Emotional and psychosexual well-being is influenced by ethnicity and birthplace in women and individuals with polycystic ovary syndrome in the UK and India.

OBJECTIVE: To assess the association of ethnicity and birthplace on emotional and psychosexual well-being in women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Community recruitment via social media campaigns. POPULATION: Women with PCOS completing an online questionnaire in September-October 2020 (UK) and May-June 2021 (India). METHODS: The survey has five components, with a baseline information and sociodemographic section followed by four validated questionnaires: Hospital Anxiety and Depression Scale (HADS); Body Image Concern Inventory (BICI); Beliefs About Obese Persons Scale (BAOP); and Female Sexual Function Index (FSFI). MAIN OUTCOME MEASURES: We used adjusted linear and logistic regression models, adjusting for age, education, marital status and parity, to evaluate the impact of ethnicity and birthplace on questionnaire scores and outcomes (anxiety and/or depression, HADS ≥ 11; body dysmorphic disorder (BDD), BICI ≥ 72). RESULTS: A total of 1008 women with PCOS were included. Women of non-white ethnicity (613/1008) reported higher rates of depression (OR 1.96, 95% CI 1.41-2.73) and lower BDD (OR 0.57, 95% CI 0.41-0.79) than white women (395/1008). Women born in India (453/1008) had higher anxiety (OR 1.57, 95% CI 1.00-2.46) and depression (OR 2.20, 95% CI 1.52-3.18) but lower BDD rates (OR 0.42, 95% CI 0.29-0.61) than women born in the UK (437/1008). All sexual domains, excluding desire, scored lower for non-white women and women born in India. CONCLUSIONS: Non-white women and women born in India reported higher emotional and sexual dysfunction, whereas white women and women born in the UK reported higher body image concerns and weight stigma. Ethnicity and birthplace need to be considered for tailored, multidisciplinary care.

Long-term and late treatment consequences: endocrine and metabolic effects.

PURPOSE OF REVIEW: Cancer therapies often result in the 'late effect of cancer treatment' whereby secondary health complications emerge years after radiotherapy and chemotherapy. This review focuses on endocrine and metabolic consequences in adult cancer survivors as late treatment effects. RECENT FINDINGS: Endocrine and metabolic disorders are among the most common late effects. Endocrine disorders include hypopituitarism, which leads to growth hormone deficiency, hypogonadism, adrenal insufficiency and hypothyroidism and related clinical manifestations. Hypogonadism in particular is associated with a wide range of health complications requiring input from the like of endocrine and fertility specialists. Immune checkpoint inhibitors are novel anticancer agents, some of which are uniquely associated with hypophysitis which requires early recognition and management, including steroid replacement. Metabolic syndrome, a significant risk for cardiovascular disease, is highly prevalent. Although the effects of cranial irradiation on the hypothalamic-pituitary system are more apparent, the relationship between chemotherapy and endocrine/metabolic disorders remains to be elucidated. There exist published guidelines for monitoring endocrine and cardiometabolic risk in cancer survivors, but the extent of monitoring appears insufficient. SUMMARY: Regular monitoring and early management of endocrine/metabolic disorders is required to prevent the elevated rates of health complications after cancer treatment, and thereby improve cancer survivorship.

Transition in endocrinology: the challenge of maintaining continuity.

OBJECTIVE: Transition from child to adult status is a crucial stage in young people's lives. It is important that young people continue to receive appropriate endocrine care throughout and following transfer from paediatric to adult services. This study examined indicators of patient loss to follow-up at initial transfer from paediatric care to identify implications for transitional care practice and research. METHODS: A retrospective analysis of patient data following transfer from paediatric services to a young person's transition clinic was conducted. Attendance data from 103 patients transferred to the Young Person's Clinic were analysed to determine the factors affecting nonattendance 1-year post-transfer. RESULTS: We found that overall one quarter of patients did not attend the young person's clinic in the first year after transfer. Those with poor attendance prior to transfer were likely to be poor attenders post-transfer. Further, those without an appointment scheduled in the first 6 months of their final paediatric transfer appointment were less likely to attend in the first year. CONCLUSIONS: Young people are at risk of losing contact during the transfer from paediatric to the young person's clinic. Measures that promote continuity of contact could reduce the risk of long-term disengagement with care. Further development and research is required to identify the best ways to help young people with endocrine conditions in the transition from child to adult status.

