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Hypophysitis is considered a rare inflammatory disease of the pituitary gland. For a long time, primary autoimmune hypophysitis has stood out as the most relevant type of hypophysitis. However, with the advent of immunotherapy for the treatment of malignancies and identification of hypophysitis as an immune-related adverse event, hypophysitis has garnered increasing interest and recognition. Therefore, awareness, early recognition, and appropriate management are becoming important as the indication for immunomodulatory therapies broaden.In this review, we discuss the epidemiology, diagnosis, and treatment of hypophysitis with a focus on recent data and highlight subtypes of particular interest while recognizing the gaps in knowledge that remain.Regardless of cause, symptoms and signs of hypophysitis may be related to mass effect (headache and visual disturbance) and hormonal disruption that warrant prompt evaluation. In the vast majority of cases, a diagnosis of hypophysitis can be made presumptively in the appropriate clinical context with radiologic findings consistent with hypophysitis and after the exclusion of other causes.Although subtle differences currently exist in management and outcome expectations between primary and secondary causes of hypophysitis, universally, treatment is aimed at symptom management and hormonal replacement therapy.

Context Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. Objective This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. Methods A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. Results We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. Conclusion Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

Contains fulltext : 245825.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Pituitary apoplexy (PA) is a rare clinical syndrome due to pituitary hemorrhage or infarction. It is characterized by the sudden onset of one or more of the following: severe headache, visual disturbance, nausea/vomiting, and or altered mental status. Most commonly, PA occurs in an underlying pituitary adenoma. The pathophysiology is not fully understood, but it is thought to involve elements of increased metabolic demand and/or compromise to the vasculature of the pituitary or pituitary tumor. Several risk factors have been described. Stabilization of the patient on presentation, replacement of hormonal deficiencies, and reversal of electrolyte abnormalities are the recommended initial steps in the management of patients with PA. Surgical decompression of the mass effect had been the recommended treatment for patients with PA; however, retrospective studies of patients with PA have demonstrated similar outcomes when a conservative approach is applied. This suggests that in highly selected clinical scenarios (mild visual deficit and improving symptoms), conservative management is possible. Further studies, however, are necessary to better stratify patients but are limited by the rarity of the condition and the acuity.

Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p

BACKGROUND Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS A single-institution cohort study of nonsyndromic, radiation-naive patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or

Background: Prolactinomas are rare in children and adolescents. As in adults, dopamine agonists (DAs) are the treatment of choice in the majority of patients. However, at what point children should be taken off of therapy and what the recurrence risk of hyperprolactinemia is following treatment withdrawal is not well described. Objective: Our objective was to systematically review our experience with DA treatment withdrawal in children and adolescents with prolactinomas. Methods: A retrospective review of patients followed for prolactinomas during the last 12 years was conducted. Variables analyzed included age, gender, initial serum prolactin levels, tumor characteristics, cabergoline dose, and results of treatment withdrawal. Clinical characteristics of patients who met eligibility criteria for DA withdrawal were compared with those who did not. Patients who underwent surgery were excluded. Results: Of 47 patients identified, 42 were included in the study. Of those, DA withdrawal was attempted in 13 (31%) and was initially successful in 3 (21%). Patients who did not meet eligibility criteria for treatment withdrawal had higher baseline prolactin levels (p = 0.018) as well as larger (p = 0.03) and more invasive (p = 0.002) tumors. Conclusions: Less than half of our patients were eligible for DA treatment withdrawal and less than one-fourth achieved remission of hyperprolactinemia following cessation of therapy. This suggests that the overall recurrence rate of prolactinomas in pediatric patients may be higher than has been reported in adults.

