“My feet are killing me!” An unusual presentation of Cushing’s syndrome

Posted on June 19, 2015 by MaryO

Adverse effects of steroid excess on bone metabolism are well established but presentation of Cushing’s syndrome with metabolic bone disease is reported to be uncommon. We describe a case of Cushing’s syndrome presenting with pathological fractures probably present for 8 years before diagnosis.

A 33 year old nurse first sustained spontaneous stress fractures of her metatarsals in 1994, with repeated fractures occurring up to 2002. In 2001 she developed hypertension, acute lumbar back pain and gained weight.

In 2002 she was admitted to hospital with chest/back pain. Lumbar spine X-ray showed new fracture of L3,old fractures of L4/5,with fractured ribs on CXR. Isotope bone scan revealed multiple hot spots. MRI showed collapse of T8 with features consistent with malignant disease. The primary malignancy was sought and a left-sided 1.5 centimetre thyroid nodule detected.

Suspicious cytology prompted thyroid lobectomy revealing follicular variant of papillary carcinoma. T8 biopsy revealed chronic infection with Propionobacteria rather than metastatic carcinoma. Despite antibiotic therapy further spontaneous vertebral fractures developed. Bone densitometry revealed Z scores of minus 2.4 at L2-4, minus 2.5 and 2.9 at the hips.

Referral to our centre prompted investigations for Cushing’s syndrome. Serum potassium was 4.1 millimols per litre, androgens, calcitonin and urinary catecholamines all normal. TSH was suppressed by T4 therapy. Urinary free cortisol values were raised,(563-959 nanomols per 24hours) with loss of diurnal rhythm in cortisol secretion (9am 429-586,midnight 397-431 nanomols per litre)and no suppression on low or high dose dexamethasone. Abdominal CT showed a 3.5 centimetre adrenal mass. These findings were consistent with adrenal dependent Cushing’s syndrome. Risedronate and metyrapone were commenced before adrenalectomy, completion thyroidectomy and ablative radioiodine.
Comment: Cushing’s syndrome may present with spontaneous fractures in both axial and appendicular skeleton in the absence of marked clinical features. This case demonstrates the importance of thorough investigation of unexplained fractures.

LM Albon, JD Rippin & JA Franklyn

From http://www.endocrine-abstracts.org/ea/0005/ea0005p26.htm

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Silibinin from milk thistle seeds as novel, non-invasive treatment strategy for Cushing Disease

Posted on June 4, 2015 by MaryO
Silibinin has an outstanding safety profile in humans and is currently used for the treatment of liver disease and poisoning. Scientists at the Max Planck Institute of Psychiatry in Munich discovered in collaboration with scientists from the Helmholtz Zentrum München in cell cultures, animal models and human tumor tissue that silibinin can be applied to treat Cushing Disease, a rare hormone condition caused by a tumor in the pituitary gland in the brain. The researchers have filed a patent and now plan clinical trials using silibinin as a non-invasive treatment strategy. Thus, in future, patients might not have to undergo brain surgery anymore.
Treatment with silibinin, a constituent of milk thistle seeds, alleviated symptoms of Cushing Disease in cell cultures, animal models and human tumor tissue. In future, patients might not have to undergo brain surgery anymore.

Cushing Disease, not to be confused with Cushing’s Syndrome, is caused by a tumor in the pituitary gland in the brain. The tumor secrets increased amounts of the stress hormone adrenocorticotropin (ACTH) followed by cortisol release from the adrenal glands leading to rapid weight gain, elevated blood pressure and muscular weakness. Patients are prone to osteoporosis and infections and may show cognitive dysfunction or even depression. In 80 to 85 % of the patients, the tumor can be removed by uncomfortable brain surgery. For inoperable cases, there is currently only one targeted therapy approved, which unfortunately causes intense side effects such as hyperglycemia in more than 20 % of the patients.

Scientists around Günter Stalla, endocrinologist at the Max Planck Institute of Psychiatry in Munich, have now discovered in cell cultures, animal models and human tumor tissue that a harmless plant extract can be applied to treat Cushing Disease. “Silibinin is the major active constituent of milk thistle seeds. It has an outstanding safety profile in humans and is already used for the treatment of liver disease and poisoning,” explains Marcelo Paez-Pereda, leading scientist of the current study published in the renowned scientific journal Nature Medicine. After silibinin treatment, tumor cells resumed normal ACTH production, tumor growth slowed down and symptoms of Cushing Disease disappeared in mice.

In 2013, the Max Planck scientists filed a patent on a broad family of chemical and natural compounds, including silibinin, to treat pituitary tumors. Compared to humans, where only 5.5 in 100,000 people worldwide develop Cushing Disease, this condition is very common in several pets. For example, 4 % of dogs and even 7 % of horses suffer from Cushing Disease. Thus, the researchers now plan to test special formulations with a very pure substance and slow release of the active component silibinin in clinical trials.

Silibinin: Mode of action

“We knew that Cushing Disease is caused by the release of too much ACTH. So we asked ourselves what causes this over production and how to stop it,” says Paez-Pereda. In their first experiments, the researchers found tremendously high amounts of the heat shock protein 90 (HSP90) in tumor tissue from patients with Cushing Disease. In normal amounts, HSP90 helps to correctly fold another protein, the glucocorticoid receptor, which in turn inhibits the production of ACTH. “As there are too many HSP90 molecules in the tumor tissue, they stick to the glucocorticoid receptor,” explains Paez-Pereda. “We found that silibinin binds to HSP90 thus allowing glucocorticoid receptor molecules to dissolve from HSP90. With silibinin, we might have discovered a non-invasive treatment strategy not only for the rare Cushing Disease but also for other conditions with the involvement of glucocorticoid receptors, such as lung tumors, acute lymphoblastic leukemia or multiple myeloma,” concludes Paez-Pereda.