Effect of aromatizable and unaromatizable androgen replacement in hypogonadal men on GH responsiveness.

OBJECTIVES: Although studies have clearly demonstrated that oestrogen replacement affects GH responsiveness by causing relative GH resistance, the effect of androgen replacement is unknown. Circumstantial evidence only suggests that androgen replacement may increase GH sensitivity and/or responsiveness. To examine the impact of androgens on GH responsiveness, hypogonadal men underwent the IGF-1 generation test in the unreplaced state, replaced with testosterone (T) and also replaced with dihydrotestosterone (DHT), its nonaromatizable metabolite. DESIGN AND PATIENTS: Twelve hypogonadal men with a normal GH axis were recruited. Each subject in random order had 4 weeks off T (NoRx), 4 weeks on T gel (TG) and 4 weeks on DHT gel (DHTG) applied daily, with 1 week washout between each preparation. An IGF-1 generation test using a subcutaneous injection of 7 mg of GH was performed at the end of each of these 4-week phases. MEASUREMENTS: Serum GHBP, total and free IGF-1, IGFBP-3 and acid-labile subunit (ALS) levels were measured at baseline and 24 h (peak) after GH administration. RESULTS: Despite a decrease in GHBP during the TG and DHTG phases, there were no observed differences in baseline, peak or increment (peak - baseline) total or free IGF-1 between the NoRx, TG or DHTG phases. CONCLUSIONS: There is no evidence of fluctuation in GH responsiveness in hypogonadal men, untreated or replaced with T or DHT alone. This implies that the increased level of oestradiol as a consequence of T replacement in hypogonadal men does not impact significantly on GH responsiveness, nor is there evidence of an androgen effect with elevated DHT levels as a consequence of either T or DHT replacement.

Two-year pilot study of newborn screening for congenital adrenal hyperplasia in New South Wales compared with nationwide case surveillance in Australia.

AIM: To assess the benefits and practicalities of setting up a newborn screening (NBS) program in Australia for congenital adrenal hyperplasia (CAH) through a 2 year pilot screening in ACT/NSW and comparing with case surveillance in other states. METHODS: The pilot newborn screening occurred between 1/10/95 and 30/9/97 in NSW/ACT. Concurrently, case reporting for all new CAH cases occurred through the Australian Paediatric Surveillance Unit (APSU) across Australia. Details of clinical presentation, re-sampling and laboratory performance were assessed. RESULTS: 185,854 newborn infants were screened for CAH in NSW/ACT. Concurrently, 30 cases of CAH were reported to APSU, twelve of which were from NSW/ACT. CAH incidence was 1 in 15 488 (screened population) vs 1 in 18,034 births (unscreened) (difference not significant). Median age of initial notification was day 8 with confirmed diagnosis at 13(5-23) days in the screened population vs 16(7-37) days in the unscreened population (not significant). Of the 5 clinically unsuspected males in the screened population, one had mild salt-wasting by the time of notification, compared with salt-wasting crisis in all 6 males from the unscreened population. 96% of results were reported by day 10. Resampling was requested in 637 (0.4%) and median re-sampling delay was 11(0-28) days with higher resample rates in males (p < 0.0001). The within-laboratory cost per case of clinically unsuspected cases was A$42 717. CONCLUSION: There seems good justification for NBS for CAH based on clear prevention of salt-wasting crises and their potential long-term consequences. Also, prospects exist for enhancing screening performance.

The impact of short-term fasting on the dynamics of 24-hour growth hormone (GH) secretion in patients with severe radiation-induced GH deficiency.

