Pituitary Hypoplasia Is the Best MRI Predictor of the Severity and Type of Growth Hormone Deficiency in Children With Congenital Growth Hormone Deficiency

Background and Objectives: Congenital idiopathic growth hormone deficiency(GHD) is associated with various MRI abnormalities, including both sellar anomalies such as pituitary hypoplasia, ectopic pituitary, empty sella and abnormalities of the pituitary stalk and extrasellar abnormalities such as Arnold Chiari malformation, corpus callosum agenesis, arachnoid cyst, septum pellucidum agenesis, enlarged ventricles, vermis dysplasia, and sphenoid cyst. However, it remains contentious whether MRI brain findings could provide an additional avenue for precisely predicting the differentiation of GHD based on severity(severe or partial) and type(isolated GHD or multiple pituitary hormone deficiency MPHD). This study aimed to ascertain the abnormality that is the best predictor of severe GHD and type of GHD amongst the different MRI findings. Methods: This was an analytical cross-sectional study conducted from 2018-2020. During the study period, we included a total of 100 subjects diagnosed to have idiopathic GHD after the exclusion of syndromic causes, system illness, presence of pituitary mass, and those with h/o cranial irradiation. Patients were divided into severe GHD and partial GHD based on peak stimulated GH of <5 ng/dl and ≥ 5 ng/dl respectively and into groups based on isolated GHD and MPHD. Patients were further divided into groups based on the presence of pituitary hypoplasia,extrasellar brain abnormalities (EBA), and presence of ectopic posterior pituitary and/or pituitary stalk abnormalities(EPP/PSA), respectively. Analyses were performed using SPSS version 24.0 software. Results: Amongst 100 subjects with idiopathic congenital GHD, 66 (66%) subjects had Isolated GHD while the remaining 34 (34%) had MPHD. 71 had severe GHD, and 29 had partial GHD. Amongst the MRI findings, pituitary hypoplasia was the most common finding observed in 53% of patients, while 23(23%) had EBA, and 25(25%) had EPP/PSA. Pituitary hypoplasia was observed to be the best predictor of severity of GHD with an odds ratio(OR) of 10.8 (95% CI 3.38-29.6) followed by ectopic posterior pituitary /pituitary stalk abnormalities (OR =2.8, 95% CI 1.5-9.5) while the presence of extrasellar abnormalities was the weakest predictor (OR =1.8, 95% CI 1.05-3.2). Pituitary hypoplasia was the only finding to significantly predict MPHD (OR=9.2). On ROC analysis, a Pituitary height SDS of -2.03 had a 73.2 % sensitivity and specificity of 79.3%(AUC =0.787,95% CI 0.7-0.873) for severe GHD and a sensitivity of 88.2 % and specificity of 66.7% (AUC =0.745, 95% CI 0.68-0.877) for MPHD. Conclusion: We observed Pituitary hypoplasia to be not only the most frequent MRI abnormality but also the best predictor of severe GHD and MPHD amongst various sellar and extrasellar abnormalities.

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)

Extra pituitary midline structural abnormalities associated with ectopic posterior pituitary detected on a new rapid MR protocol (FAST1.2)

Background Ectopic posterior pituitary (EPP) is a malformation of the hypothalamic-pituitary region. Our goal was to describe midline structural brain abnormalities in patients with EPP using a dedicated protocol (FAST1.2 protocol) of magnetic resonance imaging (MRI) to evaluate the hypothalamus and pituitary gland, highlighting their clinical-laboratory correlations. Methods A cross-sectional study of patients diagnosed with EPP, and a control group. All individuals were submitted to a dedicated MRI protocol called FAST1.2, which combines the FAST1 protocol developed by our group with 3D T2DRIVE imaging. Results We evaluated 36 individuals with EPP and 78 individuals as a control group. One patient had two posterior pituitary lobes, one inside the sella turcica and the other along the pituitary stalk; in five patients, the EPP was along the pituitary stalk; in 28 the EPP was at the infundibular recess of the third ventricle, and in two the EPP was hypothalamic. In the EPP group, eleven individuals had interhypothalamic adhesion (IHA), three septo-optic dysplasia, one a cerebellar malformation, and one a pineal cyst. We did not observe a higher frequency of severe hormonal deficiency or developmental delay in patients with IHA. In the control group, eleven patients had a pineal cyst, three pars intermedia cysts, one hydrocephalus, and one hypothalamic hamartoma. Conclusion FAST1.2 acquisition allows confident recognition of regional anatomy and recognition of midline structural abnormalities on T2DRIVE, particularly including the pituitary stalk and IHA, thereby making MRI acquisition faster with no need for intravenous contrast administration. We suggest that IHA could be associated with defects in neuronal migration, as might occur in patients with EPP.

