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    Home > Active Ingredient News > Endocrine System > Interpretation of the main points of the "Expert Consensus on the Diagnosis and Treatment of Adult Growth Hormone Deficiency (2020 Edition)"

    Interpretation of the main points of the "Expert Consensus on the Diagnosis and Treatment of Adult Growth Hormone Deficiency (2020 Edition)"

    • Last Update: 2021-05-08
    • Source: Internet
    • Author: User
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    Introduction: On April 23, 2021, the "12th National Symposium on Progress in Endocrine and Metabolic Diseases" was held in Baoding.
    At this meeting, Professor Gu Weijun from the Endocrinology Department of the First Medical Center of the Chinese People’s Liberation Army A wonderful speech was delivered on the topic of "Expert Consensus on the Diagnosis and Treatment of Growth Hormone Deficiency (GHD) (2020 Edition)".

     Professor Gu Weijun interpreted the "Consensus" from the general situation, harm, diagnosis, and growth hormone (GH) replacement therapy of adult growth hormone deficiency (GHD).

     Expert introduction Dr.
    Gu Weijun ●Deputy Director, Chief Physician, Associate Professor, and Master Supervisor of the Endocrinology Department of the First Medical Center of PLA General Hospital ●National Committee and Deputy Secretary-General of the Endocrinology Branch of the Chinese Medical Association ●Member and Secretary of the Endocrinology Branch of the Beijing Medical Association ●China Member of the Endocrinology Branch of the Association of Women Doctors ● Former Vice Chairman of the Youth Committee of the Endocrinology Branch of the Chinese Medical Association ● Former Vice Chairman of the Youth Committee of the Endocrinology Branch of the Chinese Medical Doctor Association Overview of Adult GHD 1.
    Definition of GHD First of all, Professor Gu Weijun introduced adults The definition and epidemiological status of GHD.

    GH receptors are distributed throughout the body, including fat, liver, skeletal muscle, and cardiovascular system.
    They play an important role in the body's growth and development, material metabolism and functional regulation.

    Adult GHD refers to the impairment of GH synthesis and secretion in the anterior pituitary of adults, complete or partial lack of GH, and abnormal metabolism.

    According to the age of onset, it is divided into childhood onset and adult onset.
    Among them, 15-18 years old (usually the stage of childhood onset GHD from the late adolescence to the peak bone mass and full maturity) is called transitional GHD.
    Period GHD.2.
    Epidemiological data of GHD Western countries such as the United States have about 6000 new cases of adult GHD every year, and the population prevalence of pituitary adenoma is about 1:10000.
    From this data, the annual incidence of GHD in adulthood is estimated to be about It is 1/100000.

    If the childhood-onset GHD patients are included, the annual incidence rate is about 2 per 100,000.

    The total prevalence of GHD in adulthood and childhood onset is (2~3)/10000.

    There are few relevant epidemiological data in China.
    From 2009 to 2010, 22 hospitals across the country carried out a survey of the prevalence of adult GHD after pituitary adenoma and found that the postoperative GHD rate of patients with pituitary prolactinoma and non-functional adenoma was as high as 87.
    8 %, the disease situation is severe.

     The hazards of adult GHD The etiology of adult GHD varies depending on the age of onset.
    Childhood-onset GHD is mainly idiopathic isolated GHD, which can be caused by genetic defects of the hypothalamus-pituitary axis and hypothalamic-pituitary structural brain defects, etc.
    Congenital factors, perinatal injury, brain tumors and other acquired factors; the onset of GHD in adulthood is mostly hypothalamic/pituitary tumors and/or sequelae of related treatments.
    The common causes are traumatic brain injury, subarachnoid hemorrhage and deficiencies.
    Bloody stroke is moderate, and adult idiopathic GHD is very rare.

     The clinical manifestations of adult GHD are diverse, including decreased lean body mass, dyslipidemia, cardiac dysfunction, and decreased bone density (Figure 1), and patients often have a variety of comorbidities, including lipid metabolism disorders, increased risk of cardiovascular and cerebrovascular diseases, Loss of bone mass or osteoporosis increases the risk of future death.

