PMID- 11297584
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20181130
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 86
IP  - 4
DP  - 2001 Apr
TI  - Basal, pulsatile, entropic, and 24-hour rhythmic features of secondary 
      hyperprolactinemia due to functional pituitary stalk disconnection mimic tumoral 
      (primary) hyperprolactinemia.
PG  - 1562-7
AB  - Under physiological conditions, PRL secretion is regulated precisely by various 
      stimulating and inhibiting factors. Hyperprolactinemia may arise as a primary 
      consequence of a PRL-secreting pituitary adenoma. Secondary hyperprolactinemia 
      (SH) may emerge in patients with hypothalamic disease, hypophyseal stalk 
      compression, or suprasellar extension of a (nonlactotrope) pituitary adenoma. The 
      latter may reflect diminished delivery of dopamine or other inhibitory factors to 
      normal lactotropes. We hypothesized that diurnal and ultradian rhythms of PRL 
      secretion would differ in secondary (e.g. hypothalamic) and primary (e.g. tumoral 
      states) hyperprolactinemia (PH), assuming that the underlying pathophysiologies 
      differ. To test this clinical postulate, we investigated the patterns of 24-h PRL 
      release in eight patients with SH associated with functional 
      hypothalamo-pituitary disconnection and in eight patients with PH attributable to 
      microprolactinoma. Data in each group were compared with values in healthy 
      gender-matched controls. PRL time series were obtained by repetitive 10-min blood 
      sampling, followed by high- precision immunofluorometric assay. PRL concentration 
      profiles were analyzed by the complementary tools of model-free discrete peak 
      detection, waveform-independent deconvolution analysis, cosinor regression, and 
      the approximate entropy metric to quantitate pulsatile, basal, 24-h rhythmic, and 
      pattern-dependent (entropic) PRL secretion. Patients with tumoral 
      hyperprolactinemia (PH) showed a 2-fold higher 24-h mean serum PRL concentration 
      than patients with SH (62 +/- 13 microg /L vs. 30 +/- 6.9 microg/L, respectively, 
      P = 0.029). Estimated PRL pulse frequency (events/24 h) was similar in the two 
      patient groups (18.5 +/- 0.7 vs. 17.6 +/- 0.8; P = 0.395) but elevated over that 
      in euprolactinemic controls (P < 0.0001 for both). Deconvolution analysis 
      disclosed a mean daily PRL secretion rate of 790 +/- 170 microg in PH patients 
      vs. 380 +/- 85 microg in SH patients (P = 0.030). Nonpulsatile PRL secretion 
      comprised nearly 70% of total secretion in both patient groups and 50% in 
      controls (P < 0.0001). Cosinor analysis revealed similar acrophases in all three 
      study cohorts. The mean skewness of the statistical distribution of the 
      individual PRL sample secretory rates was reduced, compared with controls (P < 10 
      (-5) for each), but equivalent in SH and PH patients (0.83 +/- 0.12 vs. 0.78 +/- 
      0.08, respectively), denoting a loss of the normal spectrum of low- and 
      higher-amplitude secretion rates. Approximate entropy, a regularity statistic, 
      was markedly elevated in both patient groups over controls (P < 10 (-6) for each) 
      and was slightly higher in PH patients than in SH patients (1.639 +/- 0.029 vs. 
      1.482 +/- 0.067, P = 0.048). In summary, patterns of PRL secretion in PH and SH 
      states exhibit an equivalently increased frequency of PRL pulses, a comparably 
      marked rise in nonpulsatile (basal) PRL secretion. Despite overlap, the 
      regularity of PRL release patterns is disrupted even more profoundly in PH 
      (tumoral), compared with SH. Assuming that the orderliness of serial PRL output 
      monitors normal integration within a feedback-controlled neurohormone axis, then 
      the more disorderly patterns of tumoral PRL secretion point to greater regulatory 
      disruption in PH. The latter may reflect abnormal secretory behavior associated 
      with lactotrope neoplastic transformation and/or isolation of the tumor cell mass 
      from normal hypothalamic controls.
FAU - Veldman, R G
AU  - Veldman RG
AD  - Department of Endocrinology and Metabolic Diseases, Leiden University Medical 
      Center, 2333AA Leiden, The Netherlands.
FAU - Frolich, M
AU  - Frolich M
FAU - Pincus, S M
AU  - Pincus SM
FAU - Veldhuis, J D
AU  - Veldhuis JD
FAU - Roelfsema, F
AU  - Roelfsema F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Circadian Rhythm
MH  - Entropy
MH  - Female
MH  - Humans
MH  - Hyperprolactinemia/blood/*etiology/*physiopathology
MH  - Male
MH  - Middle Aged
MH  - Pituitary Diseases/blood/*complications/metabolism
MH  - Pituitary Neoplasms/blood/*complications/metabolism
MH  - Prolactin/blood/metabolism
MH  - Prolactinoma/blood/*complications/metabolism
MH  - Pulsatile Flow
MH  - Reference Values
EDAT- 2001/04/12 10:00
MHDA- 2001/05/05 10:01
CRDT- 2001/04/12 10:00
PHST- 2001/04/12 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/04/12 10:00 [entrez]
AID - 10.1210/jcem.86.4.7382 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2001 Apr;86(4):1562-7. doi: 10.1210/jcem.86.4.7382.