Loading [MathJax]/extensions/MathML/mml3.js
info@auctorespublishing.com
+1-(302)-520-2644
+1-(302)-520-2644

Growth Hormone Deficiency in Children and Adult Patients with Hypopituitarism: Challenges in the Diagnosis and Management

  1. Home
  2. Journals
  3. Endocrinology and Disorders
  4. Archives
Submit Guidelines

Research Article | DOI: https://doi.org/10.31579/2640-1045/004

Growth Hormone Deficiency in Children and Adult Patients with Hypopituitarism: Challenges in the Diagnosis and Management

  • S M J Mortazavi 1
  • Reshad Hassannezhad 1
  • Reza Ranjbar 1
  • Mahnaz Etehadtavakol 1
  • Poupak Rahimzadeh 1
  • Sheyda Akhshabi 1
  • Stefano Cattaneo 1
  • Mansour Hadji Hosseinlou 1*

1 Department of Endocrine Surgery, Iran.

*Corresponding Author: Mansour Hadji Hosseinlou, Department of Endocrine Surgery, University of Tehran, Iran.

Citation: Mansour Hadji Hosseinlou, Hyperketonemia: Clinical features and diagnosis of Diabetic Ketoacidosis. J. Endocrinology and Disorders. DOI:10.31579/2640-1045/004

Copyright: © 2017. Reshad Hassannezhad. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 19 January 2017 | Accepted: 02 February 2017 | Published: 08 March 2017

Keywords: aetiology; radiotherapy; tumours; hypopituitarism; pituitary hormone

Abstract

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain.If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used.

Hypopituitarism is a complex medical condition associated with increased morbidity and mortality, requires complicated treatment regimens, and necessitates lifelong follow up by the endocrinologist.

Introduction

Aetiology

Of the various causes of hypopituitarism in adults (see box), pituitary adenoma or its treatment by surgery and/or radiotherapy is by far the commonest. Macroadenomas (greater than 1 cm) are associated with one or more trophic hormone deficits in 30% of cases direct compression and destruction of the surrounding normal pituitary leads to hyposecretion. Other postulated mechanisms include primary mass effect of the tumour on the vascular portal system/pituitary stalk, raised intrasellar pressure affecting portal circulation, and focal pituitary necrosis secondary to prolonged interruption of portal blood supply. While microadenomas (less than 1 cm) rarely affect pituitary function, prolactin producing microadenomas often present with hypogonadism because of the suppressive action of a high prolactin (PRL) level on gonadotrophins' (follicle stimulating hormone FSH and luteinising hormone LH) secretion. Among the peripituitary tumours causing central endocrine dysfunction, craniopharyngioma is the commonest.

Occurrence of hypopituitarism after pituitary surgery is influenced by tumour size, extent of invasion into surrounding structures, remaining viable normal pituitary, and the skill of the neurosurgeon. Transient postoperative diabetes insipidus (DI) is seen in 5% of cases but permanent DI occurs less frequently. At least partial recovery of pituitary function in 40%–65% of patients has been reported after surgery but postoperative deterioration has also been reported.Patients should be made aware of the possibility of hypopituitarism before surgery. Post‐surgical endocrine assessment is mandatory.

Anterior hypopituitarism may follow cranial radiotherapy used in treating various intracranial tumours, acute lymphoblastic leukaemia (prophylactic cranial radiotherapy), and those receiving total body irradiation. The impact is dependent on the total dose, fractionation, duration of treatment, and time elapsed since radiation exposure to the hypothalamic‐pituitary axis.In one series after a radiotherapy dose to the hypothalamic‐pituitary axis of 37.5 to 42.5 Gy, after five years all patients were growth hormone (GH) deficient, 90% gonadotrophin deficient, 77

Results

On the basis of the GH response to ARG+GHRH, 41 patients had very severe GHD (GH peak, 0.9 ± 0.08 μg/L; group 1), 25 patients had severe GHD (GH peak, 4.7 ± 0.4 μg/L; group 2), 18 patients had partial GHD (GH peak, 11.0 ± 0.3 μg/L; group 3), and 17 patients had normal GH responses (GH peak, 28.3 ± 4.3 μg/L; group 4). In the 35 controls (group 5), the GH response after ARG+GHRH was 40.7 ± 2.2 μg/L.

Plasma IGF-I concentrations in patients in groups 1 (76.5 ± 7.6μ g/L) and 2 (80.3 ± 7.5 μg/L) were similar and lower (P < 0>P< 0>P < 0>

Management of hypopituitarism

The treatment of hypopituitarism includes therapies directed at the underlying disease process, and endocrine replacement therapy. The pituitary tumours may be treated with medical therapy, surgery, radiotherapy, or a combination of these modalities. A macroprolactinoma, for instance, is amenable to treatment with dopamine agonists, there is a high surgical cure rate for GH secreting microadenoma by skilled surgeons.

Hormone Replacement Therapy

The goals of HRT in hypopituitarism are to achieve normal levels of the circulating hormones, to restore normal physiology as closely as possible, and to avoid the symptoms of deficiency with minimal side effects.

Discussion and Conclusion

GHD in adults is associated with increased fat mass, reduced lean mass, osteopenia, impaired fibrinolysis, altered cardiac structure and function, unfavorable glucose and lipid metabolism, reduced exercise capacity, and reduced quality of life (3, 13, 14). Reduced BMD has been widely reported in hypo pituitary patients (3, 4–8), although the roles of individual pituitary hormone deficiency and/or of replacement therapy in the development of bone loss have not been firmly elucidated.

