Resumen

El feocromocitoma es un tumor productor de catecolaminas con una prevalencia de 2 a 8 por millón de personas, que deriva en 85% de los casos de las células cromafines de la médula suprarrenal. La presente revisión, ilustrada con una serie de casos, brinda una actualización del tema que muestra situaciones de la vida real que ocurren en nuestra institución. Las dificultades para el estudio y diagnóstico, por la pobre disponibilidad de las pruebas para determinar el exceso de catecolaminas o sus metabolitos y lo infrecuente de la condición, pueden retardar la sospecha de esta patología como una posibilidad diagnóstica y diferir la interconsulta a endocrinología, necesaria para aportar en el tratamiento de los casos de feocromocitoma. Con este documento describimos lo que ocurre en nuestra población y realizamos una revisión práctica del estudio, diagnóstico y manejo actual de este tipo de tumores.

Abstract
Pheochromocytoma is a catecholamine producing tumor with a prevalence of 2 to 8 per million people, 85% arise from chromaffin cells of the adrenal medulla. The present review, illustrated with a case series, gives an update on the issue showing real life situations that occur in our institution. The difficulties in the study and diagnosis by the poor availability of tests for excess catecholamines or their metabolites and uncommon condition, can slow the suspicion of this disease as a diagnostic possibility and defer interconsultation to endocrinology, necessary for contribute to treat pheochromocytoma cases. In this paper we describe what happens in our community and realize a practical review in the study, diagnosis and current management of these tumors.

PDF

1. De Wailly P, Oragano L, Radé F, Malignant pheochromocytoma: new malignancy criteria. Langenbecks Arch Surg 2012; 397:239–46.
2. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Germ-line mutations in non syndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
3. Mittendorf E, Evans D, Lee J, Perrier N, Pheochromocytoma: Advances in Genetics, Diagnosis, Localization, and Treatment. Hematol Oncol Clin N Am 21 (2007) 509–525.
4. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Germ-line mutations in non syndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
5. Chen H , Sippel R, O’Dorisio M, Vinik A, Lloyd R, Karel, The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors. Pancreas 2010; 39: 775-783.
6. Lefebvre M, Foulkes W.D., Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol, 2014; 21: 8-17.
7. Fishbein L, Nathanson K, Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genet 205,
2012, 1-11.
8. Gimenez–Roqueplo F, Genetics of paragangliomas and pheochromocytomas [French]. Med Sci (Paris) 2012; 28:625–32.
9. Jafri M, Maher E, The genetics of pheochromocytoma: using clinical features to guide genetic testing. Eur J Endocrinol 2012:166,151–158.
10. Krishnappa R, Chikaraddi SB, Arun HN, Deshmane V, Pheochromocytoma in Indian patients: A retrospective study. Indian J Cancer 2012; 49:188-93.
11. Maher E, Neumann H, Richard S, Von Hippel–Lindau disease: A clinical and scientific review. Eur J Hum Genet (2011) 19, 617–623.
12. Opocher G, Schiavi, Genetics of pheochromocytomas and paragangliomas. Best Pract Res Clin Endocrinol Metab 24 (2010) 943–956.
13. Vicha A, Musil Z, Pacak K, Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options. Curr Opin Endocrinol Diabetes Obes 2013, 20:186–191.
14. Kola?kov K, Tupikowski K, Bednarek-Tupikowska G, Genetic Aspects of Pheochromocytoma. Adv Clin Exp Med 2012, 21, 6, 821–829.
15. Kaelin Jr. WG. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2(9): 673–682.
16. Mazzaglia P., Hereditary Pheochromocytoma and Paraganglioma. J Surg On- col 2012; 106:580–585.
17. Knudson Jr. AG, Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68(4): 820–823.
18. Hirbe A, Gutmann D, Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13: 834–43.
19. Burnichon N, mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 2012:18, 2828–2837.
20. Welander J, Soderkvist P, Gimm O, Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer. 2011: 1; 18, 253-276.
21. Jimerez C, Cote G, Arnold A, Gagel RF. Review: should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes? J Clin Endocrinol Metab 2006; 91:2851–8.
22. Walther MM, Herring J, Enquist E, Keiser HR & Linehan WM. Von Reckling- hausen’s disease and pheochromocytomas. J Urol 1999; 162(5): 1582– 1586.
23. Welander J, Soderkvist P, Gimm O. The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond. Endocr Relat Cancer
2013:20, 13–17.
24. Lenders J, Duh Q, Eisenhofer G, Gimenez-Roqueplo A, Grebe S , Murad M “et al”, Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2014 : 99(6):1915–1942.
25. Waldmann J, Langer P, Habbe N, Fendrich V, Ramaswamy A, Rothmund M, Bartsch DK , Slater EP , Mutations and polymorphisms in the SDHB, SDHD, VHL, and RET genes in sporadic and familial pheochromocytomas. Endocrine 2009 : 35 347–355.
26. Mannelli M, Ercolino T, Giache V, Simi L, Cirami C, Parenti G, Genetic screening for pheochromocytoma: should SDHC gene analysis be included? J Med Genet 2007: 44 586–587.
27. Dahia PL, Ross KN, Wright ME, Hayashida CY, Santagata S, Barontini M, Kung AL, Sanso G, Powers JF, Tischler, A HIF1 alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 2005: 1, 72–80.
28. De Jong WH, de Vries EG, Kema IP. Current status and future developments of LC–MS/MS in clinical chemistry for quantification of biogenic amines. Clin Biochem 2011: 44 95–103.
29. EisenhoferS G, Screening for Pheochromocytomas and Paragangliomas. Curr Hypertens Rep, 2012, 14:130–137.
30. Minnelli M, Lenders J , Pacak K , Parenti G , Eisenhofer G , Subclinical phaeochromocytoma. Best Pract Res Clin Endocrinol Metab 26, 2012: 507–515.
31. Van Berkel A, Lenders J, Timmers H, Biochemical diagnosis of phaeochromocytoma and paraganglioma. Eur J Endocrinol (2014) 170, R109–R119.
32. De Jong WH, Eisenhofer G, Post WJ, Muskiet FA, and de Vries EG, Kema IP. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab 2009 94 2841–2849.
33. Davidson FD. Paracetamol-associated interference in an HPLC-ECD assay for urinary free metadrenalines and catecholamines. Ann Clin Biochem
2004: 41 316–320.
34. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR , Pacak K. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab 2003: 88 2656–2666.
35. Lumachi F, Tregnaghi A, Zucchetta P, Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromocytomas: a prospective study. Nucl Med Commun. 2006: 27(7):583Y587.
36. Blanchet E, Martucci V, Pacak K, Pheochromocytoma and paraganglioma: current functional and future molecular imaging. Front Oncol.2012 :1 ,58
37. Song J, Mayo-Smith W, Current Status of Imaging for Adrenal Gland Tumors. Surg Oncol Clin N Am 23, 2014: 847–861
38. Jacques AE, Sahdev A, Sandrasagara M, Adrenal phaeochromocytoma: correlation of MRI appearances with histology and function. Eur Radiol 2008; 18:2885–92.
39. Khan S,Win Z, Szyszko T, Lloyd C, Dunn J, Alavi A , AL-Nahhas A, PET Imaging of Pheochromocytoma. PET Clin 2, 2008: 341–349.
40. Baudin E, Habra M, Deschamps F, Cote G, Dumont F, Cabanillas M “et al”, Treatment of malignant pheochromocytoma and paraganglioma. Eur J Endocrinol, 2014: 171, 111–122.
41. Havekes B, King K, Lai E, Romijn J, Corssmit E, Pacak K ,New imaging approaches to phaeochromocytomas and paragangliomas. Clin Endocrinol. 2010: 72, 137–145.
42. Goldstein RE, O’Neill JA Jr, Holcomb GW, Clinical experience over 48 years with pheochromocytoma. Ann Surg. 1999; 229(6):755-764.
43. Zuber S, Kantorovich V, Pacak K, Hypertension in Pheochromocytoma: Characteristics and Treatment. Endocrinol Metab Clin N Am 40 (2011) 295–311.
44. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007; 92(11):4069-4079.
45. Domi R, Laho H. Management of pheochromocytoma: Old ideas and new drugs. Niger J Clin Pract 2012; 15:253-257.
46. Ayala-Ramirez M, Feng L, Johnson MM, Ejaz S, Habra MA, Rich T, Busaidy N, Cote GJ, “et al”: Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab 2011: 96, 717–725.