CONTEXT: In patients with severe radiation-induced GH deficiency, we previously demonstrated that pulsatile GH secretion and diurnal rhythm are maintained in the fed state, albeit with great attenuation of the pulse amplitude. However, it remained unclear whether stressing the hypothalamic-pituitary axis could unmask neurosecretory dysregulation that is not seen under basal conditions. In addition, the impact of fasting on GH pulsatility and diurnal variation in GH-deficient patients has not been studied in detail before. STUDY SUBJECTS AND DESIGN: Twenty-four-hour GH profiles at 20-min intervals were undertaken in the fed state and in the last 24 h of a 33-h fast in eight young adult cancer survivors (two women) with severe GH deficiency after cranial irradiation for nonpituitary brain tumors in childhood and 14 matched normal controls (three women). A sensitive chemiluminescence GH assay was used with cluster analysis. RESULTS: Fasting induced a significant (P < 0.05) rise in all amplitude-dependent measures (absolute GH peak and nadir, profile mean GH, and mean pulse amplitude and area) in both groups. Pulse frequency was nonsignificantly increased (by 10%) in normals but significantly increased (by 20%) in the patients. The average increase in the individual fasting profile mean GH concentration was 3.7-fold (range 1.5-8.3) in normals, compared with 2.7-fold (range 1-4.7) in the patients (P > 0.05). Fasting amplified amplitude-related differences between patients and controls, and thus, unlike in the fed state, the day (0900-2040 h) mean GH completely demarcated patients from normals. An absolute GH peak level of 2 and 4 microg/liter and a profile mean GH level of 0.25 and 0.65 microg/liter completely separated patients from normals in the fed and the fasting states, respectively. Overall, fasting seems to induce a feminized pattern of GH secretion with relatively higher interpeak levels, preserved but diminished diurnal variation, and increased secretory disorderliness (increased approximate entropy scores). CONCLUSION: The overall pulsatile pattern of GH secretion during fasting in patients with radiation-induced GH deficiency and the relative augmentation in GH release are similar to that seen in normals emphasizing that GH neuroregulation is preserved in these patients even when the hypothalamic-pituitary axis is under physiological stress.

GH responsiveness varies during the menstrual cycle.

OBJECTIVE: The GH-IGF-1 axis is affected by oestrogen. Both endogenous and exogenous oestrogen facilitates the central drive of pulsatile GH secretion. However, the effect on IGF-1 levels is more subtle, and a reduction in GH sensitivity has been proposed. The IGF generation test has confirmed reduced GH sensitivity with high doses of exogenous oestrogen. It is not known, however, whether fluctuant levels of endogenous oestrogen modify GH sensitivity. To investigate this further, women were challenged with the IGF-1 generation test at different stages of the menstrual cycle. METHODS: Nine women (age 38(6) years (mean (s.d.)) with regular menstrual cycles were recruited. An IGF-1 generation test, s.c. injection of 7 mg GH, was performed in the early-follicular (EF), periovulatory (PO) and midluteal (ML) phases. IGF-1, insulin-like growth factor binding protein (IGFBP)-3 and acid-labile subunit (ALS) levels were measured at baseline and 24 h after GH administration. RESULTS: Oestradiol levels were lower in the EF than PO or ML phases (32.6(7.8) vs 69.6(16.2) vs 66.6(23.6) pg/ml respectively (repeated measures ANOVA, P < 0.001)). Baseline IGF-1 was lower, but increment IGF-1 (peak minus baseline) was higher in the EF than PO or ML phases (baseline: 291.8(56.6) vs 335.0(55.2) vs 346.6(78.2) ng/ml (P = 0.008); increment IGF-1: 234.6(59.2) vs 194.7(37.8) vs 185.2(37.3) ng/ml (P = 0.008)). CONCLUSIONS: Increased endogenous oestrogen levels are associated with only a modestly elevated baseline IGF-1 from midcycle onward despite a previously reported twofold increase in GH secretion. In parallel with this apparent GH insensitivity, increased endogenous oestrogen levels are associated with reduction in GH sensitivity evidenced by reduction in increment IGF-1. This may have clinical implications for women with isolated GH deficiency with regular menstrual cycles on a fixed dose of GH. This possibility requires further study.

