Efeitos tardios na função hipotálamo-hipófise após tratamento de tumores parasselares

Motta, Luiz A. Casulari Roxo da; Martinelli, Claudio; Motta, Lucília Domingues Casulari da; Abrahão, André L. Andrade; Farage Filho, Miguel; Gagliardi, Antônio R. de Toledo

doi:10.1590/S0004-282X1991000300011

Resumos

O acompanhamento a longo prazo de pacientes submetidos a tratamento de tumores da região parasselar é importante para detectar complicações tardias da terapêutica. Neste estudo avaliamos 6 pacientes com craniofaringioma, 1 com meningioma, 1 com germinoma e 1 com cisto epidermóíde, localizados na região parasselar. Eles haviam sido tratados, em média, 3,8±3,2 anos antes, por cirurgia e radioterapia (6 casos) ou somente cirurgia (3 casos). Cinco pacientes eram do sexo feminino e a média de idade era de 24,3±18,8 anos. A avaliação consistiu na infusão endovenosa de TRH (200 mg), GnRH (100 mg) e insulina regular (0,1 UI Kg/peso), bem como na dosagem dos hormônios hipofisários antes (0) e após 20, 40, 60 e 80 minutos. Encontramos os seguintes resultados: (a) resposta deficitária do GH e do cortisol era todos pacientes; (b) 7/9 pacientes não tiveram respostas adequadas do FSH e 3/9 do L.H; (c) 4/9 tiveram respostas inadequadas da prolactina e 2/8 do TSH. Concluimos que: (a) o déficit de GH e cortisol são os mais frequentes nestes pacientes; (b) a lesão após radioterapia pode localizar-se tanto no hipotálamo quanto na hipófise ou, ainda, em ambos; (c) a sensibilidade das células hipofisárias e hipotalâmicas à irradiação é diferente de acordo com os hormônios que produzem; (d) é necessário o acompanhamento endocrinológico frequente dos pacientes submetidos a tratamento de tumores parasselares, a fim de detectar déficits hormonais tardios.

Long term follow-up of patients submitted to treatment of paraselar tumours region is important for the detection of late therapeutic complications. In this study the authors conducted an evaluation of six patients with craniopharyngioma, one with germinoma, one with meningioma, and one epidermoid cyst. All above tumours were localized at paraselar region. Six out of nine patients had been treated both by surgery and by radiotherapy and the other three surgically only, on an average 3.8±3.2 years before this observation was carried out. Five patients were female with their ages average 24.3±18.8 years old. Evaluation consisted: in the first place, an intravenous infusion of thyrotropin-releasing hormone (TRH, 200 mg), gonadotropin-releasing hormone (GnRH, 100 mg), and insulin tolerance test (0,1 IU/Kg, regular insulin); and secondly, in measurements of pituitary hormones secretion at different time points - 0, 20,40, 60 and 80 minutes. We found both diminished response of growth hormone and Cortisol in all the patients. Seven out of nine patients did not have adequate response to follicle-stimulating hormone. Three out of nine responded unsatisfactory to luteinizing hormone. Four out of nine showed inadequate responses to prolactin as well as, two out of eight to thyrotropin. We concluded that: (a) growth hormone and Cortisol deficiency are the most frequent finding in these patients; (b) post-radiotherapy lesions can be located in the hypothalamus or pituitary, or even in both; (c) hypophsial and hypothalamic cell sensitivity to irradiation is different, according to their respective hormones; and (d) it is necessary a frequent endocrinologic follow-up of patients to detect late hormonal deficiences.

