Adult Growth Hormone Deficiency: How to Incorporate ... · AACE 2019 CPG algorithm for testingadultpatients with clinical suspicion of GHD Yuen KCJ, et al. EndocrPract. 2019;25(11):1191-1232

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UCSF CMEPituitary Disorders: Advances in Diagnosis and Management

San Francisco, CASaturday January 25, 2020

Adult Growth Hormone Deficiency: How to Incorporate Guidelines into Clinical Practice

Kevin C.J. Yuen, MD, FRCP(UK), FACEProfessor of Medicine and Medical Director

Barrow Neurological Institute Pituitary CenterSt. Joseph’s Hospital and Medical Center

University of Arizona College of Medicine and Creighton School of MedicinePhoenix, AZ

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Disclosures

• Received research grants to Barrow Neurological Institute from Ionis, Crinetics, Millendo, Corcept and Novartis

• Served on Advisory Boards for Pfizer, Novo Nordisk, Ipsen, and Corcept

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What are Clinical Practice Guidelines (CPG)?

“Systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical

circumstances.” (Institute of Medicine, 1990)

• Most of the content are derived from extensive literature reviews • Reflects the state of the field at time of publication, and because changes in this

area are expected, periodic updates may be implemented• Some recommendations may not be appropriate in certain situations

Bottomline: use CPG in conjunction with best clinical judgment

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GRS Workshop in Australia April 14-17, 1997

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2007 Consensus Guidelines for the Diagnosis and Treatment

of adults with GHD:GRS, ESPE, Lawson Wilkins

Society, European Society of Endocrinology, Japan Endocrine Society and

Endocrine Society of Australia

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2009 Medical Guidelines for Clinical Practice for GH Use in

GH-Deficient Adults and Transition Patients:

AACE

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2011 Evaluation and Treatment of Adult GH

Deficiency Clinical Practice Guideline:Endocrine Society

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2016 Hormone Replacement in Hypopituitarism in Adults Clinical Practice Guideline:

Endocrine Society

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2019 Guidelines for Management of GH

Deficiency in Adults and Patients Transitioning from

Pediatric to Adult Care: AACE

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Why another CPG in 2019?• Summarize current knowledge of GH stimulation tests• Summarize the increasing evidence of beneficial effects and long-term safety of GH replacement • Address skepticism about GH use:

- high cost of therapy and its true benefits- difficulty conducting GH stimulation tests in the office- concerns about safety of long-term therapy- still a misconception of true adult GHD vs physiological decline in GH

• Highlight several sub-populations of patients described to be “at risk” for adult GHD- how to test? - when and how to treat?

• Review the literature of GH use for conception and pregnancy• Dispel the myth of using GH for sports and aging• New developments

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Outline summary of the new AACE 2019 CPG

• 58 numbered recommendations: - 12 Grade A (21%), 19 Grade B (33%), 21 Grade C (36%), and 6 Grade D (10%)

• 13 question-based sub-sections

• 357 references:- 51 (14%) EL 1 (strong)- 168 (47%) EL 2 (intermediate)- 61 (17%) EL 3 (weak)- 77 (22%) EL 4 (no clinical evidence)

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Case 1: 57 y/o male with NFPA

• TSS 3 years ago and SRS 2 years ago• Now has TSH and ACTH deficiencies (on stable doses of

Levothyroxine and Hydrocortisone)• IGF-I SDS -1.5• Healthy, except for possible childhood febrile seizures• Presents with a 10 lb (4.5 kg) weight gain over 6 months,

and persistent fatigue• Family history of osteoporosis, hyperlipidemia and cancer

Read on the internet and would like to be considered for GH

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• Why treat adult GHD?

• Who to test for adult GHD?

• Use of appropriate GH stimulation tests and cut-points

• Interactions between GH and concurrent GCs and thyroid hormone

• Safety concerns associated with long-term GH replacement

• Use of GH for anti-aging

Case 1 discussion points

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Why treat adult GHD?Body composition

• lean body mass• ¯ fat mass

Bone• total body bone mass• BMD• Effects require >18–24 months treatment

Aerobic exercise capacity• VO2 max (most studies)

Quality of life (QoL)• in some aspects of QoL (proportional to degree of baseline impairment)

Improved surrogate CV risk markers ?Decreased mortality risk

BMD, bone mineral density; QoL, quality of life.Simpson H et al. Growth Horm IGF Res 2002;12:1–33.