Introduction Craniopharyngiomas are nonmalignant sellar/parasellar epithelial tumors exhibiting a bimodal age distribution. While the outcomes following the treatment of patients with childhood-onset craniopharyngiomas are well characterized, similar information in adult-onset craniopharyngiomas (AOC) is limited. We aimed to describe the long-term outcomes related to weight changes, obesity prevalence, metabolic comorbidities, and all-cause mortality in patients with AOC following treatment. Methods We identified all adults with a newly diagnosed craniopharyngioma who had initial neurosurgical treatment (1993 -2017) and > 6 months of follow-up at our institution. Medical records were reviewed for demographics, anthropometric measurements, biochemical, radiological, pathological investigations, treatment course, and outcomes. Based on body mass index (BMI), patients were categorized as obese (BMI >30 Kg/m2), overweight (BMI 25-29.9 Kg/m2), and normal weight (BMI < 25 Kg/m2). Results For the 91 patients with AOC, the mean age at diagnosis was 48.2±18 years, and 44% were women. Over a mean follow-up duration of 100.3±69.5 months, weight was significantly higher at last follow-up than before surgery (mean difference 9.4 ±14.8 kg, P= 5% weight gain. Postoperative weight gain of >5% was not associated with preoperative BMI; however, those with lower preoperative BMI experienced a higher mean percentage change in weight [normal weight (20.7 +18%) vs. overweight (13.3+18.0%) vs. obese (6.4+15%), P=0.012]. The prevalence of obesity increased significantly by the last follow-up than before the initial treatment (62 vs. 40.5%, P=0.0042). Weight gain of >5% and obesity by the last follow-up were not associated with gender, tumor size, histological subtype, the extent of resection, radiotherapy, postoperative grade of hypothalamic injury, type or number of pituitary hormone deficiencies, including diabetes insipidus. On follow-up, the proportion of patients who developed hypertension (28 vs. 40% P=0.09) or dyslipidemia (30 vs. 43%, P= 0.06) increased, but this difference was not statistically significant. Whereas the proportion with impaired glucose metabolism (impaired glucose tolerance, impaired fasting glucose, or diabetes mellitus) was significantly increased on follow-up (17.4% vs. 34%, P= 0.017). In a small subset of patients with abdominal imaging, 52% had radiographic evidence of fatty liver disease. At last follow-up, mortality was 12%, with the average age of death 71.9±19.7 years. There was no difference in survival based on BMI >30 kg/m2, ≥3 anterior pituitary hormone deficiencies, diabetes insipidus, the extent of resection, or radiotherapy use. Conclusion Patients treated for AOC experience significant long-term consequences of weight gain, obesity, impaired glucose metabolism, and earlier mortality. The mean percentage increase in weight is inversely proportional to the preoperative BMI. The average age of death (71.9 years) for patients with AOC is lower than the average life expectancy in the US (77.7 years, CDC 2020). Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Objective: To describe outcomes of patients with giant prolactinoma (≥4 cm) and identify predictors of therapeutic response. Methods: In this retrospective study, complete biochemical and structural response were defined as prolactin (PRL) ≤25 ng/mL and no visible tumor at follow-up, respectively. Results: Giant prolactinoma (median size, 4.8 cm [range, 4 to 9.8 cm]; median PRL, 5,927 ng/mL [range, 120 to 100,000 ng/mL]) was diagnosed in 71 patients. Treatments included: dopamine agonists (DAs) (n = 70, 99%), surgery (n = 30, 42%), radiation (n = 10, 14%), and somatostatin analogs (n = 2, 3%). Patients treated with DA monotherapy were older compared with those who received subsequent therapies (47 years vs. 28 years; P = .003) but had similar initial PRL and tumor size. Surgically managed patients were younger compared with the nonsurgical group (35 years vs. 46 years; P = .02) and had lower initial PRL (3,121 ng/mL vs. 6,920 ng/mL; P = .02), yet they had similar tumor response. Hypopituitarism was more common following surgery compared to medical management: adrenal insufficiency (69% vs. 27%; P

Objectives Assessment of surgical outcome in acromegaly is typically recommended at 3 to 6 months following surgery. The purpose of this study was to determine if insulin-like growth factor 1 (IGF-1) concentrations at 6 weeks were equally predictive of surgical outcomes compared with IGF-1 concentrations at 3 to 6 months postoperatively applying newer IGF-1 assays. Methods Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2013 and 2020 and had postoperative IGF-1 measured by 6 weeks and 3 to 6 months. Results At 6 weeks, 20 (35%) of the total 57 had normal IGF-1 and became abnormal in 1 at 3 to 6 months, whereas 37 (65%) of 57 had abnormal IGF-1 concentrations at 6 weeks, which normalized in 1 patient by 3 to 6 months. In patients who changed clinical status, IGF-1 at 6 weeks was within ±0.1-fold of normal. Although a difference was seen between median IGF-1 concentrations (286 vs 267 ng/mL, P = .009) at 6 weeks and 3 to 6 months, the mean reduction was small (–19.9 ng/mL). Conclusions Compared with 3 to 6 months, use of IGF-1 at 6 weeks was associated with a change in clinical status in 3.5% of patients. Therefore, in most patients, IGF-1 at 6 weeks can be used to assess clinical outcome via newer assays.

Advances in the treatment of brain tumors have led to an increase in the number of survivors of this disease. Consequently, the long-term complications associated with past and current treatments are becoming more apparent. Of relevance to patients who receive treatment of brain tumors are the potential neuroendocrine complications that develop either acutely or several years following treatment. Presentation may differ between adults and children (e.g., short stature or adult growth hormone deficiency) but in both settings can complicate treatment and impact quality of life. The risk for the development of these complications depends on the location of the tumor (proximity to the pituitary/hypothalamus) and/or the treatment delivered (chemotherapy/surgery/radiation). Given the potential overlap in symptoms attributable to the underlying brain tumor and neuroendocrine dysfunction, a high level of suspicion, appropriate investigation, and administration of treatment may reduce morbidity and mortality for patients with brain tumors experiencing neuroendocrine dysfunction.

Objectives Brain tumors, including pituitary adenomas (PA), cause anxiety and distress, with a high unmet need for information correlating with increased anxiety. Condition-specific education may alleviate anxiety. We explored patients’ experience around the diagnosis of a PA and piloted a patient education intervention to address peridiagnostic anxiety in adults diagnosed with PA. Methods Anxiety, patient satisfaction, patient knowledge, and need for information were measured prior to, immediately after, and 1 month following the appointment in this multimethods study. A phone interview to explore patient diagnostic and intervention experiences was analyzed using qualitative methods. Results A total of 17 patients participated in the study; 15 completed the interview. The baseline need for information was high. Disease-specific anxiety decreased, and patient knowledge and satisfaction increased significantly after the initial visit. Interview analysis identified 3 main themes: (1) the importance of communication; (2) the need for information; and (3) the impact of the diagnosis on patient experience. Conclusions For patients with newly diagnosed PA, the diagnostic experience was associated with high levels of anxiety. Patients expressed a need for information. Information delivery reduced anxiety and had a positive impact on patient satisfaction. Practice Implications The study findings suggest a need for a streamlined diagnostic process with readily accessible information.

