Hong-bo Yang， Meng-qi Zhang， Hui Pan， and Hui-juan Zhu*

1Department of Endocrinology，2Department of Pediatrics， Peking Union Medical College Hospital， Chinese Academy of Medical Sciences & Peking Union Medical College， Beijing 100730， China

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Management of Adult Growth Hormone Deficiency at Peking Union Medical College Hospital：A Survey among Physicians△

Hong-bo Yang1， Meng-qi Zhang2， Hui Pan1， and Hui-juan Zhu1*

1Department of Endocrinology，2Department of Pediatrics， Peking Union Medical College Hospital， Chinese Academy of Medical Sciences & Peking Union Medical College， Beijing 100730， China

adult growth hormone deficiency； management； continued medical education

Objective To evaluate physicians’ attitude and knowledge about the management of adult growth hormone deficiency （AGHD） at Peking Union Medical College Hospital and impact factors associated with better decision-making.

Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital， a major teaching hospital in Chinese Academy of Medical Sciences. Data of physicians’educational background， clinical training， patient workload per year and continuing medical education in AGHD were collected. Factors associated with appropriate answers were further analyzed by multivariate regression models.

Results One hundred and eighteen internal medicine residents， endocrine fellows， attending physicians and visiting physicians responded to the survey. Among them， 44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy. Moreover， 56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD. Logistic regression analysis of physician demographic data， educational background， and work experience found no consistent independent factors associated with better decision-making， other than continued medical education， that were associated with treatment choice.

Conclusions The physicians’ reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence. High quality continued medical education is required to improve Chinese physician management of AGHD.

Chin Med Sci J 2016； 31（3）：168-172

A DULT growth hormone deficiency （AGHD） is a debilitating condition， associated with reduced muscle mass and muscle strength， osteoporosis，obesity and increased risk factors of metabolic syndrome.1，2AGHD is resulted from tumors， pituitary surgery， radiation therapies of the head， traumatic brain disease and other hypothalamic-pituitary disease. Recombinant human growth hormone （rhGH） replacement therapy provides benefits in body composition and quality of life.3，4The Endocrine Society Clinical Guideline on Evaluation and Treatment of Adult Growth Hormone Deficiency has been published in 20065and updated in 2011.1

In Chinese population， the incidence rate of pituitary tumor and child-onset growth hormone deficiency （GHD）was about 1/100 0006and 1/86467respectively. But the prevalence of AGHD is unknown. Although there is certain progress in the management of AGHD， variance in practice also exists in Chinese physicians. There is no consensus or clinical guidelines about AGHD in China so far. And we have not found any research articles evaluating quality of care about AGHD patients in Chinese medical literature database， Medline or Embase. In the present study， we investigated the knowledge and attitude of Chinese physicians in the management of AGHD patients in general.

SUBJECTS AND METHODS

Setting

Peking Union Medical College Hospital （PUMCH） is a major academic healthcare center of modern medicine in Beijing. Its endocrinology division is one of the oldest subspecialty programs in endocrine disorders in China.8Each year our division provides care for 100 000 patients with endocrine disorders in out-patient clinic and 1300 patients in subspecialty wards.

Questionnaire

The questionnaire comprises 21 questions， including the respondents' demographic characteristics， education background and clinical experience， level of their hospital， patient workload seen per year， and experiences of continuing medical education （CME） in recent three years. Questions about the knowledge and attitude toward AGHD management were based on the key points recommended by the Endocrine Society Clinical Practice Guideline on Evaluation and Treatment of Adult Growth Hormone Deficiency.1

Subjects

The study subjects are physicians working or being trained in the department of Endocrinology in PUMCH， including residents， endocrinologists and visiting physicians. The questionnaires were answered anonymously. The response of each question was classified as appropriate if it was consistent with the recommendation of the Endocrine Society guidelines1as follows：

（1） The insulin tolerance test （ITT） and the growth hormone-releasing hormone （GHRH）-arginine test should be used to establish the diagnosis of AGHD.