Resumen

El feocromocitoma es un tumor productor de catecolaminas con una prevalencia de 2 a 8 por millón de personas, que deriva en 85% de los casos de las células cromafines de la médula suprarrenal. La presente revisión, ilustrada con una serie de casos, brinda una actualización del tema que muestra situaciones de la vida real que ocurren en nuestra institución. Las dificultades para el estudio y diagnóstico, por la pobre disponibilidad de las pruebas para determinar el exceso de catecolaminas o sus metabolitos y lo infrecuente de la condición, pueden retardar la sospecha de esta patología como una posibilidad diagnóstica y diferir la interconsulta a endocrinología, necesaria para aportar en el tratamiento de los casos de feocromocitoma. Con este documento describimos lo que ocurre en nuestra población y realizamos una revisión práctica del estudio, diagnóstico y manejo actual de este tipo de tumores.

Abstract
Pheochromocytoma is a catecholamine producing tumor with a prevalence of 2 to 8 per million people, 85% arise from chromaffin cells of the adrenal medulla. The present review, illustrated with a case series, gives an update on the issue showing real life situations that occur in our institution. The difficulties in the study and diagnosis by the poor availability of tests for excess catecholamines or their metabolites and uncommon condition, can slow the suspicion of this disease as a diagnostic possibility and defer interconsultation to endocrinology, necessary for contribute to treat pheochromocytoma cases. In this paper we describe what happens in our community and realize a practical review in the study, diagnosis and current management of these tumors.

PDF

1. De Wailly P, Oragano L, Radé F, Malignant pheochromocytoma: new malignancy criteria. Langenbecks Arch Surg 2012; 397:239–46.
2. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Germ-line mutations in non syndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
3. Mittendorf E, Evans D, Lee J, Perrier N, Pheochromocytoma: Advances in Genetics, Diagnosis, Localization, and Treatment. Hematol Oncol Clin N Am 21 (2007) 509–525.
4. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Germ-line mutations in non syndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
5. Chen H , Sippel R, O’Dorisio M, Vinik A, Lloyd R, Karel, The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors. Pancreas 2010; 39: 775-783.
6. Lefebvre M, Foulkes W.D., Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol, 2014; 21: 8-17.
7. Fishbein L, Nathanson K, Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genet 205,
2012, 1-11.
8. Gimenez–Roqueplo F, Genetics of paragangliomas and pheochromocytomas [French]. Med Sci (Paris) 2012; 28:625–32.
9. Jafri M, Maher E, The genetics of pheochromocytoma: using clinical features to guide genetic testing. Eur J Endocrinol 2012:166,151–158.
10. Krishnappa R, Chikaraddi SB, Arun HN, Deshmane V, Pheochromocytoma in Indian patients: A retrospective study. Indian J Cancer 2012; 49:188-93.
11. Maher E, Neumann H, Richard S, Von Hippel–Lindau disease: A clinical and scientific review. Eur J Hum Genet (2011) 19, 617–623.
12. Opocher G, Schiavi, Genetics of pheochromocytomas and paragangliomas. Best Pract Res Clin Endocrinol Metab 24 (2010) 943–956.
13. Vicha A, Musil Z, Pacak K, Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options. Curr Opin Endocrinol Diabetes Obes 2013, 20:186–191.
14. Kola?kov K, Tupikowski K, Bednarek-Tupikowska G, Genetic Aspects of Pheochromocytoma. Adv Clin Exp Med 2012, 21, 6, 821–829.
15. Kaelin Jr. WG. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2(9): 673–682.
16. Mazzaglia P., Hereditary Pheochromocytoma and Paraganglioma. J Surg On- col 2012; 106:580–585.
17. Knudson Jr. AG, Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68(4): 820–823.
18. Hirbe A, Gutmann D, Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13: 834–43.
19. Burnichon N, mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 2012:18, 2828–2837.
20. Welander J, Soderkvist P, Gimm O, Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer. 2011: 1; 18, 253-276.
21. Jimerez C, Cote G, Arnold A, Gagel RF. Review: should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes? J Clin Endocrinol Metab 2006; 91:2851–8.
22. Walther MM, Herring J, Enquist E, Keiser HR & Linehan WM. Von Reckling- hausen’s disease and pheochromocytomas. J Urol 1999; 162(5): 1582– 1586.
23. Welander J, Soderkvist P, Gimm O. The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond. Endocr Relat Cancer
2013:20, 13–17.
24. Lenders J, Duh Q, Eisenhofer G, Gimenez-Roqueplo A, Grebe S , Murad M “et al”, Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2014 : 99(6):1915–1942.
25. Waldmann J, Langer P, Habbe N, Fendrich V, Ramaswamy A, Rothmund M, Bartsch DK , Slater EP , Mutations and polymorphisms in the SDHB, SDHD, VHL, and RET genes in sporadic and familial pheochromocytomas. Endocrine 2009 : 35 347–355.
26. Mannelli M, Ercolino T, Giache V, Simi L, Cirami C, Parenti G, Genetic screening for pheochromocytoma: should SDHC gene analysis be included? J Med Genet 2007: 44 586–587.
27. Dahia PL, Ross KN, Wright ME, Hayashida CY, Santagata S, Barontini M, Kung AL, Sanso G, Powers JF, Tischler, A HIF1 alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 2005: 1, 72–80.
28. De Jong WH, de Vries EG, Kema IP. Current status and future developments of LC–MS/MS in clinical chemistry for quantification of biogenic amines. Clin Biochem 2011: 44 95–103.
29. EisenhoferS G, Screening for Pheochromocytomas and Paragangliomas. Curr Hypertens Rep, 2012, 14:130–137.
30. Minnelli M, Lenders J , Pacak K , Parenti G , Eisenhofer G , Subclinical phaeochromocytoma. Best Pract Res Clin Endocrinol Metab 26, 2012: 507–515.
31. Van Berkel A, Lenders J, Timmers H, Biochemical diagnosis of phaeochromocytoma and paraganglioma. Eur J Endocrinol (2014) 170, R109–R119.
32. De Jong WH, Eisenhofer G, Post WJ, Muskiet FA, and de Vries EG, Kema IP. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab 2009 94 2841–2849.
33. Davidson FD. Paracetamol-associated interference in an HPLC-ECD assay for urinary free metadrenalines and catecholamines. Ann Clin Biochem
2004: 41 316–320.
34. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR , Pacak K. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab 2003: 88 2656–2666.
35. Lumachi F, Tregnaghi A, Zucchetta P, Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromocytomas: a prospective study. Nucl Med Commun. 2006: 27(7):583Y587.
36. Blanchet E, Martucci V, Pacak K, Pheochromocytoma and paraganglioma: current functional and future molecular imaging. Front Oncol.2012 :1 ,58
37. Song J, Mayo-Smith W, Current Status of Imaging for Adrenal Gland Tumors. Surg Oncol Clin N Am 23, 2014: 847–861
38. Jacques AE, Sahdev A, Sandrasagara M, Adrenal phaeochromocytoma: correlation of MRI appearances with histology and function. Eur Radiol 2008; 18:2885–92.
39. Khan S,Win Z, Szyszko T, Lloyd C, Dunn J, Alavi A , AL-Nahhas A, PET Imaging of Pheochromocytoma. PET Clin 2, 2008: 341–349.
40. Baudin E, Habra M, Deschamps F, Cote G, Dumont F, Cabanillas M “et al”, Treatment of malignant pheochromocytoma and paraganglioma. Eur J Endocrinol, 2014: 171, 111–122.
41. Havekes B, King K, Lai E, Romijn J, Corssmit E, Pacak K ,New imaging approaches to phaeochromocytomas and paragangliomas. Clin Endocrinol. 2010: 72, 137–145.
42. Goldstein RE, O’Neill JA Jr, Holcomb GW, Clinical experience over 48 years with pheochromocytoma. Ann Surg. 1999; 229(6):755-764.
43. Zuber S, Kantorovich V, Pacak K, Hypertension in Pheochromocytoma: Characteristics and Treatment. Endocrinol Metab Clin N Am 40 (2011) 295–311.
44. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007; 92(11):4069-4079.
45. Domi R, Laho H. Management of pheochromocytoma: Old ideas and new drugs. Niger J Clin Pract 2012; 15:253-257.
46. Ayala-Ramirez M, Feng L, Johnson MM, Ejaz S, Habra MA, Rich T, Busaidy N, Cote GJ, “et al”: Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab 2011: 96, 717–725.

