Adrenocorticotropic Hormone Secretion Research Articles

Fast Feedback Inhibition of Adrenocorticotropic Hormone Secretion by Endogenous Cortisol in Humans

Background: Using high-frequency blood sampling, we demonstrate glucocorticoid fast feedback (FF) mediated by endogenous cortisol in 6 normal humans. Methods: We stimulated adrenocorticotropic hormone (ACTH) secretion by ovine corticotropin-releasing hormone (oCRH) with the experimental paradigm in which a high-frequency blood sampling was designed for plasma ACTH and cortisol determinations. Results: We saw previously unrecognized variability in the timing of key events such as onsets of ACTH and cortisol secretion, onset and offset of FF, and in FF duration. This variability mandated analyses referenced to case-wise event times rather than referenced simply to time since oCRH administration. The mean time of FF onset was 4.0 min (range 0–9; median 3) after cortisol secretion began, and the mean FF duration was 7.5 min (range 3–18; median 6.0). The FF effect was rate-sensitive and does not reflect level-sensitive cortisol feedback. In agreement with previous estimates using hydrocortisone infusions, the rate of rise of cortisol that triggered FF was approximately 44 nmol/L/min or 1.6 µg/dL/min. FF onset followed the trigger cortisol slope with an average lag of 1 min (range 0–3; median 0). Unexpectedly, this trigger cortisol slope quickly declined within the FF period. Conclusions: This experimental design may enable new physiological studies of human FF that is mediated by endogenous cortisol, including mechanisms, reproducibility, and generalizability to other activating stimuli.

Culture in 10% O2 enhances the production of active hormones in neuro-endocrine cells by up-regulating the expression of processing enzymes

To closely mimic physiological conditions, low oxygen cultures have been employed in stem cell and cancer research. Although in vivo oxygen concentrations in tissues are often much lower than ambient 21% O2 (ranging from 3.6 to 12.8% O2), most cell cultures are maintained at 21% O2 To clarify the effects of the O2 culture concentration on the regulated secretion of peptide hormones in neuro-endocrine cells, we examined the changes in the storage and release of peptide hormones in neuro-endocrine cell lines and endocrine tissues cultured in a relatively lower O2 concentration. In both AtT-20 cells derived from the mouse anterior pituitary and freshly prepared mouse pituitaries cultured in 10% O2 for 24 h, the storage and regulated secretion of the mature peptide hormone adrenocorticotropic hormone were significantly increased compared with those in cells and pituitaries cultured in ambient 21% O2, whereas its precursor proopiomelanocortin was not increased in the cells and tissues after being cultured in 10% O2 Simultaneously, the prohormone-processing enzymes PC1/3 and carboxypeptidase E were up-regulated in cells cultured in 10% O2, thus facilitating the conversion of prohormones to their active form. Similarly, culturing the mouse β-cell line MIN6 and islet tissue in 10% O2 also significantly increased the conversion of proinsulin into mature insulin, which was secreted in a regulated manner. These results suggest that culture under 10% O2 is more optimal for endocrine tissues/cells to efficiently generate and secrete active peptide hormones than ambient 21% O2.

Clinically Silent Adrenocorticotropic Hormone-Secreting Crooke Cell Adenoma Presenting as Unilateral Ear Pain

