This article is more than 5 years old. Information may no longer be current.
Lag time between multiple endocrine neoplasia diagnoses linked to morbidity, mortality
Click Here to Manage Email Alerts
In families affected by multiple endocrine neoplasia type 1, the lag time between diagnosis of the index case and diagnosis of other family members may lead to negative outcomes, including death, for the non-index cases, according to recent findings.
Gerlof D. Valk, MD, PhD, of the University Medical Centre Utrecht in the Netherlands, and colleagues evaluated 393 participants aged older than 16 years from the Dutch MEN1 Study group. During the interval between 1990 and 2014, researchers collected data for all patients from every quarter of each available year; family relationships were noted in the medical records.
Patients who were the first in their families to be diagnosed with multiple endocrine neoplasia type 1 were classified as the “index case.” The “lag time” in this study was defined as the delay between the date of the multiple endocrine neoplasia type 1 diagnosis of the index case and the date of diagnosis in a non-index case in a member of the same family. The researchers calculated the median lag times between index case diagnosis and non-index case diagnosis and determined the morbidity and mortality outcomes linked to this lag time.
The researchers found that between 1990 and 2014, the database included 58 different MEN1 families with at least two family members. A multiple endocrine neoplasia type 1 germline mutation was confirmed in all but one of the families. In 43% of the families, the index case was diagnosed prior to the availability of mutation testing (1998), and in 57% of the families, the index case was diagnosed after this time. There was a median 3.5-year lag time between the diagnosis of the index case to diagnosis of the other family members. Prior to 1998, the lag time was 8 years, and from 1998 to 2001 the lag time was 2.6 years (P < .001).
At multiple endocrine neoplasia type 1 diagnosis, 12.1% of the non-index patients had a duodenopancreatic neuroendocrine tumor with a mean lag time of 7.9 years. In 76.1% of the non-index patients, there was no duodenopancreatic neuroendocrine tumor present at diagnosis, and the duodenopancreatic neuroendocrine tumor status was unknown at diagnosis in 29 non-index cases. In non-index patients with a metastasized duodenopancreatic neuroendocrine tumor, the mean lag time was 10.9 years. In 73.3% of non-index cases, no pituitary tumor was identified at diagnosis, and 34 had unknown pituitary tumor status at diagnosis.
Microadenoma was identified in 20 patients with a mean age-adjusted lag time of 7.2 years, and five had a microadenoma with a mean lag time of 10.6 years (P = .0834).
At the time of multiple endocrine neoplasia type 1 diagnosis, 38.4% of non-index cases had primary hyperparathyroidism and 2.8% did not. A 9.5-year age-adjusted lag time was seen in those with primary hyperparathyroidism compared with 3 years in those without (P = .035). Thirteen patients had no available data regarding primary hyperparathyroidism.
There were 10 deaths among non-index patients due to a clinical manifestation that may have developed during or prior to the lag time from the index case.
“These findings suggest that morbidity and mortality can be reduced if more emphasis is placed on genetic counseling and testing of the whole family at the time the index case is diagnosed,” the researchers wrote. – by Jennifer Byrne
Disclosure: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts