Cyclic Cushing's Syndrome Research Articles

Diagnostic challenges in cyclic cushing's syndrome: a rare case due to ectopic acth secretion by lung carcinoid

Diagnostic challenges in cyclic cushing's syndrome: a rare case due to ectopic acth secretion by lung carcinoid

Cyclic cushing's syndrome: understanding the patterns of a complex endocrine disorder

Cyclic cushing's syndrome: understanding the patterns of a complex endocrine disorder

Cyclic cushing's syndrome: a diagnostic challenge

Cyclic cushing's syndrome: a diagnostic challenge

P-62 Silent Corticotroph Adenoma or Cyclic Cushing's Syndrome?

Abstract Introduction Silent corticotroph adenomas (pituitary neuroendocrine tumours (PitNET)) are a rare subset of nonfunctioning adenomas. The higher aggressiveness in terms of invasion and recurrence make these tumors dangerous and close follow-up in experienced centers is recommended. Clinical Case A 21-year-old obeseo (Body Mass Index:31.71) male patient unable to lose weight and complaining of headaches was referred to the Department of Neurosurgery for a pituitary macroadenoma. He had previously used liraglutide treatment Many purple striae were also seen on the body of the patient, who stated that his wounds did not heal easily. Visual acuity and visual field were normal. There was no neurodeficiency. Endocrinological evaluation revealed that the tumor was nonfunctioning (Table 1). Magnetic resonance imaging of the pituitary gland showed a mass lesion in the right side of the pituitary gland extending to the suprasellar and parasellar area (Knosp grade II) (Fig.1). The tumor with soft consistency was totally removed by endoscopic binostril transsphenoidal approach. The postoperative cortisol was 11.53 µg/dl (6.02-18.4) and free T4 was 1.32 ng/dL (0.93-1.7). The patient had a transient diabetes insipidus in the postoperative course, and he was discharged on the 4th day after surgery. Pathological examination revealed a pituitary adenoma immunostaining diffusely with ACTH, other hormones were unexpressed. Ki-67 was %2. Histological invasion of the dura was noted. Although the patient was clinically overweight and had purple striae suggestive of Cushing's syndrome (CS), his cortisol and ACTH levels were normal and suppressible with 1 mg dexamethasone suppression test. However, his tumour tissue showed diffuse ACTH expression, which led to the diagnosis of a silent ACTH adenoma. Since the clinical findings were not completely silent, could we assume that he suffered from cyclic CS? Cyclic (intermittent or periodic) CS is a condition characterised by alternating periods of transiently elevated cortisol levels followed by normal to reduced levels. The diagnosis of cyclic CS requires the presence of at least three confirmed episodes of elevated cortisol levels interspersed with two periods of normal cortisol levels. As we know, the cortisol secretion cycle is unpredictable and laboratory tests during the normal cortisol secretion period of the cyclic CS often show negative results as in our patient. Conclusion Postoperative follow-up of a silent corticotroph PitNET and cyclic CS patient, both of whom require close and life-long monitoring.Figure 1.Magnetic resonance imaging of the pituitary gland; coronal sections T1- weighted (a), T2-weighted (b), sagittal (c), and coronal (d) sections with T1 contrast enhancement. The mass lesion on the right side of the pituitary gland extending superiorly to the right internal carotid artery contains a hemorrhagic fluid component with heterogeneous contrast enhancement, is 16*12*9 mm in size, and corresponds to a hemorrhagic pituitary macroadenoma. Table 1.Hormonal values at presentationACTH, adrenocorticotropic hormone; DST, dexamethasone suppression test; fT4, free thyroxine; IGF-1, insulin-like growth factor 1; PRL, prolactin; TSH, thyroid-stimulating hormone.

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.

In search of the source; a challenging diagnostic work-up of ACTH dependent Cyclic Cushing syndrome

In search of the source; a challenging diagnostic work-up of ACTH dependent Cyclic Cushing syndrome