Crooke cell adenoma (CCA) is a rare tumor of the anterior pituitary. It is highly aggressive and carries significant risk of morbidity and mortality. This report focuses on the presentation of this disease process and review diagnosis and treatment. The patient is a 64-year-old male with a history of resected pituitary adenoma of unknown pathology. The patient underwent serial magnetic resonance imaging surveillance for numerous years without recurrence of tumor, however eventually developed symptoms of worsening left ear pain over 3 weeks that rapidly evolved to include ptosis. Imaging revealed a new pituitary macroadenoma. Urgent surgical resection revealed histopathological diagnosis of CCA. Corticotroph adenomas represent a rare subset of pituitary tumors. Clinically silent pituitary tumors demonstrate relatively higher rates of cavernous sinus invasion (30% versus 18%) and progression or recurrence (34% versus 6%) when compared to nonfunctioning adenomas. In CCA, only 65% of patients have clinical features of Cushing disease at presentation. Twenty-four-hour urinary free cortisol is discussed in the literature as a potential tool, where a value 4 times the upper limit of normal was predictive of higher risk of having Crooke cell changes. With a recurrence rate of up to 60%, multimodal treatment (surgery and radiation) is preferred. This case highlights early detection and treatment as keys to reducing the risk of morbidity and mortality from CCA. Currently, there are limited tools for identifying patients who are high risk for developing Crooke cell changes. Treatment modalities classically include surgery and radiotherapy. Adjuvant and novel chemotherapies are being explored.

Late-onset isolated adrenocorticotropic hormone deficiency caused by nivolumab: a case report

BackgroundImmune checkpoint inhibitors including nivolumab, an anti-programmed cell death protein 1 antibody, are recently developed cancer immunotherapy agents. Immune checkpoint inhibitors are known to cause autoimmune-related side effects including endocrine dysfunctions. However, there are few reports on late-onset isolated adrenocorticotropic hormone (ACTH) deficiency caused by nivolumab.Case presentationThe patient was a 72-year-old female. When she was 64 years old, she was diagnosed with malignant melanoma of the left thigh accompanied by left inguinal lymph node metastases, and she received several courses of chemotherapy for malignant melanoma followed by the resection of these lesions. At 71 years of age, multiple metastases were found and treatment with nivolumab 2 mg/kg every 3 weeks was initiated. Six months later, replacement with levothyroxine was started because of hypothyroidism following mild transient thyrotoxicosis. Eleven months after the beginning of nivolumab, the treatment was discontinued because of tumor expansion. Four months after the discontinuation of nivolumab, general malaise and appetite loss worsened, and 2 months later, hyponatremia (Na; 120–127 mEq/L) and hypoglycemia (fasting plasma glucose; 62 mg/dL) appeared. Her ACTH and cortisol levels were extremely low (ACTH; 9.6 pg/mL, cortisol; undetectable). Challenge tests for anterior pituitary hormones showed that responses of ACTH and cortisol secretion to corticotropin-releasing hormone were disappeared, although responses of other anterior pituitary hormones were preserved. Thus, she was diagnosed with isolated ACTH deficiency. Her symptoms were improved after treatment with hydrocortisone.ConclusionsThe present report showed a case of late-onset isolated ACTH deficiency accompanied by hyponatremia, which was diagnosed 6 months after the discontinuation of nivolumab. The effects of nivolumab last for a long time and the side effects of nivolumab can also appear several months after discontinuation of the drug. Repeated monitoring of serum sodium levels may be a beneficial strategy to find the unexpected development of adrenal insufficiency even after discontinuation of nivolumab.

Surgical treatment of ACTH-ectopic syndrome

ACTH-ectopic syndrome is a severe, multiple-symptom disease characterized by secretion of adrenocorticotropic hormone (ACTH) by ectopic tumor, increased release of adrenal cortical hormones and clinical picture of hypercorticism. Diagnosis and treatment of ACTH-ectopic syndrome is still difficult problem despite the achievements of modern medicine. There are several unresolved issues including optimal diagnostic algorithm, indications for various surgical procedures and their optimal dates. This review is devoted to these questions.

