ACTH-dependent Cushing's Syndrome Research Articles

ACTH-independent cushing's syndrome in a patient with bilateral adrenal tumors: complete remission after unilateral adrenalectomy

ACTH-independent cushing's syndrome in a patient with bilateral adrenal tumors: complete remission after unilateral adrenalectomy

Clinical Conundrum of ACTH-Independent Cushing's Syndrome in a Child with Adrenal Cortical Carcinoma: A Case Report and Review of Literature

AbstractAdrenocorticotropic hormone-independent Cushing's syndrome (CS) secondary to cortisol-secreting adrenal cortical carcinoma (ACC) in children has been seldom reported. We report on a 6-year-old girl diagnosed with CS due to a right-sided ACC. She presented with rapid onset obesity, virilization, and hypertensive urgency. Postserial diagnostic evaluation, control of hypertension, right adrenalectomy with en bloc resection of tumor mass were performed. The child had an excellent clinical and biochemical recovery with significant weight loss and return to normal serum cortisol levels.

Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome: A reappraisal.

Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone (ACTH)-dependent, of which a substantial minority are due to a source outside of the pituitary, ectopic ACTH syndrome (EAS). Differentiating among pituitary-dependent CS, Cushing's disease (CD) and an ectopic source can be problematic. Because non-invasive tests in the evaluation of CS patients often lack adequate sensitivity and specificity, bilateral inferior petrosal sinus sampling (BIPSS), a minimally invasive procedure performed during the investigation of ACTH-dependent CS, can be extremely helpful. BIPSS is considered to be the gold standard for differentiating CD from the EAS. Furthermore, although such differentiation may indeed be challenging, BIPSS is itself a complex investigation, especially in recent times due to the widespread withdrawal of corticotrophin-releasing hormone and its replacement by desmopressin. We review current published data on this investigation and, in the light of this and our own experience, discuss its appropriate use in diagnostic algorithms.

The diagnostic yield of inferior petrosal sinus sampling in Cushing syndrome in the era of ovine CRH shortage

PurposeThe ovine corticotropin-releasing hormone (oCRH) stimulation test has been routinely used in the diagnostic work-up of ACTH-dependent Cushing syndrome (CS). With oCRH currently being out-of-stock in Europe, we aimed at evaluating the diagnostic performance of inferior petrosal sinus sampling (IPSS) without oCRH stimulation.MethodsWe compared the values of 40 patients with ACTH-dependent CS and negative MRI findings in whom ACTH was measured before and after oCRH stimulation.ResultsThe ratio of central-to-peripheral ACTH measurement (IPS:P) before the combined 3, 5, and 10 min of oCRH stimulation yielded diminished sensitivity (85% vs. 97%), alongside markedly decreased specificity (57% vs. 71%), as well as reduced positive and negative predictive values (90% vs. 94% and 44% vs. 83%), respectively.ConclusionsWith the current drug shortages in Europe, ACTH measurements without oCRH stimulation in IPSS cannot be recommended. Thus, we call for desmopressin or the commercially available human CRH as a potential alternative in the confirmation of ACTH excess by IPSS in equivocal MRI findings.

Machine Learning May Be An Alternative To BIPSS In The Differential Diagnosis Of ACTH-Dependent Cushing's Syndrome.

This study aimed to develop machine learning (ML) algorithms for the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) based on biochemical and radiological features. Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve (AUROC) was used to measure performance. We used Shapley Contributed Comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. A total of 106 patients, 80 with Cushing's disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, the > 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. ML algorithms have the potential to serve as an alternative decision support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Refractory Hypokalemia Revealing Cushing’s Syndrome and Persisting after Bilateral Adrenalectomy: A Case Report and Review of the Literature

