The effect of coping strategies on health-related quality of life in acromegaly patients.

PURPOSE: Patients with acromegaly oftentimes exhibit a reduced physical and psychological health-related quality of life (HRQoL). Maladaptive coping styles are associated with poor HRQoL in a number of diseases and patients with pituitary adenomas in general exhibit less effective coping styles than healthy controls. This study aimed to assess coping strategies in acromegaly patients in order to explore leverage points for the improvement of HRQoL. METHODS: In this cross-sectional study, we administered self-report surveys for coping strategies and HRQoL (Short Form SF-36, Freiburg questionnaire on coping with illness, FKV-LIS) in patients with acromegaly. These were set into relation with a variety of health variables. RESULTS: About half of the 106 patients (44.3% female) with a mean age of 56.4 ± 1.3 years showed impaired physical and psychological HRQoL on average 11.2 years after the initial diagnosis. Body mass index, age at survey date and concomitant radiotherapy explained 27.8% of the variance of physical HRQoL, while depressive coping added an additional 9.2%. Depressive coping style and trivialization and wishful thinking were pivotal predictors of an impaired psychological HRQoL with a total explained variance of 51.6%, whereas patient health variables did not affect psychological HRQoL. CONCLUSION: Our results show that maladaptive coping styles have a substantial negative impact on psychological HRQoL in patients with acromegaly, whereas physical HRQoL is influenced to a lesser extent. Specialized training programs aimed at improving coping strategies could reduce long-term disease burden and increase HRQoL in the affected patients.

Pregnancy-related hypophysitis revisited.

OBJECTIVE: The aim of the study is to assess the distinguishing features of pregnancy-related hypophysitis (PR-Hy) compared to non-pregnancy autoimmune hypophysitis and to evaluate the changing therapeutic approaches and outcomes in PR-Hy over time. DESIGN: Retrospective analysis of all published cases with PR-Hy and 6 own cases. METHODS: A PubMed search was performed and abstracts screened for publications with information on cases with PR-Hy from which full-text review was performed. Clinical features, diagnostic findings, and outcome in relation to treatment modalities in PR-Hy were assessed. RESULTS: One hundred and forty-eight cases with PR-Hy were identified. PR-Hy was significantly delimited from non-PR-Hy by the frequent occurrence of the chiasmal syndrome (50% vs 13%, P < .0001), higher rate of intrasellar origin (94% vs 74%, P = .0005), lower rate of pituitary stalk involvement (39% vs 86%, P < .0001), and low rate of diabetes insipidus (12% vs 54%, P < .0001). The role of surgery in PR-Hy decreased over time while noninvasive treatment modalities increased. The recurrence rate after high-dose glucocorticoid therapy (33%) was high and exceeded that of surgery (2%) and conservative management (2%). In contrast to initial reports on PR-Hy, recent literature regarding outcome of mother's and child's health was positive. The frequency of spontaneous preterm delivery was not increased. Recurrent PR-Hy in a subsequent pregnancy was reported in only two females. CONCLUSION: PR-Hy has distinct features that delineate the disorder from non-PR-Hy. With increasing experience in diagnosis, availability of adequate replacement therapy, and improved treatment modalities, PR-Hy has lost its threat and the outcome is encouraging.

The importance of MRI quality and reader's experience for detecting an adenoma in Cushing's disease.

Objective: In Cushing's disease (CD), detection of an adenoma by MRI is challenging. The aim of this study is to compare real-life MRI in the initial diagnostic workup of CD with high-quality MRI performed in a tertiary center for pituitary diseases. Design and methods: We retrospectively analyzed 139 patients with CD who underwent primary transsphenoidal surgery (TSS) in our department and had both an MRI conducted at a different institution (external MRI; extMRI) and an MRI conducted at our institution (internal MRI; intMRI). Preoperative interpretation of MRI was performed independently by an external radiologist (extRAD), an internal neuroradiologist (intRAD) and a pituitary surgeon (SURG). Intraoperative detection of an adenoma and endocrinological remission provided proof of the true adenoma localization in 105 patients. Results: Interpretation of extMRI by extRAD and SURG was concordant in only 64% (89/139) of cases, while 74.1% (103/139) concordance was observed for interpretation of intMRI by intRAD and SURG. Based on extMRI, the true localization of the adenoma was correctly predicted in only 46.7% of the patients by extRAD and in 65.7% by SURG. In contrast, the sensitivity to correctly identify the adenoma on intMRI was 80.0% for intRAD and 94.3% for SURG. Conclusion: Both the quality of MRI and the reader's experience are paramount for detection of microadenomas in CD. Every effort should be made to perform high-quality initial MRI according to current standards and to ensure rating by an expert in pituitary imaging.

