Axis Cortisol Research Articles

Ectopic adrenocortical adenoma characterized by hypogonadism: a case report and review of the literature

BackgroundCurrently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas.Case presentationA 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. Review: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization.ConclusionEctopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.

FRI348 Ectopic Posterior Pituitary As A Cause Of Panhypopituitarism Presenting With Hyponatremia

Abstract Disclosure: C. Choo: None. Background: Ectopic posterior pituitary gland (EPP) can occur from defective embryogenesis affecting neuronal migration, or from neurodegeneration of the hypothalamic nuclei. While isolated growth hormone deficiency is most common, it is also associated with pan-hypopituitarism. The posterior pituitary function is often preserved. Clinical Case: We report a case of pan-hypopituitarism from congenital EPP, presenting with hyponatremia. A 63-year-old male with hyperlipidemia was admitted for gastroenteritis. Serum sodium was 106mmol/L [reference range 136-146mmol/L] on admission but he was otherwise asymptomatic and haemodynamically stable. This initially improved with intravenous fluids, however subsequently stagnated at 121mmol/L despite achieving euvolemia. Thyroid and cortisol axes were evaluated in view of persistent hyponatraemia. 8am cortisol was low at 119nmol/L with inappropriately normal ACTH 13.9 pg/mL [reference range 7.2 – 62.3 pg/mL]. Thyroid function test showed central hypothyroidism consistently on repeat testing with a low fT4 of 6.1 pmol/L and 7.7 pmol/L [reference range 8.8-14.4pmol/L] and inappropriately normal TSH of 2.98MU/L and 2.41MU/L respectively [reference range 0.65-3.70MU/L]. 1mcg short synacthen test done following suspicion of hypocortisolism peaked at 468 nmol/L. He had no symptoms or signs of hypocortisolism or hypothyroidism. He was a bachelor and had clinical features of hypogonadism including short stature (142cm), high-pitched voice, scarce sexual hair and pubescent sized testes. His mid-parental height is unknown as his parents were deceased. FSH, LH, testosterone and IGF-1 were all undetectable. Prolactin was otherwise normal 9.4ug/L [reference range 4.2-16.4ug/L]. Radiographs of the forearm showed unfused epiphyseal plates at the distal radius and ulna. Thus, the diagnosis of pan-hypopituitarism was made. Magnetic resonance imaging of the pituitary revealed a T1 hyperintense nodule at the floor of the third ventricle, suggestive of ectopic posterior pituitary. There was otherwise minimal normally enhancing tissue in the pituitary fossa, and the posterior pituitary bright spot and infundibulum were absent. He was started on hydrocortisone and subsequently levothyroxine replacement, with resolution of hyponatraemia (serum sodium 139nmol/L). He did not develop polyuria or polydipsia to suggest diabetes insipidus. Due to financial concerns however, he declined growth hormone and testosterone replacement therapy. Conclusion: Most reports of EPP are in the pediatric population often presenting with short stature. This was a seemingly ordinary case of hyponatraemia initially deemed to be from hypovolaemia. His atypical clinical features led to the eventual diagnosis of EPP with panhypopituitarism at a rather late age, highlighting the importance of a thorough clinical examination necessitating further evaluation. Presentation: Friday, June 16, 2023

SAT299 Comparison Of Plasma Cortisol-, Salivary Cortisol- And Salivary Cortisone-response To The Short Synacthen Test In Women Using Oral Contraceptives

