Management of menopause: a survey of physicians from the Middle East and Africa.

OBJECTIVE: This study evaluated physicians' perceptions, practices, confidence, comfort level and prior training in managing menopause. METHODS: A survey was conducted of a convenience sample of physicians from the Middle East and Africa (MEA) in 2019. We covered knowledge of symptoms, menopausal hormone therapy (MHT), other menopause management strategies and prior training in menopause medicine. RESULTS: Of the 254 participants, 64.2% were seniors in family medicine (36.4%), endocrinology (36.0%), gynecology (15.8%) and internal medicine (13.8%). Fewer than one-third (28.8%) correctly identified the diagnostic criteria of menopause. Almost all recognized vasomotor symptoms (99.5%), vaginal dryness (96.2%) and mood disturbance (94.3%), but to a lesser extent other symptoms. Inconsistency and critical gaps were identified in responses to competence questions on six case studies. They recalled having occasional (43.2%) or no training (19.4%) in menopause medicine and rated their preparedness to treat menopause widely. A total of 66.2% agreed that training is very important. Variation between specialties was identified. CONCLUSION: Many physicians recognize the importance of education in menopause management, but their responses revealed critical knowledge gaps that underscored the need for comprehensive, evidence-based menopause management.

Guidelines for managing diabetes in Ramadan.

BACKGROUND: Globally there are approximately 90 million Muslims with diabetes of which approximately 400 000 reside within the UK. The holy month of Ramadan is a fundamental practice of this religion of which fasting from sun-rise to sun-set is an integral part. This poses many potential risks for those with diabetes who wish to observe Ramadan. METHODS: The evidence base for best clinical management of Type 1 and Type 2 diabetes during Ramadan was reviewed. We reviewed current and previous recommendations for safe fasting during Ramadan. RESULTS: The risks associated with fasting in those with diabetes and preparing your patient for Ramadan are discussed. We have reviewed the evidence around diet-controlled diabetes and therapies including; metformin, acarbose, metglitinides, sulfonylureas, thiazolidinidiones, dipeptidyl peptidase-4 inhibitor (DPP-4), sodium glucose co-transporter -2 (SGLT-2) inhibitors, glucagon-like peptide -1 (GLP-1) receptor agonists and insulin. CONCLUSION: Up to date guidelines for the management of treatment regimes are set-out for those with Type 1 and Type 2 diabetes who wish to fast during Ramadan.

Care for People with Diabetes during Haj

Haj is one of the five cardinal components of Islam commonly known as the five pillars of Islam. Approximately two million Muslims perform it each year. Haj involves travel to the holy sites in and around Mecca and Medina during a specified short period of time in a limited space; not usually inhabited by such a large number of people. This article deals with the effects of this event on diabetes and its management. The importance of this arises from the fact during Haj; the person's life routine changes as he travels to a different place of his own for a period of 4-6 weeks where geography; weather; diet; and habits are different. During Haj most people live what is effectively a very basic life in very crowded places. Therefore; medical conditions; such as diabetes; whose management depends on a stable routine; would predictably be affected significantly. People with diabetes should have enough time to consider a management plan for their diabetes. The objectives are to achieve a good control and avoid any complications that may be particularly associated with the conditions faced during Haj

Effects of 7 years of growth hormone replacement therapy in hypopituitary adults.

