Adrenocorticotropic Hormone Syndrome Research Articles

A rare case of ectopic ACTH syndrome with rhabdomyolysis

BackgroundManifestations of hypokalaemia in ectopic adrenocorticotropic hormonesyndrome(EAS) vary from mild muscle weakness to life-threatening arrhythmia. Herein, we present a rare case of EAS with concomitant rhabdomyolysis(RM) as a result of intractable hypokalaemia.Case presentationA 64-year-old man was admitted for limb weakness and facial hyperpigmentation for 2 weeks. Lab tests revealed intractable hypokalaemia (lowest at 1.8 mmol/L) and metabolic alkalosis. The diagnosis of RM was based on a creatine kinase(CK)level of 5 times the upper limit. The elevated CK and myohemoglobin (Mb) levels returned to within the normal range after the alleviation of hypokalaemia. The patient was diagnosed with ACTH-dependent Cushing’s syndrome (CS) based on unsuppressed serum cortisol after a low-dose dexamethasone suppression test(LDDST) and remarkably elevated ACTH levels. The diagnosis of EAS was made based on the results of a high-dose dexamethasone suppression test(HDDST) and bilateral inferior petrosal sinus sampling(BIPSS). Multiple lymph nodes in the left supraclavicular fossa, right root of neck, mediastinum and bilateral hili of the lung were found with abnormal uptake of 68Ga-DOTA-NOC. Mediastinoscopic lymph node biopsy was performed. The pathological diagnosis was small-cell and large-cell neuroendocrine carcinoma with positive ACTH staining. The patient was prescribed mifepristone and received one cycle of chemotherapy. The patient could not tolerate subsequent chemotherapy and died of dyscrasia.ConclusionsRM is a rare complication of EAS with insidious onset and atypical clinical manifestations. Serum potassium levels should be vigilantly monitored to avoid RM in EAS.

Ectopic adrenocorticotropic hormone (ACTH-ectopic) syndrome and osteoporosis: Rare cases and difficult treatment

Ectopic adrenocorticotropic hormone (ACTH-ectopic) syndrome and osteoporosis: Rare cases and difficult treatment

Pulmonary nocardiosis mimicking small cell lung cancer in ectopic ACTH syndrome associated with transformation of olfactory neuroblastoma: a case report

BackgroundPulmonary nocardiosis frequently develops as an opportunistic infection in cell-mediated immunosuppressive patients, and sometimes requires differentiation from pulmonary malignancy. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a neoplastic disorder which leads to impaired cell-mediated immunity, and is commonly associated with small cell lung cancer (SCLC). Because pulmonary infection and causative malignancy can appear as pulmonary lesions with EAS, differentiation of these diseases remains a critical issue for physicians.Case presentationA 52-year-old woman with progressive lower limb paralysis and general fatigue was referred to us. She had been diagnosed with olfactory neuroblastoma (ONB) and treated with surgery and radiation therapy 10 years before the referral and had required stereotactic radiosurgery and chemotherapy 4 years later for a relapse of the ONB. On referral, she presented with Cushing’s syndrome with elevated cortisol and ACTH levels. Potassium supplement improved her symptoms; however, a month later, she was urgently hospitalized due to acute pleuritic chest pain on inspiration. Chest computed tomography revealed left lower lobular consolidations and a contralateral nodule in the right middle lobe. The clinical history and laboratory work-up suggested that her Cushing’s syndrome had most likely arisen from EAS. Additionally, the lungs were suspected as the ACTH source due to high levels of progastrin-releasing peptide and progressive pulmonary consolidation with a contralateral nodule, suggesting SCLC. However, histological examination from bronchoscopy revealed no evidence of malignancy, and Nocardia cyriacigeorgica was isolated from bronchoalveolar lavage fluid. Sulfamethoxazole/trimethoprim improved her pulmonary lesions. Somatostatin receptor scintigraphy revealed strong tracer uptake in the ONB lesions, indicating that the origin of the EAS was the olfactory tumor. However, histological examination of ONB specimens resected 10 years earlier showed no intracytoplasmic immunopositivity for ACTH.ConclusionsWe highlight a rare case of pulmonary nocardiosis, which was associated with EAS mimicking SCLC, and was related to ONB transformation. Nocardiosis has to be considered even though anamnestic, clinical, and radiological aspects suggest the presence of metastasis. Additionally, physicians should carefully monitor patients with ONB for the development of Cushing’s symptoms because the tumor can transform into an ACTH-producing form, even after long-term follow-up.

