ACTH-producing Lung Tumors Hard to Detect, But May Be Cured with Surgery

Ectopic Cushing’s syndrome can be challenging to diagnose, especially when it comes identifying the problem source. But appropriate hormone management protocols, used in combination with advanced imaging methods, may help physicians identify ectopic ACTH-producing tumors.

The findings in a case report of a young man with ectopic Cushing’s syndrome were published in the International Journal of Surgery Case Reports, under the title “Case report: Ectopic Cushing’s syndrome in a young male with hidden lung carcinoid tumor.”

Cushing’s syndrome is caused by high amounts of glucocoticosteroids in the blood. The most common cause is a malfunction of the glands that produce these hormones. In some cases, however, the disease may be caused by tumors elsewhere in the body that have the ability to produce adrenocorticotropic hormone (ACTH).

In half of all Cushing’s patients, ectopic ACTH is produced by small lung cell carcinomas or lung carcinoids (a type of slow-growing lung cancer). But some tumors in the thymus and pancreas also have been found to produce ACTH.

Researchers at Damascus University Hospital in Syria presented the case of a 26-year-old man who had ectopic Cushing’s syndrome due to lung carcinoids.

The patient presented with increased appetite and rapid weight gain for more than a year. These were associated with headache, fatigue, proximal muscle weakness, and easy bruising. He had no family history of hormonal disorder.

Based on the initial physical and symptom evaluation, the clinical team suspected Cushing’s syndrome. Blood analysis revealed high levels of cortisol and ACTH hormones, which supported the diagnosis.

Administration of dexamethasone, a treatment used to inhibit the production of glucocoticosteroids by the pituitary gland, reduced cortisol levels within normal range, but not ACTH levels. This led to the diagnosis of ectopic Cushing’s syndrome.

The next step was to identify the tumor causing the syndrome. The team conducted imaging studies of the brain, chest, and abdomen, but found no tumor.

Because ectopic ACTH is commonly produced by lung cancers, the team then analyzed the patient’s lungs. Again, they failed to detect a tumor.

The patient was discharged with prescription of 200 mg of Nizoral (ketoconazole) once-daily, calcium, and vitamin D. After three months of treatment, he remained stable, with no evidence of symptom improvement.

At this point, the team decided to surgically remove both adrenal glands in an attempt to reduce the hormone levels. Treatment with prednisolone 5 mg and fludrocortisone 0.1 mg once daily was initiated, along with calcium and vitamin D.

Eighteen months later, the patient’s condition worsened and he required hospitalization.

Imaging tests targeting the neck, chest, and abdomen were conducted again. This time, physicians detected a 2 cm mass in the middle lobe of the right lung, which was removed surgically. Detailed analysis of the small tumor confirmed that it was the source of the excessive ACTH.

“ACTH secreting tumors can be very hard to detect,” the researchers stated. “Initial failed localization is common in ectopic ACTH syndrome and it is usually due to carcinoid.”

Cases where the ectopic ACTH production is caused by a carcinoid tumor can be challenging to diagnose because tumors are small and relatively slow-growing. Imaging data is often hard to analyze and the tumors can be confused with pulmonary vessels, the researchers explained.

“In such cases we should first aim to lower blood cortisol medically or through bilateral adrenalectomy to avoid Cushing’s complications,” which should then “be followed up through imaging studies (CT, MRI, scintigraphy or PET) to detect the tumor and resect it, which is the definitive treatment of these patients,” the researchers concluded.

From https://cushingsdiseasenews.com/2017/12/12/case-report-ectopic-acth-producing-lung-tumors-can-hard-detect/

Delayed complications after transsphenoidal surgery for pituitary adenomas

World Neurosurg. 2017 Oct 5. pii: S1878-8750(17)31710-2. doi: 10.1016/j.wneu.2017.09.192. [Epub ahead of print]

Abstract

Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively and reports are sparse about their occurrence, management, and outcome.

Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia (DSH), hypopituitarism, hydrocephalus, and sinonasal complications.

Our findings from this review revealed an incidence of 0.6-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases for postoperative vasospasm occurring 8 days postoperatively, a 3.6-19.8% rate of DSH at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4-5.8% rate of hydrocephalus within 2.2 months postoperatively.

Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning.

KEYWORDS:

carotid pseudoaneurysm; cerebrospinal fluid leak; delayed complications; epistaxis; hydrocephalus; hyponatremia; hypopituitarism; pituitary; sinonasal complication; transsphenoidal surgery; tumor

Study Highlights Importance of Clinical Follow-Up in Cushing’s Patients After Adenoma Removal

A rare case of Cushing’s syndrome (CS) in a 17-year-old patient with multiple pituitary adenomas highlights the importance of clinical follow-up in order to determine the best treatment options for patients.

The study, “A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture,” was published in the journal Annals of Pediatric Endocrinology and Metabolism

CS is a very rare disease with an incidence of 0.7-2.4 cases per million, per year. It is caused by exposure to very high levels of the hormone cortisol. In children, the most common symptom is weight gain without height gain. In some rare cases, tumors known as multiple pituitary adenomas (MPAs) appear, and patients have elevated levels of adrenocorticotropic hormone (ACTH). Surgical removal through transsphenoidal surgery (TSS) is considered the best treatment, and the first TSS has a success rate of more than 90%.

However, since 15% of patients have a recurrence, ongoing monitoring and follow-up after TSS are important. The importance of this follow-up care is highlighted in a recent case report.

The study described the case of a 17-year-old male adolescent who was 149.5 cm tall (4’9″) and weighed 63.6 kg (140 lbs). The patient was referred to a hospital for the evaluation of a vertebral compression fracture and obesity. Over four years, the patient gained 23 kg (51 lbs) without an increase in height. Despite showing many of the features of CS, this patient had not been previously diagnosed with CS.

He had high levels of ACTH and cortisol, and an MRI suggested the presence of an 8-mm (0.8 cm) micro-adenoma. After TSS, the patient’s morning ACTH and cortisol levels were reduced, and a persistent headache had improved. But there was no reduction in weight.

Three months after the TSS, the patient’s body mass index did not show improvement, and both cortisol and ACTH levels were elevated again. MRI revealed a new 9 mm (0.9 cm) micro-adenoma, which was removed with a second TSS. However, cortisol and ACHT remained elevated after the second surgery, with no evidence of a pituitary tumor in MRI scans.

Researchers recommended additional options, such as total removal of the pituitary gland, radiotherapy, or removal of both adrenal glands, options that the patient and his family declined. He continued to receive treatment for osteoporosis, hypertension, and increased lipid levels.

“In conclusion, we reported the clinical course of Cushing disease with 2 distinct pituitary adenomas. Since there is no consensus as to the best treatment for relapsing or persistent Cushing disease and since only a few cases of MPA among pediatric Cushing disease have been reported, a close followup of tumor status, severity of hypercortisolism, and patients’ perspectives are the major parameters used to determine the best treatment option for each patient. In addition, early recognition and diagnosis of pediatric Cushing disease would lead to earlier recovery, improved growth, and better quality of life,” the researchers wrote.

From https://cushingsdiseasenews.com/2017/10/27/cushings-disease-rare-case-report-highlights-importance-early-diagnosis-follow-up-care/

Increase in Glucose Uptake by Cushing’s Disease-associated Tumors Could Improve Early Detection

An increase in glucose uptake by Cushing’s disease-associated pituitary tumors could improve their detection, new research shows.

The study, “Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1,” appeared in the journal Molecular and Cellular Endocrinology.

The study’s senior author was Dr. Prashant Chittiboina, MD, from the Department of Neurosurgery, Wexner Medical Center, The Ohio State University, in Columbus, Ohio.

