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Endocrinologia, Diabetes Y Nutricion Nov 2022
Topics: Humans; BNT162 Vaccine; COVID-19; Vaccination; Acute Disease; Adrenal Insufficiency
PubMed: 36428206
DOI: 10.1016/j.endien.2021.11.035 -
Endocrinology Dec 2022POU Class 1 Homeobox1 (POU1F1/Pou1f1) is a well-established pituitary-specific transcription factor, and causes, when mutated, combined pituitary hormone deficiency in...
POU Class 1 Homeobox1 (POU1F1/Pou1f1) is a well-established pituitary-specific transcription factor, and causes, when mutated, combined pituitary hormone deficiency in humans and mice. POU1F1/Pou1f1 has 2 isoforms: the alpha and beta isoforms. Recently, pathogenic variants in the unique coding region of the beta isoform (beta domain) and the intron near the exon-intron boundary for the beta domain were reported, although their functional consequences remain obscure. In this study, we generated mice carrying the Pou1f1 c.143-83A>G substitution that recapitulates the human intronic variant near the exon-intron boundary for the beta domain. Homozygous mice showed postnatal growth failure, with an average body weight that was 35% of wild-type littermates at 12 weeks, which was accompanied by anterior pituitary hypoplasia and deficiency of circulating insulin-like growth factor 1 and thyroxine. The results of RNA-seq analysis of the pituitary gland were consistent with reduction of somatotrophs, and this was confirmed immunohistochemically. Reverse transcription polymerase chain reaction of pituitary Pou1f1 mRNA showed abnormal splicing in homozygous mice, with a decrease in the alpha isoform, an increase in the beta isoform, and the emergence of the exon-skipped transcript. We further characterized artificial variants in or near the beta domain, which were candidate positions of the branch site in pre-mRNA, using cultured cell-basis analysis and found that only c.143-83A>G produced transcripts similar to the mice model. Our report is the first to show that the c.143-83A>G variant leads to splicing disruption and causes morphological and functional abnormalities in the pituitary gland. Furthermore, our mice will contribute understanding the role of POU1F1/Pou1f1 transcripts in pituitary development.
Topics: Animals; Humans; Mice; Dwarfism; Hypopituitarism; Pituitary Gland; RNA Precursors; Transcription Factor Pit-1
PubMed: 36427334
DOI: 10.1210/endocr/bqac198 -
The Journal of Clinical Endocrinology... Apr 2023Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a...
Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a classic cause of HO. HO often goes unnoticed initially as patients, families, and medical teams are focused on oncologic treatments and management of panhypopituitarism. HO is characterized by rapid weight gain in the first year after hypothalamic destruction followed by refractory obesity due to an energy imbalance of decreased energy expenditure without decreased food intake. Currently available pharmacotherapies are less effective in HO than in common obesity. While not a cure, dietary interventions, pharmacotherapy, and bariatric surgery can mitigate the effects of HO. Early recognition of HO is necessary to give an opportunity to intervene before substantial weight gain occurs. Our goal for this article is to review the pathophysiology of HO and to discuss available treatment options and future directions for prevention and treatment.
Topics: Humans; Pituitary Neoplasms; Hypothalamic Diseases; Craniopharyngioma; Obesity; Weight Gain
PubMed: 36413492
DOI: 10.1210/clinem/dgac678 -
World Journal of Clinical Cases Nov 2022Combined pituitary hormone deficiency 3 (CPHD3; OMIM: 221750) is caused by mutations within the LHX3 gene (OMIM: 600577), which located on the subtelomeric region of...
BACKGROUND
Combined pituitary hormone deficiency 3 (CPHD3; OMIM: 221750) is caused by mutations within the LHX3 gene (OMIM: 600577), which located on the subtelomeric region of chromosome 9 at band 9q34.3, has seven coding exons and six introns. LIM homeobox (LHX) 3 protein is the key regulator of pituitary development in fetal life.