Establishing a definitive diagnosis of Cushing disease (CD), given its clinical and biochemical heterogeneity, initiating effective treatment to control the effects of hypercortisolism, and managing recurrence are challenging disease aspects to address. Mifepristone is a competitive glucocorticoid receptor antagonist that is approved in the US by the Food and Drug Administration to control hyperglycemia secondary to endogenous hypercortisolism (Cushing syndrome) in patients who have glucose intolerance or type 2 diabetes mellitus and have failed surgery or are not candidates for surgery. Herein, we describe 6 patients with CD who received mifepristone as adjunct/bridge therapy in the following clinical settings: to assess clinical benefits of treatment for suspected recurrent disease, to control hypercortisolism preoperatively for severe disease, to control hypercortisolism during the COVID-19 pandemic, and to provide adjunctive treatment to radiation therapy. The patients were treated at multiple medical practice settings. Mifepristone treatment in each of the described cases was associated with clinical improvements, including improvements in overall glycemia, hypertension, and weight loss. In addition, in one case where biochemical and radiological evidence of disease recurrence was uncertain, clinical improvement with mifepristone pointed toward likely disease recurrence. Adverse events associated with mifepristone reported in the 6 cases were consistent with those previously reported in the pivotal trial and included cortisol withdrawal symptoms, antiprogesterone effects (vaginal bleeding), hypothyroidism (treated with levothyroxine), and hypokalemia (treated with spironolactone). These cases show how mifepristone can potentially be utilized as a therapeutic trial in equivocal cases of CD recurrence; as a presurgical treatment strategy, particularly during the COVID-19 pandemic; and as bridge therapy, while awaiting the effects of radiation.

Context Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear. Objective To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain. Design Cross-sectional study, 2016-2018. Setting Referral center. Patients Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center. Main outcome measure Diagnosis of OIAI was considered if positive case detection (cortisol Results In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking 20 mg); however, specificity of MME cutoff >20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function. Conclusion The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.

Opioid-induced adrenal insufficiency (OIAI) may develop in patients treated with chronic opioids due to suppression of the hypothalamic-pituitary-adrenal axis. Our objective was to describe the clinical manifestations, biochemical presentation, and clinical course of OIAI.A retrospective study of adults diagnosed with OIAI between 2006 and 2018 at an academic center. Opioid daily dose was converted into morphine milligram equivalents (MMEs).Forty patients (women, n = 29lsqb;73%]) taking chronic opioids at a daily median MME dose of 105 (60 to 200) mg and median duration of 60 (3 to 360) months were diagnosed with OIAI. Patients reported fatigue (n = 29, 73%), musculoskeletal pain (n = 21, 53%), and weight loss (n = 17, 53%) for a median of 12 (range, 1 to 132) months prior to diagnosis, and only 7.5% (n = 3) of patients were identified with OIAI through case detection. Biochemical diagnosis of OIAI was based on (1) low morning cortisol, baseline adrenocorticotropic hormone and/or dehydroepiandrosterone sulfate in 59% (n = 26) of patients or (2) abnormal cosyntropin stimulation test in 41% (n = 14) of patients. With glucocorticoid replacement, 16/23 (70%) patients with available follow-up experienced improvement in symptoms. Opioids were tapered or discontinued in 15 patients, of whom 10 were followed for adrenal function and of which 7 (70%) recovered from OIAI.Minimum daily MME in patients diagnosed with OIAI was 60 mg. OIAI causes significant morbidity, and recognition requires a high level of clinical suspicion. Appropriate glucocorticoid treatment led to improvement of symptoms in 70%. Resolution of OIAI occurred following opioid cessation or reduction.

