@article{De Sanctis_2016, title={ACQUIRED HYPOGONADOTROPIC HYPOGONADISM (AHH) IN THALASSAEMIA MAJOR PATIENTS: AN UNDERDIAGNOSED CONDITION?}, volume={8}, url={https://www.mjhid.org/mjhid/article/view/2016.001}, DOI={10.4084/mjhid.2016.001}, abstractNote={<p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Introduction</span></strong></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">In males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and a lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function and strength, a worsened sense of well being and degraded quality of life (QOL).</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Patients and methods</span></strong></p><p class="Default" style="text-align: justify; text-justify: inter-ideograph; line-height: 115%;">We studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: <span lang="EN-GB">34.3 ± 8.8</span> years) <span style="color: windowtext; mso-ansi-language: EN-GB;" lang="EN-GB">with AHH. </span><span lang="EN-GB">Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. </span>All patients were on regular transfusions and iron chelation therapy.</p><p class="MsoNormal" style="text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US; mso-no-proof: yes;">Fasting venous blood samples were collected two weeks after  transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol,  luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate).</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*.   Bone mineral density was measured at the lumbar spine (L1-L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine.</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Results</span></strong></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">The mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L  and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH proved azoospermia in 3 and  oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml was significantly higher in </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">AHH</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> patients compared to controls (45.4 % versus 8.3%, p: </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">0.043). Heart iron concentrations (T2* values) were significantly lower in</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">AHH</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> patients compared to controls (p: </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">0.004).</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> Magnetic resonance imaging in the 3 azoospermic patients revealed volume loss and reduction of pituitary signal intensity.  Using DXA, 63.6 % (7/11) of patients with AHH were osteoporotic and 36.3 % (4/11) were osteopenic.  </span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Conclusions</span></strong></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">In our thalassemic patients iron overload and chronic liver disease appear to play a role in the development of AHH.  </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Treatment of AHH in TM patients is an important and vibrant field for improving their health and QOL. Early identification and management of AHH is very crucial to avoid long-term morbidity, including sexual dysfunction and infertility.</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB"> Therapy aims to restore serum testosterone to the mid–normal range. </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Many exciting opportunities remain for further research and therapeutic development.</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Key words:</span></strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">Acquired hypogonadotropic hypogonadism, thalassemia, iron overload, liver disease.</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Introduction</span></strong></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">In males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and a lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function and strength, a worsened sense of well being and degraded quality of life (QOL).</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Patients and methods</span></strong></p><p class="Default" style="text-align: justify; text-justify: inter-ideograph; line-height: 115%;">We studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: <span lang="EN-GB">34.3 ± 8.8</span> years) <span style="color: windowtext; mso-ansi-language: EN-GB;" lang="EN-GB">with AHH. </span><span lang="EN-GB">Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. </span>All patients were on regular transfusions and iron chelation therapy.</p><p class="MsoNormal" style="text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US; mso-no-proof: yes;">Fasting venous blood samples were collected two weeks after  transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol,  luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate).</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*.   Bone mineral density was measured at the lumbar spine (L1-L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine.</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Results</span></strong></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">The mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L  and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH proved azoospermia in 3 and  oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml was significantly higher in </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">AHH</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> patients compared to controls (45.4 % versus 8.3%, p: </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">0.043). Heart iron concentrations (T2* values) were significantly lower in</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">AHH</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> patients compared to controls (p: </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">0.004).</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;"> Magnetic resonance imaging in the 3 azoospermic patients revealed volume loss and reduction of pituitary signal intensity.  Using DXA, 63.6 % (7/11) of patients with AHH were osteoporotic and 36.3 % (4/11) were osteopenic.  </span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Conclusions</span></strong></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">In our thalassemic patients iron overload and chronic liver disease appear to play a role in the development of AHH.  </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Treatment of AHH in TM patients is an important and vibrant field for improving their health and QOL. Early identification and management of AHH is very crucial to avoid long-term morbidity, including sexual dysfunction and infertility.</span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB"> Therapy aims to restore serum testosterone to the mid–normal range. </span><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Many exciting opportunities remain for further research and therapeutic development.</span></p><p class="MsoNormal" style="margin-bottom: 10.0pt; text-align: justify; text-justify: inter-ideograph; line-height: 115%; mso-layout-grid-align: none; text-autospace: none;"><strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-US;">Key words:</span></strong><span style="font-size: 12.0pt; line-height: 115%; font-family: ’Times New Roman’,’serif’; mso-ansi-language: EN-GB;" lang="EN-GB">Acquired hypogonadotropic hypogonadism, thalassemia, iron overload, liver disease.</span></p>}, journal={Mediterranean Journal of Hematology and Infectious Diseases}, author={De Sanctis, Vincenzo}, year={2016}, month={Jan.}, pages={e2016001} }