staining pattern were compared to those of 45 PitNETs from the control group. RESULTS.­: PIT1 and SF1-multilineage PitNET patients had a mean age of 41.13 (range, 14-58 years) and a mean diameter of 14.0 mm (range, 8-20 mm). The most common clinical presentation was acromegaly (6 of 8), and postoperative remission was achieved in all patients. On histomorphologic examination, a pseudopapillary pattern was seen in 5 of the tumors, either focally or diffusely. In addition to PIT1 and SF1, there was a diffuse staining with growth hormone and a predominantly perinuclear staining with cytokeratin 18. With NKX2.2, all multilineage tumors were positive, of which 5 were diffuse and 3 were focal. In the control group, 8 tumors (8 of 45) were positive, of which only 1 was diffuse and 7 were focal. CONCLUSIONS.­: In conclusion, NKX2.2 is a transcription factor that can be used as an additional tool in pituitary pathology, and PIT1 and SF1-multilineage PitNETs are specific tumors that usually present with acromegaly, show signs of a nonaggressive clinical course, have a pseudopapillary histomorphology, and express NKX2.2.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.