ESPE Abstracts (2015) 84 P-2-511

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome

Sjoerd Joustraa, Ferdinand Roelfsemaa, Eric Endertb, Bart Ballieuxa, Paul van Trotsenburgb, Erik Fliersb, Noortje Corssmita, Daniel Bernardc, Wilma Oostdijka, Jan Maarten Wita, Alberto Pereiraa & Nienke Biermasza


aLeiden University Medical Center, Leiden, The Netherlands; bAcademic Medical Center, Amsterdam, The Netherlands; cMcGill University, Montréal, Canada


Background: Loss-of-function of immunoglobulin superfamily, member 1 (IGSF1) causes an x-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency, and variable partial growth hormone deficiency in childhood. The clinical features and gene expression pattern suggest a pivotal role for IGSF1 in the pituitary, but detailed knowledge on pituitary hormone secretion in this syndrome is lacking.

Objective and hypotheses: To study in detail the 24 h pituitary hormone secretion in male patients with IGSF1 deficiency.

Method: We collected blood samples every 10 min for 24 h in eight adult male IGSF1 deficient patients and measured circulating TSH, prolactin, gonadotropins, and GH. Deconvolution, modified cosinor, and approximate entropy analyses were applied to quantify secretion rates, diurnal rhythmicity, and regularity of hormone release. Results were compared to matched healthy controls and, for TSH, to patients with untreated mild (subclinical) primary hypothyroidism.

Results: Compared to both healthy controls and patients with mild primary hypothyroidism, IGSF1 deficient patients showed decreased pulsatile secretion of TSH with decreased disorderliness and reduced diurnal variation. Basal and pulsatile secretion of GH and FSH were increased by over 200%, while LH secretion did not differ from healthy controls. We observed a bimodal distribution of prolactin secretion, i.e. severe deficiency in three and increased basal and total secretion in the other five patients.

Conclusion: The altered TSH secretion pattern is consistent with the previously hypothesized defect in TRH signalling in IGSF1 deficiency. However, the phenotype is more extensive and includes increased GH and FSH secretion without altered LH secretion, and either undetectable or increased prolactin secretion.

Funding: The work was supported by an unrestricted research grant from Ipsen Farmaceutica BV, and one of the authors was supported by a CIHR operating grant MOP-133557.