Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study.

Purpose: To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients. Methods: A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed. Results: Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up. Conclusion: The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

Safety of Withholding Perioperative Hydrocortisone for Patients With Pituitary Adenomas With an Intact Hypothalamus-Pituitary-Adrenal Axis: A Randomized Clinical Trial.

Importance: Pituitary adenoma is the second most common primary brain tumor. Perioperative hydrocortisone has been used for decades to avoid postoperative adrenal insufficiency. Recent studies suggest that withholding perioperative hydrocortisone may be safe for patients with an intact hypothalamus-pituitary-adrenal (HPA) axis. Objective: To assess the safety of withholding hydrocortisone during the perioperative period of pituitary adenoma surgery for patients with an intact HPA axis. Design, Setting, and Participants: A parallel-group, triple-masked, noninferiority randomized clinical trial was conducted at Peking Union Medical College Hospital from November 1, 2020, to January 31, 2022, among 436 patients aged 18 to 70 years with an intact HPA axis undergoing surgery for pituitary adenomas. Interventions: Hydrocortisone supplementation protocol (intravenous and subsequent oral hydrocortisone, using a taper program) or no-hydrocortisone protocol. Main Outcomes and Measures: The primary outcome was the incidence of new-onset adrenal insufficiency (morning cortisol level, <5 µg/dL with adrenal insufficiency-related symptoms) during the perioperative period (on the day of operation and the following 2 days). The secondary outcome was the incidence of adrenal insufficiency in postoperative month 3. Analysis was on an intention-to-treat basis. Results: Of the 436 eligible patients, 218 were randomly assigned to the hydrocortisone group (136 women [62.4%]; mean [SD] age, 45.4 [13.0] years) and 218 to the no-hydrocortisone group (128 women [58.7%]; mean [SD] age, 44.5 [13.8] years). All patients completed 3-month postoperative follow-up. The incidence of new-onset adrenal insufficiency during the perioperative period was 11.0% (24 of 218; 95% CI, 6.9%-15.2%) in the no-hydrocortisone group and 6.4% (14 of 218; 95% CI, 3.2%-9.7%) in the hydrocortisone group, with a difference of 4.6% (95% CI, -0.7% to 9.9%), meeting the prespecified noninferiority margin of 10 percentage points. The incidence of adrenal insufficiency at the 3-month follow-up was 3.7% (8 of 218) in the no-hydrocortisone group and 3.2% (7 of 218) in the hydrocortisone group (difference, 0.5%; 95% CI, -3.0% to 3.9%). Incidences of new-onset diabetes mellitus (1 of 218 [0.5%] vs 9 of 218 [4.1%]), hypernatremia (9 of 218 [4.1%] vs 21 of 218 [9.6%]), hypokalemia (23 of 218 [10.6%] vs 34 of 218 [15.6%]), and hypocalcemia (6 of 218 [2.8%] vs 19 of 218 [8.7%]) were lower in the no-hydrocortisone group than in the hydrocortisone group. Lower preoperative morning cortisol levels were associated with higher risks of the primary event (<9.3 µg/dL; odds ratio, 3.0; 95% CI, 1.5-5.9) and the secondary event (<8.8 µg/dL; odds ratio, 7.8; 95% CI, 2.6-23.4) events. Conclusions and Relevance: This study found that withholding hydrocortisone was safe and demonstrated noninferiority to the conventional hydrocortisone supplementation regimen regarding the incidence of new-onset adrenal insufficiency among patients with an intact HPA axis undergoing pituitary adenomectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT04621565.

Determinants of immediate and long-term remission after initial transsphenoidal surgery for acromegaly and outcome patterns during follow-up: a longitudinal study on 659 patients.

OBJECTIVE: Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features. METHODS: This prospective, single-center, longitudinal cohort study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors' institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission. RESULTS: A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524-5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522-6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006-1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224-3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified. CONCLUSIONS: Cavernous sinus invasion, age at diagnosis, and sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.

Hyperprolactinemia and Hypopituitarism in Acromegaly and Effect of Pituitary Surgery: Long-Term Follow-up on 529 Patients.

