Functional pituitary adenomas (FPAs) are associated with hormonal hypersecretion resulting in systemic endocrinopathies and increased mortality. The heterogenous composition of the FPA population has ...made modeling predictive factors of postoperative disease remission a challenge. Here, we aim to define a novel scoring system predictive of disease remission following transsphenoidal surgery (TSS) for FPAs and validate our process using supervised machine learning (SML). 392 patients with FPAs treated at one of the three Mayo Clinic campuses were retrospectively reviewed. Variables found significant on multivariate analysis were incorporated into our novel Pit-SCHEME score. The Pit-SCHEME score with a cut-off value ≥ 6 achieved a sensitivity of 86% and positive likelihood ratio of 2.88. In SML models, without the Pit-SCHEME score, the k-nearest neighbor (KNN) model achieved the highest accuracy at 75.6%. An increase in model sensitivity was achieved with inclusion of the Pit-SCHEME score with the linear discriminant analysis (LDA) model achieving an accuracy of 86.9%, which suggests the Pit-SCHEME score is the variable of most importance for prediction of postoperative disease remission. Ultimately, these results support the potential clinical utility of the Pit-SCHEME score and its prospective future for aiding in the perioperative decision making in patients with FPAs.
The clinical features of adult GH deficiency (GHD) are nonspecific, and GH stimulation testing is often required to confirm the diagnosis. However, diagnosing adult GHD can be challenging due to the ...episodic and pulsatile GH secretion, concurrently modified by age, gender, and body mass index (BMI).
PubMed searches were conducted to identify published data since 2009 on GH stimulation tests used to diagnose adult GHD. Relevant articles in English language were identified and considered for inclusion in the present document.
Testing for confirmation of adult GHD should only be considered if there is a high pretest probability, and the intent to treat if the diagnosis is confirmed. The insulin tolerance test (ITT) and glucagon stimulation test (GST) are the two main tests used in the United States. While the ITT has been accepted as the gold-standard test, its safety concerns hamper wider use. Previously, the GH-releasing hormone-arginine test, and more recently the GST, are accepted alternatives to the ITT. However, several recent studies have questioned the diagnostic accuracy of the GST when the GH cut-point of 3 μg/L is used and have suggested that a lower GH cut-point of 1 μg/L improved the sensitivity and specificity of this test in overweight/obese patients and in those with glucose intolerance.
Until a potent, safe, and reliable test becomes available, the GST should remain as the alternative to the ITT in the United States. In order to reduce over-diagnosing adult GHD in overweight/obese patients with the GST, we propose utilizing a lower GH cut-point of 1 μg/L in these subjects. However, this lower GH cut-point still needs further evaluation for diagnostic accuracy in larger patient populations with varying BMIs and degrees of glucose tolerance.
AACE = American Association of Clinical Endocrinologists BMI = body mass index GH = growth hormone GHD = GH deficiency GHRH = GH-releasing hormone GHS = GH secretagogue GST = glucagon stimulation test IGF = insulin-like growth factor IGFBP-3 = IGF-binding protein 3 ITT = insulin tolerance test ROC = receiver operating characteristic WB-GST = weight-based GST.
Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling ...(AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy.
A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed.
Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 68.7%; and after surgery: 5 10.4%,
< .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted.
Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.
Abstract People with impaired glucose tolerance or impaired fasting glucose, or ‘pre-diabetes”, are at high risk for progression to type 2 diabetes, as are those with metabolic syndrome or a history ...of gestational diabetes. Both glucose-lowering and anti-obesity pharmacotherapies have been studied to determine if the onset of type 2 diabetes can be delayed or prevented. Here we review the available data in the field. The most common theme is the reduction in insulin resistance, such as with weight loss, decreasing demands on the beta cell to improve insulin secretion and prolong its function. Overall, therapies which decrease diabetes incidence in high-risk populations delay the onset of diabetes but do not correct the underlying beta cell defect.
Purpose
The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy.
Methods
Fifty-six acromegaly experts ...from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes.
Results
In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches.
Conclusion
Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.
Cushing's Syndrome (CS) which is caused by isolated corticotropin-releasing hormone (CRH) production, rather than adrenocorticotropin (ACTH) production, is extremely rare.
We describe the clinical ...presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing.
A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml) which should have been suppressed in the presence of high cortisol.
This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.
Hypophysitis is primary or idiopathic or secondary to another disease process. The histologic subtypes of hypophysitis are lymphocytic, granulomatous, xanthomatous, xanthogranulomatous, or ...IgG4-related. Granulomatous hypophysitis is the second most common form and is characterized by multinucleated giant cells with granulomas and histiocytes. It can be idiopathic or secondary to another process such as infection, sarcoidosis, vasculitis, dendritic cell disorders, Crohn's disease (CD) or a reaction to rupture of a Rathke's cyst or pituitary adenoma. We present a case of granulomatous hypophysitis in a patient with CD who had resistance to corticosteroids but a dramatic response to immunosuppressive therapy with anti-tumor necrosis factor (TNF)-α therapy.
