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Objectives: Anaemia is a key cause of morbidity in chronic kidney disease (CKD). Androgen deficiency (AD) in males can contribute to anaemia of all causes, including in CKD. We sought to examine the prevalence of AD in men with CKD, the extent to which it contributed to anaemia and whether it was independently associated with long-term survival., Methods: This cross-sectional observational study was conducted among males aged 18 years and over with CKD stages 4 and 5. The study analysed morning blood samples with regard to their full blood count, urea and electrolytes, albumin, lipids, testosterone (T) and sex hormone binding globulin, with calculation of free testosterone by mass action equation. Mortality data were obtained 15 years later for survival analysis., Results: Among 322 patients with a mean age of 63 years, the overall prevalence of AD was 68.9%. There was a statistically significant negative correlation between erythropoiesis stimulating agent (ESA) dose and testosterone concentrations (Pearson correlation -0.193, p = 0.05). There was a positive correlation between haemoglobin (Hb) and free testosterone level among patients not on ESA therapy (Pearson correlation 0.331, p < 0.001). Kaplan-Meier plots showed p < 0.001 on log-rank analysis, indicating that AD was significantly associated with worse survival. However, in Cox regression analysis, free testosterone was not associated with survival (95% CI for free testosterone 0.997-1.000)., Conclusions: AD is highly prevalent among this population, and increases further with older age and more severe CKD warranting haemodialysis. Association of lower Hb and higher ESA dose with lower T concentration might be causative, which has important pharmaco-economic as well as clinical implications. Lower survival in men with low T, more likely reflects overall poor health rather than causation. A properly constituted randomised controlled study evaluating the effect of native T replacement is warranted in men with CKD and AD., (© 2024 John Wiley & Sons Ltd.)

Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo-pituitary disorders, whether organic or functional., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain., Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports., Results: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided., Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Objective: Functioning gonadotroph adenomas (FGAs) are rare pituitary tumours stimulating ovarian function with potential life-threatening consequences in women. However, a lack of aggregated clinical experience of FGAs impairs management in affected women. The aim of this study is to present the clinical course of FGA-induced ovarian hyperstimulation syndrome (OHSS) cases as identified by some of the largest UK pituitary endocrine tertiary centres with a view to increasing awareness and improving diagnosis and management of women with FGA., Design: A retrospective observational study; audit of eight UK regional pituitary centres for cases of FGAs., Setting: Specialist neuroendocrine centres in the United Kingdom., Patients and Measurements: Women diagnosed with FGA-induced OHSS. Description of their clinical course., Results: Seven cases of FGA were identified in women, all causing OHSS. Mean age was 33.4 years at diagnosis. Abdominal pain, irregular periods, headache, and visual disturbances were reported at presentation by 100%, 71%, 57% and 43% of women, respectively. Three of seven women underwent ovarian surgery before FGA diagnosis. Six women underwent transsphenoidal surgery (TSS) with incomplete tumour resection in five of those, but all showed improvement or resolution in symptoms and biochemistry postoperatively., Conclusion: FGA is a rare cause of spontaneous OHSS. TSS improves clinical and biochemical features of ovarian hyperstimulation in FGAs. Improved awareness of FGA will prevent inappropriate emergency ovarian surgery., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Objectives: To summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women., Background: Complaints of impaired cognition and mood are common in the peri-menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon., Design: A literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included., Patients: Perimenopausal and menopausal women., Results: Due to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a 'critical window' for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri-menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear., Conclusions: Further study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence-based conclusions can be drawn., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Objective: Testosterone replacement therapy (TRT) is recommended for the treatment of symptomatic hypogonadism in men. Data on prescription behaviours are, however, limited and conflicting. The objective of this study was to investigate clinical characteristics associated with the likelihood of being prescribed TRT by general practitioners (GP) in North-West London (NWL)., Design: Retrospective cohort study using Discover database of GP-registered patients in NWL between 2015 and 2019., Patients: We identified 20,299 men aged ≥18 years with serum total testosterone measurement (TT) and without prior TRT prescription records., Measurements: We determined whether TRT was subsequently commenced, while analysing clinical characteristics related to hypogonadism., Results: Of all men having TT measurement, 19,583 (96.4%) were not commenced on TRT (Group A) and 716 (3.5%) men were commenced on TRT (Group B). Men prescribed TRT (Group B) had higher mean age, body mass index (BMI) and higher risks of hypertension, depression type 2 diabetes and ischaemic heart disease; conversely, men in Group B had lower mean pretreatment TT and were less likely to have prostate cancer. Four-hundred and thirty-six men (24.3%) with TT < 8 nmol/L and symptoms of low libido were not prescribed TRT., Conclusions: Our study highlights several factors which may influence the decisions made by clinicians when initiating TRT in primary care. Clearer guidance for clinicians may help to improve the consistency of treatment of men with hypogonadism., (© 2021 John Wiley & Sons Ltd.)

