Presurgical Medical Treatment in Prolactinomas: Surgical Implications and Pathological Characteristics From 290 Cases.

OBJECTIVE: To review experience regarding the treatment of prolactinomas by endoscopic endonasal surgery focusing on the association between presurgical dopamine agonist (DA) treatment and perioperative outcomes, surgical morbidities, endocrine outcomes, and pathological characteristics. METHODS: A single-center series of 290 cases was analyzed retrospectively and clinical data were collected. Intratumoral collagen content was assessed by Masson trichrome staining. RESULTS: Tenacious tumor consistency (27.8% vs 9.8%, P < .001) was more common in DA-pretreated patients compared with patients who underwent initial surgery. Moreover, DA-pretreated macroadenomas presented more intraoperative blood loss (200 [100-400] mL vs 175 [100-300] mL; P = .014), longer surgical duration (177 ± 95 minutes vs 154 ± 57 minutes; P = .043), and more surgical morbidities (19.4% vs 8.9%; P = .034). Additionally, DA-pretreated macroadenomas presented a higher collagen volume fraction than that of the initial surgery group (23.6 ± 2.2% vs 13.2 ± 2.1%; P = .001). Correlation analysis revealed a close correlation between collagen volume fraction and the cumulative dose of bromocriptine (BRC) in macroadenomas (r = 0.438, P < .001). Regarding endocrine outcomes, DA-pretreated microadenomas showed a lower proportion of initial remission compared with patients who underwent initial surgery (86.7% vs 100%, P = .047). CONCLUSION: This study described increased surgical difficulty and inferior endocrine outcomes associated with tumor fibrosis secondary to presurgical BRC treatment in prolactinomas. Neurosurgeons should note that presurgical BRC treatment may render subsequent surgery more challenging.

The hypothalamic-pituitary-gonad axis in male Cushing's disease before and after curative surgery.

OBJECTIVE: Gonadal and sexual disturbances are commonly encountered in patients with Cushing's disease. Nevertheless, the prevalence of hypogonadism in male Cushing's disease, the risk factors as well as the recovery time have been scarcely reported. Therefore, we aimed to explore the prevalence of hypogonadism at baseline and its determinants. In addition, the recovery time of hypogonadism and risk factors for unrecovered gonadal axis in male Cushing's disease with biochemical remission were investigated. METHODS: We reviewed medical records of males with Cushing's disease managed between 2010 and 2020. Fifty-two male patients were enrolled according to the criteria. Each case attained biochemical remission after transsphenoidal surgery. Demographic details, clinical features, 24-hour UFC, hormonal profile [serum PRL, FSH, LH, TT, ACTH, cortisol, TT4/FT4, TT3/ FT3, TSH and IGF-1] were measured at baseline and during follow-up. The maximal tumor diameter on MRI was recorded at diagnosis. RESULTS: Hypogonadotropic hypogonadism was observed in thirty-nine patients (75%) at diagnosis. Total testosterone was negatively correlated with ACTH and 24-hour UFC. Midnight serum ACTH level at diagnosis was significantly associated with hypogonadism after adjusting for confounding factors. Thirty-two (80%) patients achieved eugonadism within 12 months after the surgery, of which twenty-eight (87.5%) achieved eugonadism within 3 months. Seven patients were persistently hypogonadal during the follow-up (≥1 year), mainly due to the hypopituitarism as a complication of the therapies such as surgery. CONCLUSION: Hypogonadotropic hypogonadism is frequent in male Cushing's disease, but it is reversible in most cases within one-year follow-up after remission.

Proinflammatory cytokines predict the incidence of diabetic peripheral neuropathy over 5 years in Chinese type 2 diabetes patients: A prospective cohort study.