Resumen

El feocromocitoma es un tumor productor de catecolaminas con una prevalencia de 2 a 8 por millón de personas, que deriva en 85% de los casos de las células cromafines de la médula suprarrenal. La presente revisión, ilustrada con una serie de casos, brinda una actualización del tema que muestra situaciones de la vida real que ocurren en nuestra institución. Las dificultades para el estudio y diagnóstico, por la pobre disponibilidad de las pruebas para determinar el exceso de catecolaminas o sus metabolitos y lo infrecuente de la condición, pueden retardar la sospecha de esta patología como una posibilidad diagnóstica y diferir la interconsulta a endocrinología, necesaria para aportar en el tratamiento de los casos de feocromocitoma. Con este documento describimos lo que ocurre en nuestra población y realizamos una revisión práctica del estudio, diagnóstico y manejo actual de este tipo de tumores.

Abstract
Pheochromocytoma is a catecholamine producing tumor with a prevalence of 2 to 8 per million people, 85% arise from chromaffin cells of the adrenal medulla. The present review, illustrated with a case series, gives an update on the issue showing real life situations that occur in our institution. The difficulties in the study and diagnosis by the poor availability of tests for excess catecholamines or their metabolites and uncommon condition, can slow the suspicion of this disease as a diagnostic possibility and defer interconsultation to endocrinology, necessary for contribute to treat pheochromocytoma cases. In this paper we describe what happens in our community and realize a practical review in the study, diagnosis and current management of these tumors.