Cushing's syndrome (CS), a rare endocrine disorder, is characterized by a diverse range of clinical manifestations due to prolonged exposure to excess glucocorticoids. CS can be divided into ACTH-dependent and ACTH-independent types, with varying degrees of clinical severity. Biochemical abnormalities, such as hypokalemia, are associated with CS, potentially resulting from the mineralocorticoid effects of cortisol. We present a unique case of Cushing's disease with a prominent and persistent feature of hypokalemia, even after a successful bilateral adrenalectomy. The patient's clinical presentation included sudden abdominal obesity, lumbago, polyuria, polydipsia, chronic constipation, muscle cramps, and profound weakness. Early diagnostic evaluation revealed severe hypokalemia requiring treatment. Despite bilateral adrenalectomy, hypokalemia persisted postoperatively, necessitating ongoing potassium supplementation. This case highlights the complex interplay of hormones in CS and the need for comprehensive clinical and biochemical assessments. Hypokalemia is prevalent in Cushing's syndrome (CS), typically resulting from renal potassium loss, influenced by cortisol's mineralocorticoid-like effects. Additionally, ACTH might inhibit 11β-HSD2, allowing cortisol to act as a mineralocorticoid. Persistent hypokalemia in our ACTH-dependent CS case, even after bilateral adrenalectomy, raises questions about the role of ACTH and 11β-HSD2. Further research is needed to clarify these mechanisms and their relationship with CS.

Diverse presentations of Cushing's syndrome during pregnancy - A case series.

Cushing's syndrome (CS) encompasses various causes of hypercortisolism including adrenocorticotropic hormone (ACTH) secreting pituitary adenoma with or without bilateral adrenal hyperplasia, an adrenal adenoma or carcinoma, ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion by a neoplasm or exogenous corticosteroid therapy. The diagnosis of CS in pregnancy presents a challenge due to overlapping clinical features of pregnancy (weight gain, striae, acne). If untreated, CS in pregnancy is associated with increased risk of maternal and fetal complications. With fewer than 250 cases currently published, we aim to review the clinical presentations, diagnostic methods, management, and outcomes of patients with CS in pregnancy to help optimise our clinical practice. This is a single-centre, retrospective review of woman with documented hypercortisolism receiving antenatal care at a tertiary maternity hospital in Perth between 2006 to 2022. Data were collated from electronic and chart reviews. OMNI calculator was used for birthweight calculations. Local ethics and patient consent were obtained. Five women and seven pregnancies were identified. Four women had a pituitary source of ACTH-dependent CS as confirmed by brain magnetic resonance imaging. One woman had an ectopic source of ACTH. Two women were diagnosed during pregnancy. All pregnancies occurring prior to treatment of the Cushing's disease were complicated by secondary hypertension and diabetes. CS represents a rare and difficult to diagnose condition in pregnancy. When untreated, maternal and fetal outcomes are compromised. Close monitoring of the associated complications with involvement of a multidisciplinary team are recommended.

P-47 Rare case of acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome

Abstract Introduction The concurrence of acromegaly and Cushing syndrome is infrequent. Pituitary adenomas are responsible for acromegaly and for Cushing syndrome in about 95% and 80% of cases respectively. Except adrenal adenoma, the other causes of Cushing syndrome remain rare. We here describe a case of a Tunisian patient with acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome with bilateral macronodules. Clinical Case A 35-year-old male patient was diagnosed with acromegaly by acrofacial dysmorphia. He had a family history of type 2 diabetes mellitus and hypertension but no endocrine diseases. He has diabetes mellitus for 15 years, hypertension and obstructive sleep apnea. Physical examination showed multiple blue nevi in the trunk. IGF-1 was elevated (1680ng/mL) and GH levels were not suppressed after an oral glucose load (nadir 78ng/mL). He had hypogonadotropic hypogonadism with normal prolactin (9,66ng/mL). Basal cortisol, FT4 and TSH levels were in the normal ranges. Pituitary MRI showed pituitary macroadenoma of 25×20.7 mm, invading both cavernous sinuses and compression of optic chiasma. He underwent transsphenoidal resection with histology confirming a prolactin, GH and LH co-secretory pituitary adenoma. He received postoperatively somatostatin analogue and cabergoline, in addition to external radiotherapy. Ultrasonography found infracentimetric EU-TIRADS 2 left nodule and multiple colloid cysts of the thyroid, testicles microlithiasis and no cardiac myxomas. Nine years after the diagnosis of acromegaly, bilateral adrenal adenomas (left:14 mm, right: 9 mm) were incidentally discovered by CT-scan done for abdominal pain. Low dose dexamethasone suppression test was carried out showing no suppression of cortisol and the low ACTH level confirmed ACTH-independent Cushing syndrome. Conclusion In our patient, at least two endocrine syndromes deserve to be mentioned. The first syndrome is Multiple Endocrine Neoplasia Type 1 but calcium and PTH levels were normal and there was no sign for neuroendocrine tumors. The second one is Carney's complex since our patient has acromegaly and multiple blue nevi which are two major criteria confirming the diagnosis. Cushing syndrome in Carney's complex is related to primary pigmented nodular adrenal disease characterized by micronodular hyperplasia. However, bilateral macronodules could be found in up to 30% of cases.