Spontaneous adrenocorticotropic hormone (ACTH) normalisation due to tumour regression induced by metyrapone in a patient with ectopic ACTH syndrome: case report and literature review

BackgroundEctopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely induced using steroidogenesis inhibitors. We presented a case of EAS in which ACTH production by a lung tumour was reduced by metyrapone (MTP) and also reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis inhibition.Case presentationA 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing’s syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2–63.3 pg/mL), cortisol (73.1 μg/dL; 6.4–21.0 μg/dL) and 24-h urinary free cortisol (UFC) (6160 μg/day; 11.2–80.3 μg/day) levels. Chest computed tomography identified a solid 26.6 × 22.9 × 30.0 mm tumour with a cavity in the upper lobe of the left lung. There was no adrenal gland enlargement. Tumour markers were not significantly elevated; ACTH levels were not suppressed by 8-mg dexamethasone. A corticotropin-releasing hormone stimulation test revealed blunted ACTH response (basal ACTH, 204.6 pg/mL; highest ACTH level during the 120-min stimulation test, 214.0 pg/mL). She was diagnosed with EAS due to a lung lesion. MTP treatment was started to reduce cortisol production. ACTH levels and cortisol and UFC levels were normalised and the ACTH-producing lung tumour was ablated after MTP treatment. In several reported cases, plasma ACTH levels reduced during steroidogenesis inhibitor treatment for EAS. Among the 10 patients, three cases of pheochromocytoma, one of thymic carcinoid and one of islet cell carcinoma were reported. In four cases, the tumour was not detected. In our case, the pathology of the lung tumour was unknown because of lack of tumour cells in biopsy. The patients were treated with ketoconazole (KTZ) and/or MTP and exhibited ACTH and cortisol/UFC suppression, but tumour regression was observed only in our case.ConclusionMTP and/or KTZ may reduce ACTH and cortisol production. The tumour spontaneously regressed after MTP treatment, indicating that MTP may reduce the tumour size without surgery. The mechanisms of therapeutic effects of steroidogenesis inhibitors and prognosis of spontaneous remission should be elucidated further via molecular biology studies.

Effects of activity of 11β-hydroxysteroid dehydrogenase type 2 on serum potassium levels in Cushing's syndrome patients

To explore the effects of different forms of glucocorticoid excess on cortisol/cortisone ratio and to reveal the mechanisms of hypokalemia in Cushing's syndrome patients. The levels of urinary free cortisol (UFF) and urinary free cortisone (UFE) were determined in 6 adult patients with ectopia adrenocorticotropic hormone (ACTH) syndrome, 6 normal serum level of potassium adults with hypercortisolism due to adrenal tumor, 5 hypokalemic adults with hypercortisolism due to adrenal tumor and 6 healthy volunteers using high-performance liquid chromatography plus tandem mass spectrometry (LC-MS/MS). For 4 groups, the results of UFF+UFE were (2 787 ± 820), (689 ± 163), (697 ± 120) and (70 ± 27)µg/L and UFF/UFE ratio 2.98 ± 0.35, 1.03 ± 0.42, 2.24 ± 0.37 and 0.42 ± 0.20 respectively. The values of UFF+UFE had no statistical difference between normal and low levels of serum potassium adults with hypercortisolism. And the ratio of UFF/UFE of hypokalemic adults with hypercortisolism was significantly higher than that of normal serum level of potassium adults with hypercortisolism. It suggested that the deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD 2) was present in hypokalemic adults with hypercortisolism. Due to a deficiency of 11β-HSD2, active cortisol can not be transformed into inactive cortisone in some patients with ACTH-independent Cushing's syndrome.

Еctopic ACTH syndrome: clinical picture, diagnosis, treatment

Diagnosis and treatment of ectopic ACTH-syndrome currently is one of the most challenging problems among other forms of endogenous hypercorticism. This syndrome is associated with presence of extrapituitary tumors characterized with different histogenesis and localization, which produce adrenocorticotropic hormone (ACTH), or – rarely – corticotrophin-releasing hormone. In most cases the ectopic synthesis of ACTH is performed in bronchial carcinoid tumors (36–46%), oat cell cancer (18–20%), medullary thyroid cancer (3–7%), pheochromocytoma (9–23%), other sites are infrequent (pancreas, thymus, parotid gland, ovaries, uterus, prostate, colon, stomach, esophagus, etc.). Much of these tumors are aggressive and are characterized with propensity to metastasize and relapse. Currently there are few contradictory data on the comparative evaluation of the effectiveness of methods of topical diagnosis of the source of ectopic ACTH-secretion, and therefore there is an urgent need to develop an optimal and most efficient algorithm for diagnostic procedures to determine the extent of the tumor in patients with ectopic ACTH-syndrome. Indications for surgery, timing and extent of surgical intervention, the effectiveness of the operation, the causes and frequency of relapses are still discussed.The present difficulties of diagnosis, as well as the lack of a unified approach to the treatment of this disease in the complex, often lead to the progression and development of a large number of serious complications functions of up to disability, which in turn does not lead to significant improvement of quality of life. Thus further research is necessary to study of this disease

