Cushing’s appears to begin its cardiovascular effects during childhood

– Cushing’s disease may begin to exert its harmful cardiovascular effects quite early, a small pediatric study has found.

Children as young as 6 years old with the disorder already may show signs of cardiovascular remodeling, with stiffer aortas and higher aortic pulse-wave velocity than do age-matched controls, Hailey Blain and Maya Lodish, MD, said at the annual meeting of the Endocrine Society.

“The study, which included 10 patients, is small, but we continue to add new patients,” said Dr. Lodish, director of the pediatric endocrinology fellowship program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Ten more children are being added to the cohort now, and she and Ms. Blain, a former research fellow at NIH, intend to grow the group and follow patients longitudinally.

Cushing’s disease has long been linked with increased cardiovascular risk in adults, but the study by Dr. Lodish and Ms. Blain is one of the first to examine the link in children. Their findings suggest that early cardiovascular risk factor management should be a routine part of these patients’ care, Dr. Lodish said in an interview.

“It’s very important to make sure that there is recognition of the cardiovascular risk factors that go along with this disease. Elevated levels of cholesterol, hypertension, and other risk factors that are in these individuals should be ameliorated as soon as possible from an early age and, most importantly, physicians should be diagnosing and treating children early, once they are identified as having Cushing’s disease. And, given that we are not sure whether these changes are reversible, we need to make sure these children are followed very closely.”

Indeed, Dr. Lodish has reason to believe that the changes may be long lasting or even permanent.

“We are looking at these children longitudinally and have 3-year data on some patients already. We want to see if they return to normal pulse wave velocity after surgical cure, or whether this is permanent remodeling. There is an implication already that it may be in a subset of individuals,” she said, citing her own 2009 study on hypertension in pediatric Cushing’s patients. “We looked at blood pressure at presentation, after surgical cure, and 1 year later. A significant portion of the kids still had hypertension at 1 year. This leads us to wonder if they will continue to be at risk for cardiovascular morbidity as adults.”

Ms. Blaine, an undergraduate at Bowdoin College, Brunswick, Maine, worked on the study during a summer internship with Dr. Lodish and presented its results in a poster forum during meeting. She examined two indicators of cardiovascular remodeling – aortic pulse wave velocity and aortic distensibility – in 10 patients who were a mean of 13 years old. All of the children came to NIH for diagnosis and treatment of Cushing’s; as part of that, all underwent a cardiac MRI.

The patients had a mean 2.5-year history of Cushing’s disease Their mean midnight cortisol level was 18.8 mcg/dL and mean plasma adrenocorticotropic hormone level, 77.3 pg/mL. Five patients were taking antihypertensive medications. Low- and high-density lipoprotein levels were acceptable in all patients.

The cardiovascular measures were compared to an age-matched historical control group. In this comparison, patients had significantly higher pulse wave velocity compared with controls (mean 4 vs. 3.4 m/s). Pulse wave velocity positively correlated with both midnight plasma cortisol and 24-hour urinary free cortisol collections. In the three patients with long-term follow-up after surgical cure of Cushing’s, the pulse wave velocity did not improve, either at 6 months or 1 year after surgery. This finding echoes those of Dr. Lodish’s 2009 paper, suggesting that once cardiovascular remodeling sets in, the changes may be long lasting.

“The link between Cushing’s and cardiovascular remodeling is related to the other things that go along with the disease,” Dr. Lodish said. “The hypertension, the adiposity, and the high cholesterol all may contribute to arterial rigidity. It’s also thought to be due to an increase in connective tissue. The bioelastic function of the aorta may be affected by having Cushing’s.”

That connection also suggests that certain antihypertensives may be more beneficial to patients with Cushing’s disease, she added. “It might have an implication in what blood pressure drug you use. Angiotensin-converting enzyme inhibitors increase vascular distensibility and inhibit collagen formation and fibrosis. It is a pilot study and needs longitudinal follow up and additional patient accrual, however, finding signs of cardiovascular remodeling in young children with Cushing’s is intriguing and deserves further study.”

Neither Ms. Blain nor Dr. Lodish had any financial disclosures.

