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/

Cushing’s Syndrome Revealing Carney Complex: A Case Report

 

Carney complex (CNC) is a rare multisystem disorder, inherited in an autosomal dominant manner and characterized by distinctive spotty skin pigmentation, myxomas and endocrine abnormalities.

We report a case of a 35-year-old patient diagnosed with Cushing’s syndrome complicated with an impaired glucose tolerance (IGT) and a severe psychiatric disturbance. The diagnosis of CNC was made by having two major criteria, namely a primary pigmented nodular adrenal disease (PPNAD) and thyroid carcinoma.

Read the entire report here: Cushing’s Syndrome Revealing Carney Complex: A Case
Report

A 12-year-old boy died from Addison’s disease after the chance of lifesaving treatment was ‘missed’

The death of a 12-year-old boy who was suffering from undiagnosed Addison’s disease was preventable, an inquest heard.

Ryan Lee Morse had been unwell from July 2012, with his parents noticing his skin darkening and him becoming lethargic and losing weight.

His condition worsened over the following months and he died during the early hours of December 8, 2012.

During the time he was unwell, Ryan’s mother, Carol Ann Morse, took him to Abernant Surgery in Abertillery several times.

She said: “Ryan was rarely ill as a child. In June 2012, which was towards the end of Ryan’s first comprehensive school year, I noticed his skin colour changing.

“His skin seemed to be getting darker.”

She said his joint areas, including elbows and knees, were getting darker. Under his eyes, it looked as if he had not slept for a month. I don’t suppose it worried me at the time because it was gradual.”

A post mortem was held on December 12 by Dr E. J. Lazda, a consultant pathologist at University Hospital of Wales in Cardiff who concluded that Ryan died as a result of Addison’s disease.

An inquest into Ryan’s death was held at Newport Coroner’s Court on Thursday.

Dr Yvette Cloette, a consultant paediatrician since 2004, was called during the early hours of December 8, 2012, by a registrar where she was told the details of Ryan’s death.

She said: “Ryan’s parents told me he had been unwell since July.

“It was thought Ryan had been particularly unwell since the Thursday before he passed away. He had to be collected from school that day. On (the) Friday morning, she said he hallucinated. His temperature did settle that afternoon but then he had diarrhoea.

“As his mum was cleaning him, she noticed his genitalia were black.

“I then examined Ryan. At this time I formed the opinion that Ryan may have had Addison’s disease. I didn’t share this with the family at the time because I didn’t have enough evidence.

“I believe that Ryan’s death was preventable. Addison’s is a disease which, once recognised, can be treated.”

She said it was easier to put things together retrospectively, as opposed to when treating an acute illness as a GP.

David Bowen, senior coroner for Gwent, paid tribute to Ryan’s family during the hearing.

“Before summing up, I think it’s right that I pay tribute to the dignity that has been shown by Mrs Morse and her family.

“It can’t have been easy for them to rehear events that took place over five years ago.

“Please accept my belated condolences.”

Mr Bowen told the inquest that Ryan had been fit and well up until July 2012.

“However at about that time, his parents began to notice a gradual change in his skin and a fluctuation in his general health.”

He had been diagnosed with a viral infection and prescribed Paracetamol, he said.

Over the next six to eight weeks, he did not improve.

Mr Bowen said: “Consequently, his mother took him back to the doctor. The GP was more concerned about the rash, it seems to me, than any of the other symptoms.

“He prescribed tablets and cream for that condition.”

Mr Bowen said that during October and November 2012, “Ryan’s health became much more of a concern for his parents.”

He suffered from headaches, pains in his legs, and occasional episodes of projectile vomiting.

On November 7, Mrs Morse took Ryan back to the GP surgery, where she described symptoms to Dr Rudling, who took samples of blood.

On November 21, they returned to receive the blood test results.

The results revealed a “slightly lower than normal” white blood cell count. The inquest heard Ryan was told he was still suffering from a viral infection that had been diagnosed some months earlier.

Mr Bowen said: “It appears that about this time, there was an outbreak of Norovirus or vomiting and sickness in the area that may have confused the diagnosis.”

Mrs Morse said: “I’d been told to bring Ryan back in January so I thought I would just get Christmas out of the way and take him back. I’d been a carer for 9-10 years but my job didn’t give me any insight into what Ryan had.”

On November 29, 2012, Ryan returned to school, but around a week later on December 6 he was so ill that his mum had to collect him early.

The following day, on December 7, Mrs Morse rang Abernant Surgery saying she needed to speak to a doctor.

Between 8.50am and 8.55am, she received a call from Dr Lyndsey Elizabeth Thomas.

Mrs Morse said: “She asked if he’d been given Paracetamol and I explained he wouldn’t take it. She asked what his temperature was like.

