Purpose To quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. Materials and Methods Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n=15) or RYGB (n=15). Results Mean HbA1c decreased from 9.7 to 6.4% after RYGB and from 9.1 to 6.1% in the IMM group. At 12 mo the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB FGF19 increased in the fasted (93±15 to 152±19 pg/ml; P=0.008) and postprandial states (AUC, 10.8 ± 1.9 to 23.4 ± 4.1 pg × hr/ml × 103; P=0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC × 103, 6.63 ± 1.3 to 15.16 ± 2.56 M × h; P=0.003) and decreased after IMM (AUC × 103 8.22 ±1.24 to 5.70 ± 0.70; P=0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r=0.54, P=0.04) and trended negatively with HbA1c (r=−0.44; P=0.09); these associations were not observed after IMM. Conclusion BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

Ectopic hormone production is well recognized, but ectopic production of prolactin has been reported infrequently. We report here the case of a 47-year-old woman who had hyperprolactinemia (213-224 ng/mL) causing galactorrhea and hypogonadism. Cabergoline treatment, 1.0 mg twice a week, did not lower the prolactin level at all, but excision of a large uterine leiomyoma corrected the hyperprolactinemia and the hypogonadism. The excised leiomyoma tissue exhibited immunostaining for prolactin, confirming by this method for the first time that a uterine leiomyoma was the cause of hyperprolactinemia. This case illustrates the need to consider an ectopic source of prolactin in a patient who has hyperprolactinemia that is not associated with a large sellar mass and is completely resistant to cabergoline.

Context Clinical guidelines recommend measurement of the serum prostate specific antigen (PSA) concentration during testosterone treatment of hypogonadal men to determine if the increase is sufficiently high to warrant urologic referral. Prior studies of the effect of testosterone treatment on PSA concentrations have been conducted in men who were mildly to moderately hypogonadal. Objective To determine the PSA response to testosterone treatment of men who are severely hypogonadal. Design Retrospective cohort study. Setting Single academic medical center. Participants Eighty-five men who were severely hypogonadal due to hypothalamic-pituitary or testicular disease. Main Outcome Measure Changes in serum PSA concentrations during testosterone treatment for up to 18 months. Results Testosterone treatment increased the median serum testosterone concentration from 36 ng/dL (IQR 20-91 ng/dL) at baseline to 395 ng/dL (IQR 266-542 ng/dL) at 6-18 months. This treatment resulted in a median increment in PSA above baseline of 0.70 ng/mL (IQR 0.10-1.85 ng/mL) at 6-18 months. Apropos current Endocrine Society clinical guidelines, 31% of the men experienced a PSA increase above baseline >1.4 ng/mL, and 13% reached an absolute PSA concentration >4.0 ng/mL. Four men were diagnosed with prostate cancer. Conclusions The PSA response to testosterone replacement in men who are severely hypogonadal due to pituitary or testicular disease is greater than that previously reported in men with mild to moderate hypogonadism. These results suggest that the magnitude of the PSA response to testosterone replacement is related to the degree of hypogonadism.

Background Thyroid lymphoma is a rare malignancy that accounts for 1-5% of thyroid malignancies. The classic presentation of thyroid lymphoma is a rapidly enlarging, painless goiter. The main modalities used to confirm lymphoma are thyroid ultrasound and FNA. We report a case of critical airway obstruction (<5 mm) requiring core needle biopsy to diagnose thyroid lymphoma, with resolution of obstruction following chemotherapy. Case A 60-year-old man with a history of hypertension and BPH presented to the hospital with two weeks of progressive shortness of breath and dysphagia. He denied weight loss, night sweats, or thyroid dysfunction. CT demonstrated thyromegaly with substernal extension along with extension into tracheal-esophageal grooves, encasing the trachea with possible right sided tracheal invasion and tracheal narrowing to 4 mm. Thyroid ultrasound demonstrated an enlarged thyroid replaced by heterogenoushypoechoic lobular masses. Additional imaging demonstrated a 4 cm perirenal mass. Laboratory evaluation demonstrated TSH 0.97 uIU/mL (0.4–4. 0 uIU/mL), free T4 0.8 ng/dL (0.6-1.5 ng/dL), anti-TPO 16.9 IU/mL (<5. 0 IU/mL), and LDH 262 U/L (<240 U/L). He underwent a bronchoscopy which showed 60% tracheal obstruction 1 cm below the vocal cords. He underwent 2 FNAs which both resulted as Bethesda 3. The first FNA demonstrated lympho-histiocytic infiltrate, scant spindled cells and follicular cell groups with oncocytic features. The second FNA demonstrated chronic lymphocytic thyroiditis. Due to worsening respiratory status, he was given high dose dexamethasone and planned for tracheal stenting. He subsequently underwent a core needle biopsy demonstrating marked atypical B cell infiltration, concerning for mature large B cell lymphoma. Immunoperoxidase studies demonstrated atypical cells positive for CD10, 20, 79a, BCL-2, 6, and PAX5 with a 90% Ki67 proliferation diagnosing diffuse large B cell lymphoma. Biopsy of his perirenal mass was negative for lymphoma or carcinoma. He began R-CHOP chemotherapy and after one cycle experienced resolution of difficulty breathing, dysphagia, and thyromegaly. Tracheal stenting and thyroidectomy were thus avoided. After 4 cycles of R-CHOP, a PET CT demonstrated no evidence of residual lymphoma. A repeat thyroid ultrasound also demonstrated resolution of both thyromegaly and hypoechoic nodules. Conclusions Patients with a rapidly enlarging goiter and obstructive symptoms should undergo evaluation for thyroid lymphoma, particularly if they have a history of Hashimoto's thyroiditis or positive TPO antibodies even when euthyroid upon presentation. Though FNA is the first line modality used to diagnose thyroid lymphoma, our case highlights the need to proceed with a timely core needle biopsy if FNA is non-diagnostic to obtain a definitive diagnosis. Once the diagnosis of thyroid lymphoma is confirmed, management with R-CHOP chemotherapy rapidly improves obstructive symptoms, avoiding unnecessary surgical intervention even in the setting of critical airway obstruction. References: Stein et al. JCEM. 2013; 98(8): 3131-3138Walsh et al. The Oncologist. 2013;18(9): 994-1003 Presentation: No date and time listed