Reasons You Have Flab Around Your Abdomen

Some diseases and conditions could be responsible for your abdominal fat.
Mita Majumdar | Updated: April 24, 2017 6:15 pm

Visceral fat or unhealthy belly fat that surrounds the liver and other organs in the abdomen puts you at risk for serious health problems, such as, metabolic syndrome, heart disease, and type 2 diabetes. But, what causes your pot belly or beer fat in the first place? The most obvious answers you will get is – ‘You are not exercising enough’, or, ‘you are eating too much of fatty foods or sugary foods’, or ‘you are not eating the right foods’, or ultimately, ‘It’s genetics! You got it from your parents’. All of these reasons are true, of course. However, some diseases/ disorders and conditions, too, could be responsible for your abdominal fat and these have nothing to do with not exercising or not eating right. Following are some of these disorders.

Cushing’s Syndrome

Cushing’s syndrome, also called hypercortisolism, is an endocrine disorder that occurs when your body is exposed to high cortisol levels over a long period of time. It is a treatable disorder, however, if it is chronic, the symptoms can last lifelong.

Symptoms: Symptoms vary according to the severity of the disorder. The characteristic symptoms include –

  • Fatty tissue deposits in the midsection
  • Fatty deposits in the upper back, especially between the shoulders, so that it resembles a hump
  • Puffy face
  • Violaceous stretch marks (pink or purple) on the arms, breast, stomach, and thighs that are more than 1 cm wide. [1]
  • Easy bruising
  • Fatigue
  • Hirsutism and irregularity in menstruation in women
  • Loss of libido and erectile dysfunction in men
  • Cognitive dysfunction, depression, unpredictable emotional outbursts, irritability is present in 70-85 percent of people with Cushing’s syndrome.[1]

Causes:

  • Overuse of corticosteroids
  • Overproduction of cortisol by the adrenal glands

Management:

  • Surgery is the first line of treatment for Cushing’s syndrome.
  • Medication include: [2]

a.Pituitary gland directed therapy

b.Adrenal-blocking drugs

c.Glucocorticoid receptor-antagonizing drugs

  • Pituitary radiotherapy

Addison’s disease

Addison’s disease, also called adrenal insufficiency, is a disorder where your adrenal glands produce insufficient hormones, especially, glucocorticoids including cortisol and aldosterone. It is a life-threatening disease that can affect anyone irrespective of their gender or age.

How do glucocorticoids influence abdominal fats? Glucocorticoids including cortisol convert the fats into energy in the liver. They also help your body respond to stress. When sufficient amount of glucocorticoids are not produced by the adrenal glands, the fats accumulate in the abdominal area, and you see it as flab around your middle.

Symptoms:

  • Hyperpigmentation
  • Extreme fatigue
  • Low blood sugar and low blood pressure
  • Salt craving as one of the functions of adrenal glands is to maintain the sodium-potassium balance in the body
  • Nausea, vomiting, abdominal pain
  • Weight loss but gain in abdominal fat

Causes:

  • Insufficient production of adrenal cortex hormones
  • Stopping of prescribed corticosteroids
  • Tuberculosis and other infections of adrenal glands
  • Spread of cancer to the adrenal glands

Management:

  • Oral corticosteroids or corticosteroid injections
  • Intravenous injections of hydrocortisone, saline solution, and dextrose in case of Addisonian crisis

Stress

Chronic stress is a very big cause of belly fat. When you are exposed to stress, a chain reaction starts in the body because of the dysregulation of HPA axis of the neuroendocrine system. HPA axis is a complex interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus produces a corticotropin releasing hormone (CRH) and vasopressin. These together stimulate the secretion of adrenocorticotropic hormone (ACTH). ACTH is transported by the blood to the adrenal glands, which then produces corticosteroids, mainly, cortisol from cholesterol. One of the functions of cortisol is to signal the body to store fat, and specifically, the fat storage occurs in the abdominal area, where the cortisol receptors are greater. Researchers have found that stress causes hyperactivation of HPA axis, leading to accumulation of fat tissue, especially in the abdomen region.

So, the more and longer you are stressed (or if you are chronically stressed), chances are that you will be carrying more belly fat!

