Reduced mortality due to malignant neoplasms in patients receiving long-term GH replacement therapy - a Swedish study based on more than 4000 patient-years

ObjectiveMost patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT.DesignCase–control study.Patients and methodsThe criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT).ResultsThe 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, <0.001) and residual tumour (3.2, <0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group.ConclusionsIn patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.

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Long-term effects of growth hormone (GH) replacement therapy on the body composition of adults with GH deficiency: A 60-month follow-up

Growth Hormone & IGF Research ◽

10.1016/s1096-6374(01)80023-x ◽

2001 ◽

Vol 11 ◽

pp. S127

Author(s):

A. Troendle ◽

E. Fontana ◽

V. Giusti ◽

F. Gomez ◽

R.C. Gaillard

Keyword(s):

Growth Hormone ◽

Body Composition ◽

Replacement Therapy ◽

Gh Deficiency ◽

The Body ◽

Long Term Effects ◽

Gh Replacement

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Comparing progression of non-functioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy

Acta Endocrinologica ◽

10.1530/eje-09-0572 ◽

2009 ◽

Vol 161 (5) ◽

pp. 663-669 ◽

Cited By ~ 32

Author(s):

D S Olsson ◽

M Buchfelder ◽

S Schlaffer ◽

B-Å Bengtsson ◽

K-E Jakobsson ◽

...

Keyword(s):

Survival Rate ◽

Replacement Therapy ◽

Pituitary Adenomas ◽

Tumour Progression ◽

Progression Free Survival ◽

Control Population ◽

Free Survival ◽

Gh Replacement ◽

Non Functioning Pituitary Adenomas

ObjectiveAn important safety issue with GH replacement therapy (GHRT) in hypopituitary patients with a history of a pituitary adenoma is the risk for tumour recurrence or enlargement.DesignCase–control study.Subjects and methodsWe studied tumour progression rate in 121 patients with hypopituitarism on the basis of non-functioning pituitary adenomas (NFPA) receiving long-term GHRT. A group of 114 NFPA patients not receiving GHRT who were matched in terms of duration of follow-up, gender, age, age at diagnosis and radiotherapy status were used as a control population. The average duration of GHRT was 10±4 years (range 2–17).ResultsIn patients with a known residual adenoma, 63% had no detectable enlargement of tumour during the study. In patients who had no visible residual tumour prior to GHRT, 90% did not suffer from recurrence. In total, the 10-year tumour progression-free survival rate in patients with NFPA receiving GHRT was 74%. In the control population not receiving GHRT, the 10-year progression-free survival rate was 70%. Radiotherapy as part of the initial tumour treatment reduced the rate of tumour progression in both GHRT and non-GHRT patients to a similar extent.ConclusionsThe rate of tumour progression was similar in this large group of GHRT patients and the control population not receiving GHRT. Our results provide further support that long-term use of GH replacement in hypopituitarism may be considered safe in patients with residual pituitary adenomas.

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The benefit of long-term growth hormone (GH) replacement therapy in hypopituitary adults with GH deficiency: Results of the German KIMS database

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2010.10.005 ◽

2011 ◽

Vol 21 (1) ◽

pp. 1-10 ◽

Cited By ~ 35

Author(s):

Christin Spielhagen ◽

Christian Schwahn ◽

Kristin Möller ◽

Nele Friedrich ◽

Thomas Kohlmann ◽

...

Keyword(s):

Growth Hormone ◽

Replacement Therapy ◽

Gh Deficiency ◽

Gh Replacement

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Safety aspects of GH replacement

Acta Endocrinologica ◽

10.1530/eje-09-0287 ◽

2009 ◽

Vol 161 (suppl_1) ◽

pp. S65-S74 ◽

Cited By ~ 26

Author(s):

Johan Svensson ◽

Bengt-Åke Bengtsson

Keyword(s):

Replacement Therapy ◽

Cardiovascular Mortality ◽

Safety Profile ◽

Mortality And Morbidity ◽

Gh Replacement ◽

Safety Aspects ◽

Long Duration

In adults, GH replacement therapy will often be maintained for decades. Owing to the long duration of GH replacement in many adults, it is essential to establish the long-term safety aspects of the treatment. In this review, studies that have investigated the safety profile of long-term GH replacement will be reviewed with an emphasis on studies based on data from the Pfizer International Metabolic Database (KIMS). These studies show that long-term GH replacement in adults is safe and that long-term GH replacement may even improve cardiovascular mortality and morbidity in GH-deficient adults.

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Discontinuing Long-Term GH Replacement Therapy—A Randomized, Placebo-Controlled Crossover Trial in Adult GH Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-2006 ◽

2012 ◽

Vol 97 (9) ◽

pp. 3185-3195 ◽

Cited By ~ 24

Author(s):

Helena Filipsson Nyström ◽

Edna J. L. Barbosa ◽

Anna G. Nilsson ◽

Lise-Lott Norrman ◽

Oskar Ragnarsson ◽

...

Keyword(s):

Replacement Therapy ◽

Crossover Trial ◽

Gh Deficiency ◽

Gh Replacement ◽

Adult Gh Deficiency

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The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up

Physiological Research ◽

10.33549/physiolres.934775 ◽

2021 ◽

pp. S61-S68

Author(s):

P. Vaňuga ◽

M. Kužma ◽

D. Stojkovičová ◽

J. Smaha ◽

P. Jackuliak ◽

...

Keyword(s):

Bone Mineral Density ◽

Growth Hormone ◽

Trabecular Bone ◽

Replacement Therapy ◽

Bone Mineral ◽

Trabecular Bone Score ◽

Mineral Density ◽

Gh Replacement

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

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