Pituitary Stalk Dysgenesis-Induced Hypopituitarism in Adult Patients: Prevalence, Evolution of Hormone Dysfunction and Genetic Analysis

Abstract

Objectives: To investigate the prevalence of pituitary stalk dysgenesis (PSD) in adult hypopituitary patients by describing the chronology of hormone deficiencies and their potential correlation with traumatic delivery, mutations in genes required for pituitary development and function and pituitary stalk visibility on MRI. Design: Retrospective and prospective study involving 231 hypopituitary patients, including 26 diagnosed with PSD. Clinical, biochemical and radiological studies were reviewed. Molecular analyses of HESX1, LHX4,PROP1 and POU1F1 genes were performed prospectively. Results: PSD was present in 11.2% of hypopituitary patients. PSD was diagnosed before 14 years of age in 46.2% of cases, between 14 and 18 years of age in 23%, and in adulthood in 30.8%. Perinatal complications or gene mutations were present in 26.9 and 4.3% of patients, respectively. At first assessment, 92.3% of patients had growth hormone (GH) deficiency. 26.9% presented as combined pituitary deficiencies and 7.6% as panhypopituitarism. Hormone deficiencies were progressive during follow-up in 84.6%. 96% progressed to multiple deficiencies and 46% to panhypopituitarism. No significant association was found between hormonal dysfunction and previous perinatal damage or breech delivery (p = 0.17), PROP1 mutations (p = 0.26) or pituitary stalk visibility on MRI (p = 0.52). No mutations in POU1F1, HESX1 and LHX-4 genes were detected. Conclusion: In this study, PSD prevalence in adult hypopituitary patients was 11.2%. Typical clinical presentation includes isolated or combined pituitary hormone deficiencies during the pediatric age, which usually progress to combined or complete hypopituitarism in adulthood. Phenotype is highly variable depending on hormone profile and age at onset.

Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome

“…In consideration of ethnic differences, as well as the difference between familial (with germline mutations) versus sporadic patients, we previously screened 33 Chinese non‐familial patients with PSIS for mutations in genes HESX1, LHX4, PROP1, OTX2 and SOX3 genes which were known to associated with familial PSIS 9, 16, 17. Only was a novel heterozygous sequence variant found in HESX1 along with a few polymorphisms found in LHX4 and SOX3 .…”

Cтан Серцево-Судинної Системи Та Ліпідний Спектр При Соматотропній Недостатності У Молодих Дорослих Із Маніфестацією В Дитячому Віці (Огляд Літератури Та Власні Спостереження)

“…Пацієнти з МДГГ мають більшу ОТ, зниження рівнів ЛПВЩ, високі рівні тригліце-ридів. Однак ризик розвитку ЦД і серцево-судинних ускладнень однаковий при ізольованому дефіциті ГР та МДГГ [4]. На сьогодні встановлено, що жирова тканина -одне з головних місць дії ГР.…”

“…Причиною ізольованого дефіциту та МДГГ може бути дисгенезія ніжки гіпофіза, причому у більшості хворих (до 96 %) з віком ступінь дефіциту ГР може прогресувати, або до ізольованого ДГР приєднується дефіцит інших гіпофізарних гормонів, аж до пангі-попітуїтаризму (46 %) [4]. Дисгенезію ніжки гіпофіза діагностують у віці до 14 років у 46,2 % пацієнтів, у віці 14-18 років -у 23 %, у дорослих -у 30,8 % ви-падків.…”

Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors

“…The WNT (Yako et al 2011) and SHH pathways (Fernandez-Rodriguez et al 2011) are important for proliferation regulation, while the BMP and FGF pathways are required for proliferation and for determining cellular migration (Kato et al 2010). Rathke's pouch formation is complete at approximately E10 .…”

“…Mutations in several transcription factors (TFs) can lead to impaired pituitary formation (Fernandez-Rodriguez et al 2011, Mortensen et al 2011. Recently, the increase in the number of identified mutations, functional studies and experiments using transgenic animals have helped us understand TF interactions and clarified the multiple steps of pituitary organogenesis.…”