Genetic variations associated with hyperplasias, adenomas of adrenal cortex

Beuschlein F. N Engl J Med. 2014;doi:10.1056/NEJMoa1310359.

Genetic variations of the catalytic subunit of cyclic protein kinase A, or PKA, were linked to the development of bilateral adrenal hyperplasias and unilateral cortisol-producing adrenal adenomas. These effects may activate corticotropin-independent Cushing’s syndrome, according to data published in The New England Journal of Medicine.

“The current study suggests that more than one-third of cortisol-producing adenomas associated with overt Cushing’s syndrome have unique somatic mutations in PRKACA (which encodes the main catalytic subunit of PKA), resulting in constitutive PKA activation,” Felix Beuschlein, MD, of the University of Munich, and colleagues wrote.

The researchers performed an exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated their recurrent mutations in candidate genes in 171 additional patients with adrenocortical tumors, according to data.

Somatic mutations in PRKACA were discovered in eight of 10 adenomas. These somatic mutations also were identified in 22 of 59 unilateral adenomas (37%) from patients with overt Cushing’s syndrome; mutations were not detectable in 40 patients with subclinical hypercortisolism or in 82 patients with other adrenal tumors, according to data.

Five of the 35 patients with cortisol-producing hyperplasias appeared to be carriers of the germline duplication of the genomic region on chromosome 19 that includes PRKACA, researchers wrote.

In vitro study data indicated that PKA catalytic subunit genetic mutations impaired inhibition by the PKA regulatory subunit, and cells from patients with germline chromosomal gains appeared to increase the protein levels of the subunit.

“Because PRKACA mediates most of the effects of inactivating PRKAR1A mutations and because mutations of PRKAR1 are associated with a variety of tumors in humans and mice, we would speculate that somatic PRKACA defects might also play a role in other forms of endocrine and nonendocrine tumors,” researchers wrote.

Disclosure: Beuschlein reports financial ties with the European Community, HRA Pharma, Novartis, Viropharma, and Wilhelm-Sander Stiftung.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B22954d9a-0fc9-4e80-b80a-d74bbdfea1a9%7D/genetic-variations-associated-with-hyperplasias-adenomas-of-adrenal-cortex

Suspected case of Cushing’s Syndrome with history of taking medicines prescribed by registered Chinese medicine practitioner

The Department of Health (DH) today (February 18) alerted clients who have consulted a registered Chinese medicine practitioner (CMP) Mr Chan Kong-kin (CMP Chan), practising at G/F, No.25, Leung Tin Village in Tuen Mun, should consult health-care professionals for advice if they have been supplied with medicines suspected to be Western medicines.

The appeal followed the DH’s investigation into two public complaints. The first complaint involved a 23-year-old woman who consulted CMP Chan for management of eczema. She was given a type of green pills, two types of yellow pills and a type of red-yellow capsules for treatment of her disease for about one year.

She developed round face and increased facial hair which are features compatible with Cushing’s syndrome and steroid overdose can cause the syndrome. The patient was admitted to a public hospital on February 5 for investigation and was discharged on February 7.

The second complaint involved a 24-year-old woman who was recommended by the first complainant to consult CMP Chan for management of allergic rhinitis and eczema. She was given similar medicines as those for the first complainant for three days.

Her condition was stable.

Today, chemical analysis by the Government Laboratory on the patients’ drug samples showed that Western medicine Dexamethasone was detected in the red-yellow capsule.

Dexamethasone is a potent steroid. Taking dexamethasone for a long time, especially when in substantial dosage, can cause side effects such as moon face, high blood pressure, high blood sugar, muscle atrophy, peptic ulcer and even osteoporosis.

DH has set up a hotline 2125 1133 for public enquiries related to the medicines prescribed by the CMP.

It will operate from 9am to 9pm, Monday to Friday.

“Preliminary investigation by the DH revealed that pills and capsules were found in the CMP’s premises and all have been seized for further investigation,” the spokesman said.

“In December 31, 2012, the DH announced that CMP Chan was found in possession of Part I poisons and unregistered pharmaceutical products in the same clinic which also involved medicines with steroid. The DH subsequently took enforcement action and the relevant legal proceeding is in progress.

The case has also been referred to the Chinese Medicine Council of Hong Kong for follow-up action,” the spokesman added

“On completion of our investigation, the DH will seek advice from the Department of Justice regarding possible contravention of the Pharmacy and Poisons Ordinance (Cap 138) for the illegal sale or possession of Part I poisons. According to the Ordinance, the maximum penalty for each offence is a fine of $100,000 and two years’ imprisonment. Besides, the DH will also refer this case to the Chinese Medicine Council of Hong Kong for possible disciplinary action”, the spokesman remarked.

