Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas

Pituitary adenomas (PAs) can be unpredictable and aggressive tumors. No reliable markers of their biological behavior have been found. Here, a proteomic analysis was applied to identify proteins in the expression profile between invasive and non-invasive PAs to search for possible biomarkers. A histopathological and immunohistochemical (adenohypophyseal hormones, Ki-67, p53, CD34, VEGF, Flk1 antibodies) analysis was done; a proteomic map was evaluated in 64 out of 128 tumors. There were 107 (84%) invasive and 21 (16%) non-invasive PAs; 80.5% belonged to III and IV grades of the Hardy–Vezina classification. Invasive PAs (n = 56) showed 105 ± 43 spots; 86 ± 32 spots in non-invasive PAs (n = 8) were observed. The 13 most prominent spots were selected and 11 proteins related to neoplastic process in different types of tumors were identified. Hint1 (Histidine triad nucleotide-binding protein 1) high expression in invasive PA was found (11.8 ± 1.4, p = 0.005), especially at high index (>10; p = 0.0002). High Hint1 expression was found in invasive VEGF positive PA (13.8 ± 2.3, p = 0.005) and in Flk1 positive PA (14.04 ± 2.28, p = 0.006). Hint1 is related to human tumorigenesis by its interaction with signaling pathways and transcription factors. It could be related to invasive behavior in PAs. This is the first report on Hint expression in PAs. More analysis is needed to find out the possible role of Hint in these tumors.

A Rare Cause of Pituitary Deficiency: Pituitary Stalk Interruption Syndrome and Magnetic Resonance Imaging Findings

Pituitary stalk interruption syndrome is a rare disease characterized by a deficiency of adenohypophyseal hormones. Clinical presentation usually occurs in childhood or in the second decade of life. The severity of hormonal deficiency is variable. It may be isolated or be accompanied by extra–pituitary anomalies. Magnetic resonance imaging findings are considered as an absent pituitary stalk, absent or smaller adenohypophysis, absent or ectopic neurohypophysis. Contrast-enhanced imaging is essential in evaluating the presence and morphology of the pituitary stalk. In the presence of clinical findings, evaluation of the hypothalamic–pituitary region using magnetic resonance imaging is necessary for diagnosis. Early diagnosed cases can maintain their normal lives with hormone replacement. In this article, we aimed to present pituitary stalk interruption syndrome and its magnetic resonance imaging findings with a case presentation

Senile hypopituitarism: Characteristics of its diagnosis and treatment

Hypopituitarism is a clinical syndrome caused by reduced production of adenohypophyseal hormones. The clinical manifestations of senile hypopituitarism are more complicated and a delay in diagnosis and treatment may lead to rapid development of pituitary crisis. Therefore, clinicians should be alerted to senile hypopituitarism. For patients with hyponatremia, hypoglycemia and unexplained coma, an evaluation of pituitary function should be performed. Hormone replacement therapy for patients with confirmed hypopituitarism should be standardized and unauthorized dose reduction or withdrawal is not allowed.

Mutations in the genes encoding for leptin and its mediators: induction of obesity with various concomitant pathological conditions

g15384delG(G133fsX15), c.215T⇒C(p.L72S), c.309C⇒A(p.N103K), c.313C⇒T(p.R105W), c.422C⇒G(p.S141C), c.104_106delTCA, c.481_482delC⇒T, and c.135del13bp mutations in LEP in the homozygous state are known to be associated with the early onset of severe obesity and disturbances of many physiological functions. Similar pathological changes are induced by mutations in LEPR, such as G⇒A substitution in the splicing donor site, deletions of 4 and 11 base pairs in the 5'-terminus of cDNA, deletion of 66 bp in the CRH domain of LEPR, compound deletion of 1 base pair in the 5'-terminus/p.R612H, and missense mutations P316T, A409E, W664R, and H684P. Disturbances in LEP and LEPR expression in homozygous subjects are associated with severe obesity, retarded sexual development, insulin resistance, disordered secretion of adenohypophyseal hormones, and immunodeficiency. Mutations in LEP cause more serious pathological changes than LEPR mutations. In the homozygous state, mutations in POMC, such as 3804C⇒A, 6906delC, 6922insC, and compound heterozygous mutations 7134delG/7013G⇒T, 6996del/6851A⇒T, 3804CA/7100insGG are associated in man with morbid obesity and acute adrenal cortical insufficiency. In the heterozygous state, these mutations predispose to obesity in the absence of concomitant disorders. Mutations in MC4R are the most common cause of obesity. They are known to induce severe pathology in homozygous subjects but significantly milder disturbances of adipose tissue metabolism in heterozygotes. In both cases, obesity is not accompanied by serious disturbances of other functions.