“I’d said Ryan was awake (that morning) and talking rubbish.”

The inquest heard Mrs Morse was asked to take Ryan to the surgery, but she said she was unable to.

“She then told me to give Ryan some dissolvable Paracetamol and see how it goes until dinner. She said fetch him up if you need to.”

Dr Lyndsey Elizabeth Thomas said her contact with Ryan was limited to a single telephone conversation with his mother on December 7.

She said: “I considered whether Ryan needed to be seen or admitted to hospital.

“I clearly recall explaining that if she had any concerns or if Ryan’s delirium or temperature didn’t improve in two hours, he would need to be seen, I would be able to go and visit him at the end of the morning surgery if necessary.”

Mrs Morse said she later noticed that her son’s genitals were black.

She rang the surgery and was put her through to Dr Rudling.

Mrs Morse said: “She said ‘it’s all to do with his hormones’. Phone Monday and we’ll fit him in. At this point I didn’t know what to think.

“I was thinking I’ll take him in on Monday and see what they say. There was no more temperature, no more sickness and no more diarrhoea.”

The inquest heard Dr Joanne Louise Rudling, who qualified in 1993, joined Abernant in August 2011.

She said her first contact with Ryan was in November 2012.

On December 7, Dr Rudling said the receptionist took a call from Ryan’s mother while she was in reception.

Dr Rudling said: “I decided to speak to Ryan’s mother in reception there and then.

“She also asked if this could be age related, I said it could be but I would have to examine him first.

“The impression I got was Ryan was improving. His mother was concerned about the darkening of his genitalia.”

Ryan’s father said goodnight around 10.15pm and went to bed. At around 11.10pm Mrs Morse could see Ryan had fallen asleep, and went to sleep herself at around 11.30pm.

She said: “I woke up and saw it was 4.10am and then I looked at Ryan and looking at his chest could see he wasn’t breathing.

“I started to do chest compressions, dialled 999, continued chest compressions until the paramedics arrived. They took over. They told me Ryan had died.”

Mr Bowen said: “This is a rare but natural disease, one which apparently GPs will not normally encounter.

“Unfortunately, neither doctor nor parents thought it necessary to refer Ryan to hospital, where the true nature of his illness may have been diagnosed.”

Recording a narrative conclusion, Mr Bowen said Ryan died of natural causes.

He said: “The opportunity to administer life-saving treatment was missed.”

Speaking after the inquest, Ryan’s sister Christina Morse said: “First of all I would like to thank everyone involved with Ryan and Ryan’s case.

“Today, after five long years, the coroner has come to the conclusion that Ryan’s death was due to natural causes and that Ryan’s death was preventable.”

From http://www.walesonline.co.uk/news/wales-news/boy-died-addisons-disease-after-13687355

Massachusetts Hospital Opens New Neurosurgery Program

Please let us know your experiences with this new program!

 

Hallmark Health and Tufts Medical Center have established a new neurosurgery program at Melrose-Wakefield Hospital to bring advanced care and services to the community. Fellowship-trained neurosurgeon Mina G. Safain, MD, has been jointly hired by Hallmark Health and Tufts Medical Center to lead the new program. He will provide care at both Melrose-Wakefield Hospital and Tufts Medical Center.

The neurosurgery program is an example of clinical integration of services between Hallmark Health and Tufts Medical Center since Hallmark Health joined Wellforce as a third founding member this past January. At that time, leaders from the organizations discussed finding ways to bring specialized care traditionally performed at academic medical centers into the community hospital setting for the benefit and convenience of patients.

“Offering neurosurgery provides a service for our patients that few community hospitals can offer,” said Steven Sbardella, MD, chief medical officer at Hallmark Health. “Our clinical relationship with Tufts Medical Center enables us to bring more highly specialized care options to our patients.”

“We are extremely excited to work with the physicians at Melrose-Wakefield Hospital and look forward to increasing the services available to care for patients with neurologic diseases,” said Carl Heilman, MD, neurosurgeon-in-chief at Tufts Medical Center. “Dr. Safain is an exceptionally talented and compassionate neurosurgeon and the perfect person to spearhead the launch of this new program.”

Dr. Safain’s clinical interests include all diseases affecting the brain, spine and peripheral nervous system.  He has specific interests in minimal access procedures for degenerative, infectious and oncologic spine disorders, as well as minimally invasive treatments for brain tumors, including neuro-endoscopy.

“The opportunity to practice in the community is very important to me,” said Dr. Safain. “I look forward to working with the esteemed staff and providers at Melrose-Wakefield Hospital and Lawrence Memorial Hospital and treating the patients in the surrounding communities.”