Insulin-like growth factor-I response to a single bolus of growth hormone is increased in obesity.

Reduced GH levels are found in obesity; despite which IGF-I levels are reported as low normal or normal. Previously peripheral responsiveness to GH has been investigated and reported to be increased in obese men and premenopausal women; however, the use of weight-based GH doses in these studies made data interpretation difficult. GH binding protein (GHBP) measurement constitutes an indirect estimate of GH receptor number. GHBP has been reported to be elevated in obesity; however, results from a recent study implied that this was only in men and premenopausal but not postmenopausal women. Therefore, we pursued this question further by challenging a cohort of healthy normal-weight and obese subjects with a non-weight-based dose of GH and examined the relationship of GHBP with the IGF-I response in the context of their body composition. Ninety-eight (40 male) healthy subjects with a wide range of ages and body mass index (BMI) were studied. Ninety-one (34 male) of these subjects were divided into groups of similar age: men and women with a BMI less than 30 [normal-weight men (NM), BMI 26 (22-29) kg/m(2) (n = 19) and women (NW), BMI 24 (19-29) kg/m(2) (n = 23) and with a BMI > 30 (obese men (OM), 41 (30-72) kg/m(2) (n = 15) and women (OW), 43 (30-68) kg/m(2) (n = 34)]. Fat mass and percentage fat were measured by a bioelectrical impedance analyzer. An IGF-I generation test, which involved a sc injection of 21 IU (7 mg) GH, was performed. At baseline serum samples were assayed for GHBP; serum IGF-I and IGFBP3 levels were measured both at baseline and 24 h after GH administration. There was a higher increment IGF-I in obese men and women, compared with the equivalent normal-weight subjects [NM vs. OM: 245 (33-342) vs. 291 (192-427) ng/ml (P < 0.05); NW vs. OW: 220 (103-435) vs. 315 (144-450) ng/ml (P < 0.0005)]. Increment IGF-I was negatively correlated with baseline IGF-I (F = 12.1) and positively correlated with GHBP (F = 18.2) (R(2) = 0.29). GHBP levels were significantly higher in OM and OW (pre- and postmenopausal) than in the equivalent normal-weight groups [NM vs. OM: 2175 (995-4190) vs. 3030 (1540-5470) pmol/liter (P < 0.05); NW vs. OW: 2131 (1010-5040) vs. 3585 (1540-5740) pmol/liter (P < 0.0005)]. GHBP levels correlated highly with BMI, percentage fat, and fat mass (R > 0.6, P < 0.0001). Baseline IGF-I was not affected by body composition. In conclusion, in obese compared with normal-weight healthy subjects, there is a larger increment IGF-I to a single bolus of GH in men, and irrespective of menopausal status, women. Increment IGF-I is associated positively with GHBP level, which in turn is associated with markers of increasing obesity in men and women. GH responsiveness is increased in obesity.

Reassessment of growth hormone status is required at final height in children treated with growth hormone replacement after radiation therapy.