Background: The impact of traumatic brain injury (TBI) on pituitary function remains unclear. Yet, applying appropriate diagnostic and treatment strategies for affected patients is crucial for mitigating morbidity related to hypopituitarism and improving patient outcomes. Currently, data regarding the prevalence of post-TBI hypopituitarism and its predisposing factors are inconsistent. The goals of this systematic review and meta-analysis were to evaluate the prevalence of acute and chronic post-TBI hypopituitarism and assess for predictors of pituitary dysfunction. Methods: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2019. Studies enrolling ≥20 adult patients with TBI and reporting on pituitary dysfunction were included. A total of 992 studies were generated by the initial search. Titles and abstracts were screened in duplicate by two independent reviewers for inclusion criteria. Of these, 265 full text manuscripts were subsequently reviewed for eligibility. Predefined data were extracted from 14 representative studies for the preliminary analysis (7 cross-sectional studies, 6 prospective studies, and 1 retrospective study). Results: There was a total of 813 (78% male) patients with TBI. Of those with available data, 124/248 (50.0%) had mild TBI, 112/476 (23.5%) had moderate TBI, and 308/569 (54.1%) had severe TBI. Mean age at TBI diagnosis was 34.2±4.6 years, with time to evaluation of pituitary function following TBI ranging from 0 days to 120 months (mean, 27.1±35.1 months). Acute and chronic hypopituitarism was reported in 10.7% and 19.6% of patients, respectively. TBI was associated with increased risk for hypopituitarism compared to the general population (RR=765.8, 95% CI 538.8-1088.5). Secondary hypogonadism was noted in 15.7% of patients, growth hormone deficiency in 15.7%, secondary adrenal insufficiency in 11.6%, secondary hypothyroidism in 8.7%, and diabetes insipidus in 0.2%. Older age (40.4±5.5 vs 36.7±1.0 years, P Conclusion: Available moderate- to low-quality evidence suggests that post-TBI hypopituitarism is common and correlates with older age and higher BMI. Secondary hypogonadism and growth hormone deficiency are the most predominant pituitary deficiencies. Further investigations are warranted to determine the most effective strategies for identifying patients at risk for post-TBI hypopituitarism in order to implement prompt assessment and management.

Introduction: The prevalence of obesity is increasing worldwide and treatment remains challenging. Certain endocrine disorders may contribute to weight gain. These are important to recognize as treatment may have beneficial impact on weight. Studies have reported an increased prevalence of obesity in patients with prolactinomas. While several studies have examined the association between weight gain and prolactinomas, the results are conflicting. Therefore, the aim of this study was to determine if BMI is higher among those with a prolactinoma compared to those without. Methods: We identified all patients ≥18 years of age referred to endocrinology between 2008–2018 with a newly diagnosed prolactinoma (defined as a prolactin levels ≥40 ng/ml on 2 separate occasions and a pituitary adenoma evident on MRI without secondary causes for hyperprolactinemia). We extracted the following variables from the medical record: patient demographics, presenting symptoms, prolactin level and tumor size at diagnosis. Comparative data was obtained from the National Health and Nutrition Examination Survey (NHANES) 2015–2016, from which we included only those ≥18 years of age who had BMI data. Results: In total 34 patients with a newly diagnosed prolactinoma (female: 27 /34, 79%, mean age at diagnosis: 35.4 ± 10.7 years) met inclusion criteria. The majority of patients (23/34, 68 %) had microadenomas defined as Conclusion: Weight gain is a presenting symptom for many patients with a newly diagnosed prolactinoma. When compared to a large cohort of adults in the US, those with a prolactinoma have higher BMI and an increased prevalence of class II obesity. Based on the correlation between BMI and log-transformed prolactin levels, we hypothesize that this weight difference may be related to hyperprolactinemia. These findings suggest that, in the appropriate context, hyperprolactinemia should be considered when a patient presents with weight gain.

Introduction: Brain tumors, including benign pituitary adenomas (PA), cause high levels of anxiety and distress. Patients with PA also report high unmet needs for information, a factor correlated with anxiety. Although many factors can contribute to anxiety, condition-specific education may alleviate anxiety for these patients. Aim: To explore the patients’ experience related to discovery of a pituitary adenoma and pilot a patient education intervention to address peri-diagnostic anxiety. Method: This mixed-methods pilot study evaluated the acceptability and effectiveness of an education intervention for adults diagnosed with PA (nonfunctioning PA or prolactinoma). At their first endocrine appointment, patients were given disease-specific information verbally, reinforced with printed material. Anxiety [Generalized Anxiety Disorder (GAD)-7 and Visual Analogue Scale for Anxiety (VAS-A)], patient satisfaction (Likert 1–5), patient knowledge of pituitary tumors [patient knowledge questionnaire (PKQ)] and need for information (Likert 1–5) was measured prior, immediately after, and 1 month following appointment. Patients participated in a semi-structured phone interview designed to explore patient diagnostic experiences pre-and post- intervention and to elicit patient evaluation of the intervention. Interviews were tape-recorded, transcribed, and analyzed using qualitative methods. Results: Seventeen patients participated in the study; 15 of these completed the interview. Baseline need for information was high (4.6± 0.6). Anxiety level by VAS-A [median (IQR) was 50 (35–71) prior, 47 (21–68) immediately after and 1 month later 31 (14–44)] and GAD-7 [median value before 9 (4–13), immediately after 7 (3–13) and 1 month later 5 (3–8)] improved significantly (P < 0.01). PKQ was high at baseline (15 ± 0.4 /18) and increased (after 15.9 ± 0.4 and 1 month 15.8 ± 0.4, P=0.045). Patient satisfaction significantly improved (2.8 vs 4.6, P < 0.01). Analysis of the semi-structured interviews identified 3 main themes: (1) Communication, (2) Need for information; and (3) Impact of the diagnosis on patient experience. Patient experience in relation to each theme was reported negatively prior to the intervention and positively post-intervention. Conclusion: The diagnostic experience is challenging for patients with newly diagnosed PA and is associated with high levels of anxiety despite most patients being notified of the benign diagnosis. Although patients desire more information, patients scored highly on the baseline PKQ. The delivery of information had a significant positive impact on patient satisfaction and led to a reduction in anxiety. While these observations are not controlled, the themes identified have important clinical implications. They suggest that patient experience can be improved by a timely, streamlined diagnostic process with readily accessible information.