“Welcoming such a highly-respected neurosurgeon as Mina Safain to our team is a tremendous benefit for our communities and patients across our system including Lawrence Memorial Hospital in Medford and Melrose-Wakefield Hospital,” said Dr. Sbardella.

Dr. Safain, together with Ran Ku, PA, a neurosurgery physician assistant with more than 12 years of experience, will provide neurosurgery coverage and expertise five days a week.

Dr. Safain received his medical degree from Yale University School of Medicine.  He completed his neurosurgery residency at Tufts Medical Center serving as chief resident during his final year.  Dr. Safain also completed fellowship training in pituitary and neuro-endoscopic surgery at Brigham and Women’s Hospital.

Dr. Safain has published and presented nationally on a range of topics related to neurosurgical diseases and minimally invasive treatments for brain tumors.

From https://www.hallmarkhealth.org/Neurosurgery-program-established-at-Melrose-Wakefield-Hospital.html

Crinetics Pharmaceuticals Awarded Two SBIR Grants to Develop New Therapeutics for Congenital Hyperinsulinism and Cushing’s Disease

SAN DIEGO, Sept. 06, 2017 (GLOBE NEWSWIRE) — Crinetics Pharmaceuticals, Inc., a rare disease therapeutics company focused on endocrine disorders and endocrine-related cancers, announced today that it was awarded two new grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) that could total $2.4 million. Both are Small Business Innovation Research (SBIR) grants and include a Fast Track grant for up to $2.1 million and a Phase I grant of $0.3 million, which will be used for the development of Crinetics’ nonpeptide, oral somatostatin agonists for congenital hyperinsulinemia, and the discovery of novel small molecule drugs for Cushing’s disease, respectively.

“We are delighted with the NIH’s continuing support of our programs to develop new drugs for patients with rare endocrine disorders,” said Stephen Betz, Ph. D., Founder and Vice President of Biology of Crinetics. “These awards will enable us to advance our efforts in both hyperinsulinemia and Cushing’s disease, expanding our pipeline to include these diseases with significant unmet medical needs, and bring these treatments to the patients who need them.”

Presently, there are no medical therapies that were specifically developed to treat the life-threatening chronic hypoglycemia precipitated by congenital hyperinsulinism (CHI). The current options for patients are limited to drugs developed for other purposes in the hope that they might help. Despite their poor profiles, these drugs are prescribed because the next line of treatment is typically a partial or full pancreatectomy. Even when successful, patients who undergo the surgery often become diabetic and must actively manage glucose with multiple daily insulin injections for the rest of their lives.

Similarly, first line treatments for Cushing’s disease are surgical and involve removal of either the ACTH-secreting tumor in the pituitary or the adrenal glands themselves. As this is often unsuccessful, contraindicated or delayed, medical therapy for these patients becomes necessary. Current treatment options include inhibitors of steroid synthesis enzymes that can prevent the production of cortisol and improve symptoms, but these treatments also induce a host of unwanted side effects due to the accumulation of other steroid products.

About Congenital Hyperinsulinism (CHI)

Hyperinsulinemic hypoglycemia (HH) is one of the most frequent causes of persistent hypoglycemia in infants and can result in seizures, developmental delays, learning disabilities, and even death. The most severe form of HH is inherited and referred to as CHI. CHI largely results from mutations in key genes in the insulin secretion pathway in the islets of Langerhans in the pancreas.

About Cushing’s Disease

Clinical signs of Cushing’s syndrome include growth of fat pads (collarbone, back of neck, face and trunk), excessive sweating, dilation of capillaries, thinning of the skin, muscle weakness, hirsutism, depression/anxiety, hypertension, osteoporosis, insulin resistance, hyperglycemia, heart disease, and a range of other metabolic disturbances resulting in high morbidity. If inadequately controlled in its severe forms, Cushing’s syndrome is associated with high mortality. The most common form of Cushing’s syndrome is Cushing’s disease which is caused by microadenomas of pituitary corticotropic cells that secrete excess adrenocorticotropic hormone (ACTH).

About the NIDDK

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. For more information about the NIDDK and its programs, visit www.niddk.nih.gov.

About Crinetics Pharmaceuticals

Crinetics Pharmaceuticals discovers and develops novel therapeutics targeting peptide hormone receptors for the treatment of rare endocrine disorders and endocrine-related cancers. Crinetics was founded by a team of scientists with a proven track record of endocrine drug discovery and development to create important new therapeutic options for endocrinologists and their patients. The company is backed by top life sciences investors, 5AM Ventures, Versant Ventures, and Vivo Capital and is headquartered in San Diego. For more information, please visit www.crinetics.com.

More: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=241628#.WbFJGNN97-Y

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