Cause:
Pathophys:Excessive HGH causes increased IGF-1 (insulin-like growth factor 1) and stimulates growth, glucose intolerance, sleep apnea, and increased plasma volume, causing hypertension, LVH, decreased systemic vascular resistance, and increased cardiac output ("hyperkinetic heart syndrome"—Ann IM 1990;113:921)
Sx:Acral enlargement (big hands and feet) (100%), amenorrhea, impotence (80% of males), headache (60%), osteoarthritis (30%), diplopia (15%), increased sweating, coarsened facial features, big tongue, sleep apnea, and, in children, gigantism
Si:Frontal hyperostosis; lantern jaw; hands with distal spadia; thick skin, esp heel pads >22 mm; bitemporal visual field defects (25%); goiter (25%); aldosterone-induced hypertension (30%) (Nejm 1972;287:795), and LVH which reverses w rx (Ann IM 1992;117:719)
Diabetes mellitus (80%); carpal tunnel syndrome (35%—Ann IM 1973;78:379); osteoarthritis; sleep apnea in most, 2/3 obstructive, 1/3 central (Ann IM 1991;115:527), helped by octreotide rx (Ann IM 1994;121:478); atherosclerotic disease (Ann IM 1974;81:11) like cardiomyopathy and CHF; colonic polyps (46%) and cancer (8%) (Ann IM 1984;101:627), screen for over age 50 yr or when disease present >10 yr; skin tags, may be a marker
Lab:
Chem:Somatomedin C (insulin-like growth factor [IGF-1]) by RIA correlates best with disease activity
HGH by RIA; oral GTT may provoke paradoxical HGH rise, HGH 1 h into GTT <0.5 ngm/cc is normal without false negatives (N. Elgee 1972)
Diabetic GTT (80%)
Xray:
MRI 1st? (Nejm 1991;324:1555), but 10+% false pos in general population (Ann IM 1994;120:817)
CT shows sellar erosion commonly, unlike Cushing’s syndrome-producing tumors
Heel pad thickness
Hands show spade-like distal phalangeal tufts, wide cartilages
Rx:
1st: Transsphenoidal surgery
2nd: Radiation by stereotactic proton beam; 50% will become hypopit after 10 yr
3rd: Long-acting somatostatin analog, octreotide 100 µgm sc q 8 h (Ann IM 1992;117:711), especially helps cardiomyopathy/atherosclerotic disease (Ann IM 1990;113:921) and sleep apnea (Ann IM 1994;121:478); adverse effects: diabetes, gallstones (Ann IM 1990;112:173)
4th: Pegvisomant (Somovert) (Med Let 2003;45:55; Nejm 2000;342:1171) sc daily; HGH receptor antagonist; $50 000-100 000/yr
Table 5.3 Treatment of Various Pituitary Adenomas
| Approach | Prolactin-Secreting Tumors | Growth Hormone-Secreting Tumors | ACTH-Secreting Tumors | TSH-Secreting Tumors | Nonfunctioning Tumors |
|---|---|---|---|---|---|
| Primary Approach | DA: microadenomas, 80-90% response; macroadenomas, 60-75% response | Surgery: microadenomas, 70% response; macroadenomas, 50% response | Surgery: microadenoma, 80-90% response, macroadenoma, 50% response | Surgery plus irradiation, 67% response | Surgery: improved vision, 70% response |
| Secondary approach | Surgery: microadenomas, 55% response; macroadenomas, 20% response | Somatostatin analogs, 60% response; DA, 20% response; irradiation, 50% response (by 12 yr) | Irradiation plus cortisol-decreasing drugs | Somatostatin analogs, 75% response | Irradiation |
| Novel medical developments | Depot long-acting DA, somatostatin receptor subtype-selective analogs | Long-acting somatostatins, somatostatin receptor subtype-selective analogs; growth hormone receptor or GHRH antagonist | Long-acting somatostatins | Gonadotropin-releasing hormone antagonists |
ACTH = adrenocorticotropin hormone; DA = dopamine agonists; GHRH = growth hormone-releasing hormone; TSH = thyroid-stimulating hormone. "Response" refers to normalization of hormone secretion or ablation of tumor mass.
Reproduced with permission from Shimon I, Melmed S. Management of pituitary tumors. Ann Intern Med. 1998;129:472-483