（2） If the causes of the GHD in children are structural lesions with multiple hormone deficiencies and proven genetic causes， a low insulin-like growth factor I （IGF-I） level at least 1 month off rhGH therapy is sufficient documentation of persistent GHD without additional provocative testing.

（3） rhGH replacement therapy offers significant clinical benefits in body composition， exercise capacity， skeletal integrity and the quality of life.

（4） rhGH dosing regimens should be individualized rather than weight-based and start with low doses and be titrated according to clinical response， side effects， and IGF-I levels.

（5） Treatment is contraindicated in the presence of an active malignancy. Thyroid and adrenal function should be monitored during rhGH therapy of adults with GHD.

Statistical analysis

Characteristics of the participants and the responses to each question have been recorded. SPSS 17.0 software was used to analyze the data. Categorical variables are expressed as percentage. Factors associated with appropriate answers were further analyzed by multivariate regression models.

RESULTS

Characteristics of respondents

The response rate was 93.8% （122/130）. Among the 122 questionnaires collected， 4 of the respondents answered less than 20% of the clinical questions and were excluded from further analysis. The remaining 118 respondents answered all questions and were further analyzed as study subjects. For valid responses， we identified 61 residents，41 attending physicians， 12 associate professors and 4 professors. All of the respondents were working in a tertiary academic healthcare center. Among them， 53.4% had more than 5 years work experience， 25.4% saw more than 10 anterior hypopituitarism patients per year and 9.3% saw more than 10 AGHD patients per year. Only 35.6% had had CME of any kind in the disease. Other features of the respondents' educational background and work experience are listed in Table 1.

Table 1. Characteristics of respondents （n=118）

Attitude towards AGHD management

In all， 53 （44.9%） respondents supported long-term recombinant growth hormone replacement therapy in AGHD patients and 36 （30.5%） respondents were against the replacement therapy. For diagnostic test， 27 （22.8%）chose IGF-I， 67 （56.8%） chose ITT and GHRH-arginine test. For patients with deficiencies in three or more pituitary axes， 57 （48.3%） suggested that provocative testing was optional. For those with irreversible nature of the cause of the GHD in children with structural lesions with multiple hormone deficiencies and those with proven genetic causes，57 （48.3%） suggested that a low IGF-I level at least 1 month off rhGH therapy was sufficient for diagnosis. Fortyfive （38.1%） preferred weight-based growth hormone dosing regimens and 53 （44.9%） indicated to start with low doses and be titrated according to clinical response， side effects and IGF-I levels. In addition， 108 （91.5%） believed that active tumor was contraindicated in rhGH replacement therapy.

Benefits of treatment with growth hormone were highly acknowledged. The benefits of rhGH replacement in improvement of body composition， muscle maturation， skeletal integrity and quality of life were believed by 85 （72.0%），93 （78.8%）， 87 （73.7%） and 106 （89.8%） respondents，respectively. Eighty-one （68.6%） respondents indicated that rhGH treatment could decrease risk factors of metabolic syndrome. For side effects and risks associated with rhGH therapy， thyroid and adrenal function during rhGH therapy were suggested to be monitored by 94 （79.6%） and 87（73.7%） respondents respectively. For issues and concerns about long-term rhGH replacement therapy， 70 （59.3%）respondents worried about patients' compliance， 109（92.3%） respondents worried about the cost， 70 （59.3%）worried about increased risks of tumorigenesis and 78（66.1%） worried about hyperglycemia.

Further， using logistic multivariate analysis we found that CME was the only factor associated with physicians' attitude towards rhGH replacement therapy （OR=6.75，95% CI=2.04-22.33， Table 2）. Physicians who stated that they had had CME in AGHD were more likely to agree that patients need long-term rhGH therapy. Physicians having CME in AGHD did respond better about the AGHD diagnosis questions， but we found no statistic significance （Table 3）.

DISCUSSION

Although both pituitary tumors and hypopituitarism are not rare，9AGHD is less recognized and treated in China comparing with Western countries. There are several research papers from single centers of China investigatingosteoprotegerin and adipocytokines in AGHD.10，11However，the epidemiological data of AGHD in Chinese population are limited， and whether physicians have clear recognition of the diagnosis and treatment of AGHD is not well known.