     Figure 1 Clinical manifestations of GHD in adults Diagnosis of GHD in adults 1.
    Screening for GHD The clinical manifestations of GHD in adults are often non-specific.
    For patients with a history of hypothalamic-pituitary disease, the possibility of GHD should be considered.
    Thralamus-pituitary disease; have undergone surgery or radiotherapy on the hypothalamus-pituitary gland; traumatic brain injury; patients with evidence of other pituitary hormone deficiencies undergo GH and insulin-like growth factor 1 (IGF-1) measurement, and adult GHD screening . If the diagnosis of adult GHD is suspected based on the patient's medical history, clinical manifestations, and serum randomized GH/IGF-1 screening results, it is recommended to perform a GH provocation test to confirm the diagnosis (Figure 2).

    Figure 2 Adult GHD diagnosis process.
    It should be noted that the random serum GH and IGF-1 levels are affected by many factors.
    Therefore, it is not recommended to be used alone for the diagnosis of adult GHD, but only for screening.

     2.
    Diagnosis of GHD-ITT is the gold standard GH provocation test.
    It uses certain methods to stimulate pituitary GH secretion in a short period of time.
    Continuous blood samples are collected to determine the peak serum GH after provocation.
    The stimulating drugs include insulin and glucagon The test methods include insulin resistance test (ITT), glucagon challenge test (GST) and macirelin challenge test.

     Among them, ITT is the gold standard for diagnosis of adult GHD: the method of operation is intravenous injection of 0.
    1-0.
    15IU/Kg of conventional insulin, blood samples are taken 30 minutes before injection, immediately before injection, and 30, 45, 60, 90, and 120 minutes after injection to determine blood glucose.
    And blood GH level; if the serum glucose concentration is lower than 2.
    2mmol/l, the peak value of serum GH is ≤5μg/L, the diagnosis is adult GHD.

     It should be noted that ischemic heart disease and epilepsy are contraindications for ITT, and the test process must be closely monitored (hypoglycemia).
    The reproducibility is poor.
    Affected by severe obesity, delayed hypoglycemia may occur.

    Consensus recommends that patients with ITT contraindications can choose GST or Maricilin provocation test.

     Table 1 Comparison of various GH provocation tests 3.
    Diagnostic precautions ➤ Excessive or insufficient replacement of other pituitary hormones may affect the results of provocation test.
    Therefore, provocation tests should be carried out in patients with stable replacement of other pituitary hormones in stable condition or systemic conditions allow; ➤After childhood-onset GHD patients reach a lifetime high, they need to stop GH treatment for at least 1 month, and then perform IGF-1 testing or GH provocation test to reassess; ➤Craniocerebral injury and subarachnoid hemorrhage can cause temporary GH deficiency It is recommended that a GH provocation test should be performed at least 12 months later; ➤Children’s craniocerebral radiotherapy will increase the risk of GHD.
    For patients who have no deficiency in the initial determination of GH, it is recommended to perform the GH provocation test again in the transitional period or adulthood to exclude Late-onset GHD. ➤For hypothalamic-pituitary organic diseases with multiple pituitary hormone deficiencies (>3 PHD) with reduced IGF-1 levels (<-2.
    0SDS), hypothalamic-pituitary axis genetic defects, or hypothalamic-pituitary structural brain Patients with defects can directly diagnose transitional GHD or adult GHD without repeating the GH provocation test.

     GH replacement therapy for adult GHD The treatment for adult GHD uses recombinant human growth hormone (rhGH) replacement therapy.
    The treatment should restore the patient's lipid metabolism, bone density, exercise capacity, etc.
    to normal, so that the target serum IGF-1 level reaches normal The gender and age-matched reference range of the population (-2~+2SDS) to improve the clinical symptoms of adult GHD patients.

     1.
    The treatment principle follows the individualized treatment plan.
    The initial treatment dose is not related to body weight and should be determined based on age, gender and combined medication; starting with a low dose, gradually increase the dose to normalize IGF-1 level; according to IGF-1 level , Clinical response and tolerability for dose adjustment (Figure 3).

