Browsing by Subject "Hypopituitarism"

Now showing 1 - 3 of 3
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    Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone marrow and spleen
    (Elsevier, 2015-06) Capitano, Maegan L.; Chitteti, Brahmananda R.; Cooper, Scott; Srour, Edward F.; Bartke, Andrzej; Broxmeyer, Hal E.; Department of Microbiology & Immunology, IU School of Medicine
    Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice.
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    Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation
    (The Endocrine Society, 2015-06) Gregory, L. C.; Humayun, K. N.; Turton, J. P. G.; McCabe, M. J.; Rhodes, S. J.; Dattani, M. T.; Department of Cellular & Integrative Physiology, IU School of Medicine
    BACKGROUND: LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, only incompletely penetrant heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies. OBJECTIVE/HYPOTHESIS: To report a unique family with a novel recessive variant in LHX4 associated with a lethal form of congenital hypopituitarism that was identified through screening a total of 97 patients. METHOD: We screened 97 unrelated patients with combined pituitary hormone deficiency, including 65% with an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) were consulted upon identification of variants. RESULTS: We identified the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased male patients of Pakistani origin with severe panhypopituitarism associated with anterior pituitary aplasia and posterior pituitary ectopia. Both were born small for gestational age with a small phallus, undescended testes, and mid-facial hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the brothers, all three children died within the first week of life. The LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved location. The absence of homozygosity for the variant in over 65 000 controls suggests that it is likely to be responsible for the phenotype. CONCLUSION: We report, for the first time to our knowledge, a novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life.
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    Revisiting Pituitary Apoplexy
    (Oxford University Press, 2022-07-26) Donegan, Diane; Erickson, Dana; Medicine, School of Medicine
    Pituitary apoplexy (PA) is a rare clinical syndrome due to pituitary hemorrhage or infarction. It is characterized by the sudden onset of one or more of the following: severe headache, visual disturbance, nausea/vomiting, and or altered mental status. Most commonly, PA occurs in an underlying pituitary adenoma. The pathophysiology is not fully understood, but it is thought to involve elements of increased metabolic demand and/or compromise to the vasculature of the pituitary or pituitary tumor. Several risk factors have been described. Stabilization of the patient on presentation, replacement of hormonal deficiencies, and reversal of electrolyte abnormalities are the recommended initial steps in the management of patients with PA. Surgical decompression of the mass effect had been the recommended treatment for patients with PA; however, retrospective studies of patients with PA have demonstrated similar outcomes when a conservative approach is applied. This suggests that in highly selected clinical scenarios (mild visual deficit and improving symptoms), conservative management is possible. Further studies, however, are necessary to better stratify patients but are limited by the rarity of the condition and the acuity.