Outcomes of Transsphenoidal Microsurgery for Prolactinomas - A Contemporary Series of 162 Cases.

INTRODUCTION: Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged. This study is aimed at defining the current role of pituitary surgery in the management of prolactinomas. MATERIALS AND METHODS: In this retrospective, consecutive single-center study, 162 patients who underwent primary microscopic TSS for prolactinomas between 2006 and 2019 were analyzed regarding surgical indication, previous dopamine-agonist (DA) treatment, early remission rates (3 months postoperatively), surgical complications and pituitary function. RESULTS: Seventy-four microprolactinomas and 88 macroprolactinomas were operated by TSS. 62.3% of the patients had received prior DA treatment. For microprolactinomas, the predominant indication for surgery was patient's wish (41.9%), while indications for macroprolactinomas varied. For enclosed microprolactinomas, the initial remission rate was 92.1%, while for macroprolactinomas, the rate was 70.4%. No significant difference of remission rates was found between DA-pretreated (65.3%) and non-pretreated (72.1%) patients (p=0.373).None of the patients suffered a significant complication. Re-operation for a postoperative cerebrospinal fluid leak was required in one patient (0.6%). Permanent postoperative deterioration of pituitary function was only observed in one of 158 patients with surgery for a prolactinoma (0.6%). Improvement of pituitary function was observed in 8 of 25 patients (32%) with preoperative deficits. CONCLUSION: Transsphenoidal microsurgery is safe and efficient for treatment of prolactinomas. It is particularly suitable for enclosed prolactinomas. The patient should be well informed of the pros and cons of the treatment options, which include DA medication and TSS, and the patient's preference should be taken into account during decision-making.

Surgery for prolactinomas: a better choice?

PURPOSE: Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged. METHODS: Based on contemporary literature and own experience, the changing role of surgery for treatment of prolactinomas is discussed. RESULTS: Today, TSS is performed by minimally invasive microscopic or endoscopic techniques. Normoprolactinemia is obtained in 71-100% of patients with microprolactinomas by TSS. Almost equal results are found in circumscribed intrasellar macroprolactinomas. In experienced hands, pituitary function is preserved in TSS. The risk of cardiac valve disease is still a concern with ergot-derived dopamine-agonists (DAs) in patients requiring long-term, high-dose dopamine-agonist (DA) treatment. Cost-utility analysis favors TSS over DA treatment. The possible negative impact of DA treatment on future surgical results is still a controversial and unsettled issue. In patients who wish to become pregnant, the advantages of microprolactinoma removal to avoid DAs and macroprolactinoma debulking to avoid symptomatic enlargement during pregnancy should be discussed with the patients. Young patients' age is an argument for surgery to circumvent the unpredictable sequelae of long-term DA treatment. Surgery should be discussed in male gender because of a higher likelihood of DA resistance and aggressive behavior of prolactinoma. CONCLUSION: Given excellent results of TSS and concerns about medical treatment, the scale of indications for TSS as an alternative to DAs has increased. The patient's wishes concerning a chance at a cure with TSS instead of a long-term treatment with DAs has become an important and accepted indication. With DA medication and TSS, two effective treatment modalities for prolactinomas are available that can be used in a complementary fashion.

Ki-67 labeling index and expression of p53 are non-predictive for invasiveness and tumor size in functional and nonfunctional pituitary adenomas.

BACKGROUND: It is still controversial whether an increased proliferation index is correlated with the tumor invasiveness of pituitary adenomas. A homogeneous large monocentric series of pituitary adenomas was retrospectively analyzed. The correlation between the proliferation indices (Ki-67 and p53 expression levels) and invasiveness and size of pituitary adenomas was investigated in primary operated and recurrent adenomas. METHOD: Four hundred thirty-nine patients after resection of pituitary adenomas were retrospectively included (43 recurrent tumors, 196 null cell adenomas, 86 somatotroph adenomas, 55 corticotroph adenomas, 55 prolactinomas, 4 thyreotroph adenomas). The maximum tumor diameter and tumor invasiveness in Knosp grading were assessed and Ki-67 and p53 immunostaining was performed. The role of invasiveness was evaluated using a cumulative odds ordinal logistic regression. For calculating the effect of tumor size, a one-way analysis of variance (ANOVA) was conducted. RESULTS: Overall and in the subgroups, no significant correlation between proliferation indices and mean tumor diameter was found. No significant predictive expression value of Ki-67 and p53 on tumor invasiveness and in recurrent tumors could be demonstrated. There was a tendency that Ki-67 LI and p53 LI are higher in recurrent corticotroph adenomas and lactotroph adenomas but values did not reach the significant level. CONCLUSION: Invasive character of pituitary adenomas is neither correlated with increased Ki-67 LI nor with increased p53 expression. Proliferation parameters are independent from adenoma size at initial presentation. The partly elevated expression of Ki-67 in recurrent tumors underlines the clinical importance of the marker.