Short-term studies of GH replacement in adult hypopituitarism have usually demonstrated beneficial effects on body composition and circulating lipids, with neutral or occasionally adverse effects on glucose tolerance. Fasting hyperinsulinemia has been reported. GH effects on cardiac function have been variable. The effects of long-term GH therapy, taking into account the consequences of increasing age, are not fully known. Thirty-three hypopituitary, initially middle-aged adults were studied over a 7-yr period; 12 patients took GH therapy (mean, 0.7 mg daily) continuously (group A); 11 took GH for only 6-18 months, a minimum of 5 yr previously (group B); and 10 patients never received GH therapy (group C). Other pituitary replacement was maintained. Effects on anthropometry, body composition (by bioimpedance analysis, total body potassium, and dual energy x-ray absorptiometry), circulating lipids, glucose and insulin concentrations, cardiac 2-dimensional and Doppler echocardiography, and exercise tolerance were assessed before and after the treatment period. Continuous GH therapy had no significant effect on body weight, but it prevented the increase in waist circumference and waist to hip ratio that occurred in the patients without GH substitution (waist to hip ratio, group A, 0.87+/-0.08 at baseline, 0.85+/-0.09 at 7 yr; group B, 0.89+/-0.11 at baseline, 0.94+/-0.11 at 7 yr; P < 0.005 for GH effect; group C, 0.87+/-0.10 at baseline, 0.92+/-0.10 at 7 yr; P < 0.005 for GH effect). A GH-induced decrease in subscapular skinfold thickness was also observed. By bioimpedance analysis, GH therapy caused an increase in total body water and fat-free mass, and a decrease in the percent body fat. Although changes occurred with time in all groups, no significant additional GH therapy effects were observed on glucose tolerance, insulin concentrations, lipid levels, cardiac dimensions, echocardiographic diastolic function, or exercise tolerance. In conclusion, prolonged GH substitution in middle-aged hypopituitary adults causes a sustained improvement in body composition. Other benefits, e.g. on lipid levels and exercise tolerance, were not apparent at 7 yr when comparisons were made with GH-untreated hypopituitary controls. Potentially adverse effects on glucose tolerance and insulinemia did not develop with prolonged GH therapy.

How much, and by what mechanisms, does growth hormone replacement improve the quality of life in GH-deficient adults?

The majority of studies (but not all) have demonstrated that adults with hypopituitarism of both childhood and adult onset have a diminished quality of life (QOL) in comparison with the normal population. Reductions in physical and mental energy, dissatisfaction with body image and poor memory have been reported most consistently. A specific role for growth hormone (GH) deficiency, as opposed to multiple pituitary hormone deficiency, has been observed for the memory deficit, which extends to both short- and long-term memory. Comparisons with normal siblings have confirmed the reduced QOL, although differences have been small. There is less consensus for a reduction in QOL when hypopituitary subjects are compared with patients with other chronic diseases, with studies supporting (in comparison with diabetics) and refuting (in comparison with patients following mastoid surgery) the reduction in QOL. GH replacement in adults has improved QOL, particularly in the domains of energy level and self-esteem, and memory has improved. The social impact of these changes may be considerable, with patients requiring fewer days' sick leave. A major placebo effect is present, however, and neutral results as well as positive have been reported in placebo-controlled trials. Where a positive effect has been observed, it has been more likely to occur in patients with a low QOL at the outset. It is otherwise impossible to predict at the outset those who will benefit from GH replacement. GH treatment has effects on body composition, exercise capacity, muscle strength, total body water and intermediary metabolism which would be expected to improve QOL. Replacement therapy also has side-effects, and it is the variable balance of the positive and negative effects, coupled with the difficulties of measuring QOL, which have led to the disparate results in the literature. There is probably also a true inter-individual variation, although the mechanisms of this are currently unknown.

Abnormal carotid arterial wall dynamics in symptom-free hypopituitary adults.

OBJECTIVE: Although vascular mortality is increased in hypopituitary adults on routine replacement, there are limited data on the atherosclerotic process during life in these patients. Measurement of arterial stiffness may provide an index of early vascular changes that predispose to the development of major vascular accidents. DESIGN: Thirty-four hypopituitary adults on conventional replacement therapy and 39 age- and sex-matched controls were studied. They had no history or clinical evidence of macrovascular disease. The common carotid artery distensibility coefficient (DC), compliance coefficient (CC) and arterial stiffness index (beta index) were calculated from high-resolution ultrasonic imaging of the two common carotid arteries and from the brachial blood pressure. RESULTS: There was no difference between patients and controls in carotid diastolic diameter (mean +/- S.E.M) (5.55 +/- 0.16 vs 5.45 +/- 0.08 mm) and pulse pressure (6.66 +/- 0.30 vs 6.58 +/- 0.24 kPa). The increase in diameter during systole was significantly lower in the hypopituitary patients (0.39 +/- 0.02 vs 0.50 +/- 0.03 mm, P < 0.001). The DC was significantly lower in patients than in controls (24.2 +/- 2.29 vs 30.1 +/- 2.01 10(-3) kPa-1, P < 0.05). The carotid CC was also significantly lower in patients than in controls (5.7 +/- 0.49 vs 7.0 +/- 0.45 10(-7) m2 kPa-1, P < 0.05). The beta index was higher in the patient group (8.4 +/- 1.3 vs 5.9 +/- 0.37, P < 0.05). When men and women were considered separately, the differences between patients and controls were statistically significant in women but not in men and were more marked in the older women subgroup. CONCLUSIONS: Asymptomatic hypopituitary adults (especially women) on conventional replacement therapy have increased stiffness of the common carotid arteries. These findings provide additional evidence for a process leading to premature atherosclerosis in this group of patients.

