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Hypopituitarism

Last updated: April 1, 2021

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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 nonsecretory pituitary macroadenoma. Other common causes include postpartum pituitary necrosis (Sheehan 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 manifests with delayed growth, while prolactin deficiency in women can manifest as lactation failure. Deficiencies of other anterior pituitary hormones, on the other hand, manifest with clinical features of hypogonadotropic hypogonadism, secondary hypothyroidism, and/or secondary adrenal insufficiency (AI). Severe pituitary damage can also result in central diabetes insipidus as a result of ADH deficiency. Hypopituitarism is diagnosed by measuring specific hormone levels (depending on the underlying hormone deficiency) and with cranial imaging (in order to identify damage to the pituitary gland and/or hypothalamus). Treatment consists of hormone replacement therapy and treatment of the underlying disorder (e.g., transsphenoidal resection of pituitary adenomas).

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 manifest with severe headache, sudden hypotension, and hypovolemic shock.

Approach [6]

Laboratory studies [6]

ACTH deficiency (central/secondary adrenal insufficiency) [7]

TSH deficiency (secondary hypothyroidism)

A normal TSH does not rule out secondary hypothyroidism; always send for serum free T4 levels.

LH/FSH deficiency (secondary hypogonadism)

The presence of regular menstrual cycles in women rules out hypogonadism.

Growth hormone deficiency

  • Testing is required if treatment is planned and optional if treatment is not planned and hormonal deficiencies exist in ≥ 3 pituitary axes.
  • IGF-1 level: typically ↓; may be normal [8]
  • Confirmatory testing: GH stimulation test [8][9]
    • Procedure
      • Record baseline serum GH level.
      • Administer stimulating agent (e.g., macimorelin).
      • Repeat serum GH levels at set intervals.
    • Interpretation: GH level (e.g., level < 2.8 mcg/L post macimorelin stimulation) supports a GH deficiency. [9]

Prolactin deficiency

  • Routine testing is not performed in the investigation of hypopituitarism.
  • Prolactin levels may be tested in:
  • Supportive finding: low-normal to low prolactin level, which does not increase with stimulation testing [10]

Posterior pituitary hormones: ADH deficiency (central diabetes insipidus)

Imaging [13]

Imaging of the pituitary is indicated in all patients to determine the underlying cause.

  • MRI brain
    • Preferred imaging modality
    • Findings depend on the underlying etiology and include pituitary adenomas (most common cause in adults), congenital malformations, and trauma.
  • CT Head (without IV contrast): used if there are contraindications to MRI or in patients requiring rapid evaluation, e.g., after suspected TBI or SAH

Approach [6]

Emergency management

Acute loss of pituitary function, e.g., via pituitary apoplexy (including Sheehan syndrome), iatrogenic (hypophysectomy), or traumatic brain injury, can lead to life-threatening complications.

Patients with suspected adrenal crisis require immediate therapy with hydrocortisone.

Maintenance therapy for pituitary hormone deficiencies

Hormone replacement in hypopituitarism [6]
Secondary adrenal insufficiency
  • Routine management: glucocorticoids with dose increases during periods of stress
Secondary hypothyroidism
Secondary hypogonadism
Growth hormone deficiency [8]
  • Children: growth hormone replacement [17]
  • Adults: GH replacement may be offered but is not usually required.
Central diabetes insipidus

In addition to pituitary hormone replacement, the underlying cause of hypopituitarism should be treated.

Hypopituitarism 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.

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  8. Iwama S, Welt CK, Romero CJ, Radovick S, Caturegli P. Isolated Prolactin Deficiency Associated With Serum Autoantibodies Against Prolactin-Secreting Cells. The Journal of Clinical Endocrinology & Metabolism. 2013; 98 (10): p.3920-3925. doi: 10.1210/jc.2013-2411 . | Open in Read by QxMD
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