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH., (© 2021 John Wiley & Sons Ltd.)

Objectives: Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea, but diagnosis can be challenging. The aim of this study was to investigate the clinical and biochemical features of FHA, compared to that of polycystic ovarian syndrome (PCOS) and assess the diagnostic performance of the different parameters for differentiating the two conditions., Design and Patients: This was a retrospective observational study. We analysed clinical and biochemical parameters of women diagnosed with FHA and PCOS following specialist assessment at the reproductive endocrine gynaecology clinic, St Mary's Hospital., Results: Compared with PCOS, women with FHA had significantly lower body mass index (BMI; 20.1 ± 2.9 vs. 31.1 ± 7.8 kg/m 2 ; p< .0001) and a thinner endometrium (3.75 ± 2.23 vs. 6.82 ± 3.32 mm; p< .0001). Women with FHA had significantly lower luteinising hormone (LH; 3.46 ± 7.31 vs. 8.79 ± 4.98 IU/L; p< .0001), and lower LH to follicle-stimulating hormone (FSH) ratio, estradiol, thyroid-stimulating hormone, free thyroxine and prolactin levels; there was no significant difference in FSH levels. BMI had the greatest predictive performance for FHA (area under the curve [AUC]: 0.93; p< .001), followed by estradiol (AUC: 0.89; p< .001), LH (AUC: 0.88; p< .001) and LH:FSH ratio (AUC: 0.86; p< .001)., Conclusions: Our data provides quantification for diagnostic accuracy of clinical parameters to differentiate FHA from PCOS, namely low BMI, estradiol, LH and LH:FSH ratio. These data could help clinicians more reliably diagnose FHA in women with secondary amenorrhoea., (© 2021 John Wiley & Sons Ltd.)

