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The Journal of Clinical Endocrinology... Jun 2020Congenital pituitary hormone deficiencies with syndromic phenotypes and/or familial occurrence suggest genetic hypopituitarism; however, in many such patients the...
CONTEXT
Congenital pituitary hormone deficiencies with syndromic phenotypes and/or familial occurrence suggest genetic hypopituitarism; however, in many such patients the underlying molecular basis of the disease remains unknown.
OBJECTIVE
To describe patients with syndromic hypopituitarism due to biallelic loss-of-function variants in TBC1D32, a gene implicated in Sonic Hedgehog (Shh) signaling.
SETTING
Referral center.
PATIENTS
A Finnish family of 2 siblings with panhypopituitarism, absent anterior pituitary, and mild craniofacial dysmorphism, and a Pakistani family with a proband with growth hormone deficiency, anterior pituitary hypoplasia, and developmental delay.
INTERVENTIONS
The patients were investigated by whole genome sequencing. Expression profiling of TBC1D32 in human fetal brain was performed through in situ hybridization. Stable and dynamic protein-protein interaction partners of TBC1D32 were investigated in HEK cells followed by mass spectrometry analyses.
MAIN OUTCOME MEASURES
Genetic and phenotypic features of patients with biallelic loss-of-function mutations in TBC1D32.
RESULTS
The Finnish patients harboured compound heterozygous loss-of-function variants (c.1165_1166dup p.(Gln390Phefs*32) and c.2151del p.(Lys717Asnfs*29)) in TBC1D32; the Pakistani proband carried a known pathogenic homozygous TBC1D32 splice-site variant c.1372 + 1G > A p.(Arg411_Gly458del), as did a fetus with a cleft lip and partial intestinal malrotation from a terminated pregnancy within the same pedigree. TBC1D32 was expressed in the developing hypothalamus, Rathke's pouch, and areas of the hindbrain. TBC1D32 interacted with proteins implicated in cilium assembly, Shh signaling, and brain development.
CONCLUSIONS
Biallelic TBC1D32 variants underlie syndromic hypopituitarism, and the underlying mechanism may be via disrupted Shh signaling.
Topics: Adaptor Proteins, Signal Transducing; Biomarkers; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Hypopituitarism; Infant; Infant, Newborn; Male; Mutation; Pedigree; Phenotype; Prognosis; Signal Transduction
PubMed: 32060556
DOI: 10.1210/clinem/dgaa078 -
Journal of Neurosurgery. Case Lessons May 2023Cryptococcosis is the most common mycosis of the central nervous system. It may develop in immunocompetent and immunocompromised patients, the latter representing most...
BACKGROUND
Cryptococcosis is the most common mycosis of the central nervous system. It may develop in immunocompetent and immunocompromised patients, the latter representing most cases. The most common presentation of the disease is meningitis, whereas intra-axial lesions in the form of cryptococcoma are less frequent with a greater tendency to present in immunocompetent patients. The presentation of pituitary cryptococcoma is exceptional. To the best of the authors' knowledge, there is only one case published in the medical literature.
OBSERVATIONS
The authors present the case of a 30-year-old male without a relevant medical history. He was referred to our center with a pituitary mass on magnetic resonance imaging and panhypopituitarism. The patient underwent endonasal endoscopic transsphenoidal tumor resection, and a histopathological diagnosis of pituitary cryptococcoma was made. Medical management included fluconazole and intravenous amphotericin.
LESSONS
This case underscores the neurosurgical and medical management of an exceptional clinical presentation of pituitary cryptococcoma in an immunocompetent patient. To the best of the authors' knowledge, there is only one case published in the medical literature. This case provides an invaluable review of the clinical, imaging, and therapeutic considerations regarding this exceptional clinical entity.
PubMed: 37158394
DOI: 10.3171/CASE2372 -
Journal of Neurological Surgery. Part... Apr 2021A novel technique is described for transpalatal hypophysectomy as an option for sellar region surgery using a microscope and/or endoscope. A straight submucosal...