Abstract Disclosure: N. Bäcklund: None. S. Lundstedt: None. T. Olsson: None. P.M. Dahlqvist: None. G. Brattsand: None. Introduction: The short Synacthen test (SST) is a cornerstone in the diagnosis of adrenal insufficiency (AI). However, cortisol levels in serum or plasma may be misleadingly elevated by estrogen containing oral contraceptives (OCs), due to increased levels of cortisol binding protein (CBG). This may falsely declare a woman with AI to be cortisol sufficient. Salivary cortisol and cortisone closely correlate with the unbound fraction of plasma cortisol and is thus less likely to be influenced by variations in CBG levels. Our hypothesis was that the salivary cortisol and cortisone response to SST would be similar in women with and without OC use. Materials and methods: A standard intravenous 250 µg SST was performed in 87 women without known diseases or medications affecting the cortisol axis, 41 using OCs containing ethinylestradiol and 46 controls. Plasma cortisol was analyzed by Roche Elecsys Cortisol II assay and salivary cortisol and cortisone by LC-MS/MS in samples collected at baseline (time 0), and 30 and 60 minutes after Synacthen injection. The effect of OCs upon plasma cortisol, salivary cortisol and salivary cortisone was assessed by a two-way ANOVA with sampling time after SST as repeated measure. Results: There was an overall effect of OCs on plasma cortisol, but not on salivary cortisol or cortisone. Plasma cortisol levels were considerably higher in the OC group vs. controls at all time points; +150% at 0 minutes; +90% at 30 minutes; and +86% at 60 minutes. There was a significant interaction between OC use and sample time point for both salivary cortisol and cortisone. Mean salivary cortisol in women using OCs was 37% higher vs. controls at 0 minutes but was instead lower in the OCs group at 30 and 60 minutes after SST (-13% and -11%, respectively). Similarly, mean salivary cortisone was also slightly higher in the OC group than controls at baseline (+13%) and somewhat lower at 30 and 60 minutes (-6% and -7%). Conclusion: Plasma cortisol levels during an SST were significantly elevated in women using OCs containing estrogen whereas OC effects upon salivary cortisol and cortisone levels were modest, especially for salivary cortisone. Analysis of salivary cortisone is a promising alternative to plasma cortisol for diagnosis of AI in women using OCs. Presentation: Saturday, June 17, 2023

Regulation of the Cortisol Axis, Glucagon, and Growth Hormone by Glucose Is Altered in Prediabetes and Type 2 Diabetes.

Insulin-antagonistic, counter-regulatory hormones have been implicated in the development of type 2 diabetes (T2D). In this cross-sectional study, we investigated whether glucose-dependent regulation of such hormones differ in individuals with T2D, prediabetes (PD), and normoglycemia (NG). Fifty-four individuals with or without T2D underwent one hyperinsulinemic-normoglycemic-hypoglycemic and one hyperglycemic clamp with repeated hormonal measurements. Participants with T2D (n = 19) were compared with a group-matched (age, sex, BMI) subset of participants without diabetes (ND, n = 17), and also with participants with PD (n = 18) and NG (n = 17). In T2D vs ND, glucagon levels were higher and less suppressed during the hyperglycemic clamp whereas growth hormone (GH) levels were lower during hypoglycemia (P < .05). Augmented ACTH response to hypoglycemia was present in PD vs NG (P < .05), with no further elevation in T2D. In contrast, glucagon and GH alterations were more marked in T2D vs PD (P < .05).In the full cohort (n = 54), augmented responses of glucagon, cortisol, and ACTH and attenuated responses of GH correlated with adiposity, dysglycemia, and insulin resistance. In multilinear regressions, insulin resistance was the strongest predictor of elevated hypoglycemic responses of glucagon, cortisol, and ACTH. Conversely, fasting glucose and HbA1c were the strongest predictors of low GH levels during hypoglycemia and elevated, i.e. less suppressed glucagon levels during hyperglycemia, respectively. Notably, adiposity measures were also strongly associated with the responses above. Altered counter-regulatory hormonal responses to glucose variations are observed at different stages of T2D development and may contribute to its progression by promoting insulin resistance and dysglycemia.

Bilateral adrenal masses with adrenal insufficiency: an unusual presentation of hepatocellular carcinoma

Adrenal insufficiency due to adrenal metastasis is rare and may be present only in 6.1% cases even in bilateral adrenal metastasis. The adrenal glands can maintain its cortisol axis until over 90% of adrenal cortex is destroyed. Bilateral large adrenal masses with adrenal insufficiency, though rare, should prompt further evaluation for a metastatic disease. We report a case of bilateral adrenal masses secondary to metastatic hepatocellular carcinoma causing adrenal insufficiency.