Effects of four years' treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults.

Short-term trials of growth hormone (GH) substitution in hypopituitary adults have shown beneficial effects on body composition. To evaluate the long-term effects on body composition, we followed thirteen GH-deficient adults (GH < 6 mU/l following standard provocative tests) for 4 years of GH replacement. At yearly intervals, serum insulin-like growth factor I (IGF-I), body weight, body mass index (BMI), waist, waist-to-hip circumference ratio (WHR) and resting systolic (SBP) and diastolic blood pressure (DBP) were determined, and body composition was assessed using three independent methods: total body potassium (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Compared to baseline, IGF-I levels increased significantly at 1 (p = 0.0001), 2 (p = 0.0004), 3 (p = 0.006) and 4 years (p = 0.002). Body weight and BMI changed minimally at 1, 2 and 3 years and increased significantly only at the fourth year (p = 0.012 and p = 0.0009, respectively) of GH therapy. Waist and WHR decreased significantly at 1, 2 and 4 years (waist: p = 0.0009, p = 0.0004, p = 0.049; WHR: p = 0.0025, p = 0.012, p = 0.047, respectively). Neither resting SBP nor DBP changed significantly. Fat-free mass (FFM) derived from TBK and BIA increased significantly at 1 (p = 0.004; p = 0.004), 2 (p = 0.003; p = 0.05), 3 (p = 0.005; p = 0.04) and 4 years (p = 0.02; p = 0.002). Using DXA, the increase in FFM was significant at 1 (p = 0.007) and 2 years (p = 0.008) but not at 3 and 4 years. Percentage body fat measured by TBK, BIA and DXA decreased significantly at 1 (p = 0.008; p = 0.003; p = 0.03), 2 (p = 0.018; p = 0.06; p = 0.049) and 4 years (p = 0.03; p = 0.002; p = 0.04). A rise in total body water, calculated from BIA, was observed at 1 year (p = 0.004) and was maintained throughout the treatment period. These data demonstrate that 4 years of GH treatment in hypopituitary adults is associated with sustained improvement in body composition.

Beta-cell function in hypopituitary adults before and during growth hormone treatment.

1. We studied beta-cell function in 40 hypopituitary adults and in 36 matched control subjects. Hypopituitary patients were studied again at 1, 3 and 6 months during a double-blind placebo-controlled trial of growth replacement lasting for 6 months. Biosynthetic human growth hormone was given subcutaneously in a daily dose of 0.02-0.05 i.u./kg at bed time. Fasting insulin, intact proinsulin and 32-33 split proinsulin were measured by two-site immunoradiometric assays. 2. Hypopituitary patients were aged 19-67 years and had a body mass index of 27.7 (18.0-41.1) kg/m2. They were receiving replacement thyroxine, adrenal steroids and sex hormones and they were growth hormone deficient. Control subjects were matched for age, sex and body mass index. Hypopituitary patients with normal glucose tolerance and with impaired glucose tolerance were compared separately with subgroups of control subjects matched for age and body mass index. 3. Twenty-six hypopituitary patients had normal glucose tolerance and 14 had impaired glucose tolerance. All control subjects had normal glucose tolerance by World Health Organization criteria. Patients with impaired glucose tolerance were significantly older than those with normal glucose tolerance (P < 0.03). Hypopituitary patients with normal glucose tolerance compared with normal control subjects had a significantly lower fasting plasma glucose concentration (P < 0.01), a lower fasting insulin concentration (P < 0.006), a lower insulin-glucose ratio (P < 0.02) and a lower percentage of insulin to total insulin-like molecules [hypopituitary patients, 90% (81-96%); control subjects, 93% (78-97%); P < 0.02]. Hypopituitary patients with impaired glucose tolerance had similar glucose and insulin concentrations and insulin-glucose ratios as matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of measurements of body composition by total body potassium, bioimpedance analysis, and dual-energy X-ray absorptiometry in hypopituitary adults before and during growth hormone treatment.

