Pediatric Hypopituitarism Workup

  • Author: Joel W Steelman, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Jul 14, 2011
 

Approach Considerations

Laboratory tests are essential in the diagnosis and assessment of patients with hypopituitarism. However, any patient with hypopituitarism must also have a magnetic resonance imaging (MRI) examination to exclude a brain tumor. A brain MRI with specific cuts of the pituitary is the preferred imaging study for hypopituitarism.[23] This may be obtained pre–gadolinium contrast and post–gadolinium contrast, which can be helpful in the delineation of the posterior pituitary and some pituitary tumors.

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Laboratory Studies

Screening for GHD using insulinlike growth factor-I (IGF-I) and insulinlike growth factor–binding protein 3 (IGFBP-3) may be useful,[24] except in cases of brain tumors.[25] Random measurement of GH levels has no diagnostic value except during early infancy, when GH levels are usually tonically elevated.

If abnormal growth patterns are seen, and GHD is strongly suspected, further provocative testing of GH secretion is typically performed under the supervision of a pediatric endocrinologist. Insulin-induced hypoglycemia is the most reliable provocative test for GHD and has the added advantage of accurately assessing the CRH-ACTH-cortisol axis. However, this test also has the greatest potential for harm, making its use limited in many pediatric endocrine practices.

Alternative GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, GHRH, propranolol with glucagon, exercise, clonidine, and epinephrine. In prepubertal children, consideration should be given to "priming" with sex steroids prior to testing.

Measurement of morning serum cortisol levels can help to exclude a CRH-ACTH-cortisol axis deficiency; a level of 20 mcg/dL virtually excludes this diagnosis.

Insulin-induced hypoglycemia probably is the criterion standard test but has limitations secondary to its inherent risks. On the other hand, ACTH stimulation testing is sensitive, reproducible, and extremely safe. Even though it directly examines the state of the adrenal cortices, indirectly it provides information about the hypothalamic-pituitary unit, because the cortisol response to exogenous ACTH is blunted in long-standing (>10 d) hypopituitarism.

Tests for adrenal insufficiency using Metyrapone or CRH are less-used laboratory examinations in pediatric patients. In patients with acute hypoglycemia, a critical sample documenting low serum glucose, while simultaneously measuring GH and cortisol levels, can be diagnostic. To assess central hypothyroidism (ie, TSH or TRH deficiency), low free thyroxine (FT4) levels assayed by dialysis and reference range or low serum TSH levels are diagnostic.[26]

Laboratory approaches to assess the pituitary-gonadal axis vary based on patient age. Young infants spontaneously secrete follicle-stimulating hormone (FSH) and leuteinizing hormone (LH) in amounts that can be detected by radioimmunoassay; they also produce substantial amounts of testosterone and estradiol. At this age, random measurements of estradiol or testosterone levels and of LH and FSH levels are adequate to assess the gonadal axis.

From later infancy until about age 4 years, spontaneous secretion of LH and FSH is reduced, but stimulated responses to GnRH are retained, making GnRH testing an option. No method reliably assesses the axis in preadolescent children older than age 4 years. Testing is typically deferred until puberty, when diagnostic findings show low random LH and FSH levels in conjunction with low sex steroid levels (eg, testosterone, estradiol).

Elevated serum sodium and serum osmolality levels, when combined with low or low-normal urine osmolality, suggest diabetes insipidus. A low serum ADH level in this context can be diagnostic for central diabetes insipidus (ie, pituitary vasopressin deficiency). A water deprivation test is definitive; this test is performed under the supervision of a pediatric endocrinologist. In patients with diabetes insipidus, serum sodium and serum osmolality levels rise during water deprivation, while urine fails to concentrate properly. A normal response to administered vasopressin differentiates central diabetes insipidus from nephrogenic diabetes insipidus.

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Contributor Information and Disclosures
Author

Joel W Steelman, MD  Endocrine Consultant, Division of Endocrinology and Diabetes, Cook Children's Medical Center

Joel W Steelman, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Society for Bone and Mineral Research, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Pfizer Honoraria Speaking and teaching

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London)  Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgments

I want to thank Simon Rhodes, PhD and Stephen Shalet, MD for kindly allowing me to republish illustrations from their work.

References

  1. Mehta A, Hindmarsh PC, Mehta H, Turton JP, Russell-Eggitt I, Taylor D, et al. Congenital hypopituitarism: clinical, molecular and neuroradiological correlates. Clin Endocrinol (Oxf). Mar 6 2009;[Medline].

  2. Parks JS, Kinoshita EI, Pfaffle RW. Pit-1 and hypopituitarism. Trends Endocrinol Metab. 1993;4:81-5.

  3. Rosenbloom AL, Almonte AS, Brown MR, et al. Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene. J Clin Endocrinol Metab. Jan 1999;84(1):50-7. [Medline]. [Full Text].

  4. Lebl J, Vosahlo J, Pfaeffle RW, et al. Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects. Eur J Endocrinol. Sep 2005;153(3):389-96. [Medline].

  5. Bottner A, Keller E, Kratzsch J, et al. PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis. J Clin Endocrinol Metab. Oct 2004;89(10):5256-65. [Medline]. [Full Text].

  6. Fluck C, Deladoey J, Rutishauser K, et al. Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C). J Clin Endocrinol Metab. Oct 1998;83(10):3727-34. [Medline]. [Full Text].

  7. Mullen, R.D., Colvin, S.C., Hunter, C.H., et al. Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development. Mol. Cell. Endocrinol. 2007;265:190-195.

  8. Kim SS, Kim Y, Shin YL, et al. Clinical characteristics and molecular analysis of PIT1, PROP1, LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging. Horm Res. 2003;60(6):277-83. [Medline].

  9. Pinto G, Netchine I, Sobrier ML, et al. Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis. J Clin Endocrinol Metab. Oct 1997;82(10):3450-4. [Medline]. [Full Text].

  10. Darzy KH, Shalet SM. Hypopituitarism following Radiotherapy. In: Wallace WHB, Kelnar CJH. Endocrinopathy after Childhood Cancer Treatment. 15. Basel: Karger; 2009:1-24.

  11. Ghigo E, Masel B, Aimaretti G, et al. Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj. Aug 20 2005;19(9):711-24. [Medline].

  12. Acerini CL, Tasker RC. Endocrine Sequelae of Traumatic Brain Injury in Childhood. Horm Res. 2007;68(suppl 5):14-17.

  13. Sklar CA. Craniopharyngioma: endocrine abnormalities at presentation. Pediatr Neurosurg. 1994;21 Suppl 1:18-20. [Medline].

  14. Mootha SL, Barkovich AJ, Grumbach MM, et al. Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents. J Clin Endocrinol Metab. May 1997;82(5):1362-7. [Medline]. [Full Text].

  15. Lindsay R, Feldkamp M, Harris D, et al. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. Jul 1994;125(1):29-35. [Medline].

  16. Regal M, Parmo C, Sierra SM, Garcia-Mayor RV. Prevaence and Incidence of Hypopituitarism in an Adult Caucasian Population in Northwestern Spain. Clin Endocrinol. 2001;55:735-740.

  17. Stochholm K, Laursen T, Green A, Laurberg P, Andersen M, Kristensen LØ, et al. Morbidity and GH deficiency: a nationwide study. Eur J Endocrinol. Apr 2008;158(4):447-57. [Medline].

  18. White SM, Campbell DJ. Primary hypopituitarism and peri-operative steroid supplementation. Anaesthesia. Mar 2009;64(3):336-7. [Medline].

  19. Choo-Kang LR, Sun CC, Counts DR. Cholestasis and hypoglycemia: manifestations of congenital anterior hypopituitarism. J Clin Endocrinol Metab. Aug 1996;81(8):2786-9. [Medline].

  20. Sane K, Pescovitz OH. The clitoral index: a determination of clitoral size in normal girls and in girls with abnormal sexual development. J Pediatr. Feb 1992;120(2 Pt 1):264-6. [Medline].

  21. Garcia-Filion P, Epport K, Nelson M, Azen C, et al. Neuroradiographic, Endocrinologic, and Ophthalmic Correlates of Adverse Developmental Outcomes in Children With Optic Nerve Hypoplasia: A Prospective Study. Pediatrics. 2008;121:e653-e659.

  22. Borchert M, Garcia-Filion P. The Syndrome of Optic Nerve Hypoplasia. Current Neurology and Neuroscience Reports. 2008;8:395 - 403.

  23. Argyropoulou MI, Kiortsis DN. MRI of the hypothalamic-pituitary axis in children. Pediatr Radiol. Nov 2005;35(11):1045-55. [Medline].

  24. Rosenfeld RG. Disorders of growth hormone and insulin-like growth factor secretion and action. Pediatric Endocrinology. 1996;117-169.

  25. Weinzimer SA, Homan SA, Ferry RJ, Moshang T. Serum IGF-I and IGFBP-3 concentrations do not accurately predict growth hormone deficiency in children with brain tumours. Clin Endocrinol. 1999;51(3):339-45.

  26. Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol (Oxf). Feb 18 2009;[Medline].

  27. Toogood AA, Stewart PM. Hypopituitarism: Clinical Featues, Diagnosis, and Management. In: Barkan AL. Endocrinology and Metabolism Clinics of North America. 37. 1. Philadelphia: Elsevier Saunders; 2008:235-261.

 
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The left photograph shows an untreated 21-month-old girl with congenital hypopituitarism. The right panel depicts the same child aged 29 months, following 8 months of growth hormone therapy.
Regulation of the development of the mammalian anterior pituitary gland by transcription factors. Following, inductive signals between the developing diencephalon and the oral ectoderm, early transcription factors guide the formation of rudimentary Rathke's Pouch (rRP) and then subsequent gene regulatory pathways control the determination, proliferation, and differentiation events that establish the specialized hormone-secreting cells. AP = anterior pituitary, IP = intermediate pituitary, PP = posterior pituitary. Modified by S. Rhodes from Mullen, R.D., Colvin, S.C., Hunter, C.H., Savage, J.J., Walvoord, E.C., Bhangoo, A.P.S., Ten, T., Weigel, J., Pfäffle, R.W., and Rhodes, S.J. (2007). Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development. Mol. Cell. Endocrinol., 265-266: 190-195.
Summary of Neuroendocrine Dysfunction following radiotherapy (courtesy of Stephen M Shalet, MD)
 
 
 
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