Introduction: Transsphenoidal surgery is recommended as first line therapy in the vast majority of patients with acromegaly. Successful surgical intervention is determined by normalization of insulin like-growth factor (IGF) - 1 and adequate suppression of growth hormone (GH) during glucose GH suppression test or random GH levels Aim: To determine if IGF-1 levels at 6 weeks were equally predictive of surgical outcomes when compared to IGF-1 levels at 3–6 months postoperative. Methods: Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2010–2019 and had post-operative IGF-1 level measured at 6 weeks and 3–6 months. IGF-1 was measured using the Siemens Immulite assay until 2016 when it was replaced by a LC-MS/MS assay. IGF-1 measurements at 6 weeks are obtained based on clinician discretion. Results: 69 patients (mean age 49 ± 14.8, female 31/69, 44.9%) with acromegaly had surgery and IGF-1 follow-up measurements at 6 weeks and 3–6 months. Persistent acromegaly was noted in 45/69 at 3–6 months. The median IGF-1 pre-operative was 701 ng/ mL (289–1600), 6 weeks postoperative was 286 ng/ mL (109–1038) and at 3–6 months was 267 ng/ mL (77–996). The median pre-operative IGF-1 was significantly higher than the median IGF-1 level at 6 weeks and 3–6 months (P= Conclusion: In the vast majority of patients, 6 weeks post-operative IGF-1 can be used to assess response to surgery avoiding a delay in treatment. However, we would recommend repeating IGF-1 levels at 3–6 months in those who have marginally elevated IGF-1 above normal (≤ 1.12), without cavernous sinus invasion and a post-operative GH of

Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred >3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P < 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.

The clinical relevance of the metabolically healthy overweight/obese (MHO) phenotype is controversial and the relationships between weight change and the development of cardiometabolic risk factors is unknown. Therefore, we aim to: (1) Assess the long-term risk of developing one or more components of the metabolic syndrome in MHO adults compared with metabolically healthy normal weight (MHNW); (2) Evaluate risk of a composite of death, cardiovascular disease (CVD), and risk of developing type 2 diabetes between adults defined according to baseline body mass index and metabolic health.Retrospective cohort study of adults 18-65 years of age seen at our institution between 1998 and 2000 who lived in Olmsted County. Metabolically healthy was defined as the absence of all components of the metabolic syndrome (except for waist circumference). Main outcome was the development of metabolic risk factors. The secondary outcome was a composite of mortality, CVD and heart failure.Of the 18 070 individuals with complete data at baseline, 1805 (10%) were MHO (mean age 38±11 years) and 3047 were MHNW (mean age 35±11 years). After a median follow-up of 15 years, interquartile range 10-17, 80% of MHO vs 68% of MHNW developed at least one cardiometabolic risk factor (P0.001). In multivariate analysis, MHO individuals who gained ⩾10% of their body weight were more likely to have developed metabolic complications compared to MHO individuals that did not gain weight (P=0.001 for 10-15%, P0.001 for15% weight gain). The risk for the secondary composite end point was similar between MHO and MHNW, number of events 218/1805 vs 217/3048 for MHO and MHNW, respectively, (hazard ratio: 1.16, 95% confidence interval: 0.96-1.40).MHO are more likely to develop metabolic complications than MHNW, especially if they gain weight.

Hypopituitarism is defined as a deficiency in 1 or more pituitary hormones. The pituitary gland is composed of the anterior pituitary, which originates from an invagination of the oral ectoderm and forms the Rathke pouch, and the posterior pituitary, which is derived from the neural ectoderm of the diencephalon. The anterior pituitary is composed of 5 types of hormone-producing cells: Somatotrophs produce growth hormone; gonadotrophs, follicle-stimulating hormone and luteinizing hormone; thyrotrophs, thyrotropin; 4 lactotrophs, prolactin; and corticotrophs, corticotropin. Identification of hypopituitarism is important because of its association with premature death due to respiratory and cardiovascular complications.

Objectives Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). Methods Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. Results Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). Conclusions Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Objective: Opioid-induced adrenal insufficiency (OIAI) is reported in up to 29% of chronic opioid users through suppression of the hypothalamus-pituitary-adrenal axis. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, healthcare provider (HCP) awareness of OIAI is crucial. The aim of the present study was to assess the knowledge and current practices of HCPs regarding OIAI and to identify factors associated with decreased awareness. Methods: We carried out a cross-sectional, anonymous survey of HCPs in internal medicine specialties that prescribe or care for patients taking chronic opioids. Results: Of 91 (30%) participants who completed the survey, 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n = 33, 36%), followed by endocrinologists (n = 13, 14%) and various other specialties (n = 45, 49%). While 61 (67%) of respondents prescribed opioids, only 17 (19%) were comfortable in their knowledge of opioid side effects. Among nonendocrine providers, 53 (68%) identified adrenal insufficiency as a known opioid-induced endocrinopathy. Compared to other providers, endocrinologists were more likely to recognize opioid-related endocrinopathies (69% versus 24%, P = .01) and to identify the correct symptoms for OIAI (38% versus 9%, P