Table 2. Attitude towards rhGH therapy among physicians

Table 3. Attitude towards diagnosis procedures among physicians with or without CME （n=118）

The current guideline recommended that rhGH replacement therapy provided significant benefits in body composition， skeletal integrity and the quality of life. And the final decision to treat AGHD patients requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.1Our results show that the physicians' reported diagnosis and treatment of AGHD at this major academic healthcare center in Beijing was often inconsistent with current evidence. Although a high rate of the physicians we investigated knew well about the benefits and contraindications of rhGH treatment， only 44.9% of them thought that AGHD patients should accept recombinant growth hormone replacement therapy. Only 56.8% of the physicians agreed that the ITT and the GHRH-arginine test should be used unless there is a proven genetic/structural lesion persistent from childhood.

Our results show that CME was strongly associated with treatment choice. Physician demographic data，educational background and work experience had no relationship with better decision-making. As we all know，CME is delivered by faculty who are experts in their clinical areas and helps physicians maintain competence and learn about new and developing areas of their field. Due to the lack of clinical recognition of AGHD， CME courses specifically developed for AGHD in China are rare， and most of the CME courses are only available in major academic healthcare centers. We therefore propose that the quantity of CME be increased. Besides， Chinese literatures in this area in recent 5 years are scarce， and need to be updated. We hope to improve the clinical recognition of AGHD byhigh quality CME， so that better-designed multicenter studies can be performed to assess the rhGH treatment effect on Chinese adult patients of growth hormonedeficient， and then it will be possible to establish the clinical practice guideline applicable for the Chinese population.

REFERENCES

1. Molitch ME， Clemmons DR， Malozowski S， et al. Evaluation and treatment of adult growth hormone deficiency：an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011； 96：1587-609.

2. Uzunova I， Kirilov G， Zacharieva S， et al. Individual risk factors of the metabolic syndrome in adult patients with growth hormone deficiency—a cross-sectional case-control study. Exp Clin Endocrinol Diabetes 2015； 123：39-43.

3. Ahmad AM， Hopkins MT， Thomas J， et al. Body composition and quality of life in adults with growth hormone deficiency； effects of low-dose growth hormone replacement. Clin Endocrinol 2001； 54：709-17.

4. Hoffman AR， Kuntze JE， Baptista J， et al. Growth hormone（GH） replacement therapy in adult-onset GH deficiency：effects on body composition in men and women in a double-blind， randomized， placebo-controlled trial. J Clin Endocrinol Metab 2004； 89：2048-56.

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6. Huang WQ， Zheng SJ， Tian QS， et al. Statistical analysis of central nervous system tumors in China. J Neurosurg 1982； 56：555-64.

7. Bao X， Shi Y， Du Y， et al. Prevalence of growth hormone deficiency of children in Beijing. Chin Med J 1992； 105：401-5.

8. Wilson JD. Peking Union Medical College Hospital， a palace of endocrine treasures. J Clin Endocrinol Metab 1993； 76：815-6.

9. Schneider HJ， Aimaretti G， Kreitschmann-Andermahr I，et al. Hypopituitarism. Lancet 2007； 369：1461-70.

10. Li ZP， Zhang M， Gao J， et al. Study of the correlation between growth hormone deficiency and serum leptin，adiponectin， and visfatin levels in adults. Genet Mol Res 2014； 13：4050-6.

11. Xia J， Li L， Ren W， et al. Correlation of increased plasma osteoprotegerin and cardiovascular risk factors in patients with adult growth hormone deficiency. Int J Clin Exp Med 2015； 8：3184-92.

for publication September 25， 2015.

Tel： 86-10-69155100， Fax： 86-10-69155073， E-mail： huijuanzhu@hotmail.com

△Supported by National Natural Science Foundation of China （81400774） and PUMC Youth Fund （33320140164 and 3332016128）.