Partial ectopic posterior pituitary: A rare imaging entity with literature review.

Abnormal development of the posterior pituitary gland can lead to an ectopic location of the neurohypophysis, commonly seen at the median eminence of the hypothalamus or along the infundibular stalk. A partial ectopic posterior pituitary (PEPP) is a very rare variant of the ectopic posterior pituitary, defined as the presence of a double bright spot of neurohypophysis seen in both orthotopic and ectopic locations. We report a two-year-old male toddler with bilateral optic nerve hypoplasia and severe visual impairment who presented to the endocrine outpatient clinic for hypopituitarism evaluation. Magnetic resonance imaging (MRI) of the brain revealed a hypoplastic pituitary gland and infundibulum with a double bright spot of neurohypophysis in the expected normal location and along the median eminence. Severe hypoplasia of both optic nerves and the optic chiasm was also seen. Septum pellucidum was present with no evidence of other brain malformations. The findings are in the septo-optic dysplasia spectrum associated with hypothalamic-pituitary dysfunction and a very rare entity called PEPP. To our knowledge, only a handful of reported cases of this rare entity exist in the literature.

Anabolic Deficiencies in Heart Failure: Ready for Prime Time?

"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment. The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF. Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF. There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."

Insulin-like growth factor-1 (IGF-1) as predictor of cardiovascular mortality in heart failure patients: data from the T.O.S.CA. registry.

INTRODUCTION: Data from the "Trattamento Ormonale nello Scompenso CArdiaco" (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry. METHODS: At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM. RESULTS: 337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV-V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels. CONCLUSIONS: Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF.

Rare case of skeletal third class in a subject suffering from Solitary Median Maxillary Central Incisor syndrome (SMMCI) associated to panhypopituitarism.

BACKGROUND: The median solitary maxillary central incisor syndrome (SMMCI) is a rare malformative syndrome consisting of multiple defects, mainly found on the body midline. It can be correlated to the etiopathological and phenotypic pattern of panhypopituitarism. This case-report describes the rare case of a patient suffering from SMMCI and panhypopituitarism, showing an unusual craniofacial morphology. CASE PRESENTATION: From the cephalometric analysis, a skeletal class III was identified (despite the other cases described in literature described as skeletal class II), derived from hypomaxillia and mandibular protrusion. A convex lip profile, with tendency to mandibular hyper-divergency, airway patency, anterior and posterior cross-bite were observed. At the clinical examination, a maxillary cant was evident on the frontal plane that appeared asymmetric, with the prevalence of the third lower part of the face. There were some dysmorphic signs such as: small nose, rectilinear eyelid line and reduced interocular distance. CONCLUSIONS: The present clinical case shows how, despite the literature, SMMCI can be associated with a III skeletal class, with maxillary hypoplasia and mandibular protrusion. The interdisciplinary collaboration between dentist and pediatrician is therefore important for the early interception of the malocclusions associated with these syndromes.

Secondary pituitary hormonal dysfunction patterns: tumor size and subtype matter.

PURPOSE: Patients with sellar masses (SM) frequently have secondary hormonal deficiency (SHD) at initial presentation. While larger SM are more likely to present with SHD, it is unclear whether SHD at presentation is influenced by the type of SM. METHODS: We conducted a retrospective analysis of patients with SM prospectively enrolled in our comprehensive provincial neuropituitary registry between November 2005 and December 2018. SM were subdivided based on size: < 1 cm, 1-1.9 cm, 2-2.9 cm, and > 3 cm. RESULTS: A total of 914 patients met the inclusion criteria, including: 346 nonfunctioning adenomas (NFA), 261 prolactinomas (PRLoma), 51 growth hormone adenomas, 36 adrenocorticotropic adenomas, 93 Rathke's cleft cysts, 70 craniopharyngiomas and 57 meningiomas. The overall rate of SHD at presentation was highest in PRLoma (62.8%) and craniopharyngiomas (64.3%) and lowest in meningiomas (14%). While larger SM were significantly more likely to have SHD, the rate of SHD within each group was significantly different despite similar size (p < 0.001). Of the two largest groups of SM (NFA and PRLoma), NFA had significantly higher odds ratio (3.34, CI 1.89-5.89) of having multiple SHDs when compare with PRLoma, even when corrected for age, gender and size of tumor (p < 0.001). CONCLUSION: Our study shows that the rate and distribution of SHD in SM vary dependent upon the size of the tumor and specific pathology; in particular, NFA are more likely to present with multiple SHDs. Our data will help clinicians in determining adequate hormonal testing strategy for different SM.

Anabolic Deficiencies in Heart Failure: Ready for Prime Time?

"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment. The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF. Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF. There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."