The most appropriate way to manage GH replacement in the transition period to adulthood in children treated with GH for GH deficiency (GHD) is controversial. The Growth Hormone Research Society suggests that the retesting of GH status at final height (FH) is unnecessary in the presence of severe organic GHD, and cranial irradiation falls into this etiological category. This recommendation has never been validated. To investigate whether patients diagnosed in childhood as GHD secondary to irradiation require retesting after FH, GH status has been reassessed in a large cohort of irradiated children treated with GH during childhood. Seventy-three children underwent biochemical assessment of GH status after irradiation and again at FH after GH therapy had been discontinued; 66 and 67 of the 73 patients underwent two provocative tests at the two time points, respectively. The characteristics of the cohort include a median age at irradiation of 5 yr (range, 1-11 yr), a median biological effective dose (BED) of irradiation to the hypothalamic pituitary axis of 54 Gy (range, 23-82 Gy), and a median time of GH status reassessment after FH of 0.4 yr (range, 0-8.4 yr). During childhood, patients with all degrees of GHD (peak GH responses to provocative test < 6.7 ng/ml) are treated, whereas in adulthood, only patients with severe GHD (peak GH responses to provocative test < 3 ng/ml) are considered for GH replacement. GH status has been grouped as follows: group 1, peak GH less than 3 ng/ml to both tests (severe GHD); group 2, one test with a peak GH less than 3 ng/ml and the other test with a peak of 3 ng/ml or greater; group 3, peak GH of 3-6.7 ng/ml to both tests; group 4, one test with a peak GH of 3-6.7 ng/ml and the other test with a peak of more than 6.7 ng/ml; and group 5, peak GH more than 6.7 ng/ml to both tests (normal GH status). In childhood, the number of patients in groups 1, 2, 3, and 4 were 33, 22, 17, and one, respectively. At retesting, severe GHD was diagnosed in 21 (64%) of 33 patients who were diagnosed in childhood with severe GHD (group 1) and 17 (44%) of 39 patients who were diagnosed in childhood with moderate GHD (groups 2 and 3). In total, 35 (48%) of 73 patients in the whole cohort and 12 (36%) of 33 patients with severe GHD in childhood did not fulfill the severe GHD biochemical criteria for GH replacement in adulthood. Using multiple linear regression, GH status at retesting is predicted by BED, age at irradiation, and use of chemotherapy. In conclusion, the diagnosis of severe GHD in childhood secondary to irradiation should not be taken as irrefutable evidence of permanent severe organic GHD, and our recommendation is that retesting of GH status at FH should be mandatory.

Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement.

Final height (FH) outcome is important in survivors of childhood brain tumors. GH replacement is indicated in those found to be GH deficient (GHD). More recently, GnRH analogs (GnRHa) have been introduced to delay early or rapidly progressing puberty to allow more time for linear growth. Studies to FH are important to determine the effectiveness of growth-promoting strategies. Our aim was to assess whether evolving endocrine strategies have improved FH outcome and to determine whether GnRHa therapy has contributed auxologically. FH data were examined in 58 children (31 males and 27 females) with radiation-induced GHD who had been treated with GH. All had received a combination of cranial (CI; n = 17) or craniospinal (CSI; n = 41) irradiation with or without chemotherapy for a brain tumor. Eleven patients received GnRHa therapy. Throughout the 25 yr of the study patients came closer to achieving target height (i.e. a reduction in height loss), both those receiving CI (r = 0.5; P = 0.03) and those receiving CSI (r = 0.6; P < 0.001). The patients receiving GH therapy before 1988 compared with from 1988 onward had a similar age at irradiation [mean (+/-SD), 5.8 (3.0) vs. 6.2 (2.9) yr; P = 0.6], but experienced a more prolonged time interval from completing irradiation to starting GH [5.4 (2.4) vs. 3.3 (1.6) yr; P < 0.001]. Forward stepwise regression analysis revealed that height loss is affected by age at irradiation (P < 0.001), previous spinal irradiation (P = 0.02), chemotherapy (P < 0.001), and exposure to GnRHa therapy (P < 0.001). In the 11 patients treated with GnRHa therapy FH SD scores were improved compared with FH predictions calculated from a model derived from the patients not treated with GnRHa [-0.8 (1.6) vs. -2.4 (0.8) SD score; P < 0.001]. We have demonstrated an overall improvement in FH in children treated with GH for GHD after therapy for brain tumors over the last 25 yr. In the subset of children in whom the growth prognosis was adversely affected by early puberty, the combination of GnRHa and GH improved their prospects of achieving target height. The improved auxological outcome may reflect 1) the use of more standardized GH schedules and better dosing regimens, 2) a reduction in the time interval between finishing radiotherapy and receiving GH replacement, and 3) the use of GnRHa in addition to GH replacement in carefully selected patients.