A 43-year-old woman with a 9-year history of ileal and colonic CD presented to the Pituitary Center with headaches, visual disturbance, fatigue, nausea, and secondary amenorrhea. She was not on active therapy for her CD at the time of presentation and had no gastrointestinal symptoms. Hormonal evaluation revealed hyperprolactinemia, secondary hypothyroidism and adrenal insufficiency. MRI revealed a 12 × 12 × 19 mm sellar lesion abutting the optic chiasm, reported as a macroadenoma. The patient underwent endoscopic transsphenoidal biopsy of the pituitary mass. Pathology revealed granulomatous hypophysitis. Evaluation for secondary causes of hypophysitis, apart from CD, was negative. Despite a course of high dose prednisone, her symptoms and MRI findings worsened and she developed symptoms consistent with diabetes insipidus. Using a personalized medicine approach, she was started on anti-(TNF)-α therapy with infliximab combined with azathioprine, which are indicated for treatment of CD. Her headaches and polyuria resolved and her menstrual cycles resumed. MRI at 3 months and more than 1.5 years after initiation of anti-TNF-α therapy revealed durable resolution of the pituitary mass.
To our knowledge, this is the first report of successful use of anti-TNF-α therapy for a patient with granulomatous hypophysitis, in this case associated with a previous diagnosis of CD. Although glucocorticoids are used frequently as first-line therapy for primary hypophysitis, granulomatous hypophysitis can be corticosteroid resistant and other immunosuppressive approaches may need to be considered within the context of the patient.
The American Association of Clinical Endocrinologists (AACE) has created a transculturalized diabetes chronic disease care model that is adapted for patients across a spectrum of ethnicities and ...cultures. AACE has conducted several transcultural activities on global issues in clinical endocrinology and completed a 3-city series of conferences in December 2017 that focused on diabetes care for ethnic minorities in the U.S. Proceedings from the "Diabetes Care Across America" series of transcultural summits are presented here. Information from community leaders, practicing health care professionals, and other stakeholders in diabetes care is analyzed according to biological and environmental factors. Four specific U.S. ethnicities are detailed: African Americans, Latino/Hispanics, Asian Americans, and Native Americans. A core set of recommendations to culturally adapt diabetes care is presented that emphasizes culturally appropriate terminology, transculturalization of white papers, culturally adapting clinic infrastructure, flexible office hours, behavioral medicine-especially motivational interviewing and building trust-culturally competent nutritional messaging and health literacy, community partnerships for care delivery, technology innovation, clinical trial recruitment and retention of ethnic minorities, and more funding for scientific studies on epigenetic mechanisms of cultural impact on disease expression. It is hoped that through education, research, and clinical practice enhancements, diabetes care can be optimized in terms of precision and clinical outcomes for the individual and U.S. population as a whole.
To review the current literature regarding dopamine agonists (DAs) and the risk of the development of cardiac valve disease.
PubMed searches were performed to identify all of the available published ...data on DAs and valve disease in patients with hyperprolactinemia.
Most of the available echocardiographic data from patients treated for hyperprolactinemia are from case-control studies, and prospective data are limited. The majority of the studies do not support an increased risk of clinically significant valve disease in hyperprolactinemic patients treated with cabergoline. Evidence for the use of echocardiography is needed to limit unnecessary procedures and healthcare costs. Based on the published literature describing Parkinson's disease (PD) patients, the daily and cumulative doses of cabergoline are important factors. Considerations to minimize exposure to cabergoline, such as surgical resection of adenomas or medication withdrawal in responders, may be appropriate depending on the clinical setting.
There is no conclusive evidence that cabergoline causes clinically significant cardiac valve disease at the usual doses for the treatment of hyperprolactinemia. Although current recommendations from regulatory agencies advise routine echocardiography for patients receiving cabergoline, evidence-based criteria would be useful both to identify patients at risk and generate appropriate screening protocols.
Purpose
Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing’s Disease (CD). Recurrence rates after a first TSS range between 3 and 22% within 3 years. Management of ...recurrent or persistent CD may include repeat TSS or stereotactic radiosurgery (SRS). We performed a meta-analysis to explore the overall efficacy of TSS and SRS for patients with CD after an initial surgical intervention.
Methods
EMBASE, PubMed, SCOPUS, and Cochrane databases were searched from their dates-of-inception up to December 2021. Inclusion criteria were comprised of patients with an established diagnosis of CD who presented with persistent or biochemically recurrent disease after a first TSS for tumor resection and were treated with a second TSS or SRS.
Results
Search criteria yielded 2,116 studies of which 37 articles from 15 countries were included for analysis. Mean age ranged between 29.9 and 47.9 years, and mean follow-up was 11–104 months. TSS was used in 669 (67.7%) patients, while SRS was used in 320 (32.4%) patients, and remission rates for CD were 59% (95%CI 0.49–0.68) and 74% (95%CI 0.54–0.88), respectively. There was no statistically significant difference in the remission rate between TSS and SRS (P = 0.15). The remission rate of patients with recurrent CD undergoing TSS was 53% (95%CI 0.32–0.73), and for persistent CD was 41% (95%CI 0.28–0.56) (P = 0.36).
Conclusion
Both TSS and SRS are possible approaches for the treatment of recurrent or persistent CD after a first TSS. Our data show that either TSS or SRS represent viable treatment options to achieve remission for this subset of patients.
PDF