CASE SUMMARY
We have diagnosed and treate an 11-year-old boy with combined pituitary hormone deficiency (CPHD). The main clinical manifestations were pituitary hormone deficiency, hydrocele of the tunica vaginalis, pituitary dwarfism, gonadal dysplasia, micropenis, clonic convulsion, and mild facial dysmorphic features. We collected peripheral blood from the patient, the patient's older brother, as well as their parents, and sequenced them by using high-throughput whole-exosome sequencing, which was verified by Sanger sequencing. The results showed that there were two compound heterozygous variants of c.613G>C (p.V205L) and c.220T>C (p.C74R) in the LHX3 gene. c.613G>C (p.V205L) was inherited from his mother and c.220T>C (p.C74R) from his father. His brother also has both variants and symptoms.
CONCLUSION
This study reported ununreported genetic mutations of LHX3, and recorded the treatment process of the patients, providing data for the diagnosis and treatment of CPHD.
PubMed: 36387827
DOI: 10.12998/wjcc.v10.i31.11486 -
Medical Research Archives Oct 2022Snakebite is a preventable yet often-neglected public health hazard with high chronic disability and mortality, mainly faced by rural communities in the...
BACKGROUND
Snakebite is a preventable yet often-neglected public health hazard with high chronic disability and mortality, mainly faced by rural communities in the tropics/subtropics. Endocrinological disorders following snakebite (especially Russell's viper in India) are notably underrecognized and can lead to remarkable morbidity, poor quality of life, and cardiovascular mortality. Anterior pituitary insufficiency has been the most common ailment following Russell's viper envenomation amid those endocrinological dysfunctions. On the contrary, the posterior pituitary and nearby hypothalamus mostly remain unharmed, so central diabetes insipidus is extremely rare following a viperid snakebite envenomation.
CASE PRESENTATION
The authors present a patient developing panhypopituitarism with evident spontaneous central diabetes insipidus 29 years after Russell's viper envenomation. Relevant investigations ruled out other possible etiologies, and he responded well to hormonal replacement therapy.
CONCLUSIONS
Panhypopituitarism with concurrent central diabetes insipidus may occur following snakebite (especially in Russell's viper envenomation). Early recognition and proper management of these complications are quintessential to preventing further misdiagnosis, under-recognition, morbidity, impaired quality of life, and mortality.
PubMed: 36382205
DOI: 10.18103/mra.v10i10.3195 -
Children (Basel, Switzerland) Oct 2022Brain tumors are the second most frequent type of all pediatric malignancies. Depending on their localization, patients with brain tumors may present neurological or... (Review)
Review
INTRODUCTION
Brain tumors are the second most frequent type of all pediatric malignancies. Depending on their localization, patients with brain tumors may present neurological or ophthalmological symptoms, but also weight anomalies and endocrine disorders ranging from growth hormone deficiency, anomalies of puberty, diabetes insipidus to panhypopituitarism. Immediately at diagnosis, all patients with brain tumors require a complete assessment of the hypothalamic-pituitary function in order to address eventual endocrine disorders. Moreover, children and adolescents undergoing brain surgery must receive peri- and postoperative hydrocortisone stress therapy. Post-operative disorders of water homeostasis are frequent, ranging from transient diabetes insipidus, as well as syndrome of inappropriate antidiuretic hormone secretion to persistent diabetes insipidus. Late endocrine disorders may result from surgery near or within the hypothalamic-pituitary region. Pituitary deficits are frequent after radiotherapy, especially growth hormone deficiency. Thyroid nodules or secondary thyroid cancers may arise years after radiotherapy. Gonadal dysfunction is frequent after chemotherapy especially with alkylating agents.
CONCLUSION
Early detection and treatment of specific endocrine disorders at diagnosis, perioperatively, and during long-term follow-up result in improved general and metabolic health and quality of life.
PubMed: 36360345
DOI: 10.3390/children9111617 -
Neurology India 2022Despite the evolution of endoscopic techniques, large pituitary adenomas with unfavorable characteristics and irregular anatomical configurations continue to pose a...
