Saturday, May 2, 2009

Untreated Growth Hormone Deficiency Contributes to the Phenotype of Patients With History of Cushing's Disease


Presented at ECE

    By Chris Berrie
    ISTANBUL, Turkey -- May 1, 2009 -- Untreated growth hormone deficiency (GHD) may contribute to the phenotype of patients with a history of Cushing's disease (CD), according to a prospective cohort study presented here on April 28 at the 11th European Congress of Endocrinology (ECE).

    The study was based on information from the KIMS (Pfizer International Metabolic) Database.

    "KIMS is a database that follows adult patients with severe growth hormone deficiency, and the majority of them are replaced with growth hormone, and some patients are untreated and serve as a comparative control, group," explained Maria Koltowska-Häggström, MD, KIMS Medical Outcomes, Pfizer Endocrine Care, Sollentuna, Sweden.
    "This database contains more than 14,000 patients, and almost 60,000 years of patient follow-up."

    Here, both CD and GHD were specifically considered, with each characterised by visceral obesity, decreased lean body mass, decreased bone mineral density, dyslipidaemia, glucose intolerance, and reduced quality of life. Most of these conditions can be reversed by GH replacement in deficient adults.

    The objective of this study was thus to evaluate the contribution of GHD to the controlled CD phenotype, in comparison to GHD due to nonfunctioning pituitary adenoma (NFPA), before and after 3 years of GH treatment.
    Age- and gender-matched patient cohorts were retrieved from the KIMS database according to those patients with controlled CD (n = 322; mean age, 46.3 years; female, 74%) and those with GHD due to NFPA (n = 748; mean age, 47.7 years; female, 71%).

    The relevant patient treatment characteristics for these CD and NFPA groups were time since last treatment (6.9 vs 5.4 years, respectively) and treatment received (surgery, 48% vs 54%; radiation, 9% vs 1%; surgery and radiation, 39% vs 39%).

    Prospective measures were assessed before and after 3 years of GH treatment, which included insulin-like growth factor (IGF)-1, body mass index (BMI), waist circumference, blood pressure, lipids, fasting glucose, haemoglobin A1C (Hb A1C), and quality of life as judged by the Adult GHD Assessment (AGHDA) scores.

    Before GH replacement therapy, the patients with controlled CD, compared with those with GHD due to NFPA (respectively), showed more favourable mean total cholesterol (5.7 vs 5.9 mmol/L; P < .05), and low-density lipoprotein (LDL) cholesterol (3.5 vs 3.8 mmol/L; P < .01), but a poorer mean quality of life (AGHDA score, 14.6 vs 11.3; P < .001).

    For the mean GH therapies, both patients groups started on 0.22 mg/day, and after 3 years of treatment their maintenance doses were 0.39 mg/day and 0.37 mg/day, respectively.

    After 3 years, these respective groups showed similar significant increases in mean IGF-1 standard deviation scores (2.18 vs 2.05; P < .001 for both), in fasting glucose (0.5 vs 0.3 mmol/L; P < .001 for both), and in Hb A1C (0.2%, P < .001, vs 0.1%, P < .01). Both groups also showed similar significant reductions in total cholesterol (-0.6 vs. -0.5 mmol/L; P < .001 for both) and LDL cholesterol (-0.6 vs -0.5 mmol/L; P < .001 for both).

    In contrast, only patients with controlled CD showed a significant increase in BMI (0.3, P < .01 vs 0.0 kg/m2), and only the NFPA group showed a significant decrease in waist circumference (-1.1 vs -1.2 cm, P < .001).

    Significant improvements in quality of life were seen in both treatment groups, although these were significantly greater in the controlled CD group (-6.0 vs -5.0; P < .001 for both).

    "At baseline, these patients with Cushing's disease have a poorer quality of life than patients with nonfunctioning pituitary adenoma, and respond to treatment in a similar beneficial way," said Dr. Koltowska-Häggström.

    The indications are thus that untreated GHD may indeed contribute to the phenotype of controlled CD and "they should be treated," said Dr. Koltowska-Häggström.

    Funding for this study was provided by Pfizer.

    [Presentation title: Effects of 3 Years Growth Hormone (GH) Replacement in Adult-Onset Growth Hormone Deficiency (GHD) Due to Controlled Cushing's Disease (CD). Abstract P547]

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