CONTENTS CONTEÚDO

Luiz A. Casulari Roxo da Motta^I; Claudio Martinelli^I; Lucília Domingues Casulari da Motta^III; André L. Andrade Abrahão^IV; Miguel Farage Filho^V; Antônio R. de Toledo Gagliardi^VI

^IMédico do Núcleo de Neuroendocrinologia, UNC, HBDF - Trabalho realizado na Unidade de Neurocirurgia (UNC) do Hospital de Base do Distrito Federal (HBDF) e na Área de Endocrinologia (AEND) da Faculdade de Ciências da Saúde da Universidade de Brasília (UnB)

^IIMédico Residente, AEND, UnB - Trabalho realizado na Unidade de Neurocirurgia (UNC) do Hospital de Base do Distrito Federal (HBDF) e na Área de Endocrinologia (AEND) da Faculdade de Ciências da Saúde da Universidade de Brasília (UnB)

^IIIProfessora Assistente, Departamento de Ginecologia e Obstetrícia, UnB- Trabalho realizado na Unidade de Neurocirurgia (UNC) do Hospital de Base do Distrito Federal (HBDF) e na Área de Endocrinologia (AEND) da Faculdade de Ciências da Saúde da Universidade de Brasília (UnB)

^IVEstagiário, AEND, UnB - Trabalho realizado na Unidade de Neurocirurgia (UNC) do Hospital de Base do Distrito Federal (HBDF) e na Área de Endocrinologia (AEND) da Faculdade de Ciências da Saúde da Universidade de Brasília (UnB)

^VChefe da UNC, HBDF - Trabalho realizado na Unidade de Neurocirurgia (UNC) do Hospital de Base do Distrito Federal (HBDF) e na Área de Endocrinologia (AEND) da Faculdade de Ciências da Saúde da Universidade de Brasília (UnB)

^VIProfessor de Endocrinologia, AEND, UnB- Trabalho realizado na Unidade de Neurocirurgia (UNC) do Hospital de Base do Distrito Federal (HBDF) e na Área de Endocrinologia (AEND) da Faculdade de Ciências da Saúde da Universidade de Brasília (UnB)

RESUMO

O acompanhamento a longo prazo de pacientes submetidos a tratamento de tumores da região parasselar é importante para detectar complicações tardias da terapêutica. Neste estudo avaliamos 6 pacientes com craniofaringioma, 1 com meningioma, 1 com germinoma e 1 com cisto epidermóíde, localizados na região parasselar. Eles haviam sido tratados, em média, 3,8±3,2 anos antes, por cirurgia e radioterapia (6 casos) ou somente cirurgia (3 casos). Cinco pacientes eram do sexo feminino e a média de idade era de 24,3±18,8 anos. A avaliação consistiu na infusão endovenosa de TRH (200 mg), GnRH (100 mg) e insulina regular (0,1 UI Kg/peso), bem como na dosagem dos hormônios hipofisários antes (0) e após 20, 40, 60 e 80 minutos. Encontramos os seguintes resultados: (a) resposta deficitária do GH e do cortisol era todos pacientes; (b) 7/9 pacientes não tiveram respostas adequadas do FSH e 3/9 do L.H; (c) 4/9 tiveram respostas inadequadas da prolactina e 2/8 do TSH. Concluimos que: (a) o déficit de GH e cortisol são os mais frequentes nestes pacientes; (b) a lesão após radioterapia pode localizar-se tanto no hipotálamo quanto na hipófise ou, ainda, em ambos; (c) a sensibilidade das células hipofisárias e hipotalâmicas à irradiação é diferente de acordo com os hormônios que produzem; (d) é necessário o acompanhamento endocrinológico frequente dos pacientes submetidos a tratamento de tumores parasselares, a fim de detectar déficits hormonais tardios.

