Cushing's Syndrome Caused by an Ectopic Pituitary Adenoma

Abstract A 49-year old woman with a 5-year history of Cushing's syndrome was evaluated. Biochemical measurements revealed high cortisol and adrenocorticotropic hormone (ACTH) levels consistent with the ACTH-dependent type of Cushing's syndrome. However, the source of ACTH seemed to be autonomous as she demonstrated abnormal feedback control, with lack of response to metyrapone and high doses of dexamethasone. A search for an ectopic ACTH-secreting nonpituitary neoplasm was unsuccessful. Transsphenoidal pituitary exploration revealed a normal pituitary gland, but an ectopic pituitary adenoma was found incidentally in the mucosa of the sphenoid sinus. This adenoma stained strongly positive for ACTH on immunocytochemical studies. Resection of this lesion led to remission of the Cushing's syndrome. This variant of ACTH-dependent Cushing's syndrome can mimic the ectopic ACTH-dependent type and should be looked for in patients who fail to respond to pituitary operation.

Download Full-text

The role of bilateral inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302007000800019 ◽

2007 ◽

Vol 51 (8) ◽

pp. 1329-1338 ◽

Cited By ~ 22

Author(s):

Andrea Utz ◽

Beverly M.K. Biller

Keyword(s):

Cushing’S Syndrome ◽

Venous Drainage ◽

Cushing's Syndrome ◽

Blood Levels ◽

Inferior Petrosal Sinus ◽

Ectopic Acth ◽

Inferior Petrosal Sinus Sampling ◽

Neoplastic Lesion ◽

Before And After ◽

Acth Secreting

Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome is most often due to a pituitary corticotroph adenoma, with ectopic ACTH-secreting tumors representing approximately 15% of cases. Biochemical and radiological techniques have been established to help distinguish between these two entities, and thus aid in the localization of the neoplastic lesion for surgical resection. The test that offers the highest sensitivity and specificity is bilateral inferior petrosal sinus sampling (BIPSS). BIPSS is an interventional radiology procedure in which ACTH levels obtained from venous drainage very near the pituitary gland are compared to peripheral blood levels before and after corticotropin hormone (CRH) stimulation. A gradient between these two locations indicates pituitary Cushing's, whereas the absence of a gradient suggests ectopic Cushing's. Accurate BIPSS results require hypercortisolemia to suppress normal corticotroph ACTH production and hypercortisolemia at the time of the BIPSS to assure excessive ACTH secretion. In some cases, intrapituitary gradients from side-to-side can be helpful to localize small corticotroph adenomas within the sella. BIPSS has rare complications and is considered safe when performed at centers with experience in this specialized technique.

Download Full-text

Ectopic ACTH-secreting tumor of the thymus revealed by a Cushing’s syndrome: case report and review of literature

Indian Journal of Thoracic and Cardiovascular Surgery ◽

10.1007/s12055-017-0554-6 ◽

2017 ◽

Vol 34 (1) ◽

pp. 65-68

Author(s):

Zied Chaari ◽

Hazem Zribi ◽

Sonia Ouerghi ◽

Mohamed-Sadok Boudaya ◽

Tarek Kilani ◽

...

Keyword(s):

Case Report ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Review Of Literature ◽

Ectopic Acth ◽

Acth Secreting

Download Full-text

Prolonged remission after long-term treatment with steroidogenesis inhibitors in Cushing's syndrome caused by ectopic ACTH secretion

Acta Endocrinologica ◽

10.1530/eje-11-0949 ◽

2012 ◽

Vol 166 (3) ◽

pp. 531-536 ◽

Cited By ~ 13

Author(s):

S T Sharma ◽

L K Nieman

Keyword(s):