Ascites

Ascites is the buildup of fluid in the abdominal space. Ascites usually occurs in people with cancer, and it is then called malignant ascites. Onset of ascites is generally the terminal phase in cancer. Ascites also occurs in patients with liver cirrhosis, kidney failure, or heart disease.

Symptoms:

The first sign of ascites is an increase in abdominal girth accompanied by weight gain. [4] Although it looks like it is belly fat, it is actually the fluid that causes the bulging.

Other symptoms include:

  • Shortness of breath
  • Nausea and vomiting
  • Swelling in the feet and ankle
  • Decreased appetite, sense of fullness, bloating
  • Fatigue
  • Haemorrhoids

Management:

If the ascites is not causing any discomfort, it may not require any treatment. Treatment of ascites can have many side effects. Talk to your doctor before you go in for management/ treatment.

Abdominal hernia

Abdominal hernia is a swelling or a bulge in the abdominal area where an organ or fatty tissue pushes through a weak spot in the abdominal wall. The abdominal wall is made up of tough connective tissue and tendons that stretch from the ribs to the groin. Depending on the position of the weakness in your abdominal wall, the hernia can be inguinal (groin), femoral (upper thigh), umbilical (belly button), hiatal (upper stomach), or even incisional. Incisional hernia can occur when the intestine pushes through a weak spot at the site of abdominal surgery.

Symptoms:

  • Visible bulge that may or may not cause discomfort
  • Feeling of heaviness in the abdomen
  • Sharp pain when you strain or lift objects

Causes:

  • Constipation and diarrhoea
  • Persistent coughing and sneezing
  • Straining or suddenly lifting a heavy object

Management:

  • Umbilical hernia, common in young children, mostly resolves by itself as the abdominal muscles get stronger.
  • Other abdominal hernia normally do not resolve by themselves. Doctors suggest waiting and watching.
  • If treatment is required, surgery is the only option. Surgery involves pushing the hernia back into the abdomen and repairing the abdominal wall.

Menopause

Menopause is certainly not a disease or a disorder. It is the time in a woman’s life when she stops menstruating and cannot become pregnant because her ovaries stop producing the required amounts of hormones oestrogen and progesterone. A woman reaches menopause when she has not had her periods for 12 months.

Symptoms:

  • Hot flashes and/ or night sweats
  • Vaginal dryness
  • Mood swings
  • Sleep disturbances

It is very common to gain belly fat during menopause. This is because of the low oestrogen levels. Oestrogen seems to influence the distribution of fat in the body, in a way that the fat is redistributed from the hips, buttocks, and thighs to the belly. However, a study published in the journal Metabolism reported that though women did significantly gain belly fat, especially deep inside the belly, relative fat distribution is not significantly different after menopause. [5] But the fact remains that women do gain flab in the abdomen after menopause.

Belly fat can be seriously harmful. If your belly fat is not because of the above-mentioned conditions, you can lose it by adopting a healthy lifestyle that includes sleeping enough, exercising regularly, eating right, and reducing stress.

Reference

  1. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clinical Epidemiology. 2015;7:281-293. doi:10.2147/CLEP.S44336.
  1. Feelders RA, Hofland LJ. Medical treatment of Cushing’s disease. J Clin Endocrinol Metab. 2013;98:425–438.
  1. Kyrou I, Chrousos GP, Tsigos C. Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci. 2006 Nov;1083:77-110.
  1. Sinicrope FA. Ascites. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.
  2. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism. 2009 Mar;58(3):311-5. doi: 10.1016/j.metabol.2008.09.030.

