Pituitary hyperplasia in childhood primary hypothyroidism: a review

Child's Nervous System volume 37, pages749–762(2021)Cite this article

Abstract

Introduction

Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for this medically treatable condition. Given the paucity of information on this topic, it is timely to provide clinicians with a comprehensive summary of available research.

Methods

A search of published studies in Pubmed, PsychInfo and Cochrane Database with the terms “pituitary hyperplasia” or “pituitary hypertrophy” and “hypothyroidism” was performed and the results filtered for English language, pediatric (0-18 years) population and CT or MRI confirmed findings. 55 studies met the inclusion criteria. Data for a total of 110 patients with pituitary hyperplasia following primary hypothyroidism were extracted. The study population included 29 males and 81 females (M: F= 0.35:1). Patient age varied from 3 weeks to 18 years with a mean age of 10.22 years.

Results

The most common clinical presentations included growth retardation, constipation and features of myxedema which were present in 78, 36 and 18 percent of children included in our review. Neuroimaging showed the mean (SD) pituitary height being 13.48 mm (4.72 mm). All of the patients achieved resolution of their pituitary mass and clinical as well as biochemical abnormalities 1 to 26 months after initiation of thyroid hormone replacement therapy, with an average time interval of 7.22 months. Our review has tried to delve in the pathophysiology as well as clinical, biochemical and radiological aspects of pediatric pituitary hyperplasia secondary to primary hypothyroidism and provide recommendations for treatment and follow-up. This may help anyone concerned gain a substantial knowledge on this topic.

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References

  1. 1.

    Fernandez-Real JM, Ricart-Engel W, Maroto-Genover A, Macia F (1995) Primary hypothyroidism and concomitant bilateral ovarian masses. J Pediatr Endocrinol Metab 8:263–266

    CAS  PubMed  Google Scholar 

  2. 2.

    Niepce B (1851) Traite du goitre et du cretinism. Bailliers, Paris

    Google Scholar 

  3. 3.

    Shukla P, Bulsara KR, Luthra P (2019) Pituitary hyperplasia in severe primary hypothyroidism: a case report and review of the literature. Case Rep Endocrinol 2019:1–7. https://doi.org/10.1155/2019/2012546

    Article  Google Scholar 

  4. 4.

    Cao J, Lei T, Chen F, Zhang C, Ma C, Huang H (2018) Primary hypothyroidism in a child leads to pituitary hyperplasia: a case report and literature review. Med (United States) 97:e12703. https://doi.org/10.1097/MD.0000000000012703

    Article  Google Scholar 

  5. 5.

    Okuno T, Sudo M, Momoi T (1980) Pituitary hyperplasia due to hypothyroidism. J Comput Assist Tomogr 4:600–602

    CAS  PubMed  Google Scholar 

  6. 6.

    Nishi Y, Sakano T, Hyodo S, Masuda H, Kitamura Y, Shindo H, Sakoda K, Uozumi T, Usui T (1984) Pituitary abnormalities detected by high resolution computed tomography with thin slices in primary hypothyroidism and Turner syndrome. Eur J Pediatr 142:25–28. https://doi.org/10.1007/BF00442585

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Floyd JL, Dorwart RH, Nelson MJ, Mueller GL, DeVroede M (1984) Pituitary hyperplasia secondary to thyroid failure: CT appearance. Am J Neuroradiol

  8. 8.

    Bilaniuk LT, Moshang T, Cara J, Weingarten MZ, Sutton LN, Samuel LR, Zimmerman RA (1985) Pituitary enlargement mimicking pituitary tumor. J Neurosurg 63:39–42

    CAS  PubMed  Google Scholar 

  9. 9.

    Yamamoto Y, Kunishio K, Sunami N, Asari S, Yunoki S (1987) A case of pituitary hyperplasia associated with primary hypothyroidism. Neurol Surg 15:903–908

    CAS  Google Scholar 

  10. 10.

    Farley JD, Toth EL, Ryan EA (1988) Primary hypothyroidism presenting as growth delay and pituitary enlargement. Can J Neurol Sci / J Can Sci Neurol 15:35–37

    CAS  Google Scholar 

  11. 11.

