Katarina Link

Survivors of childhood acute lymphoblastic leukaemia, with radiation‐induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment

OBJECTIVE  Adult survivors of childhood acute lymphoblastic leukaemia (ALL) often exhibit GH deficiency (GHD), due to prophylactic cranial radiotherapy (CRT). It is not known whether the observed risk for adiposity in these patients is associated with impaired insulin sensitivity and whether the insulin sensitivity is affected by GH replacement therapy.

Adult survivors of childhood acute lymphoblastic leukaemia with GH deficiency have normal self-rated quality of life but impaired neuropsychological performance 20 years after cranial irradiation.

Objective  Cranial radiotherapy (CRT) was, until recently, important for achieving long‐term survival in acute lymphoblastic leukaemia (ALL). Because survival rates have improved markedly, the long‐term complications, such as GH deficiency (GHD) and neuropsychological impairment, have become increasingly important.

GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

OBJECTIVE Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise β-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with β-cell function in participants of this trial. RESEARCH DESIGN AND METHODS GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the second injection with GAD-alum or placebo using competitive binding experiments with [125I]-labeled and unlabeled human GAD65. RESULTS At baseline, GADA affinities ranged from 1.9 × 107 to 5.0 × 1012 L/mol (median 2.8 × 1010 L/mol) and were correlated with GADA titers (r = 0.47; P = 0.0009), fasting (r = −0.37; P = 0.01) and stimulated (r = −0.40; P = 0.006) C-peptide concentrations, and HbA1c (r = 0.39; P = 0.007). No significant changes in affinity were observed from baseline to week 24. Patients with GADA affinities in the lower first quartile (<4 × 109 L/mol) had better preserved fasting C-peptide concentrations at baseline than those with higher affinities (mean 1.02 vs. 0.66 nmol/L; P = 0.004) and retained higher concentrations over 30 months of follow-up (mean 1.26 vs. 0.62 nmol/L; P = 0.01). CONCLUSIONS Intervention with GAD-alum in LADA patients had no effect on GADA affinity. Our data suggest that patients with low GADA affinity have a prolonged preservation of residual β-cell function.

Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency

OBJECTIVE In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV‐mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs.

Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy.

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 GH deficiency (GHD), with and without GH therapy. DESIGN Case-control study. METHODS We examined 44 (21 women) GHD patients (median 25 years) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls for BMD with dual-energy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (n=16) and without GH therapy (n=13) and matched controls were followed 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, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to -0.5; P<0.03) and became lower at the femoral neck (P=0.05), and at L2-L4 (P<0.03), compared with 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 IGF1 level of -0.7 s.d. and male patients reached the level of +0.05 s.d. CONCLUSIONS On average, 25 years after diagnosis, GH-deficient ALL patients experienced a significant decrease in Z-scores at femoral neck, and if Z-scores continue to decrease, there could be 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.

Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia.

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.

Risk for severe hypoglycaemia with unawareness in GH‐deficient patients during the insulin tolerance test

Objective  The insulin tolerance test (ITT) has been suggested as the gold standard for diagnosing GH deficiency (GHD). The ITT is, however, potentially hazardous. Glucose monitoring during the ITT varies between centres and there is surprisingly little information on the actual level of blood glucose nadir and the duration of hypoglycaemia in patients undergoing the ITT. The aim of the present study was to closely monitor the blood glucose level and to register the presence of symptoms and signs of hypoglycaemia during the ITT.

High risk of hypogonadism in young male cancer survivors

Cancer and its treatment in childhood and young adulthood can cause hypogonadism, leading to increased risk of long‐term morbidity and mortality. The aim of this study was to evaluate the risk of presenting with biochemical signs of hypogonadism in testicular cancer survivors (TCS) and male childhood cancer survivors (CCS) in relation to the type of treatment given.