Coexistence of Ectopic Posterior Pituitary and Sellar/Suprasellar Arachnoid Cyst: A Case Report

Background: The ectopic posterior pituitary (EPP) is a rare condition characterized by the ectopic location of the posterior pituitary lobe associated with varying degrees of stalk anomalies. The arachnoid cysts (AC) are benign lesions of the arachnoid, which account for 1% of all intracranial space-occupying lesions. Sellar/suprasellar ACs account for approximately 1% of all ACs. This is the first case of coexistence EPP with sellar/suprasellar AC. Case Report: A 67-year-old woman presented with 6 months history of fatigue. Her medical history was positive for irregular menstruation. Her endocrine examinations indicated low free thyroxine level with low TSH level, low oestradiol with low gonadotrophin level, slightly elevated prolactin level. Her Insulin-like growth factor-1 was below the normal levels. Dynamic contrast hypophysis MRI revealed a sellar cystic lesion with a dimension of 18 × 14 × 14 mm, extending from the suprasellar cistern, traversing the diaphragma sellae and reaching the level of the floor of the 3rd ventricle, consistent with sellar/suprasellar AC. There was no wall enhancement. The optic chiasm was compressed. The precontrast T1-weighted magnetic resonance images did not demonstrate the characteristic bright spot of posterior pituitary within the sella, which was higher in position, in the region of the median eminence. The pituitary stalk was not present. Conclusion: Although speculative, we have a hypothesis to explain how the EPP and sellar/- suprasellar AC coexist in this patient. Due to the absence of stalk, CSF may enter the sella tursica from the central aperture of the diaphragma sellae through which normally the stalk passes.

ACQUIRED ECTOPIC POSTERIOR PITUITARY BRIGHT SPOT DUE TO VASCULOTOXIC SNAKEBITE

Objective: Vasculotoxic envenomation is an uncommon cause of hypopituitarism. Most described cases have varying extent of anterior pituitary dysfunction, but posterior pituitary involvement is extremely rare. Methods: Clinical, biochemical, and radiologic evaluation of a young female who presented with secondary amenorrhea was performed. A brief literature review of envenomation-induced hypopituitarism is included. Results: A 26-year-old female presented with secondary amenorrhea since the age of 20 years. She had normal stature. Her past medical history was significant for a vasculotoxic snakebite 12 years back requiring hemodialysis, but no hormonal testing was done at that time. Current evaluation showed anterior hypopituitarism. An insulin-induced hypoglycemia test confirmed deficiencies of cortisol and growth hormone axes (peak values 348 nmol/L and 0.03 ng/mL). There was no diabetes insipidus. Magnetic resonance imaging revealed a hypoplastic anterior pituitary with an ectopic posterior pituitary. In view of normal stature and secondary amenorrhea, a diagnosis of envenomation-induced hypopituitarism with ectopic posterior pituitary (EPP) was made. A brief literature review of envenomation-induced hypopituitarism showed both acute and delayed presentation, male predominance, and variable lag period (weeks to years). Nearly half of all patients were asymptomatic. The most common axis involved in acute presentation was the cortisol axis, whereas the thyroid and gonadotroph axes were commonly involved in delayed hypopituitarism. Conclusion: Vasculotoxic envenomation is a rare cause of acquired hypopituitarism. EPP in the index case was probably due to the “axonal dieback” phenomenon and subsequent regeneration of the axons at a more caudal site. This case, being the first instance of acquired EPP following envenomation, expands the spectrum of envenomation-induced hypopituitarism.