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ENDO: Chronic Opioid Therapy Risks Hypopituitarism

From MedPage Today:

Chronic opioid therapy significantly increases the risk of multiple hormonal deficiencies that warrant evaluation, according to data from small retrospective study.

Hypogonadotrophic hypogonadism topped the list, occurring in 16 of 25 patients, Murray Gordon, MD, of Allegheny General Hospital in Pittsburgh, reported at the Endocrine Society meeting.

Ten patients each had growth hormone deficiency and adrenal insufficiency. On average, the 25 patients had 1.68 disorders associated with hypopituitarism.

About half of the patients had combined deficiencies.

"Patients treated with chronic opioid therapy should be thoroughly evaluated for hypothalamic-pituitary dysfunction," said Dr. Gordon. "Larger prospective studies are required to confirm these findings. The effects of treatments need to be assessed in patients with hypopituitarism associated with chronic use of opioids."

Though infrequently documented in medical literature, isolated reports of adverse endocrine effects from chronic opioid use date back more than a century, said Dr. Gordon.

Opioids' known effects on endocrine pathways include suppression of gonadotropin-releasing hormone, suppression of adrenocorticotropic hormone, and suppression of growth hormone.

However, little information has accumulated regarding the effects of chronic opioid use on hypothalamic-pituitary function.

To examine the issue, Dr. Gordon and colleagues retrospectively reviewed medical records of chronic opioid users referred for assessment of hypothalamic-pituitary function.

The study population comprised 14 men and 11 women, all of whom had received opioids for more than six months.

The forms of chronic opioid therapy consisted of fentanyl patch for seven patients, hydrocodone for five, oxycodone (Oxycontin) for four, sustained-release morphine and methadone for three patients each, an intrathecal morphine pump for two, and hydromorphone for one.

All the patients underwent dynamic pituitary testing and measurement of baseline pituitary function.

Hypogonadotrophic hypogonadism was defined as low testosterone or estradiol with inappropriately nonelevated gonadotropins.

Ten men and six women met the criteria for the condition. All of the men had low testosterone levels and low gonadotropin levels.

All of the women had low estradiol levels and either low or low-normal gonadotropins. Three of the six were premenopausal, and all six were amenorrheic.

The investigators defined adrenal insufficiency as low levels of cortisol and adrenocorticotropic hormone (ACTH) or a low stimulated peak cortisol level.

The 10 patients with adrenal insufficiency had lower cortisol levels (P<0.007), basal ACTH levels (P<0.001), and stimulated peak cortisol levels (P<0.03) compared with patients who had normal adrenal function.

Growth hormone deficiency was defined as a low insulin-like growth factor-1 (IGF-1) or a low stimulated peak growth hormone level.

Patients with the deficiency had significantly lower IGF-1 levels (P<0.007) and a significantly lower peak stimulated growth hormone level (P<0.001).

All of the patients had either a peak hormone level <3 ng/mL or a peak stimulated hormone level <5 ng/mL in association with low IGF-1 and multiple pituitary deficiencies.

The investigators found no evidence of hypothyroidism in any patient.

MRI scans of 24 of the 25 patients revealed a normal pituitary in 15, six with heterogenous pituitaries, and three with partial empty sella.

There were 9 patients with single deficiencies, and 16 with combined deficiencies. 64% had hypogonadotrophic hypogonadism, 60% had adrenal insufficiency, and 64% had growth hormone deficiency.

Posted: 6/22/2009 12:12:00 PM

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'Magic mint' hallucinogen under fire in U.S.

From USA Today:

Saturnino Allende crouches beside a mountain path and gently puts his fingers around the stem of a plant with rough, tongue-shaped leaves.

"This is it," he says about the powerful hallucinogen Salvia divinorum, known as "magic mint." In just a few years, it has emerged from Mexico's Indian villages into one of the hottest drugs in the USA and a crucial cash crop for poor farmers here.

The good times may be coming to an end, as 11 states have rushed to pass laws that restrict the use of salvia, and the U.S. Drug Enforcement Administration is studying whether it should be banned nationwide.

"There was no legitimate purpose for that herb, and the things it was being used for were potentially harmful," says Thom Collier, a former state representative who wrote the Ohio law that outlawed salvia in April. "We thought it would be better to deter this sooner than later."

A ban in Nebraska takes effect in September. California and Maine prohibit selling salvia to minors, and Louisiana and Tennessee limit it to animal consumption, as in scientific research. Ten countries ban salvia, and six others have restrictions on selling it, according to the Salvia divinorum Research and Information Center, a website about salvia.

Wholesalers are already making fewer trips to Mexico's Sierra Mazateca as the legal markets dry up. Carlos Campos, president of Aztecas Plants, says his company has a warehouse full of salvia in the Mexican city of Orizaba. He told farmers who grow the crop to cut production.

"This is an important part of their economy," Campos says. "These legal issues really hurt."

The United States and Mexico don't keep figures on salvia sales, but Campos said business was booming until just recently. In 2008, he exported 8 tons of salvia leaves to the U.S. and Europe, up from 550 pounds in 2002.

Videos on websites such as YouTube showing users laughing hysterically after a few puffs helped spur salvia's popularity. A 2008 report by the U.S. Department of Health and Human Services said 1.8 million Americans have used the herb, and 756,000 had used it the previous year.

On a recent afternoon, Steve Pollard, owner of Arena Ethnobotanicals, an importer based in Britain and San Diego, and Campos handed out roasted chicken, tortillas and beer to about 50 Mazatecs who had hiked two hours through the mountains to sell their salvia leaves.

By mid-afternoon Campos' truck was filled with black garbage bags containing 1,185 pounds of dried salvia leaf.

Before salvia, this region about 170 miles southeast of Mexico City was better known for its psychedelic mushrooms. Albert Hoffman, the inventor of LSD, came here to try them with the Mazatec medicine men. So did the Beatles' George Harrison.

The magic mushrooms, salvia leaves and psychedelic seeds of morning glories make up the Mazatec medicine man's "tool kit" to help diagnose illnesses, says Jose Luis Díaz, an expert on traditional psychedelics at the National Autonomous University of Mexico.

The local healers grind the leaves into a drink and feed it to a patient. "It's done in silence, in a dark place, to avoid any outside stimulus that might interfere with the experience," Díaz says.

The hallucinations can be intensely emotional and include feelings of floating above the body or having visions, Díaz says. Most foreigners smoke the leaf, says John Boyd, CEO of Arena Ethnobotanicals. "Head shops" and Internet sites sell leaves fortified with salvia extract, making them five to 35 times stronger.

"It's not a party drug, and it's not a substitute for marijuana," Boyd says. "Most people try it once, put it in a drawer and never touch it again."

Many farmers here say they don't really understand the legal issues over salvia. Federico Basilio looks confused when a reporter refers to the leaves as an enervante, or drug.

"I don't really know how they use (salvia) up there," Basilio says of the USA. "But for us, it's been a good crop."

Posted: 6/22/2009 9:12:00 AM

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