From http://www.psych.mpg.de/2034377/PM1507

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HSA issues alert on 2 illegal pain relief products

Posted on June 4, 2015 by MaryO

SINGAPORE: The Health Sciences Authority (HSA) on Wednesday (Jun 3) issued an alert on two illegal health products sold in Singapore, one of which caused a consumer to be hospitalised for adverse reactions.

HSA added that investigations are ongoing and laboratory tests have found undeclared potent medicinal ingredients in the products.

A woman in her 40s has been hospitalised for “delirium (confusion), high blood sugar, electrolyte imbalance in her blood and suspected Cushing’s syndrome (characterised by a round face or ‘moon face’ and upper body obesity within thin limbs)” after consuming an illegal pain relief product, said HSA.

The woman had been consuming the “powder packed in unlabelled pink sachets” for pain relief over a prolonged period of time because she believed it had “miraculous powers”, HSA added. The powder was found to contain the illegal ingredients Chlorpheniramine and Dexamethasone.

The patient had bought the powder from “an auntie who sells powdered medicine” – a woman in her 60s who would personally deliver the products to the addresses provided by the customers, said HSA.

HSA raided the peddler’s home and discovered another illegal health product – black pills labelled “special effect rheumatism pill”. They were found to contain Dexamethasone and Chlorpheniramine, as well as Bromhexine.

Dexamethasone could cause diabetes, high blood pressure, cataracts and Cushing’s syndrome, among other adverse reactions. Chlorpheniramine and Bromhexine could cause symptoms including diarrhoea, nausea and vomiting.

The authority advised members of the public who have purchased or are consuming the products to:

Consult a doctor as soon as possible before stopping usage as sudden discontinuation of steroids without proper medical supervision can cause serious withdrawal symptoms

Avoid buying health products from street peddlers, unknown websites or sellers, or even from well-meaning friends or relatives

Be wary of health products not properly labelled with ingredient information or make exaggerated claims like “instant pain relief”

Seek appropriate medical treatment from a doctor for the management of acute and chronic medical conditions such as arthritis and rheumatism

via HSA issues alert on 2 illegal pain relief products – Channel NewsAsia.

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Cushing’s Syndrome

Posted on May 22, 2015 by MaryO
Prof André Lacroix, MDcorrespondence,  Richard A Feelders, MD, Constantine A Stratakis, MD, Lynnette K Nieman, MD
Published Online: 21 May 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(14)61375-1

Summary

Chronic exposure to excess glucorticoids results in diverse manifestations of Cushing’s syndrome, including debilitating morbidities and increased mortality.

Genetic and molecular mechanisms responsible for excess cortisol secretion by primary adrenal lesions and adrenocorticotropic hormone (ACTH) secretion from corticotroph or ectopic tumours have been identified. New biochemical and imaging diagnostic approaches and progress in surgical and radiotherapy techniques have improved the management of patients.

The therapeutic goal is to normalise tissue exposure to cortisol to reverse increased morbidity and mortality. Optimum treatment consisting of selective and complete resection of the causative tumour is necessay to allow eventual normalisation of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function, and avoidance of tumour recurrence. The development of new drugs offers clinicians several choices to treat patients with residual cortisol excess.

However, for patients affected by this challenging syndrome, the long-term effects and comorbidities associated with hypercortisolism need ongoing care.

Read the entire article (there is a fee of $31.50US) here.

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Enzyme that triggers muscle wasting could be key to REVERSING signs of ageing | Daily Mail Online

Posted on May 21, 2015 by MaryO

Drawing on expertise from both the University of Birmingham and Queen Elizabeth Hospitals Birmingham, they applied their knowledge of Cushing’s syndrome to the new problem (sarcopenia).

Cushing’s is hormonal disorder caused by high levels of cortisol. Patients suffer from the syndrome see marked changes in their body composition.

The effects can be devastating for patients who can develop features such as muscle wasting and weakness, weight gain, thinning of the bones, diabetes, high blood pressure and heart disease.

Dr Hassan-Smith said: ‘Looking at this particular enzyme seemed like an intriguing way forward.

‘We knew how it works in relation to Cushing’s Syndrome, which is characterised by similar symptoms, and thought it would be worthwhile applying what we knew to the ageing population.’

Currently there are no treatments for sarcopenia, the team explained.

But pharmaceutical companies are developing and testing ways to block or switch off the enzyme, with a focus on treatments for conditions including diabetes.

The team is excited about taking the results of their study forward into future research, with one eye on adapting the inhibitors already in development to combat muscle ageing.

Dr Hassan Smith added: ‘The next stage is a “proof of concept” study to look at the effects of these inhibitive pharmaceuticals on muscle function, before opening it up into a clinical trial.

‘It’s an as yet unexplored area that could yield beneficial results for a problem that is becoming more prevalent as our lifespans increase.’

The study was published in the journal of Clinical Endocrinology and Metabolism.

 

via Enzyme that triggers muscle wasting could be key to REVERSING signs of ageing | Daily Mail Online.

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