Acromegaly Diagnosis Falls Short, Better Monitoring Needed

Sex differences in symptoms and early manifestations recognized by patients before clinicians, and identification and screening for common comorbidities still lacking despite published guidelines.

With Shlomo Melmed, MBChB, Whitney Woodmansee, MD, and  Lisa Nachtigall, MD

Acromegaly is a rare disease, with an incidence of 3.3 per million per year. Yet for the few patients affected, there’s room for improvement in diagnosing the condition earlier, and a need to screen for comorbidities, 1,2 based on findings from two separate studies.

In fact, only 29.5% of patients were diagnosed by an endocrinologist, while the condition was initially suspected by other specialists for 37.2% of patients.Equally important, patients were found to raise concerns about signs to their physician before any indication of a need to screen was initiated by the practitioner, according to the researchers.

Physicians should heed patient complaints to arrive at valid diagnosis sooner.

Screening for Concomitant Conditions Needed, Adjusting for Patients’ Sex

A French research team analyzed 472 patients enrolled in the ACRO-POLIS study,1 conducted at 25 hospital departments that treated acromegaly throughout France, and their findings were published in the journal Endocrine.

They examined records for adults who had been diagnosed with acromegaly in the past five years, combing through demographic and clinical data from medical reports and patient questionnaires. On average, the patients were 51.9 years, with BMI of 27.7 kg/m2.1 Of the study participants, 42.8% were male. On average, the patients completed the questionnaires about 30 months after having received a formal diagnosis.

Certain symptoms tended to show up first, Caron et al found,1 and often the types of signs differed by sex. Most common to be noticed were morphological manifestations, such as enlarged hands and feet, as well as broadened facial features, occurring in nearly 88% of patients. Asthenia was seen in 79.2% of all patients. Associations between signs and symptoms were assessed by multiple correspondence analysis.

Women tended to report the following: headache, carpal or cubital tunnel syndrome, constipation, and thyroid nodules, whereas men were more likely to indicate symptoms such as prognathism, sleep apnea, congestive heart failure, and sexual-related problems, as well as erectile dysfunction.

When the researchers assessed for frequency of manifestations, three symptoms appeared most often: exaggerated morphological changes, and respiratory difficulties, most notably, new onset snoring and sleep apnea.

Patients Symptom Complaints Not Readily Acknowledged

Discrepancies in symptoms complaints were identified between the physicians' case report forms and patient questionnaires, with the greatest frequency of noted differences seen predominantly in functional signs such as snoring, weight gain, and asthenia.1

Acromegaly is known as a disease with a delayed diagnosis, which was confirmed in this study, in which the average time between patient-observed symptom onset and clinical diagnosis was 14.2 years (+-11.3 years; 95% CI: 13.1, 15.2).1

Macroadenoma was found across 80.5% of patients; microadenoma was identified in 19.5% of men and women.1

The new study,1 the authors wrote, ''provides real-world insight into the frequency of signs, symptoms, and comorbidities at acromegaly diagnosis, and their occurrence in the years preceding diagnosis in an effort to further improved early detection of the disease."

The findings offer a stark reminder to physicians of the need to both become more alert to the symptoms likely to present for acromegaly and to heed patient-reported complaints during a consultation, as this is likely to prompt an earlier diagnosis,1 the researchers wrote.

The authors did not reply to several requests for direct comment but their conclusions were endorsed by Shlomo Melmed, MBChB, FRCP, MACP, professor of medicine and executive vice president of academic affairs at Cedars-Sinai Medical Center in Los Angeles who reviewed the findings for EndocrineWeb; he had no involvement in the study.

"These findings offer a strong indication that we are not doing a good job [in detecting acromegaly]," said Dr. Melmed. "I'm aware of previous studies showing a 10-year gap and a 12-year gap," he said, but ''the 14-year gap between the onset of symptoms and time of diagnosis is quite startling." This suggests that endocrinologists have some room for improvement in both recognize symptoms in a more timely fashion, and being able to deliver a  diagnosis sooner.