Clinical investigation of pituitary incidentalomas: A two-center study.

Recent advances in imaging technology resulted in an increase in pituitary incidentalomas (PIs) detection. PIs were reported to be present in 1.6% persons with magnetic resonance imaging of the brain. Whereas, there were few studies about PIs with detailed investigation. We aimed to investigate the clinical and endocrinological characteristics of PIs. We evaluated 65 patients diagnosed with PIs who underwent detailed clinical and endocrinological evaluations. Of the 65 patients, 33 (50.8%) had non-functional pituitary adenomas (NFPAs), 11 (16.9%) had Rathke's cleft cysts (RCCs), 7 (10.8%) had functional pituitary adenomas (FPAs), 6 (9.2%) had benign extra-pituitary tumors (BEPTs), and 8 (12.3%) had malignant tumors (MTs). Compared with patients with NFPAs, those with MTs were significantly younger and had a significantly lower body mass index, lower prevalence of hypertension, and lower prevalence of dyslipidemia. Patients with MTs had significantly higher prevalence of central diabetes insipidus than those with NFPAs. In addition, patients with NFPAs had significantly higher prevalence of pituitary apoplexy than those with FPAs, BEPTs, and MTs. In conclusion, our study demonstrated clinical and endocrinological characteristics of PIs. Highly detailed clinical and endocrinological investigations should be performed for PIs. In addition, MTs should be considered in the differential diagnosis for young and lean patients with central diabetes insipidus.

Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.

Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency.

OBJECTIVE: To define phenotypic groups and identify predictors of disease severity in patients with phosphoglucomutase-1 deficiency (PGM1-CDG). STUDY DESIGN: We evaluated 27 patients with PGM1-CDG who were divided into 3 phenotypic groups, and group assignment was validated by a scoring system, the Tulane PGM1-CDG Rating Scale (TPCRS). This scale evaluates measurable clinical features of PGM1-CDG. We examined the relationship between genotype, enzyme activity, and TPCRS score by using regression analysis. Associations between the most common clinical features and disease severity were evaluated by principal component analysis. RESULTS: We found a statistically significant stratification of the TPCRS scores among the phenotypic groups (P < .001). Regression analysis showed that there is no significant correlation between genotype, enzyme activity, and TPCRS score. Principal component analysis identified 5 variables that contributed to 54% variance in the cohort and are predictive of disease severity: congenital malformation, cardiac involvement, endocrine deficiency, myopathy, and growth. CONCLUSIONS: We established a scoring algorithm to reliably evaluate disease severity in patients with PGM1-CDG on the basis of their clinical history and presentation. We also identified 5 clinical features that are predictors of disease severity; 2 of these features can be evaluated by physical examination, without the need for specific diagnostic testing and thus allow for rapid assessment and initiation of therapy.

Molecular analysis of the PROP1 and HESX1 genes in patients with septo-optic dysplasia and/or pituitary hormone deficiency / Análise molecular dos genes PROP1 e HESX1 em pacientes com displasia septo-ótica e/ou deficiência hormonal hipofisária

OBJECTIVE: The present study aimed at evaluating the PROP1 and HESX1 genes in a group of patients with septo-optic dysplasia (SOD) and pituitary hormone deficiency (combined - CPHD; isolated GH deficiency - GHD). Eleven patients with a clinical and biochemical presentation consistent with CPHD, GHD or SOD were evaluated. SUBJECTS AND METHODS: In all patients, the HESX1 gene was analyzed by direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced. RESULTS: A polymorphism (1772 A > G; N125S) was identified in a patient with SOD. We found three patients carrying the allelic variants 27 T > C; A9A and 59 A > G; N20S in exon 1 of the PROP1 gene. Mutations in the PROP1 and HESX1 genes were not identified in these patients with sporadic GHD, CPHD and SOD. CONCLUSION: Genetic alterations in one or several other genes, or non-genetic mechanisms, must be implicated in the pathogenic process.

OBJETIVO: O presente estudo teve como objetivo avaliar os genes PROP1 e HESX1 em um grupo de pacientes com displasia septo-óptica (DSO) e deficiência hormonal hipofisária (combinada - DHHC; ou deficiência isolada de GH - DGH). Onze pacientes com apresentação clínica e bioquímica consistente com DHHC, DGH ou DSO foram avaliados. SUBJECTS AND METHODS: Em todos os pacientes, o gene HESX1 foi analisado pelo sequenciamento direto e, nos casos de DHHC, o gene PROP1 foi também sequenciado. RESULTADOS: Um polimorfismo no gene HESX1 (1772 A > G; N125S) foi identificado em um paciente com DSO. Foram encontrados três pacientes portadores da variação alélica 27 T > C; A9A e 59 A > G; N20S no éxon 1 do gene PROP1. Mutações no gene PROP1 e HESX1 não foram identificadas nesses pacientes com DGH, DHHC e DSO esporádicos. CONCLUSÃO: Alterações genéticas em um ou diversos outros genes ou mecanismos não genéticos devem estar implicados nesse processo patogênico.

