Cushing\'s syndrome (CS) secondary to adrenocorticotropic hormone (ACTH) producing tumours is a severe condition with a challenging diagnosis. Ectopic ACTH-secretion often involves neuroendocrine tumours (NET) in the respiratory tract. ACTH-secreting small intestine neuro-endocrine tumours (siNET) are extremely rare entities barely reported in literature. This review is illustrated by the case of a 75-year old woman with fulminant ectopic CS caused by a ACTH-secreting metastatic siNET. Severe hypokalemia, fluid retention and refractory hypertension were the presenting symptoms. Basal and dynamic laboratory studies were diagnostic for ACTH-dependent CS. Extensive imaging studies of the pituitary and thorax-abdomen areas were normal, while [68Ga]Ga-DOTATATE PET-CT revealed increased small intestine uptake in the left iliac fossa. The hypercortisolism was well controlled with somatostatin analogues, after which a debulking resection of the tumour was performed. Pathological investigation confirmed a well-differentiated NET with sporadic ACTH immunostaining and post-operative treatment with somatostatin analogues was continued with favourable disease control.

Ectopic Cushing\'s syndrome (CS) occurs rarely in patients with pancreatic neuroendocrine neoplasms. Early recognition of symptoms is critical given the high morbidity and mortality associated with CS. A database of pancreatic neuroendocrine neoplasms (NENs) seen at the Moffitt Cancer Center between 1/2008 and 4/2022 was reviewed and cases of ectopic CS were identified. Information was extracted on tumor characteristics, clinical signs and symptoms, therapies, and outcomes. Thirteen cases were identified, ranging in age from 16 to 65 years at the initial time of diagnosis (median 42). Twelve of 13 patients had metastatic tumors at presentation. All were well-differentiated at diagnosis although two were described as transformed to poorly differentiated on rebiopsy. A total of 4 patients also experienced Zollinger-Ellison syndrome. Three patients underwent bilateral adrenalectomy to manage uncontrolled CS. Median overall survival of was 56 months from the time of initial cancer diagnosis but only 18 months from diagnosis of CS. Our study showed that ectopic CS is a highly morbid condition when occurring in pancreatic NENs and is associated with aggressive disease. Bilateral adrenalectomy can be considered for syndrome control. To our knowledge, this is the largest institutional case-series of ACTH-secreting metastatic pancreatic NEN.

Cushing\'s syndrome has been believed to be a paraneoplastic syndrome of renal cell carcinomas. However, there appears to be a dearth of compelling evidence to substantiate this notion. The only eligible documentation of Cushing\'s syndrome due to ectopic adrenocorticotropic hormone secretion by renal cancer in English literature dates back to 1988, and it pertains to a deceased patient discovered during an autopsy. Here, we present the first case of Cushing\'s syndrome as a paraneoplastic feature of renal cancer which showed complete resolution following surgical removal of the tumor. Additionally, we conduct review of the literature on this particular subject.

Equine endocrine disease is an important area for equine research, requiring an appropriate case definition for inclusion and criteria for exclusion from disease. Defining a case for research may be different from criteria for clinical diagnosis. Further, clinical diagnosis recommendations have been changing regularly, making this area challenging for equine scientists. This review discusses the diagnosis of major equine endocrine diseases, pituitary pars intermedia dysfunction, equine metabolic syndrome and insulin dysregulation, focusing on the most appropriate diagnostic methods for research case definitions. Different diagnostic methods, including use of reference intervals and clinical decision limits, will be discussed with their relative merits for use in case definition for research.

