scholarly journals ACTH-Dependent Cushing’s Syndrome in an Elderly Woman with Pituitary, Adrenal, and Intrathoracic Lesions

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A107-A107
Author(s):  
Emily A Japp ◽  
Alice C Levine
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Middle Lobe ◽  
Receptor Expression ◽  
Laboratory Evaluation ◽  
Ectopic Acth ◽  
Case Record ◽  
Pet Ct ◽  
Free Cortisol ◽  
Right Middle Lobe

Abstract A 77-year-old female with rheumatoid arthritis on etanercept, depression on venlafaxine, and treated hypothyroidism presented with easy bruising and muscle weakness. She denied any steroid use. She had normal BP and BMI, but appeared mildly Cushingoid with round facies, and increased dorsocervical and supraclavicular fat. Laboratory evaluation showed: ACTH 70.8 pg/mL (< 63.3), cortisol 24.3 ug/dL, 24 h urine free cortisol 223 ug (< 50), salivary cortisol 0.428 ug/dL, DHEA-S 165.7 ug/dL (< 142.8), LH 0.1 mIU/mL, FSH 2.7 mIU/mL, and hgbA1C 6.1 % (< 5.6 %). All other hormonal testing was normal. MRI of the pituitary showed a 4 x 2 x 3 mm hypoenhancing defect of the anterior pituitary. CT of the chest and abdomen showed a 1.1 cm left adrenal nodule, and a 1 cm non-specific right middle lobe lung nodule. Inferior petrosal sinus sampling (IPSS) with CRH did not show a central ACTH step-up. PET/CT with DOTATATE showed mildly increased tracer uptake in the right middle lobe measuring 1 cm with SUV max 3.7, and a 0.6 cm left apical subpleural nodule with SUV max 1.9. The patient underwent a right middle lobectomy and pathology was positive for typical carcinoid. Post-operatively, she needed hydrocortisone replacement for 9 months. ACTH was 19.7 pg/dL, cortisol 9.5 ug/dL, DHEA-S 31.3 ug/dL, LH 61.8 mIU/mL, and FSH 112.4 mIU/mL. Her Cushingoid features and myopathy resolved. This case highlights several challenges in the diagnosis and source localization in patients with ACTH-dependent Cushing’s Syndrome (CS). In this slim, elderly female, the typical features of CS were subtle. In addition, dynamic biochemical testing with high dose dexamethasone does not reliably distinguish eutopic from ectopic ACTH-dependent CS, as the sensitivity and specificity range from 60–80%. Thus, the diagnosis largely depends on sophisticated imaging and IPSS. The patient had pituitary, adrenal, and lung lesions. The pituitary lesion initially pointed towards a central ACTH source, but IPSS was negative. The prevalence of pituitary incidentalomas is high, at 10.6% based on autopsy data, with an increasing proportion being recognized in the elderly. Adrenal incidentalomas are also often noted in older individuals, but that was clearly not the cause of CS in this patient with a non-suppressed DHEA-S and elevated ACTH. PET/CT with DOTATATE has emerged as a sensitive test for the detection of often small tumors producing ectopic ACTH and was positive in the lung lesion. In spite of newer localization techniques, the source of ectopic ACTH often remains unidentified (12.5% in a large retrospective case-record study). False negatives on PET/CT with DOTATATE imaging may be due to cortisol’s suppressive effect on the somatostatin receptor expression in neuroendocrine tumors. Thus, in cases of ACTH-dependent CS with negative IPSS, ectopic ACTH must remain as a likely source, and be re-explored after medical treatment of the hypercortisolism.

scholarly journals Clinical Characteristics and Treatment Outcomes in Endogenous Cushing’s Syndrome: A 15-Year Experience from Thailand

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wasita Warachit Parksook ◽  
Nitchakarn Laichuthai ◽  
Sarat Sunthornyothin
Keyword(s):  
Treatment Outcomes ◽  
Cushing’S Syndrome ◽  
Clinical Characteristics ◽  
Remission Rate ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Normal Body Mass Index ◽  
Ectopic Acth ◽  
Free Cortisol

The most common subtype of endogenous Cushing’s syndrome (CS) is Cushing’s disease (CD), with higher proportions of adrenal CS reported from Asia, compared to other continents. However, little was known about CS in this territory. This study was to investigate the distribution, clinical characteristics, and treatment outcomes of CS in a single tertiary hospital in Thailand. We performed a retrospective evaluation of 82 patients with endogenous CS during 2001–2015. The most common subtype was CD, followed by adrenal CS and ectopic ACTH syndrome (EAS), respectively. Weight gain was the most common presentation. Normal body mass index (BMI), Asian cutoff, was observed in 33% of patients. Specific features of CS (plethora, muscle weakness, bruising, and/or wide purplish striae) were documented in less than half of patients. The median age, adrenocorticotropic hormone (ACTH), and urinary free cortisol (UFC) concentrations were significantly different among 3 subtypes of CS and were highest among patients with EAS. An initial remission rate after transsphenoidal surgeries in CD was 62%, with higher rates in pituitary microadenomas compared to macroadenomas. All patients with unilateral adrenal disease achieved CS remission after adrenal surgeries. Patients with EAS achieved CS remission mostly from bilateral adrenalectomy. The highest mortality rate was observed in the EAS group. These findings were consistent with previous studies in Asia, with more proportions ACTH-independent CS.

