eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hypopituitarism: Differential Diagnoses & Workup

Author: Lawrence A Wetterau, MD, Assistant Professor, Section of Endocrinology, Children's Hospital Central California
Contributor Information and Disclosures

Updated: May 5, 2009

Differential Diagnoses

Adrenal Insufficiency
Hypogonadism
Ambiguous Genitalia and Intersexuality
Hyponatremia
Diabetes Insipidus
Hyposomatotropism
Growth Failure
Hypothyroidism
Growth Hormone Deficiency
Jaundice, Neonatal
Hypernatremia
Microphallus
Hypoglycemia

Other Problems to Be Considered

Delayed puberty
Psychosocial deprivation

Workup

Laboratory Studies

  • To evaluate growth hormone deficiency (GHD), tests for insulinlike growth factor-I (IGF-I) and insulinlike growth factor–binding protein 3 (IGFBP-3) are useful for screening, although their use is limited in very young children or children with brain tumors.4 When 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 corticotropin-releasing hormone (CRH)–adrenocorticotropic hormone (ACTH)–cortisol axis. However, this test also has the greatest potential for harm; thus, it is not routinely used in most pediatric centers.
    • Alternative GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, growth hormone–releasing hormone (GHRH), propranolol with glucagon, exercise, clonidine, and epinephrine. In prepubertal children, consideration should be given to "priming" with sex steroids prior to testing.
    • A random serum GH level is rarely helpful; the exception is during early infancy when GH levels usually are tonically elevated.
  • Measurement of morning serum cortisol levels can help 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.
  • As an alternative, metyrapone, which transiently induces adrenal insufficiency by blocking 11-hydroxylase activity, can be used to stimulate cortisol secretion. This test is quite variable and has some inherent risk.
  • 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.
  • CRH stimulation testing can also be considered. It is of equivalent value to the ACTH stimulation test.
  • In patients with acute hypoglycemia, a critical sample documenting low serum glucose, while simultaneously measuring GH and cortisol levels, can also be diagnostic.
  • To assess central hypothyroidism (ie, thyroid-stimulating hormone (TSH) or thyrotropin-releasing hormone (TRH) deficiency), low free thyroxine (FT4) levels assayed by dialysis and reference range or low serum TSH levels are diagnostic.5
  • 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 gonadotropin-releasing hormone (GnRH) are retained, making GnRH testing an option.
    • No method reliably assesses the axis in preadolescent children older than 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 antidiuretic hormone (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.

Imaging Studies

  • A brain MRI with specific cuts of the pituitary is the preferred imaging study for hypopituitarism. 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.

More on Hypopituitarism

Overview: Hypopituitarism
Differential Diagnoses & Workup: Hypopituitarism
Treatment & Medication: Hypopituitarism
Follow-up: Hypopituitarism
Multimedia: Hypopituitarism
References
Further Reading
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References

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Keywords

hypopituitarism, growth hormone deficiency, GHD, multiple pituitary hormone deficiency, MPHD, pituitary hypothalamus, hypoglycemia, short stature, jaundice, hyponatremia, sepsis, microgenitalia, growth failure, diabetes insipidus, gonadotropin deficiency, cold intolerance, constipation, micropenis, obesity, craniofacial abnormalities, Kallmann syndrome, KS, septo-optic dysplasia, anencephaly, holoprosencephaly, Pallister-Hall syndrome, histiocytosis, tuberculosis, tuberculosis, sarcoidosis, lymphocytic hypophysitis, hemochromatosis, craniopharyngioma, germinoma, glioma, astrocytoma, pituitary adenoma, treatment, diagnosis

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Contributor Information and Disclosures

Author

Lawrence A Wetterau, MD, Assistant Professor, Section of Endocrinology, Children's Hospital Central California
Lawrence A Wetterau, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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
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, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and 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: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
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