Background: Secondary oligo/amenorrhoea occurs in 3%-5% of women of reproductive age. The two most common causes are polycystic ovary syndrome (PCOS) (2%-13%) and functional hypothalamic amenorrhoea (FHA) (1%-2%). Whilst both conditions have distinct pathophysiology and their diagnosis is supported by guidelines, in practice, differentiating these two common causes of menstrual disturbance is challenging. Moreover, both diagnoses are qualified by the need to first exclude other causes of menstrual disturbance., Aim: To review clinical, biochemical and radiological parameters that could aid the clinician in distinguishing PCOS and FHA as a cause of menstrual disturbance., Results: FHA is uncommon in women with BMI > 24 kg/m 2 , whereas both PCOS and FHA can occur in women with lower BMIs. AMH levels are markedly elevated in PCOS; however, milder increases may also be observed in FHA. Likewise, polycystic ovarian morphology (PCOM) is more frequently observed in FHA than in healthy women. Features that are differentially altered between PCOS and FHA include LH, androgen, insulin, AMH and SHBG levels, endometrial thickness and cortisol response to CRH. Other promising diagnostic tests with the potential to distinguish these two conditions pending further study include assessment of 5-alpha-reductase activity, leptin, INSL3, kisspeptin and inhibin B levels., Conclusion: Further data directly comparing the discriminatory potential of these markers to differentiate PCOS and FHA in women with secondary amenorrhoea would be of value in defining an objective probability for PCOS or FHA diagnosis., (© 2020 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: Poor sperm function is a major cause of infertility. There is no drug therapy to improve sperm function. Semen oxidative stress is a recently identified pathway for sperm damage. Commercial antioxidants such as L-carnitine and acetyl-L-carnitine (LAL) are commonly self-administered by infertile men. However, concerns have been raised whether inappropriate LAL therapy causes reductive stress-mediated sperm damage. It is imperative to investigate whether: (1) LAL improves sperm function by reducing reactive oxidative species (ROS); (2) LAL has differential effects on sperm function between men with normal and elevated ROS., Methods: A prospective cohort study of routine clinical practice was performed in infertile men with abnormal sperm quality. Changes in sperm function and semen ROS levels following three months of oral LAL therapy were compared between participants with baseline seminal normal ROS (≤10RLU/SEC/10 6 sperm; n = 29) and High ROS (>10 RLU/SEC/10 6 sperm; n = 15) levels measured using an established colorimetric-luminol method., Results: In normal ROS group, sperm function did not change following LAL therapy. In high ROS group, LAL therapy reduced semen ROS fivefold, increased sperm count by 50% (mean count in mill/ml: 21.5 + 7.2, baseline; 32.6 + 9.5, post-treatment, P = .0005), and total and progressive sperm motility each by 30% (mean total sperm motility in % 29.8 + 5.0, baseline: 39.4 + 6.2, post-treatment, P = .004; mean progressive sperm motility in % 23.1 + 4.6, baseline: 30.0 + 5.5, post-treatment, P = .014 vs. baseline)., Conclusions: We report for the first time that LAL only improves sperm quality in infertile men who have baseline high-ROS levels prior to treatment. These data have important potential implications for couples with male infertility and their clinicians., (© 2020 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: There are no current pharmacological therapies to improve sperm quality in men with sub-fertility. Reducing the exposure to lifestyle risk factor (LSF) is currently the only intervention for improving sperm quality in men with sub-fertility. No previous study has investigated what proportion of men with sub-fertility are exposed to adverse lifestyle factors. Furthermore, it is not known to what extent men with sub-fertility are aware of lifestyle factors potentially adversely impacting their fertility., Methods: A cross-sectional anonymous questionnaire-based study on self-reported exposure and awareness of LSF was conducted in 1149 male partners of couples investigated for sub-fertility in a tertiary andrology centre in London, UK., Results: Seventy per cent of men investigated for sub-fertility had ≥1 LSF, and twenty-nine per cent had ≥2 LSF. Excessive alcohol consumption was the most common LSF (40% respondents). Seventeen per cent of respondents used recreational drugs (RD) regularly, but only 32% of RD users believed RD impair male fertility. Twenty-five per cent of respondents were smokers, which is higher than the UK average (20%). Twenty-seven per cent of respondents had a waist circumference (WC) >36 inches (91 cm), and 4% had WC >40 inches (102 cm). Seventy-nine per cent of respondents wanted further lifestyle education to improve their fertility., Conclusions: Our data suggest that men with sub-fertility are as follows: (a) exposed to one or more LSF; (b) have incomplete education about how LSF may cause male sub-fertility; (c) want more education about reducing LSF. Further studies are needed to investigate the potential of enhanced education of men about LSF to treat couples with sub-fertility., (© 2020 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

The clinical sequelae of oestrogen deficiency during menopause are undoubted. However, the pathophysiological role of testosterone during the menopause is less clear. Several randomized, placebo-controlled clinical trials suggest that testosterone therapy improves sexual function in postmenopausal women. Some studies suggest that testosterone therapy has additional effects, which include increased bone mineral density and decreased serum high-density lipoprotein (HDL) cholesterol. Furthermore, the long-term safety profile of testosterone therapy in postmenopausal women is not clear. This article will provide a concise and critical summary of the literature, to guide clinicians treating postmenopausal women., (© 2018 John Wiley & Sons Ltd.)