Ectopic Adrenocorticotropic Hormone Syndrome in Small Cell Lung Cancer Associated with Refractory Hypokalemia: A Case Report

Small cell lung cancer (SCLC) is aggressive cancer with high mortality without appropriate early treatmenr. The patient can present with paraneoplastic syndromes, such as Cushing syndrome, because of an inappropriate secretion of ectopic adrenocorticotropic hormone (ACTH) with severe hypokalemic metabolic alkalosis, Parathyroid hormone with hypercalcemia, and hyponatremia due to inappropriate anti-diuretic hormone (ADH) secretion. Patients with SCLC and paraneoplastic syndrome, are with poor prognostic factor. Diagnosis must be made early with immediate treatment. We report a 57-year-old male patient who had severe refractory hypokalemia, metabolic alkalosis, and hypertension as manifestations of an inappropriate secretion of ACTH-secreting from small cell carcinoma of the lung. He was treated with high doses of spironolactone to control the symptomatic refractory hypokalemia, and Metyrapone to control the ectopic ACTH secretion. Aggressive chemotherapy was initiated soon after lung mass biopsy, with SCLC diagnosis.

Effects of Oxytocin on Cell Proliferation in a Corticotroph Adenoma Cell Line.

BackgroundOxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells.MethodsReverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot.ResultsOXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells.ConclusionAlthough the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.

Clinical study of electroacupuncture on perioperative analgesia in patients with thyroid surgery under cervical plexus block

To investigate the change trend and correlation between the perioperative pain degree and neuroendocrine hormone levels in the perioperative period on patients with thyroid surgery by electroacupuncture combined with cervical plexus block. Forty patients with elective thyroidectomy were enrolled and divided into a control group and an observation group according to the random number table method, 20 cases in each group. In the control group, cervical plexus block was performed. In the observation group, the cervical plexus block combined with electroacupuncture (EA) were given. After the cervical plexus block was completed, the EA was applied at the bilateral Hegu (LI 4) and Neiguan (PC 6) for 30 min. The visual analog scale (VAS) was used to assess the pain level before anesthesia (T0), 2 h after operation (T1), 12 h after operation (T2), 24 h after operation (T3) and 48 h after operation (T4). Blood samples such as adrenocorticotropic hormone (ACTH), C-reactive protein (CRP) and β-endorphin (β-EP) were collected to measure the level of neuroendocrine hormones, and to analyze the correlation between ACTH, CRP, β-EP and VAS scores. The VAS scores at T1, T2, T3 were higher than those at T0 in the two groups (all P<0.05). The VAS scores T1, T2 and T3 in the observation group were lower than those in the control group (all P<0.05). The ACTH and CRP in the control group at T1, T2 and T3 were significantly higher than those at T0 (all P<0.05). The β-EP in the observation group at T1, T2 and T3 was significantly higher than that at T0 (all P<0.05). The ACTH and CRP in the observation group at T1, T2 and T3 were lower than those in the control group,and the β-EP level was higher than that in the control group (all P<0.05).The VAS score was significantly positively correlated with ACTH and CRP levels, and negatively correlated with β-EP. EA stimulation can inhibit the secretion of ACTH and CRP, promote the release of β-EP, reduce the perioperative pain score, and inhibit the body's stress response.

Transsphenoidal Approaches for Microsurgical Resection of Pituitary Adenomas in Pediatric Patients

Pituitary adenomas are uncommon in the pediatric population. Although medical treatment can be effective in treating prolactinomas and some growth hormone-secreting tumors, resection is indicated in the setting of pituitary apoplexy, large or giant pituitary adenomas causing mass effect or visual loss, or when medical therapy becomes ineffective or intolerable. Modern microsurgical transsphenoidal approaches are potential avenues for resection in pediatric patients. We evaluated the outcomes and safety of this approach. A retrospective cohort analysis was performed from February 2002 through May 2017 for patients younger than 19 years of age that underwent a transsphenoidal approach for pituitary adenoma resection. Among a total of 634 patients who underwent transsphenoidal approach for pituitary adenoma resection, 24 pediatric cases were identified. Prolactinomas (29.2%) and adrenocorticotropic hormone-secreting (20.8%) pituitary adenomas were the most commonly encountered histologies. Gross total resection was achieved in 75.0% of patients, and complete hormone function normalization was seen in 91.7% of patients. Eight patients (33.3%) required postoperative hormone replacement therapy. Twelve patients (50.0%) underwent fat/fascia use and 1 patient (4.2%) underwent lumbar puncture perioperatively for management of cerebrospinal fluid leak. There were no tumor recurrences during a follow-up period of 24.7 ± 32.1 months. A modern transsphenoidal microsurgical approach proved to be a safe, well-tolerated, and effective modality in the setting of pediatric pituitary adenomas.

Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma.

An effective treatment for the management of adrenocorticotropic hormone-secreting pituitary adenomas (ACTH-PA) is currently lacking, although surgery is a treatment option. We have integrated information obtained at the metabolomic and proteomic levels to identify critical networks and signaling pathways that may play important roles in the metabolic regulation of ACTH-PA and therefore hopefully represent potential therapeutic targets. Six ACTH-PAs and seven normal pituitary glands were investigated via gas chromatography-mass spectrometry (GC-MS) analysis for metabolomics. Five ACTH-PAs and five normal pituitary glands were subjected to proteomics analysis via nano liquid chromatography tandem-mass spectrometry (nanoLC-MS/MS). The joint pathway analysis and network analysis was performed using MetaboAnalyst 3.0. software. There were significant differences of metabolites and protein expression levels between the ACTH-PAs and normal pituitary glands. A proteomic analysis identified 417 differentially expressed proteins that were significantly enriched in the Myc signaling pathway. The protein–metabolite joint pathway analysis showed that differentially expressed proteins and metabolites were significantly enriched in glycolysis/gluconeogenesis, pyruvate metabolism, citrate cycle (TCA cycle), and the fatty acid metabolism pathway in ACTH-PA. The protein–metabolite molecular interaction network identified from the metabolomics and proteomics investigation resulted in four subnetworks. Ten nodes in subnetwork 1 were the most significantly enriched in cell amino acid metabolism and pyrimidine nucleotide metabolism. Additionally, the metabolite–gene–disease interaction network established nine subnetworks. Ninety-two nodes in subnetwork 1 were the most significantly enriched in carboxylic acid metabolism and organic acid metabolism. The present study clarified the pathway networks that function in ACTH-PA. Our results demonstrated the presence of downregulated glycolysis and fatty acid synthesis in this tumor type. We also revealed that the Myc signaling pathway significantly participated in the metabolic changes and tumorigenesis of ACTH-PA. This data may provide biomarkers for ACTH-PA diagnosis and monitoring, and could also lead to the development of novel strategies for treating pituitary adenomas.

Behavioral, hormonal, and neurochemical outcomes of neonatal repeated shaking brain injury in male adult rats

It is well known that an abusive environment in childhood is related to individual anxiety behavior in adulthood. Though an imbalance of adrenocorticosteroid receptors and a dysfunction of monoaminergic neuron systems have been proposed, the underlying mechanisms are not fully understood. To address these problems, we recently developed a new model of shaking brain injury (SBI) in neonatal rats. These model rats showed transient microhemorrhages in the gray matter of the cerebral cortex and hippocampus. Using this model, we assessed the effects of neonatal repeated mild SBI on subsequent behavior and the stress response, and we further examined the possible contribution of adrenocorticosteroid receptors in the hippocampus and central monoaminergic neuron systems mediating such abnormalities. Behavioral screening examination with a novel open-field test showed that the rats with postnatal day (P) 3–7 shaking had significantly reduced locomotor activity and exploration behaviors than those with late (P8–14) shaking periods, indicating a critical period for neonatal SBI. In the elevated plus maze (EPM) and the light/dark transition (L/D) tests, the model rats spent less time in the open arm of the EPM and the light box of the L/D test, indicating anxiety-like behavior as adults. In adults, the novel EPM-induced adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) responses were significantly increased by neonatal SBI. Further experiments showed that the expression of mineralocorticoid receptor (MR), but not glucocorticoid receptor (GR), was significantly downregulated in the hippocampus of this model rat. These results suggest that neonatal SBI-induced downregulation of MRs in the hippocampus attenuates negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis, which results in abnormal secretion of ACTH and CORT. Furthermore, the neurochemical analysis showed that shaken rats had higher dopamine (DA), serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and noradrenaline (NA) levels in the dorsal part of the medial prefrontal cortex (dmPFC). In the amygdala, higher 5-HIAA and lower NA levels were observed. Both areas are known to be anxiety and stress-related. Taken together, the effects of neonatal SBI on the monoaminergic systems may also be involved in the changes of behavioral and hormonal responses in this model.

Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment.

Background Central adrenal insufficiency (CAI) is characterized by impaired adrenocorticotropin (ACTH) secretion because of a disease or injury to the hypothalamus or the pituitary, leading to a reduced cortisol production. CAI suspicion arises more frequently in patients with pituitary tumors, cranial irradiation/surgery/injury/infections, as well as after exogenous glucocorticoid withdrawal. Nevertheless, a late diagnosis is not uncommon because CAI may present with nonspecific signs or symptoms, as fatigue or hyponatremia. Content The PubMed database was searched (years 1980-2018), using "central adrenal insufficiency" and "ACTH deficiency" as keywords. Subsequently, reference sections of the retrieved articles were searched. Summary Dynamic tests are needed when morning basal cortisol levels are not sufficient to exclude or to confirm CAI. Short Synacthen Test (SST) is the most used, and Endocrine Society's guidelines recommend a cortisol peak >500 nmol/L to exclude CAI. Despite thresholds, understanding the pretest probability of ACTH deficiency (the clinical background of the patient) is essential because the diagnostic accuracy of SST in case of a negative result is suboptimal. Glucocorticoid replacement therapy, able to replicate cortisol circadian rhythm, is required in patients with CAI; fludrocortisone treatment is not necessary. Short-acting glucocorticoid drugs (hydrocortisone or cortisone acetate) are the most used; lower doses than previously used are nowadays recommended to reduce cortisol-related comorbidities. Promising results have been obtained with modified-release hydrocortisone, especially regarding glucose metabolism in patients with primary adrenal insufficiency. Outlook An accurate clinical diagnosis and a careful individualized therapy are mandatory in patients with CAI.

Relaxin-3 regulates corticotropin-releasing factor gene expression in cultured rat hypothalamic 4B cells

The ancestral insulin/relaxin peptide superfamily member relaxin-3 is an important regulator of food intake and behaviors related to anxiety and motivation. Relaxin family peptide receptor 1 (RXFP1) and RXFP3 are expressed in the rat hypothalamic paraventricular nucleus (PVN). Corticotropin-releasing factor (CRF) is produced in the PVN in response to stressors and promotes adrenocorticotropic hormone secretion from the anterior pituitary. We hypothesized that relaxin-3 directly regulates Crf expression in the hypothalamus and investigated its effect on Crf expression in cultured hypothalamic 4B cells. Relaxin-3 increased Crf mRNA levels and stimulated Crf promoter activity. Both protein kinase A and C pathways contributed to relaxin-3-induced Crf promoter activity. Rxfp1 and Rxfp3 mRNA and their proteins were expressed in cultured hypothalamic 4B cells. Relaxin-3 decreased Rxfp1 mRNA and protein levels and increased Rxfp3 mRNA and protein levels. These results suggested that the action of relaxin-3 in cultured hypothalamic 4B cells may be regulated through both RXFP1 and RXFP3.

Cushing Syndrome due to Ectopic Adrenocorticotropic Hormone Secretion by a Pulmonary Carcinoid Tumor in a Patient with Pneumoconiosis

ABSTRACT Objective: Sites with a high prevalence of pneumoconiosis are especially challenging to physicians. The presence of pneumoconiotic nodules on chest computed tomography (CT) scans makes it ...

