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Hypopituitarism

Hypopituitarism is a medical term describing deficiency (hypo) of one or more hormones of the pituitary gland. The pituitary produces a number of important regulating hormones, and its function is mainly regulated by the hypothalamus. In endocrinology, deficiency of multiple hormones of the anterior lobe is generally referred to as hypopituitarism, while deficiency of the posterior lobe generally only leads to diabetes insipidus. If both lobes malfunction, the term panhypopituitarism (generalised hypopituitarism) is used. more...

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Physiology

The primary hormones of the anterior pituitary are proteins and include

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

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 produces antidiuretic hormone (ADH) and oxytocin, the former regulating plasma osmolarity and the latter regulating uterine contractions during childbirth.

Growth hormone is often the first hormone lost, so most people with hypopituitarism lack GH as well as one or more others. As for the posterior pituitary, ADH 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:

  • Congenital hypopituitarism
    • Hypoplasia of the pituitary
      • Isolated idiopathic congenital hypopituitarism
      • Associated with other congenital syndromes and birth defects
        • Septo-optic dysplasia
        • Holoprosencephaly
        • Chromosome 22 deletion syndrome
        • Rapaport syndrome
    • Single gene defect forms of anterior pituitary hormone deficiency
  • Acquired hypopituitarism
    • trauma (e.g., skull base fracture)
    • surgery (e.g., removal of pituitary neoplasm)
    • tumor (secretory and non-secretory pituitary or hypothalamic neoplasms)
    • inflammation (e.g. sarcoidosis or autoimmune hypohysitis)
    • radiation (e.g., after cranial irradiation for childhood leukemia)
    • shock
      • (Sheehan's syndrome is hypopituitarism after heavy bleeding in childbirth)
    • hemochromatosis
  • other diseases.

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.

Replacement therapy

Hypopituitarism and panhypopituitarism are treated by replacement of appropriate hormones. Since the most of the anterior pituitary hormones are proteins 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.

Read more at Wikipedia.org


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Growth hormone replacement therapy
From Townsend Letter for Doctors and Patients, 6/1/04 by Jule Klotter

Studies presented at the 85th Annual Meeting of the Endocrine Society (June 2003) indicate that hypopituitary patients who do not receive growth hormone therapy have a higher risk for tumors, particularly brain tumors and colon cancer than the general population. Dr. Johan Svensson and colleagues in Sweden completed two retrospective studies. In the first, they compared the incidence of fatal and non-fatal health problems in 1,411 hypopituitary adults with the normal population. In the second, they compared 289 hypopituitary patients on long-term growth hormone treatment (average treatment length was 60 months) to the general population. They discovered that "hypopituitary patients who were not taking growth hormone had an increased risk of cancer--predominantly colorectal cancer." They also learned that hypopituitary adults--whether or not they received growth hormone therapy--were more likely to have a stroke than the general population.

Dr. Patrick Wilton and colleagues used Pfizer's International Growth Database and the company's International Metabolic Database to track cancer risk among children and adults, respectively, who use growth hormone replacement. These postmarketing surveillance databases receive voluntary information from physicians with patients' and parents' permission. The researchers found that hypopituitary children who received growth hormone had the same likelihood of developing a tumor as normal children. Similarly, cancer rates among hypopituitary adults on growth hormone therapy for 6 months or longer matched the rate among the normal adult population. However, the incidence of intracranial tumors (primarily benign) and skin tumors was higher among hypopituitary patients. Wilton noted that many of the hypopituitary patients had received radiation therapy, which fosters intracranial tumor development.

Because hypopituitary adults lose fat mass and gain lean body mass while on replacement therapy, growth hormone has been tested on obese people. Dr. Stewart Albert led a study in which 39 obese patients (body mass index of 37) with an average age of 36 received nightly low-dose injections of growth hormone or placebo for three months. The GH dose corresponds to the amount of growth hormone found in persons without a weight problem. In previous studies with obese patients, high doses of GH had caused adverse side effects. During Dr. Albert's study, people taking GH lost about five pounds of body fat, mostly from the abdominal area.

Growth hormone replacement therapy has been linked to a deterioration of glucose tolerance. M. Bramnert et al. published a study of 19 GH-deficient adults who received low-dose GH (J Clin Endocrinol Metab 2003 Apr;88(4): 1453-4). These Swedish researchers found that "GH replacement therapy with a low-dose GH in GH-deficient adult subjects is associated with a sustained deterioration of glucose metabolism as a consequence of the lipolytic effect of GH, resulting in enhanced oxidation of lipid substrate." They recommend that glucose metabolism be carefully monitored during long-term GH therapy.

Bramnert, M. et al. Growth hormone replacement therapy induces insulin resistance-activating the glucose-fatty acid cycle. J Clin Endocrinol Metab 2003 Apr;88(4): 1453-4

New Research Shows Potential Benefit of growth Hormone for Obesity and Heart Disease, without Previously Feared Increased Risk of Cancer. (Press release) www.endosociety.org

COPYRIGHT 2004 The Townsend Letter Group
COPYRIGHT 2004 Gale Group

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