Microadenomas – tumors in the pituitary gland measuring less than 10 mm in diameter – that release corticotropin, or corticotropinomas, can lead to Cushing’s disease. The presurgical detection of these microadenomas could improve surgical outcomes in patients with Cushing’s.

But current tumor visualization methodologies – magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) – failed to detect a significant percentage of pituitary microadenomas.

Stimulation with corticotropin-releasing hormone (CRH), which increases glucose uptake, has been suggested as a method of increasing the detection of adenomas with 18F-FDG PET, by augmenting the uptake of 18F-FDG – a glucose analog.

However, previous studies aiming to validate this idea have failed, leading the research team to hypothesize that it may be due to a delayed elevation in glucose uptake in corticotropinomas.

The scientists used clinical data to determine the effectiveness of CRH in improving the detection of corticotropinomas with 18F-FDG PET in Cushing’s disease.

They found that CRH increased glucose uptake in human and mouse tumor cells, but not in healthy mouse or human pituitary cells that produce the adrenocorticotropic hormone (ACTH). Exposure to CRH increased glucose uptake in mouse tumor cells, with a maximal effect at four hours after stimulation.

Similarly, the glucose transporter GLUT1, which is located at the cell membrane, was increased two hours after stimulation, as was GLUT1-mediated glucose transport.

These findings indicate a potential mechanism linking CRH exposure to augmented glucose uptake through GLUT1. Expectedly, the inhibition of glucose transport with fasentin suppressed glucose uptake.

The researchers consistently observed exaggerated evidence of GLUT1 in human corticotropinomas. In addition, human corticotroph tumor cells showed an increased breakdown of glucose, which indicates that, unlike healthy cells, pituitary adenomas use glucose as their primary source of energy.

Overall, the study shows that corticotropin-releasing hormone (CRH) leads to a specific and delayed increase in glucose uptake in tumor corticotrophs.

“Taken together, these novel findings support the potential use of delayed 18F-FDG PET imaging following CRH stimulation to improve microadenoma detection in [Cushing’s disease],” researchers wrote. The scientists are now conducting a clinical trial to further explore this promising finding.

From https://cushingsdiseasenews.com/2017/10/12/glucose-uptake-in-cushings-disease-could-improve-presurgical-tumor-detection/

An unusual case of Cushing’s syndrome due to bihormonal ACTH–prolactin secreting pituitary macroadenoma with rapid response to cabergoline

  1. Shalini Kunasegaran1,2,
  2. Michael S Croxson1,
  3. Ian Holdaway1,
  4. Rinki Murphy1

+Author Affiliations


  1. 1Department of EndocrinologyAuckland District Health BoardAuckland, New Zealand

  2. 2Department of EndocrinologyWaitemata District Health BoardTakapuna, New Zealand
  1. Correspondence to Dr Shalini Kunasegaran, shal84@gmail.com
  • Accepted 13 July 2017
  • Published 7 August 2017

Summary

A 23-year-old man presenting with florid Cushing’s syndrome was found to have high plasma ACTH and very high serum prolactin. Pituitary MRI showed a large invasive macroadenoma.

Low-dose cabergoline promptly suppressed both ACTH and prolactin levels within 2 weeks, with unexpected clinical and biochemical hypocortisolism requiring hydrocortisone replacement. Secondary hypogonadism was reversed. Clinical and biochemical remission of his Cushing’s syndrome together with significant shrinkage of his macroadenoma has been maintained for 1 year on cabergoline 0.5 mg twice weekly. Reduction in pituitary

Reduction in pituitary tumour volume and brisk fall in serum prolactin in response to low-dose cabergoline is regularly observed in patients with macroprolactinomas, but the concurrent fall in the plasma ACTH level and hypocortisolism was a pleasant surprise.

We assume that he most likely has a single bihormonal adenoma that is enriched with dopamine-2 receptors.

From http://casereports.bmj.com/content/2017/bcr-2017-219921.short?rss=1

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