Purpose: Studies on hyperprolactinemia and hypopituitarism in acromegaly are limited. We aimed to analyze the preoperative status, postoperative alterations, and correlated factors of hyperprolactinemia and hypopituitarism in acromegaly patients. Methods: This is a single-center cohort study with long-term follow-up. We prospectively enrolled 529 acromegaly patients. Hyperprolactinemia and hypopituitarism were evaluated by testing hypothalamus-pituitary-end organ (HPEO) axes hormones before and after surgery. Results: Hyperprolactinemia (39.1%) and hypopituitarism (34.8%) were common in acromegaly. The incidences of axis-specific hypopituitarism varied (hypogonadism, 29.7%; hypothyroidism, 5.9%; adrenal insufficiency, 5.1%), and multiple HPEO axes dysfunction was diagnosed in 5.3% of patients. Patients with preoperative hyperprolactinemia [hazard ratio (HR)=1.39 (1.08-1.79); p=0.012], hypogonadism [HR=1.32 (1.01-1.73); p=0.047], and hypothyroidism [HR=3.49 (1.90-6.44); p<0.001] had higher recurrence rates than those without. Age, sex, body mass index, tumor size, invasiveness, prolactin staining, ki-67 index, and GH/IGF-1 levels were significantly correlated with preoperative hypopituitarism and hyperprolactinemia. At median 34-month follow-up after surgery, hyperprolactinemia in 95% and axis-specific hypopituitarism in 54%-71% of patients recovered, whereas new-onset hypopituitarism (hypogonadism, 6.2%; hypothyroidism, 4.0%; adrenal insufficiency, 3.2%) was also diagnosed. A shorter tumor diameter was associated with the normalization of preoperative hyperprolactinemia after surgery. Cavernous sinus non-invasion, a shorter tumor diameter, cure at follow-up, and a lower GH nadir level were associated with the improvement of preoperative hypopituitarism after surgery. A larger tumor diameter was associated with the newly developed hypopituitarism after surgery. Conclusion: Hyperprolactinemia and hypopituitarism are common among acromegaly patients and predict worse surgical outcomes. After surgery, improvement and worsening of HPEO axes function co-exist. Correlated factors are identified for clinical management.

Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children: A Randomized Clinical Trial.

Importance: Because studies have suggested that atropine might slow the progression of myopia in children, randomized clinical trials are warranted to understand this potential causal relationship. Objective: To evaluate the efficacy and safety of atropine, 0.01%, eyedrops on slowing myopia progression and axial elongation in Chinese children. Design, Setting, and Participants: This was a randomized, placebo-controlled, double-masked study. A total of 220 children aged 6 to 12 years with myopia of -1.00 D to -6.00 D in both eyes were enrolled between April 2018 and July 2018 at Beijing Tongren Hospital, Beijing, China. Cycloplegic refraction and axial length were measured at baseline, 6 months, and 12 months. Adverse events were also recorded. Interventions: Patients were randomly assigned in a 1:1 ratio to atropine, 0.01%, or placebo groups to be administered once nightly to both eyes for 1 year. Main Outcomes and Measures: Mean changes and percentage differences in myopia progression and axial elongation between atropine, 0.01%, or placebo groups. Results: Of 220 participants, 103 were girls (46.8%), and the mean (SD) age was 9.64 (1.68) years. The mean (SD) baseline refractive error and axial length were -2.58 (1.39) D and 24.59 (0.87) mm. Follow-up at 1 year included 76 children (69%) and 83 children (75%) allocated into the atropine, 0.01%, and placebo groups, respectively, when mean myopia progression was -0.49 (0.42) D and -0.76 (0.50) D in the atropine, 0.01%, and placebo groups (mean difference, 0.26 D; 95% CI, 0.12-0.41 D; P < .001), with a relative reduction of 34.2% in myopia progression. The mean (SD) axial elongation in the atropine, 0.01%, group was 0.32 (0.19) mm compared with 0.41 (0.19) mm in the placebo group (mean difference, 0.09 mm; 95% CI, 0.03-0.15 mm; P = .004), with relative reduction of 22.0% in axial elongation. Fifty-one percent and 13.2% of children progressed by at least 0.50 D and 1.00 D in the atropine, 0.01%, group, compared with 69.9% and 34.9% in the placebo group. No serious adverse events related to atropine were reported. Conclusions and Relevance: While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life. Trial Registration: http://www.chictr.org.cn Identifier: ChiCTR-IOR-17013898.