Low levels of oestrogen effect the HPG axis with no feedback to the anterior pituitary to inhibit the secretion of FSH and LH. FSH and LH are secreted at abnormal elevated levels. Improper levels of these hormones will cause a failure to initiate puberty, undergo menarche, and develop secondary sex characteristics. If sufficient functional ovarian tissue is present, limited menstrual cycles can occur.The pathogenesis of 46,XX gonadal dysgenesis is unclear, as it can manifest from a variety of dysregulations. Interruption during ovarian development in embryogenesis can cause 46,XX gonadal dysgenesis with cases of abnormalities in the FSH receptor
and mutations in steroidogenic acute regulatory protein (StAR protein) which regulates steroid hormone production. 46,XY gonadal dysgenesis
46,XY gonadal dysgenesis is characteristic of male hypogonadism with karyotype 46,XY.In embryogenesis, the development of the male gonads is controlled by the testis determining factor located on the sex-determining region of the Y chromosome (SRY). The male gonad is dependent on SRY and the signalling pathways initiated to several other genes to facilitate testis development.The aetiology of 46,XY gonadal dysgenesis can be caused by mutations in the genes involved in testis development such as SRY, SOX9, WT1, SF1, and DHH. If a single or combination of these genes are mutated or deleted, downstream signalling  is disrupted, leading to malformation of male external genitalia.SRY acts on gene SOX9 which drives Sertoli cell formation and testis differentiation. An absence in SRY causes SOX9 to not be expressed at the appropriate time or concentration, leading to a deficiency in testosterone and anti-Müllerian hormone production.
A weekly dosage of Methotrexate (with or without daily Prednisone) may induce partial or complete response in some patients while others may require Cyclosporine or Cyclophosphamide.Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.Experimental data suggests that treatment with calcitrol (the active form of vitamin D) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines. Prognosis
The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia. Epidemiology
T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders. History
LGLL was discovered in 1985 by Thomas P. Loughran Jr. while working at Fred Hutchinson Cancer Research Center. Specimens from patients with LGLL are banked at the University of Virginia for research purposes, the only bank for such purposes. References


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