AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Hypopituitarism is a clinical syndrome of deficiency in pituitary hormone production. This may result from disorders involving the pituitary gland, hypothalamus, or surrounding structures. Panhypopituitarism refers to involvement of all pituitary hormones; however, only one or more pituitary hormones are often involved, resulting in partial hypopituitarism. Pituitary hormones of clinical significance include adrenocorticotropic hormone (ACTH, ie, corticotropin), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH, ie, thyrotropin), and antidiuretic hormone (ADH).

Pathophysiology

When pituitary hormone production is impaired, target gland hormone production is reduced because of a lack of trophic stimulus. Normally, subphysiologic target hormone levels stimulate the pituitary gland to increase trophic hormone production; however, in hypopituitarism, the pituitary gland response is absent, suboptimal, or inappropriate with biologically inert hormone production. This results in progressive secondary failure of the target glands. Patients with hypopituitarism typically present with low target hormone levels accompanied by low levels of the corresponding trophic hormone.

The trophic hormone level may appear to be within the reference range with a corresponding subphysiologic target hormone level. Such a trophic hormone level would be inappropriately low for the subphysiologic target hormone level. Sometimes, the assayed trophic hormone level may be biologically inert.

Mortality/Morbidity

Four retrospective studies from the United Kingdom and Sweden show that mortality is increased by 1.3- to 2.2-fold in hypopituitarism compared to age- and sex-matched cohorts. Morbidity is variable and may result from hormone deficiency or underlying disease. Underlying disorders, such as tumors, intracranial lesions, or systemic disease, may be asymptomatic or result in morbidity that masks the hormone deficiency.

• Deficiency of ACTH with adrenal crisis or TSH with myxedema may be life threatening.
• GH deficiency causes more morbidity in children than in adults.
• Sudden compromise of ACTH production may result in more profound morbidity than slowly progressive deficiency.
• Gonadotropin deficiency with hypogonadism may cause morbidity insidiously.
• Morbidity is more profound in congenital hypopituitarism.

Race

No racial predilection exists.

Sex

Postpartum hypopituitarism causes an overall increase in the prevalence of hypopituitarism in women.

Age

All ages are affected.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Presentation varies from asymptomatic to acute collapse, depending on the etiology, rapidity of onset, and predominant hormones involved.

• Initially, a patient with any hormone deficiency may be asymptomatic. Individuals with the following deficiencies present with the indicated condition:
• • ACTH deficiency - Adrenal insufficiency
  • TSH deficiency - Hypothyroidism
  • Gonadotropin deficiency - Hypogonadism
  • GH deficiency - Individuals with GH deficiency present with failure to thrive and short stature in children. Most adults are asymptomatic, but some may experience fatigue and weakness.
  • ADH deficiency - Polyuria and polydipsia
• Other presenting features may be attributable to the underlying cause.
• • A patient with a space-occupying lesion may present with headaches or visual field deficits.
  • A patient with large lesions involving the hypothalamus may present with polydipsia and syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

Physical

• Physical examination findings may be normal in subtle presentations.
• Patients may present with features attributable to deficiency of target hormones, including hypothyroidism, adrenal insufficiency, hypogonadism, and failure to thrive.

Causes

• Tumors - Craniopharyngiomas, pituitary adenomas
• Infiltrative processes - Sarcoidosis, histiocytosis X, hemochromatosis
• Infections - Tuberculosis, syphilis, meningitis
• Ischemia and infarction - Sheehan syndrome, apoplexy
• Empty sella syndrome
• Iatrogenic - Radiation, surgery, withholding previous chronic glucocorticoid replacement
• Trauma to the hypophysis
• Congenital - Kallmann syndrome
• Autoimmune - Lymphocytic hypophysitis

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

Hormonal studies should be performed in pairs of target gland and their respective stimulatory pituitary hormone for proper interpretation.