Endocrine Remission after Pituitary Stereotactic Radiosurgery: Differences in Rates of Response for Matched Cohorts of Cushing’s Disease and Acromegaly Patients

To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenomas after radiosurgery after controlling for several known prognostic factors. An institutional review board approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching based on patient gender, age at radiosurgery, time interval between the last resection and radiosurgery, use of previous radiotherapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined, off of suppressive medications, as a normal serum IGF-1 (GH-secreting) or a normal 24-hour urine free-cortisol (ACTH-secreting). Endocrine remission and the incidence of new hypopituitarism after single fraction radiosurgery were described and compared between groups. Two-hundred and forty-two (242) patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. A total of 75% of patients had cavernous sinus invasion and 10% had suprasellar extension at the time of radiosurgery. The median radiosurgical marginal dose was 25 Gy to the 50% isodose line between each group. After multivariable adjustment, factors associated with increased time to endocrine remission included patient age (HR 1.016, p = 0.023), cavernous sinus invasion (HR 1.793, p = 0.004), and patients with acromegaly (HR 2.912, p < 0.001). The incidence of a new hypopituitarism developing after SRS was 29% and did not appreciably differ by adenoma subtype (p = 0.180). After radiosurgery, patients with ACTH-secreting tumors achieve endocrine remission sooner than those with GH-secreting tumors. These results provide insight into the relative tumor biology and post-radiosurgical disease course that will serve to further improve clinical outcomes and patient management in the future.

Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas.

somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing's disease (CD). The aim of the study is to verify whether USP8 mutation may predict early and late outcome of pituitary surgery in patients with CD operated at a single institution. We performed a retrospective genetic analysis of 92 adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Specimens were screened for USP8 hotspot mutations in the exon 14 with Sanger sequencing. Hormonal and surgical data were compared between USP8 variant carriers and wild-type tumors. USP8 variants were detected in 22 adenomas (23.9%) with higher prevalence in women (28.9% vs. 5.3% in men; p < 0.05). No significant difference in hormonal levels and tumoral features in relation to USP8 status was observed. Interestingly, USP8-variant carriers were more likely to achieve surgical remission than wild-type adenomas (100% vs. 75.7%; p = 0.01). Conversely, recurrence of CD occurred in 23% of USP8-mutated patients and in 13% of patients with wild-type adenoma. The recurrence-free survival did not differ significantly between the two groups (p = 0.42). ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated by a single neurosurgeon. Recurrence rates are not related with USP8-variant status.

Patient-Level Factors Influencing Hospital Costs and Short-Term Patient-Reported Outcomes After Transsphenoidal Resection of Sellar Tumors.

Identifying which factors influence treatment costs of transsphenoidal surgery for removal of sellar lesions can be complex. To identify which patient-level factors are associated with higher costs and evaluate the relationship between expenditures and short-term patient-reported outcomes. We used an institutional database tool to review prospectively collected data on patients (≥10 yr old) undergoing transsphenoidal sellar surgery. Hospital costs, demographic data, disease-specific variables, hospital-related measures, and patient-reported outcomes (Euro-QOL 5D [EQ-5D] responses) were collected for all patients. One hundred seventeen patients met the inclusion criteria. A multivariable logistic regression model for hospital costs showed a significant association between higher costs and adrenocorticotropic hormone-secreting tumors (odds ratio [OR] 86.34, 95% confidence interval [CI] 3.43-2176.42), larger tumor size (OR 1.13, 95% CI 1.01-1.28), and in-hospital complications (OR 14.98, 95% CI 2.21-101.68). The largest contributor to hospital costs in our cohort was facility cost (75%), followed by pharmacy (13%) and supply (7%) costs. Most patients (65.8%) had stable or improved EQ-5D responses at 1-mo follow-up. Stability or improvement in EQ-5D was more likely in patients with lower preoperative EQ-5D scores (P < .015) and with higher postoperative EQ-5D scores (P < .001) on univariate analysis. Most patients undergoing transsphenoidal surgery for sellar tumors experience stable or improved postoperative quality of life, even shortly after surgery. Factors associated with increased costs of surgery included larger tumor size and in-hospital complications. Using these data, further study can be directed at determining which interventions may improve the value of transsphenoidal surgery.