BACKGROUND: Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up. METHODS: We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up. FINDINGS: Among the 106 chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (p<0.05). In multivariate models, increased plasma levels of TNF-α (hazard ratio, HR: 8.74 [95% confidence interval, CI: 1.05-72.68]; p <0.05) and ICAM-1 (HR 23.74 [95% CI:1.47-383.81]; p<0.05) were both associated with incident DPN, after adjusting for known DPN risk factors. INTERPRETATION: Increased plasma levels of proinflammatory factors, especially TNF-α and ICAM-1, predicted the incidence of DPN over 5 years in Chinese diabetes patients, but larger longitudinal studies are required for confirmation. FUNDING: National Natural Science Foundation of China, Shanghai Talent Development Fund Program, Shanghai Shenkang Hospital Developing Center Clinical Scientific and Technological Innovation Program, Shanghai Science and Technology Committee Program, Shanghai General Hospital Program of Chinese traditional and Western medicine combination and Shanghai Municipal Commission of Health and Family Planning Clinical Research Project.

Low serum phosphate and magnesium levels are associated with peripheral neuropathy in patients with type 2 diabetes mellitus.

AIMS: To determine the relationship of serum phosphate, serum magnesium and peripheral nerve function in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 254 patients diagnosed with T2DM were included. Peripheral nerve function was evaluated by nerve conduction study with the use of electromyography. Composite z scores of conduction velocity, latency, and amplitude were constructed, respectively. Demographic, medical and laboratory data including serum phosphate and magnesium were collected. RESULTS: Serum phosphate and serum magnesium levels were significantly lower in patients with diabetic peripheral neuropathy (DPN) (P < 0.01). And the percentages of DPN patients were lower in high tertile of serum phosphate and serum magnesium (P < 0.05). Furthermore, composite z score of conduction velocity (CV) (P = 0.012) were positively associated with serum phosphate levels and the composite z score of amplitude (P < 0.001) and CV (P = 0.041) were positively associated with serum magnesium levels. After adjusting potential related factors (age, gender, smoking, diabetes duration, body mass index, systolic blood pressure, glycated hemoglobin, total cholesterol, estimated glomerular filtration rate), serum levels of phosphate and magnesium were still related to status of DPN in logistic regression (P < 0.05). CONCLUSION: Lower serum phosphate and magnesium significantly correlated with parameters of nerve conduction in T2DM patients. Serum phosphate and magnesium might underlie the pathophysiologic features of DPN.

Management of prolactinoma: a survey of endocrinologists in China.

Objective To assess the current management of prolactinoma among endocrinologists in China. Methods An online survey of a large sample of endocrinologists was conducted in China. The questionnaire included 21 questions related to controversial issues about the management of prolactinomas. Doctors in the endocrinology department of a university-affiliated hospital or a comprehensive secondary hospital in 12 cities from East, West, South, North and Middle China were surveyed. Results A total of 290 valid questionnaires were collected, and the response rate was 40%. When hyperprolactinemia occurred, 97% of the respondents would test thyroid-stimulating hormone routinely. 22% of the respondents considered that prolactin levels <100 ng/mL exclude the presence of a prolactinoma. Only 9% of the respondents believed that prolactin >250 ng/mL could occur in all the following situations as macroprolactinoma, mircoprolactinoma, macroprolactinemia and drug-induced hyperprolactinemia. Surgery was not recommended by 272 (94%) endocrinologists as the first choice for treating microprolactinomas. 58% and 92% of endocrinologists would start drug treatment for microprolactinomas and macroprolactinomas at diagnosis. 70% and 40% chose to withdraw treatment after 2-3 years of prolactin normalization in microprolactinomas and macroprolactinomas. In case of pregnancy, 57% of the respondents considered bromocriptine as choice for women patients. Drug discontinuation after pregnancy was advocated in 63% and 27% for microprolactinoma and macroprolactinoma. Moreover, 44% of endocrinologists believed that breastfeeding was allowable in both micro- and macroprolactinoma. Conclusion This is the first study to investigate the management of prolactinomas among endocrinologists in China. We found that the current clinical treatment was not uniform. Therefore, it is necessary to strengthen the training of endocrinologists to improve clinical diagnosis and treatment practices.

Long-term follow-up of female prolactinoma patients at child-bearing age after transsphenoidal surgery.