An exhaustive battle of salt: A challenging case of Adipsic Diabetes Insipidus following resection of Craniopharyngioma

Introduction: Even though rare, Adipsic Diabetes Insipidus (ADI) is a potentially life-threatening complication of craniopharyngioma: due to the mass effect of the tumor or perioperative consequences leading to severe hypernatremic dehydration. Even in expert hands, management of water balance, in the absence of thirst is extremely challenging. Case Description: A 25-year-old gentleman, an electrician presented to the neurosurgical casualty with worsening headaches, impaired vision, and features of raised intracranial pressure over 2 months. He was found to have a large cystic suprasellar mass with well-defined margins measuring 2.7cm x 2.7cm x 3cm with chiasmal compression, suggestive of craniopharyngioma, complicating with bitemporal hemianopia, hypogonadotropic hypogonadism (LH 0.78IU/L, FSH 1.2IU/L, Testosterone 33ng/dL), secondary hypothyroidism, cranial diabetes insipidus, prediabetes sparing the cortisol axis. He underwent transcranial resection of the tumor, revealing WHO grade1 adamantinomatous craniopharyngioma followed by radiotherapy. The post-operative period was complicated with severe hypernatremia despite escalating doses and changing dosage forms of desmopressin from parenteral to nasal spray to oral tablets. Two weeks following discharge, he presented with severe hypernatremia (176mEq/L), polyuria, weight loss, hypotension, and altered sensorium where his lack of thirst was appreciated. Conclusions: In those with ADI, for the management of water balance, a “personalized approach” with the involvement of both patient and family is of paramount importance. With appropriate dose titration of desmopressin, careful fluid prescription, and frequent monitoring of electrolytes even at best centers, it is a battle that is hard to win.

An impaired pituitary–adrenal signalling axis in stable cirrhosis is linked to worse prognosis

Background & AimsInadequate adrenal function has been described in patients with cirrhosis. We investigated (i) the pituitary–adrenal axis at different clinical stages and (ii) the clinical impact of decreased serum cortisol levels in stable patients with advanced chronic liver disease (ACLD). MethodsWe included 137 outpatients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement in the prospective VICIS study (NCT03267615). Patients were stratified into six clinical stages: S0: subclinical portal hypertension (PH) (HVPG 6–9 mmHg), S1: clinically significant PH (HVPG ≥10 mmHg) without varices, S2: presence of varices, S3: previous variceal bleeding, S4: previous non-bleeding decompensation, and S5: further decompensation. ResultsFifty-one patients had compensated ACLD (S0: n = 13; S1: n = 12; S2: n = 26), whereas 86 patients had decompensated ACLD (S3: n = 7; S4: n = 46; S5: n = 33). Serum total cortisol (t-Cort) showed a strong correlation with estimated serum free cortisol (f-Cort; Spearman’s ρ: 0.889). With progressive clinical stage, median ACTH levels (from S0: 44.0 pg/ml to S5: 20.0 pg/ml; p = 0.006), t-Cort (from S0: 13.9 μg/dl to S5: 9.2 μg/dl; p = 0.091), and cortisol binding globulin (from S0: 49.3 μg/ml to S5: 38.9 μg/ml; p <0.001) decreased, whereas f-Cort (p = 0.474) remained unchanged. Lower t-Cort levels independently predicted bacterial infections (asHR: 1.11; 95% CI: 1.04–1.19; p = 0.002), further decompensation (asHR: 1.08; 95% CI: 1.02–1.12; p = 0.008), acute-on-chronic liver failure (ACLF; asHR: 1.11; 95% CI: 1.04–1.19; p = 0.002), and liver-related death (asHR: 1.09; 95% CI: 1.01-1.18; p = 0.045). ConclusionsThe pituitary–ACTH–adrenal–cortisol axis is progressively suppressed with increasing severity of cirrhosis. Lower t-Cort is an independent risk factor for bacterial infections, further decompensation of ACLF, and liver-related mortality—even in stable outpatients with cirrhosis. Clinical trial numberVienna Cirrhosis Study (VICIS; NCT: NCT03267615). Impact and ImplicationsIn a cohort of stable outpatients, we observed progressive suppression of the pituitary–adrenal axis with increasing clinical stage of advanced chronic liver disease (ACLD). Increased levels of bile acids and systemic inflammation (assessed by interleukin-6 levels) could be involved in this suppression. Serum total cortisol (t-Cort) was strongly correlated with serum free cortisol (f-Cort) and lower t-Cort levels were independently associated with a higher risk of adverse clinical outcomes, including bacterial infections, further decompensation, acute-on-chronic liver failure, and liver-related death.

