Complex Rhythmicity and Age Dependence of Growth Hormone Secretion Are Preserved in Patients With Acromegaly: Further Evidence for a Present Hypothalamic Control of Pituitary Somatotropinomas

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Abstract

Context:

Traditionally, acromegaly is viewed as a disease resulting from GH hypersecretion from an autonomous pituitary somatotropinoma.

Objective:

To test the hypothesis that GH secretion in acromegaly is still subjected to normal hypothalamic control, we studied the daily rhythmicity of GH secretion in normal controls and patients with newly diagnosed, untreated acromegaly.

Design and Setting:

This was an observational inpatient study in the General Clinical Research Center at the University of Michigan.

Patients or Other Participants:

One hundred four normal controls and 67 acromegalic patients were included in the study.

Intervention:

The intervention consisted of frequent blood sampling over 24 hours.

Main Outcome Measure(s):

We hypothesized that acromegalic patients would show rhythmicity, sexual dimorphism, and age-related decline of GH secretion similar to normal controls.

Results:

Both normal controls and the patients exhibited 3 major GH waves with the highest values at 12:00 PM, 5:00 PM, and 1:00 AM (P < .001 for all). Both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). The amplitude of the maximal (nocturnal) GH secretory wave (1:00 AM) as compared with the nadir GH secretion (9:00 AM) was clearly different between the 2 groups, with a significantly smaller magnitude in acromegaly (P < .001). A subsequent subanalysis of both groups was performed separately for both genders. Similar to the entire groups, both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). Patients with clearly elevated GH values have shown an age-related decline of GH secretion (r = −0.35, P < .001), similar to controls.

Conclusions:

The analysis of GH profiles in multiple patients with untreated acromegaly discloses the persistence of the hallmarks of the central control of GH regulation, ie, nictohemeral rhythmicity, sexual dimorphism, and an age-related decline of GH output.

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