BACKGROUND: Chronic opioid use may lead to adrenal insufficiency due to central suppression of the hypothalamic-pituitary-adrenal axis. Opioid induced adrenal insufficiency (OIAI) is likely under-recognized and its prevalence is unclear. OBJECTIVE: To determine the prevalence of OIAI in patients taking opioids for chronic pain and to identify predictors of OIAI. METHODS: A prospective study of patients admitted to the Pain Rehabilitation Center (PRC) at an academic medical center completed between 2016 and 2018. Inclusion criteria were: 1) age ≥18 years, 2) intermittent or continuous opioid use of at least 90 days, 3) am cortisol measurement on admission. Exclusion criteria were: 1) known pituitary or adrenal dysfunction, 2) exogenous glucocorticoid use within 3 months. Each patient’s opioid daily dose was converted into a morphine mg equivalent (MME). All patients had a functional 5-minute walk test and measurements of quality of life on admission to the PRC. Diagnosis of OIAI was based on the endocrine evaluation. RESULTS: One hundred sixty-two patients (median age of 53.5 years (range 21-84), 67% women, 95 % Caucasian) met inclusion criteria. Patients used opioids daily (141, 87%) or as needed (21, 13.0%) at a median MME of 30 mg (3-840), median duration of 60 months (3-360). In addition to morning cortisol (CORT), 112 (69.1%) patients had measurements of corticotropin (ACTH) and 106 (65.4%) - dehydroepiandrosterone sulfate (DHEAS). CORT was directly correlated with both DHEAS (p=0.04) and ACTH (p20 mg), however specificity of MME cutoff >20 mg to predict OIAI development was only 34%. After opioid discontinuation, 3/8 patients recovered adrenal function when reassessed at 14 months (5-14). CONCLUSION: The prevalence of OIAI based on the endocrine evaluation was 5%, with MME being the only predictor for OIAI development. Patients on MMED of 20 mg and above should be monitored for OIAI. Abnormalities in the hypothalamic-pituitary-adrenal axis were frequent, affecting 14-21% of patients taking opioids, possibly contributing to patients’ symptoms, physical performance and well-being.

Background: Thymic hyperplasia (TH) is a known, but often under-recognized finding associated with Graves' disease (GD). The exact pathophysiology of GD-related TH is poorly understood, but is thought to be benign. Limited case reports or series indicate resolution or improvement of TH following successful treatment of GD. Although TH is often incidentally found, discovery can be alarming resulting in potentially inappropriate intervention. Therefore, increased awareness regarding GD-related TH is necessary to avoid this. Aim: To describe the natural history of GD-related TH and assess for risk factors which may be associated with the development of TH. Methods: Retrospective review of patients referred to a tertiary referral center with GD with an anterior mediastinal mass on computed tomography (CT) scan suspected to be TH. Clinical Cases: In total, six patients (30-51 years of age) were discovered to have an anterior mediastinal mass on CT scan at time of GD diagnosis. The majority were women (5/6). Although three patients had a family history of thyroid autoimmunity, only one patient had a co-existing autoimmune condition (Vitiligo). Two patients were active smokers. All patients presented to the emergency room with significant thyrotoxic symptoms including tachycardia (107-170 beats per minute) and weight loss (18.3 ± 11.8 kg) with four requiring admission. One patient presented with thyroid storm. Laboratory testing revealed high circulating thyroid hormone levels at diagnosis with mean free T4 level of 4.24 ± 1.56 ng/dL (0.6-1.76) as well as high mean thyroid-stimulating immunoglobulin activity level of 306.2% (≤122). Clinically significant Graves'-associated orbitopathy was observed in 67% of patients. Tachycardia was the cited reason for requested CT imaging in all patients. The size of thymus glands varied with the largest measuring 9cm x 1cm x 5cm. All thymic masses were consistently characterized as homogeneous without discrete lesions or calcifications. Though only two patients received follow-up chest imaging, both patients demonstrated > 50% reduction in thymus size at six months and no patients underwent biopsy or surgical excision. All but one of our patients required definitive therapy for poorly controlled hyperthyroidism on thionamides (Three had surgery of whom two had severe Graves' orbitopathy and two underwent radioactive iodine therapy). Conclusions: While the true incidence of GD-associated TH is unknown, increased use of imaging modalities may result in further incidental discoveries. Therefore, clinicians need to be aware of the association between benign TH and GD to avoid unnecessary invasive interventions. Furthermore, our findings suggest that GD-related TH may be a marker of GD severity with a lower likelihood of GD remission using thionamides necessitating definitive therapy.

Background: Opioid crisis was declared a nationwide public health emergency by the Department of Health Services in 2017. Despite ongoing efforts to minimize opioid prescriptions, opioid use remains prevalent. Chronic opioid use is associated with significant adverse effects including suppression of the hypothalamus-pituitary-adrenal axis. Opioid induced adrenal insufficiency (OIAI) is reported to affect up to 29% among chronic opioid users. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, medical provider awareness of symptoms, diagnosis and therapy of OIAI is key. Objective: To assess the knowledge and current practices in care of patients with OIAI and to identify factors associated with decreased awareness of OIAI. Methods: Healthcare providers from the internal medicine specialties who prescribe or care for patients taking chronic opioids were invited to participate in a cross-sectional, web-based, anonymous survey conducted at our center. Results: Of 91 participants who completed the survey (30% response rate), 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n=33, 36%), followed by endocrinologists (n=13, 14%) and various other specialties (n=45, 49%). While 61 (67%) of respondents reported prescribing opioids, only 17 (19%) stated being comfortable in their knowledge of opioid side effects. Only one non-endocrine provider reported making at least one diagnosis of OIAI. Among non-endocrine providers, 58 (74%) identified hypogonadism and 53 (68%) identified AI as known opioid-induced endocrinopathies, however hirsutism and hypothyroidism were also incorrectly chosen by 16 (20%) and 28 (36%) respectively. Compared to other providers, endocrinologists were more likely to recognize possible opioid-related endocrinopathies (26% vs 92%, respectively, P

Insulin-like growth factors (IGFs) are implicated in the development of diabetic nephropathy (DN) and are shown to increase proliferation and extracellular matrix production in mesangial cells. The IGF system is complex and is composed of ligands, receptors, six binding proteins (IGF BPs) and a novel zinc metalloproteinase – pregnancy-associated plasma protein (PAPP)-A. PAPP-A increases the local bioavailability of IGF through the cleavage of IGF BP-4. Mesangial expansion is a major component of DN, and PAPP-A is shown to be increased in the glomeruli of patients with DN. Therefore, we determined the expression of PAPP-A and components of the IGF system in normal human mesangial cells (HMCs) and their regulation by factors known to be involved in DN. Under basal conditions, HMCs expressed PAPP-A, IGF1 receptor and all six IGF BPs. Interleukin (IL)-1β was the most potent stimulus for PAPP-A expression (5-fold) followed by tumor necrosis factor (TNF)-α (2.5-fold). This PAPP-A was secreted, cell associated and proteolytically active. IL1β also increased IGF BP-1expression (3-fold) with either reduction or no effect on other IGF BPs. Generally, TNF-α treatment decreased IGF BP expression. No treatment effect on PAPP-A or IGF BPs was seen with IL6, IGFs, advanced glycation end products or prolonged hyperglycemia. In addition, stimulation of HMCs with IGF1 alone or IGF1 complexed to wild-type, but not protease-resistant, IGF BP-4 led to increased [3H]-thymidine incorporation. In conclusion, these novel findings of PAPP-A and its regulation by proinflammatory cytokines, as well as the comprehensive analysis of the IGF system regulation in HMCs, suggest a mechanism by which inflammatory states such as DN can impact IGF activity in the kidney.

Background Zollinger-Ellison syndrome is a rare cause of tumoral hypergastrinemia; 1 of 5 patients with this syndrome also has multiple endocrine neoplasia type 1. The diagnosis of this disease is complicated by the widespread use of proton pump inhibitors that can elevate serum gastrin levels, the cornerstone for biochemical diagnosis. Abrupt discontinuation of proton pump inhibitors could lead to adverse outcomes. Clinician awareness of the relationship between Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 could lead to a safer diagnostic pathway. Methods We conducted a retrospective review of a cohort of patients with multiple endocrine neoplasia type 1. Results There were 287 patients with multiple endocrine neoplasia type 1 (73 with gastrinoma) evaluated between 1997 and 2014. Two patients experienced adverse events after proton pump inhibitor therapy was discontinued to re-measure serum gastrin level during the evaluation of severe peptic ulcer disease. In both cases, the diagnosis of multiple endocrine neoplasia type 1 was made after proton pump therapy was discontinued. Conclusion Abrupt discontinuation of proton pump therapy can lead to adverse outcomes in patients with Zollinger-Ellison syndrome. Clinical assessment for features of multiple endocrine neoplasia type 1 (eg, serum calcium levels, personal and family history of hypercalcemia, pituitary or pancreatic tumors) could identify patients with higher risk for a tumoral source of hypergastrinemia where imaging studies can help support the diagnosis without the potential side effects of abrupt discontinuation of proton pump inhibitor therapy.

Measuring the plasma corticotropin (ACTH) concentration is an important step in determining the underlying cause in patients with hypercortisolemia. Interfering substances in immunoassays can lead to erroneous results impacting clinical management. We describe a case series of 12 patients, the majority of whom were being investigated for possible Cushing's syndrome and in whom inconsistencies between the clinical picture and biochemical testing raised concerns of assay interference. ACTH assay interference resulted in falsely elevated ACTH concentrations using the Siemens Immulite assay and consequently led to additional unnecessary testing. Communication between physician and laboratory as well as appropriate investigation (including sample dilution, use of blocking antibodies and testing on an alternate platform) resulted in assay interference identification. Recognition of biochemical results which are clinically discrepant remains an essential step in patient assessment.

Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution.A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995-2015.A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not.In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly.CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.