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 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.

scholarly journals Cyclic Cushing's syndrome

2010 ◽  
Vol 56 (4) ◽  
pp. 44-51
Author(s):  
E I Marova ◽  
I A Voronkova
Keyword(s):  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Plasma Cortisol Level ◽  
Average Life Expectancy ◽  
Ectopic Acth ◽  
Number Of Patients ◽  
Free Cortisol ◽  
Cortisol Levels

The cyclic Cushing's syndrome is a rare disease characterized by multiple episodes of elevated cortisol levels alternating with periods of its normal secretion. The so-called hypercorticism cycles may be either regular or episodic with intercycle intervals as long as a few days to several years. Most researchers agree that the reliable diagnosis of cyclic Cushing's syndrome should be based on laboratory detection of 3 peaks and 2 falls of plasma cortisol level. Cyclic Cushing's syndrome may be either ACTH dependent or independent. A review of 65 verified cases indicates that this condition may be caused by pituitary corticotropinoma (54%), ectopic ACTH-producing tumour (26%), and adrenal tumour (roughly 11%). The cause of the disease remains uncertain in 9% of the patients. Pathophysiological mechanisms of cyclic Cushing's syndrome are poorly known. In certain cases of bilateral macronodular adrenal hyperplasia or adrenal corticosteroma, it may be associated with the presence of ectopic receptors or anomalous expression of normally located receptors. The majority of the patients presenting with cyclic Cushing's syndrome exhibit symptoms of classical hypercorticism that manifest themselves either on a permanent or cyclic basis. In a small number of patients, clinical signs of cyclic Cushing's syndrome are virtually absent. Variations of the clinical picture and conflicting results of hormonal assays taken together make cyclic Cushing's syndrome difficult to diagnose. Therefore, physicians must be aware of this condition and actively search for it in all patients believed to have an enhanced cortisol production despite normal results of laboratory analysis. Frequent changes of urinary or salivary free cortisol levels are reliable and convenient criteria for cyclic Cushing's syndrome in patients suspected to have this condition. Results of cortisol stimulation or suppression tests are likely to lead to a false conclusion due to spontaneous falls and rises in serum cortisol levels at the time of analysis. Given laboratory confirmation of cyclic Cushing's syndrome, subsequent studies should be focused on the elucidation of its cause. The average life expectancy of patients with cyclic Cushing's syndrome remains to be determined.

scholarly journals Mifepristone Effects on Tumor Somatostatin Receptor Expression in Two Patients with Cushing's Syndrome due to Ectopic Adrenocorticotropin Secretion

2012 ◽  
Vol 97 (2) ◽  
pp. 455-462 ◽  
Author(s):  
C. de Bruin ◽  
L. J. Hofland ◽  
L. K. Nieman ◽  
P. M. van Koetsveld ◽  
A. M. Waaijers ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Quantitative Pcr ◽  
Cushing’S Syndrome ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion

Context: Two patients presented with Cushing's syndrome due to ectopic ACTH secretion. Initial localization studies included computed tomography, magnetic resonance imaging, and octreoscans (111In-pentreotide scintigraphy), which were negative in both patients. They were treated with the glucocorticoid receptor antagonist mifepristone, with improvement in their clinical symptoms. Follow-up octreoscans after, respectively, 6 and 12 months showed the unequivocal presence of a bronchial carcinoid in both patients. Objective: The objective of the study was to correlate in vivo and in vitro findings in patients with ectopic ACTH-producing syndrome. Methods: We determined the expression of somatostatin and dopamine receptors by immunohistochemistry (patients 1 and 2), quantitative PCR, and in vitro culturing of tumor cells (patient 1 only). In Vitro Results: Both tumors were strongly positive for somatostatin receptor type 2 (sst2) on immunohistochemistry, whereas one of the tumors (patient 1) was also dopamine receptor subtype 2 (D2) positive on both immunohistochemistry and quantitative PCR. Octreotide (a sst2 preferring analog) and cabergoline (D2 agonist) both decreased the ACTH levels in the cultured tumor cells of patient 1. Conclusion: We describe two patients with ACTH-producing bronchial carcinoids, in whom a direct down-regulatory effect of glucocorticoid levels on tumoral sst2 receptor expression is suggested by a remarkable change in octreoscan status after successful mifepristone therapy. Further studies will have to demonstrate whether glucocorticoid lowering or antagonizing therapy may be used to improve the diagnostic accuracy of somatostatin receptor scintigraphy in patients with ectopic ACTH production of unknown primary origin.

scholarly journals Ectopic Cushing's syndrome caused by a pulmonary ACTH-secreting tumor in a patient treated with octreotide

2012 ◽  
Vol 56 (7) ◽  
pp. 461-464 ◽  
Author(s):  
Pedro Rodrigues ◽  
José Luís Castedo ◽  
Margarida Damasceno ◽  
Davide Carvalho
Keyword(s):  
Cushing’S Syndrome ◽  
Left Lung ◽  
Clinical Manifestations ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
High Dose ◽  
Ectopic Acth ◽  
Octreotide Lar ◽  
Ultrastructural Studies ◽  
Free Cortisol