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Potential impact of untreated GHD vs benefits of GH replacement on CV risk

CRP, C-reactive protein; CV, cardiovascular; GH, growth hormone; GHD, growth hormone disorder; LDL, low-density lipoprotein; TG, triglyceride; TNF, tumor necrosis factor.

UNTREATED ADULT GHD

CV RISK FACTORS

CONVENTIONALLipids (total cholesterol, LDL, TG) Glucose intolerance/hyperglycemiaβ-cell function ¯Insulin resistance Metabolic syndrome

SURROGATE CV RISK MARKERSCRP Pro-inflammatory cytokines (IL-6, TNF-a) Adipokines (adiponectin , leptin /«)Pregnancy-associated plasma protein A Coagulation system (pro-coagulation )Endothelial dysfunction

INCREASED INDIVIDUAL CV RISK

REPLACEMENT

¯¯¯

¯¯¯¯¯

«

¯

IMPROVED

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Life expectancy in adults with NFPA receiving GH replacement therapy

CI, confidence interval; GH, growth hormone; GHRT, growth hormone replacement therapy; NFPA, non-functioning pituitary adenomaOlsson DS et al. Eur J Endocrinol 2017;176:67–75.

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Who to test for adult GHD?Acquired

Skull-based lesionsPituitary adenoma, craniopharyngioma, Rathke’s cleft cyst, meningioma, glioma/astrocytoma, hamartoma, chordoma, lymphoma, metastases

Brain injuryTBI, sports-related head trauma, blast injury, perinatal insults

Infiltrative/granulomatous diseaseLangerhans cell histiocytosis, autoimmune hypophysitis, sarcoidosis, TB, amyloidosis

Surgery to sella, suprasellar and parasellar region

Cranial irradiation

CNS infectionsBacterial, viral, fungal, parasital

Infarction/hemorrhageApoplexy, Sheehan’s syndrome, SAH, stroke, snake bite

Empty sella

Hydrocephalus

Idiopathic

Congenital

GeneticTranscription factor defects (PIT-1, PROP-1, LHX3/4, HESX-1, PITX-2)GHRH receptor gene defectsGH gene defectsGH receptor/post-receptor defects

Associated with brain structural defectsSingle central incisor Cleft lip/palate

Yuen KCJ, et al. Endocr Pract. 2019;25(11):1191-1232.

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Pulsatile pattern of 24-hr GH secretion in a 30 y/o vs 60 y/o healthy adult vs an adult with GHD

GH

(µg/

L)

25

20

15

10

05

0

Clock time09:00 21:00 09:00

Sleep

GH, growth hormone; GHD, growth hormone disorder.

Random points of overlap with GH levels

in healthy adults

30 yo healthy adult

60 yo healthy adult

Adult with GHD

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Serum IGF-I levels throughout life

IGF, insulin-like growth factor.Hilding A et al. J Clin Endocrinol Metab 1999; 84:2013–9

Men (n = 81)

20

40

160

640

10

320

80

10 20 10090807060504030Age (years)

IGF-

I (µ g

/L)

Women (n = 71)

Normal range

IGF-I more reliable for screening for diagnosis

in young adults

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AACE 2019 CPG algorithm for testing adult patients with clinical suspicion of GHD


Adult patient with clinical suspicion of GHD

Organic GHD0, 1 or 2 hormone deficiencies

Low IGF-I (<0 SDS)

Further testing required

History of hypothalamic-pituitary tumors, surgery, cranialirradiation, empty sella, pituitary apoplexy, traumatic brain

injury, subarachnoid hemorrhage, autoimmune hypophysitisor Rathke’s cleft cyst

Low suspicionNormal IGF-I (≥0 SDS)

Observe

High suspicionLow IGF-I (<0 SDS)

Organic GHD≥3 hormone deficiencies

Low IGF-I (<−2.0 SDS)

No further testing required

Treat


MacimorelinPeak GH ≤2.8 µg/L

Treat

GST(see Legend)

ITTPeak GH ≤ 5.0 µg/L

Treat

Legend for GSTTreat if:- peak GH ≤ 3.0 µg/L in normal-weight (BMI < 25 kg/m2) patients - peak GH ≤ 3.0 µg/L in overweight (BMI 25-30 kg/m2) patients with a high pre-test probability

- peak GH ≤ 1.0 µg/L in overweight (BMI 25-30 kg/m2) patients with a low pre-test probability

- peak GH ≤ 1.0 µg/L in obese (BMI > 30 kg/m2) patients

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Lower GH cut-point recommended for the GSTROC curve analysis to determine the GH cut-point for the GST

GH, growth hormone; GST, glucagon stimulation test; ROC, receiver operating characteristics.Gomez JM et al. Clin Endocrinol (Oxf) 2002;56:329–34.

