Depression and Impulsivity Self-Assessment Tools to Identify Dopamine Agonist Side Effects in Patients With Pituitary Adenomas.

Background: Dopamine agonists (DA) are the first line therapy for prolactinoma and symptomatic hyperprolactinemia; use as an adjuvant treatment for acromegaly and Cushing's disease is rare. Some patients develop de novo psychiatric symptoms or have exacerbation of pre-existing conditions during DA therapy. A practical, clinically sensitive depression and impulse control disorders (ICD; particularly hypersexuality and gambling disorders) detection tool is important for identifying at risk patients. The Barratt Impulsivity Scale (BIS-11) and the 9-item Patient Health Questionnaire (PHQ-9) are sensitive in identifying impulsivity and depression. Objective: Detail use of the BIS-11 and PHQ-9 as screening tools for depression and ICD in patients with pituitary disease at a high-volume academic pituitary center. Methods: DA-treated and naïve patients with pituitary disease were included. Patients with a known history of depression or psychiatric disorder were excluded. PHQ-9 standardized interpretation criteria were utilized to classify depression severity. For BIS-11, threshold was established based on previous studies. Statistical analysis was with SPSS version 25. Results: Seventy-six DA-treated and 27 naïve patients were included. Moderate and moderately severe depression were more prevalent in DA-treated patients; severe depression only found in DA-treated patients. A normal BIS-11 score was noted in 76.69%; higher scores (not significant) were noted in DA-treated patients. There was a positive correlation between higher BIS-11 and PHQ-9 scores; higher in DA-treated patients (r = 0.52, p < 0.001) than DA-naïve patients. Patients with BIS-11 scores ≥60 were younger and received lower cumulative DA doses compared to patients with BIS scores <60. There was no association between male sex and BIS-11 ≥60 and male sex did not increase the odds of increased scores (OR = 0.66, CI95% 0.25-1.76, p = 0.41). No significant difference was found for macroadenoma, prolactin levels, testosterone levels, hypogonadism, testosterone replacement in men, and increased impulsivity or depression scores. Conclusion: Use of PHQ-9 and BIS-11 is practical for routine screening of depression and ICD during outpatient pituitary clinic visits for patients with pituitary disease both naïve to treatment and during DA therapy. We recommend close follow-up after initiation of DA therapy for younger patients, regardless of dose.

Cystic appearance on magnetic resonance imaging in bihormonal growth hormone and prolactin tumors in acromegaly.

PURPOSE: To investigate demographic, imaging and laboratory characteristics, and treatment outcomes of acromegaly patients who have bihormonal (BA) growth hormone (GH) and prolactin (PRL) immunoreactive adenomas compared to patients who have densely granulated GH adenomas (DGA) and sparsely granulated GH adenomas (SGA). METHODS: Retrospective review of single-center surgically treated acromegaly patients; pathology was analyzed by a single neuropathologist using 2017 WHO criteria. Preoperative magnetic resonance imaging was assessed to evaluate tumor size, cystic component, invasion and T2 signal intensity. RESULTS: Seventy-seven patients; 19 BA (9 mammosomatotroph and 10 mixed GH and PRL adenomas) were compared with 30 DGA, and 28 SGA. Patients with BA were older than SGA (49.6 vs 38.5 years, p = 0.035), had a higher IGF-1 index (3.3 vs 2.3, p = 0.040) and tumors were less frequently invasive (15.8% vs 57.1%, p = 0.005). BA more frequently had a cystic component on MRI than both SGA and DGA (52.6% vs 14.3%, and 22%, p = 0.005 and 0.033, respectively). When all histological types were combined, biochemical remission postoperatively was more common in non-cystic than cystic tumors (50% vs 22.5%, p = 0.042). Somatostatin receptor ligand response rate was 66.7%, 90.9% and 37.5% in BA, DGA and SGA patients, respectively (p = 0.053). CONCLUSION: Imaging characteristics are an increasingly important adenoma behavior determinant. An adenoma cystic component may suggest that a GH adenoma is a BA. Cystic tumors exhibited lower rates of surgical remission in this series; therefore, optimized individual patient treatment is needed, as patients could be candidates for primary medical treatment.

High prevalence of adrenal insufficiency at diagnosis and headache recovery in surgically resected Rathke's cleft cysts-a large retrospective single center study.

