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Reduced microvascular perfusion and reactivity in adult GH deficient patients is restored by GH replacement
1Third Department of Internal Medicine, Faculty of Medicine I, Charles University, Prague, Czech Republic. vhana@lf1.cuni.cz
Insights
Growth hormone deficiency (GHD) in adults impairs skin microcirculation and vascular reactivity. GH replacement therapy restores these functions, potentially improving cardiovascular health and thermoregulation in GHD patients.
Area of Science:
- Endocrinology
- Cardiovascular Science
- Microcirculation Research
Background:
- Adults with growth hormone deficiency (GHD) exhibit increased cardiovascular risk and mortality.
- Endothelial dysfunction, an early sign of atherogenesis, is prevalent in GHD.
- Microcirculation and vascular reactivity changes may serve as early indicators of vascular complications.
Purpose of the Study:
- To assess microcirculation and vascular reactivity in adults with GHD.
- To evaluate the impact of growth hormone (GH) replacement therapy on these parameters.
- To compare findings in GHD patients with and without GH treatment against a control group.
Main Methods:
- Laser-Doppler flowmetry was used to measure skin microvascular perfusion and reactivity on the forearm.
- Two dynamic tests, post-occlusive reactive hyperemia (PORH) and thermal hyperemia (TH), were employed.
- Measurements were taken before and after 6 and 12 months of GH replacement therapy in 13 adult GHD patients.
Main Results:
- Peak flow and perfusion velocity during thermal hyperemia were significantly reduced in GHD patients before treatment but normalized with GH therapy.
- Post-occlusive reactive hyperemia (PORH) was also reduced in GHD patients, with normalization observed during GH treatment.
- GH replacement therapy restored microvascular function to levels comparable to healthy controls.
Conclusions:
- Adults with GHD have significantly impaired skin microcirculation and vascular reactivity.
- GH replacement therapy effectively restores these microcirculatory functions.
- Improved vascular reactivity may mitigate the increased cardiovascular morbidity associated with GHD and address impaired thermoregulation.
Background:
An increased cardiovascular risk and mortality in hypopituitary patients receiving conventional hormonal treatment without GH replacement have been shown in several studies. Various atherogenic risk factors including endothelial dysfunction - an early event in the atherogenesis - are more expressed in adults with GH-deficiency (GHD). Changes in microcirculation and vascular reactivity could represent an early marker of developing vascular changes.
Objective:
To evaluate the microcirculation and vascular reactivity in a GHD state before and during GH replacement. SUBJECTS, METHODS AND DESIGN: Thirteen adult patients (ten men, mean age 40+/-9 years) with severe GHD were studied. The skin microvascular perfusion and reactivity were measured by laser-Doppler flowmetry on the forearm. Two dynamic tests for vascular perfusion and reactivity were used - postocclusive reactive hyperemia (PORH) and thermal hyperemia (TH) at 44 degrees C. Measurements were performed before and after 6 and 12 months on GH replacement with a dose of GH that normalized IGF-I serum levels. The parameters of tissue perfusion and vascular reactivity measured in GHD were compared with values during GH treatment and with the results of the control group.
Results:
Peak flow during TH in GHD patients was significantly reduced before GH treatment when compared with healthy subjects (means+/-s.e.m., 68+/-6.6 vs 111+/-8.3 perfusion units (PU), P<0.001) and normalized on GH treatment (109+/-12.7 PU). The velocity of perfusion increase during TH before treatment was significantly reduced in GHD as well (0.84+/-0.07 vs 1.53+/-0.19 PU/s, P<0.03) and normalized on GH treatment (1.38+/-0.24 PU/s). The PORH was also significantly reduced in GHD compared with controls (PORH(max) 414+/-63 vs 528+/-58%, P<0.05) and during GH treatment was restored to values not different from controls (642+/-86%, P=NS).
Conclusions:
Skin microcirculation and vascular reactivity measured by laser-Doppler flowmetry is significantly reduced in GHD adults and is restored during GH replacement therapy. Reduced tissue perfusion and reactivity probably reflect the endothelial dysfunction in the GHD state. Reduced nitric oxide production and bioavailability and also other factors like increased sympathetic activity and reduced conversion of thyroxine to triiodothyronine in the GHD state can contribute to changes in microcirculation. Restoration of vascular reactivity by GH replacement might have favorable clinical consequences on the increased vascular morbidity of GHD patients. Reduced skin microvascular perfusion and reactivity in GHD probably contribute to the impaired thermoregulation - a clinical symptom of GHD.