Specificity

Sensitivity

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Previous GST studies suggesting the effects of central adiposity and glucose intolerance in decreasing peak GH levels

GH, growth hormone; GST, glucagon stimulation test.

Yuen et al. Pituitary 2013 Jun;16:220–30

Dichtel et al. J Clin Endocrinol Metab 2014 Dec;19:4712–9

Diri et al. Pituitary 2015 Dec;18:884–92

Wilson et al. Growth Horm IGF Res 2016 Feb;26:24–31

Hamrahian et al. Pituitary 2016 Jun;19:332–41

Retrospective

Prospective

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Mechanism of action of macimorelin

GH, growth hormone; GHRH, growth hormone-releasing hormone; IGF, insulin-like growth factor.Camina JP et al. Endocrine 2003 Oct;22(1):5-12.

Macimorelin acetate

Pituitary gland

GH

Ghrelin

Stomach

GHRH SRIF

Liver

IGF

Hypothalamus

+ –

+ +

–

–

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Features of the macimorelin test

Garcia JM et al. J Clin Endocrinol Metab 2013;98:2422–9.

Only 1.5 hoursNo hospitalization

4 blood draws

Non-parenteral

administration

Less time consuming

Fewer blood draws

No contra-

indications

Well-tolerated

Oral administration

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Macimorelin dosage and administration

EMA Macimorelin Aeterna Zentaris SmPC. Available at: https://www.ema.europa.eu/en/documents/product-information/macimorelin-aeterna-zentaris-epar-product-information_en.pdf, Accessed 11 June 2019; FDA Macrilen Highlights of Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000LBL.pdf Accessed 11 June 2019

Quick Guide toAdministration

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≤120 kg=1 pouch>120 kg=2 pouches

Weigh your patient


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1 pouch=120 ml water2 pouches=240 ml water

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(a small amount of undissolved particles will remain)

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Example: A patient weighing 70 kg will need 70 ml of reconstituted Macrilen solution.

Calculate volumeDissolve in water Stir gently (for 2-3 minutes)


5

Use a syringe (without a needle) with graduations in mL to measure the exact volume of solution.

Measure exact volume 6

Transfer the exact required volume of Macrilen solution into drinking glass.


7 8

Draw venous blood samples for GH determination at 30, 45, 60, and 90 minutes.

Draw blood samplesTransfer exact volume Administer solution

Have patient drink the entire volume of Macrilen solution in drinking glass within 30 seconds.

X kg = X mL solution(Patientweight)

(Macrilen solution)

30min

45min

60min

90min

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Oral macimorelin GH testDiagnostic accuracy and correlation analysis compared to the GHRH-arginine test

AUC, area under the curve; GH, growth hormone; GHRH, growth hormone-releasing hormone; ROC, receiver operator characteristics.Garcia JM et al. J Clin Endocrinol Metab 2013;98:2422–9.

0

20

40

60

80

100

0 20 40 60 80 100100-specificity (false positive rate)

Sens

itivi

ty (t

rue

posit

ive

rate

)

ROC AUC=0.923

4.5 ng/ml: 90% sens; 79% spec; 15% misclass

2.7 ng/ml: 82% sens; 92% spec; 13% misclass

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• Greater pituitary GH secretion than the ITT• Sensitivity (87%) and specificity (96%) with cut-point of 2.8 ng/ml vs ITT cutpoint of 5.1 ng/ml • Highly reproducible and good safety profile

Now approved by the FDA and EMA*

High risk Intermediate risk

Low risk Controls

Peak GH concentrations in macimorelin and ITT stratified by likelihood of having adult GHD

Validation Phase 3 study comparing with the ITT

*Not commercialized yet in the EU. ITT, insulin tolerance test.Garcia JM et al. J Clin Endocrinol Metab 2018;103:3083–99.