Adapted from http://www.thehealthsite.com/diseases-conditions/reasons-you-have-flab-around-your-abdomen-f0417/

 

What You Should Know About Pituitary Tumors

Ask the Experts

Igor Kravets, MD
Endocrinologist, Assistant Professor Division of Endocrinology,
Diabetes and Metabolism
Stony Brook Medicine
Raphael Davis, MD
Neurosurgeon, Professor and Chair Department of Neurosurgery
Co-Director, Stony Brook University Neurosciences Institute

 

Where do pituitary tumors form?
Dr. Kravets: A pituitary tumor is an abnormal growth of cells in the pituitary gland, which is a small, pea-sized organ located in the center of the brain, behind the nose and eyes. The pituitary is a “master gland” of the body; it produces many hormones that control other endocrine glands and certain functions of the body.
Are they mostly benign or malignant?
Dr. Davis: Most pituitary tumors are benign (non-cancerous). However, because of the location of the pituitary gland at the base of the skull, pituitary tumors can cause problems since they grow upward. Eventually some will press against the area where the optic nerves intersect, causing vision problems. They can also cause hormonal imbalance.What causes pituitary tumors?
Dr. Kravets: No one knows for sure what causes pituitary tumors. About one to five percent of pituitary tumors occur within families. Most are not inherited, however there are certain, rare, inherited conditions such as multiple endocrine neoplasia type 1 (MEN 1), that carry a higher risk of pituitary tumors.

What are the different types of pituitary tumors?
Dr. Davis: Adenomas are benign tumors that develop on the pituitary gland behind the eyes. These tumors can change levels in hormone production or cause vision loss. Craniopharyngiomas are benign tumors that develop at the base of the brain where it meets the pituitary gland. They commonly affect children 5 to 10 years of age, but adults can sometimes be affected in their 50s and 60s.

What are the symptoms?
Dr. Kravets: Symptoms vary depending on the type and size of a pituitary tumor but not all pituitary tumors cause symptoms. Many pituitary tumors are not diagnosed until symptoms appear. Some pituitary tumors are found incidentally on brain imaging obtained for a reason unrelated to the pituitary. Certain symptoms may develop when pituitary tumors grow so large that they exert pressure on surrounding structures.

Such symptoms include:
• Changes in vision (particularly loss of peripheral/outer edge vision)
• Headache

Other symptoms are related to either deficiency or excessive production of certain hormones. Common symptoms caused by such hormonal disturbances include:
• Menstrual cycle changes (irregular or lack of menstrual periods
• Erectile dysfunction or loss of sex drive
• Weight changes
• Production of breast milk by a woman who has not given birth
• Accelerated or stunted growth in a child or teenager
• Growth of the hands, feet, forehead and jaw in adults
• Development of a round face, a hump between the shoulders or both

How is a pituitary tumor diagnosed?
Dr. Kravets: An endocrinologist will ask you about the symptoms you are experiencing, and about your personal and family health history. He or she will perform a physical exam and order tests of your blood and urine. A magnetic resonance imaging (MRI) scan or computerized tomography (CT or CAT) scan may also be ordered to obtain detailed images of the brain and the pituitary gland. In rare instances, a biopsy (surgical procedure to remove a small sample of the tumor for examination) is required.

What treatments are available?
Dr. Davis: Treatments may include surgery, radiation therapy or medication. Transsphenoidal surgery is surgery performed through the nose and sphenoid sinus (located in the very back part of the nose, just beneath the base of the brain) to remove a pituitary tumor. It can be performed with an endoscope, microscope or both and is a team effort between neurosurgeons and ear, nose and throat (otolaryngology/ENT) surgeons. Radiation therapy uses high-energy x-rays to kill the tumor cells and is recommended when surgery is not an option, if the pituitary tumor remains, or if the tumor causes symptoms that are not relieved by medicine.

Why choose Stony Brook?
Dr. Kravets: Our Pituitary Care Center provides access to all of the coordinated expert care you need in one location, close to home — which can make the course of your treatment easier. Our team includes specialists from endocrinology, neurosurgery, otolaryngology (ENT), radiation oncology, neuropathology, neuroradiology, neuro-ophthalmology, and patient education and support.

To make an appointment with one of our Pituitary Care Center endocrinologists, call
(631) 444-0580. To make an appointment with one of our Pituitary Care Center neurosurgeons,
call (631) 444-1213. To learn more, visit stonybrookmedicine.edu/pituitary.

