Consensus on diagnosis and management of Cushing's disease: a guideline update

Fleseriu, Maria; Auchus, Richard J.; Bancos, Irina; Ben-Shlomo, Anat; Bertherat, Jérôme; Biermasz, Nienke R.; Boguszewski, César Luiz; Bronstein, Marcello D.; Buchfelder, Michael; Carmichael, John D.; Casanueva, Felipe F.; Castinetti, Frédéric; Chanson, Philippe; Findling, James W.; Gadelha, Mônica R.; Geer, Eliza B.; Giustina, Andrea; Grossman, Ashley; Gurnell, Mark; Ho, Ken K. Y.; Ioachimescu, Adriana G.; Kaiser, Ursula B.; Karavitaki, Niki; Katznelson, Laurence; Kelly, Daniel F.; Lacroix, André; McCormack, Ann; Melmed, Shlomo; Molitch, Mark E.; Mortini, Pietro; Newell‐Price, John; Nieman, Lynnette K.; Pereira, Alberto M.; Petersenn, Stephan; Pivonello, Rosario; Raff, Hershel; Reincke, Martín; Salvatori, Roberto; Scaroni, Carla; Shimon, Ilan; Stratakis, Constantine A.; Swearingen, Brooke; Tabarin, Antoine; Takahashi, Yutaka; Theodoropoulou, Marily; Tsagarakis, Stylianos; Valassi, Elena; Varlamov, Elena V.; Vila, Greisa; Wass, John; Webb, Susan M.; Zatelli, Maria Chiara; Biller, Beverly M. K.

doi:10.1016/s2213-8587(21)00235-7

Cited by 344 publications

(419 citation statements)

References 280 publications

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“…Importantly, no statistically significant bleeding events were reported [ 25 , 26 ]. A recent consensus on management of CS provided expert recommendation for anticoagulation, advising the consideration of it for all patients with the highest risk of VTE [ 4 ]. As such, patients with a history of VTE, thrombophilic states, severe hypercortisolism, use of estrogen/testosterone, prolonged preoperative or postoperative hospitalization, and high postoperative cortisol levels or GC overreplacement should be considered for anticoagulation [ 4 ].…”

Section: Should This Patient Be Anticoagulated? When and For How Long?mentioning

confidence: 99%

“…As such, patients with a history of VTE, thrombophilic states, severe hypercortisolism, use of estrogen/testosterone, prolonged preoperative or postoperative hospitalization, and high postoperative cortisol levels or GC overreplacement should be considered for anticoagulation [ 4 ]. Holding estrogen/testosterone supplementation perioperatively has also been suggested [ 4 ]. In addition, clinicians should take into account other factors that may increase VTE risk, such as active cancer, smoking, immobilization, and older age.…”

Section: Should This Patient Be Anticoagulated? When and For How Long?mentioning

confidence: 99%

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confidence: 99%

“…The first line treatment for most patients with CD is transsphenoidal pituitary surgery (TSS), which generally achieves remission in 70% to 90% of microadenoma cases but is lower for macroadenomas [ 3 , 4 ]. Surgery should ideally be performed in a high-volume center by an experienced pituitary surgeon [ 3 , 4 ]. While surgery is expected to induce remission and improve cortisol-related morbidities, the perioperative period, from the time of diagnosis until at least 3 months postoperatively, is marked by the highest rate of morbidity and mortality [ 6 , 7 ].…”

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confidence: 99%

“…We aim to provide comprehensive and evidence-based information to help clinicians with perioperative care of patients with CD ( Fig. 1 [ 4 , 9 , 11 , 12 ]).…”

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confidence: 99%

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Perioperative Management of a Patient With Cushing Disease