GH le

vel (

ng/m

l)

MAC evaluable at first try

99%

MAC not evaluable at first try, evaluable on repeat

1%

ITT evaluable at first try

82%

ITT not repeated

6%

ITT evaluable on request

9%

ITT not evaluable twice

3%

ITT (N=157) Macimorelin (N=154)

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Estimated specificities and sensitivities of macimorelin and ITT

ITT, insulin tolerance test.Garcia JR, et al. Presented at ENDO 2019, New Orleans, March 24, 2019

A cut-off point of 5.1 ng/ml instead of 2.8 ng/ml, increases sensitivity without decreasing specificity

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Accepted GH cut-points (µg/L) for GH stimulation tests used in the US by different consensus guidelines to diagnose adult GHD

GRS 2007 AACE 2009 Endocrine Society 2011 (Molitch et al.)

Endocrine Society 2016(Fleseriu et al.)

AACE 2019

ITT < 3.0 ≤ 5.0 < 3.0 to 5.0 ≤ 3.0 to 5.0 ≤ 5.0

GHRH-arginine- BMI < 25 kg/m2

- BMI 25-30 kg/m2

- BMI ≥ 30 kg/m2

< 11.0< 8.0< 4.0

≤ 11.0≤ 8.0≤ 4.0

< 11.0< 8.0< 4.0

< 11.0< 8.0< 4.0

No recommendation (not commercially

available since 2008)

Glucagon- BMI < 25 kg/m2

- BMI 25-30 kg/m2

- BMI ≥ 30 kg/m2

All patients < 3.0regardless of BMI




≤ 3.0≤ 3.0 or ≤ 1.0

≤ 1.0

Macimorelin Not commercially available

Not commercially available



≤ 2.8*

Arginine Not recommendations ≤ 0.4 No recommendations No recommendations No longer recommended to be used

*5.1 µg/L may be considered in patients with high pre-test probability

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0.4–0.5 mg/day(higher for transition

and younger patients)

0.2–0.3 mg/day

Recommendations for starting GH doses in adults with GHD

• Use lower GH doses (0.1–0.2 mg/day) in patients with DM, obesity, and previous GDM

• Target IGF-I SDS between -2 and +2

Age < 30 years Age 30 - 60 years

AACE 2009 and 2019

0.1–0.2 mg/day

Age > 60 years

GRS 2007: - young men and women, start at 0.2-0.3 mg/day- older individuals, start at 0.1 mg/day- target IGF-I SDS < +2

Endo Society 2011: - age 30 – 60 years, start at 0.2-0.3 mg/day- target IGF-I SDS between 0 and +2

Endo Society 2016: - age < 60 years, start at 0.2-0.4 mg/day- age > 60 years, start at 0.1-0.2 mg/day - target IGF-I SDS to the mid-range

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Interactions between GH therapy and concurrent GCs and thyroid hormone

GRS 2007, AACE 2009, Endo Society 2011, Endo Society 2016 and AACE 2019

GH therapy may unmask clinical central hypothyroidism and hypoadrenalism

levothyroxine and hydrocortisone doses

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Safety concerns associated with long-term GH replacement

• DM and glucose intolerance – use low GH doses • History of active malignancy and proliferative diabetic retinopathy -

contraindicated• Strong family history of cancer – careful consideration • Previous history of cancer – careful consideration, discuss with oncologist,

initiate > 5 years after cancer remission, and use low GH doses• History of CVD – GH replacement exerts positive effects on some CV risk

markers • Recurrence of pituitary adenoma – no increase in relative risk • Cancer risk – no increased risk (possibly even reduced risk)• Mortality risk – no increased risk (possibly even reduced risk)


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Use of GH for anti-aging

• No studies have assessed long-term (> 6 months) efficacy or safety of GH for anti-aging purposes

• Meta-analysis of 31 studies in healthy elderly subjects reported small changes in body composition but increased AEs (Liu et al. Ann Intern Med 2007;146:104-115), while animal studies have shown reduced life spans and premature onset of age-related cognitive changes (Bartke A. World J MensHealth. 2019;37:19-30)

Use of GH for marketing, distributing, or administration for any reason other than the well-defined approved uses of the drug is illegal and strongly discouraged


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Case 2: 21 y/o male with panhypopituitarism due to suprasellar germinoma

• S/p chemotherapy and cranial DXT• On DDAVP, Hydrocortisone, and Levothyroxine• IGF-I SDS -0.1• Underwent Macimorelin test: serum GH levels

0.06, 3.22, 3.27, 2.84 and 1.29 µg/L • Amenable to resume GH therapy• Childhood GH dose was 2.0 mg/day

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• When to retest and which test to use?

• To treat or not to treat? If treat, what dose to resume GH therapy?