O-10 Lymph node ACTH washout determined the source of ACTH secretion in a patient with Cushing's Syndrome due to medullary thyroid cancer

Abstract Introduction Ectopic ACTH syndrome constitutes 18% of Cushing's syndrome cases, and in rare cases, ACTH secretion from medullary thyroid cancer cells is the source of ectopic ACTH production. Here we report a catastrophic Cushing's syndrome case owing to medullary thyroid cancer in which the source of ACTH production was demonstrated by lymph node ACTH washout. Clinical Case A 23 year-old male was admitted to other clinics with complaints of inability to lose weight despite diet and exercise, and weight gain of approximately 40 kg, which had been going on for the last two years. At his application, his weight was 160 kg and his body mass index was 42.51 kg/m2. On physical examination, clinical stigmata suggesting Cushing's syndrome such as moon face, buffalo hump, supraclavicular fat deposition, acanthosis nigricans, centripedal obesity, purple striae on the abdomen were noted. The biochemical and hormonal evaluation confirmed ACTH-dependent Cushing's syndrome (Table 1). To establish the source of excess ACTH, first, a pituitary MRI was performed which revealed a 4×2 mm adenoma on the left side of the gland. In PET-CT, a 24×20 mm hypoechoic nodule in the inferior of the right thyroid lobe, and several pathological lymph nodes at the right side of the neck were detected. Serum calcitonin levels were high (6528 ng/L) and fine-needle aspiration biopsy from the thyroid nodule documented medullary thyroid cancer. The patient underwent bilateral total thyroidectomy and right cervical lymph node dissection. The pathology report was compatible with metastatic medullary thyroid cancer. After surgery, the remission of hypercortisolemia was not achieved and the patient was started on metyrapone treatment before the permanent treatment plan. Postoperative Gallium-68 DOTA PET-CT indicated residual disease and increased uptake in retropharyngeal, bilateral cervical level 2-4, right level 3, bilateral central, and bilateral lower cervical lymph nodes. The persistence of hypercortisolemia after surgery was most likely attributed to residual disease, however, it was considered that pituitary adenoma may also be the cause of ACTH secretion. Therefore, to confirm the source of ACTH secretion, ACTH washout samples were taken from the cervical lymph nodes and were found to be high as 958 ng/L. Reoperation was performed for recurrent mass and lymph node metastases. Conclusion Medullary thyroid cancer should definitely be considered in cases of ectopic ACTH syndrome. ACTH washing from the suspected lymph node may be an option for diagnostic purposes. In addition to the patient's primary tumor, hypercortisolism should also be treated.Table 1.Cushing's assessment tests