• ACTH and Cortrosyn stimulation test
• TSH and thyroxine
• FSH, LH, and either estradiol or testosterone (as appropriate for sex)
• Prolactin
• GH provocative testing

Imaging Studies

MRI or computed axial tomography of the pituitary

Other Tests

Other tests to ascertain the likely underlying etiology are indicated by the patient's presentation.

Procedures

Cortrosyn stimulation testing

Histologic Findings

Findings depend on etiology (eg, tumors, infiltrations, infections, empty sella).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Medical care consists of hormone replacement as appropriate and treatment of the underlying cause.

• Glucocorticoids are required if the ACTH-adrenal axis is impaired. This is particularly important in sudden collapse due to pituitary apoplexy or acute obstetric hemorrhage with pituitary insufficiency. In such circumstances, do not delay initiation of a possibly life-saving treatment pending a definitive diagnosis.
• Treat secondary hypothyroidism with thyroid hormone replacement.
• Treat gonadotropin deficiency with sex-appropriate hormones. In men, testosterone replacement is used and modified if the patient desires fertility. In women, estrogen replacement is used with or without progesterone as appropriate.
• GH is replaced in children as appropriate. GH is not routinely replaced in adults unless the patient is symptomatic.

Surgical Care

Surgical care depends on the underlying cause and the severity of hypopituitarism.

• In pituitary apoplexy, prompt surgical decompression may be life saving if head imaging reveals tumor mass effect.
• Extirpate macroadenomas that do not respond to medical therapy.

Consultations

Include an endocrinologist, a neurosurgeon, and a radiologist as appropriate.

Diet

No special diet is necessary unless dictated by an underlying disease process. Salt use in adrenal insufficiency may be liberalized in special circumstances (eg, excessive diaphoresis).

Activity

No restrictions are necessary unless dictated by an underlying disease process.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goal of pharmacotherapy is to restore target hormones to physiologic levels.

Drug Category: Glucocorticoids

These agents are used in adrenal insufficiency. They cause profound and varied metabolic effects in addition to modifying the body's immune response to diverse stimuli. The naturally occurring glucocorticoids and many synthetic steroids have both glucocorticoid and mineralocorticoid activity.

Drug Category: Thyroid hormones

These agents are used in hypothyroidism.

Drug Category: Growth hormones

These agents are used in the treatment of children who have growth failure associated with chronic renal insufficiency up to the time of renal transplantation. Use in conjunction with optimal management of chronic renal insufficiency.

Drug Category: Sex hormones

These hormones are used for replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone or estrogen.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• In very ill hospitalized patients or in patients undergoing major procedures, stress-dose steroids are required and are quickly tapered to a maintenance schedule after the procedure.
• Minor procedures or illnesses may not necessitate a change in steroid dose or may require a simple doubling of the usual daily dose until the illness resolves.
• Other hormone replacements are continued at their usual maintenance doses as appropriate.

Further Outpatient Care

• Follow-up care involves adjusting hormone replacement to physiologic maintenance levels using the lowest dose. Monitor the patient to avoid overreplacement.
• All patients with hypopituitarism should carry some identification. This is often in the form of an identification bracelet worn on the wrist or neck. Some vendors include more than 20 lines of information in a tiny pendant.

In/Out Patient Meds

• Glucocorticoids for adrenal insufficiency
• Levothyroxine for hypothyroidism
• Estrogen for hypogonadal women or testosterone for hypogonadal men
• GH replacement for GH deficiency in the pediatric age group

Deterrence/Prevention

• Good obstetric care has reduced the incidence of postpartum hypopituitarism.
• Radiation therapy that minimizes exposure to the pituitary reduces incidence and time of onset of hypopituitarism.
• Experienced neurosurgeons employing high-resolution microscopic hypophyseal surgery may reduce the likelihood of subsequent hypopituitarism.

Complications

• An adrenal crisis is life threatening and should be treated promptly.
• When hypothyroidism occurs concurrently with adrenal insufficiency, glucocorticoids replacement should precede thyroid hormone replacement. This reduces the likelihood of possible adrenal insufficiency resulting from increased demands due to enhanced metabolism.