Ten years on: Safety of short synacthen tests in assessing adrenocorticotropin deficiency in clinical practice.

Since 1988, when a retrospective study of patients attending this unit was published, we have advocated the use of the short synacthen test (SST) as the primary screening investigation to detect ACTH deficiency. However, others have published comparisons of SST and insulin tolerance tests that suggest a significant false negative rate with SST, leading to concern that some patients who pass the SST are in danger from the clinical consequences of ACTH deficiency. To address this, we audited biochemical results and clinical outcome in 63 patients who did not have ACTH deficiency detected (i.e. who passed the test) by SST after pituitary surgery. Twelve of the 63 patients who passed a SST after pituitary surgery became ACTH-deficient later as diagnosed by SST: 4 within the first year, 2 of whom had received postoperative radiotherapy (3 had symptoms of tiredness and 1 was admitted to the hospital with a viral infection); 8 in yr 3-5, 7 of whom had received postoperative radiotherapy (all had either no symptoms or symptoms of tiredness alone). Thus, the predictive value of the SST in excluding ACTH deficiency is approximately 97% (2 of 63 patients who initially passed the SST were found to be ACTH-deficient within 12 months without having received postoperative radiotherapy). Only 1 patient was ill enough to require hospital admission. Setting the risk of false negatives with SST against the morbidity and manpower implications associated with insulin tolerance tests, SST remains the primary screening test for ACTH deficiency in our practice. However, a high index of clinical suspicion to detect false negative results must be maintained.

A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency.

OBJECTIVE: Mutations in the GH-releasing hormone (GHRH) receptor (GHRHR) gene (GHRHR) cause autosomal recessive familial isolated GH deficiency (IGHD). We searched for GHRHR mutations in two siblings with IGHD type IB and a history of parental consanguinity. DESIGN: We analyzed peripheral genomic DNA of an index patient. After identifying a novel mutation in the GHRHR, we performed functional studies in order to confirm that the mutation causes receptor malfunction. METHODS: The entire GHRHR was analyzed in the index case by denaturing gradient gel electrophoresis. Abnormally migrating bands were isolated and sequenced. The mutated area was then sequenced in all family members whose DNA was available. The newly found mutation was inserted into a GHRHR cDNA. Wild-type and mutant cDNAs were expressed into CHO cells and the cyclic AMP (cAMP) response to GHRH was measured. In order to determine whether the mutant receptor was properly expressed on the cell membrane surface, CHO cells were transfected with wild-type or mutant GHRHR cDNA containing a FLAG epitope tag in the extracellular N-terminus. RESULTS: Both patients were homozygous for a new missense mutation in codon 176, corresponding to the second transmembrane domain of the receptor protein that replaces alanine with valine (A176V). The mother and three unaffected siblings were heterozygous for the mutation; DNA from the father was not available. Cells expressing the A176V receptor had a significantly reduced cAMP response to GHRH, despite appropriate expression on the cell surface. CONCLUSIONS: We describe two siblings with IGHD due to a new mutation in the GHRHR that disrupts GHRH signaling and leads to GHRH resistance.

Acquired prolactin deficiency indicates severe hypopituitarism in patients with disease of the hypothalamic-pituitary axis.