BACKGROUND: Rathke's cleft cysts (RCC) are lesions that arise from Rathke's pouch. Though frequently incidental, resulting symptoms in a minority of cases are indicators for surgical resection, which may prove beneficial. OBJECTIVE: To characterize a cohort of surgically-resected RCC cases at Oregon Health & Science University; tabulate associated hormonal imbalances and symptoms, possible symptom reversal with surgery, determine recurrence risk; identify predictors of recurrence and headache improvement. METHOD: Electronic records of all RCC resected cases (from 2006-2016; 11 years) were retrospectively reviewed. Patients had been evaluated by one neuroendocrinologist using a uniform protocol. RESULTS: A pathological RCC diagnosis was established in 73 of 814 (9%) surgical pituitary cases. The RCC cohort was 77% (n = 56/73) female, mean age was 39.5 ± 14.9 years at first surgery, and at presentation headache was reported in 88% and visual defects/diplopia in 18% of patients. Initial RCC maximum diameter was 1.3 ± 0.7 cm. The most frequent hormonal deficit was cortisol; 24% of patients had a new adrenal insufficiency (AI) diagnosis, however, 36% also had AI at 3 months post-operatively. Mean follow up was 4.0 ± 4.5 years. Two-thirds of patients (41/62) had headache improvement 3 months post-operatively. Post-operative imaging revealed no residual cyst in 58% (38/65). In those patients with no residual RCC, 29% had recurrence and 71% had long lasting cure. From the 42% (27/65) of patients with residual cyst on post-operative imaging; 59% (16/27) remained stable, 26% (7/27) progressed and 15% (4/27) regressed. CONCLUSION: Symptomatic RCC present mostly in women, with a high proportion reporting headaches. Prevalence of AI at diagnosis is high. Surgery may not achieve adrenal axis recovery, but renders a high percentage of headache improvement. Approximately 25% of RCC will recur by 4 years postoperatively. Clinicians should cautiously screen patients with symptomatic RCC, regardless of lesion size for AI.

Dopamine agonist therapy induces significant recovery of HPA axis function in prolactinomas independent of tumor size: a large single center experience.

Our objective was to compare prevalence and rates of recovery of hypothalamic-pituitary-adrenal axis dysfunction in prolactinoma patients before and after dopamine agonist therapy with nonfunctioning pituitary adenoma patients pre-transsphenoidal and post-transsphenoidal surgery. We retrospectively compared hypothalamic-pituitary-adrenal axis function in patients with prolactinomas naïve to dopamine agonist therapy with a cohort of nonfunctioning pituitary adenoma patients matched for gender and tumor size by classification (n = 57; 30 male/27 female; 27 microadenoma/30 macroadenoma). Patients with <52 weeks follow up, previous medical therapy, surgery, or radiation therapy were excluded. At baseline, there was no difference between groups for age, mean tumor size, or prevalence of adrenal insufficiency. Recovery from baseline adrenal insufficiency was demonstrated in patients with microprolactinomas and macroprolactinomas at a 52 week follow up (p = 0.003 and p = 0.004). These rates were similar to nonfunctioning pituitary adenoma patients after surgery. We show, in a large uniform study, that adrenal insufficiency significantly recovered after dopamine agonist treatment, independent of tumor size and gender in patients with prolactinomas naïve to therapy.

Polycystic ovarian syndrome and Cushing's syndrome: a persistent diagnostic quandary.

OBJECTIVE: To retrospectively review institutional records of female patients of reproductive age with Cushing's disease (CD) and determine if and how many had been previously diagnosed as having solely polycystic ovarian syndrome (PCOS). To determine whether clinical patterns might be useful in identifying appropriate candidates for hypercortisolism screening in women suspected of PCOS. STUDY DESIGN: The study included 50 patients with pathologically proven CD at Oregon Health & Science University, Northwest Pituitary Center between 2006 and 2011. Physical, clinical, and biochemical features for hypercortisolism were compared. RESULTS: Of 50 patients with pathologically proven CD, 26 were women of reproductive age. Of these, half had previously been diagnosed with and treated initially solely for PCOS. Hirsutism and menstrual abnormalities were more common in the group with an initial PCOS diagnosis than in the group with an initial CD diagnosis. CONCLUSIONS: Prolonged exposure to hypercortisolism has been linked with increased mortality and morbidity. Tests for hypercortisolism in all the PCOS cases we report led to an appropriate CD diagnosis. Future research should focus on when and which (if not all) women with suspected PCOS should be tested for hypercortisolism.