Prognosis

• If adequately replaced, prognosis in hypopituitarism is good. Morbidity is often related to the underlying disease process.

Patient Education

• Education emphasizes the need for lifelong hormone replacement, increasing glucocorticoid replacement during stress, and seeking prompt medical attention as appropriate.
• Regular monitoring to avoid excessive hormone replacement is important.
• For excellent patient education resources, visit eMedicine's Endocrine System Center and Growth Hormone Deficiency Center. Also, see eMedicine's patient education articles Anatomy of the Endocrine System, Hypopituitary, Growth Hormone Deficiency, and Understanding Growth Hormone Deficiency Medications.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• A diagnosis of hypopituitarism may be missed if apparently normal pituitary hormone levels are interpreted with respective subnormal target organ hormone levels.
• Adrenal insufficiency should be treated upon suspicion and definitive diagnosis made posttherapy.
• Adrenal replacement should precede thyroxine replacement to avoid a possible addisonian crisis.
• Hypopituitarism may manifest several years after radiation and in chronic Sheehan syndrome.
• Replace all appropriate hormones.
• Patients on GH and sex steroid replacement should be monitored for neoplasms.
• In acute pituitary failure, as in Sheehan syndrome, the ACTH stimulation study finding may be normal because the adrenal glands are not atrophied in the acute setting.

Special Concerns

• Provide long-term follow-up care for complications of underreplacement or overreplacement.
• Stressful situations warrant an adjustment in therapy.
• Unlike adults, children require GH replacement.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Clayton RN. Mortality, cardiovascular events and risk factors in hypopituitarism. Growth Horm IGF Res. Feb 1998;8 Suppl A:69-76. [Medline].
• Constine LS, Woolf PD, Cann D, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med. Jan 14 1993;328(2):87-94. [Medline].
• Dexter RN. Hypopituitarism. In: Becker KL, ed. Principles and Practice of Endocrinology and Metabolism. 1995. 2^nd ed. Baltimore, Md: Williams and Wilkins; 1995:169-80.
• Garcia-Heras J, Kilani RA, Martin RA, Lamp S. A deletion of proximal 20p inherited from a normal mosaic carrier mother in a newborn with panhypopituitarism and craniofacial dysmorphism. Clin Dysmorphol. Jul 2005;14(3):137-40. [Medline].
• Harzallah L, Migaw H, Harzallah F, Kraiem Ch. Diabetes insipidus and panhypopituitarism revealing pituitary metastasis of small cell lung carcinoma: a case report. Ann Endocrinol (Paris). Apr 2005;66(2 Pt 1):117-20. [Medline].
• Koh WJ, Kwon OJ. Mycobacterium avium complex lung disease and panhypopituitarism. Mayo Clin Proc. Jul 2005;80(7):961-2. [Medline].
• Lasheen I, Doi SA, Al-Shoumer KA. Glucocorticoid replacement in panhypopituitarism complicated by myelinolysis. Med Princ Pract. Mar-Apr 2005;14(2):115-7. [Medline].
• Thorner MO, Vance ML, Horvath E. The anterior pituitary. In: Williams Textbook of Endocrinology. 8^th ed. Philadelphia, Pa: WB Saunders and Co; 1992:221-310.
• Vance ML. Hypopituitarism. N Engl J Med. Jun 9 1994;330(23):1651-62. [Medline].
• Wolfgang KHO. Hypopituitarism. In: Bardin CW, ed. Current Therapy in Endocrinology and Metabolism. 6^th ed. St. Louis, Mo: Mosby-Year Book; 1997:27-31.
• Yamakita N, Yasuda K. Pulmonary Mycobacterium avium complex infection in patients with panhypopituitarism not receiving hormone replacement therapy. Mayo Clin Proc. Feb 2005;80(2):291. [Medline].

Article Last Updated: Sep 26, 2007