P-61 From Cushing to Nelson Syndrome: Diagnostic challenges and Surgical Dilemma

Abstract Introduction Diagnosis of the origin of ACTH-dependent Cushing's syndrome (CS) can be difficult in some cases, especially when MRI of the pituitary gland does not reveal an adenoma. Inferior petrosal (IPSS) or cavernous sinus sampling (CSS) with CRH stimulation helps confirm the central origin in most cases. CSS also helps lateralize the tumor within the pituitary gland with a sensitivity of 80%. Because transsphenoidal pituitary surgery is successful in the majority of MRI-negative cases, bilateral adrenalectomy is performed less frequently. Even with advanced radiologic studies, the origin may not be detected. Adrenalectomy may be an option in these cases. However, loss of feedback inhibition of the hypothalamic-pituitary-adrenal axis; can lead to aggressive transformation of an existing ACTH-secreting pituitary adenoma into Nelson's syndrome within 1-5 years. Clinical Case A 46-year-old female patient complaining of hot flashes and unable to lose weight was evaluated for CS and referred to the Department of Neurosurgery for a pituitary adenoma (Table 1). Since the adenoma was &amp;lt;6mm CSS with CRH stimulation was performed. The results did not support central origin (Table 2). Ectopic ACTH secretion was considered, but without finding the origin of the tumor on radiological examination, and treatment with ketoconazole and metyrapone was started for CS. However the patient then discontinued outpatient follow-up. The patient presented to our clinic 6 years later with a new pituitary MRI showing tumor growth (Fig.1b). She complained of fatigue and obesity. She was depressed and anxious. The skin on her face, hands and hump was dark and patchy (Fig.1c). During these years, she consulted several endocrinologists. MRI was performed annually. Brain MRI had showed a fronto-basal extraaxial mass lesion. The patient underwent microsurgical resection and pathology revealed a microcystic meningioma (WHO grade I). 3 months later bilateral nodular hyperplasia of adrenal gland was detected; she underwent bilateral laparoscopic adrenalectomy (no neoplasia). ACTH gradually increased up to 418pg/ml; the diagnosis of Nelson's syndrome was established. The patient underwent endoscopic transsphenoidal adenomectomy. The ACTH level was found to be 12pg/ml on the 2nd postoperative day. Pathological examination revealed a ACTH secreting pituitary adenoma (Ki-67:7%). CS patients suffer from emotional lability due to the effects of elevated cortisol and to the physical changes of their body. Proximal muscle weakness and obesity causes fatigue symptoms. The diagnosis is often delayed until complications occur. Differential diagnosis could be difficult and challenging. Patient's emotional lability could adversely affect treatment/follow-up compliance. The presented case had meningioma resection which could be delayed until remission from CD and bilateral adrenalectomy which could be avoided by endoscopic pituitary surgery. This case is a good example of the need for pituitary centers of excellence.Figure.Fig.1.a. MRI scan of the pituitary gland at first admission shows (a) a lesion extending posteriorly inferior to the right half of the pituitary gland, hyperintense at T2-weighted, iso-hypointense at T1-w, with heterogeneous contrast enhancement consistent with pituitary microadenoma (4mm*2mm) Fig.1.b. Progression in size of the adenoma (6mm*4mm) Fig.1.c. Darkening of the skin due to hypersecretion of ACTH. Table 1.Cavernous sinus sampling with corticotropin-releasing hormone stimulation Table 2.Laboratory tests in different times

P-03 A report of recurring pregnancy-induced Cushing's Syndrome

Abstract Introduction The incidence of pregnancy-induced Cushing's syndrome (CS) is very low. However, the diagnosis of CS in pregnant patients is very difficult because of an overlapping signs and symptoms. Clinical Case A 20-year-old woman with polycystic ovarian syndrome (PCOS) was successfully treated with clomiphene for infertility and pregnant in September of 2016 for the first time. She experienced out of proportion abdominal obesity, excessive striosis, exacerbation of hirsutism and myasthenia during the first trimester of her pregnancy. Initial diagnosis of ovarian hyperstimulation syndrome (OHSS) was made and due to concomitant intrauterine growth retardation (IUGR), the pregnancy was electively terminated at the 8th week. All associated symptoms spontaneously regressed within 2-3 months after the abortion. The second pregnancy was induced with a pulse treatment of letrozole 5 mg, followed by 3 every other day injections of 100 units recombinant follicle-stimulating hormone. Within the first 4 weeks into the second pregnancy, the patient developed recurrence of OHSS symptoms. In addition to the prior symptoms and progressive proximal myasthenia, the patient developed hypertension, round moon-like face, back hump, and suprasternal fat pad consistent with the typical features of CS. In week 14 of pregnancy, the patient complained from acute-onset bilateral blindness and hypertension (blood pressure of 180/120 mmHg), which soon progressed into loss of consciousness and grand-mal seizure. She was admitted to the intensive care unit (ICU). Admission laboratory testing included those to assess the function of the pituitary-adrenal axis (HPA) due to the presence of symptoms related to CS. Based on available clinical information a diagnosis of hemolysis, elevated liver enzymes, and a low platelet count (HELLP) syndrome was made and emergency termination of pregnancy was carried out at the gestational age of 14 weeks. The patient`s clinical signs such as hypertension and acute blindness were totally subsided soon after the therapeutic abortion. Diagnosis of ACTH independent CS was made based on elevated 8 a.m. serum cortisol level unresponsive to low-dose dexamethasone (45-41 µg/ dL). Conclusion Diagnosis of CS in pregnancy is challenging as the physiological changes during pregnancy may mimic those of CS. Long-term treatment of gestational CS has not been as successful. However, in the case of adrenal hyperplasia, bilateral adrenalectomy offers a certain cure. Our patient had a therapeutic abortion due to severe maternal complications and development of CS during the early gestational age. The patient was reeducated on the subject of contraception and the possibility of adrenalectomy for future pregnancies. Due to the temporal relation between the occurrence of CS after each pregnancy the diagnosis of gestational hypercortisolism was made, and for further pregnancies bilateral adrenalectomy was recommended.