SUMMARY

Long term follow-up of patients submitted to treatment of paraselar tumours region is important for the detection of late therapeutic complications. In this study the authors conducted an evaluation of six patients with craniopharyngioma, one with germinoma, one with meningioma, and one epidermoid cyst. All above tumours were localized at paraselar region. Six out of nine patients had been treated both by surgery and by radiotherapy and the other three surgically only, on an average 3.8±3.2 years before this observation was carried out. Five patients were female with their ages average 24.3±18.8 years old. Evaluation consisted: in the first place, an intravenous infusion of thyrotropin-releasing hormone (TRH, 200 mg), gonadotropin-releasing hormone (GnRH, 100 mg), and insulin tolerance test (0,1 IU/Kg, regular insulin); and secondly, in measurements of pituitary hormones secretion at different time points - 0, 20,40, 60 and 80 minutes. We found both diminished response of growth hormone and Cortisol in all the patients. Seven out of nine patients did not have adequate response to follicle-stimulating hormone. Three out of nine responded unsatisfactory to luteinizing hormone. Four out of nine showed inadequate responses to prolactin as well as, two out of eight to thyrotropin. We concluded that: (a) growth hormone and Cortisol deficiency are the most frequent finding in these patients; (b) post-radiotherapy lesions can be located in the hypothalamus or pituitary, or even in both; (c) hypophsial and hypothalamic cell sensitivity to irradiation is different, according to their respective hormones; and (d) it is necessary a frequent endocrinologic follow-up of patients to detect late hormonal deficiences.

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Agradecimentos - Aos senhores Quintino Lopes do Nascimento e João Eleutério Sobrinho, pelo apoio técnico indispensável.

Dr. Luis Augusto Casulari Roxo da Motta - Núcleo de Neuroendocrinologia, Unidade de Neurocirurgia - Hospital de Base do Distrito Federal - 70355 Brasília DF - Brasil.

1. Ahmed SR, Shalet SM. Hypothalamic growth hormone releasing factor deficiency following cranial irradiation. Clin Endocrinol 1984, 21:483.
2. Arslanian SA, Becker DJ, Lee PA, Drash AL, Foley TP. Growth hormone therapy and tumour recurrence: findings in children with brain neoplasms and hypopituitarism. Am J Dis Child 1985, 139:347.
3. Blacklay A, Grossman A, Ross RJM, Savage MO, Davies PSW, Plowman PN, Coy DH, Besser GM. Cranial irradiation for cerebral and nasopharyngeal tumours in children: evidence for the production of hypothalamic defect in growth hormone release. J Endocr 1986, 108:25.
4. Clayton PE. Does GH cause relapse of brain tumours? Lancet 1987, 1:711.
5. Costin G. Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function. Am J Dis Child 1988, 142:847.
6. Papavasiliou C, Zannos ML. Irradiation of the head: immediate effect on GH secretion in children. J Clin Endocrinol Metab 1977, 44:791.
7. Dickinson WP, Berry DH, Dickinson L, Irvin M, Schedewie H, Fiser RH, Elders MJ. Differential effects of cranial radiation on GH response to arginine and insulin infusion. J Pediatr 1978, 92:754.
8. Duffner PK, Cohen ME. Thomas PRM, Lansky SB. The long-term effects of cranial irradiation on the central nervous system. Cancer 1985, 56:1841.
9. Duffner PK, Cohen ME. Voorhess ML, MacGillivray MH, Brecher ML, Panahon AJ, Gilani BB. Long-term effects of cranial irradiation on endocrine function in children with brain tumours: a prospective study. Cancer 1985, 56:2189.
10. Frier BM, Corral RJM. Symptomatic hypothalamic hypopituitarism following radiotherapy. Posgrad Med J 1979, 55:812.
11. Fuks Z. Glatstein E. Marsa GW, Bagshaw MA, Kaplan HS. Longterm effects of external radiation on the pituitary and thyreoid glands. Cancer 1976, 37:1152.
12. Harrop JS, Davies TJ, Capra LG, Marks V. Hypothalamic-pituitary function following sucessful treatment of intracranial tumours. Clin Endocrinol 1976. 5:313.
13. Keller RJ, Wolfsdorf J. Isolated GH deficiency after cerebral edema complicating diabetic ketoacidosis. N Engl J Med 1987, 316:857.
14. Lam KSL, Tse VKC. Wang C, Yeung RTT, Ma JTC, o JHC. Early effects of cranial irradiation on hypothalamic-pituitary function. J Clin Endocrinol Metab 1987, 64:418.
15. Larkins RG. Martin FIR. Hypopituitarism after extracranial irradiation: evidence for hypothalamic origen. Br M J 1973, 1:152.
16. Leibel SA, Sheline GE. Radiation therapy for neoplasms of the brain. J Neurosurg 1987. 66:1.
17. Littley MD, Shalet SM. Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 1989, 70:145.
18. Lufkin EG. Kao PC, Fallon WN, Mangan MA. Combined testing of anterior pituitary gland with insulin, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone. Am J Med 1983. 75:471.
19. Mechanick JI. Hochberg FH, La Rocque A. Hypothalamic dysfunction following whole-- brain irradiation. J Neurosurg 1986, 65:490.
20. Richards GE. Wara WM, Grumback MM, Kaplan SL, Sheline GE. Conte FA. Delayed onset of hypopituitarism: sequelae of therapeutic irradiation of central nervous system, eye, and ear tumours. J Pediatr 1976, 89:553.
21. Rogers PC, Komp D, Rogol A, Sabio H. Possible effects of GH on development of acute lymphoblastic leukaemia. Lancet 1977, 2:434.
22. Sack J, Sazbon L, Lunenfeld B, Najenson T. Hypothalamic-pituitary function in patients with prolonged coma. J Clin Endocrinol Metab 1983, 56:635.
23. Samaan NA, Bakdash MM, Caderao JB, Cangir A, Jesse RH Jr, Ballantyne AJ. Hypopituitarism after external irradiation: evidence for the hypothalamic and pituitary origen. Ann Intern Med 1975, 83:771.
24. Shalet SM, Beardwell CG, MacFarlane IA, Jones PHM, Pearson D. Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood. Acta Endocrinol 1977, 84:673.
25. Snyder PJ, Jacobs LS, Rabello MM, Sterling FH, Shore RN, Utiger RD, Daughday WH. Diagnostic value of thyrotropin-releasing hormone in pituitary and hypothalamic diseases: assesment of thyrotrophin and prolactin secretion in 100 patients. Ann Intern Med 1974, 81:751.
26. Woodruft KH, Lyman JT, Lawrence JH, Tobitas CA, Born JL, Fabrikant JI. Delayed sequelae of pituitary irradiation. Hum Pathol 1984. 15:48.