    Ahmed M, Banna M, Sakati N, Woodhouse N (1989) Pituitary gland enlargement in primary hypothyroidism: a report of 5 cases with follow-up data. Horm Res Paediatr 32:188–192

    CAS  Google Scholar 

  12. 12.

    Nishi Y, Hamamoto K, Kajiyama M, Fujita A, Kawamura I, Kagawa Y, Kajima T, Yamanaka M, Uozumi T (1989) Pituitary enlargement, hypertrichosis and blunted growth hormone secretion in primary hypothyroidism. Acta Paediatr Scand 78:136–140

    CAS  PubMed  Google Scholar 

  13. 13.

    Atchison JA, Lee PA, Albright AL (1989) Reversible suprasellar pituitary mass secondary to hypothyroidism. JAMA J Am Med Assoc 262:3175–3177

    CAS  Google Scholar 

  14. 14.

    Hung W, Fitz CR, Lee EDH (1990) Pituitary enlargement due to lingual thyroid gland and primary hypothyroidism. Pediatr Neurol 6:60–62

    CAS  PubMed  Google Scholar 

  15. 15.

    Kuroiwa T, Okabe Y, Hasuo K, Yasumori K, Mizushima A, Masuda K (1991) MR imaging of pituitary hypertrophy due to juvenile primary hypothyroidism: a case report. Clin Imaging 15:202–205

    CAS  PubMed  Google Scholar 

  16. 16.

    Adams C, Dean HJ, Israels SJ, Patton A, Fewer DH (1994) Primary hypothyroidism with intracranial hypertension and pituitary hyperplasia. Pediatr Neurol 10:166–168

    CAS  PubMed  Google Scholar 

  17. 17.

    Desai MP, Mehta RU, Choksi CS, Colaco MP (1996) Pituitary enlargement on magnetic resonance imaging in congenital hypothyroidism. Arch Pediatr Adolesc Med 150:623–628

    CAS  PubMed  Google Scholar 

  18. 18.

    Damjanović S, Popović V, Petakov M, Djurović M, Dieguez C, Casanueva FF (1996) Pituitary enlargement due to primary hypothyroidism: growth hormone response to GHRH, GHRP-6 and GHRH plus GHRP-6. J Pediatr Endocrinol Metab 9:549–553

    PubMed  Google Scholar 

  19. 19.

    Riedl S, Frisch H (1997) Pituitary hyperplasia in a girl with gonadal dysgenesis and primary hypothyroidism. Horm Res Paediatr 47:126–130. https://doi.org/10.1159/000185447

    CAS  Article  Google Scholar 

  20. 20.

    Ehirim PU, Kerr DS, Cohen AR (1998) Primary hypothyroidism mimicking a pituitary macroadenoma. Pediatr Neurosurg 28:195–197

    CAS  PubMed  Google Scholar 

  21. 21.

    Young M, Kattner K, Gupta K (1999) Pituitary hyperplasia resulting from primary hypothyroidism mimicking macroadenomas. Br J Neurosurg 13:138–142

    CAS  PubMed  Google Scholar 

  22. 22.

    Yamagishi S, Yokoyama-Ohta M (1999) A rare case of pituitary hyperplasia with suprasellar extension due to primary myxoedema: case report. J Int Med Res 27:49–52

    CAS  PubMed  Google Scholar 

  23. 23.

    Papakonstantinou O, Bitsori M, Mamoulakis D, Bakantaki A, Papadaki E, Gourtsoyiannis N (2000) MR imaging of pituitary hyperplasia in a child with growth arrest and primary hypothyroidism. Eur Radiol 10:516–518. https://doi.org/10.1007/s003300050087

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Bonomi M, Proverbio MC, Weber G, Chiumello G, Beck-Peccoz P, Persani L (2001) Hyperplastic pituitary gland, high serum glycoprotein hormoneα -subunit, and variable circulating thyrotropin (TSH) levels as hallmark of central hypothyroidism due to mutations of the TSHβ gene 1. J Clin Endocrinol Metab 86:1600–1604

    CAS  PubMed  Google Scholar 

  25. 25.

    Kocova M, Netkov S, Sukarova-Angelovska F (2001) Pituitary pseudotumor with unusual presentation reversed shortly after the introduction of thyroxine replacement therapy. J Pediatr Endocrinol Metab 14:1665–1669

    CAS  PubMed  Google Scholar 

  26. 26.