Evaluating the usefulness of plasma chromogranin A measurement in cyclic ACTH-dependent Cushing's syndrome.

Cushing's syndrome, a clinical condition characterized by hypercortisolemia, exhibits distinct clinical signs and is associated with cyclic cortisol secretion in some patients. The clinical presentation of cyclic Cushing's syndrome can be ambiguous and its diagnosis is often challenging. We experienced a 72-year-old woman with cyclic ACTH-dependent Cushing's syndrome caused by a pulmonary carcinoid tumor. Diagnosis was challenging because of the extended trough periods, and the responsible lesion was initially unidentified. A subsequent follow-up computed tomography revealed a pulmonary lesion, and ectopic ACTH secretion from this lesion was confirmed by pulmonary artery sampling. Despite the short peak secretion period of ACTH (approximately one week), immunostaining of the surgically removed tumor confirmed ACTH positivity. Interestingly, stored plasma chromogranin A levels were elevated during both peak and trough periods. The experience in evaluating this patient prompted us to investigate the potential use of plasma chromogranin A as a diagnostic marker of ACTH-dependent Cushing's syndrome. A retrospective study was conducted to determine the efficacy of plasma chromogranin A in three patients with ectopic ACTH syndrome (EAS), including the present case, and six patients with Cushing's disease (CD) who visited our hospital between 2018 and 2021. Notably, plasma chromogranin A levels were higher in patients with EAS than in those with CD. Additionally, a chromogranin A level in the present case during the trough phase was lower than that in the peak phase, and was similar to those in CD patients. The measurement of plasma chromogranin A levels could aid in differentiating EAS from CD.

Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria.

Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. The objective of this work is to examine the alteration of gut microbiota in patients with CS. We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.

False-Negative Inferior Petrosal Sinus Sampling in Young-Onset Cushing Disease: What Happens Next

Introduction: False-negative results during inferior petrosal sinus sampling (IPSS) may complicate the diagnostic evaluation of patients with ACTH-dependent Cushing syndrome (CS). The management of these patients can be confusing for clinicians and lead to delayed management. Methods: We studied patients with young-onset (Results: We recorded a rare incidence of false-negative IPSS results in 5 out of the 142 IPSS procedures (3.5%), performed in 4 unique patients. Patients with negative IPSS did not differ in demographic (age and sex) or biochemical (diurnal ACTH/cortisol or 24-hour urinary free cortisol) data from the remaining. Additional workup was performed in three of the four patients including evaluation for ectopic sources of CS and repeat IPSS. Two of these patients also received medical treatment for suppression of cortisol production. One patient decided to proceed with pituitary exploration without additional evaluation. All patients finally underwent surgery and achieved remission. Discussion/Conclusion: In patients with CD, IPSS may rarely lead to false-negative results. Management of these patients usually includes screening for ectopic sources of ACTH/CRH secretion, repeating IPSS if ectopic workup is negative, and considering medical management until final diagnosis of the source of hypercortisolism is made.

Is this pancreatic NET responsible for an ectopic ACTH-dependent Cushing's syndrome?

Is this pancreatic NET responsible for an ectopic ACTH-dependent Cushing's syndrome?

Laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA): an alternative approach for severe Cushing's syndrome.