Abstract #1397393: A Case of HPA Axis Recovery in the Setting of Immune Checkpoint Inhibitor-induced Hypophysitis

Immune checkpoint inhibitor-related hyophysitis resulting in the loss of anterior pituitary hormones is well described in the literature. Patients with hypophysitis frequently develop secondary adrenal insufficiency, which is usually permanent. We present an unusual case of a patient who had recovery of her hypothalamic pituitary adrenal (HPA) axis. A 32-year-old woman was diagnosed with locally advanced estrogen, progesterone, and human epidermal growth factor 2 receptor negative breast cancer. She received neoadjuvant chemotherapy with pembrolizumab and then underwent a bilateral mastectomy. While on pembrolizumab the patient’s thyroid and cortisol axis were monitored every month. She endorsed increasing fatigue after eight months of pembrolizumab therapy. Her workup showed morning ACTH level was 6.6 (reference range 7.2-63 pg/mL), and her cortisol level was 2.2 (6.7-22.6 mcg/dL), which was confirmed on repeat testing. A diagnosis of secondary adrenal insufficiency was made, and the patient was started on hydrocortisone 10mg at 8 am and 5 mg at 2 pm. Her pituitary hormonal profile was otherwise normal. An MRI brain was not done as the patient denied any symptoms of headache or visual changes. The pembrolizumab was held and the patient had repeat HPA axis testing. She was asked to hold her hydrocortisone 24 hours prior to the assessment of her pituitary adrenal axis. This was conducted every month. After four months of hydrocortisone replacement, her cortisol axis recovered as her labs showed an ACTH of 47.2 and cortisol of 17.4 (6.7-22.6 mcg/dL). The patient was asked to discontinue hydrocortisone and counseled to report if she had any symptoms of adrenal insufficiency. The patient continued to feel well off hydrocortisone therapy with no symptoms of adrenal insufficiency. Her ACTH and cortisol levels remained normal. Recovery from secondary adrenal insufficiency associated with immune checkpoint inhibitor related hypophysitis is rarely seen. This case suggests that certain individuals may recover, potentially those who are younger or do not completely lose ACTH secretion. Repeated pituitary hormone testing for the first six months after the development of hypophysitis may identify more patients with HPA axis recovery and lead to less long-term use of steroids.

Stereotactic radiosurgery for Rathke's cleft cysts: an international multicenter study.

Rathke's cleft cysts (RCCs) are sellar collections from an incompletely regressed Rathke's pouch. Common symptoms of RCCs can include headaches, visual loss, and endocrinopathy. Surgery is required in some cases of symptomatic or growing RCCs. Recurrence after surgery is common (range 10%-40%). Stereotactic radiosurgery (SRS) has been used in an attempt to control growth and symptoms, but outcomes are not well known. The authors sought to study the outcomes of RCCs following Gamma Knife surgery for both salvage and initial treatment. The outcomes of 25 patients with RCCs who underwent SRS between 2001 and 2020 were reviewed. Four patients received initial SRS and 21 were treated with salvage SRS. Diagnosis was based on imaging or histopathology. Cyst control was defined as stability or regression of the cyst. Kaplan-Meier analysis was used to determine time to recurrence and determine potential factors for recurrence. The respective median clinical follow-up and margin dose were 6.5 years and 12 Gy. Overall control was achieved in 19 (76%) of 25 patients, and 4 recurrences required further intervention. The average time to recurrence was 35.6 months in those RCCs that recurred. Visual recovery occurred in 14 (93.3%) of 15 patients and no new post-SRS visual deficits occurred. The presence of a pretreatment visual deficit was often an indicator of RCC regrowth. All 3 patients with pretreatment hyperprolactinemia experienced resolution after SRS. New endocrinopathy related to SRS was noted in 5 (20%) of 25 patients, all of which were thyroid and/or cortisol axis related. Upfront SRS was used in 4 patients. No new endocrinopathies or visual deficits developed after upfront SRS, and the 1 patient with a pretreatment visual deficit recovered. One of the 4 patients with upfront SRS experienced a recurrence after 7.5 years. SRS produced effective recovery of visual deficits and carries a low risk for new visual deficits. Cyst control was achieved in approximately three-fourths of the patients. Following SRS, patients without pretreatment visual deficits are less likely to have RCC regrowth. Endocrinopathy can occur after SRS, similar to other sellar mass lesions. Initial SRS shows the potential for long-term cyst control, with improvement of symptoms and a low risk for complications.