• Safety concerns regarding long-term GH replacement

• Fertility and pregnancy

• Use of GH for sports

• Long-term adherence

Case 2 discussion points

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AACE 2019 CPG algorithm for testing transition patients with clinical suspicion of GHD

Adult patient with clinical suspicion of GHD

Organic GHD0, 1 or 2 hormone deficiencies

Low IGF-I (<0 SDS)


Idiopathic isolated childhood GHD or suspected hypothalamic GHD

Low suspicionNormal IGF-I (≥0 SDS)

Observe

High suspicionLow IGF-I (<0 SDS)

Congenital defectsGenetic defectsOrganic disease

≥ 3 hormone deficienciesLow IGF-I (<-2.0 SDS)

No further testing required

Treat


MacimorelinPeak GH ≤2.8

µg/LTreat

GST(see

Legend)

ITTPeak GH ≤ 5.0

µg/LTreat

Legend for GSTTreat if:- peak GH ≤ 3.0 µg/L in normal-weight (BMI < 25 kg/m2) patients - peak GH ≤ 3.0 µg/L in overweight (BMI 25-30 kg/m2) patients

with a high pre-test probability - peak GH ≤ 1.0 µg/L in overweight (BMI 25-30 kg/m2) patients

with a low pre-test probability - peak GH ≤ 1.0 µg/L in obese (BMI > 30 kg/m2) patients


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How to resume GH therapy in transition patients?

GRS 2007: intermediate doses between the pediatric doses required during the growth years and the adult dose

Endo Society 2011: younger pts (< 30 yrs) may benefit from higher initial doses (0.4-0.5 mg/day); for patients transitioning from pediatric doses, even higher doses may be appropriate

Endo Society 2016: no recommendation

AACE 2009 and AACE 2019: restart at ~50% of the pediatric dose

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Safety concerns regarding long-term GH replacement

• Risk of secondary neoplasms in childhood cancer survivors- increased risk more likely related to previous exposure to cranial irradiation

2018 Endo Society CPG (Sklar CA, et al. JCEM 2018) and 2019 AACE CPG recommend carefully considering GH to childhood cancer survivors with confirmed GHD

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• Not approved by the FDA

• Several studies support use of GH while seeking fertility, and continuing GH during pregnancy does not appear to impact mother or fetus- Giampietro A, et al. Fertil Steril. 2009- Vila G, et al. Fertil Steril. 2015- Bassiouny YA, et al. Fertil Steril. 2016- Correa FA, et al. J Endocr Soc. 2017

More data still needed on safety of GH use in women with GHD to assist conception and during pregnancy before it can be routinely recommended

AACE 2019 CPG recommendations on GH use during conception and pregnancy


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Use of GH for sports

• GH improves body composition but may not improve strength, worsen exercise capacity and increase AEs (Hermansen K, et al. Growth Horm IGF Res. 2017;34:38-44)

• Detecting GH abuse is challenging- short t1/2 of exogenous GH- urine sampling of GH not viable- what biomarkers to test for?

Use of GH for marketing, distributing, or administration for any reason other than the well-defined approved uses of the drug is illegal and strongly discouraged


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Improving long-term adherence

• See some patients more frequently (“individualized care”)

• Provide electronic resources (cater to “the millennials”)

• Have an open and non-judgmental conversation with patient (ask “open-ended” questions about adherence barriers)

• Review the risks of untreated GHD with the patient

• Review the benefits and safety of long-term GH replacement therapy

• RN to spend time reviewing the patient’s injection technique

• Medication reminder systems and longer duration of GH prescriptions

• Regular educational and motivational supportBozzola M, et al. Horm Res Paediatr. 2014; 81(5):331-335.

Mohseni S, et al. J Pedistr Endocrinol Metab. 2018;3:13-20.

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Problems with daily GH injections

• Inconvenient, painful and distressing

• Non-adherence increases over time

• Life circumstances can interfere with adherence

By decreasing injection frequency, long-acting GH preparations may improve adherence and thereby potentially improve clinical outcomes

Why consider LAGH preparations?

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Overview of LAGH preparations currently under development

Yuen KC, et al. Expert Rev Endocrinol Metab. 2019 Nov 13:1-18.

Technology used Product (Company) Modification to the GH molecule Frequency of administration

Current status

Depot LB03002 (LG Life Sciences, Ltd) Microparticles containing GH incorporated into sodium hyaluronate and dispersed in an oil base of medium-chain TG

7 days Approved and marketed in S Korea for childhood GHD. Approved but not marketed in Europe.