OBJECTIVE: Prolactin deficiency has been the subject of many scientific studies, but there is a paucity of information regarding prolactin deficiency in humans. In this report, adults with disease of the hypothalamic-pituitary axis (HPA) were studied to determine the prevalence of severe acquired prolactin deficiency (APD) and the pathophysiological characteristics associated with it. PATIENTS AND METHODS: APD was defined as a serum prolactin level persistently below the detection limit of the assay, i.e. less than 50 mU/l (normal range: male 85-444, female 85-530). Patients with a diagnosis of acromegaly, prolactinoma or with congenital or drug induced prolactin deficiency were excluded. Three hundred and sixty-nine patients (190 women, age range 17-79 years) with disease of the HPA, meeting the specified criteria were identified. RESULTS: Twenty-two (13 women, age range 29-76 years), showed evidence of APD. Thirteen of the 22 patients with APD had been treated for Cushing's disease. In all, 62 patients treated for Cushing's disease were identified, resulting in a prevalence of APD in treated Cushing's disease of 20.97%. Excluding treated Cushing's disease, the prevalence of APD in the remainder of the cohort was 2.93%. Nineteen patients with APD (86.4%) and 183 without APD (52.7%) underwent surgery in the region of the HPA (P = 0.0042). In contrast, nine patients with APD (40.9%) and 283 without APD (80.4%) had received radiotherapy, with fields which included the HPA (P < 0.001). No patient with isolated APD was identified. All patients with APD had evidence of severe GH deficiency (GHD) with a peak GH response to provocative stimuli of < 1.6 mU/l and a median IGF-I standard deviation score (SDS) of -4.85 (quartiles -9.56 to -2.80). Of the 13 patients with APD and Cushing's disease, all were gonadotrophin and TSH-deficient, six were adrenocorticotropic hormone (ACTH)-deficient and six (46.1%) had cranial diabetes insipidus (CDI). Of the remaining nine patients with APD, total anterior pituitary hormone failure was present in all and CDI was present in two (22.2%). CONCLUSIONS: The presence of APD indicates severe hypopituitarism in adults with HPA disease. It is universally associated with severe GHD. It is more common after surgery to the HP region. It has a low overall prevalence except in patients surgically treated for Cushing's disease.

Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan.

OBJECTIVE: Growth hormone deficiency (GHD) is associated with adverse changes in lipid profile. However, changes in lipids through life in a homogeneous group of GHD subjects have not been defined. PATIENTS AND MEASUREMENTS: We examined lipid levels in a group of untreated severely GHD patients with a mutation in the GHRH receptor gene from a rural community in North-east Brazil. Lipid profiles in 15 GHD subjects [eight children and adolescents (one male), age (median [range]) 13.2 (5.4-19.9) years; seven adults (one male), age 47 (33-66) years] were compared with those in 29 indigenous controls from the same extended kindred [17 children and adolescents (six male), age 10.2 (5.3-18.4) years; 12 adults (eight male), age 54.5 (33-80) years]. All GHD subjects had a peak GH response of < 0.5 ng/ml in response to an insulin tolerance test and extremely reduced IGF-1 levels (median 5.5 ng/ml). Data were compared between cohorts and with an age- and sex-matched white American reference population. RESULTS: Abnormalities were confined to plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. More GHD children had levels of plasma TC and LDL-C above the 95th percentile for our reference population (3/8 and 4/7, respectively) compared to controls (0/17 and 1/15, respectively) (P < 0.05). In the adults, median TC and LDL-C levels were higher in the GHD than controls (P < 0.05) (6.3 vs. 4.1 mmol/l; 4.4 vs. 2.7 mmol/l, respectively). Median Z-scores, calculated using values from the reference population, were not different between GHD children and adults for both TC (+0.8 vs.+0.4) and LDL-C (+1.4 vs.+0.7). CONCLUSIONS: The lipid profile in children as well as in adults with very severe GHD is adversely modified. There would appear to be no significant worsening of the lipid abnormality with duration of GHD or achievement of adulthood.

Late endocrine, metabolic and skeletal sequelae following treatment of childhood cancer.

With an ever increasing adult population of childhood cancer survivors there is a need to focus on the late effects of cancer therapy. It is essential that, after discharge from the paediatric oncologists, the patients are not lost from the health system but are under continued surveillance with access to the appropriate physicians. Endocrine and metabolic consequences may affect a patient's life both soon after cancer treatment and also for many years in the future. In this review we consider the following potential problems: growth hormone deficiency and replacement in adulthood, cardiovascular risk factors, osteopaenia, thyroid and parathyroid dysfunction.