    Plehwe WE, Fabinyi GC (2003) Anterior pituitary hyperplasia due to primary autoimmune hypothyroidism. J Clin Neurosci 10:217–218

    PubMed  Google Scholar 

  27. 27.

    Bhansali A, Sreenivasulu P, Khandelwal N, Masoodi SR (2004) Reversibility of thyrotroph hyperplasia after L-thyroxine replacement therapy in patients with juvenile primary hypothyroidism. J Pediatr Endocrinol Metab 17:655–661

    CAS  PubMed  Google Scholar 

  28. 28.

    Hopper NW, Albanese A (2005) Primary hypothyroidism in a child mimicking a pituitary macroadenoma. Horm Res 63:61–64

    CAS  PubMed  Google Scholar 

  29. 29.

    Ashley WW, Ojemann JG, Park TS, Wippold FJ (2005) Primary hypothyroidism in a 12-year-old girl with a suprasellar pituitary mass: rapid regression after thyroid replacement therapy: case report. J Neurosurg 102:413–416

    PubMed  Google Scholar 

  30. 30.

    Alves C, Alves AC (2008) Primary hypothyroidism in a child simulating a prolactin-secreting adenoma. Childs Nerv Syst 24:1505–1508

    PubMed  Google Scholar 

  31. 31.

    Lee C-Y, Hsu H-H, Lai H-Y, Lee S-T (2008) Rapid progression of hypothyroidism-related pituitary hyperplasia. J Neurosurg Pediatr 2:212–214

    PubMed  Google Scholar 

  32. 32.

    Eom KS, See-Sung C, Kim JD, Kim JM, Kim TY (2009) Primary hypothyroidism mimicking a pituitary macroadenoma: regression after thyroid hormone replacement therapy. Pediatr Radiol 39:164–167

    PubMed  Google Scholar 

  33. 33.

    Şimşek E, Şimşek T, Savaş-Erdeve Ş, Erdoğmuş B, Döşoğlu M (2009) Pituitary hyperplasia mimicking pituitary macroadenoma in two adolescent patients with long-standing primary hypothyroidism: case reports and review of literature.

  34. 34.

    Aijing X, Tang L (2010) Pituitary hyperplasia in children with short stature and primary hypothyroidism. Indian Pediatr 47:877–880. https://doi.org/10.1007/s13312-010-0149-4

    Article  PubMed  Google Scholar 

  35. 35.

    Inamo Y (2011) A 5-year-old boy with atrophic autoimmune thyroiditis caused by thyroid-stimulation blocking antibodies. J Pediatr Endocrinol Metab 24:591–594

    PubMed  Google Scholar 

  36. 36.

    Cekmez F, Pirgon O, Bilgin H (2011) Pituitary macroadenoma due to primary hypothyroidism in a 12-year-old girl. Br J Biomed Sci 68:208

    CAS  PubMed  Google Scholar 

  37. 37.

    Aquilina K, Boop FA (2011) Nonneoplastic enlargement of the pituitary gland in children: a review. J Neurosurg Pediatr 7:510–515

    PubMed  Google Scholar 

  38. 38.

    Franceschi R, Rozzanigo U, Failo R, Bellizzi M, Di Palma A (2011) Pituitary hyperplasia secondary to acquired hypothyroidism: case report. Ital J Pediatr 37:15. https://doi.org/10.1186/1824-7288-37-15

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Han L, Wang J, Shu K, Lei T (2012) Pituitary tumorous hyperplasia due to primary hypothyroidism. Acta Neurochir 154:1489–1492

    PubMed  Google Scholar 

  40. 40.

    Omran A, Peng J, Shrestha B, Ashhab MU, Yin F (2012) Male child with Van Wyk-Grumbach’s syndrome and other complications of long-standing primary hypothyroidism: a case report. Case Rep Pediatr 2012:1–5

    Google Scholar 

  41. 41.