Background: Sperm cryopreservation (freezing) should be offered to all men with cancer due to risk of infertility. However, many men with cancer already have impaired spermatogenesis prior to sperm cryopreservation. Furthermore, physical ill-health may hinder attendance of freeze visits. Investigating both the distribution of sperm functions and freeze attendance rates in men with newly diagnosed cancer, may identify patients benefiting from targeted reproductive fertility support., Methods: We performed a retrospective study of 2906 male patients undergoing sperm cryopreservation prior to cancer therapy at a single UK tertiary centre between 1989 and 2013; all patients were asked to attend three hospital semen collection visits prior to cancer therapy., Results: Fifteen per cent (433/2906) of men with newly diagnosed cancer had severely impaired semen quality (i.e., sperm total motile count, TMC < 1 million) during the first semen collection visit. However, patients with severely impaired semen quality had the poorest attendance of subsequent semen collection visits despite being requested to do so (non-attendance in TMC < 1 million: 43.4%; TMC < 1-30 million: 35.7%, P < 0.05 vs. <1 million; TMC > 30 million: 33.2%, P < 0.01 vs. <1 million)., Conclusions: This study expands understanding of the semen quality of men with newly diagnosed cancer, and their ability to adhere to fertility preservation recommendations. Our data suggest that patients with the poorest semen quality paradoxically suffer the poorest attendance rates of sperm cryopreservation appointments prior to commencing cancer therapy. We suggest that additional support may be of clinical benefit to men with newly diagnosed cancer and TMC < 1 million sperm., (© 2018 John Wiley & Sons Ltd.)

Gynaecomastia may be due to medication, chronic liver or kidney disease, hypogonadism (primary or secondary to pituitary disease) or hyperthyroidism. Having excluded these aetiologies, it is imperative to be vigilant for underlying malignancy causing gynaecomastia. These include human chorionic gonadotrophin-secreting testicular and extratesticular tumours and oestrogen-secreting testicular tumours and feminising adrenal tumours., (© 2017 John Wiley & Sons Ltd.)

Background and Objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin., Design and Patients: A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions., Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P < 0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH., Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response., (© 2015 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.)

Background: Cardiovascular complications represent the biggest cause of mortality in acromegaly. It is therefore important to optimally stratify acromegalic patients according to disease activity and complication risk. GH is secreted in a pulsatile manner from the pituitary gland, but GH pulsatility is not routinely assessed clinically. The coefficient of variation of serum GH (GHCV) during oral glucose tolerance test (OGTT) quantifies the variation of GH secretion in patients with acromegaly, but has not been reported previously., Aim: To investigate whether GHCV during OGTT is associated with clinical parameters predicted to relate with hypothalamo-pituitary dysfunction during acromegaly, such as radiotherapy treatment, pituitary deficiency and cardiac disease., Methods: GHCV was calculated during 584 OGTTs and compared with nadir serum GH and IGF-1 in 111 acromegalic patients treated at a single centre., Results: Acromegalic patients treated with radiotherapy had a 37% lower level of GHCV when compared to the nonradiotherapy group (mean GHCV: 0·298 ± 0·015, no radiotherapy; 0·189 ± 0·007, radiotherapy; P < 0·001). Neither serum IGF-1 nor nadir GH was significantly altered in the radiotherapy group. Mean GHCV was 50% lower in the acromegalic patients with cardiac failure when compared to acromegalic patients with normal echocardiogram (0·161 ± 0·034 vs 0·297 ± 0·055; P < 0·05). Neither serum IGF-1 nor nadir GH was significantly altered during cardiac failure., Conclusion: Our preliminary data suggest that GHCV during OGTT may be reduced during acromegaly in patients with previous radiotherapy, pituitary deficiencies and cardiac disease. Larger studies are required to determine whether GHCV could provide help to assess the morbidity status of patients with treated acromegaly., (© 2015 John Wiley & Sons Ltd.)