PDF

1. De Wailly P, Oragano L, Radé F, Malignant pheochromocytoma: new malignancy criteria. Langenbecks Arch Surg 2012; 397:239–46.
2. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Germ-line mutations in non syndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
3. Mittendorf E, Evans D, Lee J, Perrier N, Pheochromocytoma: Advances in Genetics, Diagnosis, Localization, and Treatment. Hematol Oncol Clin N Am 21 (2007) 509–525.
4. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Germ-line mutations in non syndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
5. Chen H , Sippel R, O’Dorisio M, Vinik A, Lloyd R, Karel, The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors. Pancreas 2010; 39: 775-783.
6. Lefebvre M, Foulkes W.D., Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol, 2014; 21: 8-17.
7. Fishbein L, Nathanson K, Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genet 205,
2012, 1-11.
8. Gimenez–Roqueplo F, Genetics of paragangliomas and pheochromocytomas [French]. Med Sci (Paris) 2012; 28:625–32.
9. Jafri M, Maher E, The genetics of pheochromocytoma: using clinical features to guide genetic testing. Eur J Endocrinol 2012:166,151–158.
10. Krishnappa R, Chikaraddi SB, Arun HN, Deshmane V, Pheochromocytoma in Indian patients: A retrospective study. Indian J Cancer 2012; 49:188-93.
11. Maher E, Neumann H, Richard S, Von Hippel–Lindau disease: A clinical and scientific review. Eur J Hum Genet (2011) 19, 617–623.
12. Opocher G, Schiavi, Genetics of pheochromocytomas and paragangliomas. Best Pract Res Clin Endocrinol Metab 24 (2010) 943–956.
13. Vicha A, Musil Z, Pacak K, Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options. Curr Opin Endocrinol Diabetes Obes 2013, 20:186–191.
14. Kola?kov K, Tupikowski K, Bednarek-Tupikowska G, Genetic Aspects of Pheochromocytoma. Adv Clin Exp Med 2012, 21, 6, 821–829.
15. Kaelin Jr. WG. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2(9): 673–682.
16. Mazzaglia P., Hereditary Pheochromocytoma and Paraganglioma. J Surg On- col 2012; 106:580–585.
17. Knudson Jr. AG, Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68(4): 820–823.
18. Hirbe A, Gutmann D, Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13: 834–43.
19. Burnichon N, mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 2012:18, 2828–2837.
20. Welander J, Soderkvist P, Gimm O, Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer. 2011: 1; 18, 253-276.
21. Jimerez C, Cote G, Arnold A, Gagel RF. Review: should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes? J Clin Endocrinol Metab 2006; 91:2851–8.
22. Walther MM, Herring J, Enquist E, Keiser HR & Linehan WM. Von Reckling- hausen’s disease and pheochromocytomas. J Urol 1999; 162(5): 1582– 1586.
23. Welander J, Soderkvist P, Gimm O. The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond. Endocr Relat Cancer
2013:20, 13–17.
24. Lenders J, Duh Q, Eisenhofer G, Gimenez-Roqueplo A, Grebe S , Murad M “et al”, Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2014 : 99(6):1915–1942.
25. Waldmann J, Langer P, Habbe N, Fendrich V, Ramaswamy A, Rothmund M, Bartsch DK , Slater EP , Mutations and polymorphisms in the SDHB, SDHD, VHL, and RET genes in sporadic and familial pheochromocytomas. Endocrine 2009 : 35 347–355.
26. Mannelli M, Ercolino T, Giache V, Simi L, Cirami C, Parenti G, Genetic screening for pheochromocytoma: should SDHC gene analysis be included? J Med Genet 2007: 44 586–587.
27. Dahia PL, Ross KN, Wright ME, Hayashida CY, Santagata S, Barontini M, Kung AL, Sanso G, Powers JF, Tischler, A HIF1 alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 2005: 1, 72–80.
28. De Jong WH, de Vries EG, Kema IP. Current status and future developments of LC–MS/MS in clinical chemistry for quantification of biogenic amines. Clin Biochem 2011: 44 95–103.
29. EisenhoferS G, Screening for Pheochromocytomas and Paragangliomas. Curr Hypertens Rep, 2012, 14:130–137.
30. Minnelli M, Lenders J , Pacak K , Parenti G , Eisenhofer G , Subclinical phaeochromocytoma. Best Pract Res Clin Endocrinol Metab 26, 2012: 507–515.
31. Van Berkel A, Lenders J, Timmers H, Biochemical diagnosis of phaeochromocytoma and paraganglioma. Eur J Endocrinol (2014) 170, R109–R119.
32. De Jong WH, Eisenhofer G, Post WJ, Muskiet FA, and de Vries EG, Kema IP. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab 2009 94 2841–2849.
33. Davidson FD. Paracetamol-associated interference in an HPLC-ECD assay for urinary free metadrenalines and catecholamines. Ann Clin Biochem
2004: 41 316–320.
34. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR , Pacak K. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab 2003: 88 2656–2666.
35. Lumachi F, Tregnaghi A, Zucchetta P, Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromocytomas: a prospective study. Nucl Med Commun. 2006: 27(7):583Y587.
36. Blanchet E, Martucci V, Pacak K, Pheochromocytoma and paraganglioma: current functional and future molecular imaging. Front Oncol.2012 :1 ,58
37. Song J, Mayo-Smith W, Current Status of Imaging for Adrenal Gland Tumors. Surg Oncol Clin N Am 23, 2014: 847–861
38. Jacques AE, Sahdev A, Sandrasagara M, Adrenal phaeochromocytoma: correlation of MRI appearances with histology and function. Eur Radiol 2008; 18:2885–92.
39. Khan S,Win Z, Szyszko T, Lloyd C, Dunn J, Alavi A , AL-Nahhas A, PET Imaging of Pheochromocytoma. PET Clin 2, 2008: 341–349.
40. Baudin E, Habra M, Deschamps F, Cote G, Dumont F, Cabanillas M “et al”, Treatment of malignant pheochromocytoma and paraganglioma. Eur J Endocrinol, 2014: 171, 111–122.
41. Havekes B, King K, Lai E, Romijn J, Corssmit E, Pacak K ,New imaging approaches to phaeochromocytomas and paragangliomas. Clin Endocrinol. 2010: 72, 137–145.
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43. Zuber S, Kantorovich V, Pacak K, Hypertension in Pheochromocytoma: Characteristics and Treatment. Endocrinol Metab Clin N Am 40 (2011) 295–311.
44. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007; 92(11):4069-4079.
45. Domi R, Laho H. Management of pheochromocytoma: Old ideas and new drugs. Niger J Clin Pract 2012; 15:253-257.
46. Ayala-Ramirez M, Feng L, Johnson MM, Ejaz S, Habra MA, Rich T, Busaidy N, Cote GJ, “et al”: Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab 2011: 96, 717–725.

La tiroiditis es un fenómeno inflamatorio de la tiroides, de causas diversas, incluyendo raramente traumas de la región anterior del cuello. Se presenta el caso de un paciente con depresión mayor de curso crónico, con síntomas sicóticos y farmacodependencia, quien intenta suicidarse mediante ahorcamiento. Ingresa con un Glasgow de 3/15, por lo cual requiere intubación orotraqueal inmediata, posterior traslado a unidad de cuidados intensivos y ventilación mecánica durante diez días. Durante este periodo desarrolla taquicardia persistente, diaforesis y alteraciones del sensorio, se encontró TSH en 0,00 (0,4- 4 mUI/ml); una T3 total en 2,42, (0,8-2,0 ng/ml) y T4 libre >6 (0,93-1,70 ng/dL), la gammagrafía de tiroides con tecnecio 99 mostró bloqueo de la captación. Se sospechó tormenta tiroidea y recibió propranolol 80 mg vía oral cada 8 horas en forma continua e hidrocortisona 50 mg intravenosa cada 8 horas durante
5 días. Los controles, dos semanas después, muestran TSH en 0,00 (0,4-4 uUI/ml) y una T4 libre de 1,78 (0,93-1,70 ng/dl) y cuatro días después normalización de la T4 libre (1,45 ng/dl), acompañado de mejoría clínica de los síntomas adrenérgicos.
Se presenta el caso de un paciente con tiroiditis postrauma, entidad que debe ser sospechada en pacientes con trauma en el cuello que presenten síntomas de tirotoxicosis.

Abstract

Thyroiditis is an inflammatory disorder of the thyroid, which stems from a variety of causes including in some rare cases trauma to the neck. We present the case of a male patient with chronic depression associated with psychotic symptoms and drug abuse that tried to commit suicide through hanging. The patient had a Glasgow Coma Scale 3/15 requiring orotracheal intubation, a stay in the intensive care unit and mechanical ventilation for 10 days. While in the ICU the patient developed persistent tachycardia, diaphoresis and changes in mental status. A suppressed TSH was found with a level of 0,00 (0,4-4 uUI/ml) and high thyroid hormone level (total T 2,42, (normal value 0,8-2,0 ng/ml) and free T >6 (normal value 0,93-1,70 ng/dL). A technetium-99 thyroid scintygraphy showed blocked uptake. With those findings, a thyroid storm was suspected and management was begun with propranolol 80 mg per mouth every 8 hours and IV hydrocortisone 50 mg every 8 hours for 5 days. Two weeks later, the TSH was 0,00 (0,4-4 uUI/ ml) and the free T4 was 1,78 (normal value 0,93-1,70 ng/dl). Four days later, the free T4 concentration was normal (1,45 ng/dl) with a clinical improvement of the adrenergic symptoms. Inconclusion, thyroiditis should be suspected in patients with neck trauma with compatible clinical manifestations.