A novel technique is described for transpalatal hypophysectomy as an option for sellar region surgery using a microscope and/or endoscope. A straight submucosal tunnel (approximately 20 mm in diameter; 40-50 mm long-half the length required by conventional transsphenoidal hypophysectomy) is dissected in favorable alignment with the main tumor axis, providing a direct view that allows the surgeon to operate on large suprasellar tumors, even in cases of extra-axial expansion. In a 25-year period, over 50 patients benefited from this surgery. Macroadenomas devoid of extra-axial expansions were totally excised (76.5%), otherwise, partially (23.5%). Forty-nine patients (98%) were extubated soon after surgery. Mean surgery duration was 3 hour 32 minute, with 2 days 6 hour before free feeding was restored. Postoperative hospitalization under neurosurgical care averaged 6 days 6 hour. Currently, patients undergoing the procedure do not require nasal tampons and can eat soft foods soon after recovery from anesthesia. Although two patients (3.9%) presented with oronasal fistulae postoperatively, no episodes of severe hemorrhage occurred during surgery and there were no cases of liquoric fistulae, visual impairment, panhypopituitarism, or severe syndrome of inappropriate antidiuretic hormone secretion. The new surgical approach is safe, effective, and well accepted by patients, who reported low levels of discomfort. Postsurgical complications or sequela are currently rare, but further operations should be performed using more appropriate materials, instruments, and equipment to allow comparisons with other techniques.
PubMed: 33777637
DOI: 10.1055/s-0039-1694051 -
World Neurosurgery Aug 2021Pituitary apoplexy (PA) is a rare, but life-threatening, condition characterized by pituitary infarction and hemorrhage, most often in the setting of a preexisting... (Review)
Review
BACKGROUND
Pituitary apoplexy (PA) is a rare, but life-threatening, condition characterized by pituitary infarction and hemorrhage, most often in the setting of a preexisting adenoma. The risk factors and mechanisms associated with PA are poorly understood. Although neurovascular manifestations of coronavirus disease 2019 (COVID-19) infection have been documented, its association with PA has not yet been determined.
METHODS
From a prospectively collected database of patients treated at a tertiary care center for pituitary adenoma, we conducted a retrospective medical record review of PA cases during the COVID-19 pandemic from March 2020 to December 2020. We also conducted a literature review to identify other reported cases.
RESULTS
We identified 3 consecutive cases of PA and concomitant COVID-19 infection. The most common symptoms at presentation were headache and vision changes. The included patients were successfully treated with surgical decompression and medical management of the associated endocrinopathy, ultimately experiencing improvement in their visual symptoms at the latest follow-up examination. COVID-19 infection in the perioperative period was corroborated by polymerase chain reaction test results in all the patients.
CONCLUSIONS
With the addition of our series to the literature, 10 cases of PA in the setting of COVID-19 infection have been confirmed. The present series was limited in its ability to draw conclusions about the relationship between these 2 entities. However, COVID-19 infection might represent a risk factor for the development of PA. Further studies are required.
Topics: Adenoma; Adult; COVID-19; Female; Headache; Humans; Hypopituitarism; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms
PubMed: 34129968
DOI: 10.1016/j.wneu.2021.06.004 -
JAAD Case Reports Sep 2023
PubMed: 37680570
DOI: 10.1016/j.jdcr.2023.07.003 -
Cureus Jan 2021Untreated and rapid correction of neonatal hypernatremia leads to severe neurological complications. We describe the case of a six-week-old female who presented with...
Untreated and rapid correction of neonatal hypernatremia leads to severe neurological complications. We describe the case of a six-week-old female who presented with failure to thrive, and further workup revealed hypernatremic dehydration. Initially, she did not respond to treatment to correct the hyperosmotic state. Treatment with desmopressin was then initiated to determine the cause of hypernatremia. Central diabetes insipidus was confirmed as the patient responded to desmopressin. Serum sodium levels then dropped significantly, and the patient had three seizures within 24 hours. Cerebral edema was ruled out through computed tomography (CT) and electroencephalogram. Following the diagnosis of central diabetes insipidus, anterior pituitary hormone levels were obtained and found to be decreased. An investigation into the possible cause of panhypopituitarism led to the final diagnosis of septo-optic dysplasia, including absent septum pellucidum, optic nerve hypoplasia, and panhypopituitarism.
PubMed: 33552768
DOI: 10.7759/cureus.12450 -
BMC Endocrine Disorders Jan 2022The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar...
BACKGROUND
The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis.
CASE PRESENTATION
A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible.