Lung carcinoid tumor is one of the major tumors causing ectopic ACTH syndrome, and the most common clinical treatment is surgical resection of the lesion. We herein report a suspected pulmonary carcinoid tumor with difficulty in surgical resection and poor response to drug therapy, which was successfully treated with radiofrequency ablation combined with intraoperative biopsy of the lesion. A 48-year-old female patient, with hypercortisolism (reddening of the face, full moon face, hirsutism, acne, and weight gain) detected three months ago. Small and high-dose dexamethasone suppression tests were not suppressed, Cushing\'s syndrome was under consideration. PET-CT examination suggested mild FDG uptake in two nodules in the anterior basal segment of the lower lobe of the right lung, the possibility of ectopic ACTH lesions was considered because of the clinical presentation. Due to difficult surgical approach of the lesion, high risk of surgery and the patient\'s anxiety, CT-guided thermal ablation combined with puncture biopsy was considered to treat the lesions. Image-guided thermal ablation can effectively inactivate ectopic ACTH lesions in the lung, rapidly improve the symptoms of high cortisol, and can be combined with biopsy for pathologic diagnosis. Therefore, this technique can be considered for treating pulmonary ACTH lesions that are difficult to resect surgically.

We aimed to perform a retrospective analysis of a rare subtype of corticotroph adenoma, Crooke\'s cell adenoma, to better understand its clinical features.
We collected T-PIT-positive pituitary adenomas and screened Crooke\'s cell adenomas from January 2020 to December 2021 in our center. Case reports of such tumors were also collected through a literature search. Clinical data such as biochemical tests, imaging examinations, and pathological data of the above cases were analyzed.
A total of 101 T-PIT-positive patients were treated in our center in the last 2 years, and 4 were finally pathologically diagnosed with Crooke\'s cell adenomas. All of these patients were male with elevated adrenocorticotropic hormone levels, and 50.0% presented with hypercortisolemia, Cushing\'s syndrome, visual impairment, and headache. The tumor diameter was significantly larger in these 4 patients (37.0 mm) than in the other patients (26.0 mm), and their tumor invasive behavior was more pronounced. Cases reported in the literature were mainly female (72.8%), and the clinical presentation was also dominated by Cushing\'s syndrome (65.1%) and hormonal dysfunction. Tumors were more common as macroadenomas (33.2 mm) and suprasellar growths (63.8%). The tumor recurrence rate was as high as 55.6%, with 6 cases progressing to pituitary carcinomas and 7.7% of tumor-related deaths. Our further integrated analysis of our center and reported cases revealed that gender, Cushing\'s syndrome, visual dysfunction, hormonal disorders, and tumor growth characteristics were statistically different in different tumor categories.
Crooke\'s cell adenoma is a tumor subtype with obvious clinical aggressive behavior, and an in-depth analysis of its clinical characteristics may assist in developing a comprehensive treatment plan.

Clinically silent corticotroph tumors are usually macroadenomas that comprise 20% of ACTH tumors. They frequently progress to aggressive tumors with high recurrence, invasiveness, and on rare occasions, they may become hormonally active causing Cushing\'s disease. Trustable biomarkers that can predict their aggressive course, as well as their response to traditional or new therapies, are paramount. Aberrant β-Catenin expression and localization have been proposed as responsible for several malignancies including pituitary tumors. Nevertheless, the role of β-Catenin in the aggressive transformation of silent corticotropinomas and their response to Temozolomide salvage treatment have not been explored yet. In this work, we present a case of a silent corticotroph tumor that invaded cavernous sinus and compressed optic chiasm and, after a first total resection and tumor remission it recurred six years later as an aggressive ACTH-secreting tumor. This lesion grew with carotid compromise and caused Cushing\'s signs. It required multiple medical treatments including Cabergoline, Ketoconazole, TMZ, and radiotherapy. Besides, other two surgeries were needed until it could be controlled. Interestingly, we found α-SMA vascular area reduction and differential β-Catenin cell localization in the more aggressive tumor stages characterized by high Ki-67 indexes and p53 expression. Our results may indicate a role of angiogenesis and β-Catenin trigged events in the pituitary tumor progression, which could in turn affect the response to TMZ and/or conventional treatments. These molecular findings in this unusual case could be useful for future management of aggressive pituitary tumors.

