PITUITARY-STALK INTERRUPTION SYNDROME - A CLINICAL-BIOLOGICAL-GENETICASSESSMENT OF ITS PATHOGENESIS

The detection of pituitary stalk interruption syndrome (PSIS) by magne tic resonance imaging is a diagnostic marker of permanent GH deficienc y (GHD), but the pathogenesis of PSIS is unknown. Fifty-one patients ( 27 males) with GHD and PSIS were classified according to whether the G HD was isolated (group 1, 16 cases) or associated with other anterior pituitary abnormalities (group 2, 35 cases). The 2 groups had similar characteristics (frequencies of perinatal abnormalities, ages at occur rence of first signs and at diagnosis, height, GH peak response to sti muli other than GHRH), but associated malformations were less frequent in group 1 (12%) than in group 2 (54%; P < 0.01), hypoglycemia occurr ed in 25% of group 1 and 70% of group 2 (P < 0.01), and the GH peak re sponse to GHRH was less than 10 mu g/L in 0% of group 1 (4 cases evalu ated) and 57% of group 2 (21 cases; P < 0.05). Thirty-one cases (61%; 25 from group 2) had features suggesting an antenatal origin: familial form (4 cases), microphallus(10 boys), and/or associated malformation s (50%; 21 cases). Twenty-seven cases (53%, 22 from group 2) had featu res suggesting a hypothalamic origin. The three group 1 patients with a GH peak of 1 mu g/L or less had no large GH-N gene deletion. One fam ilial form had no linkage between the GHD phenotype and abnormal GH-N locus, and the only mutation described to date in the GHRH receptor ge ne was absent. The two patients with low plasma PRL levels had no Pit- 1 gene abnormality. Thus, most of the patients with GHD associated wit h multiple anterior pituitary abnormalities and PSIS have features sug gesting an antenatal origin. The GH-N, GHRH receptor, and Pit-1 genes do not-seem to be implicated in PSIS.