Depot CP016 (Critical Pharmaceuticals)

Supercritical carbon dioxide, formed when carbon dioxide exceeds its thermodynamic critical point, used to create the depot

14 days (planned) Pre-clinical studies

PEGylated BBT-031 (Bolder Biotechnology) Site-specific PEGylated GH analog 7 days (planned) Pre-clinical studies

PEGylated Jintrolong (GeneSciencePharmaceuticals, Ltd)

40-kDa PEG linked to GH 7 days Approved in China for childhood GHD

Prodrug TransCon ACP-001 (Ascendis) GH transiently linked to carrier molecule via a self-cleaving linker, and releases GH unmodified

7 days Phase 3 in children completed and presented, phase 3 in adults in planning stages

GH molecule bound to albumin

Somapacitan NNC0195-0092 (Novo Nordisk)

Single point mutation in GH, with non-covalent albumin binding moiety attached

7 days Phase 3 in children, phase 3 and extension study in adults

GH molecule bound to Fab Ab

AG-B1512 (AhngookPharmaceutical Co., Ltd.)

Recombinant human GH genetically fused to a polypeptide linker and an anti-HSA Fab antibody

14-28 days (planned) Pre-clinical studies

GH fusion protein ProFuse GH (Asterion) GH-binding protein 1 month (planned) Pre-clinical studiesGH fusion protein GX-H9 (Genexine, Inc. and

Handok, Inc.)Hybridization of non-cytolytic immunoglobulin Fc portion of IgD and IgG4

7-14 days Phase 2 in children and adults, pending phase 3 trial in adults

GH fusion protein LAPSrhGH/HM10560A (Hanmi Pharmaceutical Co., Ltd.)

Homodimeric aglycosylated IgG4 Fc fragment 7-14 days Phase 2 in children and adults

GH fusion protein MOD-4023 (Pfizer, Inc.) Carboxyl-terminal peptide of hCG β-subunit 7 days Phase 3 in children, phase 3 in adults failed primary end-point and further studies planned for pen devices

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Questions regarding LAGH preparations

• Where is the place of LAGH in relation to naïve GH-deficient patients and patients already on daily GH?

• Are all the LAGH preparations the same?• Will the effects of LAGH preparations be durable with long-term use? • Any prolonged metabolic consequences and side effects?• Can LAGH preparations with large molecular sizes penetrate all tissues equally?• When to measure IGF-I levels and is it the same for all LAGH preparations?• Are LAGH cost-effective?• Will LAGH receive regulatory approval if convenience not accepted as an added

value?• Will LAGH truly improve adherence and outcomes?• Will the safety profile of LAGH be different to daily GH?

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Summary of changes of AACE 2019 CPG compared to previous CPG

• Recently described non-tumoral causes of adult GHD

• More emphasis on clinical suspicion when ordering and interpreting GH stimulation tests

• More emphasis on re-testing, how to re-test, and recommendations on re-initiation and benefits of continuing GH therapy in transition patients

• Recommendations of BMI-specific cut-points for the GST and deleted the prior recommendation of using arginine test for assessing adult GHD

• Recommendation regarding the place of macimorelin when testing for adult GHD, and interpretation of its results

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Summary of changes of AACE 2019 CPG compared to previous CPG

• Emphasizing the importance of standardized GH and IGF-I assays for diagnosis and guiding GH dosing

• More detailed recommendations on initiation and monitoring of GH replacement

• Insufficient data to recommend routine GH use for conception and pregnancy

• Increasing data supporting the safety of long-term GH use

• Strong emphasis of NOT using GH for sports and aging

• Discussion of current status of LAGH preparations

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Outstanding knowledge and treatment gaps

• Are the currently available GH stimulation tests reliable and accurate when used in different types of GHD?

• Is there a better biomarker than IGF-I?• What is the optimal IGF-I target to titrate GH doses to?• How long to treat with GH? • Safety data of GH > 20 yr follow-up• Safety data of GH for fertility (male and female) and pregnancy• Safety data of GH in the elderly (> 80 yrs)• Optimal interval between completion of cancer treatment and initiation of

GH therapy• Reliable diagnostic methodology in assessing GH misuse for unapproved

conditions

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THANK YOU FOR YOUR ATTENTION!

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Documents

Adult Growth Hormone Deficiency: How to Incorporate ... · AACE 2019 CPG algorithm for testingadultpatients with clinical suspicion of GHD Yuen KCJ, et al. EndocrPract. 2019;25(11):1191-1232