Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study.

OBJECTIVE: The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow-up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment. DESIGN AND PATIENTS: Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up terminated if the patient underwent surgery, received cabergoline or was lost to follow-up. MEASUREMENTS: Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm. RESULTS: The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow-up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty-three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth. CONCLUSION: Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.

True hyperprolactinemia in men without visible pituitary adenoma.

PURPOSE: Men with mild to moderate hyperprolactinemia rarely present with normal pituitary on MRI with no visible adenoma, a condition entitled also "idiopathic hyperprolactinemia" or "non-tumoral hyperprolactinemia". We have characterized a cohort of hyperprolactinemic men with normal pituitary imaging. DESIGN: We have identified 13 men with true hyperprolactinemia and normal pituitary MRI. Baseline clinical and hormonal characteristics and response to medical treatment were retrospectively retrieved from medical records. RESULTS: Mean age at diagnosis was 51 ± 16 years (range, 20-77); mean serum prolactin level at presentation was 91 ng/ml (range, 28-264), eight men presented with low baseline testosterone. Initial complaints leading to diagnosis included sexual dysfunction in ten men and gynecomastia in five. All patients were treated with cabergoline, except for one who was given bromocriptine; none required pituitary surgery. All patients normalized prolactin and testosterone with subsequent clinical improvement reported by most men. Currently, after a mean follow-up of 72 months, ten patients continue treatment with caborgoline (median weekly dose, 0.25 mg), whereas three men discontinued treatment. CONCLUSIONS: Men with symptomatic hyperprolactinemia may rarely present with normal pituitary imaging. Medical treatment can lead to hormonal improvement with clinical benefit.

Clinical characteristics and disease outcome of patients with non-medullary thyroid cancer and brain metastases.

Brain metastases from non-medullary thyroid carcinoma (NMTC) are rare, with a reported frequency of ~1%, and patient survival time is <1 year after diagnosis. The optimal management of brain metastases in this setting continues to be debated. The aim of the present study was to evaluate a series of patients with brain metastases from NMTC attending a single tertiary medical center. The electronic database of Rabin Medical Center was reviewed for all patients with NMTC and distant metastases who were diagnosed and treated between 1970 and 2014. Those with brain metastases were identified and formed the study group. Data were collected from medical records comprising clinicopathological characteristics, time intervals for diagnosis and treatment, treatment modalities and outcome. Of the 172 patients with NMTC and distant metastases, 10 possessed brain metastases. These included 6 females and 4 males of median age 53.5 years (range, 18-81 years). All patients had lung metastases and 7 demonstrated bone metastases. The median interval between the diagnoses of NMTC and brain metastases was 40 months (range, 9-207 months). Of the 10 patients, 1 presented with brain metastases at primary diagnosis. Treatment of the brain metastases consisted of surgery, radiotherapy (external beam, stereotactic), and radioiodine, alone or in combination. A total of 2 patients received tyrosine kinase inhibitors. The median overall survival time from diagnosis of brain metastasis was 15 months. A total of 2 patients remained alive at the last follow-up (32 and 300 months, respectively). The present study demonstrated that brain metastases may occur in ≤6% of patients with NMTC and distant metastases. Brain metastases rarely present at diagnosis of NMTC and are associated with metastases in other distant sites. Systematic screening for brain metastases requires consideration in all patients with NMTC and distant metastases. Some patients show an indolent evolution with overall survival of >2 years, supporting an aggressive treatment approach.

Incidence of Nonthyroidal Primary Malignancy and the Association with (131)I Treatment in Patients with Differentiated Thyroid Cancer.

BACKGROUND: The occurrence of nonthyroidal primary malignancy (NTPM) and the potential association of with radioiodine (RAI) treatment are important concerns in patients with differentiated thyroid cancer (DTC), but incidence data are conflicting. The aims of the present study were to investigate the incidence of NTPM and its association with RAI treatment in a cohort of DTC patients treated at a single tertiary medical center. METHODS: The data of 1943 patients with DTC recorded in the Rabin Medical Center Thyroid Cancer Registry were cross-matched with data from the Israeli National Cancer Registry to identify those diagnosed with an NTPM. Patient medical files were reviewed. Second primary malignancy (SPM) was defined as new malignancy diagnosed at least two years after DTC diagnosis. RESULTS: For 1434 of the 1943 patients (73.8%), the American Joint Committee on Cancer TNM stage was 1-2. The mean follow-up was 9.3 years. Of the 1943 patients, 1574 (81%) were treated with RAI, and 1467 were followed for at least 2 years, and of these, 1145 patients (78%) received a cumulative dose of ≤200 mCi. A total of 409 NTPMs were diagnosed in 368/1943 patients with DTC (18.9%; 265 female, mean age 53.9 ± 15 years), including 173 SPMs (42.3%) in 166/368 patients. The most common NTPM and SPM was breast cancer followed by hematologic malignancies. In patients followed for ≥2 years, SPMs were diagnosed in 9% of RAI-treated patients and 10.5% of non-RAI-treated patients. SPM rates were 10.2% and 7.8% for a cumulative RAI dose of ≤100 mCi and >100 mCi respectively. Hazard ratios for SPM in patients that received/did not receive RAI treatment was 1.27 (95% confidence interval 0.88-1.82; p = 0.1). There was no correlation between first or cumulative RAI dose and diagnosis of SPM. CONCLUSIONS: NTPMs are not uncommon in patients with DTC and usually antecede the DTC. In a population of mostly low-risk DTC patients, in whom limited activities of RAI are usually administered, this treatment is apparently not associated with an overall increased risk of SPMs compared with subjects not receiving RAI treatment.