Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission.

Improvement in Attention Processing After Surgical Treatment in Functional Pituitary Adenomas: Evidence From ERP Study

Cognitive abilities are impaired in patients with pituitary adenoma. However, studies on attention processing impairment in preoperative patients and attention processing recovery after transsphenoidal adenomectomy are lacking. The study aims to identify the electrophysiological change that relates to attention processing in pituitary patients before and after treatment. Twenty five preoperative pituitary patients and 25 follow-up postoperative patients were recruited. 27 healthy controls (HCs) were matched to the patients with age, gender, and education. Event-related potentials were used to investigate the attention processing in the preoperative patients, postoperative patients, and HCs. Across three groups, all emotional stimuli evoked P200 components. Compared with the HCs or postoperative patients, the amplitudes of P200 in the preoperative patients were higher. Moreover, The amplitudes of P200 decreased in the postoperative patients, which were similar to that in the HCs. The attention processing was improved after surgery, but no significant differences were detected between the postoperative patients and HCs. Abnormal hormone levels may be relevant to the factor that impair attention processing. Compared with that of the HCs and postoperative patients, the P200 component elicited by negative stimuli is higher in preoperative patients, which may illustrate compensatory activity after attention impairments. Furthermore, these data indicate that improvements in attention processing may be attributed to the amelioration of endocrine disorders. This study shows that the P200 component may be used to diagnose attention processing in preoperative pituitary patients and prove the improvement of attention processing in postoperative patients.

Case Report: Consecutive Adrenal Cushing’s Syndrome and Cushing’s Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations

The occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.

A rare case of a functioning gonadotroph tumor accompanied by erythrocytosis in an elderly man

Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically “silent” and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.

Three Successful Pregnancies in a Patient with Recurrent Cushing’s Disease

The association of pregnancy and Cushing’s disease (CD) is rare. A 28-year-old woman was admitted for clinical suspicion of Cushing’s syndrome. The investigations confirmed the diagnosis of CD with secondary hypogonadotropic hypogonadism due to an invasive pituitary macroadenoma. The patient underwent transsphenoidal adenomectomy, and histopathology showed an adrenocorticotropic hormone pituitary adenoma. Initial remission of CD ensued, and fertility was restored as the patient had 2 uncomplicated pregnancies. Five years and 10 months after surgery, a third spontaneous pregnancy was confirmed with underlying recurrent CD. Having mild hypercortisolism, CD was managed expectantly. The outcome was a healthy full-term neonate with no maternal complications during pregnancy or labor. Our case highlights the challenge faced by physicians of choosing the optimal approach to active CD in pregnancy. In cases where maternal and fetal complications are mild, conservative approach may be used and specific treatment can be postponed until after delivery.

Early postoperative measurement of growth hormone level for prognosis of surgical outcomes in acromegaly

Aim.To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly. Materials and methods.A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery. Results.Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%). Conclusion.The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.

Risk Factors for Rhinosinusitis After Endoscopic Transsphenoidal Adenomectomy

Objective Patients undergoing endoscopic transsphenoidal adenomectomy (eTSA) for pituitary tumors are at risk for postoperative complications, including rhinosinusitis. We aimed to determine if preoperative sinonasal disease is a risk factor for postoperative rhinosinusitis (PRS). Study Design Retrospective review. Setting Tertiary academic center in U.S. Subjects and Methods Patients with a diagnosis of pituitary adenoma who underwent eTSA between 2007-2016. PRS patients were matched to non-PRS patients or sex, age, tumor size, skull base reconstruction with intranasal tissue grafting, and concurrent septoplasty. Groups were statistically analyzed for potential preoperative risk factors of sinonasal disease (patient-reported, radiographic, endoscopic). Results 49 of 987 patients who underwent eTSA developed PRS (44.9% male, 71.4% Caucasian, mean age 49.3y). On analysis of individual risk factors, there was a significantly higher proportion of patients with a history of prior sinonasal surgery in the PRS group than the non-PRS group (25.5% vs. 6.5%, p = 0.01); however, this group difference became insignificant on multivariate analysis. There were no significant group differences with regard to history of sinus infections, nasal symptoms, seasonal allergies, radiographic abnormalities, or sinonasal disease on endoscopy. Conclusion This is the first study to investigate preoperative sinonasal disease as a risk factor for PRS after eTSA. The risk factors considered did not demonstrate definitive risk for PRS, although a history of prior sinonasal surgery should be investigated further.

The rules for predicting remission in patients with Cushing disease after successful endoscopic transnasal adenomectomy

BACKGROUND: The recurrence rate after successful transnasal adenomectomy in Cushings disease (CD) can reach 47%. We have previously shown that patients with ACTH levels less than 7 pg/ml recurred over 3 years 4.5 times less often than patients with higher levels of ACTH, patients with cortisol levels below 123 nmol/l in 3.4 times less than at higher values of this hormone, however, these indicators are dissociated in 41% of cases, so it is not possible use them for prediction separately. AIM: To develop a method for managing patients after successful transnasal adenomectomy depending on prognosis. METHODS: A monocenter retrospective comparative study included 349 patients (52 men, 297 women) with a confirmed diagnosis of CD, who underwent effective endoscopic transsphenoidal adenomectomy in 20072014. Various combinations of postoperative morning levels of ACTH and cortisol were analyzed. RESULTS: Based on the developed forecasting methods and their best characteristics, the following rules were formulated. If postoperative morning ACTH is less than 7 pg/ml and/or postoperative morning cortisol is less than 123 nmol/l, then the patient will remain in remission for 1 year with probability of 99% (95% CI 97%100%) and for 3 years with probability of 86% (95% CI 80%91%). CONCLUSION: The rules for predicting remission for 1 and 3 years for patients after neurosurgical treatment for CD are proposed. These rules are based on combinations of ACTH and cortisol levels.