Pituitary stalk interruption syndrome: phenotype, predictors, and pathophysiology of perinatal events.

There is limited data regarding Pituitary Stalk Interruption Syndrome (PSIS) from India. Moreover, the pathophysiological link between perinatal events and PSIS is unclear. We aim to elucidate the predictors of PSIS among patients with growth hormone deficiency (GHD) and perinatal events in PSIS by comparing cohorts of PSIS and genetically proven GHD without PSIS. Among 179 GHD patients, 56 PSIS and 70 genetically positive GHD (52-GHRHR, 15-POU1F1, and 3-PROP1) patients were included. Perinatal events, clinical anomalies, pituitary hormone deficiency, and imaging findings were recorded. We compared PSIS-isolated GHD (PSIS-IGHD) subgroup with GHRHR-IGHD and PSIS-combined pituitary hormone deficiency (PSIS-CPHD) subgroup with POU1F1/PROP1-CPHD. PSIS patients (45 males, median age: 12.5years) most commonly presented with short stature. At last follow-up (median age: 17.35years), gonadal (during pubertal-age), thyroid and cortisol axes were affected in 81.6%, 62.5%, and 62.5%. 10/13 (77%) of PSIS children with initial IGHD diagnosis manifested hypogonadism during pubertal age. Male predominance, sporadic presentation, and clinical anomalies were significantly higher in both PSIS subgroups than in the respective genetic subgroups. Breech presentation was higher in PSIS-CPHD than POU1F1/PROP1-CPHD (44.4% vs 5.5%, p = 0.004). Neonatal hypoglycemia (22% vs. 0%, p = 0.05) and jaundice (42 vs. 5%, p = 0.004) were higher in PSIS-CPHD than PSIS-IGHD. Later age at presentation and frequent hypogonadism were observed in our PSIS cohort. Male sex, sporadic presentation, clinical anomalies, and breech presentation predicted PSIS at presentation. Breech presentation in PSIS is likely due to stalk interruption rather than hormonal deficiency.

The biobehavioural effectiveness of spiritual-hypnosis-assisted therapy in PTSD with childhood trauma

BackgroundPosttraumatic Stress Disorder (PTSD) is a serious psychological trauma disorder. Treatment of psychological trauma tends to focus on patients' memory. Clinical Spiritual-Hypnosis Assisted Therapy is a culturally sensitive treatment that combines elements of psychodynamic hypnosis, cognitive–behavioral and humanistic therapies.MethodsThe current interventional single-blind randomized control study assessed the biobehavioural effectiveness of spiritual-hypnosis on cortisol and PTSD symptomatology in adults with childhood trauma. Participants were divided into spiritual hypnosis (n = 15) and a control group (n = 14) that received fluoxetine. This study used PCL-C & CTQ to screen the presence and severity of PTSD symptoms.ResultsSpiritual hypnosis was significantly better than fluoxetine at reducing PTSD symptoms, while both treatments had similar effects on cortisol modification.ConclusionsSpiritual-Hypnosis Assisted Therapy for PTSD patients with childhood trauma appears to have a noteworthy effect in reducing PTSD clinical symptoms and results in a comparable to the pharmacological treatment modification of the HPA axis cortisol markers.

Biochemical assessment of adrenal insufficiency after adrenalectomy for non-cortisol secreting tumors: clinical correlation and recommendations.