We compared fat-free mass (FFM) and percentage body fat mass (BFM) values derived from total body potassium (TBK), bioelectrical impedance analysis (BIA), and dualenergy X-ray absorptiometry (DXA) in hypopituitary adults before and after 6 mo treatment with growth hormone. Before growth hormone treatment, FFM values from the three methods correlated strongly. FFM values from TBK were lower than FFM values derived from BIA and DXA (mean +/- SD: 53.7 +/- 14.3 compared with 49.1 +/- 9.2 kg, P < 0.0001; DXA compared with TBK: 54.7 +/- 16.4 and 49.2 +/- 9.7 kg, P < 0.0002). BFM values from TBK were significantly higher than the BIA-derived (P < 0.002) but not different from the DXA-derived values. There was no difference in FFM and BFM values derived from DXA and BIA methods. The differences between BIA and TBK methods and between DXA and TBK methods were observed in the obese but not in the nonobese subjects. The increase in FFM derived from BIA with growth hormone was greater than that derived from TBK ([median(range)]; BIA: +5.2(-0.1, +13.8) compared with TBK: +0.9(-4.8, +8.6) kg, P < 0.001, but the changes with placebo were not different. The changes in FFM and BFM derived from DXA was growth hormone and placebo were not significantly different from those derived by using TBK or BIA. We conclude that FFM and BFM values derived from TBK, BIA, and DXA correlate highly and that TBK-derived values for FFM are lower than those derived from BIA and DXA in obese patients.

The effects of prolonged growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults.

OBJECTIVE: Short-term GH replacement in hypopituitary adults increases bone turnover; data on the consequences of longer-term GH treatment are limited. We report on the effects of 12-18 months of GH replacement treatment with biosynthetic human GH on bone metabolism and bone mass in hypopituitary adults. DESIGN: Patients were studied before and after GH treatment for 12 months (n = 11) and 18 months (n = 27) respectively in an open trial. GH dose was 0.04 +/- 0.01 IU/kg daily. MEASUREMENTS: Plasma calcium, phosphate and intact PTH concentrations, 24-hour urinary calcium excretion, 3 markers of bone formation (total alkaline phosphatase, osteocalcin and procollagen 1 carboxy terminal peptide (P1CP)) and serum concentration of carboxyterminal cross-linked telopeptide of type 1 collagen (ICTP), as a marker of bone resorption, were measured at 6-month intervals. Lumbar spine and total body bone mineral mass was measured by dual-energy X-ray absorptiometry. RESULTS: Small increases were observed in plasma calcium and phosphate concentrations at 12 months of GH therapy but the differences at 18 months were not statistically significant. Serum intact PTH concentration did not change. Plasma total alkaline phosphatase increased significantly on GH from 75 +/- 26 to 92 +/- 30 (P < 0.01) and 85 +/- 31 U/I (NS) at 12 and 18 months respectively. Serum osteocalcin increased from 6.5 +/- 3.7 to 15.7 +/- 6.2 (P < 0.0001) and 16.6 +/- 5.7 micrograms/I (P < 0.001) at 12 and 18 months respectively and P1CP increased significantly from 106.0 +/- 47.3 micrograms/I to 165.5 +/- 95.3 (P < 0.0001) and 177.2 +/- 72.2 micrograms/I (P < 0.01) at 12 and 18 months respectively. Plasma ICTP concentration increased also from 3.4 +/- 1.8 to 7.3 +/- 3.4 (P < 0.0001) and 7.0 +/- 2.7 micrograms/I (P < 0.003) at 12 and 18 months of GH therapy respectively. No significant change was observed in total body or lumbar spine bone mass, over the 18 months of GH treatment CONCLUSIONS: Replacement therapy with GH in hypopituitary adults for 6-18 months produced a sustained increase in bone turnover (both formation and resorption). Bone mass was maintained but did not increase over the study period.

Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults.

OBJECTIVES: The role of growth hormone in maintaining normal body composition and bone strength in adults has attracted much interest recently. We have assessed body composition and bone mass in GH deficient hypopituitary adults on conventional replacement therapy and compared them with matched controls. DESIGN AND SUBJECTS: A cross-sectional study of 64 growth hormone deficient hypopituitary adults (29 males and 35 females) on conventional replacement therapy and a large number of healthy control subjects matched for age, sex and body mass index (BMI). MEASUREMENTS: Skinfold thicknesses at two sites (triceps and subscapular), waist and hip girth circumferences were assessed by standard methods. Body composition was assessed using total body potassium (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA). Bone mineral mass was assessed at the lumbar spine and the total body by DEXA. Not every patient and control participated in every measurement. RESULTS: Obesity was common in the hypopituitary patients; BMI (mean +/- SD) was 27.5 +/- 4.6 kg/m2 and body weight was 111.8 +/- 18.5% of the maximal ideal for height (P < 0.001). The sum of subscapular and triceps skinfolds was significantly higher in hypopituitary patients than in controls (men 46 + 15 vs 37 +/- 14 mm, P < 0.05; women 55 +/- 13 vs 47 +/- 17 mm, P < 0.05). Waist to hip circumference ratio was significantly greater in female hypopituitary patients than in matched controls but was not significantly different in men (men 0.94 +/- 0.07 vs 0.91 +/- 0.07, NS; women 0.84 +/- 0.09 vs 0.77 +/- 0.05, P < 0.001). The difference between patients and controls in the sum of skinfolds and the waist to hip ratio were present in non-obese (BMI < 26 kg/m2) subjects (21 patients and 32 controls). TBK corrected for body weight was significantly lower in hypopituitary patients (n = 44) than in controls (n = 31) (men 43.5 +/- 5.6 vs 50.1 +/- 5.9 mmol/kg, P < 0.003; women: 34.0 +/- 3.2 vs 40.6 +/- 5.3 mmol/kg, P < 0.0001). BIA-derived body water content (corrected for body weight) was significantly lower in hypopituitary patients (n = 56) than in controls (n = 57) (0.492 +/- 0.064 vs 0.545 +/- 0.067 l/kg, P < 0.0004). Percentage body fat derived from all the three methods was significantly higher in hypopituitary patients than in normal controls in both sexes (from TBK: men 34.7 +/- 9.4 vs 28.8 +/- 7.0%, P < 0.05; women 37.8 +/- 8.7 vs 30.4 +/- 9.7%, P < 0.01; from BIA: men 29.3 +/- 8.5 vs 23.2 +/- 8.4%, P < 0.01; women 34.6 +/- 8.1 vs 29.3 +/- 9.1% P < 0.01; and from DEXA: men 24.8 +/- 6.8 vs 20.4 +/- 6.1%, P < 0.05; women 38.9 +/- 7.9 vs 32.5 +/- 9.8%, P < 0.01). There was a significant difference between non-obese patients and controls in BIA-derived percentage fat in both sexes and in TBK-derived percentage fat in females only. Bone mineral density (BMD) of the lumbar spine in the L2-L4 region was lower in hypopituitary patients than in controls (men 1.116 +/- 0.129 vs 1.311 +/- 0.131 g/cm2, P < 0.0001; women 1.001 +/- 0.122 vs 1.131 +/- 0.138 g/cm2, P < 0.001). Spine BMD was also reduced in hypopituitary patients compared to the young adult and age and weight matched reference data. Total body BMD was significantly lower in patients than in controls (men 1.186 +/- 0.102 vs 1.250 +/- 0.080 g/cm2, P < 0.05; women 1.080 +/- 0.077 vs 1.149 +/- 0.073 g/cm2, P < 0.005). CONCLUSIONS: Hypopituitary adults on conventional therapy have abnormal body composition with increased fat content, reduced body water content and reduced bone mineral mass.