Ectopic ACTH syndrome is a rare disease often associated with severe hypercortisolism. When feasible, optimal management is surgical excision of the tumor. A 33-year-old male patient was admitted to the hospital in 1993 with clinical manifestations suggestive of Cushing's syndrome. He presented high plasma ACTH and markedly elevated urinary free cortisol excretion that was not suppressed with high-dose dexamethasone administration. Pituitary MRI scan was normal. No central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. Thoracic CT scan showed a 1.7 cm nodule at the left lung. Pulmonary fine needle cytology and immunocytochemical and ultrastructural studies, together with the presence of bone metastases, led to the diagnosis of an ACTH-producing neuroendocrine carcinoma. He was initially submitted to chemotherapy and has been on treatment with octreotide LAR since 1998, having shown a favorable clinical, biochemical and imaging response. We highlight the excellent long-term response to medical therapy with octreotide LAR, without tachyphylaxis, probably due to its antiproliferative effect.

scholarly journals Ectopic Acth-Producing Pulmonary Carcinoid: A Rare Case of Simulating the Cushing’s disease

2020 ◽  
Vol 3 (4) ◽  
pp. 01-04
Author(s):  
Manouchehr Nakhjavan
Keyword(s):  
Cushing’S Syndrome ◽  
Mediastinal Lymph Node ◽  
Left Lung ◽  
Cushing's Syndrome ◽  
Whole Body ◽  
High Dose ◽  
Ectopic Acth ◽  
Pulmonary Carcinoid ◽  
High Dose Dexamethasone ◽  
Free Cortisol

Excess amounts of blood glucocorticosteroids, either exogenous or endogenous, results in Cushing’s syndrome (CS). the current study presents a 45-year-old man, ACTH dependent Cushing’s syndrome. The basal cortisol and urine free cortisol level were significantly suppressed following high dose dexamethasone suppression test and pituitary MRI showed microadenoma with a size of less than 6 mm. After bilateral inferior petrosal sinus sampling, we investigated the ectopic source of ACTH production. The computed tomography revealed a mediastinal lymph node, and the whole body octreotide scan revealed octreotide avid lesion in the medial aspect of the left lung. The patient underwent left lung lobectomy and the pathological study indicated the carcinoid tumor of the left lung.

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.

scholarly journals Pitfalls in the diagnosis of Cushing's syndrome

2007 ◽  
Vol 51 (8) ◽  
pp. 1207-1216 ◽  
Author(s):  
Lucio Vilar ◽  
Maria da Conceição Freitas ◽  
Manuel Faria ◽  
Renan Montenegro ◽  
Luiz Augusto Casulari ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
High Dose ◽  
Endocrine Disorders ◽  
Ectopic Acth ◽  
Late Night ◽  
Non Invasive ◽  
Free Cortisol ◽  
Dexamethasone Suppression

Among endocrine disorders, Cushing's syndrome (CS) is certainly one of the most challenging to endocrinologists due to the difficulties that often appear during investigation. The diagnosis of CS involves two steps: confirmation of hypercortisolism and determination of its etiology. Biochemical confirmation of the hypercortisolaemic state must be established before any attempt at differential diagnosis. Failure to do so will result in misdiagnosis, inappropriate treatment, and poor management. It should also be kept in mind that hypercortisolism may occur in some patients with depression, alcoholism, anorexia nervosa, generalized resistance to glucocorticoids, and in late pregnancy. Moreover, exogenous or iatrogenic hypercortisolism should always be excluded. The three most useful tests to confirm hypercortisolism are the measurement of 24-h urinary free cortisol levels, low-dose dexamethasone-suppression tests, and determination of midnight serum cortisol or late-night salivary cortisol. However, none of these tests is perfect, each one has different sensitivities and specificities, and several are usually needed to provide a better diagnostic accuracy. The greatest challenge in the investigation of CS involves the differentiation between Cushing's disease and ectopic ACTH syndrome. This task requires the measurement of plasma ACTH levels, non-invasive dynamic tests (high-dose dexamethasone suppression test and stimulation tests with CRH or desmopressin), and imaging studies. None of these tests had 100% specificity and their use in combination is usually necessary. Bilateral inferior petrosal sinus sampling is mainly indicated when non-invasive tests do not allow a diagnostic definition. In the present paper, the most important pitfalls in the investigation of CS are reviewed.

scholarly journals Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreea Liliana Serban ◽  
Lorenzo Rosso ◽  
Paolo Mendogni ◽  
Arianna Cremaschi ◽  
Rita Indirli ◽  
...  
Keyword(s):  
Ct Scan ◽  
Rectal Carcinoma ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Pet Ct ◽  
The Right ◽  
Acth Secreting

BackgroundEctopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing’s syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.Case presentationA 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing’s syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0–46; basal cortisol levels: 44.2 µg/dl, nv 4.8–19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing’s syndrome.ConclusionsThe present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.

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