Hypertension, Diabetes, Hypokalemia, and Metabolic Alkalosis

Abstract: Prostate adenocarcinoma is a very rare cause of ectopic adrenocorticotropic hormone (ACTH) syndrome. We report the case of a 70-year-old man who presented with clinical and biochemical features of ACTH-dependent Cushing syndrome secondary to prostate carcinoma. On admission, his blood pressure was 170/100 mm Hg. Physical examination revealed signs of excessive production of cortisol. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Elevated serum cortisol, ACTH, and urine free cortisol levels were found. Cortisol was not suppressed with an overnight 1-mg oral dexamethasone suppression test (DST), 2-day low-dose DST, or overnight 8.0-mg high-dose DST. Chest computed tomography showed multiple parenchymal nodules in the right lung, consistent with metastatic disease. Whole-body bone scintigraphy revealed numerous foci of increased radiotracer uptake in the femur and axial skeleton, consistent with metastatic disease. Bone survey (radiography) showed generalized osteolytic metastases. Histologic analysis of a prostatic biopsy showed prostate adenocarcinoma. Immunostaining of the prostate adenocarcinoma for ACTH was positive. The severe metabolic alkalosis due to glucocorticoid-induced mineralocorticoid excess was treated with potassium supplements and spironolactone. This case is a remarkable example of the complex metabolic endocrine manifestations that can accompany prostate adenocarcinoma.

Paraneoplastic syndromes in patients with laryngeal and hypopharyngeal cancers.

Paraneoplastic syndromes are systemic, nonmetastatic manifestations associated with a variety of malignant neoplasms and occurring in a minority of cancer patients. Paraneoplastic syndromes in association with cancers of the larynx and hypopharynx are considered rare. The world literature is reviewed, dividing paraneoplastic syndromes into 4 main groups, ie, cutaneous (acanthosis nigricans, Bazex's syndrome, Bowen's disease, bullous pemphigoid, dermatomyositis, pruritus, Sweet's syndrome, yellow nail syndrome, and tylosis), endocrine (carcinoid syndrome, adrenocorticotropic hormone syndrome, Schwartz-Bartter syndrome, hypercalcemia), hematologic (Trousseau's syndrome), and neurologic (cerebellar degeneration, Eaton-Lambert myasthenic syndrome). A paraneoplastic syndrome may precede the clinical manifestations of a persistent or recurrent tumor or of asymptomatic metastases, and its onset may even, in a minority of cases, be the presenting sign of a malignancy. Otolaryngologists and head and neck surgeons should have a knowledge of the paraneoplastic syndromes in order to facilitate their detection of malignancies or recurrences.

The use of ketoconazole in ectopic adrenocorticotropic hormone syndrome

The authors report a patient with ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) resulting from small cell lung cancer. Treatment with ketoconazole (KCZ) resulted in significant suppression of serum cortisol levels. The authors confirmed KCZ to be a useful adjunct in the treatment of Cushing's syndrome.

The Conundrum of Cushing's Syndrome

Cushing's syndrome has presented clinicians with fascinating diagnostic and therapeutic difficulties for more than half a century. Additional causative mechanisms and different means of treatment continue to be advanced. Although the syndrome usually results from a disordered function originating in the pituitary or the adrenal glands, pathologic hypercortisolism is also well known to result from ectopic secretions. The ectopic corticotropin (ACTH) syndrome, which is characteristic of the latter disorders, is usually associated with very high levels of ACTH secretion, great excesses of cortisol, bilateral adrenal hypertrophy, pigmentation, hypokalemia, hyperglycemia, and hypertension. The very high levels of cortisol accelerate the pace of the disorder, and the underlying malignancy modifies the clinical expression of the endocrine disease. Instead of a classically obese, plethoric patient with Cushing's syndrome, victims are usually severely wasted. 1 In his 1979 review of the Cushing syndromes, Gold 2 proposed a useful diagnostic algorithm that integrated ACTH assays

Edema in the Ectopic ACTH Syndrome

Excerpt To the editor: Peripheral edema may be a prominent feature of the ectopic adrenocorticotropic hormone (ACTH) syndrome, and has been attributed to mineralocorticoid excess (1,2). However, in...