Study Reveals Unexpected Results when Tracking Comorbidities

In a separate assessment of acromegaly,2 a team of US researchers looked at the frequency of comorbidities, screening for them in a study know as SODA (Somatuline [lanreotide, LAN] Depot for Acromegaly (SODA).  Led by Whitney Woodmansee, MD, professor of medicine and director of the Neuroendocrine/Pituitary Program at the University of Florida Gainesville, the researchers evaluated 241 patients who were enrolled in the study.

The Endocrine Society released clinical practice guidelines on acromegaly in 2014.3 "We wanted to look back and see what clinicians are really doing [in terms of following the guidelines]," said Dr. Woodmansee. "It's not just about treating the acromegaly and getting the IGF level controlled. Just as important, you should also be screening for and managing comorbidities associated with acromegaly."

“We found that screening was lacking,” she told EndocrineWeb, but she acknowledged that their findings carried caveats due to the study design, which relied on patient-reported data. And SODA started before 2014, which was prior to the release of the guidelines.

Yet, overall, the University of Gainesville researchers found that less than 50% of people with acromegaly had undergone screening tests.2  The testing fell out as follows:

  • Just shy of 30% had had a sleep study even though 79.2% were found to have sleep apnea.
  • Echocardiograms were done in 46.1% of the study patients with 46.8% demonstrating abnormal findings.
  • Colonoscopy was done in 48.1% of patients, of which 35.3% were found to have polyps.
  • Gallbladder imaging was done in only 18.7% of these patients, and 17.8% of them had confirmed gallstones.

Blood work results were reported less frequently at both the one and two year follow-up visits with a hemoglobin A1c (HbA1c) captured in only one in three (30.8%) patients after the first year, and for 41.2% of patients at two years.2

Common comorbidity findings were: Pituitary hormone deficiencies were most often detected, and a TSH deficiency was the most endocrine-related sign found in nearly 70% of the participating patients.2

What’s the clinician takeaway according to the Florida research team? "If you are taking care of a patient with acromegaly, you will want to consider screening for comorbid conditions," Dr. Woodmansee said.

Clinically Remarkable Findings to Inform Patient Care, Experts Agree

The study of symptom manifestations offers clinicians’ valuable information,1 Dr. Melmed said. Besides the much-prolonged delay in diagnosis, another notable finding was that  ''80% of the tumors found were macroadenomas.'' While the majority of specialists may expect that frequency, he said that US registries generally record a rate closer to 70%. 

In reporting on patterns of comorbidities,2 the researchers validated and confirmed what has been known and reported in earlier studies, Dr. Melmed said. These findings should lend some urgency for clinicians to review current diagnostic practices, raise awareness of common comorbidities, and reinforce the value of listening to and noting patient complaints.1,2

Also, the recognition that snoring presents often is certainly worth noting,2 he said. "What's new in that list [of frequency of comorbid conditions] is how often the problem of snoring arises" in patients with confirmed acromegaly. 

Similary, Lisa Nachtigall, MD, clinical co-director of the Neuroendocrine and Pituitary Clinical Center at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School said, "Many of the patterns observed in the French study build on results from previous findings,."2 

"The novelty of this study had to do with an approach to assessment of the onset of symptoms prior to diagnosis as well as the differences that may exist between men and women,2 in this regard, and the discrepancy between physician-identified versus patient-reporting of signs and symptoms," Dr. Nachtigall told EndocrineWeb; she wasn’t involved in either study and agreed to review themHowever, she echoed a study limitation acknowledged by the authors, that the patient reports are subject to recall bias.

Despite the study limitations, 2 Dr. Nachitgall also cited some intriguing findings with regard to the high rate of TSH deficiency and the low laboratory testing of HbA1c and infrequency that sleep studies were ordered since it is known that both diabetes and sleep apnea commonly occur in individuals with acromegaly.

Dr. Melmed is a consultant for Chiasma, Midatech, and Ionis. Dr. Nachtigall is a consultant for Ipsen and Pfizer. Dr. Woodmansee is on the scientific advisory board of Strongbridge Biopharma and formerly on the scientific advisory board of Ipsen Biopharmaceutcals, Inc. The French researchers have been consultants and speakers for Ipsen, among others.


The study led by Dr. Woodmansee was funded by Ipsen Biopharmaceuticals, which makes a drug to treat acromegaly.

Continue Reading:
Getting Health Messages Right Can Prompt Better Patient Responsiveness
close X