Multidisciplinary Postoperative Care Pathway to Reduce Readmissions following Endoscopic Transsphenoidal Pituitary Surgery: Improving Quality of Patient Care.

Background Thirty-day unplanned readmission following endoscopic transsphenoidal pituitary surgery (ETPS) occurs in up to 14% of patients. Delayed hyponatremia is one of the most common causes, accounting for 30% of readmissions and often occurs within 1 week of surgery. The authors' prior retrospective review identified endocrinology follow-up as protective factor. Objectives Implementation of a multidisciplinary postoperative care (POC) pathway: (1) to reduce 30-day hospital readmissions following ETPS and (2) improve inpatient and outpatient coordination of care with endocrinologist. Methods This study is a single institution temporal cohort study of patients prior to (control cohort) and after implementation of the POC pathway (intervention cohort). The POC pathway utilized postdischarge 1 to 1.5 L/d fluid restriction, postoperative days 5 to 7 serum sodium, and endocrinology follow-up within 1 week of discharge to stratify patients into tiered hyponatremia regimens. Results A total of 542 patients were included in the study, 409 (75%) in the control cohort and 133 (25%) in the intervention cohort. All-cause readmission was significantly reduced following implementation of the POC pathway (14 vs. 6%, p = 0.015). Coordination with endocrinologist significantly increased in the inpatient (96 vs. 83%, p < 0.001) and outpatient (77 vs. 68%, p = 0.042) settings. Patients who were not in the POC pathway had the highest risk of readmission (odds ratio: 2.5; 95% confidence interval: 1.1-5.5). Conclusion A multidisciplinary POC pathway incorporating endocrinologist in conjunction with postdischarge weight-based fluid restriction and postoperative serum sodium levels can safely be used to reduce 30-day readmissions following ETPS.

30-Day Readmissions and Coordination of Care Following Endoscopic Transsphenoidal Pituitary Surgery: Experience with 409 Patients.

Objective The study aimed to (1) quantify readmission rates and common causes of readmission following endoscopic transsphenoidal pituitary surgery (ETPS); (2) identify risk factors that may predict readmission within 30 days; (3) assess postoperative care coordination with endocrinology follow-up; and (4) identify patients for whom targeted interventions may reduce 30-day readmissions. Methods Retrospective quality improvement review of patients with pituitary adenoma who underwent ETPS from December 2010 to 2018 at a single tertiary care center. Results A total of 409 patients were included in the study, of which 57 (13.9%) were readmitted within 30 days. Hyponatremia was the most common cause of readmission (4.2%) followed by pain/headache (3.9%), cerebrospinal fluid leak (3.4%), epistaxis (2.7%), hypernatremia (1.2%), and adrenal insufficiency (1.2%). Patients with hyponatremia were readmitted significantly earlier than other causes (4.3 ± 2.2 vs. 10.6 ± 10.9 days from discharge, p = 0.032). Readmitted patients had significantly less frequent outpatient follow-up with an endocrinologist than the nonreadmitted cohort (56.1 vs. 70.5%, p = 0.031). Patients who had outpatient follow-up with an endocrinologist were at lower risk of readmission compared with those without (odds ratio: 0.46; 95% confidence interval: 0.24-0.88). Conclusion Delayed hyponatremia is one of the most common causes of 30-day readmission following ETPS. Postoperative follow-up with an endocrinologist may reduce risk of 30-day readmission following ETPS. Implications for Clinical Practice A multidisciplinary team incorporating otolaryngologist, neurosurgeons, and endocrinologist may identify patients at risk of 30-day readmissions. Protocols checking serum sodium within 1 week of surgery in conjunction with endocrinologist to tailor fluid restriction may reduce readmissions from delayed hyponatremia.

PRIMARY ADRENAL INSUFFICIENCY SECONDARY TO CHRONIC POSACONAZOLE USE.

