PSIS With Phenotypic Features of Prader Willi and Fragile X Syndrome

Pituitary stalk interruption syndrome (PSIS) is a congenital pituitary anatomical defect characterized by triad of interrupted or thin pituitary stalk, hypoplasia or aplasia of anterior lobe and absent or ectopic posterior pituitary on MRI. PSIS is known to have a heterogenous phenotype involving variable combination of pituitary hormonal deficiencies. [1] We present this case diagnosed with PSIS who had phenotypical features of Prader-Willi and Fragile X Syndrome but was negative on chromosomal array and analysis. Case Presentation: 19 yo M presented to clinic accompanied with his mother who provided most of the history. As per the mother, the patient was initially evaluated for hypogonadism due to lack of pubic and axillary hair with underdeveloped penis and testes, till the age of 17 years. Later on he was found to have hypothyroidism and was on replacement for the above. The patient was born through C-section at term, had developmental delays with respect to achieving milestones. On Examination, the patient had BMI of 35.5 (Weight: 105.2 kg, Height: 172 cm). Exam was significant for bilateral gynecomastia with glandular tissue, absence of facial hair, minimally palpable testes, phimosis, minimal pubic hair. He was noted to have enlarged ear lobes and helices with mild hypertelorism. On evaluation patient had learning disability, borderline IQ (nonverbal IQ of 74). Labs were significant for FSH: 0.344 (normal 1.5-12.4), LH; 0.1 (normal 1.70-8.60), Prolactin: 6.31 (normal 2.64-13.13), TSH: 3.80 (normal 0.30-4), T3: 156 (normal 82-179), fT4: 0.409 (normal 0.30-1.90), Testosterone < 0.025, IgF-1 <32, ACTH 14, cortisol 2.1 after cosyntropin test cortisol 13.3. He was started on replacement for secondary adrenal insufficiency. In view of the patient’s obesity, panhypopituitarism, questionable intellectual disability (non-verbal) IQ of 74), and enlarged ear lobes and helices, the patient was strongly suspected to have Prader Willi and Fragile X syndrome, however chromosomes and array were negative for both. MRI brain was recommended that was consistent with PSIS: hypoplastic enhancing pituitary soft tissue within Sella consistent with anterior lobe, ectopic posterior pituitary in region of hypothalamus and unidentifiable pituitary stalk. Conclusion: Pituitary stalk interruption syndrome is diagnosed radiologically and involves multiple pituitary hormonal deficiencies that can gradually progress requiring lifelong hormonal replacement therapy and follow up. It is associated with a wide phenotypic spectrum suggesting both hormonal deficiencies and coexisting developmental defects. Work still needs to be done to further explore the molecular etiology of this rare syndrome however due to wide phenotypical presentation of this syndrome it is imperative to evaluate for PSIS at an early age if there is suspicion of any isolated or combined hormonal deficiency in addition to abnormal morphology to identify individuals with PSIS as they need close monitoring for progression of syndrome and lifelong hormonal replacement eventually. References: 1 Vergier J, Castinetti F, Saveanu A, Girard N, Brue T, Reynaud R. Diagnosis of endocrine disease: Pituitary stalk interruption syndrome: etiology and clinical manifestations. Eur. J. Endocrinol. 2019 Nov;181(5):199-209 (https://eje.bioscientifica.com/view/journals/eje/181/5/EJE-19-0168.xml?body=fullHtml-10422)