• Clinical science

Hypopituitarism

Abstract

Hypopituitarism refers to the inadequate production of one or more anterior pituitary hormones as a result of damage to the pituitary gland and/or hypothalamus. These hormones include growth hormone (GH), prolactin, thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). In some cases, the posterior pituitary hormones (e.g., ADH) may also be affected, which is known as panhypopituitarism. The most common cause of hypopituitarism is compression of the pituitary gland by a non-secretory pituitary macroadenoma. Other common causes include postpartum pituitary necrosis (Sheehan's syndrome), traumatic brain injury, hypophysectomy, and/or irradiation of the pituitary gland. Clinical manifestations vary significantly and depend on the specific hormone deficiency, the age of disease onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism: Growth hormone deficiency during childhood presents with growth retardation, while prolactin deficiency manifests as lactation failure among women. Deficiencies of other anterior pituitary hormones, on the other hand, manifest with clinical features of hypogonadotropic hypogonadism, secondary hypothyroidism, and/or secondary adrenal insufficiency. Severe pituitary damage can also result in central diabetes insipidus as a result of ADH deficiency. Diagnosis of hypopituitarism involves measuring specific hormone levels (depending on the underlying hormone deficiency) and cranial imaging (in order to identify damage to the pituitary gland and/or hypothalamus). Treatment of hypopituitarism consists of hormone replacement therapy and treatment of the underlying disorder (e.g., transsphenoidal resection of pituitary adenomas).

Etiology

References:[1][2][3][4][5][6][7]

Pathophysiology

References:[8][9][10]

Clinical features

Symptoms are variable and depend on the specific hormone deficiency, the age of disease onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism.

Pituitary apoplexy, which results in acute hypocortisolism and hypothyroidism, can present with severe headache, sudden hypotension, and hypovolemic shock!

References:[9]

Diagnostics

Since the pattern of hormone deficiency may vary, each hormone deficiency must be tested individually.

  • GH deficiency
    • IGF-1 levels (insulin-like growth factor)
    • GH levels (even after administering arginine and exogenous GHRH)
  • Prolactin deficiency: No routine test is available
  • Gonadotropin deficiency
    • Males
      • ↓ or normal LH, which does not increase even after administering exogenous GnRH (GnRH stimulation test)
      • DHEA, testosterone (in a serum sample collected between 8 and 10 am)
    • Females: the presence of regular menstrual cycles effectively rules out gonadotropin deficiency; no further diagnostic test is required.
      • FSH and LH and do not rise after a GnRH stimulation test
      • ↓ Estradiol
      • Lack of withdrawal bleeding after administering medroxyprogesterone acetate for 10 days (progesterone challenge test)
      • However, withdrawal bleeding occurs after administering an estrogen preparation for 21 days followed by a progesterone preparation for 7 days (estrogen/progesterone challenge test)
  • TSH deficiency: T3, T4, ↓ or normal TSH (see secondary hypothyroidism)
  • ACTH deficiency (see secondary adrenal insufficiency)
  • Central diabetes insipidus: low urine osmolality (< 300 mOsmol/L); which persists despite water deprivation; but increases once exogenous desmopressin is administered (see desmopressin test)
  • If a pituitary hormone deficiency is identified → perform cranial imaging (preferably MRI) to identify pituitary adenomas

References:[9][11][12]

Treatment

Management consists of treating the underlying cause (e.g., transsphenoidal resection in cases of pituitary macroadenomas) and hormone replacement therapy.

  • Growth hormone deficiency
    • Children: GH hormone replacement;
    • Adults: GH hormone replacement is usually not required
  • TSH deficiency: : administration of levothyroxine (see hypothyroidism)

Patients with TSH deficiency should not be treated with levothyroxine until ACTH deficiency has been ruled out and/or treated because levothyroxine increases the clearance of cortisol and may precipitate an adrenal crisis!

Immediate treatment with glucocorticoids, without waiting for diagnostic confirmation, is required when acute ACTH deficiency is suspected (e.g., following pituitary apoplexy) to prevent an adrenal crisis!

  • GnRH deficiency
    • Males
      • If fertility is desired: exogenous gonadotropins (e.g., HCG) should be administered
      • If fertility is not desired: testosterone replacement therapy
    • Females: estrogen replacement therapy with/without progesterone
  • Prolactin deficiency: no treatment is required
  • Central diabetes insipidus: desmopressin

In addition to hormone replacement therapy, the underlying cause of hypopituitarism should be treated, e.g., via transsphenoidal resection in the case of pituitary macroadenomas!

References:[5][13]

last updated 10/16/2018
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