Metastatic Adrenocorticotropic Hormone-Secreting Breast Cancer Treated with Bilateral Adrenalectomy

Objective: Endogenous Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion occurs most commonly from small-cell lung carcinoma. Ectopic ACTH secretion from a neuroendocrine tumor of the breast is very rare, with only 7 previously reported cases in the literature. Methods: We describe a rare case of a metastatic ACTH-producing neuroendocrine carcinoma of the breast causing Cushing syndrome that was managed with bilateral simultaneous retroperitoneoscopic adrenalectomy. Results: A 51-year-old female with a history of bilateral mastectomy for ACTH-secreting neuroendocrine carcinoma of the breast presented with medically intractable Cushing syndrome. Elevated 24-hour urine free cortisol and ACTH levels and clinical findings of diabetes, vertebral compression fractures, and venous thromboembolism were present. Computed tomography scan of the abdomen demonstrated bilateral adrenal hyperplasia. The patient underwent simultaneous retroperitoneoscopic bilateral adrenalectomy. Histopathology...

Thymic Carcinoid with Adrenocorticotropic Hormone-Producing Ectopic Cushing Syndrome and Empty Sella

Ectopic Cushing's syndrome secondary to thymic carcinoid is a rare disorder that may be difficult to diagnose and manage. We describe a case of severe Cushing's syndrome secondary to a large adrenocorticotropic hormone (ACTH) producing thymic carcinoid in a patient with history of primary hyperaldosteronism. A 43-year-old female with a 20-year history of an aldosterone-secreting adrenocortical adenoma status post right adrenalectomy presented with acute onset of proximal muscle weakness, swelling, facial hirsutism, and severe hypokalemia. Ectopic Cushing's Syndrome was suspected based on the sudden symptom onset and markedly elevated 24-hr urine cortisol and ACTH levels. MRI revealed an empty pituitary sella and a large (7.3 cm) mediastinal mass visible on chest CT. The mass was resected by video-assisted thoracoscopic surgery, resulting in resolution of symptoms and cortisol levels. Pathology assessment confirmed well-differentiated thymic carcinoid with positive ACTH staining. The case highlights clinical features, challenges in diagnostic work up, treatment modalities, and associated endocrine findings in a thymic carcinoid abutting the heart and presenting with ectopic ACTH secretion.

Pediatric pituitary adenomas in Northeast Mexico. A follow-up study

PurposeTo review incidence, treatment and outcome of pediatric pituitary adenomas (PAs).MethodsA follow-up study patients with the age of ≤19 years old who were treated from 1995 to 2015 in Mexico.ResultsOut of 1244 diagnosed PA, 43 patients were children (35 females, 8 males) with a mean age of 17.2 years. The majority were macroadenomas (70%) with prolactinomas (PRL) dominating (63%) followed by non-functioning adenomas (21%). In total, 40% were diagnosed as invasive. Growth hormone (GH) secreting adenomas, adrenocorticotropic hormone secreting and mixed GH-PRL secreting were rare. The treatment modalities were dopamine agonists and surgery. The average treatment time was 44 months with an average follow-up period of 104 months. Sixty-eight percent (27/40) of the patients had complete response after long time follow-up. Thirty-one percent did not respond to treatment whereof three patients died due to advanced disease and late intervention. The principal causes for treatment failure were treatment resistance, late intervention and poor patient compliance.ConclusionsSixty eight percent had complete treatment response without any sign of disease, while ~31% did not respond to treatment or did not comply to follow up/treatment. Optimized early diagnose, treatment methods with early intervention, long time follow-up and with better measures for patient compliance should improve outcomes.