CONTEXT: Prolactinoma is the most common subtype of functional pituitary adenoma. Effective therapy is required for women of child-bearing age to achieve remission at serum prolactin level and regain reproductive function. PURPOSE: To evaluate long-term outcomes, including menstrual recovery, after transsphenoidal surgery on female prolactinoma patients by experienced neurosurgeons. DESIGN: Observational study. PATIENTS: Consecutive female prolactinoma patients aged from 16 to 45 years were included. Histological analysis after surgery revealed adenoma with positive staining for prolactin. Plurihormonal cell adenomas were excluded. MAIN MEASUREMENTS: Clinical manifestations, surgical indications, serum prolactin level before and after surgery, surgical complications, pituitary fuctions, drug maintenance, the status of menstruation, and pregnancy. RESULTS: Sixty-three consecutive female patients with a mean age of 29.5 ± 1.1 years were included. Based on magnetic resonance imaging findings before surgery, 31 (49.2%) patients had microadenoma, and the remaining 32 (50.8%) had macroadenoma. The median follow-up after transsphenoidal surgery was 53 (33-74) months, and long-term surgical remission was achieved in 50 (79.37%) patients with 28 (90.32%) microadenomas and 22 (68.75%) macroadenomas. No meningitis or persistent cerebrospinal fluid leaks occurred. Only one case suffered from persistent diabetes insipidus at follow-up. No severe pituitary dysfunction was observed in microprolactinoma patients. Of patients with menstrual disorders, 85% regained regular menstrual cycles after surgery. Nineteen patients in this cohort desired pregnancy and 15 of them successfully gave birth after surgery. All 17 microadenoma patients with modern surgical indications achieved normal prolactin levels and regular menstrual cycles with only one patient on drug therapy at follow-up. CONCLUSION: Long-term follow-up showed a high remission rate in female prolactinoma patients, especially in microadenoma patients, after surgery. Transsphenoidal surgery performed by experienced neurosurgeons may offer a valuable approach to treat female microprolactinoma patients of child-bearing age with modern indications for surgery.

Peripheral neuropathy is associated with insulin resistance independent of metabolic syndrome.

BACKGROUND: To determine the association of insulin resistance, metabolic syndrome (MetS) with peripheral neuropathy (PN). METHODS: This cross-sectional study consisted of 2035 subjects in Shanghai who were classified as with MetS and without MetS. The new International Diabetes Federation (IDF) criterion was used to define MetS. HOMA-IR was applied to evaluate insulin resistance. All subjects underwent complete foot examination. PN was assessed according to the neuropathy symptom and neuropathy disability scores. Binary logistic regression was performed to analyze the contributions of insulin resistance, features of MetS to PN. RESULTS: (1) The percentage of PN was 4.0% in our study. Patients with MetS (47.7%) had a higher percentage of PN (5.5% vs. 2.6%, respectively, P = 0.001). With the components of MetS increased (non-MetS, three, four, five), a linear increase in the proportion of peripheral neuropathy was observed (2.6%, 4.8%, 5.6% and 7.2%; respectively, P for trend = 0.001). (2) In patients with PN, the average age of patients was significantly older than the corresponding non-PN patients. Waist circumference, fasting blood glucose, HbA1c, proportion of treatment for diabetes and hypertension were significantly higher in PN group compared with non-PN group in MetS patients. (3) The frequency of dysglycemia was the highest in PN patients both with and without MetS (96.2% and 82.1%, P = 0.084). (4) After adjusting for gender and smoking history, the PN was associated with MetS [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2, 3.2; P = 0.006], and age (OR 1.1; 95% CI 1.1, 1.1; P < 0.001). When HOMA-IR was added to this binary logistic regression, the association of PN with MetS disappeared (P = 0.110), but the PN was still associated with HOMA-IR (OR 1.2; 95% CI 1.1, 1.4, P < 0.001). CONCLUSIONS: In metabolic syndrome, insulin resistance might play an important role in the development of peripheral neuropathy.