CONCLUSION
Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Autoimmune Hypophysitis; Brain Neoplasms; Cisplatin; Diagnosis, Differential; Etoposide; Germinoma; Humans; Immunoglobulin G; Male; Sella Turcica
PubMed: 35033046
DOI: 10.1186/s12902-021-00930-3 -
Sexual Development : Genetics,... 2022LIM homeodomain (LIM-HD) family genes are transcription factors that play crucial roles in a variety of functions during embryonic development. The activities of the... (Review)
Review
LIM homeodomain (LIM-HD) family genes are transcription factors that play crucial roles in a variety of functions during embryonic development. The activities of the LIM-HD proteins are regulated by the co-regulators LIM only (LMO) and LIM domain-binding (LDB). In the mouse genome, there are 13 LIM-HD genes (Lhx1-Lhx9, Isl1-2, Lmx1a-1b), 4 Lmo genes (Lmo1-4), and 2 Ldb genes (Ldb1-2). Amongst these, Lhx1 is required for the development of the müllerian duct epithelium and the timing of the primordial germ cell migration. Lhx8 is necessary for oocyte differentiation and Lhx9 for somatic cell proliferation in the genital ridges and control of testosterone production in the Leydig cells. Lmo4 is involved in Sertoli cell differentiation. Mutations in LHX1 are associated with müllerian agenesis or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. LHX9 gene variants are reported in cases with disorders of sex development (DSD). Mutations in LHX3 and LHX4 are reported in patients with combined pituitary hormone deficiency having absent or delayed puberty. A transcript map of the Lhx, Lmo, and Ldb genes reveal that multiple LIM-HD genes and their co-regulators are expressed in a sexually dimorphic pattern in the developing mouse gonads. Unraveling the roles of LIM-HD genes during development will aid in our understanding of the causes of DSD.
Topics: Pregnancy; Male; Female; Mice; Animals; LIM-Homeodomain Proteins; 46, XX Disorders of Sex Development; Mullerian Ducts; Gonads; Homeodomain Proteins; Transcription Factors; DNA-Binding Proteins; LIM Domain Proteins
PubMed: 34518474
DOI: 10.1159/000518323 -
Case Reports in Women's Health Oct 2021Clinicians face many challenges regarding conception and pregnancy management for women with panhypopituitarism. Fertility in women with panhypopituitarism is often...
Clinicians face many challenges regarding conception and pregnancy management for women with panhypopituitarism. Fertility in women with panhypopituitarism is often reduced, and they are at risk of obstetric complications. The authors describe the case of a woman with congenital panhypopituitarism who had a successful pregnancy after ovulation induction and optimization of hormonal replacement therapy. This case report emphasizes the importance of careful adjustment of hormonal replacement therapy in managing pregnant women with panhypopituitarism.
PubMed: 34471611
DOI: 10.1016/j.crwh.2021.e00351 -
Hormone Research in Paediatrics 2020The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes...
OBJECTIVE
The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes and metabolic derangements. The aim of the study was to analyze the prevalence of long-term endocrine and metabolic comorbidities in a national cohort of CP patients based on the age at diagnosis and histology criteria.
DESIGN
A retrospective-prospective longitudinal cohort analysis.
METHODS
Forty-six patients with CP treated from 1979 onwards (19 with childhood-onset disease) in a single university institution were included in our study. Median follow-up from presentation was 12.8 years (interquartile range: 8.3-22.2 years) and comparable between age-at-diagnosis and histological subtype groups. Data on tumor histology were extracted from patients' records and re-evaluated if tissue samples were available (n = 32).
RESULTS
Childhood-onset patients presented more frequently with headache, and adult-onset with visual impairment. Prevalence of at least one pituitary axis affected increased from 54% at presentation to 100% at follow-up in childhood-onset and from 41 to 93% in adult-onset CP. Growth hormone deficiency, central diabetes insipidus, and panhypopituitarism were more prevalent in childhood-onset adamantinomatous CP (aCP) and least prevalent in adult-onset papillary CP (pCP). At follow-up, metabolic syndrome (MetS) was diagnosed in 80% of childhood-onset and 68% of adult-onset patients (p = 0.411). In the latter group, it tended to be more frequent in the aCP than pCP subtype (80 vs. 50%, p = 0.110).
CONCLUSIONS
Long-term endocrine and metabolic complications are very frequent in childhood- and adult-onset CP patients of both histological subtypes. The prevalence of MetS was higher compared to the largest cohort previously reported.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Comorbidity; Craniopharyngioma; Endocrine System Diseases; Female; Humans; Male; Metabolic Diseases; Middle Aged; Pituitary Neoplasms; Prevalence; Retrospective Studies; Young Adult
PubMed: 32460296
DOI: 10.1159/000507702