Varlamov

Vila

Fleseriu

2022

Journal of the Endocrine Society

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Patients with Cushing’s disease (CD) may present with both chronic and acute perioperative complications that necessitate multidisciplinary care. This review highlights several objectives for these patients before and after transsphenoidal surgery. Preoperative management includes treatment of electrolyte disturbances, cardiovascular comorbidities, prediabetes/diabetes, as well as prophylactic consideration(s) for thromboembolism and infection(s). Preoperative medical therapy (PMT) could prove beneficial in patients with severe hypercortisolism or in cases of delayed surgery. Some centers use PMT routinely, although the clinical benefit for all patients is controversial. In this setting, steroidogenesis inhibitors are preferred because of rapid and potent inhibition of cortisol secretion. If glucocorticoids are not used perioperatively, an immediate remission assessment postoperatively is possible. However, perioperative glucocorticoid replacement is sometimes necessary for clinically unstable or medically pretreated patients and for those patients with surgical complications. A nadir serum cortisol < 2-5µg/dl during 24-74 hours postoperatively is generally accepted as remission; higher values suggest non-remission, while a few patients may display delayed remission. If remission is not achieved, additional treatments are pursued. The early postoperative period necessitates multidisciplinary awareness for early diagnosis of adrenal insufficiency (AI) to avoid adrenal crisis, which may be also potentiated by acute postoperative complications. Preferred glucocorticoid replacement is hydrocortisone, if available. Assessment of recovery from postoperative AI should be undertaken periodically. Other postoperative targets include decreasing antihypertensive/diabetic therapy if in remission, thromboprophylaxis, infection prevention/treatment, and management of electrolyte disturbances and/or potential pituitary deficiencies. Evaluation of recovery of thyroid, gonadal and growth hormone deficiencies should be also performed in the following months postoperatively.

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Section: Should This Patient Be Anticoagulated? When and For How Long?mentioning

confidence: 99%

Section: Should This Patient Be Anticoagulated? When and For How Long?mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…We aim to provide comprehensive and evidence-based information to help clinicians with perioperative care of patients with CD ( Fig. 1 [ 4 , 9 , 11 , 12 ]).…”

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confidence: 99%

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Perioperative Management of a Patient With Cushing Disease

Varlamov

Vila

Fleseriu

2022

Journal of the Endocrine Society

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Cushing Syndrome

Reincke

Fleseriu

2023

JAMA

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ImportanceCushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders.ObservationsCushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate.Conclusions and RelevanceThe incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.

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Diagnosis and Management of Pituitary Adenomas

Tritos

Miller

2023

JAMA

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ImportancePituitary adenomas are neoplasms of the pituitary adenohypophyseal cell lineage and include functioning tumors, characterized by the secretion of pituitary hormones, and nonfunctioning tumors. Clinically evident pituitary adenomas occur in approximately 1 in 1100 persons.ObservationsPituitary adenomas are classified as either macroadenomas (≥10 mm) (48% of tumors) or microadenomas (&lt;10 mm). Macroadenomas may cause mass effect, such as visual field defects, headache, and/or hypopituitarism, which occur in about 18% to 78%, 17% to 75%, and 34% to 89% of patients, respectively. Thirty percent of pituitary adenomas are nonfunctioning adenomas, which do not produce hormones. Functioning tumors are those that produce an excess of normally produced hormones and include prolactinomas, somatotropinomas, corticotropinomas, and thyrotropinomas, which produce prolactin, growth hormone, corticotropin, and thyrotropin, respectively. Approximately 53% of pituitary adenomas are prolactinomas, which can cause hypogonadism, infertility, and/or galactorrhea. Twelve percent are somatotropinomas, which cause acromegaly in adults and gigantism in children, and 4% are corticotropinomas, which secrete corticotropin autonomously, resulting in hypercortisolemia and Cushing disease. All patients with pituitary tumors require endocrine evaluation for hormone hypersecretion. Patients with macroadenomas additionally require evaluation for hypopituitarism, and patients with tumors compressing the optic chiasm should be referred to an ophthalmologist for formal visual field testing. For those requiring treatment, first-line therapy is usually transsphenoidal pituitary surgery, except for prolactinomas, for which medical therapy, either bromocriptine or cabergoline, is usually first line.Conclusions and RelevanceClinically manifest pituitary adenomas affect approximately 1 in 1100 people and can be complicated by syndromes of hormone excess as well as visual field defects and hypopituitarism from mass effect in larger tumors. First-line therapy for prolactinomas consists of bromocriptine or cabergoline, and transsphenoidal pituitary surgery is first-line therapy for other pituitary adenomas requiring treatment.

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Consensus on diagnosis and management of Cushing's disease: a guideline update

Cited by 344 publications

References 280 publications

Perioperative Management of a Patient With Cushing Disease

Perioperative Management of a Patient With Cushing Disease

Cushing Syndrome

Diagnosis and Management of Pituitary Adenomas

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