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

2012 ◽  
Vol 166 (3) ◽  
pp. 531-536 ◽  
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.

DRUG CONTROL OF CUSHING'S SYNDROME

1976 ◽  
Vol 82 (2) ◽  
pp. 330-341 ◽  
Author(s):  
D. F. Child ◽  
C. W. Burke ◽  
D. M. Burley ◽  
Lesley H. Rees ◽  
T. Russell Fraser
Keyword(s):  
Side Effects ◽  
Cushing’S Syndrome ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Term Treatment ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Long Term Treatment ◽  
Dose Trial

ABSTRACT Eighteen patients with Cushing's syndrome (16 pituitary-dependent Cushing's disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 weeks. Control of cortisol overproduction and clinical improvement was achieved but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 weeks, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days–1 year). This low regimen which consists of aminoglutethimide 500–750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b. d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases.

scholarly journals Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Carlotta Pozza ◽  
Chiara Graziadio ◽  
Elisa Giannetta ◽  
Andrea Lenzi ◽  
Andrea M. Isidori
Keyword(s):  
Cushing’S Syndrome ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Chemotherapeutic Agents ◽  
Peroxisome Proliferator ◽  
Significant Activity ◽  
Ectopic Acth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ectopic Acth Secretion ◽  
Free Cortisol

Cushing’s syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing’s disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptorγ“PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors.

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

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.

scholarly journals Vandetanib induces a marked anti-tumor effect and amelioration of ectopic Cushing’s syndrome in a medullary thyroid carcinoma patient

2016 ◽  
Vol 2016 ◽  
Author(s):  
Hashem Bseiso ◽  
Naama Lev-Cohain ◽  
David J Gross ◽  
Simona Grozinsky-Glasberg
Keyword(s):  
Cushing’S Syndrome ◽  
Tumor Size ◽  
Cushing's Syndrome ◽  
Whole Body ◽  
List Type ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Ectopic Cushing’S Syndrome ◽  
Free Cortisol

Summary A 55-year-old woman diagnosed with sporadic MTC underwent total thyroidectomy 20 years ago. After the first surgery, elevated calcitonin levels in parallel with local disease persistence were noted and therefore she underwent repeated neck dissections. During follow-up, multiple foci of metastatic disease were noted in the neck and mediastinal lymph nodes, lungs and bones; however, the disease had an indolent course for a number of years, in parallel with a calcitonin doubling time of more than two years and without significant symptoms. During a routine follow-up visit 2 years ago, findings suggestive of Cushing’s syndrome were observed on physical examination. The biochemical evaluation demonstrated markedly elevated serum calcitonin level, in parallel with lack of cortisol suppression after an overnight 1 mg dexamethasone suppression test, lack of cortisol and ACTH suppression after high-dose IV dexamethasone 8 mg, elevated plasma ACTH up to 79 pg/mL (normal <46 pg/mL) and elevated 24-h urinary free cortisol up to 501 µg/24 h (normal 9–90 µg/24 h). After a negative pituitary MRI, she underwent IPSS, which was compatible with EAS. Whole-body CT demonstrated progressive disease at most of the tumor sites. Treatment with vandetanib at a dosage of 200 mg/day was commenced. The patient showed a significant, rapid and consistent clinical improvement already after two months of treatment, in parallel with biochemical improvement, whereas a decrease in tumor size was demonstrated on follow-up CT. Learning points: Ectopic Cushing’s syndrome due to ectopic ACTH secretion (EAS) by MTC is an uncommon and a poor prognostic event, being associated with significant morbidity and mortality. We demonstrate that vandetanib is effective in controlling the signs and symptoms related to the EAS in patients with advanced progressive MTC. We demonstrate that vandetanib is effective in decreasing tumor size and in inducing tumor control.

Long-Term Treatment of Central Cushing's Syndrome with Rosiglitazone

2007 ◽  
Vol 115 (05) ◽  
pp. 292-297 ◽  
Author(s):  
M. Morcos ◽  
B. Fohr ◽  
J. Tafel ◽  
F. Pfisterer ◽  
A. Hamann ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Term Treatment ◽  
Long Term Treatment

scholarly journals Metyrapone for Long-Term Medical Management of Cushing’s Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Andrea N. Traina ◽  
Ashley Farr ◽  
Ritu Malik ◽  
Robert J. Bingham
Keyword(s):  
Surgical Resection ◽  
Cushing’S Syndrome ◽  
Treatment Options ◽  
Cushing's Syndrome ◽  
Term Treatment ◽  
Significant Morbidity ◽  
Short Term ◽  
Short Term Treatment ◽  
Long Term Treatment

