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- Follin, Cecilia, et al.
(författare)
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Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 164:5, s. 695-703
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with growth hormone deficiency (GHD), with and without GH therapy. DESIGN: Case-control study. METHODS: 44 (21 women) GHD patients (median 25 years), treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls were examined for BMD with DXA (Dual-energy X-ray absorptiometry). Two subgroups; with (0.5 mg/day) (n=16) and without GH therapy (n=13), and matched controls, were followed for 5 and 8 years, respectively. RESULTS: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P > 0.3). After another 8 years with GHD, Z-scores at femoral neck had decreased significantly compared to baseline (0.0 to -0.5; P<0.03), and became lower at femoral neck (P=0.05), and at L2-L4 (P<0.03), compared to controls. After 5 years of GH therapy only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF-I level of -0.7 SD and in men the level was +0.05 SD. CONCLUSIONS: On average 25 years since diagnosis GH deficient ALL patients experienced a significant decrease in Z-scores at femoral neck and if Z-scores continuous to decrease there is a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.
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| 2. |
- Follin, Cecilia, et al.
(författare)
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Cardiovascular Risk, Cardiac Function, Physical Activity, and Quality of Life with and without Long-Term Growth Hormone Therapy in Adult Survivors of Childhood Acute Lymphoblastic Leukemia.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3726-3735
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Tidskriftsartikel (refereegranskat)abstract
- Context: Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease. Objective: Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m(2)). Design and Setting: We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic. Study Participants: Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated. Interventions: One ALL group (n = 16) received GH for 5 yr, and the other ALL group (n = 13) did not receive GH therapy. Main Outcome Measures: We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires. Results: In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P = 0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P = 0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P = 0.008) and a significant reduction in the prevalence of metabolic syndrome (P = 0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P > 0.3). Conclusion: GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.
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| 3. |
- Follin, Cecilia
(författare)
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Late complications of childhood acute lymphoblastic leukaemia (ALL), with special reference to hormone secretion, cardiovascular risk and bone health
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An increased prevalence of cardiovascular (CV) risk factors and cardiac abnormalities has been shown among adult GH deficient ALL survivors subjected to cranial irradiation. The ALL treatment includes many known risk factors for low bone mineral density (BMD), but little is known about pituitary insufficiencies, except for GH deficiency. In study I we evaluated the impact of 2 years GH therapy on CV risk and cardiac function and in study II, 5 years of GH therapy and 8 years without. In study III, BMD was evaluated 20 years after diagnosis, and also after another 5 years with GH therapy and 8 years without. In study IV we evaluated the prevalence of PRL and thyroid hormone insufficiency and the effect of GH therapy on these levels. We have shown that GH therapy in ALL survivors, both of short - and long term duration decreases the prevalence of metabolic syndrome and of CV risk factors. An improvement in cardiac systolic function was recorded after 2 years of GH therapy, but after 5 years, this improvement was not sustained. Twenty years after diagnosis, BMD was normal among ALL patients compared to matched controls, but during follow up BMD Z-score had decreased, irrespective of a low dose of GH therapy. ALL survivors were PRL insufficient 20 years after diagnosis, with a further decline in PRL levels after another 5 and 8 years, irrespective of GH therapy, indicating a progressive radiation effect. In contrast, normal thyroid hormone function was recorded.
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| 4. |
- Follin, Cecilia, et al.
(författare)
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Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia.
- 2014
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 17:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. The survival rate in the Scandinavian countries is now around 85 %. ALL patients treated with cranial radiotherapy (CRT) are at risk for growth hormone deficiency (GHD), but little is known about other pituitary insufficiencies, e.g. ACTH. Adult ALL patients (median age at study 25 years), treated with 24 Gy (18-30) of CRT during childhood were investigated. We performed an insulin tolerance test (ITT) to evaluate cortisol secretion. We measured basal serum ACTH and cortisol levels before and after 5 years of GH therapy. 14 out of 37 (38 %) ALL patients had a subnormal cortisol response to an ITT (257-478 nmol/L) while there was no significant difference in basal cortisol levels between 44 patients and controls (P > 0.3). Female, but not male ALL patients had significantly lower ACTH levels compared to controls (P = 0.03). After 5 years of GH therapy only male ALL patients had significantly lowered basal plasma cortisol (P = 0.02). ALL survivors, treated with a moderate dose CRT, have a central adrenal insufficiency 20 years after diagnosis. An increased awareness of the risk for an adrenal insufficiency is of importance and life-long surveillance of the entire hypothalamic-pituitary axis is recommended in these patients.
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| 5. |
- Follin, Cecilia, et al.
(författare)
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Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia.
- 2013
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 79:1, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population. OBJECTIVE: To study the long-term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients, and the prevalence of lactation failure. DESIGN: CASE-CONTROL STUDY: PATIENTS: We examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range 8-27) after ALL diagnosis and 44 matched population controls. MEASUREMENTS: PRL secretion (area under the curve; AUC) after GHRH-arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy. RESULTS: Compared to controls ALL patients had significantly lower basal and AUC PRL after GHRH-Arginine (P = 0.03, P = 0.02), and AUC PRL after TRH (P = 0.001). After 5 and 8 years, PRL levels decreased further (P = 0.01, P = 0.03), but thyroid hormones remained normal at baseline and at follow up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure. CONCLUSIONS: Long-term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk. © 2012 Blackwell Publishing Ltd.
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| 6. |
- Holmer, Helene, et al.
(författare)
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Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma
- 2011
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Ingår i: European Journal of Endocrinology. - : Bio Scientifica. - 0804-4643 .- 1479-683X. ; 165:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Context: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. Objective: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. Design and participants: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. Results: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (PZ0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels less than= -2.0 S.D. Furthermore, 75% of those with a Z-score less than= -2.0 S.D. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. Conclusions: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.
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