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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Side Effect Management
Investigation and management of erythrocytosis
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<blockquote data-quote="madman" data-source="post: 184359" data-attributes="member: 13851"><p><em><span style="color: rgb(184, 49, 47)">Erythrocytosis refers to an erythrocyte count above the sex-specific normal range and can be subclassified into relative erythrocytosis, caused by a reduction in plasma volume (hemoconcentration), or absolute erythrocytosis, caused by increased erythrocyte mass.</span></em> <span style="color: rgb(44, 130, 201)"><em>Primary erythrocytosis refers to the autonomous production of erythrocytes, typically from a myeloproliferative neoplasm (polycythemia vera [PV]). In contrast, secondary erythrocytosis is caused by a physiologically appropriate response to elevated serum erythropoietin levels. </em></span>Up to 4% of ambulatory men and 0.4% of ambulatory women in Canada have erythrocytosis, based on hemoglobin levels greater than 165 g/L or 160 g/L, respectively.1 <em><span style="color: rgb(184, 49, 47)">Differentiating PV from other causes of erythrocytosis is critical because early recognition and treatment of PV can prevent many of its vasomotor and thrombotic complications. Polycythemia vera is rare, with an incidence and prevalence of 0.84 and 22 per 100 000, respectively.2,3 Although the prevalence of secondary erythrocytosis is difficult to estimate, it is higher than that of PV. Secondary erythrocytosis affects 6%–8% of patients with chronic obstructive pulmonary disease4 and 2%–8% of patients with obstructive sleep apnea.5,6</span></em> In this review, we summarize a contemporary approach to differentiating PV from other causes of erythrocytosis and review the natural history, diagnosis, and management of PV (Box 1).</p><p></p><p></p><p></p><p></p><p><strong>KEY POINTS</strong></p><p></p><p>• <span style="color: rgb(184, 49, 47)">Primary erythrocytosis — or autonomous production of excess erythrocytes — most commonly occurs due to polycythemia vera (PV), a myeloproliferative neoplastic process that may be asymptomatic or may present with thrombosis, constitutional or vasomotor symptoms, or splenomegaly. </span></p><p></p><p>• <span style="color: rgb(184, 49, 47)">Secondary erythrocytosis, which is more common than PV, has a broad differential diagnosis that includes hypoxic lung disease, cyanotic congenital heart disease, <strong>medications (e.g., testosterone)</strong> and erythropoietin-producing malignant disorders. </span></p><p></p><p>• <span style="color: rgb(184, 49, 47)">Differentiating between PV and secondary erythrocytosis requires clinical evaluation and specialized investigations including measurement of the serum erythropoietin level and Janus kinase 2 mutation testing. </span></p><p></p><p>• <span style="color: rgb(184, 49, 47)">To reduce the risk of thrombosis, most patients with PV are treated with low-dose acetylsalicylic acid and phlebotomy to achieve a target hematocrit value of less than 0.45, whereas patients at high risk for thrombosis may receive cytoreductive therapy. </span></p><p></p><p>• <span style="color: rgb(184, 49, 47)">Treatment of secondary erythrocytosis should be directed at the underlying cause, and phlebotomy is not routinely recommended </span></p><p></p><p></p><p></p><p></p><p><strong>Box 2:</strong> <span style="color: rgb(184, 49, 47)"><strong>Causes of secondary erythrocytosis</strong></span>14</p><p></p><p><strong>Hypoxia-driven </strong></p><p></p><p><span style="color: rgb(184, 49, 47)">Generalized tissue hypoxia </span></p><p></p><p>• Smoking</p><p>• Carbon monoxide poisoning</p><p>• Hypoxic lung disease</p><p>• Obstructive sleep apnea</p><p>• Right to left cardiopulmonary shunt (e.g., cyanotic congenital heart disease)</p><p>• High altitude Local renal hypoxia</p><p>• Renal artery stenosis</p><p>• Hydronephrosis</p><p>• Renal cysts (polycystic kidney disease) Drug-associated</p><p>• Testosterone</p><p>• Erythropoietin Pathologic erythropoietin production</p><p>• Renal cell carcinoma</p><p>• Hepatocellular