Social, educational and vocational outcomes in patients with childhood-onset and young-adult-onset growth hormone deficiency.

OBJECTIVE: Hypopituitarism diagnosed in childhood, adolescence and young adulthood has the potential to affect growth and somatic development. Less is known about the impact of such a diagnosis on other aspects of development. DESIGN: An analysis of the KIMS database (Pfizer International Metabolic Database) was performed to explore social, educational and vocational outcomes of adult patients diagnosed in childhood, adolescence and young adulthood compared with adult-onset controls. PATIENTS: A total of 2952 adult patients diagnosed with hypothalamic pituitary conditions before the age of 25 were divided into two groups: childhood-onset [<16 years (CO)] (n = 1782) and young-adult-onset [16 to <25 years (YAO)] (n = 1170). A total of 1617 adult patients diagnosed with a nonfunctioning pituitary adenoma at the age of 25 or older formed the adult-onset control group (AO). MEASUREMENTS: KIMS Patient Life Situation Form which provided information on social, educational and vocational outcomes. RESULTS: Compared with the AO control group, CO and YAO patients were between 4·5 and 8·0 times more likely to live with their parents in adulthood; CO and YAO patients were also less likely to live in partnership and to have children. The impact on educational and vocational outcomes was less marked than on social outcomes with no significant differences compared with the AO control group. Educational and vocational outcomes showed the lowest level in male and female CO and YAO patients who had been previously diagnosed with a brain tumour. CONCLUSIONS: Social outcomes were more affected than educational and vocational outcomes. Although CO patients are more adversely affected, YAO patients were also failing to achieve social milestones. This has consequences for the delivery of endocrine care in both paediatric and adult services.

Pregnancy outcomes in women with growth hormone deficiency.

OBJECTIVE: To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. DESIGN: We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. SETTING: Outpatient clinics. PATIENT(S): A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. INTERVENTION(S): Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. MAIN OUTCOME MEASURE(S): Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. RESULT(S): Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. CONCLUSION(S): These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes.

Pregnancy in acromegaly patients treated with pegvisomant.

To summarize all available data on pregnancy outcome of acromegaly patients exposed to the growth hormone receptor antagonist pegvisomant (PEGV) during pregnancy as present in the Pfizer's Global Safety Database. Pfizer's Global Safety Database contains adverse event data obtained from the following sources: spontaneous reports, health authorities, Pfizer-sponsored post-marketing surveillance program (ACROSTUDY), customer engagement programs, and clinical studies, reported regardless of outcome. The safety database was searched up to 10th March 2014. From the 35 pregnancy cases, 27 involved maternal [mean age (range) 33.3 years (23-41) and 8 paternal (33.7 years (32-38)] PEGV exposure. Two female patients were reported with two pregnancy cases each. Fetal outcome was normal in 14 (4 paternal) of the 18 reported as live birth, while 4 cases (1 paternal) did not specify the birth outcome. At conception, PEGV mean dose (range) was 15.3 mg/d (4.3-30). In 3 cases of maternal exposure of the 18 cases reporting live birth, PEGV was continued throughout the pregnancy in a dose of 12.1 mg/d (10-15). In 5 cases (all maternal) an elective termination of the pregnancy was performed with no reported fetal abnormalities, 2 cases (maternal) reported a non-PEGV-related spontaneous abortion and in 1 maternal case an ectopic pregnancy occurred. In 9 cases (3 paternal), the fetal outcome was not reported. Three women reported gestational diabetes; one woman continued PEGV treatment during pregnancy. Although the number of reported pregnancies with exposure to PEGV is very small, the presented data reflect the largest series of data available to date and do not suggest adverse consequences of PEGV on pregnancy outcome. Nevertheless, it should be stressed that PEGV should not be used during pregnancy unless absolutely necessary.

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients.

OBJECTIVE: Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTH-insufficient patients experience a dose-dependent deterioration in QoL. DESIGN, PATIENTS AND METHODS: This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a mean±s.d. hydrocortisone equivalent (HCeq) dose of 22.3±8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. RESULTS: At baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq≤10 mg had the best and patients receiving ≥25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. CONCLUSION: Adult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.

Overall and cause-specific mortality in GH-deficient adults on GH replacement.

OBJECTIVE: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. DESIGN: In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available. METHODS: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. RESULTS: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). CONCLUSIONS: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.