Severe uncontrolled Cushing's syndrome (CS) is an acute life-threatening condition. As it is often not responsive to medical therapy, emergency bilateral adrenalectomy (BA) may present the only therapeutic option. Moreover, multiple bone fractures, representing one of the clinical consequences of hypercortisolism, may not permit both prone and lateral patient's positioning during surgery, thus making minimally invasive approaches nonfeasible. We report our preliminary experience with an alternative approach in this selected patients' category. Among 613 patients who underwent endoscopic adrenalectomy at our centre (34-5.6% BA) between January 1997 and October 2021, 3 patients were scheduled for laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA). Surgery was performed with patient in supine position, with fastened arms and legs to allow Trendelenburg and anti-Trendelenburg movements and lateral rotations. The procedure consisted in a synchronous bilateral adrenalectomy. A modern multi-articulated operative table provided rotations on the right and left side to perform left and right adrenalectomy, respectively. One male and two female patients with a mean age of 34 ± 3.1years underwent La-TABA. Mean operative time was 200 ± 138.3min. No perioperative complications were registered. Mean postoperative hospital stay was 8 ± 4.4days. In very severe ACTH-dependent CS, BA should be performed as soon as possible. La-TABA may represent the most appropriate therapeutic option, as this patients' category is not able to tolerate prone and lateral positioning required during the conventional surgery. Despite the higher technical complexity of the procedure compared with the other endoscopic approaches to adrenalectomy, it retains the benefits of minimally invasive surgery in terms of postoperative complications and recovery.

Cushing Syndrome Caused by Pituitary and Adrenal Hybrid Tumor: A Rare Case Report

Introduction: Cushing syndrome is a rare endocrine disorder caused by a variety of underlying etiologies. It can be due to exogenous or endogenous high cortisone levels (ACTH-dependent or ACTH-independent). We herein report a case of ACTHdependent Cushing syndrome caused by pituitary and adrenal hybrid adenoma. Case report: A 42-year-old female presented with a complaint of hematemesis. She had hirsutism, central obesity and violaceous striae on her abdomen and thigh. On detailed clinical examination and relevant investigation, we found that the cause of hematemesis was esophagitis with necrotic gastric ulcer due to Cushing syndrome caused by the pituitary and adrenal hybrid adenoma. Discussion: Cushing syndrome is a rare endocrine disorder characterized by increased exogenous or endogenous serum cortisol levels, which lead to various clinical presentations. Early identification of the disease and its cause is critical. The entire clinical presentation must be considered for correct diagnosis, which is generally delayed due to the overlapping symptoms of the disease with various specialities. Conclusion: Diagnosis and management of Cushing’s syndrome continues to present considerable challenges and necessitates referral to higher centers. Its diverse presentation warrants a complete clinical, physical, radiological and endocrine examination.

THU505 Severe Acute Hypercortisolism From Stable Pre-existing Lung Nodule

Abstract Disclosure: N. Raza: None. S. Wagle: None. R.N. Kiani: None. K. Kaput: None. A 63-year-old male with uncontrolled hypertension and Rheumatoid arthritis was admitted for acute psychosis, progressive asthenia, and severe refractory hypokalemia. He was afebrile on admission and blood pressure was 151/99 mmHg. Physical examination lacked typical Cushingoid appearance of moon facies, central obesity, or purple striae. Labs showed a potassium of 1.8 (ref: 3.3-5 mmol/L), HbA1c 6.0% (ref&amp;lt;=5.6 %), 24-hour urinary free cortisol of 9438 (ref&amp;lt;=60.0 ug/d) and random ACTH level of 229 (ref:7.7-63.3pg/ml). The presentation was felt to be consistent with ectopic ACTH dependent Cushing's syndrome. He was treated with ketoconazole 400 mg BID, Deep veinous thrombosis prophylaxis and trimethoprim-sulfamethoxazole daily for PJP prophylaxis. CT chest/abdomen/pelvis was performed and showed a 1.9 cm right middle lobe pulmonary nodule. Past records were reviewed and showed a stable lung nodule from 2020 (2.5 years earlier). Elective lung biopsy was discussed, and the patient was discharged home with plan for outpatient biopsy. Prior to his biopsy, he was readmitted with worsening agitation, hypertension, and extremity edema. After extensive discussion with CT surgery, a decision was made to perform robotic-assisted thoracoscopic resection of the right middle lobe with mediastinal lymph node dissection. Post-surgery his BP improved, agitation resolved, and cortisol level declined to 3.4 (ref: 6.0 - 18.4 ug/dL). Final pathology showed a well differentiated neuroendocrine tumor, low grade. Lymphovascular invasion was present, and one lymph node was positive for tumor. ACTH immunostaining was performed and was also positive. Ectopic ACTH dependent Cushing syndrome represents a rare condition, contributing to 5-20% of Cushing’s cases. Lung carcinoid tumor is one of the major causes of ectopic ACTH syndrome and typically resolves with surgery. Unusual in our case is the stability of the lung lesion prior to his acute decompensation and lymph node positivity. To date, we have not identified a reason for the indolent nature of his tumor. He is currently on a hydrocortisone taper and is actively undergoing treatment planning with our multidisciplinary peer review process. Essential to his management is the coordination of multiple providers, which includes complex medical decision making and treatment decisions. In the future, lung carcinoid should be considered in the differential for persons with difficult to control hypertension and a stable pulmonary nodule Presentation: Thursday, June 15, 2023