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Term Treatment ◽

Sustained Remission ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

Free Cortisol ◽

Long Term Treatment ◽

History Of

Spontaneous remission is rare in ectopic ACTH syndrome (EAS). We describe four patients with presumed EAS in whom long-term treatment with steroidogenesis inhibitors was followed by prolonged remission of hypercortisolemia. Biochemical testing was consistent with EAS, but imaging failed to identify a tumor. Patients were treated with ketoconazole alone or with mitotane and/or metyrapone to control hypercortisolemia. Dexamethasone was added when a block and replace strategy was used. Treatment with steroidogenesis inhibitors for 3–10 years in these patients was followed by a prolonged period of remission (15–60 months). During remission, the first patient had an elevated ACTH, low cortisol and 24-h urinary free cortisol (UFC), and adrenal atrophy on computerized tomography scan during remission, suggesting a direct toxic effect on the adrenal glands. Cases 2 and 3 had normal to low ACTH levels and low-normal UFC, consistent with an effect at the level of the ectopic tumor. They did not have a history of cyclicity and case 3 has been in remission for ∼5 years, making cyclic Cushing's syndrome less likely. Case 4, with a history of cyclic hypercortisolism, had normal to slightly elevated ACTH levels and low-normal UFC during remission. The most likely etiology of remission is cyclic production of ACTH by the ectopic tumor. Spontaneous and sustained remission of hypercortisolemia is possible in EAS after long-term treatment with steroidogenesis inhibitors; a drug holiday may be warranted during chronic therapy to evaluate this. The pathophysiology remains unclear but may involve several different mechanisms.

Download Full-text

New developments in the medical treatment of Cushing's syndrome

Endocrine Related Cancer ◽

10.1530/erc-12-0191 ◽

2012 ◽

Vol 19 (6) ◽

pp. R205-R223 ◽

Cited By ~ 28

Author(s):

R van der Pas ◽

W W de Herder ◽

L J Hofland ◽

R A Feelders

Keyword(s):

Medical Treatment ◽

Medical Therapy ◽

Cushing’S Syndrome ◽

Treatment Options ◽

Cushing's Syndrome ◽

Treatment Modalities ◽

Primary Therapy ◽

Ectopic Acth ◽

Considerable Morbidity ◽

Acth Secreting

Cushing's syndrome (CS) is a severe endocrine disorder characterized by chronic cortisol excess due to an ACTH-secreting pituitary adenoma, ectopic ACTH production, or a cortisol-producing adrenal neoplasia. Regardless of the underlying cause, untreated CS is associated with considerable morbidity and mortality. Surgery is the primary therapy for all causes of CS, but surgical failure and ineligibility of the patient to undergo surgery necessitate alternative treatment modalities. The role of medical therapy in CS has been limited because of lack of efficacy or intolerability. In recent years, however, new targets for medical therapy have been identified, both at the level of the pituitary gland (e.g. somatostatin, dopamine, and epidermal growth factor receptors) and the adrenal gland (ectopically expressed receptors in ACTH-independent macronodular adrenal hyperplasia). In this review, results of preclinical and clinical studies with drugs that exert their action through these molecular targets, as well as already established medical treatment options, will be discussed.

Download Full-text

ACTH-Producing Thymic Carcinoid: A Rare Cause of Cushing’s Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.2025 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A990-A990

Author(s):

Lisette Patricia Rodriguez ◽

Wende Michele Kozlow

Keyword(s):

Cushing’S Syndrome ◽

Mediastinal Mass ◽

Cushing's Syndrome ◽

Anterior Mediastinal Mass ◽

Thymic Carcinoid ◽

Acth Secretion ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

History Of

Abstract Background: Thymic carcinoids are rare neoplasms that account for less than 5% of all thymic tumors. Approximately 25% of these tumors will result in Cushing’s syndrome due to ectopic ACTH secretion. These tumors can also be associated with MEN1 syndrome. This is a case report of a patient with history of macroprolactinoma now presenting with Cushing’s syndrome due to ectopic ACTH production from a thymic carcinoid tumor. Clinical Case: This is a 57 year old male with history of pituitary macroprolactinoma diagnosed in 2011, now status post transsphenoidal resection and external beam radiation therapy, with persistent hyperprolactinemia on cabergoline, who presented to our clinic for a routine follow up visit. Patient had already developed secondary hypogonadism and secondary hypothyroidism as a consequence of treatment for the macroprolactinoma. He complained of worsening fatigue and weight gain ongoing for several months. Laboratory studies revealed an hemoglobin A1c of 8.3% (nl < 5.7%), TSH 0.24 MIU/L (0.4-4.5 MIU/L), free T4 1.2 ng/dL (0.8-1.8 ng/dL), 8 AM cortisol 31.4 mcg/dL (4-22 mcg/dL), ACTH 185 pg/mL (6-50 pg/dL), prolactin 29.6 ng/mL (2-18 ng/mL), IGF-1 88 ng/mL (50-317 ng/mL). Follow up labs confirmed cushings syndrome: cortisol AM-DST 36.4 mcg/dL (< 2 mcg/dL), free urinary cortisol 291.9 mcg/24h (2-50 mcg/24h). Pituitary MRI showed empty sella turcica. Cortisol after an 8 mg DST 32.5 mcg/dL (< 5 mcg/dL). CT chest, abdomen and pelvis revealed an heterogeneously enhancing solid anterior mediastinal mass measuring 4.9 x 3.1 x 4.3 cm. Whole body OctreoScan showed a markedly hyperintense large mass adjacent to the right heart border measuring 47 x 32 mm. He was referred to cardiothoracic surgery and underwent a right video-assisted thoracic surgery with resection of the anterior mediastinal mass. Pathology revealed a thymic well-differentiated neuroendocrine tumor with strong cytoplasmic staining for ACTH. It was also positive for OSCAR, Cam5.2, synaptophysin, CD56, and S100. Ki67 stain was positive in fewer than 1% of tumor cells. Final diagnosis was carcinoid tumor. Conclusion: Cushing’s syndrome secondary to ectopic ACTH secretion from a thymic carcinoid is rare. The presence of two MEN1-associated tumors in this patient, macroprolactinoma and thymic carcinoid, is highly suggestive of a clinical diagnosis of MEN 1.