SAT320 Cyclic Cushing Syndrome Caused By An ACTH-Producing Pheochromocytoma

Abstract Disclosure: Y.B. Omotosho: None. M.E. Wierman: None. K. Bukhari: None. K. Pacak: None. R. McGlotten: None. L.K. Nieman: None. Background: Although pheochromocytomas (Pheo) predominantly produce catecholamines, they also rarely produce Adrenocorticotropin (ACTH) and present with Cushing syndrome (CS). Cyclic CS is an uncommon presentation of hypercortisolism. We here report a unique case of cyclic ectopic ACTH secretion from a Pheo. Clinical case: A 72-year-old female was referred to the NIH with a five-year history of intermittent episodes of unintentional weight gain, hair loss, skin thinning, striae, tremors, labile emotions, glucose intolerance, and a sense of impending doom, interspersed with anorexia, weight loss, normal glucose levels, headaches, and fatigue. The external evaluation documented ACTH-dependent CS with episodes of hypercortisolism, thought to be occult ectopic ACTH secretion. On admission, blood pressure ranged from 122/75 to 171/78 mmHg, and she had a Cushingoid habitus. The biochemical investigation showed basal ACTH 219 pg/ml (NL 5- 46 pg/ml); serum cortisol of 76.9 mcg/dl after 1mg dexamethasone (Dex) suppression test (NL <1.8 mcg/dl), with Dex level of 903; cortisol increased from 13.3 mcg/dl to 15.5 mcg/dl after 8mg Dex, Dex level 4680 ng/ml; plasma normetanephrine 1.8 nmol/L, (NL < 0.9 nmol/L); metanephrine 0.6 nmol/L (NL <0.5 nmol/L); norepinephrine 1493 pg/mL (NL 70-750 pg/mL); epinephrine 298 pg/mL (NL <111 pg/mL); chromogranin A 1314 ng/mL (NL <93 ng/mL). MRI pituitary was normal and bilateral inferior petrosal sinus sampling did not show a central: peripheral gradient before or after desmopressin administration. CT abdomen showed a right adrenal nodule measuring 2.3 cm x 1.8 cm, with pre-and post-contrast Hounsfield units of 30 and 106, and 54% washout. The adrenal mass showed intense activity on 68Ga-DOTATATE and 18F-DOPA PET/CT scans. The patient underwent a right adrenalectomy; the 2.7 x 2.3 x 1.5 cm mass was a Pheo with immunohistochemical staining for ACTH, chromogranin A, and synaptophysin. Post-operatively, blood pressure normalized, and medications were reduced from preoperative metoprolol, lisinopril, and doxazosin to low-dose metoprolol at discharge. Morning cortisol and ACTH levels were <1 mcg/dl and <5 pg/ml. Physiologic replacement of hydrocortisone (15 mg on awakening and 5 mg in the afternoon) was started and switched to prednisone 5mg daily for ACTH deficiency and convenience. The pituitary-adrenal axis remained suppressed at her 6-month follow-up visit. Conclusion: Cyclic CS poses a diagnostic challenge. Here, desmopressin helped to exclude Cushing's Disease. Although ACTH-producing Pheo is rare, it should be considered in the context of ACTH-dependent hypercortisolism if an adrenal mass is present. Presentation: Saturday, June 17, 2023

Ectopic Cyclic Cushing's syndrome, A Diagnostic Challenge: A Case Report

Introduction: Cyclic Cushing's syndrome is a not widely known pathology with low incidence; however, an increase in the number of cases has been observed in recent years. The intermittent clinical symptoms and discordant laboratory results make it a complicated diagnosis; therefore, close follow-up is crucial. We describe a case of ectopic cyclic Cushing's syndrome in a woman in her seventies who presented weight gain, proximal myopathy, moderate hypokalemia and uncontrolled hypertension; in the first evaluation hypercortisolism was found, however, 2 months later cortisol presented normal levels. Subsequently, a close follow-up was carried out and the study protocol was continued once the presence of 3 peaks and 2 valleys was demonstrated, obtaining compatible values for ectopic ACTH-dependent cyclic Cushing's syndrome. In thoracoabdominal MRI a spiculated lesion was found in the left basal lung field surrounding 25% of the aorta. Due to the location of the lesion, the patient refused surgical treatment, being currently under adequate control with the use of ketoconazole and octreotide injections. Conclusions: The possibility of cyclic Cushing's syndrome diagnosis should be kept in mind in those patients with symptoms suggestive of Cushing's syndrome that remit sporadically and whose laboratory studies show intermittent results of hypercortisolism and normocortisolism, since early identification allows opportune treatment and therefore better prognosis.

Cyclic cushing syndrome: a case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Diagnostic and therapeutic challenges in cyclic Cushing's syndrome: A systematic literature review