Efeitos tardios na função hipotálamo-hipófise após tratamento de tumores parasselares

Late effects on hypothalamic-pituitary function following treatment of paraselar tumours.

Datas de Publicação

Publicação nesta coleção
22 Fev 2011
Data do Fascículo
Set 1991

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Ahmed SR, Shalet SM. Hypothalamic growth hormone releasing factor deficiency following cranial irradiation. Clin Endocrinol 1984, 21:483.

[2] 2. Arslanian SA, Becker DJ, Lee PA, Drash AL, Foley TP. Growth hormone therapy and tumour recurrence: findings in children with brain neoplasms and hypopituitarism. Am J Dis Child 1985, 139:347.

[3] 3. Blacklay A, Grossman A, Ross RJM, Savage MO, Davies PSW, Plowman PN, Coy DH, Besser GM. Cranial irradiation for cerebral and nasopharyngeal tumours in children: evidence for the production of hypothalamic defect in growth hormone release. J Endocr 1986, 108:25.

[4] 4. Clayton PE. Does GH cause relapse of brain tumours? Lancet 1987, 1:711.

[5] 5. Costin G. Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function. Am J Dis Child 1988, 142:847.

[6] 6. Papavasiliou C, Zannos ML. Irradiation of the head: immediate effect on GH secretion in children. J Clin Endocrinol Metab 1977, 44:791.

[7] 7. Dickinson WP, Berry DH, Dickinson L, Irvin M, Schedewie H, Fiser RH, Elders MJ. Differential effects of cranial radiation on GH response to arginine and insulin infusion. J Pediatr 1978, 92:754.