1. Meurisse M, Gollogly L, Degauque C, Fumal I, Defechereux T, Hamoir E. Iatrogenic thyrotoxicosis: causal circumstances, pathophysiology, and principles of treatment-review of the literature. World J Surg. 2000;24(11):1377-85.
2. Blum M, Schloss MF. Martial-arts thyroiditis. N Engl J Med. 1984;311(3):199- 200.
3. Stang MT, Yim JH, Challinor SM, Bahl S, Carty SE. Hyperthyroidism after parathyroid exploration. Surgery. 2005;138(6):1058-64; discussion 64-5.
4. Lederer SR, Schiffl H. Transient hyperthyroidism after total parathyroidectomy for tertiary hyperparathyroidism: a report of two cases.Wien Klin Wochenschr. 2008;120(13-14):432-4. doi: 10.1007/s00508-008-0996-3.
5. Salazar Thieroldt E, Boado Lama J, Molinero Abad S, Miján de la Torre A. Transient hyperthyroidism after total laryngectomy for laryngeal cancer. Nutr Hosp. 2014 Oct 24;31(n01):380-383.
6. Yoon SJ, Kim DM, Kim JU, Kim KW, Ahn CW, Cha BS, et al. A case of thyroid storm due to thyrotoxicosis factitia. Yonsei Med J. 2003;44(2):351-4.
7. Leckie RG, Buckner AB, Bornemann M. Seat belt-related thyroiditis documented with thyroid Tc-99m pertechnetate scans. Clin Nucl Med. 1992;17(11):859-60.
8. Nishihara E, Miyauchi A, Matsuzuka F, Sasaki I, Ohye H, Kubota S, et al. Acute suppurative thyroiditis after fine-needle aspiration causing thyrotoxicosis. Thyroid. 2005;15(10):1183-7.
9. Kobayashi A, Kuma K, Matsuzuka F, Hirai K, Fukata S, Sugawara M. Thyrotoxicosis after needle aspiration of thyroid cyst. J Clin Endocrinol Metab. 1992;75(1):21-4.
10. Carney JA, Moore SB, Northcutt RC, Woolner LB, Stillwell GK. Palpation thyroiditis (multifocal granulomatour folliculitis). Am J Clin Pathol. 1975;64(5):639-47.
11. Ramirez JI, Petrone P, Kuncir EJ, Asensio JA. Thyroid storm induced by strangulation. South Med J. 2004;97(6):608-10.
12. Wartofsky L. Clinical criteria for the diagnosis of thyroid storm. Thyroid. 2012;22(7):659-60.
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Contexto: Los valores de referencia para pruebas tiroideas deben estandarizarse en la población local. En Colombia no tenemos datos propios.
Objetivo: Describir los niveles de hormonas tiroideas (TSH y T4 libre) en adultos de Medellín, Colombia.
Métodos: Estudio retrospectivo, con información obtenida de la base de datos electrónica de Dinámica IPS.
Criterios de inclusión: Adultos (18-50 años), con medición simultánea de TSH y T4 libre (T4L), ambos dentro del valor de referencia suministrado por el proveedor de la prueba (Abbott).
Criterios de exclusión: mujeres embarazadas, hipotiroidismo primario conocido y anticuerpos anti-TPO o antitiroglobulina positivos. Los datos se compararon con una curva normal. Se realizó un análisis de regresión lineal entre T4L y TSH o LogTSH.
Resultados: Se obtuvieron datos desde febrero 1 hasta abril 30 de 2015, n = 2.438 personas, el 80,5% eran mujeres, el promedio de edad 35,74±8,4 años. El promedio de TSH fue 2,19±1,10 mUI/L y el de T4L 1,00±0,11 ng/dl. Los valores de T4L se distribuyen de forma normal, pero los de TSH se distribuyeron como una curva asintótica hacia la izquierda. El 95% de los valores de T4L fueron entre 0,74-1,26 ng/dl y de TSH entre 0,36 y 4,55 mUI/L. No hubo diferencias entre TSH y T4 libre por sexo o por edad. El análisis de regresión lineal no mostró relación entre la T4L y TSH o LogTSH.
Conclusiones: En adultos entre 18 a 50 años, el 95% de los valores de TSH oscilan entre 0,36-4,55 mUI/ L y para T4 L entre 0,74-1,26 ng/dl. No hubo diferencias por sexo o décadas de edad. Tampoco entre valores de TSH y T4L.

Abstract
Context: Reference values for thyroid tests should be standardized in local adult people. In Colombia we do not have own data.
Objective: To describe serum levels of thyroid hormones (TSH and free T4) in adults from Medellin, Colombia.
Methods: Retrospective study based in information from an electronic database.
Inclusion criteria: Adults 18-50 years-old adults with simultaneous measurement of TSH and free T4 (FT4), both values within the reference value supplied by Abbot.
Exclusion criteria: pregnant women, primary hypothyroidism and positive TPO or thyroglobulin antibodies. Data were compared with a normal curve. Linear regression analysis between FT4 and TSH and between FT4 and LogTSH was performed.
Results: Data from February 1 to April 30 2015 were obtained, n=2.438 individuals, 80.5% were women, age mean±SD35.74±8.4 years. TSH values were mean±SD 2.19±1.10 mUI/L and FT4 1.00±0.11 ng/dl. FT4 were distributed as a normal curve, meanwhile TSH showed an asymptotic curve to the left. Ninety five percent of FT4 values were between 0.74-1.26 ng/dl and TSH 0.36-4.55 mUI/L. There was no difference between TSH and FT4 by gender or by age. Linear regression analysis do not showed any relationship between TSH and FT4.
Conclusions: In adult population 95% of serum TSH and FT4 ranging between 0.36-4.55 uUI/L and 0.74-1.26 ng/dl respectively. There were no differences by gender or age groups, or relationship between TSH and FT4.

1. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by The American Association of Clinical Endocrinologist and The American Thyroid Association. Endocr Pract. 2012 Nov-Dec;18(6):988-1028.
2. Baloch Z, Carayon P, Conte-Devolx B, Rasmussen U.F., Henry JF, LiVolsi V et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. National Academy of Clinical Biochemistry. Thyroid. 2003 Jan;13(1):3-126.
3. Langén VL, Niiranen TJ, Mäki J, Sundvall J, Jula AM. Thyroid-stimulating hormone reference range and factors affecting it in a nationwide random sample. Clin Chem Lab Med. 2014 Dec; 52(12):1807-13.
4. Kratzsch J, Fiedler GM, Leichtle A, Brügel M, Buchbinder S, Otto L, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem 2005; 51:1480.
5. Vadiveloo T, Donnan PT, Murphy MJ, Leese GP. Age- and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS). J Clin Endocrinol Metab 2013; 98:1147.
6. Vanderpump MPJ, Tunbridge WMG, French JM, Appleton D, Bates D, Rodgers H et al. The incidence of thyroid disorders in the community; a twenty year follow up of the Whickham survey. Clin Endocrinol 1995; 43:55-68.
7. Biondi B. The Normal TSH Reference Range: ¿What Has Changed in the Last Decade? J Clin Endocrinol Metab, 2013 Sep;98(9):3584-7.
8. P. Laurberg, S. Andersen, A. Carl´e, J. Karmisholt, N. Knudsen, and I. B. Pedersen. The TSH upper reference limit: where are we at?. Nat Rev Endocrinol. 2011 Apr;7(4):232-9
9. Brabant G, Beck-Peccoz P, Jarzab B et al. Is there a need to redefine the upper normal limit of TSH? Eur J Endocrinol. 154; 5:633–637, 2006.
10. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab, 90; 9: 5483–5488, 2005.
11. Dickey RA, Wartofsky L, Feld S. Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 15; 9: 1035–1039, 2005.
12. Surks MI. TSH reference limits: new concepts and implications for diagnosis of subclinical hypothyroidism. Endocrine Practice 2013, vol 19, No.6.
13. Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thy roxine and TSH in the regulation of thyroid function. Eur J Endocrinol, 162; 6: 1123– 1129, 2010.
14. Wardle CA, Fraser WD, Squire CR. Pitfalls in the use of thyrotropin concentration as a first-line thyroid-function test. Lancet 2001; 357:1013-4.
15. C. A. Spencer, J. G. Hollowell, M. Kazarosyan, and L. E. Braverman, National Health and Nutrition Examination Survey III Thyroid-StimulatingHormone (TSH)-thyro- peroxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction. J Clin Endocrinol Metab, vol. 92, no. 11, pp. 4236–4240, 2007.
16. Andersen S1, Bruun NH, Pedersen KM, Laurberg P. Biologic variation is important for interpretation of thyroid function tests. Thyroid. 2003 Nov; 13 (11):1069-78.
17. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANESIII). J Clin Endocri nol Metab.2002.87 ;( 2):489–499.
18. Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab 97:1554, 2012.
19. T. E. Hamilton, S. Davis, L. Onstad, and K. J. Kopecky, Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism, J Clin Endocrinol Metab, vol. 93, no. 4, pp. 1224–1230, 2008.
20. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the U.S. population: implications for the prevalence of subclinical hypothyroidism. The Journal of Clinical Endocrinology and Metabolism, 92; 12:4575–4582, 2007.
21. Boucai L, Hollowell JG, Surks MI. An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid. 2011; 21: 5-11.
22. Surks M, Boucai L. Age and race- based serum thyrotropin reference limits. J Clin Endocrinol Metab 95: 496-502- 2010.
23. Hoermann R, Midgley J. TSH Measurement and Its Implications for Personalised Clinical Decision-Making. Journal of Thyroid Research. Volume 2012. doi: 10.1155/2012/438037.