The effects of short and long-term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance.

The effects of replacement with biosynthetic human GH on carbohydrate tolerance and lipid metabolism were studied in 40 hypopituitary adults during a randomized double blind, placebo-controlled trial for 6 months, followed by a 12-month open trial. The daily GH dose was 0.04 +/- 0.01 IU/kg. Fasting plasma glucose, serum fructosamine, plasmid lipids, lipoproteins, and plasma C-peptide concentrations were measured, and an oral glucose tolerance test was performed every 6 months. There was no change in fasting triglyceride levels at any stage of the study. There was no significant change in fasting total or LDL cholesterol, total HDL cholesterol, high density lipoprotein2 (HDL2) cholesterol, HDL3 cholesterol, apoprotein-A1, or apoprotein-B during GH or placebo treatment in the placebo-controlled 6-months study. In the open phase of the trial, total and low density lipoprotein cholesterol showed a sustained downward trend during GH therapy. Compared to the pretreatment level, the HDL cholesterol concentration was significantly higher at 18 months. Cholesterol subfractions HDL2 and HDL3 and apoprotein-A1 and -B were not different from the pretreatment levels. The total/HDL cholesterol ratio decreased significantly at 12 and 18 months. During the controlled phase, fasting plasma glucose was similar during GH and placebo administration, but fasting insulin and C-peptide increased during GH therapy, but not during placebo treatment. The mean area under the curve (AUC) for glucose increased by a small, but significant, extent over the 6 months of GH treatment and was higher at 6 months than during placebo treatment. The AUC for insulin also increased during GH treatment. During the open trial, the fasting plasma glucose level increased at 6 and 12 months, and the fasting plasma insulin level increased at 6, 12, and 18 months of GH treatment. The plasma glucose AUC during the oral glucose tolerance test was significantly higher at 6 months, and the plasma insulin AUC was significantly higher at 6, 12, and 18 months of GH therapy. In conclusion, GH therapy has some metabolic effects that are considered beneficial and others that are less desirable.

Contractile properties of the quadriceps muscle in growth hormone-deficient hypopituitary adults.

1. Growth hormone-deficient hypopituitary adults often complain of weakness and fatigue. The cause of the fatigue is unknown but could be an increased proportion of fast, fatiguable, type 2 fibres in the muscle. The aim of this study was to examine the contractile properties of the quadriceps muscle in a group of these patients compared with healthy controls. Changes in these properties were also examined in a small subset of the patients following growth hormone replacement. 2. Isometric strength, half-relaxation time from a twitch (t1/2) and the force-frequency relationship were measured using electrically evoked contractions in 14 growth hormone-deficient patients and 14 age- and sex-matched controls. Six patients were restudied following 6-24 month's replacement therapy with growth hormone (daily dose 0.04 +/- 0.01 i.u./kg). 3. The growth hormone-deficient patients had a significantly lower t1/2 than the controls (46.1 +/- 6.1 ms versus 56.1 +/- 10.5 ms respectively; P = 0.0072; mean +/- SD). The 10/100% ratio was also significantly lower in growth-hormone-deficient patients (38.6 +/- 9.9% versus 52.3 +/- 8.0%; P = 0.0005), as was muscle strength (349 +/- 99 N versus 493 +/- 215 N; P = 0.036). Following growth hormone replacement, muscle strength increased significantly (P < 0.05). The 10/100% ratio also increased towards control values, but this change was not significant. 4. These results demonstrate that the relaxation times of the quadriceps are significantly shorter and that the force-frequency relationship shifted to the right in growth hormone-deficient patients, which is consistent with a greater proportion of type 2 fibres within the muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults.