carcinoma</p><p>• Cerebellar hemangioblastoma</p><p>• Uterine leiomyomata</p><p>• Parathyroid carcinoma</p><p>• Meningioma Miscellaneous</p><p>• Erythrocytosis after renal transplantation</p><p>• <span style="color: rgb(184, 49, 47)">Idiopathic erythrocytosis*</span></p><p><span style="color: rgb(184, 49, 47)"></span></p><p><span style="color: rgb(184, 49, 47)"></span></p><p><span style="color: rgb(184, 49, 47)">*Diagnosis of exclusion </span></p><p></p><p></p><p></p><p></p><p><strong>Box 3:<span style="color: rgb(184, 49, 47)"> World Health Organization 2016 polycythemia vera diagnostic criteria</span></strong>16</p><p></p><p><span style="color: rgb(0, 0, 0)"><strong>Diagnosis of polycythemia vera requires all 3 major criteria OR the first 2 major criteria and the minor criterion </strong></span></p><p></p><p><span style="color: rgb(184, 49, 47)">Major criteria </span></p><p></p><p>• Hemoglobin level > 165 g/L in men, > 160 g/L in women OR hematocrit > 0.49 in men, > 0.48 in women OR increased erythrocyte mass</p><p></p><p>• Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic,<span style="color: rgb(184, 49, 47)"> mature megakaryocytes*</span></p><p></p><p>• Presence of JAK2 V617F or JAK2 exon 12 mutation Minor criterion</p><p></p><p>• Subnormal serum erythropoietin level</p><p></p><p></p><p><span style="color: rgb(184, 49, 47)">*Bone marrow biopsy is not required for patients with sustained absolute erythrocytosis, defined as a hemoglobin level greater than 185 g/L in men (hematocrit 0.55) or greater than 165 g/L in women (hematocrit 0.50) if the third major criterion and the minor criterion are met </span></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p><span style="color: rgb(0, 0, 0)"><strong>Conclusion </strong></span></p><p></p><p><span style="color: rgb(184, 49, 47)"><em><strong>Secondary erythrocytosis can be distinguished from PV in most patients with a focused clinical evaluation and, where available, determination of the erythropoietin level and JAK2 V617F mutation testing. The goals of treatment in PV are to alleviate symptoms reduce the risk of thromboembolism and monitor patients for transformation to myelofibrosis or acute leukemia.</strong></em></span><span style="color: rgb(44, 130, 201)"><em><strong> T</strong></em><strong><em>he majority of patients with PV should be treated with low-dose ASA and phlebotomy to achieve a target hematocrit value of less than 0.45. Cytoreduction, most commonly with hydroxyurea, should be considered in patients at high risk for thrombosis. Treatment of secondary erythrocytosis should be directed at the underlying cause.</em></strong></span></p></blockquote><p></p>
[QUOTE="madman, post: 184359, member: 13851"] [I][COLOR=rgb(184, 49, 47)]Erythrocytosis refers to an erythrocyte count above the sex-specific normal range and can be subclassified into relative erythrocytosis, caused by a reduction in plasma volume (hemoconcentration), or absolute erythrocytosis, caused by increased erythrocyte mass.[/COLOR][/I] [COLOR=rgb(44, 130, 201)][I]Primary erythrocytosis refers to the autonomous production of erythrocytes, typically from a myeloproliferative neoplasm (polycythemia vera [PV]). In contrast, secondary erythrocytosis is caused by a physiologically appropriate response to elevated serum erythropoietin levels. [/I][/COLOR]Up to 4% of ambulatory men and 0.4% of ambulatory women in Canada have erythrocytosis, based on hemoglobin levels greater than 165 g/L or 160 g/L, respectively.1 [I][COLOR=rgb(184, 49, 47)]Differentiating PV from other causes of erythrocytosis is critical because early recognition and treatment of PV can prevent many of its vasomotor and thrombotic complications. Polycythemia vera is rare, with an incidence and prevalence of 0.84 and 22 per 100 000, respectively.2,3 Although the prevalence of secondary erythrocytosis is difficult to estimate, it is higher than that of PV. Secondary erythrocytosis affects 6%–8% of patients with chronic obstructive pulmonary disease4 and 2%–8% of patients with obstructive sleep apnea.5,6[/COLOR][/I] In this review, we summarize a contemporary approach to differentiating PV from other causes of erythrocytosis and review the