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

PS-BPR01-9: A CASE OF CYCLIC CUSHING'S SYNDROME DIAGNOSED WITH HYPERTENSION AND LEG EDEMA

Background: Cushing's syndrome (CS) is associated with hypertension in approximately 80% of cases, which contributes to the increased mortality risk. Few cases of intermittent hypertension due to cyclic CS(CCS) have been reported. Case presentation: A 66-year-old woman with no specific medical history was referred to our hospital for evaluation of hypertension and leg edema. The Cardiovascular examination showed no abnormality in her cardiac function. Laboratory findings revealed hypokalemia, hyperglycemia, and metabolic alkalosis. She was tentatively initiated on calcium channel blocker (CCB) and insulin therapy. The endocrine examination revealed elevated ACTH and cortisol without circadian variation, which responded to neither the 8 mg dexamethasone suppression test nor CRH stimulation, leading to the diagnosis of ACTH-dependent CS. CT, FDG/PET CT, and Octreotide scan showed no obvious lesion other than bilateral adrenal enlargement. Enhanced MRI showed a normal pituitary gland with neither adenoma nor pituitary stalk deviation/tilt. Since the etiology of CS was not confirmed, metyrapone administration was initiated as symptomatic treatment. Her serum ACTH and cortisol fell rapidly after the initiation of metyrapone, and her blood pressure (BP) and blood glucose levels improved accordingly, even without the use of CCB and insulin. Since both ACTH and cortisol became normalized after discharge, metyrapone was tapered off after 4 months. Furthermore, CT showed normalization of the adrenal enlargement. For the next two months, her ACTH and cortisol remained within the normal limits, and her BP, serum potassium and blood glucose were well controlled. However, she visited our hospital because of re-elevated BP thereafter and was found to have re-elevated ACTH and cortisol with bilateral adrenal enlargement as well as re-decreased serum potassium. Since her BP and serum potassium levels were not controlled well even after she resumed taking metyrapone, the dose of metyrapone was increased, spironolactone was added, and CCB was resumed. Another two months later, her ACTH and cortisol normalized without metyrapone again, and her BP was well-controlled accordingly. This cyclical course of ACTH/cortisol elevation strongly suggested CCS. Conclusion: CCS is a clinical syndrome that exhibits a periodic or irregular increasing pattern in cortisol, which is a rare type of CS. Confirmation of CCS diagnosis is only possible during periods of relapse. In the present case, elevated BP was an indicator of hormonal fluctuations that could be appropriately treated. We report here a case of CCS that was diagnosed because of a good correlation between BP and hormone levels.

Late Night Salivary Cortisol in the diagnosis of neoplastic hypercortisolism (including cyclic Cushing's syndrome).

Late night salivary cortisol (LNSC) is a mainstay in the diagnosis of neoplastic hypercortisolism (Cushing's syndrome) with a sensitivity and specificity of > 90% in patients with syndromic signs and symptoms. Intermittent hormonogenesis (day to day variation) is common in milder Cushing's disease whereas true cyclic Cushing's syndrome (weeks to months of tumor quiescence) is unusual. In both cases, LNSC is useful as a sensitive evaluative diagnostic tool, although its lower specificity may lead to false positive results in patients without Cushing's disease. Furthermore, intermittent hormonogenesis may lead to false negative LNSC results in patients with mild Cushing's disease. Finally, LNSC is useful as an approach to follow patients after pituitary surgery to detect a recurrence even many years after a full remission.

SAT-142 Periodic Cushing Syndrome in a Patient with an Intestinal Neuroendocrine Tumor (NET). A Novel Case Report

Introduction A major diagnostic enigma regarding ACTH-dependent Cushing syndrome is the distinction between the source of ACTH, which may have either a pituitary or ectopic origin. We present the first described patient with cyclic Cushing syndrome caused by an intestinal neuroendocrine tumour (NET) detected by 68GA-DOTATATE PET-CT, despite functional tests that were indicative of pituitary Cushing disease. Clinical Case A 53-year old man was admitted to outpatient clinic because of muscle weakness. His phenotype and clinical findings (progressively worsening upper and lower limb weakness, emotional disturbances, easy bruising, a Buffalo hump, prediabetes and leucocytosis) led to the diagnosis of Cushing syndrome. Initial laboratory tests established the diagnosis with an abnormal diurnal cortisol and ACTH secretion (night cortisol F: 22.1μg / dl), absence of suppression with dexamethasone 1mg and increased free urinary free cortisol 24h (243.5μg /24h). Abdominal CT scanning revealed a left-sided adrenal adrenocortical adenoma 1.5 mm in max diameter. Pituitary MRI and somatostatin scintigraphy were normal. Low dexamethasone suppression test was indicative of Cushing (F: 14μg / dl) followed by a combined CRH stimulation test during bilateral inferior petrosal sinus sampling. Pituitary / peripheral ACTH ratio pre-infusion of CRH and 3 min after CRH infusion was compatible with right-sided pituitary origin of ACTH hypersecretion. Pending the results of the laboratory, the patient showed a remission of his symptoms along with a laboratory-confirmed recession of active hypercortisolaemia (LDDST test), and this led to the suspicion of periodic Cushing syndrome. The patient was followed with clinical and laboratory examinations weekly, with recurrence of symptoms 2 months later followed by a new remission 3 months later. A PETGA CT SCAN with 68GA-HA-DOTATATE was performed, which showed an increased uptake of the radioisotope in the small intestine. A surgical excision of the affected small bowel region was performed according to the guidelines for intestinal NETs. Histology confirmed the existence of a well-differentiated neuroendocrine neoplasm of the small intestine of 1.1 cm diameter, grade 1 (WHO 2010). Immunophenotype was positive for serotonin and ACTH. Postoperatively, the patient showed a complete remission of symptomatology and regression of hypercortisolaemia over a 18-month period. Follow-up abdominal MRI and 68GA-HA-DOTATATE revealed no pathological findings. Conclusion: Our patient is the first case of ectopic Cushing disease caused by intestinal NET. The differential diagnosis between pituitary and ectopic Cushing syndrome due to ACTH or CRH hypersecretion is not easy and frequently complicated by the periodicity of the disease. In patients with no visible pituitary lesions on MRI we suggest further investigation for ectopic ACTH- driven Cushing syndrome.