[8] 8. Duffner PK, Cohen ME. Thomas PRM, Lansky SB. The long-term effects of cranial irradiation on the central nervous system. Cancer 1985, 56:1841.

[9] 9. Duffner PK, Cohen ME. Voorhess ML, MacGillivray MH, Brecher ML, Panahon AJ, Gilani BB. Long-term effects of cranial irradiation on endocrine function in children with brain tumours: a prospective study. Cancer 1985, 56:2189.

[10] 10. Frier BM, Corral RJM. Symptomatic hypothalamic hypopituitarism following radiotherapy. Posgrad Med J 1979, 55:812.

[11] 11. Fuks Z. Glatstein E. Marsa GW, Bagshaw MA, Kaplan HS. Longterm effects of external radiation on the pituitary and thyreoid glands. Cancer 1976, 37:1152.

[12] 12. Harrop JS, Davies TJ, Capra LG, Marks V. Hypothalamic-pituitary function following sucessful treatment of intracranial tumours. Clin Endocrinol 1976. 5:313.

[13] 13. Keller RJ, Wolfsdorf J. Isolated GH deficiency after cerebral edema complicating diabetic ketoacidosis. N Engl J Med 1987, 316:857.

[14] 14. Lam KSL, Tse VKC. Wang C, Yeung RTT, Ma JTC, o JHC. Early effects of cranial irradiation on hypothalamic-pituitary function. J Clin Endocrinol Metab 1987, 64:418.

[15] 15. Larkins RG. Martin FIR. Hypopituitarism after extracranial irradiation: evidence for hypothalamic origen. Br M J 1973, 1:152.

[16] 16. Leibel SA, Sheline GE. Radiation therapy for neoplasms of the brain. J Neurosurg 1987. 66:1.

[17] 17. Littley MD, Shalet SM. Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 1989, 70:145.

[18] 18. Lufkin EG. Kao PC, Fallon WN, Mangan MA. Combined testing of anterior pituitary gland with insulin, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone. Am J Med 1983. 75:471.

[19] 19. Mechanick JI. Hochberg FH, La Rocque A. Hypothalamic dysfunction following whole-- brain irradiation. J Neurosurg 1986, 65:490.

[20] 20. Richards GE. Wara WM, Grumback MM, Kaplan SL, Sheline GE. Conte FA. Delayed onset of hypopituitarism: sequelae of therapeutic irradiation of central nervous system, eye, and ear tumours. J Pediatr 1976, 89:553.

[21] 21. Rogers PC, Komp D, Rogol A, Sabio H. Possible effects of GH on development of acute lymphoblastic leukaemia. Lancet 1977, 2:434.

[22] 22. Sack J, Sazbon L, Lunenfeld B, Najenson T. Hypothalamic-pituitary function in patients with prolonged coma. J Clin Endocrinol Metab 1983, 56:635.

[23] 23. Samaan NA, Bakdash MM, Caderao JB, Cangir A, Jesse RH Jr, Ballantyne AJ. Hypopituitarism after external irradiation: evidence for the hypothalamic and pituitary origen. Ann Intern Med 1975, 83:771.

[24] 24. Shalet SM, Beardwell CG, MacFarlane IA, Jones PHM, Pearson D. Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood. Acta Endocrinol 1977, 84:673.

[25] 25. Snyder PJ, Jacobs LS, Rabello MM, Sterling FH, Shore RN, Utiger RD, Daughday WH. Diagnostic value of thyrotropin-releasing hormone in pituitary and hypothalamic diseases: assesment of thyrotrophin and prolactin secretion in 100 patients. Ann Intern Med 1974, 81:751.

[26] 26. Woodruft KH, Lyman JT, Lawrence JH, Tobitas CA, Born JL, Fabrikant JI. Delayed sequelae of pituitary irradiation. Hum Pathol 1984. 15:48.