natural history, diagnosis, and management of PV (Box 1). [B]KEY POINTS[/B] • [COLOR=rgb(184, 49, 47)]Primary erythrocytosis — or autonomous production of excess erythrocytes — most commonly occurs due to polycythemia vera (PV), a myeloproliferative neoplastic process that may be asymptomatic or may present with thrombosis, constitutional or vasomotor symptoms, or splenomegaly. [/COLOR] • [COLOR=rgb(184, 49, 47)]Secondary erythrocytosis, which is more common than PV, has a broad differential diagnosis that includes hypoxic lung disease, cyanotic congenital heart disease, [B]medications (e.g., testosterone)[/B] and erythropoietin-producing malignant disorders. [/COLOR] • [COLOR=rgb(184, 49, 47)]Differentiating between PV and secondary erythrocytosis requires clinical evaluation and specialized investigations including measurement of the serum erythropoietin level and Janus kinase 2 mutation testing. [/COLOR] • [COLOR=rgb(184, 49, 47)]To reduce the risk of thrombosis, most patients with PV are treated with low-dose acetylsalicylic acid and phlebotomy to achieve a target hematocrit value of less than 0.45, whereas patients at high risk for thrombosis may receive cytoreductive therapy. [/COLOR] • [COLOR=rgb(184, 49, 47)]Treatment of secondary erythrocytosis should be directed at the underlying cause, and phlebotomy is not routinely recommended [/COLOR] [B]Box 2:[/B] [COLOR=rgb(184, 49, 47)][B]Causes of secondary erythrocytosis[/B][/COLOR]14 [B]Hypoxia-driven [/B] [COLOR=rgb(184, 49, 47)]Generalized tissue hypoxia [/COLOR] • Smoking • Carbon monoxide poisoning • Hypoxic lung disease • Obstructive sleep apnea • Right to left cardiopulmonary shunt (e.g., cyanotic congenital heart disease) • High altitude Local renal hypoxia • Renal artery stenosis • Hydronephrosis • Renal cysts (polycystic kidney disease) Drug-associated • Testosterone • Erythropoietin Pathologic erythropoietin production • Renal cell carcinoma • Hepatocellular carcinoma • Cerebellar hemangioblastoma • Uterine leiomyomata • Parathyroid carcinoma • Meningioma Miscellaneous • Erythrocytosis after renal transplantation • [COLOR=rgb(184, 49, 47)]Idiopathic erythrocytosis* *Diagnosis of exclusion [/COLOR] [B]Box 3:[COLOR=rgb(184, 49, 47)] World Health Organization 2016 polycythemia vera diagnostic criteria[/COLOR][/B]16 [COLOR=rgb(0, 0, 0)][B]Diagnosis of polycythemia vera requires all 3 major criteria OR the first 2 major criteria and the minor criterion [/B][/COLOR] [COLOR=rgb(184, 49, 47)]Major criteria [/COLOR] • Hemoglobin level > 165 g/L in men, > 160 g/L in women OR hematocrit > 0.49 in men, > 0.48 in women OR increased erythrocyte mass • Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic,[COLOR=rgb(184, 49, 47)] mature megakaryocytes*[/COLOR] • Presence of JAK2 V617F or JAK2 exon 12 mutation Minor criterion • Subnormal serum erythropoietin level [COLOR=rgb(184, 49, 47)]*Bone marrow biopsy is not required for patients with sustained absolute erythrocytosis, defined as a hemoglobin level greater than 185 g/L in men (hematocrit 0.55) or greater than 165 g/L in women (hematocrit 0.50) if the third major criterion and the minor criterion are met [/COLOR] [COLOR=rgb(0, 0, 0)][B]Conclusion [/B][/COLOR] [COLOR=rgb(184, 49, 47)][I][B]Secondary erythrocytosis can be distinguished from PV in most patients with a focused clinical evaluation and, where available, determination of the erythropoietin level and JAK2 V617F mutation testing. The goals of treatment in PV are to alleviate symptoms reduce the risk of thromboembolism and monitor patients for transformation to myelofibrosis or acute leukemia.[/B][/I][/COLOR][COLOR=rgb(44, 130, 201)][I][B] T[/B][/I][B][I]he majority of patients with PV should be treated with low-dose ASA and phlebotomy to achieve a target hematocrit value of less than 0.45. Cytoreduction, most commonly with hydroxyurea, should be considered in patients at high risk for thrombosis. Treatment of secondary erythrocytosis should be directed at the underlying cause.[/I][/B][/COLOR] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Side Effect Management
Investigation and management of erythrocytosis
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