Conclusion

Hypopituitarism is associated with increased mortality and morbidity, necessitates complicated treatment regimens, and significantly affects the economy of the healthcare system. Strategies to limit the use of conventional radiotherapy may well lead to a reduced incidence of hypopitutarism. It is probable that hormonal treatment that approaches normal physiology might have a favourable influence on the adverse outcomes; therefore optimising replacement and lifelong follow up is appropriate.

References

  1. Regal M, Paramo C, Sierra S M. et al Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf) 200155735–740.
    View at Publisher | View at Google Scholar
  2. Rosen T, Bengtsson B‐A. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990336285–288.
    View at Publisher | View at Google Scholar
  3. Bates A S, Van't Hoff W, Jones P J. et al The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996811169–1172.
    View at Publisher | View at Google Scholar
  4. Bulow B, Hagmart L, Mikoczy Z. et al Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf) 19974675–81.
    View at Publisher | View at Google Scholar
  5. Tomlinson J W, Holden N, Hills R K. et al Association between premature mortality and hypopituitarism. Lancet 2001357425–431.
    View at Publisher | View at Google Scholar
  6. Vance M L. Hypopituitarism. N Engl J Med 19943301651–1662.
    View at Publisher | View at Google Scholar
  7. Arafah B M. Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 1986621173–1179.
    View at Publisher | View at Google Scholar
  8. Arafah B M, Prunty D, Ybarra J. et al The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. J Clin Endocrinol Metab 2000851789–1793.
    View at Publisher | View at Google Scholar
  9. Comtois R, Beauregard H, Somma M. et al The clinical and endocrine outcome to transsphenoidal microsurgery of non‐secreting pituitary adenomas. Cancer 199168860–866.
    View at Publisher | View at Google Scholar
  10. Marazuela M, Astigarraga B, Vicente A. et al Recovery of visual and endocrine function following transsphenoidal surgery of large non‐functioning pituitary adenomas. J Endocrinol Invest 199417703–707.
    View at Publisher | View at Google Scholar
  11. Webb S M, Rigla M, Wägner A. et al Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab 1999843696–3700.
    View at Publisher | View at Google Scholar
  12. Harris P E, Afshar F, Coates P. et al The effects of transsphenoidal surgery on endocrine function and visual fields in patients with functionless pituitary tumours. Q J Med 198971417–427.
    View at Publisher | View at Google Scholar
  13. Littley M D, Shalet S M, Beardwell C G. et al Hypopituitarim following external radiotherapy for pituitary tumors in adults. Q J Med 198970145–160.
    View at Publisher | View at Google Scholar
  14. Littley M D, Shalet S M, Beardwell C G. et al Radiation induced hypopituitarism is dose dependent. Clin Endocrinol (Oxf) 198931363–373.
    View at Publisher | View at Google Scholar
  15. Feigl G C, Bonelli C M, Berghold A. et al Effects of gamma knife radiosurgery of pituitary adenomas on pituitary function. J Neurosurg 200297415–421.
    View at Publisher | View at Google Scholar
  16. Cogan J C, Phillips J A, III, Sakati N. et al Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. J Clin Endocrinol Metab 1993761224–1228.
    View at Publisher | View at Google Scholar
  17. Wajnrajch M P, Gertner J M, Harbison M C. et al Nonsense mutation in the human growth hormone‐releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet 19961288–90.
    View at Publisher | View at Google Scholar
  18. Goudie R B, Pinkerton P H. Anterior hypophysitis and Hashimoto's disease in a young woman. J Pathol Bacteriol (Lond) 196283584–585.
    View at Publisher | View at Google Scholar
  19. Thodou L, Asa S L, Kontogeorgos G. et al Lymphocytic hypophysitis: clinicopathological findings. J Clin Endocrinol Metab 1995802302–2311.
    View at Publisher | View at Google Scholar
  20. Hashimoto K, Takao T, Makino S. Lymphocytic adenohypophysitis and lymphocytic infundibuloneurohypophysitis. Endocr J 1997441–10.  
    View at Publisher | View at Google Scholar
  21. Beressi N, Beressi J P, Cohen R. et al Lymphocytic hypophysitis—a review of 145 cases. Ann Intern Med 1999150327–341.
    View at Publisher | View at Google Scholar
  22. Bellastella A, Bizzarro A, Coronella C. et al Lymphocytic hypophysitis: a rare or underestimated disease? Eur J Endocrinol 2003149363–376.
    View at Publisher | View at Google Scholar
  23. Benvenga S, Campenni A, Ruggeri R M. et al Clinical review 113: hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 2000851353–1361.
    View at Publisher | View at Google Scholar
  24. Aimaretti G, Ambrosio M R, Di Somma C. et al Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury. Clin Endocrinol (Oxf) 200461320–326.
    View at Publisher | View at Google Scholar
  25. Kelly D F, Gonzalo I T, Cohan P. et al Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid haemorrhage: a preliminary report. J Neurosurg 200093743–752.
    View at Publisher | View at Google Scholar
  26. Arafah B M, Harrington J F, Madhoun Z T. et al Improvement of pituitary function after surgical decompression for pituitary tumour apoplexy. J Clin Endocrinol Metab 199071323–328.
    View at Publisher | View at Google Scholar
  27. Randeva H S, Schoebel J, Byrne J. et al Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf) 199951181–188.
    View at Publisher | View at Google Scholar
  28. Shalet S M, Toogood A, Rahim A. et al The diagnosis of growth hormone deficiency in children and adults. Endocr Rev 199819203–223.
    View at Publisher | View at Google Scholar
a