Background: The peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate gonadotrophin-releasing hormone (GnRH) secretion. Kisspeptin is currently being evaluated as a novel therapeutic for women with infertility. However, some animal studies suggest that kisspeptin may also stimulate growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH) secretion, with implications for its safety; no previous study has investigated whether kisspeptin stimulates these pituitary hormones in humans., Aim: To determine whether kisspeptin-54 modulates GH, prolactin and TSH secretion in healthy women., Design and Participants: Prospective, single-blinded, placebo-controlled, one-way crossover study. Five healthy women received 7 days of twice-daily subcutaneous bolus vehicle (month 1) or 6·4 nmol/kg kisspeptin-54 (month 2)., Measurements: Serum samples were analysed post hoc for GH, prolactin and TSH., Results: Mean serum GH, PRL and TSH did not change during the first 4 h following kisspeptin-54 injection when compared with vehicle. The mean frequency or amplitude of GH pulses (which influence GH function) did not change acutely following kisspeptin-54 injection when compared with vehicle. No chronic changes in serum GH, PRL or TSH were observed over the 7-day period of twice-daily kisspeptin-54 injections when compared with vehicle., Conclusion: While we cannot exclude any effect of kisspeptin-54 on GH, prolactin or TSH secretion, we observed no significant changes in these hormones at a dose of kisspeptin-54 administration known to stimulate gonadotrophin secretion in a small study of healthy women. These data have important implications for the potential of kisspeptin to treat patients with infertility., (© 2014 John Wiley & Sons Ltd.)

Background: Kisspeptin is a novel hypothalamic peptide which stimulates endogenous gonadotrophin releasing hormone (GnRH) secretion. A single subcutaneous bolus injection of kisspeptin-54 increases circulating luteinizing hormone (LH) levels in women, but its acute effects on LH pulsatility are not known., Aims: To investigate the effects of a single subcutaneous (sc) injection of kisspeptin-54 administration on LH pulsatility in healthy female volunteers., Methods: Six healthy female adult volunteers underwent 10-minute blood sampling for serum LH measurement for 8 h during the follicular phase of menstrual cycle. Sc bolus injection of saline or kisspeptin-54 (0·15, 0·30 or 0·60 nmol/kg) was administered 4 h after commencing the study. A previously described, blinded deconvolution method was used to detect LH pulses., Results: Mean number of LH pulses was increased significantly following 0·30 and 0·60 nmol/kg kisspeptin-54 when compared with saline (mean increase in number of LH pulses per 4 h, following injection: -0·17 ± 0·54, saline; +2·33 ± 0·56, 0·30 nmol/kg kisspeptin-54, P < 0·05 vs saline; +2·33 ± 0·80, 0·60 nmol/kg kisspeptin-54, P < 0·05 vs saline). LH pulse secretory mass increased following injection of 0·60 nmol/kg in five of six subjects, but the mean change in all subjects was non-significant when compared with saline (mean increase in pulse secretory mass in IU/l following injection: +0·35 ± 0·40, saline; +2·61 ± 1·17, 0·60 nmol/kg kisspeptin-54, P = 0·10 vs saline)., Conclusions: A single injection of kisspeptin-54 temporarily stimulates the number of LH pulses in healthy women. Further studies are required to investigate the therapeutic potential of kisspeptin-54 injection to restore LH pulsatility in patients with reproductive disorders caused by impaired GnRH secretion., (© 2013 John Wiley & Sons Ltd.)

Background: Despite NIH clinical recommendations, many clinicians are reluctant to replace vitamin D in patients with hypercalcaemia with primary hyperparathyroidism (PHP) due to concerns over aggravating hypercalcaemia. Furthermore, the optimum level of vitamin D replacement in PHP remains unclear., Methods: We performed a large retrospective study to determine whether a relationship exists between serum 25-hydroxyvitamin D levels, calcium and other important biochemical markers in patients with PHP. Serum, plasma and urinary biochemical measurements were collected from 251 patients with hypercalcaemia diagnosed with PHP., Results: When examining overall mean circulating levels during clinical follow-up, serum 25-hydroxyvitamin D correlated highly significantly with plasma parathyroid hormone (PTH) (r = -0.23, P = 0.0003) and serum phosphate (r = 0.16, P = 0.0119). No significant relationship was observed between serum calcium and 25-hydroxyvitamin D (r = 0.002, P = 0.98). Mean plasma PTH during clinical follow-up was 51% lower in patients with serum 25-hydroxyvitamin D > 60 nm when compared with patients who had 25-hydroxyvitamin D < 20 nm (P < 0.01)., Conclusions: Patients with PHP who have 25-hydroxyvitamin D levels > 60 nm have significantly reduced PTH hypersecretion when compared with patients with deficient vitamin D levels, without exhibiting worse hypercalcaemia., (© 2012 John Wiley & Sons Ltd.)