    Lee HJ, Kim JK (2013) Nongoitrous autoimmune thyroiditis with facial palsy. Ann Pediatr Endocrinol Metab 18:214–217

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Hu Y, Wang Q, Li G, Sun X, Liu C (2013) Ultrasonic morphology of uterus and ovaries in girls with pituitary hyperplasia secondary to primary hypothyroidism. Horm Metab Res 45:669–674

    CAS  PubMed  Google Scholar 

  43. 43.

    Mills NJW, Wong SC, Sabin MA, Hewitt JK (2013) Reactive pituitary hyperplasia associated with paediatric primary hypothyroidism. J Paediatr Child Health 49:421–422

    PubMed  Google Scholar 

  44. 44.

    Larson NS, Pinsker JE (2013) Primary hypothyroidism with growth failure and pituitary pseudotumor in a 13-year-old female: a case report. J Med Case Rep 7:149

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Namburi RP, Karthik TS, Ponnala AR (2014) Autoimmune hypothyroidism presenting as pituitary hyperplasia. Indian J Pediatr 81:937–939

    PubMed  Google Scholar 

  46. 46.

    Sterkenburg AS, Niekrens C, Hoffmann A, Warmuth-Metz M, Flitsch J, Müller HL (2013) Reactive pituitary enlargement mimicking a sellar mass. Klin Padiatr 226:377–378

    PubMed  Google Scholar 

  47. 47.

    Genenş M, Akcan N, Abalı ZY, Baş F, Uyguner O, Poyrazoğlu Ş, Toksoy G, Bundak R, Darendeliler F (2015) Multiple pituitary hormone deficiency associated with pituitary hyperplasia: a case report.

  48. 48.

    Siddiqi AI, Grieve J, Miszkiel K, Baldeweg SE (2015) Tablets or scalpel: pituitary hyperplasia due to primary hypothyroidism. Radiol Case Rep 10:1099

    PubMed  Google Scholar 

  49. 49.

    Kurnaz E, Savaş-Erdeve Ş, Keskin M, Doğan V, Çetinkaya S, Aycan Z (2016) A case with atrophic autoimmune thyroiditis-related hypothyroidism causing multisystem involvement in early childhood. Turk J Pediatr 58:446–451

    PubMed  Google Scholar 

  50. 50.

    Gaspari L, Paris F, Leboucq N, Bonafé A, Sultan C (2016) Reversible growth failure and complete GH deficiency in a 4-year-old girl with very early Hashimoto’s thyroiditis and subsequent hyperplasia of pituitary thyrotroph cells. Eur J Pediatr 175:1119–1122

    PubMed  Google Scholar 

  51. 51.

    Kocova M, Zdraveska N, Kacarska R, Kochova E (2016) Diagnostic approach in children with unusual symptoms of acquired hypothyroidism. When to look for pituitary hyperplasia? J Pediatr Endocrinol Metab 29:297–303

    PubMed  Google Scholar 

  52. 52.

    Kim SJ, Yoon JH, Kim HK, Kang HC (2017) Spontaneous ovarian hyperstimulation syndrome in a young female subject with a lingual thyroid and primary hypothyroidism. Korean J Intern Med 32:559–562

    PubMed  Google Scholar 

  53. 53.

    Devru N, Dharmshaktu P, Kumar G, Dutta D, Kulshreshtha B (2018) Phenotypic presentation of adolescents with overt primary hypothyroidism. J Pediatr Endocrinol Metab 31:415–420

    CAS  PubMed  Google Scholar 

  54. 54.

    Shivaprasad KS, Siddardha K (2019) Pituitary hyperplasia from primary hypothyroidism. N Engl J Med 380:e9

    CAS  PubMed  Google Scholar 

  55. 55.

    Braz D, Bastos D, Mota G, Matos Rezek Rodrigues S, Nobrega N, Oliveira L, Florencio A, Lofrano-Porto A, Oliveira R, Lopes F, Castro LC (2019) SUN-580 pituitary hyperplasia secondary to primary hypothyroidism in pediatrics: a diagnosis not to be forgotten. J Endocr Soc 3. https://doi.org/10.1210/js.2019-sun-580

  56. 56.

    Sea JL, Head MJ, Chiu HK (2020) MON-058 precocious puberty and hypothyroidism in a pediatric case. J Endocr Soc 4:1442–1449

    Google Scholar 

  57. 57.

