Growth hormone-secreting pituitary tumors
1. What is the normal function of growth hormone in children and adults?
In children, growth hormone (GH) is responsible for linear growth. In children and adults, GH has many effects on intermediary metabolism, including protein synthesis and nitrogen balance, carbohydrate metabolism, lipolysis, and calcium homeostasis.
2. How are levels of GH normally regulated?
Pituitary secretion of GH is regulated primarily by two hypothalamic hormones: stimulatory GH-releasing hormone (GH-RH) and inhibitory somatostatin. Secretion of GH is also affected by adrenergic and dopaminergic hormones as well as by other central nervous system and peripheral factors.
3. Does GH directly affect peripheral tissues?
No. Most (although not all) effects of GH are mediated by another hormone called insulin-like growth factor 1 (IGF-1). IGF-1 is made by the liver and other organs in response to stimulation by GH. IGF-1 feeds back to the pituitary gland and suppresses GH secretion. Unlike GH, IGF-1 has a long half-life in plasma; thus plasma IGF-1 levels are helpful in the diagnosis of GH abnormalities.
4. What are the clinical features of excessive production of GH in children?
In children who have not yet undergone puberty and whose long bones still respond to GH, excessive GH causes accelerated linear growth. The result is gigantism.
5. Describe the clinical features of excessive production of GH in adults.
In adults, excessive GH causes acromegaly. Acromegaly is rare, with an incidence of approximately 5 cases per million people per year, and often progresses gradually and insidiously. The pathologic and metabolic effects of acromegaly are summarized in Table 21-1.
TABLE 21-1.
CLINICAL EFFECTS OF ACROMEGALY
| CLINICAL EFFECT | CAUSE |
| Coarse features | Periosteal formation of new bone |
| Enlarged hands and feet | Soft tissue hypertrophy |
| Excess sweating | Hypertrophy of sweat glands |
| Deepened voice | Hypertrophy of larynx |
| Skin tags | Hypertrophy of skin |
| Upper airway obstruction and sleep apnea | Hypertrophy of tongue and upper airway |
| Osteoarthritis | Hypertrophy of joint cartilage and osseous overgrowth |
| Carpal tunnel syndrome | Hypertrophy of joint cartilage and osseous overgrowth |
| Hypertension, congestive heart failure | Cardiac hypertrophy |
| Hypogonadism | Multifactorial |
| Diabetes mellitus, glucose intolerance | Insulin antagonism, other factors |
| Colonic polyps | Colonic hypertrophy |
6. What is the single best clue in examining a patient suspected of having acromegaly?
An old driver’s license picture or other old photographs provide the best clues. Patients with acromegaly are often unaware of the gradual disfigurement due to the disease or attribute it to aging. Comparing serial photographs can help establish the diagnosis as well as date its onset.
7. From what do patients with acromegaly die?
Acromegaly increases cardiovascular and metabolic risk factors, including hypertension, glucose intolerance, cardiomyopathy, and sleep apnea. The mortality from inadequately treated acromegaly is about double the expected rate in healthy age-matched subjects. Major causes of death are hypertension, cardiovascular disease, heart failure, and diabetes. Improved treatment has decreased this risk, but there is still a 30% higher risk of mortality in patients with acromegaly.
8. The husband of a patient with acromegaly complains that he cannot sleep because his wife snores. Is this relevant?
Sleep apnea occurs in 50% to 70% of patients with acromegaly. It can be due to soft tissue overgrowth of the upper airway or to altered central respiratory control. Sleep apnea may contribute to morbidity and mortality in acromegaly by producing hypoxia and pulmonary hypertension.
9. If I suspect that a patient may have acromegaly, what test should I order?
The single best screening test for acromegaly is measurement of the plasma level of IGF-1. Unlike those for GH levels, which are pulsatile and higher at night, blood specimens for IGF-1 measurement can be drawn any time of day. In adults, acromegaly is essentially the only condition that causes elevated IGF-1 values. In children, IGF-1 levels are more difficult to interpret because IGF-1 is normally high in growing children. IGF-1 levels may be less accurate in mild acromegaly, malnutrition, or hepatic or renal disease.
10. The patient’s IGF-1 value is not elevated, but I still think that she may have acromegaly. What other test should I order?
