Effect of 5 Years of GH Replacement on Atherosclerosis
Condition: Hypopituitarism; Pituitary Tumors; Growth Hormone Deficiency
MeSH terms: Pituitary Neoplasms; Hypopituitarism; Atherosclerosis
Study type: Observational

Summary: 
      Adult patients with hypopituitarism under adequate conventional hormone replacement therapy
      have reduced life expectancy due to excess vascular events (1-4). Deficiency in GH secretion
      (GHD) is likely to play a major role in determining the excess mortality, since it is
      associated with lipid abnormalities, visceral adiposity, glucose intolerance, insulin
      resistance, hypertension, cardiac abnormalities and increased intima-media thickness (IMT) at
      major arteries (5).

      Beneficial effects of growth hormone (GH) replacement on cardiovascular risk factors have
      been demonstrated in several studies of hypopituitary GHD patients (5). GH replacement
      improves body composition and lipid profile (5): it is accepted that management of
      dyslipidaemia is crucial in primary and secondary prevention of cardiovascular disease and
      part of the excess vascular risk associated with hypopituitarism is likely to be due to
      dyslipidaemia (6). A meta-analysis of blinded, randomized, placebo-controlled trials with low
      doses and long-duration GH treatment showed that GH replacement has beneficial effects on
      cardiovascular risk by improving lean and fat body mass, total and LDL cholesterol levels,
      and diastolic blood pressure (7). Besides, GH replacement also induces improvement in
      cardiovascular markers (8), and cardiac performance (9). In small cohorts of GHD adults,
      beneficial effects of GH replacement for 6-24 mos have also been reported on surrogate
      parameters of atherosclerosis, such as intima-media thickness (IMT) at major arteries
      (10-13), while 6 months of GH deprivation is associated with an impairment of the
      cardiovascular risk profile (12). In a consistent series of men and women with
      hypopituitarism we reported, however, that two years of GH replacement is not adequate to
      normalize IMT levels at common carotid arteries (13).

      To give further insights on the likelihood of reversal of early atherosclerosis in severe GHD
      patients after prolonged GH replacement, we designed this 5-yr prospective, controlled study.
      Only men aged ≤50 yrs and with severe GHD were enrolled to avoid gender and aging
      interference (13). Main outcome measure was IMT at common carotid arteries; secondary measure
      was prevalence of insulin-resistance syndrome according with the American College of
      Endocrinology (14).
    

Detailed description: 
      This is an observational,5-yr prospective, controlled study. At study entry, all subjects
      underwent serum assay of IGF-I, systolic and diastolic blood pressure (SBP, DBP) measurement,
      total-, and HDL-cholesterol, triglycerides, glucose, and insulin level after an overnight
      fasting, and common carotid arteries ultrasonography. The oral glucose load (oGTT) was
      performed by measuring blood glucose every 30 minutes for 2 hours after the oral
      administration of 75 g of glucose diluted in 250 ml of saline solution. The conversion
      factors (mg/dl to mmol/l) for lipids and glucose were as follows: cholesterol 0.02586,
      triglycerides 0.01129, and glucose 0.05551. According with previous studies (13,19-21) blood
      pressure was measured at the right arm, with the subjects in relaxed sitting position. The
      average of six measurements (three taken by each of two examiners, in the same day, between
      8.00-9.00 in the morning) with a mercury sphygmomanometer was used in all analysis.

      In the patients, all parameters and carotid ultrasonography were re-evaluated after 12, 24,
      36, 48 and 60 months while in controls they were re-evaluated after 60 months.

      At study entry and at study end, in all of the patients and controls the prevalence of
      insulin-resistance syndrome (IRS) was evaluated according with the American College of
      Endocrinology (14) based on the presence of at least two criteria of the following:
      triglycerides levels ≥1.7 mmol/liter, HDL-cholesterol levels ≤1.0 mmol/liter, blood pressure
      above 130/85 mmHg, fasting glucose between 6.1 and 7 mmol/liter or 2 hr after oGTT between
      7.7 and 11.1 mmol/liter.
    

Intervention name(s): Recombinant Growth Hormone, Genotropin (Pfizer)
Intervention type(s): Drug
Intervention MeSH terms: Hormones
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Three groups are studied: 1) Males with severe GHD undergoing GH replacement; 2) Males with
        severe GHD who did not undergo GH replacement because of either refusal or presence of risk
        factors for this treatment; 2) control men, age-matched with the patients.
      
Keywords: GH; IGF-I; GH deficiency; Atherosclerosis; Insulin resistance syndrome