Contexto: Los valores de referencia para pruebas tiroideas deben estandarizarse en la población local. En Colombia no tenemos datos propios.
Objetivo: Describir los niveles de hormonas tiroideas (TSH y T4 libre) en adultos de Medellín, Colombia.
Métodos: Estudio retrospectivo, con información obtenida de la base de datos electrónica de Dinámica IPS.
Criterios de inclusión: Adultos (18-50 años), con medición simultánea de TSH y T4 libre (T4L), ambos dentro del valor de referencia suministrado por el proveedor de la prueba (Abbott).
Criterios de exclusión: mujeres embarazadas, hipotiroidismo primario conocido y anticuerpos anti-TPO o antitiroglobulina positivos. Los datos se compararon con una curva normal. Se realizó un análisis de regresión lineal entre T4L y TSH o LogTSH.
Resultados: Se obtuvieron datos desde febrero 1 hasta abril 30 de 2015, n = 2.438 personas, el 80,5% eran mujeres, el promedio de edad 35,74±8,4 años. El promedio de TSH fue 2,19±1,10 mUI/L y el de T4L 1,00±0,11 ng/dl. Los valores de T4L se distribuyen de forma normal, pero los de TSH se distribuyeron como una curva asintótica hacia la izquierda. El 95% de los valores de T4L fueron entre 0,74-1,26 ng/dl y de TSH entre 0,36 y 4,55 mUI/L. No hubo diferencias entre TSH y T4 libre por sexo o por edad. El análisis de regresión lineal no mostró relación entre la T4L y TSH o LogTSH.
Conclusiones: En adultos entre 18 a 50 años, el 95% de los valores de TSH oscilan entre 0,36-4,55 mUI/ L y para T4 L entre 0,74-1,26 ng/dl. No hubo diferencias por sexo o décadas de edad. Tampoco entre valores de TSH y T4L.

Abstract
Context: Reference values for thyroid tests should be standardized in local adult people. In Colombia we do not have own data.
Objective: To describe serum levels of thyroid hormones (TSH and free T4) in adults from Medellin, Colombia.
Methods: Retrospective study based in information from an electronic database.
Inclusion criteria: Adults 18-50 years-old adults with simultaneous measurement of TSH and free T4 (FT4), both values within the reference value supplied by Abbot.
Exclusion criteria: pregnant women, primary hypothyroidism and positive TPO or thyroglobulin antibodies. Data were compared with a normal curve. Linear regression analysis between FT4 and TSH and between FT4 and LogTSH was performed.
Results: Data from February 1 to April 30 2015 were obtained, n=2.438 individuals, 80.5% were women, age mean±SD35.74±8.4 years. TSH values were mean±SD 2.19±1.10 mUI/L and FT4 1.00±0.11 ng/dl. FT4 were distributed as a normal curve, meanwhile TSH showed an asymptotic curve to the left. Ninety five percent of FT4 values were between 0.74-1.26 ng/dl and TSH 0.36-4.55 mUI/L. There was no difference between TSH and FT4 by gender or by age. Linear regression analysis do not showed any relationship between TSH and FT4.
Conclusions: In adult population 95% of serum TSH and FT4 ranging between 0.36-4.55 uUI/L and 0.74-1.26 ng/dl respectively. There were no differences by gender or age groups, or relationship between TSH and FT4.

1. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by The American Association of Clinical Endocrinologist and The American Thyroid Association. Endocr Pract. 2012 Nov-Dec;18(6):988-1028.
2. Baloch Z, Carayon P, Conte-Devolx B, Rasmussen U.F., Henry JF, LiVolsi V et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. National Academy of Clinical Biochemistry. Thyroid. 2003 Jan;13(1):3-126.
3. Langén VL, Niiranen TJ, Mäki J, Sundvall J, Jula AM. Thyroid-stimulating hormone reference range and factors affecting it in a nationwide random sample. Clin Chem Lab Med. 2014 Dec; 52(12):1807-13.
4. Kratzsch J, Fiedler GM, Leichtle A, Brügel M, Buchbinder S, Otto L, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem 2005; 51:1480.
5. Vadiveloo T, Donnan PT, Murphy MJ, Leese GP. Age- and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS). J Clin Endocrinol Metab 2013; 98:1147.
6. Vanderpump MPJ, Tunbridge WMG, French JM, Appleton D, Bates D, Rodgers H et al. The incidence of thyroid disorders in the community; a twenty year follow up of the Whickham survey. Clin Endocrinol 1995; 43:55-68.
7. Biondi B. The Normal TSH Reference Range: ¿What Has Changed in the Last Decade? J Clin Endocrinol Metab, 2013 Sep;98(9):3584-7.
8. P. Laurberg, S. Andersen, A. Carl´e, J. Karmisholt, N. Knudsen, and I. B. Pedersen. The TSH upper reference limit: where are we at?. Nat Rev Endocrinol. 2011 Apr;7(4):232-9
9. Brabant G, Beck-Peccoz P, Jarzab B et al. Is there a need to redefine the upper normal limit of TSH? Eur J Endocrinol. 154; 5:633–637, 2006.
10. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab, 90; 9: 5483–5488, 2005.
11. Dickey RA, Wartofsky L, Feld S. Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 15; 9: 1035–1039, 2005.
12. Surks MI. TSH reference limits: new concepts and implications for diagnosis of subclinical hypothyroidism. Endocrine Practice 2013, vol 19, No.6.
13. Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thy roxine and TSH in the regulation of thyroid function. Eur J Endocrinol, 162; 6: 1123– 1129, 2010.
14. Wardle CA, Fraser WD, Squire CR. Pitfalls in the use of thyrotropin concentration as a first-line thyroid-function test. Lancet 2001; 357:1013-4.
15. C. A. Spencer, J. G. Hollowell, M. Kazarosyan, and L. E. Braverman, National Health and Nutrition Examination Survey III Thyroid-StimulatingHormone (TSH)-thyro- peroxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction. J Clin Endocrinol Metab, vol. 92, no. 11, pp. 4236–4240, 2007.
16. Andersen S1, Bruun NH, Pedersen KM, Laurberg P. Biologic variation is important for interpretation of thyroid function tests. Thyroid. 2003 Nov; 13 (11):1069-78.
17. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANESIII). J Clin Endocri nol Metab.2002.87 ;( 2):489–499.
18. Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab 97:1554, 2012.
19. T. E. Hamilton, S. Davis, L. Onstad, and K. J. Kopecky, Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism, J Clin Endocrinol Metab, vol. 93, no. 4, pp. 1224–1230, 2008.
20. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the U.S. population: implications for the prevalence of subclinical hypothyroidism. The Journal of Clinical Endocrinology and Metabolism, 92; 12:4575–4582, 2007.
21. Boucai L, Hollowell JG, Surks MI. An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid. 2011; 21: 5-11.
22. Surks M, Boucai L. Age and race- based serum thyrotropin reference limits. J Clin Endocrinol Metab 95: 496-502- 2010.
23. Hoermann R, Midgley J. TSH Measurement and Its Implications for Personalised Clinical Decision-Making. Journal of Thyroid Research. Volume 2012. doi: 10.1155/2012/438037.