    Sapkota S, Sapkota S, Karn M (2020) Pituitary hyperplasia due to Himalayan endemic hypothyroidism. Clin Case Rep Wiley Online Library. https://doi.org/10.1002/ccr3.3595

  58. 58.

    Hu YY, Li GM, Hu WW, Wang Y (2014) Characteristics of girls with pituitary hyperplasia and sexual precocity secondary to primary hypothyroidism. Acta Paediatr Int J Paediatr 103:e43–e48. https://doi.org/10.1111/apa.12444

    CAS  Article  Google Scholar 

  59. 59.

    Ciocca DR, Puy LA, Stati AO (1985) Immunocytochemical evidence for the ability of the human pharyngeal hypophysis to respond to change in endocrine feedback. Virchows Arch A Pathol Anat Histopathol 405:497–502. https://doi.org/10.1007/BF00737175

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Alkhani AM, Cusimano M, Kovacs K, Bilbao JM, Horvath E, Singer W (1999) Cytology of pituitary thyrotroph hyperplasia in protracted primary hypothyroidism. Pituitary 1:291–295

    CAS  PubMed  Google Scholar 

  61. 61.

    Scheithauer BW, Kovacs K, Randall RV, Ryan N (1985) Pituitary gland in hypothyroidism. Histologic and immunocytologic study. Arch Pathol Lab Med 109:499–504

    CAS  PubMed  Google Scholar 

  62. 62.

    Vidal S, Horvath E, Kovacs K, Cohen SM, Lloyd RV, Scheithauer BW (2000) Transdifferentiation of somatotrophs to thyrotrophs in the pituitary of patients with protracted primary hypothyroidism. Virchows Arch 436:43–51. https://doi.org/10.1007/PL00008197

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Honbo KS, Van Herle AJ, Kellett KA (1978) Serum prolactin levels in untreated primary hypothyroldism. Am J Med 64:782–787

    CAS  PubMed  Google Scholar 

  64. 64.

    Bellini MA, Neves I (1956) The skull in childhood myxedema; its roentgen appearance. Am J Roentgenol Radium Ther Nucl Med.

  65. 65.

    Yamada T, Tsukui T, Ikejiri K, Yukimura Y, Kotani M (1976) Volume of sella turcica in normal subjects and in patients with primary hypothyroidism and hyperthyroidism. J Clin Endocrinol Metab 42:817–822

    CAS  PubMed  Google Scholar 

  66. 66.

    Zhao YL, Cheng JL, Zhang MM (2009) Hard nut to crack in diagnosis of pituitary hyperplasia secondary to primary hypothyroidism and reasons of misdiagnosis. Natl Med J China. https://doi.org/10.3760/cma.j.issn.0376-2491.2009.10.010

  67. 67.

    Chan AW, Macfarlane IA, Foy PM, Miles JB (1990) Pituitary enlargement and hyperprolactinaemia due to primary hypothyroidism: errors and delays in diagnosis. Br J Neurosurg 4:107–112

    CAS  PubMed  Google Scholar 

  68. 68.

    Du J, Ji H, Jin J, Gao S, Yan X, Hu S (2020) Pituitary adenoma secondary to primary hypothyroidism: two case reports. Med (United States) 99:e19222. https://doi.org/10.1097/MD.0000000000019222

    Article  Google Scholar 

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Affiliations

  1. Department of Neurosurgery, Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal

    Shabal Sapkota

  2. School of Medicine, Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal

    Mitesh Karn

  3. Department of Medical Oncology, Birat Medical College, Biratnagar, Nepal

    Sulav Sapkota

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  1. Shabal Sapkota
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  2. Mitesh Karn
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  3. Sulav Sapkota
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Concept by Shabal Sapkota. Write-up, literature search, and data analysis by Shabal Sapkota, Sulav Sapkota, and Mitesh Karn. Final work seen and approved by all the authors.

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Correspondence to Shabal Sapkota.

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Sapkota, S., Karn, M. & Sapkota, S. Pituitary hyperplasia in childhood primary hypothyroidism: a review. Childs Nerv Syst 37, 749–762 (2021). https://doi.org/10.1007/s00381-020-05014-6

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Keywords

  • Hypothyroidism
  • Pediatrics
  • Pituitary hyperplasia
  • Review