Anatomic considerations

The pituitary sits in a depression in the skull located just below the third ventricle of the brain; the hypothalamus is located immediately above (see Fig. 59–1). The pituitary has two divisions: the anterior pituitary (or adenohypophysis) and posterior pituitary (or neurohypophysis). Both divisions are under hypothalamic control. As indicated in Figure 59–1, the hypothalamus communicates with the anterior pituitary by way of release-regulating factors delivered through a system of portal blood vessels. In contrast, communication with the posterior pituitary is neuronal.

Hormones of the anterior pituitary

The anterior pituitary produces six major hormones. Production and release of these hormones is controlled largely by the hypothalamus. Functions of the anterior pituitary hormones are summarized briefly as follows:

Hormones of the posterior pituitary

The posterior pituitary has only two hormones: oxytocin and antidiuretic hormone (ADH). The principal function of oxytocin is to facilitate uterine contractions at term. ADH promotes renal conservation of water.

Although oxytocin and ADH are considered hormones of the posterior pituitary, these agents are actually synthesized in the hypothalamus. The cells that make oxytocin and ADH are called neurosecretory cells. As indicated in Figure 59–1, these cells originate in the hypothalamus and project their axons to the posterior pituitary. Oxytocin and ADH are produced within the bodies of these cells and then undergo transport down axons to the axon terminals for storage. When appropriate stimuli impinge upon the bodies of the neurosecretory cells, impulses are sent down the axon, causing hormone release.

Hypothalamic release-regulating factors

The hypothalamus has the primary responsibility for regulating the release of hormones from the anterior pituitary. To accomplish this, the hypothalamus employs seven different release-regulating factors (see Fig. 59–1). Most of these factors stimulate the release of anterior pituitary hormones. However, two of these factors inhibit hormone release. As indicated in Figure 59–1, the hypothalamic release-regulating factors are delivered to the anterior pituitary via portal blood vessels. Although the hypothalamic releasing factors are of extreme physiologic importance, only five of them—growth hormone–releasing hormone, thyrotropin-releasing hormone, gonadotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin—have clinical applications. These are the only hypothalamic release-regulating factors discussed in this chapter.

Feedback regulation of the hypothalamus and anterior pituitary

With few exceptions, the release of hypothalamic and anterior pituitary hormones is regulated by a negative feedback loop, as illustrated in Figure 59–2. In this example, the loop begins with the secretion of releasing-factor X from the hypothalamus. Factor X then acts on the anterior pituitary to stimulate release of hormone A. Hormone A then acts on its target gland to promote release of hormone B. Hormone B has two actions: (1) it produces its designated biologic effects and (2) it acts on the hypothalamus and pituitary to inhibit further release of factor X and hormone A. This feedback inhibition of the hypothalamus and pituitary suppresses further release of hormone B itself, thereby keeping levels of hormone B within an appropriate range.

Regulation of release

The factors that regulate GH release are summarized in Figure 59–3. As indicated, the hypothalamus first releases growth hormone–releasing hormone (GH-RH), which stimulates release of GH from the pituitary. Growth hormone then acts on the liver and other tissues to cause release of insulin-like growth factor-1 (IGF-1). IGF-1 has two actions: it (1) promotes growth and (2) acts on the hypothalamus and pituitary to suppress release of GH-RH and GH, thereby completing a negative feedback loop.

One additional hormone—somatostatin—helps regulate GH release. As shown in Figure 59–3, somatostatin, which is produced in the hypothalamus, acts on the pituitary to inhibit GH release.

Biologic effects

Growth hormone deficiency

Growth hormone excess

Therapeutic uses

Growth hormone deficiency in adults.

In adults with GH deficiency—be it childhood-onset or adult-onset—replacement therapy can increase lean body mass, decrease adipose mass, and increase lumbar spine density. Unfortunately, GH also increases systolic blood pressure and fasting blood glucose. Furthermore, although GH increases muscle mass, it does not increase strength.

Other uses.

In addition to the uses noted above, GH is approved for pediatric growth failure associated with chronic renal insufficiency, cachexia or wasting in patients with AIDS, short-bowel syndrome, and short stature associated with Turner’s syndrome or Noonan’s syndrome. Individual GH preparations that are approved for these indications are listed in Table 59–1.

TABLE 59–1 

Somatropin (Human Growth Hormone): Preparations, Indications, and Dosages

Trade Name	Approved Indications	Dosage
Genotropin, Genotropin-Miniquick	GFAW pediatric GH deficiency	0.16–0.24 mg/kg/wk subQ, divided into 6 or 7 equal daily doses
	Pediatric NGHD short stature	Up to 0.47 mg/kg/wk subQ, divided into 6 or 7 equal daily doses
	GFAW Prader-Willi syndrome	0.24 mg/kg/wk subQ, divided into 6 or 7 equal daily doses
	GFAW Turner’s syndrome	0.33 mg/kg/wk subQ, divided into 6 or 7 equal daily doses
	Adult GH deficiency	0.04–0.08 mg/kg/wk subQ, divided into 7 equal daily doses
Humatrope, HumatroPen	GFAW pediatric GH deficiency	0.18 mg/kg/wk subQ or IM, divided into either (a) 6 equal daily doses or (b) 3 equal doses administered every other day
	Pediatric NGHD short stature	Up to 0.37 mg/kg/wk subQ, divided into 6 or 7 equal daily doses
	GFAW Turner’s syndrome	0.375 mg/kg/wk (max) subQ, divided into either (a) 7 equal daily doses or (b) 3 equal doses administered every other day
	Adult GH deficiency	0.006–0.0125 mg/kg/day subQ
Norditropin	GFAW pediatric GH deficiency	0.024–0.034 mg/kg subQ 6–7 days/wk
	GFAW Turner’s syndrome	0.067 mg/kg/day subQ
	GFAW Noonan’s syndrome	Up to 0.066 mg/kg/day subQ
	Adult GH deficiency	0.004–0.016 mg/kg/day subQ
Nutropin, Nutropin AQ	GFAW pediatric GH deficiency	0.3 mg/kg/wk subQ, divided into 7 equal daily doses
	Pediatric NGHD short stature	0.3 mg/kg/wk subQ, divided into 7 equal daily doses
	GFAW chronic renal insufficiency	0.35 mg/kg/wk subQ, divided into 7 equal daily doses
	GFAW Turner’s syndrome	0.375 mg/kg/wk subQ, divided into 3–7 equal daily doses
	Adult GH deficiency	0.006 mg/kg/day subQ initially, increased to 0.025 mg/kg/day (max) in patients under 35 yr, or to 0.0125 mg/kg/day (max) in patients over 35 yr
Omnitrope	GFAW pediatric GH deficiency	0.1–0.24 mg/kg/wk subQ, divided into 6 or 7 equal daily doses
	Adult GH deficiency	0.04–0.08 mg/kg/wk subQ, divided into 7 equal daily doses
Saizen	GFAW pediatric GH deficiency	0.06 mg/kg subQ or IM 3 days/wk
	Adult GH deficiency	0.005 mg/kg/day subQ initially, increased to no more than 0.01 mg/kg/day after 4 wk
Serostim	Cachexia or wasting in AIDS	4–6 mg subQ daily at bedtime (dose depends on patient’s weight). For adults under 35 kg, dosage is 0.1 mg/kg subQ once daily at bedtime
Tev-Tropin	GFAW pediatric GH deficiency	0.1 mg/kg subQ 3 times a week
Zorbtive	Short-bowel syndrome	0.1 mg/kg subQ daily for 4 wk

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