Background: Acromegaly is characterized by the hypersecretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). This leads to an increased cardiovascular, cerebrovascular and metabolic morbidity resulting in excess mortality. There is controversy over which biomarker, GH or IGF-1, better predicts this increased morbidity and mortality. The relationship between the cumulative exposure to GH and IGF-1 with co-morbidities in acromegaly has not previously been reported., Objective: To investigate the relationship between the cumulative exposure to GH and IGF-1 with cardiovascular, cerebrovascular and metabolic co-morbidities., Methods: Records of 116 acromegalic patients were retrospectively examined. Cardiovascular and cerebrovascular histories, serum GH and IGF-1, fasting glucose and oral glucose tolerance test results, were reviewed for the duration of follow-up. IGF-1 index was calculated by dividing each serum IGF-1 value by the upper limit of reference range for IGF-1. GH and IGF-1 burdens were calculated for each patient by multiplying known disease duration (in years) by mean level of basal GH or IGF-1 index recorded during the patients' entire follow-up., Results: Patients with abnormal glucose tolerance had a significantly higher mean GH burden compared with euglycaemic patients (P = 0·005). Ischaemic heart disease was also associated with a higher GH burden (P = 0·009) whereas cerebrovascular disease and cardiomyopathy were associated with a significantly higher mean IGF-1 burden (P = 0·018, P = 0·011 respectively)., Conclusion: This study identifies associations of raised GH and IGF-1 burden with cardiovascular, cerebrovascular and metabolic complications of acromegaly. Results from this study therefore suggest that consideration of the overall level of GH and IGF-1 exposure may provide important information for the management and surveillance of patients with treated acromegaly., (© 2011 Blackwell Publishing Ltd.)

Background: Nadir GH during oral glucose tolerance test (OGTT) is the gold-standard test of GH secretion in treated acromegaly. However, it was recently reported that variability in GH is reduced postradiotherapy, making basal GH a potential surrogate marker for nadir GH in such patients., Objective: We aimed to investigate how predictive basal GH is of nadir GH and IGF-I, and whether radiotherapy influenced these relationships., Design: A total of 226 pairs of basal and nadir GH values from 76 treated acromegalic patients were analysed. Basal GH was defined as the fasting serum GH immediately prior to OGTT., Results: A highly positive linear correlation (Pearson correlation = 0.955, P < 0.01) between basal and nadir GH was found. Negative predictive value for basal GH < 1 microg/l with respect to nadir GH > 1 microg/l was 100% (53/53 in radiotherapy group, 15/15 in nonradiotherapy group). Positive predictive values for basal GH > 2 microg/l with respect to nadir GH > 1 microg/l for patients treated and not treated with radiotherapy were 96.7% (88/91) and 95.2% (20/21), respectively. No significant difference between concordance of basal and nadir GH with IGF-I in assessment of disease activity was found. Discordance between IGF-I and nadir or basal GH < 1 microg/l was lower in the radiotherapy group than nonradiotherapy group, but this was nonsignificant., Conclusions: Basal GH < 1 microg/l and > 2 microg/l are highly predictive of nadir GH < 1 microg/l and > 1 microg/l, respectively, regardless of previous radiotherapy. Basal GH is as good as nadir GH in concordance with IGF-I. We therefore suggest basal GH is a useful test of disease activity in treated acromegaly, and can reliably replace OGTT unless basal GH is between 1 microg/l and 2 microg/l.