Bilateral adrenal hemorrhage is an extremely uncommon and life-threatening condition. It is caused by multiple etiologies, including antiphospholipid syndrome, disseminated histoplasmosis, trauma, severe stress, and granulomatous disease. The authors present a unique case of a 64-year-old alcoholic male, who was admitted after fall and right hip fracture. On day seven of admission, the patient started to develop hypotension, leukocytosis, and tachycardia. CT abdomen was done, which ruled out infectious causes, however, it showed bilateral adrenal hemorrhages. Patient adrenocorticotrophic hormone (ACTH) stimulation test was positive for adrenal insufficiency and was started on hydrocortisone replacement. Our case highlights the fact that adrenal insufficiency after bilateral adrenal hemorrhage can be slow and can manifest as late as seven days and prompt therapy with steroids is warranted to avoid life-threatening adrenal insufficiency.

BACKGROUND: Synthetic adrenocorticotropic hormone (Tetracosactide) has been used in the treatment of refractory glomerular diseases. Literature surrounding the use of this medication is limited to small case series and there is conflicting data on the rate of adverse events associated with this medication.
UNASSIGNED: Glomerulonephritis not in remission after at least 6 months of treatment with conservative care. Stable doses of concurrent immunosuppression were permitted.
METHODS: Membranous nephropathy, IgA nephropathy, minimal change disease, and focal and segmental glomerulosclerosis.
METHODS: Intramuscular synthetic adrenocorticotropic hormone (Tetracosactide, Synacthen Depot) with doses of either 1 mg weekly or 1 mg twice weekly.
RESULTS: Five of 12 patients had at least a partial remission with Tetracosactide. Median time to response was 6 months for responders. Five of the 12 patients had adverse events documented, 2 of which led to treatment discontinuation. No patients with focal and segmental glomerulosclerosis responded to treatment.
CONCLUSIONS: Higher rate of adverse events than previously reported with synthetic adrenocorticotropic hormone and uncertain treatment efficacy.
BACKGROUND: L’hormone adrénocorticotrope synthétique (tétracosactide) a été utilisée pour le traitement des maladies glomérulaires réfractaires. La littérature portant sur l’utilisation de ce médicament est limitée à de petites séries de cas et les données sur le taux d’événements indésirables associés à ce médicament sont contradictoires.
UNASSIGNED: Glomérulonéphrites qui ne sont pas en rémission après un minimum de six mois de traitement conservateur. Des doses stables de traitement immunosuppresseur concomitant étaient autorisées.
METHODS: Néphropathie membraneuse, néphropathie à IgA, néphropathie à lésion glomérulaire minime, hyalinose segmentaire et focale.
METHODS: Des doses soit de 1 mg par semaine soit de 1 mg deux fois par semaine d’hormone adrénocorticotrope synthétique (Tetracosactide, Synacthen Depot) administrées par voie intramusculaire.
UNASSIGNED: Cinq patients sur douze ont connu au moins une rémission partielle avec le tétracosactide. Le délai de réponse médian était de six mois pour les patients qui répondaient au traitement. Cinq des douze patients ont eu des réactions indésirables documentées, dont deux ont entraîné l’arrêt du traitement. Aucun des patients présentant une hyalinose segmentaire et focale n’a répondu au traitement.
UNASSIGNED: Un taux de réactions indésirables plus élevé que celui rapporté précédemment avec l’hormone adrénocorticotrope synthétique et une efficacité incertaine du traitement.

Aldosterone is a mineralocorticoid hormone that maintains sodium and potassium homeostasis. Excess aldosterone secretion causes sodium influx and potassium outflow, leading to hypertension and in some cases hypokalemia. Conn\'s syndrome, or primary aldosteronism, is the most common cause of secondary hypertension, accounting for 20% or more of people with resistant hypertension. We present a young male with hypertension, blurry vision in the right eye, and hypokalemia who was on further investigation found to have an aldosterone-secreting adrenal adenoma. He was treated with retroperitoneoscopic right-sided adrenalectomy and his blood pressure improved. Conn\'s syndrome should be suspected in any hypertensive patient with hypokalemia. Adrenal venous sampling is the best investigation to measure aldosterone levels and also to lateralize the source. Surgical resection is the treatment of choice.