Data regarding changes in cortisol axis after adrenalectomy for non-cortisol secreting tumors and their correlation with adrenal insufficiency are limited. Our aim was to analyze these changes and their clinical correlations to guide management after adrenalectomy for non-Cushing's tumors. Following IRB approval, postoperative cortisol axis changes were analyzed in patients who underwent unilateral adrenalectomy for non-Cushing's tumors. A morning serum cortisol of ≥ 10μg/dl was accepted as a sufficient adrenal response. 223 adrenalectomies were analyzed. In 63% of patients, POD1 serum cortisol was ≥ 10μg/dl and in 37% &lt; 10μg/dl. No patient with a POD1 cortisol ≥ 10μg/dl developed AI symptoms, whereas symptoms of AI were observed in 4% of those with &lt; 10μg/dl. In patients with a POD1 cortisol of &lt; 10μg/dl, the rate of steroid replacement therapy initiation was 100%, 8%, and 25% when the decision was based on serum cortisol, clinical symptoms, and serum cortisol plus ACTH stimulation test results, respectively. In 90% of asymptomatic patients, hypocortisolemia resolved uneventfully within a week on repeat morning cortisol testing. 75% of patients with hypocortisolemia on POD1 demonstrated an adequate cortisol response to ACTH stimulation test. Although postoperative hypocortisolemia was observed in 37% of patients undergoing unilateral adrenalectomy for non-cortisol secreting tumors, majority did not develop symptoms of adrenal insufficiency. All three steroid initiation approaches appeared safe, with management based on clinical symptoms or selective ACTH stimulation testing sparing more patients from steroids compared to steroid initiation based on POD 1 cortisol levels alone.

Abstract 94: Efficacy of cabergoline treatment in men with giant prolactinomas

Introduction: Giant prolactinomas in males are rare tumours in whom outcome data is scarce.Aims and Objectives: To evaluate the outcomes of therapy in men with ‘giant prolactinomas’ (>4 cm).Results: Of twenty-five males with macroprolactinoma following up in the Endocrinology Clinic; ten fulfilled the criteria of Giant Prolactinoma and were included in this retrospective study. The mean age was 34.2±12.67 years. Headache (n=10) and visual field defects (n=8) followed by hypogonadal symptoms (n=8) were the common presenting symptoms. A significant decrease of the Prolactin (PRL) values was observed in all patients (6420±1343.3 to 97.5±1.72 ng/dl; p= 0·0005). Persistent normalization of PRL levels was achieved in 7/10 patients. Significant tumour shrinkage (5±0.40 to 2.7±0.28 cm, p = 0·02) was achieved in 8/10 patients, with a volume reduction > 90% in three, >50% in four and >25% in one patient.Gonadotropin deficiency (n=9); TSH deficiency (n=4) and Cortisol deficiency (n=4) were uncovered on initial laboratory evaluation. The gonadotropin axis recovered in 1/9 and cortisol axis in 3/4 deficient subjects after normoprolactinaemia was achieved. The thyrotropin axis was affected irreversibly.Discussion and Conclusion: In male subjects with giant prolactinomas, recovery in other pituitary axes did not occur in spite of normalizing PRL levels and achieving tumour shrinkage.

Abstract 70: High dose intravenous therapy augments complete anterior pituitary hormoanl recovery in primary autoimmune hypophysitis

Background: Glucocorticoid treatment of primary autoimmune hypophysitis (PAH) is well established; however, dose, route, and recovery predictors are not well-defined.Aims: Systematic review of published literature for use of glucocorticoids as first line of management in PAH- to analyze treatment protocol, baseline and post-treatment clinical, hormonal, and radiological features.Results: 152 cases (females-69.8%; age-41±13.9 years) with PAH [(94-oral steroid group (OSG); 58-intravenous steroid group (IVSG)] were included. Clinical recovery [headache, 79% vs.97%; visual deficits, 58% vs.90%; cranial nerve palsy, 50% vs.87%] between OSG and IVSG were comparable. Complete anterior pituitary hormonal (APH) recovery was significantly higher in IVSG (39.02% vs.20.89%, p=0.04) predominantly due to corticotroph axis recovery (56.7% vs. 27.3%), whereas recovery of other APH axes were not different. Persistent APH deficit was higher in OSG (52.2% vs. 29.3%, p=0.02). Radiologically, regression of pituitary enlargement (72% vs. 64%) and resolution of stalk thickening (76% vs. 64%) between groups was not different. Trend towards lesser recurrence in IVSG (19.3% vs. 32.9%) was seen. Prednisolone equivalent dose (mg)/day was significantly higher in IVSG [30 (24-65) vs. 136 (73-136)] with similar treatment duration (weeks) [8 (8-20) vs. 10 (6-10)]. Reported major adverse effects did not differ between groups. DI predicted poor hormonal recovery in IVSG, while no other parameter affected recovery.Conclusion: High-dose pulse IVS leads to better APH recovery and may decrease recurrence. Preserving the cortisol axis prevents long-term hormone replacement and adrenal crisis in future.