OBJECTIVE: Posaconazole (PSO) is commonly used in the treatment of invasive fungal infections. PSO-induced primary adrenal insufficiency (PAI) is rare, and we present what we think to be the third case report of its incidence. We want to bring awareness to this rare but significant side effect that can impact management and monitoring of patients on this medication. METHODS: After clinical assessment, the patient was evaluated with diagnostic studies including measurements of cortisol, adrenocorticotropic hormone, renin activity, and aldosterone levels. Imaging studies such as abdominal computed tomography were also performed. RESULTS: A 65-year-old man with a history of hemophagocytic lymphohistiocytosis on a dexamethasone taper, complicated with mucormycosis on PSO presented to the emergency department with weakness, fatigue, decreased appetite, orthostatic hypotension, low morning cortisol (0.4 µg/dL), low adrenocorticotropic hormone (3.4 pg/mL), elevated plasma renin (16.7 ng/mL/hour), and low-normal aldosterone (1.7 ng/dL). Abdominal computed tomography imaging revealed bilaterally intact adrenal glands. A diagnosis of PSO-induced PAI was made. Fludrocortisone was initiated in addition to glucocorticoids with improvement of fatigue, appetite, blood pressure, and normalization of sodium and potassium. A month after discontinuing PSO, steroids and fludrocortisone were discontinued with measured morning cortisol of 13 µg/dL and an adrenocorticotropic hormone level of 53.9 pg/mL, both normal. CONCLUSION: Available data suggest that the adverse effect profile of PSO is more favorable than other triazoles. However, our case is the third report suggesting that PAI may be an underrecognized side effect. Awareness of this complication is particularly important in patients with severe or resistant fungal infections.

Imaging Characteristics of a Hypervascular Pituitary Spindle Cell Oncocytoma on Magnetic Resonance Imaging and Digital Subtraction Angiography.

BACKGROUND: Spindle cell oncocytomas (SCOs) are rare neuroendocrine tumors of the posterior pituitary that are often misdiagnosed as nonfunctional pituitary tumors. Fewer than 50 cases of SCOs have been described in the literature, and many of these reports have documented the tumors to be hypervascular on imaging or histology. CASE DESCRIPTION: We present the first cerebral angiography imaging findings of an SCO before primary resection. The discovery of a prominent tumor blush, enlarged meningohypophyseal feeders bilaterally, and prominent tumor draining veins aided in preoperative planning and subsequent successful endoscopic transsphenoidal surgical resection. CONCLUSIONS: Despite being a rare entity, SCOs should be included in the differential diagnosis when working up a hypervascular sellar tumor. Flow voids may be present on initial magnetic resonance imaging evaluation. Subsequent digital subtraction angiography can be used to further investigate abnormal vasculature and aid in surgical planning.

Transarterial embolization of a hyperfunctioning aldosteronoma in a patient with bilateral adrenal nodules.

Primary hyperaldosteronism often results in resistant hypertension and hypokalemia, which may lead to cardiovascular and cerebrovascular complications. Although surgery is first line treatment for unilateral functioning aldosteronomas, minimally invasive therapies may be first line for certain patients such as those who cannot tolerate surgery. We present a case of transarterial embolization (TAE) of an aldosteronoma. The patient presented with a cerebrovascular accident, and subsequently developed uncontrolled hypertension, hypokalemia, and a myocardial infarction. Following TAE, potassium returned to normal levels and blood pressure control was improved. There were no postoperative complications. TAE thus may be a safe and effective alternative to surgery.

Utility of plasma free metanephrines in diagnosis of factitious pheochromocytoma.

OBJECTIVE: To report a case of epinephrine-induced factitious pheochromocytoma in a young woman with a past medical history of Conn's syndrome. METHODS: We present a case report with clinical and laboratory details, review related reports in the literature, and demonstrate the usefulness of plasma free metanephrine levels in facilitating the diagnosis of factitious pheochromocytoma. RESULTS: A 34-year-old woman was admitted to our hospital for confirmation and localization of an occult pheochromocytoma. After thorough investigation, we discovered that the patient was surreptitiously injecting epinephrine in order to induce symptoms and signs consistent with a pheochromocytoma. Analysis of the patient's biochemical profile during and between her catecholaminergic crises revealed plasma epinephrine and free metanephrine levels that would be highly unusual for a patient with a pheochromocytoma. CONCLUSION: This case illustrates the utility of implementing the ratio of plasma epinephrine to free metanephrine levels in distinguishing factitious from organic pheochromocytoma.

Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications.

BACKGROUND: Major depressive disorder (MDD) is associated with increased risk for premature coronary heart disease and bone loss. Single time measurements of plasma IL-6, a good predictor of future risk for both cardiovascular disease and osteoporosis, revealed significant elevations in depressed patients. The objective of this study was to rigorously compare plasma IL-6 levels, measured over 24 h, in MDD patients and healthy controls. Given the activating role of IL-6 on the hypothalamic-pituitary-adrenal (HPA) axis, and the relevance of its dysregulation in MDD, we also analyzed the relations between IL-6 and cortisol levels. METHODS: We studied nine patients and nine controls, individually matched by gender, age (+/-5 yr), body mass index (+/-2 kg/m2), and menstrual cycle phase. Diagnosis of MDD was confirmed by structured clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I diagnostic criteria. Self-reported mood ratings were assessed by multiple visual analog scales. The rhythmicity and complexity of IL-6 and cortisol secretion were tested by cosinor analyses, approximate entropy (ApEn) and cross-ApEn algorithms. RESULTS: MDD patients had significant mean IL-6 elevations from 1000-1200 h and at 1500 h (P ranging from <0.05 to <0.01) vs. controls. In addition, in MDD, the circadian rhythm of IL-6 was shifted by 12 h, and its physiological complexity was reduced, with no difference in the cross-ApEn of IL-6 and cortisol between the two groups, and significant time-lagged correlations only in the controls. IL-6 levels correlated significantly with mood ratings. CONCLUSIONS: We report profound morning elevations of plasma IL-6 and a reversal of its circadian rhythm in MDD patients, in the absence of hypercortisolism. These findings may be relevant to the increased risk for coronary heart disease and bone loss in MDD.

Intramuscular administration of ACTH1-24 vs. 24-hour blood sampling in the assessment of adrenocortical function.

The standard intravenous short Synacthen test (SSST) has long been accepted as one of the most reliable diagnostic tests of adrenocortical insufficiency. Intramuscular (i.m.) administration of ACTH obviates the need of venous cannulation and can be used as an alternative to the intravenous test. Nevertheless, reports of correlation between cortisol response to i.m. ACTH1-24 and 24-hr average cortisol concentration are scarce. We studied this relation in 64 nonobese healthy men. Blood samples for serial cortisol measurements were collected hourly over 24 hrs. The following day, blood samples were collected at baseline and at 30 and 60 min after intramuscular (i.m.) administration of 250 microg of ACTH1-24. All healthy men reached 24-hr serum cortisol peak values (Cmax) between 0600 h and 1000 h. Following i.m. ACTH1-24, cortisol levels significantly increased at both 30 (C30ACTH) and 60 (C60ACTH) minutes, when compared to baseline values. C30ACTH and C60ACTH significantly correlated with Cmax and with the 24-hr time-integrated cortisol concentration (AUC0-24). Morning mean cortisol was calculated as the average of serum concentrations measured between 0600 h and 1000 h (C(av)6-10) and correlated very well with AUC0-24. In conclusion, we confirmed that i.m. administration of ACTH1-24, followed by a single blood sampling at 60 min for cortisol measurement represents a valid, convenient and cost- effective screening test of adrenal function.

Behavioral, adrenal, and sympathetic responses to long-term administration of an oral corticotropin-releasing hormone receptor antagonist in a primate stress paradigm.