Download Full-text

SAT-118 Rapid Decompensation from Complications of Severe Hypercortisolism in an Unusual Presentation of an Ectopic ACTH-Secreting Neuroendocrine Tumor

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.020 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Amit Kartar Singh Sumal ◽

Charles Liao ◽

Julie Chen

Keyword(s):

Neuroendocrine Tumor ◽

Cushing’S Syndrome ◽

Cushing Syndrome ◽

Pulseless Electrical Activity ◽

Cushing's Syndrome ◽

Bilateral Adrenalectomy ◽

Unknown Primary ◽

Who Grade ◽

Ectopic Acth ◽

Acth Secreting

Abstract Background: Ectopic Cushing’s syndrome from an ACTH-secreting neuroendocrine tumor (NET) is a rare condition whose onset and disease progression is often more aggressive than other forms of Cushing’s syndrome due to complications from severe hypercortisolism. Clinical Case: A 75-year old woman presented with profound proximal muscle weakness, severe hypokalemia, Cushingoid features, and biopsy-proven Candida esophagitis. Initial testing was consistent with ACTH-dependent Cushing syndrome: elevated 24 hour urinary cortisol excretion (1,310.54 mcg/24h; n <50 mcg/24h), abnormal 1 mg dexamethasone suppression test (68.3 ug/dL), and elevated ACTH level (200 pg/mL; n: 7.2–63.3 pg/mL). MRI was negative for a pituitary lesion but abdominal CT revealed an 8.8 cm liver mass with biopsy consistent with a well-differentiated neuroendocrine tumor, WHO Grade 2. Subsequent 68Ga-DOTATATE-PET/CT noted DOTATATE uptake in the liver lesion, a 0.9 cm right pulmonary nodule, and the pancreatic tail without CT correlate. Initially, the patient was prescribed mifepristone and spironolactone for hypokalemia. Given her NET of unknown primary, metastatic disease, and immunocompromised state due to hypercortisolism, the patient was not a candidate for surgical resection of her NET but was instead referred for bilateral adrenalectomy. However, she rapidly decompensated from complications of her hypercortisolism prior to surgery. Her weakness progressed to immobility, and she developed acute psychosis manifested as agitation and mutism. The patient was immediately admitted to the hospital where she developed new-onset atrial flutter and myelosuppression requiring multiple transfusions. She underwent urgent bilateral adrenalectomy, but despite surgery, her post-operative course was complicated by hypoxemic respiratory failure and shock. The patient shortly thereafter expired from pulseless electrical activity arrest. Conclusion: This atypical case of an ectopic ACTH-secreting NET highlights the life-threatening complications associated with severe hypercortisolism, including: opportunistic infection, severe metabolic abnormalities, psychosis, myopathy, and critical illness that can incite myelosuppression and unstable arrhythmias. These patients can quickly deteriorate and are at high risk for mortality. Early diagnosis and swift reversal of their hypercortisolism with bilateral adrenalectomy are oftentimes needed to prevent these potentially fatal complications.

Download Full-text