A Comparison of the Blood Glucose, Growth Hormone, and Cortisol Responses to Two Doses of Insulin (0.15 U/kg vs. 0.10 U/kg) in the Insulin Tolerance Test: A Single-Centre Audit of 174 Cases.

Objective The insulin tolerance test (ITT) is the gold standard endocrine test used to assess the integrity of the growth hormone (GH) and cortisol axes. The ITT has potential risks, and severe hypoglycaemia may necessitate intravenous glucose rescue. There is no clear consensus as to the optimal insulin dose for the ITT. Therefore, we sought to compare the standard dose (0.15 U/kg) and a low-dose ITT (0.1 U/kg). Design Single-centre audit of ITT data (2012–2021). Patients and Measurements. Patients who underwent an ITT to assess possible GH deficiency/adrenal insufficiency were included. Glucose, GH, and cortisol were measured at baseline and 30, 45, 60, 90, and 120 minutes following I.V. insulin bolus (0.15 U/kg or 0.10 U/kg). Results Of the ITTs performed, only 3/177 (1.7%) did not achieve adequate hypoglycaemia (≤2.2 mmol/L) with a single insulin dose. In total, 174 patients (43.5 ± 12.1 yrs, mean ± standard deviation) were included for analysis (0.15 U/kg: n = 113, 0.10 U/kg: n = 61). All 174 subjects had adequate hypoglycaemia regardless of baseline fasting blood glucose level or insulin dose. Neither nadir glucose nor glucose delta (i.e., baseline minus nadir) differed between insulin doses. Trends in both cortisol and GH responses over time were similar between groups, and a greater proportion of patients receiving the standard dose had an adequate cortisol response (77/106 (72.6%) vs. 32/60 (53.3%), p=0.01). The rates of glucose rescue did not differ in a subset of 79 patients, with on-demand glucose rescue in 4/35 (11%) for the standard dose and 2/44 (5%) for the low dose (p=0.25). Conclusions Our results suggest that the low-dose ITT produces comparable glucose, cortisol, and GH responses to the higher dose. Given the risks associated with hypoglycaemia, the low dose appears to be preferable to the standard dose ITT in most circumstances.

Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes

ContextRoux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.ObjectiveIntegrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB.Design and SettingFollow-up of single-center randomized study.PatientsThirteen patients with obesity and T2D compared to 22 healthy subjects.InterventionsBlood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.ResultsAfter RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01).ConclusionsWe propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.

Neural network modeling for prediction of recurrence, progression, and hormonal non-remission in patients following resection of functional pituitary adenomas.