THU012 Incidental Pituitary Adenoma In A Patient With Ectopic ACTH Secreting Cushing Syndrome - A Diagnostic Conundrum

Abstract Disclosure: M.S. Nali: None. R.R. Yatavelli: None. Background: Cushing’s syndrome (CS) is a rare condition with an estimated incidence of 2-3 cases/million. Endogenous CS can be divided into ACTH -dependent (80%) and ACTH Independent (20%) with Ectopic Cushing’s syndrome (ECS) accounting for 10-20% of all cases of ACTH-dependent CS. Herein we present a case with indolent onset ACTH-dependent CS who on initial work-up showed a pituitary microadenoma raising the suspicion for Cushing disease, but the source of excess ACTH was found to be from a pulmonary neuroendocrine tumor. Clinical Case: A 44-yr-old female with history of type 1 DM, Obesity, BMI 43.60, Sleep apnea was evaluated elsewhere for suspected Cushing’s due to increased insulin requirements and progressive weight gain. Outside labs showed cortisol of 4.5 ug/dl on 1 mg DST &amp; 8 mg DST cortisol was 3 ug/dl. MRI of the pituitary showed a 3.5x 2.8x 1.8 mm microadenoma &amp; she was initially presumed to have Cushing’s disease secondary to pituitary microadenoma. The patient was seen by neurosurgery who referred to endocrine for localization of cortisol excess by IPSS. Clinically she had moon facies, hirsutism, dorsocervical fat pad, violaceous striae on abdomen. On further laboratory evaluation her ACTH: 88 (0-46) and random cortisol 14 ug/dl with normal rest of pituitary hormones. Her 24-hour urine free Cortisol was 45ug/d (3.5 - 45) and late-night salivary cortisol: 74 &amp;&amp;lt;50 (Ref. range &amp;lt;100 ng/dl) on couple of nights, respectively. Due to non-suppressed cortisol on high dose DST, a CT chest was obtained which showed a 2cms non calcified nodule in the left lower lobe of lung. Transbronchial biopsy was performed, cytopathology showed well differentiated neuroendocrine tumor, likely carcinoid and stained strongly positive for ACTH confirming ectopic ACTH producing tumor. Gallium-68 Dotatate Scan showed abnormal increased uptake in the known left lung nodule. The patient was recommended for surgical removal of neuroendocrine tumor, but she could not tolerate anesthesia and had to undergo stereotactic body radiation therapy (SBRT) for the lung lesion. Repeat ACTH levels 2 months post SBRT showed the ACTH levels were elevated and lesion was still persistent on imaging, however on discussion with rad oncology, the neuroendocrine tumors tend to take longer to show response on imaging and plan is to repeat imaging and biochemical work up in couple of months. Conclusion: The diagnosis of CS and recognizing the source of hormonal excess poses significant challenges Pituitary adenomas are incidentally discovered in up to 10% of the normal population &amp; IPSS is advised for patients with ACTH-dependent Cushing's syndrome and an adenoma smaller than 6 mm, however in patients with equivocal findings, it is important to look for other sources of ACTH prior to any invasive procedure. The source of ectopic ACTH secretion should be established after diagnosis because the excision of an ACTH-producing tumor can be curative. Presentation: Thursday, June 15, 2023