Treating Chronic Opioid Users? Endos, You're On Your Own

Richard M. Plotzker, MD

During the last election season, a candidate for the state legislature stood in a public place, shaking hands as he campaigned for votes. I asked him what made his positions unique. He wanted to bring more jobs to our state, he said, and to address the growing number of adverse events from opioid use in our state. He was unable to tell me which of the other four candidates wanted fewer jobs and more narcotic misadventures. Thus, even our highly polarized United States Congress can agree that this widespread scourge could use more public resources.

Narcotic use—for widely accepted analgesia of severe acute and chronic pain, as well as medical care at the fringes or self-directed abuse—has been around for a very long time. History records the Opium Wars in Asia in the 19th century. The dangers of illicit narcotics have been part of the American public school curriculum forever, either through experts speaking at school assemblies or as part of the mandated health class curriculum that I remember from my high school years.

The Evolution of Our Opioid Crisis

Heroin use has waxed and waned periodically, with surges among inner-city residents 50 years ago, another surge among returning Vietnam veterans 10 years later, and renewed attention when AIDS became prevalent among IV drug users. Physicians mostly did damage control, running detoxification or methadone maintenance programs, or trying to reverse endocarditis, HIV infection, or other complications of IV injection.

As medical students, our psychiatry rotations usually covered the psychiatric consequences of addiction. In our anesthesiology electives, we watched the senior anesthesiologist include a narcotic in the protocol, then reverse it with some naloxone.

As residents, we received a dual message: Someone with renal colic needed pain relief now, someone brought into the emergency department with pinpoint pupils and hypoventilation needed naloxone now. Anyone with chronic intractable pain went to the oncologists or hospice.

By the 1980s, multiple grand rounds speakers promoted the compassionate use of longer-acting products, downplaying the side effects as a reasonable tradeoff for better quality of life for a terminally ill patient. A subsequent trend was to offer these medicines to people with chronic pain but indefinite longevity, with financial or other professional demerits pointed at physicians who undertreated pain.

This changed the population of opioid users, from the surreptitious or illegal users of a generation ago (who still exist in considerable numbers) to terminally ill people (involving a consensus to accept untoward effects) to a more active cohort of patients with chronic use, often initiated and sometimes maintained by physicians but also including those who transfer their source of opioids from medically supervised prescription to whatever supply source they can access.

As a result, the physician now has an expanded medical role, moving from suppressing that "fifth vital sign," which contributed to some of the current problem, to the new dilemma of managing the many medical consequences of chronic, sometimes inconsistent opioid use. These complications include but are not limited to infections related to self-administration, constipation, pulmonary suppression, and occasional transient congestive heart failure.

A New Reality for Endocrinologists

Endocrinology does not escape this new reality as patients seek help for less dramatic but persistent short- and long-term endocrinologic sequelae. Several reviews^[1,2] in the endocrinology and pain-control literature may help physicians who have encountered this in some form for a considerable time but only recently have been called upon to make decisions about replacement therapy and preventing long-term consequences of hormonal deficiency.

Most of the focus of these reviews seems to be on the hypothalamic-pituitary-gonadal axis in men. As far back as the 19th century, at least one observer described the men of the opium dens as trending toward an effeminate appearance. Gonadotropin-releasing hormone (GnRH) suppression has been identified as a consistent effect, along with low testosterone levels.

However, GnRH levels tend not to drop to unequivocal deficiencies with opioids. The clinician may see a borderline level, resulting in the unappealing dilemma of having to treat a side effect of one chemical with another chemical. Or someone using the opioid for something other than its analgesic effect, be it addiction or euphoria, will add another drug in the quest for satiety in preference to stopping the offending agent.

This can be a challenging judgment for the clinician, particularly when it puts the doctor and patient in ideologic conflict. For patients who get their opioids from pain centers, endocrine monitoring of testosterone has become more common. But users who obtain drugs from others or get them through intermittent medical care generally do not have ongoing monitoring.

Moreover, that legitimate testosterone prescription, also a controlled substance, may have market value. Selling the testosterone can, in turn, fund more opioids while leaving the intended person without the androgen replacement.

Although the long-term effects of hypogonadism in men can be multisystemic, it is not entirely clear whether narcotics users will acquire some of the known cardiovascular or osseous sequelae of prolonged GnRH suppression.

In premenopausal women, it is easier to make a clinical judgment from symptoms of estrogen deficiency.^[1,2] But again, the lab evaluation is often equivocal. Prolactin stimulation has been described but is usually transient, and thus is unlikely to be the cause of symptoms.

Information Is Lacking

Laboratory studies of adrenal control are often inconclusive, despite their importance when a critically ill user arrives in the emergency department. ACTH may be suppressed. Glycemic control among those with diabetes often deteriorates; opioid use tends to suppress insulin secretion, so glucose levels may rise.

The effect of opioids on eating needs to be taken into account as well. People who secure their opioids from illicit sources will prioritize their resources toward getting drugs, often at the expense of a food purchase. Those with a more secure supply from a medical source may be more likely to overeat, either as a direct effect of the drug or in a quest for satiety in multiple forms, including food.

Although chronic opioid use has been around for a long time, there remains a paucity of information about the effects of opioids on the various hormonal systems; the distinction between supervised and unsupervised users; and when replacement therapy for hormone deficiencies is preferable to eliminating the narcotic analgesic.

As more clinicians in mainstream practice contend with these decisions, more reliable consensus on what to do in certain circumstances will need to emerge. At present, these patients pose a challenge to our best judgment and, sometimes, to our objectivity.

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