CRH is a main regulator of the stress response. This neuropeptide and its specific receptors, CRHR-1 and CRHR-2, are disseminated throughout the central nervous system. There is a significant interspecies difference in the distribution of CRHR within the central nervous system. CRH-R1 antagonists may attenuate stress-related behavior in rats without compromising adrenal function, but few studies have addressed the same question in higher mammals. Antalarmin (AA) is a specific CRHR-1 antagonist suitable for oral administration. Social separation is a potent stressor for rhesus monkeys. Therefore, we sought to investigate the hormonal responses to chronic administration of AA using a primate stress model. Eight preadolescent (4-6 kg) male rhesus monkeys received AA (20 mg/kg.d) or placebo (PBO) orally. All animals were on a regular day/light cycle and were fed with standard monkey chow daily. The study (114 d) was comprised of the following consecutive phases: adaptation, baseline, separation (stress), recovery, and cross-over. During social separation, solid panels separated the individuals. Cerebrospinal fluid (CSF) and femoral venous blood samples were obtained once a week on the fourth day of separation under ketamine anesthesia. Serum samples were also obtained 1 and 2 h after separation. CSF samples were assayed for CRH, AA, norepinephrine (NE) and epinephrine (EPI). Plasma was assayed for ACTH, cortisol, NE, and EPI. AA was detected in the plasma of each monkey while they were taking the active drug and in none of the animals on PBO. Among the behaviors assessed, environmental exploration, a behavior inhibited by stress, was increased during AA administration. However, AA at this dose did not affect other anxiety-related behavioral end points, including self-directed behavior, vocalization, or locomotion. We also observed that: 1) ACTH decreased between adaptation and baseline, indicating that the animals had adjusted to the novel environment; 2) ACTH and cortisol increased significantly after social separation, indicating that social separation was an adequate model for acute stress; 3) NE and EPI increased significantly during acute stress in the AA and PBO groups (P < 0.005, NE; P < 0.001, EPI); 4) after chronic stress, by d 4 of separation, ACTH levels were no longer significantly different from baseline, and NE and EPI remained slightly elevated when compared with baseline (P < 0.05, NE; P < 0.01, EPI); and 5) all the animals remained healthy and gained the expected weight during the study. In summary, oral chronic administration of a specific CRH-R1 antagonist to rhesus monkeys does not blunt the sympathoadrenal response to stress while increasing environmental exploration, a behavior that is normally suppressed during stressful events. Taken together, these findings suggest that CRHR-1 antagonists may be a valid treatment for stress-related disorders.

Antagonistas do hormônio liberador da corticotrofina: atualização e perspectiva / Corticotropin releasing hormone antagonists: update and perspectives

Modelos genéticos e estudos epidemiológicos têm contribuído para a compreensão da fisiopatologia das doenças relacionadas ao estresse. O hormônio liberador da corticotrofina (CRH) pertence à família dos chamados peptídeos relacionados ao CRH, junto com a urocortina, urocortina II (ou peptídeo relacionado à estressecopina) e urocortina III (ou estressecopina). O CRH é o maior estimulador da secreção hipofisária de ACTH em humanos, e tem um papel importante na resposta fisiológica ao estresse. O CRH e seus receptores (tipos 1 e 2) estão difusamente distribuídos em todo o sistema nervoso central (SNC) e, em menor proporção, em tecidos periféricos. A distribuição dos receptores no SNC mostra ampla variabilidade entre as espécies. Os neurônios do CRH modulam a função autonõmica e do sistema límbico. O CRH tem importantes efeitos, também, nos sistemas cardiovascular, metabólico e comportamental. As ações regionais deste peptídeo no SNC e na periferia são vários e apenas parcialmente conhecidos. Ações aberrantes do CRH estão implicadas em algumas condições psiquiátricas, incluindo depressão e ansiedade. Esta teoria tem sido corroborada por dados em ratos transgênicos que não expressam CRH e estudos pré-clínicos envolvendo a administração de antagonistas do CRH em macacos Rhesus. Embora ainda não disponível para uso clínico de rotina, dados preliminares de estudos conceituais envolvendo a administração oral de antagonistas do CRH em humanos são encorajadores. Entretanto, ainda permanece um desafio o desenvolvimento de antagonistas não peptídicos seletivos do receptor de CRH. Além disso, são extremamente necessários testes com estudos clínicos randomizados, que deverão trazer novas luzes sobre esta área.

The case for more aggressive screening and treatment of mild thyroid failure.

"Subclinical" (mild) thyroid failure is not benign: it tends to progress to overt thyroid failure and it has adverse clinical effects. We believe it should be screened for more aggressively in the general population, and treated with levothyroxine.