Hypopituitarism

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Overview

Hypopituitarism is a medical term describing the deficiency (hypo) of one or more hormones of the pituitary gland. The hypothalamus regulates pituitary secretion by the production of releasing hormones and posterior pituitary hormones and hence its dysfunction can also lead to hypopituitarism.

In endocrinology, deficiency of one or multiple hormones of the anterior pituitary is generally referred to as hypopituitarism, while deficiency of the posterior lobe generally only leads to central diabetes insipidus. The deficiency of all anterior pituitary hormones is termed panhypopituitarism.

Physiology

The hormones of the anterior pituitary include 2 proteins, 3 glycoproteins and a polypeptide:

  1. prolactin (PRL) - stimulates milk production in the breast
  2. growth hormone (GH) - growth and glucose homeostasis
  3. luteinizing hormone (LH) - menstrual cycle and reproduction
  4. follicle stimulating hormone (FSH) - same
  5. thyroid stimulating hormone (TSH) - stimulates thyroxine production in the thyroid
  6. adrenocorticotropic hormone (ACTH) - stimulates glucocorticoid production in the adrenal gland

These hormones are secreted in individually characteristic pulsatile patterns, often with distinct circadian rhythm, rather than at steady rates throughout 24 hours.

The posterior pituitary is the site of release of the nonapeptide hormones antidiuretic hormone (ADH) and oxytocin, the former regulating plasma osmolarity and the latter regulating uterine contractions during childbirth as well milk ejection from the breasts.

Multiple hormone deficiencies

Deficiency of a single pituitary hormone occurs less commonly than deficiency of more than one hormone. Sometimes referred to as progressive pituitary hormone deficiency or partial hypopituitarism, there is usually a predictable order of hormone loss.

Generally, growth hormone is lost first, then luteinizing hormone deficiency follows. The loss of follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotopic hormones and prolactin typically follow much later. The progressive loss of pituitary hormone secretion is usually a slow process, which can occur over a period of months or years. Hypopituitarism does occasionally start suddenly with rapid onset of symptoms

Most people with hypopituitarism lack growth hormone as well as one or more others. As for the posterior pituitary, antidiuretic hormone deficiency is the main problem, while oxytocin deficiency rarely causes clinically significant problems.

Causes

Hypopituitarism and panhypopituitarism can be congenital or acquired. A partial list of causes and forms:

Diagnosis

Hypopituitarism may come to medical attention by symptoms or features of pituitary hormone deficiency (e.g., poor growth, hypoglycemia, micropenis, delayed puberty, polyuria, impaired libido, fatigue, and many others), or because the physician has diagnosed one of the many disorders and conditions associated with hypopituitarism listed above and tests for it. A provocative test (triple bolus test) measures the secretory response of the pituitary to a stimulus (other hormones, drugs, exercise, etc.) by measuring serum levels of the hormone involved.

Complete differential diagnosis for hypopituitarism

  • Ischemic nerosis of the pituitary
  • Latrogenic
  • Parasellar tumor/pituitary compression
  • Craniopharyngioma
  • Chromophobe adenoma
  • Intracranial cartoid branch aneurysm
  • Lymphoma
  • Meningioma
  • Metasteses
  • Optic nerve neurinoma

Replacement therapy

Hypopituitarism and panhypopituitarism are treated by replacement of appropriate hormones. Since most of the anterior pituitary hormones are proteins or glycoproteins released in pulsatile patterns, whose functions are to induce secretion of smaller molecule hormones (thyroid hormones and steroids), it is simpler and less expensive for most purposes to simply replace the target gland hormones. There are a few exceptions, such as fertility induction.

  • GH is replaced with growth hormone.
  • TSH is replaced with thyroxine.
  • ACTH is usually replaced with hydrocortisone but any glucocorticoid may be used.
  • LH and FSH are most often replaced by supplying the appropriate sex steroids (e.g., testosterone or estrogen and progestin). Virtually all people who need T or E2 replacement for hypopituitarism rarely have spontaneous, effective spermatogenesis or follicular maturation. Both GnRH by subcutaneous pump and gonadotropins (Pergonal) by daily subcutaneous injections have been used effectively to induce fertility.
  • Prolactin is not usually replaced, as infant formula is readily available, simpler, and much cheaper.
  • ADH is replaced most commonly with oral, nasal, and sometimes intravenous or subcutaneous desmopressin.
  • Oxytocin is most important during labor and delivery at the end of pregnancy, and can be replaced in that circumstance by pitressin.

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