The 67-year-old woman slipped off her shoes before stepping onto her doctor’s scale. At her home, in Maplewood, N.J., the bathroom scale had documented the same 25-pound weight loss she and her internist now saw. It happened suddenly, over the past few months. Initially she blamed a bout of Covid-19 that she picked up during a trip with friends to Morocco three months earlier. But that seemed unlikely: The illness felt like no more than a bad cold and lasted only one week.
It wasn’t as if she were wasting away, and she rather liked the way she looked at this new weight. Still, she hadn’t been dieting, so it worried her. Just a few weeks earlier, a friend lost weight unintentionally like this and was diagnosed with metastatic cancer.
By the time she got to this appointment with her primary-care doctor, the woman, an emergency-room physician, had already done some investigating. She saw her ob-gyn, who gave her the all-clear. A recent colonoscopy and mammogram were normal. Still, she wanted to hear what her internist, Dr. James Rommer, would make of her unintended weight loss.
Rommer had known the woman for many years. He saw her before her left-knee replacement surgery the previous year; not long afterward, she called to tell him that her blood pressure was high. He started her on a blood-pressure medication and had increased it at each of her follow-up visits.
She didn’t feel sick, the patient told Rommer. She had no nausea, no stomach pain. Her appetite was good. Maybe she was a little more tired than usual, but that could be left over from the holidays, she said.
Her blood pressure was elevated but otherwise her exam was normal. Rommer agreed the weight loss was concerning; patients don’t usually lose weight by accident. He outlined his plan: For the weight loss, he would order some basic lab tests — blood count, chemistries, liver and thyroid studies. And for her new and persistent high blood pressure, he would look for a couple of unusual tumors that can raise blood pressure by putting out excessive cortisol or epinephrine, the fight-or-flight hormones made by the adrenal glands. If all that was normal, he would get a CT scan of her chest, abdomen and pelvis to make sure he wasn’t missing anything.
A Life-Threatening Deficiency
The patient was at the gym the next morning when her phone rang. Rommer’s voice was grave as he explained the unexpected finding from her lab tests. Her liver and kidney results and blood counts had been normal. But her cortisol, which Rommer had thought might be elevated, was practically undetectable. That could be dangerous. He asked if she felt safe to drive.
Cortisol is one of the body’s most powerful stress hormones. It acts on nearly every organ in the body, helping to maintain normal function after episodes of physiological stress such as illness or surgery. When the body is unable to produce adequate amounts of cortisol, recovery from any type of stress can be difficult and sometimes impossible. Deficiencies of the hormone can be life-threatening.
Hearing this unexpected result, the patient’s first thought was that there had been a lab error. She felt fine, she told Rommer. Patients with adrenal insufficiency, as it’s called, usually notice muscle weakness and wasting. They have nausea and vomiting. She had no such symptoms and was in the middle of her usual workout. Rommer insisted that she needed to be seen immediately. This was an emergency.
The patient showered and changed out of her sweaty gym clothes and arranged to see an endocrinologist, Dr. Marie Nevin, who worked with a close friend and was located in nearby Morristown, N.J.
Nevin greeted the patient cheerfully. First order of business, she told the patient, was to double check the abnormal lab result. Again the woman’s cortisol level was dangerously low. Another hormone, called adrenocorticotropic hormone (ACTH), which triggers the release of cortisol, was also low. They would have to figure out why these two hormones were so out of whack, and the patient would have to be started on daily doses of hydrocortisone to replace the cortisol her body wasn’t making in adequate amounts.
But before starting treatment, it was important to find out if the cortisol was low because the adrenal gland simply wasn’t making it or if it was because of the low ACTH. The patient was given an injection of ACTH, which should prompt the adrenal glands to release very high levels of cortisol. An hour later the cortisol level was higher, but still not as high as it should be. That suggested that both the adrenal glands and the pituitary gland, which makes ACTH, were not working properly.
Nevin sent off tests to see if other pituitary or adrenal hormones were affected. They weren’t. She also looked for the most common causes of these kinds of disorders. Was this some type of autoimmune issue? She sent tests to look for the kinds of autoantibodies known to attack these parts of the body. All negative. There were diseases that could affect the adrenal or pituitary glands: H.I.V., tuberculosis and tumors that, because of their size or their unregulated secretion of hormones, might disrupt those organs’ function. Dozens of tubes of blood were filled and sent off to a variety of labs. She had none of the disorders that could cause this dramatic drop.
An M.R.I. of the brain showed a tumor on the pituitary, but it was tiny. Further testing showed it wasn’t producing any hormones at all. It was what is known as an incidentaloma, too small and inert be the cause of her symptoms.
The Medicine Works
Nevin was puzzled. She had seen her share of patients with adrenal insufficiency. They looked sick: tired and listless with weak and painful muscles; their blood pressure was sometimes so low they could hardly stand up. None of that was true for this patient. She looked physically fit. Her blood pressure was high, not low. It was true that she had lost weight, but the overall picture didn’t fit. Still, she believed the lab results.
She scanned the literature for other possible causes of her patient’s sluggish glands. She found a couple of case reports of patients who developed adrenal insufficiency after a Covid-19 infection. Could the patient’s bout with Covid a few months earlier be the culprit? The timing was right, but there was no way to tell at this point.
The patient did well on the twice daily hydrocortisone treatment. She started regaining her lost weight, and her mild fatigue subsided. She asked the doctor if she was going to have to be on this medication forever. Nevin told her that she probably would. At least that was true for most patients with adrenal insufficiency.
After two weeks on the hydrocortisone, the patient started having trouble sleeping. She reduced the dose and suddenly she could sleep again. When the sleeplessness returned a few weeks later, she cut the dose again. All this occurred nearly a year ago. The patient continues to take a small dose of the hydrocortisone every day. Strangely, her high blood pressure improved, and she was able to stop the hypertension medications. Nevin tells me she still doesn’t understand why.
Nor did Nevin understand why this patient was not as sick as most who have adrenal insufficiency. Her hypothesis is that the deficiency was discovered early. Because the symptoms are vague, patients with critically low stress-hormone levels can elude diagnosis for months, sometimes years.
A few months after this diagnosis, a newly published study showed that 14 percent of people with Covid-19 developed adrenal insufficiency that often improved on its own over time. As with so much about this virus, why the deficiency occurs, or why it resolves, is still not well understood.
While there is no way to know for certain if it was the Covid infection that caused the patient’s adrenal insufficiency, both she and Nevin, inspired by the recent study, plan to try to get her off the medication sometime this year. It will be a slow process — but from the patient’s perspective, totally worth it.
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