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Abstract Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy.

Abstract Context Recombinant human growth hormone (rhGH) replacement therapy is often prescribed in patients with nonfunctioning pituitary adenoma (NFPA) or craniopharyngioma, Objective To study whether rhGH therapy in patients with adult growth hormone deficiency (AGHD) increases the risk of pituitary tumor recurrence. Design Retrospective, observational study. Setting Tertiary care center. Patients We studied 283 consecutive patients with AGHD due to NFPA or craniopharyngioma between 1995 and 2018. Intervention rhGH treatment at standard doses was initiated in 123 patients (43.5%). The remaining 160 patients served as controls. Main Outcome Measure Risk of tumor recurrence in rhGH-treated and control patients. Results In univariate analysis, recurrence of the pituitary tumor was less frequent in rhGH-treated patients (19.5%) than in controls (29.7%; hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.32–0.86; P = .01). Multivariate Cox analysis demonstrated that the risk of tumor recurrence was associated with detection of residual disease at the baseline magnetic resonance imaging (HR 9.17; 95% CI, 4.88–17.22; P < .001) and not having performed radiotherapy (HR 16.97; 95% CI, 7.55–38.16; P < .001), while rhGH treatment was no longer associated with a lower risk of recurrence (HR 0.82; 95% CI, 0.47–1.44; P = .50). Conclusions We found no association between rhGH replacement and the risk of tumor recurrence in patients with AGHD caused by NFPA or craniopharyngioma. These data add to the mounting evidence that rhGH therapy has a neutral effect on the recurrence of pituitary tumors. Précis Replacement therapy with rhGH is prescribed to patients with adult growth hormone deficiency. Our study found no increased risk of pituitary tumor recurrence.

IntroductionPatients undergoing transsphenoidal pituitary surgery (TSS) are at risk for several serious complications, including the syndrome of inappropriate antidiuretic hormone and subsequent hyponatremia.ObjectiveIn this study, we examined the effect of 1 week of post-discharge fluid restriction to 1.0 L daily on rates of post-operative readmission for hyponatremia.MethodsWe retrospectively analyzed all patients undergoing TSS from 2008 to 2014 and prospectively recorded patient data from 2015 to 2017. Patients were divided into a control cohort (2008–2014), who were discharged with instructions to drink to thirst; and an intervention cohort (2015–2017) who were instructed to drink less than 1.0 L daily for 1 week post-operatively.ResultsThis study included 788 patients; 585 (74.2%) in the control cohort and 203 (25.8%) in the intervention cohort. Overall, 436 (55.3%) were women, the median age was 47 (range 15–89), and average BMI was 29.4 kg/m2 (range 17.7–101.7). Patients were relatively well matched. Of patients in the intervention group, none was readmitted for hyponatremia (0/203), compared to 3.41% (20/585) in the control group (p = 0.003). Patients in the intervention group also had significantly higher post-operative week one sodium levels (140.1 vs 137.5 mEq/L; p = 0.002). No fluid balance complications occurred in patients who followed this protocol.ConclusionHyponatremia can be a life-threatening complication of TSS, and prevention of readmission for hyponatremia can help improve patient safety and decrease costs. Mandatory post-discharge fluid restriction is a simple and inexpensive intervention associated with decreased rates of readmission for hyponatremia and normal post-operative sodium levels.

PurposeSilent corticotroph adenomas (SCAs) are clinically silent and non-secreting, but exhibit positive adrenocorticotropic hormone (ACTH) immunostaining. We characterized a single center cohort of SCA patients, compared the SCAs to silent gonadotroph adenomas (SGAs), identified predictors of recurrence, and reviewed and compared the cohort to previously published SCAs cases.MethodsRetrospective review of SCA and SGA surgically resected patients over 10 years and 6 years, respectively. Definitions; SCA—no clinical or biochemical evidence of Cushing’s syndrome and ACTH positive immunostaining, and SGA—steroidogenic factor (SF-1) positive immunostaining. A systematic literature search was undertaken using Pubmed and Scopus.ResultsReview revealed 814 pituitary surgeries, 39 (4.8%) were SCAs. Mean follow-up was 6.4 years (range 0.5–23.8 years). Pre-operative magnetic resonance imaging demonstrated sphenoid and/or cavernous sinus invasion in 44%, 33% were > 50% cystic, and 28% had high ACTH levels pre-operatively. Compared to SGAs (n = 70), SCAs were of similar size and invasiveness (2.5 vs. 2.9 cm, p = 0.2; 44 vs. 41%, p = 0.8, respectively), but recurrence rate was higher (36 vs. 10%, p = 0.001) and more patients received radiation therapy (18 vs. 3%, p = 0.006). Less cystic tumors (0 vs. 50%, p < 0.001) and higher pre-operative ACTH levels (54 vs. 28 pg/ml, p = 0.04) were predictors of recurrence for SCAs.ConclusionThis review is unique; a strict definition of SCA was used, and single center SCAs were compared with SGAs and with SCAs literature reviewed cases. We show that SCAs are aggressive and identify predictors of recurrence. Accurate initial diagnosis, close imaging and biochemical follow up are warranted.

Background Total hypophysectomy it is a classical procedure that currently has many indications especially in patients with Cushing syndrome without good endocrine control. Expanded endonasal endoscopic techniques grant us an alternative standpoint to the classic trans-sphenoidal microscopic approach and a comprehensive assessment of the process Method The author provides technical nuances and describe step by step the radical endoscopic hypophysectomy. The study of cadaveric specimens adds clarifying dissections. Conclusions Radical hypophysectomy is an easily replicable and safe procedure. The most important morbidity is the intraoperative cerebrospinal fluid (CSF) leakage, which is inherent to this technique and can be successfully prevented with a pedicled nasoseptal flap reconstruction.

Abstract BACKGROUND: Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone–secreting pituitary adenoma. OBJECTIVE: To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. METHODS: We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. RESULTS: Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). CONCLUSION: Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.

Purpose Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications. Methods We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27–61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2–4.2 mIU/L), with median fT4 2.52 ng/dL (0.9–1.7 ng/dL). Results Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease −72 %), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach. Conclusions Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50 %). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.

Endoscopic, transnasal management of pituitary gland neoplasms is a widely accepted alternative to the traditional microscopic approach. This study aimed to determine outcomes and complication rates for the largest UK series of endoscopic, trans-sphenoidal hypophysectomies reported to date. We performed a retrospective analysis of 136 primary resections and 35 revision cases performed at a tertiary referral centre. Total tumour resection was confirmed in over 85 per cent of primary and revision cases, with biochemical remission in 60 per cent. The incidence of complications such as epistaxis, sphenoid sinus problems, endocrine insufficiency, visual disturbance, post-operative haemorrhage, cranial nerve injury and mortality was significantly lower, compared with similar series using the microscopic approach. Despite its steep 'learning curve', our series demonstrates that the endoscopic approach not only allows superior anatomical visualisation and therefore facilitates full oncological resection of tumours, but also reduces the incidence of peri-operative complications.

A 57-year-old woman presented with severe lethargy, dizziness and nausea 1 week after transsphenoidal resection of a growth hormone secreting pituitary adenoma. She was found to have severe hyponatremia of 115 mmol/L. Importantly, she was neurologically intact and clinically euvolaemic. Her fluid intake was restricted and her sodium levels increased to 131 mmol/L over 4 days. She made a full recovery.She was diagnosed with isolated second-phase diabetes insipidus, a state of symptomatic hypoosmolar hyponatremia that usually occurs 7–10 days after transsphenoidal surgery. The sodium levels improve with fluid restriction.