Contexto: Los valores de referencia para pruebas tiroideas deben estandarizarse en la población local. En Colombia no tenemos datos propios.
Objetivo: Describir los niveles de hormonas tiroideas (TSH y T4 libre) en adultos de Medellín, Colombia.
Métodos: Estudio retrospectivo, con información obtenida de la base de datos electrónica de Dinámica IPS.
Criterios de inclusión: Adultos (18-50 años), con medición simultánea de TSH y T4 libre (T4L), ambos dentro del valor de referencia suministrado por el proveedor de la prueba (Abbott).
Criterios de exclusión: mujeres embarazadas, hipotiroidismo primario conocido y anticuerpos anti-TPO o antitiroglobulina positivos. Los datos se compararon con una curva normal. Se realizó un análisis de regresión lineal entre T4L y TSH o LogTSH.
Resultados: Se obtuvieron datos desde febrero 1 hasta abril 30 de 2015, n = 2.438 personas, el 80,5% eran mujeres, el promedio de edad 35,74±8,4 años. El promedio de TSH fue 2,19±1,10 mUI/L y el de T4L 1,00±0,11 ng/dl. Los valores de T4L se distribuyen de forma normal, pero los de TSH se distribuyeron como una curva asintótica hacia la izquierda. El 95% de los valores de T4L fueron entre 0,74-1,26 ng/dl y de TSH entre 0,36 y 4,55 mUI/L. No hubo diferencias entre TSH y T4 libre por sexo o por edad. El análisis de regresión lineal no mostró relación entre la T4L y TSH o LogTSH.
Conclusiones: En adultos entre 18 a 50 años, el 95% de los valores de TSH oscilan entre 0,36-4,55 mUI/ L y para T4 L entre 0,74-1,26 ng/dl. No hubo diferencias por sexo o décadas de edad. Tampoco entre valores de TSH y T4L.

Abstract
Context: Reference values for thyroid tests should be standardized in local adult people. In Colombia we do not have own data.
Objective: To describe serum levels of thyroid hormones (TSH and free T4) in adults from Medellin, Colombia.
Methods: Retrospective study based in information from an electronic database.
Inclusion criteria: Adults 18-50 years-old adults with simultaneous measurement of TSH and free T4 (FT4), both values within the reference value supplied by Abbot.
Exclusion criteria: pregnant women, primary hypothyroidism and positive TPO or thyroglobulin antibodies. Data were compared with a normal curve. Linear regression analysis between FT4 and TSH and between FT4 and LogTSH was performed.
Results: Data from February 1 to April 30 2015 were obtained, n=2.438 individuals, 80.5% were women, age mean±SD35.74±8.4 years. TSH values were mean±SD 2.19±1.10 mUI/L and FT4 1.00±0.11 ng/dl. FT4 were distributed as a normal curve, meanwhile TSH showed an asymptotic curve to the left. Ninety five percent of FT4 values were between 0.74-1.26 ng/dl and TSH 0.36-4.55 mUI/L. There was no difference between TSH and FT4 by gender or by age. Linear regression analysis do not showed any relationship between TSH and FT4.
Conclusions: In adult population 95% of serum TSH and FT4 ranging between 0.36-4.55 uUI/L and 0.74-1.26 ng/dl respectively. There were no differences by gender or age groups, or relationship between TSH and FT4.

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Los mayores picos de mineralización se producen en los primeros 2 años de vida y la pubertad, en los que la masa ósea aumenta 40% y 60%; a los 20 años se estabiliza y, luego, se inicia una pérdida progresiva. El volumen de masa ósea es variable según la edad, el sexo y la raza, es afectado por factores ambientales, genéticos, hormonales y nutricionales. El objetivo del estudio fue conocer el impacto de los hábitos relacionados con el proceso de mineralización durante la etapa de la juventud. Los participantes completaron una ficha clínica. La densidad mineral ósea fue valorada por medio de densitometría, se midieron los niveles de calcio en orina para identificar posibles pérdidas, se calculó el índice de masa corporal (IMC) a partir del peso y la talla. El 5% de la población participante presentó un Z-score inferior a -2,0 y los factores relacionados fueron consumo de cafeína, alcohol y poca actividad física.

Abstract
The highest peaks of mineralization is in the first two years of life and puberty, bone mass increases 40% to 60%, at twenty stabilizes and begins a gradual loss. The volume of bone mass varies according to age, sex and race, which affect environmental, genetic, hormonal and nutritional factors. The aim of the study was to determine the impact of the habits related mineralization process during the stage of youth. Participants completed clinical record. BMD was assessed by densitometry; Calcium levels were measured in urine for loss, BMI was calculated from weight and height. 5% of the participating population present a Z-score less than -2,0 and related factors were caffeine, alcohol and little physical activity.