[Pituitary adenomas]. / Hypophysenadenome.

Despite characteristic symptoms the diagnosis of clinically relevant pituitary adenomas is often delayed until an advanced stage due to the rarity of the disease. The typical clinical manifestations are presented in this review article. The recent discovery of the USP8 mutation in Cushing's disease and of X­linked acrogigantism (X-LAG) syndrome in early onset gigantism were milestones in the search for the molecular etiology of pituitary adenomas. The triad of endocrinological, radiological and ophthalmological diagnostics are the main pillars for the diagnostic work-up of pituitary adenomas. The standard treatment modalities, which include surgery, medical treatment and irradiation, have been further developed and refined. For transsphenoidal excision of pituitary adenomas, microsurgery and endoscopy are two equivalent surgical techniques with relatively few complications. Surgery represents the first-line treatment of pituitary adenomas. Prolactinomas are an exception as the medical treatment with dopamine agonists is highly efficient. Nowadays, new medical treatment options are available for acromegaly and Cushing's disease and are used for second-line treatment. The alkylating chemotherapeutic agent temozolomide is used for the first-line chemotherapy of rare aggressively growing pituitary adenomas. Irradiation is indicated if surgical and medical treatment options are insufficiently successful. Stereotactic one-stage irradiation (radiosurgery) is especially suitable for well-demarcated invasive residual or recurrent adenomas in the cavernous sinus. A new development is hypofractionated radiosurgery for protection of structures at risk. Fractionated irradiation is necessary with large radiation volumes and for pituitary adenomas with a close proximity to the optic tract.

Acute pituitary disease in pregnancy: how to handle hypophysitis and Sheehan's syndrome.

Pregnancy-related hypophysitis (PR-Hy) that typically occurs during late pregnancy and the early postpartum period is considered an autoimmune disorder. Knowledge and awareness of characteristic clinical symptoms and specific endocrine and neuroradiological features mostly enables a correct diagnosis and guarantees best possible management. In the presence of mild clinical symptoms, a "wait-and-watch" approach is recommended. Transsphenoidal surgery or glucocorticoid therapy is indicated if progressive clinical signs or severe visual symptoms are observed. Reported cases indicate that transsphenoidal surgery performed during pregnancy can reverse visual symptoms and has a minimal risk to the health of the fetus and mother. Glucocorticoid therapy has a high initial response rate, but recurrence can occur after discontinuation. In late-pregnancy hypophysitis, the options of delaying therapy until the child is born or, if symptoms are severe, of inducing delivery prior to therapy have to be considered. Sheehan's syndrome (SS) is characterized by irreversible, partial or complete hypopituitarism due to pituitary infarction. The predominating causative event is massive peripartum hemorrhage (PPH). A considerable diagnostic delay is mostly observed. PPH and the typical postpartum findings of agalactia and amenorrhea should alert for the diagnosis of SS and prompt endocrine evaluation. Timely hormone replacement therapy is paramount to reduce morbidity and mortality and improve quality of life of afflicted women. Adrenal failure is a major endocrinological risk both of hypophysitis and of Sheehan syndrome. Early recognition and treatment is paramount to avoid life-threatening adrenal crisis.

High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates.

Vitreoretinal diffuse large B-cell lymphoma is a rare disorder, occurring as primary ocular disease or as secondary involvement by primary central nervous system lymphoma. It is usually diagnosed by cytologic, immunocytochemical, and molecular examination of vitreous aspirates. However, distinguishing vitreoretinal diffuse large B-cell lymphoma from uveitis remains difficult, and clonality analysis may be either unsuccessful or misleading. Diffuse large B-cell lymphoma arising in immune-privileged sites (eg, the central nervous system) shows a high frequency of MYD88 mutations. Therefore, we retrospectively assessed the frequency of MYD88 mutations in vitreoretinal lymphoma (VRL) and their diagnostic potential in 75 vitrectomy samples of 69 patients, and validated our results in a separate cohort (n = 21). MYD88 mutations were identified in 20 of 29 (69%) clinically, histologically, and molecularly confirmed VRL, including 6 cases of the test cohort initially diagnosed as reactive (3/6) or suspicious (3/6) for lymphoma. MYD88 mutations, especially L265P, are very frequent in VRL and their detection significantly improves the diagnostic yield of vitrectomy specimens.