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Pituitary stalk interruption syndrome: phenotype, predictors, and pathophysiology of perinatal events

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Abstract

Purpose

There is limited data regarding Pituitary Stalk Interruption Syndrome (PSIS) from India. Moreover, the pathophysiological link between perinatal events and PSIS is unclear. We aim to elucidate the predictors of PSIS among patients with growth hormone deficiency (GHD) and perinatal events in PSIS by comparing cohorts of PSIS and genetically proven GHD without PSIS.

Methods

Among 179 GHD patients, 56 PSIS and 70 genetically positive GHD (52-GHRHR, 15-POU1F1, and 3-PROP1) patients were included. Perinatal events, clinical anomalies, pituitary hormone deficiency, and imaging findings were recorded. We compared PSIS-isolated GHD (PSIS-IGHD) subgroup with GHRHR-IGHD and PSIS-combined pituitary hormone deficiency (PSIS-CPHD) subgroup with POU1F1/PROP1-CPHD.

Results

PSIS patients (45 males, median age: 12.5 years) most commonly presented with short stature. At last follow-up (median age: 17.35 years), gonadal (during pubertal-age), thyroid and cortisol axes were affected in 81.6%, 62.5%, and 62.5%. 10/13 (77%) of PSIS children with initial IGHD diagnosis manifested hypogonadism during pubertal age. Male predominance, sporadic presentation, and clinical anomalies were significantly higher in both PSIS subgroups than in the respective genetic subgroups. Breech presentation was higher in PSIS-CPHD than POU1F1/PROP1-CPHD (44.4% vs 5.5%, p = 0.004). Neonatal hypoglycemia (22% vs. 0%, p = 0.05) and jaundice (42 vs. 5%, p = 0.004) were higher in PSIS-CPHD than PSIS-IGHD.

Conclusion

Later age at presentation and frequent hypogonadism were observed in our PSIS cohort. Male sex, sporadic presentation, clinical anomalies, and breech presentation predicted PSIS at presentation. Breech presentation in PSIS is likely due to stalk interruption rather than hormonal deficiency.

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Funding

The authors did not receive any financial support for the submitted work.

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Author notes

  1. Chakra Diwaker and Puja Thadani have contributed equally as the first author.

Authors and Affiliations

  1. Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India

    Chakra Diwaker, Saba Samad Memon, Anurag Ranjan Lila, Sneha Arya, Brijesh Krishnappa, Manjiri Karlekar, Virendra A. Patil, Nalini Shah & Tushar Bandgar

  2. University Hospitals Coventry and Warwickshire (UHCW) NHS Trust, Coventry, England, UK

    Puja Thadani

  3. Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India

    Vijaya Sarathi

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  1. Chakra Diwaker
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Contributions

CD and PT contributed equally as first author. ARL conceived the presented idea. CD and PT collected and analyzed the data with the help of SSM, MK, and BK. CD and SSM wrote the manuscript in consultation with VS, ARL, TB, NS and VP. Genetic analysis was done by SA. Final version of the manuscript was checked by all authors.

Corresponding author

Correspondence to Tushar Bandgar.

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This was a retrospective study approved by the Institutional ethics committee with a waiver of consent.

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Diwaker, C., Thadani, P., Memon, S.S. et al. Pituitary stalk interruption syndrome: phenotype, predictors, and pathophysiology of perinatal events. Pituitary 25, 645–652 (2022). https://doi.org/10.1007/s11102-022-01243-x

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