Panhipopituitarismo: presentación de un caso clínico / Panhypopituitarism: clinical case

El Panhipopituitarismo es el déficit de las hormonas producidas en la adenohipofisis, clínicamente evidente cuando se ha destruido el 70 a 75 de la glándula. Las manifestaciones dependen del tipo de hormona afectada, edad, causa y rapidez de inicio. El déficit hormonal es progresivo: comienza con disminución de la GH, luego de la FSH /LH, TSH y finalmente la ACTH. Una mujer de 63 años de edad ingresa a UCI del hospital Abel Gilbert, con cuadro clínico de estupor, sudoración profusa, despigmentación de la piel, pérdida del vello axilar y pubiano. Antecedentes obstétricos: histerectomía por sangrado profuso y sepsis posparto. Por los datos clínicos y de laboratorio concluimos que se trataba de un Síndrome de Sheehan.

The panhypopituitarism is a deficit of the hormones produced by the adenohypophysis this is clinically evident when the 75 to 70 of the gland is destroyed. The symptoms depend on the type of hormone affected, age, cause and onset. The hormonal deficiency is progressive: it starts with a decrease of GH then of FSH/LH, TSH and finally ACTH. We have a clinical case of 63 year old woman admitted to ICU of Able Gilbert Hospital with a clinical case of stupor, hyperhidrosis, depigmentation of the skin, loss of pubic and axillary hair. Has an obstetric history of hysterectomy post-operative hemorrhaging and sepsis. Due the symptoms and lab findings we conclude that the diagnosis is Sheehan Syndrome.

Reassessment of Growth Hormone(GH) Status and Metabolic Disturbance in Young Adults with Childhood-onset GH Deficiency / 대한소아내분비학회지

PURPOSE: Adults with GH deficiency(GHD) have abnormal body composition, reduced physical performance, altered lipid metabolism, increased cardiovascular diseases, and reduced quality of life. Administration of GH to these patients reduce clinical abnormalities to normal ranges. Therefore, patients with childhood-onset GHD might need to continue GH replacement after the attainment of final height. Recently studies have shown that a high proportion of patients with childhood-onset GHD are no longer GHD when retested at young adult. METHODS: GH secretion was reevaluated with insulin and clonidine after completion of GH treatment in 29 young adult patients(21.3+/-2.8 yrs, 17 men, 12 women) with childhood-onset GHD diagnosed at a mean age of 11.4+/-3.5 yr. The mean duration of GH treatment was 3.7+/-3.0 yrs. Eleven(11 men) with idiopathic patients presented in 2(18%) isolated GHD and 9(82%) in multiple pituitary hormonal deficiencies. Eighteen(6 men, 12 women) with organic patients presented in 4(22%) isolated GHD and 14(88%) in multiple pituitary hormomal deficiencies, which was caused from craniopharyngioma, germinoma & other lesions. Blood sampling were done as usual method for checking LH, FSH and TSH concentration after injection of gonadotropin releasing hormone & thyrotropin releasing hormone. Serum cortisol levels were also checked after insulin injection and all hormonal concentrations were measured with radioimmunoassay method. Total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein(LDL)-cholesterol concentrations were measured by standard techniques. Bone density was measured in the level of lumbar spine and femur with DEXA. M-mode, two-dimensional and pulsed Doppler echocardiographic studies were performed. Quality of life was assessed from Beck depression inventory questionnaire with age-matched control. RESULTS: All patients with idiopathic and organic GHD were confirmed as GHD through combined pituitary function retesting at young adult. The additional pituitary hormonal deficiencies were increased in numbers. Their total cholesterol and triglyceride levels were increased especially in patients with organic GHD. There were no specific abnormal findings in echocardiographic findings compared to normal reference. Bone density with DEXA showed osteopenia(T score <-1) was found in 20/24(83%) and osteoporosis(T score <-2.5) in 8/24(33%) in young adult GHD. Quality of life was evaluated with BDI questionnaire and showed mild depression in 32% and moderate to severe depression in 11%. CONCLUSION: 82% of patients with idiopathic and 88% of organic GHD have additional pituitary hormonal deficiencies in childhood, showing multiple pituitary hormonal deficiencies rather than isolated GHD and has GHD permanently in all young adults with idiopathic and organic GHD and that is a little different findings from other foreign reports and needs to follow up in future.