BACKGROUND
Despite the evolution of endoscopic techniques, large pituitary adenomas with unfavorable characteristics and irregular anatomical configurations continue to pose a challenge for the dexterity, skills, and patience of endoscopic surgeons. Transcranial surgery retains a significant role in these situations where the tumor access, hemostasis, and dissection around adjoining neurovascular tissues can be controlled efficaciously.
OBJECTIVE
In this report, we describe our experience with transcranial surgery for pituitary adenomas highlighting its safety and versatility in peripheral centers.
METHODS
We accessed the case files and imaging records of pituitary tumors operated between 2001 and 2019 at a private hospital in a major Indian city. The records were analyzed with emphasis on postoperative clinical course, visual, and endocrinological outcomes. The data was analyzed with respect to differences between transcranial and transsphenoidal procedures. Categorical variables were compared with Chi-square test/Fischer's exact test and difference in means evaluated with Welch's t-test.
RESULTS
A total of 178 procedures were performed in 173 patients with pituitary adenoma, who were the subjects of this study. Ninety-eight (56.7%) patients were treated by transsphenoidal excision whereas 80 (46.2%) underwent transcranial procedures (75 primary and five secondary). In the patients operated transcranially, we observed three deaths and nine patients suffered from significant morbidity. Visual outcomes were similar to the group operated transsphenoidally. However, incidence of panhypopituitarism was significantly higher in transcranial procedures; the extent of resection was poorer than transsphenoidal surgeries owing to more extensive nature of tumors.
CONCLUSIONS
In low-volume centers, the endoscopic skills required for transsphenoidal resection of large and complex pituitary adenomas may be scarce. Transcranial surgery, dependent on familiar microsurgical techniques and equipment, may still be viable, safe, and an effective option.
Topics: Humans; Pituitary Neoplasms; Neurosurgery; Sphenoid Bone; Microsurgery; Treatment Outcome; Retrospective Studies; Adenoma
PubMed: 36352606
DOI: 10.4103/0028-3886.359173 -
Problemy Endokrinologii Jul 2022Hypopituitarism is a state of complete or partial deficiency of pituitary hormones, including adrenal insufficiency, hypothyroidism, hypogonadism, growth hormone...
Hypopituitarism is a state of complete or partial deficiency of pituitary hormones, including adrenal insufficiency, hypothyroidism, hypogonadism, growth hormone deficiency, and, rarely, diabetes insipidus.The article describes a clinical case of hypopituitarism due to a pituitary tumor in a postmenopausal woman. Difficulties in diagnosing hypopituitarism were due to a history of primary hypothyroidism. The first identified component of panhypopituitarism in the patient, (central hypothyroidism) had previously been seen as laboratory indications of medication-induced hyperthyroidism.The non-specific nature of the clinical symptoms, as well as a relatively rare combination of endocrine diseases, led to a long examination period and delayed diagnosis of the pituitary tumor.Whether the development of hypopituitarism in a patient with a nonfunctional pituitary tumor is an indication for transsphenoidal pituitary surgery remains a controversial issue. The decision for surgery is made taking into account the characteristics of the course of the disease in a particular patient. In this clinical case, a conservative tactic was chosen with hormone replacement therapy for glucocorticoid and thyroid deficiency.
Topics: Female; Humans; Pituitary Neoplasms; Postmenopause; Delayed Diagnosis; Adenoma; Hypopituitarism; Hypothyroidism
PubMed: 36337016
DOI: 10.14341/probl13128 -
Surgical Neurology International 2022Patients diagnosed with pituitary apoplexy and presenting with acute visual deterioration require urgent surgical resection. This is also commonly associated with...
BACKGROUND
Patients diagnosed with pituitary apoplexy and presenting with acute visual deterioration require urgent surgical resection. This is also commonly associated with pituitary hypopituitarism that requires hormonal replacement for correction. This study was undertaken to evaluate the clinical recovery of 45 patients diagnosed with symptomatic pituitary apoplexy who underwent early (within 72 h of symptom onset) endoscopic transsphenoidal surgical resection with an emphasis on visual, ocular craniopathy, and endocrinological outcome.