      Figure 3 Individualized dosage formulation of rhGH 2.
    Precautions ➤If there is a lack of other axis hormones, adjust the remaining hormones to stable before GH treatment; ➤Have a history of malignant tumors (except for basal cell carcinoma or performance cell skin cancer), RhGH is not recommended for patients with active proliferative or severe non-proliferative diabetic retinopathy; ➤It is not recommended for adult GHD pregnant women to use rhGH during pregnancy; ➤For patients with a family history of strong tumors, use rhGH treatment with caution; ➤For those with GH For adult GHD patients who are willing to treat and have a history of cancer, treatment options need to be cautious.
    After the cancer has been in remission for at least 5 years and the patient’s oncologist has fully communicated and discussed, deciding whether to start low-dose rhGH treatment.

     3.
    The course of treatment rhGH treatment usually starts to produce benefits at 6 months.

    If the quality of life, body composition and bone density improve objectively, long-term administration is recommended.

    If no obvious or objective treatment benefit is obtained after at least 12 to 18 months, then rhGH treatment may be considered to be discontinued.
    Follow-up is recommended 6 months after discontinuation of the drug.
    Some patients may consider resuming treatment due to a better quality of life during treatment.  4.
    Follow-up and monitoring Consensus recommends that after formulating a treatment plan, long-term follow-up and monitoring of patients should be incorporated into routine work to ensure the maximum benefit for patients.

    Monitoring items include clinical symptoms, weight, height, BMI, waist circumference, hip circumference, blood pressure, lipid metabolism, glucose metabolism, IGF-1, pituitary function, bone metabolism indicators, bone density, quality of life questionnaire assessment, etc.
    (Table 2).

     Table 2 rhGH treatment detection indicators and the benefits and risks of periodic GH replacement therapy.
    Benefits: GH treatment can significantly improve the clinical symptoms and reduce the occurrence of related complications in adult GHD patients.
    Specifically, GH replacement therapy can improve body composition and Exercise capacity, reduce cardiovascular risk, increase bone quality, and improve the quality of life of patients.

    Studies have confirmed that compared with untreated patients, GH treatment can increase the survival rate of postoperative pituitary tumors by 15%.

     Safety: Concerns about the safety of GH treatment are mainly related to sugar metabolism and tumor regeneration/recurrence.

     The overall effect of GH treatment on the occurrence of diabetes is not clear, and the conclusions of different studies are quite different.
    The 2019 AACE guidelines point out that if diabetes and impaired glucose tolerance occur during GH treatment, or if GH treatment is considered for patients with pre-existing diabetes, It is recommended to add and/or adjust hypoglycemic drugs and use low-dose GH treatment, or suspend/stop GH treatment, and before considering resuming GH replacement therapy for these patients, focus on optimizing hypoglycemic treatment to achieve the best blood sugar level (recommended intensity: B.
    Level of evidence: 1).

     In terms of tumor regeneration/recurrence, the 2019 version of the AACE guidelines recommends: There is no data showing that GH replacement therapy will increase the cancer risk of adult GHD patients or accelerate the risk of tumor recurrence in the hypothalamic pituitary area.
    However, for safety reasons, long-term continuous monitoring should still be carried out And standard cancer screening (Strength of Recommendation: B, Level of Evidence: 1).

    The 2011TES guidelines point out that although the development of new cancers and new-onset diabetes is a concern, the safety of growth hormone therapy (using appropriate replacement doses) appears to be beneficial in long-term surveillance studies.

    GH administration did not increase the recurrence rate of pituitary adenomas (RR, 0.
    887: 95% CI: 0.
    56 to 1.
    33).  Summary Professor Gu Weijun concluded that although the clinical features of adult GHD are not specific, it is very harmful.

    Therefore, IGF-1 screening for high-risk populations should be carried out as soon as possible to improve the diagnosis speed and diagnosis rate; standard GH replacement therapy should be initiated in time after the diagnosis is confirmed, and the IGF-1 level should be raised to the normal reference value range to improve the clinical symptoms of patients .

    Clinicians should make clinical decisions on the basis of fully understanding the benefits and risks of GH replacement therapy, and conduct long-term follow-up and monitoring of patients after formulating treatment plans to ensure the greatest benefit for patients.

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