A man in his sixties with dyspnoea and oedema.

A man in his sixties with chronic obstructive pulmonary disease was hospitalised due to oedema and dyspnoea during the previous weeks. He was hypertensive, with 10kg weight gain, generalised oedema, proximal myopathy and moon face. The assessment was consistent with ectopic ACTH-dependent Cushing's syndrome. A 15mm lung tumour was detected on CT, with inconclusive cytological examination, and negative FDG/PET CT and octreotide scintigraphy. He developed necrotising pancreatitis and a duodenal perforation, which were surgically treated. His cortisol levels and Cushingoid appearance normalised after surgery, and it was concluded that his hypercortisolism was part of a physiological response. He remained clinically in habitual shape until two years later, when he again developed Cushingoid stigmata. A new octreotide scintigraphy was negative, but FDG/PET CT revealed increased FDG uptake in the lung lesion. Before a lung biopsy was performed, the patient developed necrotising pancreatitis. He was treated conservatively and died in respiratory failure. Autopsy revealed a NET in the lung and necrotising pancreatitis. The case demonstrates diagnostic challenges in the assessment of ectopic ACTH-dependent cyclic Cushing's syndrome. Is also suggests that pancreatitis could be triggered by hypercortisolism.

Long-term results of bilateral adrenalectomy in a patient with cyclic Cushing's syndrome

Long-term results of bilateral adrenalectomy in a patient with cyclic Cushing's syndrome

Diabetes profile during cyclic Cushing syndrome: about one case

Diabetes profile during cyclic Cushing syndrome: about one case

Cyclic Cushing's syndrome: a difficult diagnosis

Cyclic Cushing's syndrome: a difficult diagnosis

Cyclic Cushing's syndrome: a diagnostic challenge

Cyclic Cushing's syndrome: a diagnostic challenge

Cyclic Cushing's syndrome - a diagnostic challenge

Cyclic Cushing's syndrome - a diagnostic challenge

Cushing's Syndrome: Screening and Diagnosis.

Endogenous Cushing's syndrome (CS) is a rare disease, and usually characterized by hypertension, diabetes, obesity, osteoporosis, facial rounding, dorsocervical fat pad, thin skin, purple striae, hirsutism, and mood disorders. Efficient diagnostic and screening strategies lead to the diagnosis of a significantly higher number of cases of CS. As a screening test for CS, the Endocrine Society's Clinical Practice Guidelines recommend a single test with a high diagnostic accuracy, among the 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), and 24h urinary free cortisol (UFC). In normal subjects, administering a higher than physiological dose of glucocorticoids prompts the suppression of cortisol secretion. The 1-mg DST explores this normal feedback reaction from the hypothalamic-pituitary-adrenal axis (HPA). It is a simple dynamic test, usually performed in outpatients. A morning serum cortisol level <50nmol/L suffices to exclude CS, unless there is a strong clinical suspicion to suggest otherwise. The HPA axis reaches a nadir just after a person has fallen asleep, but its circadian rhythm is impaired in CS patients, who feature higher cortisol values at night, which are easy to measure in saliva (the LNSC assay). Saliva collection is also suitable for outpatients since cortisol is stable at room temperature and the collection device can be mailed to the laboratory for analysis. UFC levels reflect the integrated tissue exposure to free cortisol over 24h, and thus provide a particular picture of endogenous hypercortisolism. In most cases, high UFC levels coincide with severe hypercortisolism. UFC is used not only to diagnose CS, but also to monitor its response to medical treatment. All screening tests have procedural snares: some drugs can interfere with the DST; false-positive or false-negative LNSC results may be due to an inadequate soaking of the device or to cyclic CS; and in the case of UFC it is important to ensure that patients provide complete urine collections with appropriate total volumes. Measuring cortisol with antibody-based immunoassays can also generate false-positive results due to cross-reactivity between cortisol, cortisone and other metabolites. Structurally-based assays, such as liquid chromatography with tandem mass spectrometry, only measure cortisol and have only recently become available for use in routine clinical practice. This review summarizes the recent literature on the clinical and biochemical aspects of CS diagnostics with a view to helping physicians choose the best screening test for diagnosing endogenous hypercortisolism.