Functional pituitary adenomas (FPAs) cause severe neuro-endocrinopathies including Cushing's disease (CD) and acromegaly. While many are effectively cured following FPA resection, some encounter disease recurrence/progression or hormonal non-remission requiring adjuvant treatment. Identification of risk factors for suboptimal postoperative outcomes may guide initiation of adjuvant multimodal therapies. Patients undergoing endonasal transsphenoidal resection for CD, acromegaly, and mammosomatotroph adenomas between 1992 and 2019 were identified. Good outcomes were defined as hormonal remission without imaging/biochemical evidence of disease recurrence/progression, while suboptimal outcomes were defined as hormonal non-remission or MRI evidence of recurrence/progression despite adjuvant treatment. Multivariate regression modeling and multilayered neural networks (NN) were implemented. The training sets randomly sampled 60% of all FPA patients, and validation/testing sets were 20% samples each. 348 patients with mean age of 41.7years were identified. Eighty-one patients (23.3%) reported suboptimal outcomes. Variables predictive of suboptimal outcomes included: Requirement for additional surgery in patients who previously had surgery and continue to have functionally active tumor (p = 0.0069; OR = 1.51, 95%CI 1.12-2.04), Preoperative visual deficit not improved after surgery (p = 0.0033; OR = 1.12, 95%CI 1.04-1.20), Transient diabetes insipidus (p = 0.013; OR = 1.27, 95%CI 1.05-1.52), Higher MIB-1/Ki-67 labeling index (p = 0.038; OR = 1.08, 95%CI 1.01-1.15), and preoperative low cortisol axis (p = 0.040; OR = 2.72, 95%CI 1.06-7.01). The NN had overall accuracy of 87.1%, sensitivity of 89.5%, specificity of 76.9%, positive predictive value of 94.4%, and negative predictive value of 62.5%. NNs for all FPAs were more robust than for CD or acromegaly/mammosomatotroph alone. We demonstrate capability of predicting suboptimal postoperative outcomes with high accuracy. NNs may aid in stratifying patients for risk of suboptimal outcomes, thereby guiding implementation of adjuvant treatment in high-risk patients.

NCOG-53. PREDICTORS OF ENDOCRINE OUTCOME AFTER ENDOSCOPIC TRANSSPHENOIDAL SURGERY FOR NON-FUNCTIONING PITUITARY ADENOMAS

Abstract BACKGROUND Although endoscopic transsphenoidal surgery (ETSS) is an established treatment for patients with nonfunctioning pituitary adenomas (NFPAs), data are limited regarding the rates and predictors of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS. OBJECTIVE To analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS Among a cohort of 601 consecutive patients who underwent ETSS for NFPA between 2010 and 2018 at Washington University in Saint Louis, recovery or development of new hypopituitarism was retrospectively analyzed in 209 patients. RESULTS Preoperative endocrine deficits were observed in 59.8% of patients (125/209), and the deficit rates were 76.8% for male gonadal axis (86/112), 42.5% for thyroid axis, 25.8% for growth hormone axis, and 15.8% for cortisol axis. Recovery of preoperative pituitary deficit was noted in all four axes, with highest recovery in the cortisol axis with a 1-year cumulative recovery rate of 44.3%. New-onset postoperative hypopituitarism occurred most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Multivariate analyses revealed axis-specific predictors of postoperative recovery and de novo deficiency. Older age was a negative predictor for recovery of both male hypogonadism (P= 0.04) and adrenal insufficiency (P=0.046), and a larger tumor volume was a negative predictor for recovery of hypothyroidism (P=0.043). Although higher body mass index was generally associated with any new postoperative pituitary deficit (P=0.03), most predictors of new onset deficits also differed by hormone axis. CONCLUSIONS Dynamic changes in pituitary hormonal levels were observed in a significant fraction of patients following ETSS in NFPA patients. The specific hormonal axis dictated postoperative endocrine vulnerability, recovery, and predictors of recovery or loss of endocrine function.

Cold stress promotes IL-33 expression in intestinal epithelial cells to facilitate food allergy development

BackgroundThe causative factors and pathogenesis of food allergy (FA) is not fully understood yet. Cold stress (CS) occurs frequently in human life that influences physiological activities in the body. In this study, we aimed to investigate the chronic CS (CS) effects on promoting the expression of IL-33 in intestinal epithelial cells. MethodsCS was carried out by placing mice at 4 °C for 1 h daily for 7 consecutive days. We developed a mouse model used to test the effects of CS on the FA development. ResultsWe found that, similar to conventional FA mouse model, CS induced the core body temperature to drop markedly in mice, increased intestinal epithelial barrier permeability and facilitated FA development. CS promoted interleukin (IL)-33 expression in intestinal epithelial cells through the adrenocorticotropic hormone (ACTH)/cortisol axis and via inducing the Il33 promoter methylation. CS facilitated the FA development in mice, that could be blocked by depletion of IL-33 expression in intestinal epithelial cells. ConclusionsCS induces IL-33 expression in intestinal epithelial cells to promote Th2 polarization in the intestinal tissues and facilitates FA development.

Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery.

Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.