People who have been supplied with medicines by the concerned CMP and are in doubt should consult health-care professionals as soon as possible.

They should submit the medicines to the Chinese Medicine Division of DH at 16/F, AIA Kowloon Tower, Landmark East, 100 How Ming Street, Kwun Tong, during office hours for disposal.

Source: HKSAR Government

From http://7thspace.com/headlines/453015/suspected_case_of_cushings_syndrome_with_history_of_taking_medicines_prescribed_by_registered_chinese_medicine_practitioner.html

Polycystic ovarian syndrome and Cushing’s syndrome: A persistent diagnostic quandary

European Journal of Obstetrics & Gynecology and Reproductive Biology, 02/10/2014  Clinical Article

Brzana J, et al. – This study aims to retrospectively review institutional records of female patients of reproductive age with Cushing’s disease (CD) and determine if and how many had been previously diagnosed as having solely PCOS. To determine whether clinical patterns might be useful in identifying appropriate candidates for hypercortisolism screening in women suspected of PCOS. Prolonged exposure to hypercortisolism has been linked with increased mortality and morbidity. Tests for hypercortisolism in all the PCOS cases authors report led to an appropriate CD diagnosis. Future research should focus on when and which (if not all) women with suspected PCOS should be tested for hypercortisolism.

Methods

  • The study included 50 patients with pathologically proven CD at Oregon Health & Science University, Northwest Pituitary Center between 2006 and 2011.
  • Physical, clinical, and biochemical features for hypercortisolism were compared.

Results

  • Of 50 patients with pathologically proven CD, 26 were women of reproductive age.
  • Of these, half had previously been diagnosed with and treated initially solely for PCOS.
  • Hirsutism and menstrual abnormalities were more common in the group with an initial PCOS diagnosis than in the group with an initial CD diagnosis.

From http://www.mdlinx.com/endocrinology/newsl-article.cfm/5055779/ZZ4747461521296427210947/?news_id=2364&newsdt=021014&subspec_id=1509&utm_source=Focus-On&utm_medium=newsletter&utm_content=Top-New-Article&utm_campaign=article-section

Botch-up Costs Doctor an Adrenal Gland

Chennai, India: The state consumer forum has asked a Coimbatore hospital to pay 15 lakh to a doctor whose adrenal gland was surgically removed after a botched-up diagnosis.

In May 2006, A Indumathi, an ophthalmologist, started showing symptoms like rapid weight gain, hypertension, joint pain, puffiness of face and fatigue. She approached Kovai Medical Centre & Hospital in Coimbatore, where the consultant endocrinologist conducted various tests. Her condition was diagnosed as Cushing’s syndrome, a hormonal disorder, and she was advised to undergo surgery for removal of the left adrenal gland.

On September 18, she was operated on. However, the symptoms persisted and the doctor told her it would take some more time to get relief. She waited three more months, but when her condition worsened, she approached the doctor again. He asked her to undergo another surgery for removing her right adrenal gland.

Not willing to take a chance, Indumathi approached Christian Medical College, Vellore, in December, where doctors told her she was suffering from Cushing’s disease, not syndrome. After a month of treatment, she recovered.

She then approached the state commission saying she was misdiagnosed and because of the wrong surgery, she has to regularly go for blood tests for the rest of her life and could develop life-threatening complications. She said she also incurred medical expense of around 5 lakh and had to leave her medical practice for six months.

Denying the charges, the hospital said tests conducted on her showed she was suffering from Cushing’s syndrome. She, being a doctor, was aware of the test reports and gave consent for surgery, it said.

The state consumer disputes redressal commission bench comprising its president Justice(rtd )RRegupati and judicial member J Jayaram, in a recent order, said after a wrong diagnosis and surgery, the hospital should have been more diligent in reassessment but instead suggested removing the right adrenal gland. The bench said the hospital wrongly diagnosed her and removed “a precious, healthy adrenal gland.”

Stating it was a case of “gross negligence and deficiency in service,” the bench asked the hospital and two doctors to pay Indumathi 4 lakh towards medical and travelling expense, 1 lakh for loss of professional income and 10 lakh for “lifelong mental agony.”

From http://timesofindia.indiatimes.com/city/chennai/Botch-up-costs-doctor-a-gland-hospital-fined-Rs-15-lakh/articleshow/29925290.cms

Dr Friedman: Meeting on Thyroid and Hormonal Problems

friedman

Dr. Theodore Friedman will host a free meeting on thyroid and hormonal problems on Sunday February 16 from 7-8 PM PST at Anshe Emes synagogue-1490 S. Robertson Blvd., Los Angeles, CA 90035.

The meeting will be videoconferenced to those who cannot make it in person.

To sign up for the videoconference, email mail@goodhormonehealth.com by February 14.

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