1. Caritat Bagur C, Ejercicio físico y masa ósea (I). Evolución ontogénica de la masa ósea e influencia de la actividad física sobre el hueso en las diferentes etapas de la vida. Apunts Med Esport. 2007;42:40-6. - Vol. 42 Núm.153.
2. Heaney RP, Abrams S, Lawson-Hughes B, Looker A, Marcus R, Matkovic V, et al. Peak bone mass. Osteoporos Int. 2000;11: 985-1009.
3. Shreyasee Amin, osteoporosis, 2012 American College of Rheumatology.
4. Balance control in elderly people with osteoporosis Wei-Li Hsu, Chao-Yin Chen, Jau-Yih Tsauo, Rong-Sen Yang Journal of the Formosan Medical Association - 20 March 2014 (10.1016/j.jfma.2014.02.006).
5. Caple C, Schub T, Pravikoff D, Osteoporosis: prevención, CINAHL Nursing Guide, 2011.
6. Schurman L, bagur a, claus-hermberg h, messina o, negri a, mastaglia s, et al. guías 2012 para el diagnóstico, la prevención y el tratamiento de la osteoporosis. (Spanish). Medicina (Buenos Aires) [serial on the Internet]. (2013, Jan), [cited March 28, 2014]; 73(1): 55-74. Available from: MedicLatina.
7. Aguilera-Barreiro M, Rivera-Márquez J, Trujillo-Arriaga H, Ruiz-Acosta J, Rodríguez-García M. Impacto de los factores de riesgo en osteoporosis sobre la densidad mineral ósea en mujeres perimenopáusicas de la Ciudad de Querétaro, Méxi- co. (Spanish). Archivos Latinoamericanos De Nutrición [serial on the Internet]. (2013, Mar), [cited March 28, 2014]; 63(1): 21-28. Available from: MedicLatina.
8. Strayer DA, Schub T, Pravikoff D, osteoporosis, CINAHL Nursing Guide, November 25, 2011.
9. Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994; 9: 1137-1141.
10. Bachrach LK, Hastie T, Wang MC, Narasimhan B, and Hispanick Black and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab 84:4702-4712 2003.
11. S. Ferrari, M. L. Bianchi, J. A. Eisman, Show All (9), Osteoporosis in young adults: pathophysiology, diagnosis, and management, Osteoporosis International, 2012, Page 1.
12. M. Reyes Pérez-Fernández, Raquel Almazán Ortega, José M. Martínez Portela, M. Teresa Alves Pérez, M. Carmen Segura-Iglesias, Román Pérez-Fernández, Hábitos saludables y prevención de la osteoporosis en mujeres perimenopáusicas de un ámbito rural, Gaceta Sanitaria, Volume 28, Issue 2, March–April 2014, Pages 163- 165, ISSN 0213-9111, http://dx.doi.org/10.1016/j.gaceta.2013.09.006.

Los mayores picos de mineralización se producen en los primeros 2 años de vida y la pubertad, en los que la masa ósea aumenta 40% y 60%; a los 20 años se estabiliza y, luego, se inicia una pérdida progresiva. El volumen de masa ósea es variable según la edad, el sexo y la raza, es afectado por factores ambientales, genéticos, hormonales y nutricionales. El objetivo del estudio fue conocer el impacto de los hábitos relacionados con el proceso de mineralización durante la etapa de la juventud. Los participantes completaron una ficha clínica. La densidad mineral ósea fue valorada por medio de densitometría, se midieron los niveles de calcio en orina para identificar posibles pérdidas, se calculó el índice de masa corporal (IMC) a partir del peso y la talla. El 5% de la población participante presentó un Z-score inferior a -2,0 y los factores relacionados fueron consumo de cafeína, alcohol y poca actividad física.

Abstract
The highest peaks of mineralization is in the first two years of life and puberty, bone mass increases 40% to 60%, at twenty stabilizes and begins a gradual loss. The volume of bone mass varies according to age, sex and race, which affect environmental, genetic, hormonal and nutritional factors. The aim of the study was to determine the impact of the habits related mineralization process during the stage of youth. Participants completed clinical record. BMD was assessed by densitometry; Calcium levels were measured in urine for loss, BMI was calculated from weight and height. 5% of the participating population present a Z-score less than -2,0 and related factors were caffeine, alcohol and little physical activity.

1. Caritat Bagur C, Ejercicio físico y masa ósea (I). Evolución ontogénica de la masa ósea e influencia de la actividad física sobre el hueso en las diferentes etapas de la vida. Apunts Med Esport. 2007;42:40-6. - Vol. 42 Núm.153.
2. Heaney RP, Abrams S, Lawson-Hughes B, Looker A, Marcus R, Matkovic V, et al. Peak bone mass. Osteoporos Int. 2000;11: 985-1009.
3. Shreyasee Amin, osteoporosis, 2012 American College of Rheumatology.
4. Balance control in elderly people with osteoporosis Wei-Li Hsu, Chao-Yin Chen, Jau-Yih Tsauo, Rong-Sen Yang Journal of the Formosan Medical Association - 20 March 2014 (10.1016/j.jfma.2014.02.006).
5. Caple C, Schub T, Pravikoff D, Osteoporosis: prevención, CINAHL Nursing Guide, 2011.
6. Schurman L, bagur a, claus-hermberg h, messina o, negri a, mastaglia s, et al. guías 2012 para el diagnóstico, la prevención y el tratamiento de la osteoporosis. (Spanish). Medicina (Buenos Aires) [serial on the Internet]. (2013, Jan), [cited March 28, 2014]; 73(1): 55-74. Available from: MedicLatina.
7. Aguilera-Barreiro M, Rivera-Márquez J, Trujillo-Arriaga H, Ruiz-Acosta J, Rodríguez-García M. Impacto de los factores de riesgo en osteoporosis sobre la densidad mineral ósea en mujeres perimenopáusicas de la Ciudad de Querétaro, Méxi- co. (Spanish). Archivos Latinoamericanos De Nutrición [serial on the Internet]. (2013, Mar), [cited March 28, 2014]; 63(1): 21-28. Available from: MedicLatina.
8. Strayer DA, Schub T, Pravikoff D, osteoporosis, CINAHL Nursing Guide, November 25, 2011.
9. Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994; 9: 1137-1141.
10. Bachrach LK, Hastie T, Wang MC, Narasimhan B, and Hispanick Black and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab 84:4702-4712 2003.
11. S. Ferrari, M. L. Bianchi, J. A. Eisman, Show All (9), Osteoporosis in young adults: pathophysiology, diagnosis, and management, Osteoporosis International, 2012, Page 1.
12. M. Reyes Pérez-Fernández, Raquel Almazán Ortega, José M. Martínez Portela, M. Teresa Alves Pérez, M. Carmen Segura-Iglesias, Román Pérez-Fernández, Hábitos saludables y prevención de la osteoporosis en mujeres perimenopáusicas de un ámbito rural, Gaceta Sanitaria, Volume 28, Issue 2, March–April 2014, Pages 163- 165, ISSN 0213-9111, http://dx.doi.org/10.1016/j.gaceta.2013.09.006.

La acromegalia y el gigantismo hipofisiario son entidades de muy baja prevalencia pero a pesar de esto es sorprendente que en la historia de la humanidad hay en todas las épocas, descripciones de casos, sobre todo de gigantismo, que nos muestran que es una entidad que siempre nos ha acompañado.
Si revisamos desde cuando existen documentos o relatos sobre la existencia de gigantes, la sorpresa es que están descritos desde los relatos de la Biblia. Según las referencias que aparecen en los libros del Antiguo Testamento, en el Génesis (Génesis 6,1-2) y en el Deuteronomio (Deuteronomio 13,11) se hace referencia a la existencia de gigantes como una raza de seres nacidos de la unión entre hermosas mujeres y ángeles de Dios y se denominan nephilims. Al parecer, parte de la justificación bíblica para el diluvio universal fue que Dios quería acabar con esta raza de gigantes debido a sus orígenes y a sus comportamientos. Posteriormente, otra descripción bíblica que hace referencia a los gigantes es cuando al llegar los israelitas a la tierra de Canaan envían a un grupo por adelantado para observar el tipo de pobladores que había en estas tierras y al regresar estos exploradores relatan la presencia de gigantes que habitan las tierras de Canaan. A pesar de su presencia, los israelitas deciden invadir estos territorios con la convicción de que Dios está con ellos y no permitirá que nada le suceda a su pueblo.

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