We describe a family with multiple endocrine neoplasia type 2A (MEN2A) caused by the D631Y RET mutation resulting in an atypical phenotype. The index case was a 24-year-old man with history of recurrent anaplastic ependymoma incidentally found to have the D631Y RET mutation. At first assessment, four family members had evidence of large pheochromocytomas. One patient was found to have micromedullary thyroid cancer at 79 years of age. None of the patients had primary hyperparathyroidism. Patients with MEN2A caused by a D631Y RET mutation most commonly present with pheochromocytomas. Medullary thyroid cancer is a less common part of the syndrome when compared with other RET mutations.

Objective: The 72-hour fast is used to document Whipple's triad and understand the mechanism of hypoglycemia. Although hypoglycemia develops within 24 hours in the majority of fasts, identifying possible determinants of fast duration may help to predict the need for admission. Therefore, we determined the relation between anthropometric features on fast duration and assessed end of fast parameters on maximal tumor size, extent of disease, or tumor recurrence. Methods: A retrospective analysis of patients with insulinoma in the past 25 years who underwent a 72-hour fast was conducted. Electronic medical records were reviewed to obtain anthropometric patient data and tumor characteristics. Results: A total of 233 patients underwent the 72-hour fast. The mean age at diagnosis was 50 ± 16 years, with a body mass index (BMI) of 29 ± 7 kg/m2, and 66% (153 of 233) were female. Duration of fast was not associated with gender (P = .2), age (P = .3), or BMI (P = .7). A shorter fast duration was inversely related to end of fast C-peptide (P = .0075) but not insulin (P = .13) or proinsulin (P = .28) concentration. End of fast C-peptide was associated with increased tumor size (P = .036) and multiplicity (P =.01). Proinsulin was associated with increased tumor size (P Conclusion: Duration of fast was not significantly related age, gender, weight, or BMI, although end-of-fast C-peptide and proinsulin may provide some information regarding tumor characteristics. Consequently, the duration of fast cannot be predicted a priori and should be allowed to run for the planned length unless hypoglycemia develops. Abbreviation: BMI = body mass index

Objective Thyroglobulin (Tg) quantitation by immunometric assays is compromised by anti-thyroglobulin antibodies (TgAbs), potentially resulting in falsely low Tg concentrations. TgAb screening is recommended when measuring Tg, but current TgAb immunoassays do not detect all possible TgAbs in circulation. We assessed the impact of a change in TgAb assay on apparent disease status of patients with differentiated thyroid carcinoma (DTC). Methods Patients seen at the Mayo Clinic, Rochester, Minnesota, for follow-up of DTC, who had been tested using 2 different TgAb assays (Beckman Access and Roche Elecsys) were identified. Electronic medical records were reviewed to evaluate any impact the change in TgAb assay had on clinical disease status assessment and follow-up. Results A total of 1,457 patients were tested using both assays. A change in TgAb status was found in 124 (8.5%) patients; a total of 117 patients who were TgAbnegative on the Beckman assay became TgAb-positive with the Roche assay. Additional testing was performed in 5 of these patients. Seven patients previously considered TgAb-positive were now TgAb-negative. In all 7 cases, physicians documented that they considered these patients now to be truly TgAb-negative and free of disease. Conclusion Discrepancies in TgAb status are seen when using different TgAb assays. Relying on Tg and TgAb measurements to determine disease status may lead to underestimation of residual cancer. A multimodal (clinical, biochemical, and radiologic) approach to follow up on patients with DTC should be continued, pending the development of Tg quantitation methods that are highly sensitive and not affected by TgAb interference. (Endocr Pract. 2014;20:1032-1036)

Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas.We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014.Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas.Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy.ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.

Background In patients with multiple endocrine neoplasia type 1 (MEN-1), pancreaticoduodenal (PD) neuroendocrine tumors (NETs) are associated with early mortality, yet, the best treatment strategy, remains uncertain. Aim To assess patient important outcomes (mortality and metastasis) of PD NETs and predictors of outcomes in patients with MEN-1. Methods Retrospective cohort of patients with MEN-1 who attended the Mayo Clinic, Rochester, MN from 1997-2014. Results We identified 287 patients with MEN-1; 199 (69%) patients had 217 PD NETs. Among those with a PD NETs, 129 (65%) had surgery of which 90 (70%) had their primary surgery performed at Mayo Clinic. The median postoperative follow-up was 8 years during which, 13 (14%) patients died. The mean (± standard deviation) age of death was 51(±9) years. Tumor size, metastasis at surgery, or tumor type were not predictive of mortality, but for every year older at surgery the odds of metastasis increased by 6%. Surgery was not performed in 70 (35%) patients. Among those who were observed/medically managed without known metastatic disease, mean tumor growth was 0.02 cm/yr (range, - 0.13 - 0.4 cm/yr). Four patients (7%) died at a median age of 77 (range, 51-89) years. Conclusion PD NETs are common in patients with MEN-1 and are associated with early mortality even after surgical intervention. Active surveillance is a viable option in nonaggressive PD NETs, although definitive factors identifying such patients are lacking. Therefore, counselling regarding risks and benefits of current treatment options remains integral to the care of patients with MEN-1. This article is protected by copyright. All rights reserved.

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases—MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995–2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53–1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70–1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51–2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.