OBJECTIVES: The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH in a large number of hypopituitary adults. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH daily dose was 0.04 (0.02-0.05) IU/kg s.c. PATIENTS: Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19-67 years) on conventional replacement therapy were studied. MEASUREMENTS: Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. RESULTS: During the 6-month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.9 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/- 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW increased on GH (P < 0.01) but not on P. No change was observed in waist-to-hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist-to-hip ratio decreased significantly on GH at 12 months. LBM increased on GH treatment from 49.6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10.1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6,12 and 18 months respectively. TBW also increased at 6 and 12 months of GH treatment. Exercise time increased significantly at 6, 12 and 18 months of GH treatment. Muscle strength in selected muscle groups increased significantly at 6, 12 or 18 months of GH treatment. Randomization resulted in the placebo group having a greater GHQ score (higher morbidity) than the GH group before therapy. Over the controlled phase, GHQ scores improved on placebo but not on GH and CPRS score was unchanged in either group. In the open phase, the GHQ score did not change on GH therapy but CPRS score improved at 6 and 12 months. CONCLUSIONS: Growth hormone replacement therapy in adults for 6 months increased lean body mass, total body water and exercise tolerance, and decreased body fat. Growth hormone replacement for longer than 6 months maintains the advantageous effects seen in shorter-term studies and may have additional effects on body fat distribution, muscle strength and psychological well-being.

Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults.

BACKGROUND AND OBJECTIVES: Excess impaired glucose tolerance and diabetes mellitus have been reported in hypopituitary adults on conventional replacement therapy including glucocorticoids. We investigated the effect of the glucocorticoid component on glucose tolerance and intermediary metabolites in hypopituitary adults. DESIGN: A 3-hour 75-g oral glucose tolerance test (OGTT) was performed on two study days, at least one week apart. On one study day, the glucocorticoid replacement morning dose was taken 60 minutes before the OGTT, and on the other it was left until after the OGTT. All other pituitary replacement therapies were kept unchanged on the two study days. PATIENTS: Eight hypopituitary adults (3 males and 5 females; aged 46-76 years) on conventional replacement therapy were studied. Their duration of hypopituitarism was mean (range) 15 (5-31) years. Their mean body mass index (BMI) was 28.4 (24.1-35.1) kg/m2. Their total daily cortisol dose was 26 (15-30) mg. MEASUREMENTS: Plasma glucose, insulin, non-esterified fatty acids (NEFA), glycerol and 3-hydroxybutyrate were measured at 30-minute intervals and plasma cortisol levels were measured hourly. RESULTS: Fasting glucose and insulin concentrations were similar on the glucocorticoid day (GD) and the non-glucocorticoid day (NGD) (glucose (mean +/- SD) 4.9 +/- 0.9 vs 4.4 +/- 0.5 mmol/l; insulin (median (range)) 5 (1-17) vs 2 (1-15) mU/l, respectively). Post-glucose glycaemia was higher on the GD than on the NGD with a significantly higher glucose area under the curve (AUC) (45.0 +/- 8.2 vs 38.9 +/- 11.7 mmol/l h, P < 0.05). Post-glucose insulinaemia was also higher on the GD than on the NGD with significantly higher insulin AUC (270 (47-909) vs 207 (46-687) mU/l h, P < 0.02). Impaired glucose tolerance was found in three patients on the GD, one of whom continued to have impaired glucose tolerance on the NGD. The areas under the curves of NEFA, glycerol and 3-hydroxybutyrate were not significantly different on the two days. On the NGD, plasma cortisol levels were undetectable (< 50 nmol/l) in all patients and on the GD the median (range) peak was 500 (330-740) nmol/l dropping to 125 (60-330) nmol/l at 180 minutes. The difference in glucose AUC between the two days correlated with the maximal plasma cortisol levels (Spearman's p = 0.83, P < 0.01). CONCLUSIONS: Glucocorticoid replacement therapy taken pre-prandially in hypopituitary adults induces mild elevations in circulating glucose and insulin levels even with acceptable plasma cortisol concentrations. Optimal regimens for glucocorticoid replacement require more study.