METHODS
This is a retrospective analysis of a consecutive series of patients diagnosed with pituitary apoplexy between 2011 and 2020 treated by early (within 72 h of symptom onset) endoscopic transsphenoidal surgical resection. All tumors were histologically proven as pituitary adenomas. Clinical and neuro-ophthalmological examinations, imaging studies, and endocrinological evaluation were retrospectively reviewed. Patients with a minimum of 6 months follow-up were included in the study. The influence of patients' demographics, extent of visual and ocular motility impairment, preoperative endocrinological dysfunction, tumor size and extent, degree of resection, and surgical complications were analyzed as potential prognostic factors for recovery.
RESULTS
Forty-five patients were included in this retrospective study. Ages ranged from 27 to 57 years (mean: 42 years). All patients presented with headache and variable degrees of visual loss and visual field deficit. Ophthalmoplegia was present in 22 (48.9%) patients with 17 (37.8%) having bilateral ocular cranial nerve palsy. All patients had variable degrees of endocrinological deficiencies. All patients showed evidence of low cortisol, 14 (31.1%) showed hypothyroidism and 11 (24.4%) showed hypogonadism. There was evidence of hyperprolactinemia in 16 (35.6%) patients. All patients harbored a pituitary macroadenoma. Tumor resection was complete in 33 (73%) of patients, with residual tumor related to cavernous sinus or retrosellar extension. Operative complications were mainly related to short-term nasal complications occurring in 14 (31%) patients. Cerebrospinal fluid leak requiring revision surgery occurred in only one patient harboring a modified SIPAP Grade 3s tumor. Transient diabetes insipidus occurred in 9 (20%) patients, with 2 (4.4%) requiring long-term hormonal replacement. The mean follow-up was 25 months. Baseline visual improvement was achieved in 39 (86.7%) patients. Ocular cranial nerve palsy showed complete recovery in 17 (77.2%) patients. Endocrine follow-up showed that patients with panhypopituitarism (11 [24.4%]) failed to recover.
CONCLUSION
The current surgical series showed safety in terms of low complication rate and efficacy in terms of clinical outcome. The significant prognostic factor related to visual recovery was the degree of preoperative visual deficit. Recovery of ocular cranial neuropathy showed a higher recovery rate when it was unilateral as opposed to bilateral. Pituitary hormonal recovery was less favorable with pituitary panhypopituitarism being a poor prognostic factor.
PubMed: 36324938
DOI: 10.25259/SNI_642_2022 -
Journal of Neurosurgery. Case Lessons Oct 2022Pituitary abscess is a rare clinical entity, typically precipitated by Staphylococcus, Pseudomonas, or Aspergillus infection. Although Nocardia species-associated...
BACKGROUND
Pituitary abscess is a rare clinical entity, typically precipitated by Staphylococcus, Pseudomonas, or Aspergillus infection. Although Nocardia species-associated central nervous system abscesses have been documented in immunocompromised patients, no case of Nocardia pituitary abscesses has been previously reported.
OBSERVATIONS
A 44-year-old man presented with hemoptysis and was found to have a cavitary right lung nodule, which was presumed histoplasmosis, prompting antifungal treatment. Several months later, he developed panhypopituitarism. Magnetic resonance imaging identified a pituitary mass, which subsequently underwent transsphenoidal endoscopic biopsy. Infectious workup was negative, and the patient was discharged on intravenous ertapenem therapy. Over several months, he developed progressive headaches, and updated imaging confirmed interval enlargement of the mass with new cavernous sinus invasion. He underwent repeat endoscopic biopsy, which yielded positive cultures for Nocardia farcinica and prompted successful treatment with trimethoprim-sulfamethoxazole and linezolid.
LESSONS
The current study highlights a previously unreported clinical entity, the first pituitary abscess attributable to Nocardia sp. or N. farcinica, which arose in a young, immunocompetent individual. Although rare, atypical infections represent an important component in the differential diagnosis for sellar mass lesions.
PubMed: 36317239
DOI: 10.3171/CASE22266