Cushing’s syndrome is characterized by any cause of excess cortisol in the blood and produces many physiologic consequences. Left untreated, Cushing’s is associated with significant morbidity and mortality. Seventy percent of endogenous cases of Cushing’s syndrome are secondary to a pituitary tumor; because of this, the primary mode of management is surgical resection of the tumor. Should hypercortisolism persist following surgical resection, further treatment options are limited. Metyrapone is an orphan medication that is often used in the diagnosis of the disease and occasionally for short-term treatment prior to surgery. Long-term treatment with metyrapone is usually discouraged due to the contradictory increase in ACTH production, acne, hirsutism, hyperkalemia, edema, and other mineralocorticoid effects. We present a patient with refractory Cushing’s syndrome successfully treated for nearly 6 years with metyrapone with minimal adverse effects. This orphan medication may be a viable long-term treatment option for this difficult disease.

scholarly journals Successful Long-Term Treatment of Refractory Cushing’s Disease with High-Dose Mifepristone (RU 486)

2001 ◽  
Vol 86 (8) ◽  
pp. 3568-3573 ◽  
Author(s):  
James W. Chu ◽  
Dwight F. Matthias ◽  
Joseph Belanoff ◽  
Alan Schatzberg ◽  
Andrew R. Hoffman ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Mineralocorticoid Receptor ◽  
Cushing's Syndrome ◽  
Term Treatment ◽  
Cushing's Disease ◽  
High Dose ◽  
Metabolic Disturbances ◽  
Long Term Treatment

An extremely ill patient, with Cushing’s syndrome caused by an ACTH-secreting pituitary macroadenoma, experienced complications of end-stage cardiomyopathy, profound psychosis, and multiple metabolic disturbances. Initially treated unsuccessfully by a combination of conventional surgical, medical, and radiotherapeutic approaches, he responded dramatically to high-dose long-term mifepristone therapy (up to 25 mg/kg·d). Treatment efficacy was confirmed by the normalization of all biochemical glucocorticoid-sensitive measurements, as well as by the significant reversal of the patient’s heart failure, the resolution of his psychotic depression, and the eventual unusual return of his adrenal axis to normal. His 18-month-long mifepristone treatment course was notable for development of severe hypokalemia that was attributed to excessive cortisol activation of the mineralocorticoid receptor, which responded to spironolactone administration. This case illustrates the efficacy of high-dose long-term treatment with mifepristone in refractory Cushing’s syndrome. The case also demonstrates the potential need for concomitant mineralocorticoid receptor blockade in mifepristone-treated Cushing’s disease, because cortisol levels may rise markedly, reflecting corticotroph disinhibition, to cause manifestations of mineralocorticoid excess.

scholarly journals Long-term low-dose ketoconazole treatment in bilateral macronodular adrenal hyperplasia

2014 ◽  
Vol 2014 ◽  
Author(s):  
Sophie Comte-Perret ◽  
Anne Zanchi ◽  
Fulgencio Gomez
Keyword(s):  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
List Type ◽  
Adrenal Hyperplasia ◽  
Benign Condition ◽  
Steroid Secretion ◽  
Free Cortisol

Summary Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery. Learning points Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features. Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated. However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.

scholarly journals Long term dual antiplatelet therapy after myocardial infarction: retrospective analysis in an outpatient population

2021 ◽  
Author(s):  
Gennaro Ratti ◽  
Antonio Maglione ◽  
Emilia Biglietto ◽  
Cinzia Monda ◽  
Ciro Elettrico ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Term Treatment ◽  
Multivessel Disease ◽  
Coronary Syndrome ◽  
Anticoagulant Drugs ◽  
Long Term Treatment ◽  
Risk Condition ◽  
History Of

Long term treatment with ticagrelor 60 mg and low-dose aspirin are indicated after acute coronary syndrome (ACS). We retrospectively reviewed aggregate data of 187 patients (155 M and 38 F) (mean age 63.8±9 years) in follow up after ACS with at least one high risk condition (Multivessel disease, diabetes, GFR<60 mL/min, history of prior myocardial infarction, age >65 years) treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The results were compared with findings (characteristics of the patients at baseline, outcomes, bleeding) of PEGASUS-TIMI 54 trial and Eu Label. The highrisk groups were represented as follows: multivessel disease 105 pts (82%), diabetes 63 pts (33%), GFR< 60 mL/min 27 pts (14%), history of prior MI 33 pts (17%), >65 year aged 85 pts (45%). Treatment was withdrawn in 7 patients: 3 cases showed atrial fibrillation and were placed on oral anticoagulant drugs, one developed intracranial bleeding, in three patients a temporary withdrawal was due to surgery (1 colon polyposis and 2 cases of bladder papilloma). Chest pain without myocardial infarction occurred in 16 patients (revascularization was required in 9 patients). Dyspnea was present in 15 patients, but was not a cause for discontinuation of therapy. Long term treatment with ticagrelor 60 mg twice daily plus aspirin 100 mg/day showed a favourable benefit/risk profile after ACS.  In this study all patients had been given ticagrelor 90 mg twice daily for 12 months and the 60 mg twice daily dosage was started immediately thereafter, unlike PEGASUS-TIMI 54 trial in which it was prescribed within a period ranging from 1 day to 1 year after discontinuation of the 90 mg dose. This makes our results more consistent with current clinical practice. However, a careful outpatient follow-up and constant counseling are mandatory to check out compliance to therapy and adverse side effects.

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