Increased episodic release and disorderliness of prolactin secretion in both micro-and macroprolactinomas

Ronald Groote Veldman, Gerrit Van Den Berg, Steven M. Pincus, Marijke Frölich, Johannes D. Veldhuis, Ferdinand Roelfsema

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


To quantify prolactin (PRL) secretion patterns, ten untreated (female) microprolactinoma patients and six (male) macroprolactinoma patients underwent repetitive blood sampling every 10 min over 24 h. PRL release activity was analyzed from plasma PRL concentration (immunofluorimetric assay) profiles via a model-independent discrete peak detection program (Cluster) and a waveform-independent deconvolution technique (Pulse). Diurnal variations were analyzed by cosinor analysis. The number of distinct PRL pulses (mean±S.E.M.) was increased in patients: microprolactinoma 18.6±0.6/24h versus female controls 12.4±0.6 (P=6.7x10-8), and macroprolactinoma 18.0±0.9 versus male controls 13.5 ±0.8/24 h (P=0.003). In patients, PRL pulse height, amplitude, pulse area and interpeak nadir concentrations were each greatly elevated compared with gender-matched controls. By 2-component deconvolution analysis, the mean nadir PRL secretion rate in microprolactinoma patients was augmented 20-fold at 0.408±0.089 μg/1 per min versus in female controls 0.019±0.009 μg/l per min (P<0.001); and in macroprolactinoma by 130-fold at 2.067±0.693 μg/1 per min versus male controls 0.016±0.001 μg/1 per min (P=0.001). Corresponding 24 h mean PRL secretion rates were in women, 0.658±0.147 and 0.044±0.018 (P<0.001), and in men, 3.309±1.156 and 02035±0.010 μg/1 per min (P=0.001), being respectively 15- and 94-fold increased in tumors. The estimated PRL production per day was 160±15 and 187±20 μg in male and female controls respectively. PRL production was 2860±640 μg in female patients with microadenomas (P<0.001), and 37800±5900 μg in male macroadenoma patients (P=0.001). Cosinor analysis of the plasma concentrations revealed a significant rhythm in nine of ten patients with a microadenoma, and in five of six with a macroadenoma. The same method applied to pulse height and amplitude disclosed a significant rhythm for PRL pulse height, but not for pulse amplitude, suggesting preserved rhythmicity of baseline interpulse nadir PRL concentrations. Approximate entropy (ApEn), a scale- and model- independent regularity statistic, averaged 1.6559±0.028 in microprolactinoma patients versus 0.8128±0.079 in female controls (P=1.7x10-8); ApEn in macroadenomas was 1.5674±0.054 versus male controls 0.8773±0.076 (P=1.7x10-5), signifying greater secretory irregularity in the patients. Compared with microadenomas, macroadenomas exhibited a higher mean plasma concentration, overall mean PRL secretion rate, nadir secretion rate and pulse area, but similar peak frequency. We conclude that PRL secretion by prolactinomas is characterized by increased plasma PRL episodicity of release, increased total (15- to 100-fold) and basal (20- to 130-fold) secretion rates, and increased disorderliness of minute-to-minute secretion. These abnormalities of secretory control are very similar to those for GH and ACTH identified earlier in acromegaly and Cushing's disease respectively, thus suggesting mechanistic generality of pituitary tumor secretory derangements, independent of the particular hormone.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalEuropean journal of endocrinology
Issue number3
StatePublished - Mar 1999

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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