All health and health-related information contained in this article is intended to be general and/or educational in nature and should not be used as a substitute for a visit with a healthcare professional for help, diagnosis, guidance, and treatment. The information is intended to offer only general information for individuals to discuss with their healthcare provider. It is not intended to constitute a medical diagnosis or treatment or endorsement of any particular test, treatment, procedure, service, etc. Reliance on information provided is at the user’s risk. Your healthcare provider should be consulted regarding matters concerning the medical condition, treatment, and needs of you and your family. Stony Brook University/SUNY is an affirmative action, equal opportunity educator and employer.

From https://www.stonybrookmedicine.edu/patientcare/pituitarytumors

Diagnosis and Treatment of Pituitary Adenomas

A Review
JAMA. 2017;317(5):516-524. doi:10.1001/jama.2016.19699

Importance  Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important.

Observations  Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (≥10 mm).

Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy. Prolactinomas account for 32% to 66% of adenomas and present with amenorrhea, loss of libido, galactorrhea, and infertility in women and loss of libido, erectile dysfunction, and infertility in men; they are generally treated with the dopamine agonists cabergoline and bromocriptine.

Growth hormone–secreting tumors account for 8% to 16% of tumors and usually present with enlargement of the lips, tongue, nose, hands, and feet and are diagnosed by elevated insulin-like growth factor 1 levels and growth hormone levels; initial treatment is surgical. Medical therapy with somatostatin analogues, cabergoline, and pegvisomant is often also needed.

Adrenocorticotropic hormone (ACTH)–secreting tumors account for 2% to 6% of adenomas and are associated with obesity, hypertension, diabetes, and other morbidity. Measurement of a late-night salivary cortisol level is the best screening test but petrosal sinus sampling for ACTH may be necessary to distinguish a pituitary from an ectopic source.

The primary treatment of Cushing disease (hypercortisolism due to ACTH-producing adenomas, which is the cause in approximately 65% of the cases of hypercortisolism) is adenoma resection and medical therapies including ketoconazole, mifepristone, and pasireotide.

Hyperthyroidism due to thyroid-stimulating hormone–secreting tumors accounts for 1% of tumors and is treated with surgery and somatostatin analogues if not surgically cured. Clinically nonfunctioning adenomas account for 15% to 54% of adenomas and present with mass effects; surgery is generally required, although incidentally found tumors can be followed if they are asymptomatic.

Conclusions and Relevance  Patients with pituitary adenomas should be identified at an early stage so that effective treatment can be implemented. For prolactinomas, initial therapy is generally dopamine agonists. For all other pituitary adenomas, initial therapy is generally transsphenoidal surgery with medical therapy being reserved for those not cured by surgery.

Read the full text here: http://jamanetwork.com/journals/jama/article-abstract/2600472

Topical Ocular Glucocorticoid Leads to Cushing’s Syndrome in 9-Year-Old

In a case report published online January 19 in Pediatrics, iatrogenic Cushing’s syndrome (CS) is described in a 9-year-old girl who received topical ocular glucocorticoid (GC) treatment for bilateral iridocyclitis.

Daisuke Fukuhara, MD, PhD, from the Kyorin University School of Medicine in Mitaka, Japan, and colleagues present the case of a 9-year-old girl suffering from idiopathic uveitis. She arrived at the ophthalmology department with a complaint of painful eyes, and was diagnosed with bilateral iridocyclitis and started on betamethasone sodium phosphate eye drop treatment.

The authors note that the patient was referred to the pediatric department with stunted growth, truncal obesity, purple skin striae, buffalo hump, and moon face six months after initiation of topical ocular GC treatment. She was diagnosed with iatrogenic CS as her serum cortisol and plasma adrenocorticotropic hormone levels were undetectable. The clinical symptoms of CS were improved after the doses of topical ocular GC were reduced. On genetic analysis, the patient was found to have a single heterozygous nucleotide substitution in the 3′ untranslated region of the NR3C1 gene.

“However, additional investigations are required to determine if our findings can be extrapolated to other patients,” the authors write. “In conclusion, clinicians should be aware that even extremely low doses of topical ocular steroid therapy can cause iatrogenic CS.”

Full Text (subscription or payment may be required)

From http://www.empr.com/news/iatrogenic-cushings-syndrome-topical-ocular-glucocorticoid-iridocyclitis/article/632840/

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