Bone health and cardiovascular risk in hypopituitary patients on complete hormone replacement, including GH

Abstract: Growth hormone deficiency (GHD) is associated with decreased bone mineral density (BMD). Low BMD is correlated to increased fracture risk. There are no studies on fracture risk in GHD patients on GH therapy and no studies on BMD in adults with childhood onset (CO) craniopharyngioma (CP) on GH therapy. We have shown a doubled fracture incidence in CO GHD women and decreased incidence of fractures in adult onset (AO) GHD men. We have also shown decreased BMD in adult women with CO CP on GH therapy, in comparison to matched controls, but not in CO CP men. The cause is not known but insufficient sex steroid and GH replacements, particularly during adolescence, in CO GHD and CP women, and an adequate substitution rate of testosterone and GH in AO GHD and CO CP men are possible explanations.

GHD is also associated with increased cardiovascular mortality and morbidity. The impact of long-term GH replacement on cerebral- and cardiovascular diseases and diabetes mellitus (DM) in hypopituitary patients and the prevalence of cardiovascular morbidity and risk factors in adults with childhood onset (CO) craniopharyngioma (CP) are unknown. We have shown that the life-long incidence of non-fatal stroke was tripled in GHD women and doubled in men, but a decline was seen among both genders during the periods where most patients had GH replacement. Life-long incidence of non-fatal cardiac events was similar in the patient and control cohorts, but declined in GHD men during the periods where most patients had GH replacement. GHD women had higher prevalence of type 2 DM and lipid-lowering medication, whereas GHD men had higher prevalence of antihypertensive medication. This cardio-protective medication, together with the GH therapy may have resulted in the decline in non-fatal stroke risk, particularly noted in GHD women, and in significantly lower non-fatal cardiac risk that was seen in GHD men. We have also shown that patients with a CO CP, on GH therapy, had increased cardiovascular morbidity and particularly women were at risk. Of CP women 60% had increased risk for cardiovascular disease.

Insulin tolerance test (ITT) is the recommended test for diagnosing GHD. We have shown that GHD patients during an ITT had very low nadir blood glucose levels and few symptoms of hypoglycemia and in 31% unawareness was seen. If the ITT is still going to be recommended, we ask for more uniform recommendations.