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.