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Biomedical subjects

Ulla Feldt-Rasmussen

Publications and source records attributed to Ulla Feldt-Rasmussen.

At least 19 recordsLinked to original sources
PubMed2005

Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist.

CONTEXT: Pegvisomant is a GH receptor antagonist that blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin (SMS) analogs, does not suppress the activity of the GH-producing adenoma. OBJECTIVE: We assessed the effects of cotreatment with pegvisomant and SMS in acromegaly on GH secretion, IGF-I levels, and glucose tolerance. DESIGN, PATIENTS, AND INTERVENTIONS: Eleven patients with persistent disease despite previous therapy underwent the following fixed treatment algorithm: 1) on SMS therapy, 2) off therapy for 2 months, 3) 6-wk treatment with 10 mg/d pegvisomant, 4) 6-wk treatment with 15 mg/d pegvisomant, and 5) 3-month treatment with 15 mg pegvisomant plus SMS. Blood was sampled in the fasting state and during an oral glucose tolerance test. RESULTS: Total serum IGF-I levels (micrograms per liter) decreased after pegvisomant, but the lowest levels were obtained with cotreatment [458 +/- 67 (SMS), 562 +/- 78 (active), 376 +/- 51 (10 mg), 269 (15 mg), 195 +/- 24 (combined) (P < 0.0001)]. Free and bioactive IGF-I changed in a similar pattern. Steady-state pegvisomant levels (micrograms per liter) were obtained, but SMS cotreatment increased pegvisomant levels by 20% (P = 0.02) [2631 +/- 616 (10 mg), 6536 +/- 1413 (15 mg), 8030 +/- 1914 (combined)]. Pegvisomant increased endogenous GH levels (micrograms per liter), which was countered by SMS cotreatment [5.1 +/- 1.3 (SMS), 8.9 +/- 2.9 (active), 14.6 +/- 4.9 (10 mg), 19.7 +/- 6.5 (15 mg), 11.8 +/- 2.8 (combined) (P < 0.01)]. Plasma glucose levels (millimoles per liter) were highest during SMS and lowest during pegvisomant 15 mg [2-h oral glucose tolerance test: 10.3 +/- 0.7 (SMS), 8.9 +/- 0.7 (active), 7.2 +/- 0.7 (10 mg), 6.5 +/- 0.5 (15 mg), 8.0 +/- 0.8 (combined) (P = 0.02)]. CONCLUSIONS: Dual blockade of the GH axis with pegvisomant and a SMS analog is feasible in acromegaly.

Acromegaly↗
PubMed2005

Isolated growth hormone (GH) deficiency in adult patients: baseline clinical characteristics and responses to GH replacement in comparison with hypopituitary patients. A sub-analysis of the KIMS database.

BACKGROUND: Isolated growth hormone deficiency (IGHD) provides the ideal model to characterize GHD without interference from other pituitary deficiencies or their treatment. No study has addressed the question whether adult patients with IGHD differ in clinical presentation or in responsiveness to GH replacement from adult patients with multiple pituitary hormone deficiencies (MPHD) receiving conventional replacement therapy. PATIENTS AND METHODS: Data were retrieved from the outcomes research database KIMS (Pfizer international metabolic database). Patients with IGHD accounted for 9.6% (274/2868) of all GHD patients. Patients were separated according to the timing of onset. In the adult-onset (AO) group, 167 patients with IGHD were compared to 1992 patients with MPHD. In the childhood-onset (CO) group, 107 patients with IGHD were compared to 602 patients with MPHD. To assess the effect of GH replacement after one year, a longitudinal sub-analysis in the AO group was performed comparing 89 IGHD patients to 1234 MPHD patients. The same study was done in the CO group comparing 66 IGHD patients to 386 MPHD patients. Because IGHD patients were significantly younger than MPHD patients, data analysis was also performed after adjustment for gender and age. RESULTS: In the AO group, non-functioning and secreting pituitary adenomas were the most common primary diagnoses in both IGHD and MPHD. Medical history revealed a high prevalence of hypertension and fractures in both subgroups, but also of non-insulin dependent diabetes mellitus. The prevalence of obesity was high and the waist circumference was elevated. The lipid profile was unfavourable in both IGHD and MPHD. IGF-I concentration and SDS were comparable in both subgroup. Quality of life assessed by QoL-AGHDA was equally poor in both IGHD and MPHD. GH replacement therapy induced favourable changes without distinction. In the CO group, the most common cause in both subgroups was idiopathic. Fracture rate was similarly prevalent in both IGHD and MPHD. Obesity was prominent in both subgroups, but BMI and waist circumference were lower in IGHD. Adverse lipid changes were similarly found in both IGHD and MPHD. IGF-I concentration and SDS were significantly higher in the IGHD subgroup compared to the MPHD subgroup. The QoL-AGHDA score was equally abnormal in both IGHD and MPHD. GH replacement achieved similar significant improvement in both subgroups. CONCLUSIONS: GHD patients with AO-IGHD and AO-MPHD present with a similar clinical expression and respond similarly to GH replacement. Patients with CO-IGHD are less severely affected by GHD than CO-MPHD patients, but, nevertheless, both groups show a comparable adverse lipid profile and poor quality of life and respond favourably to GH replacement. These findings support the concept that GH alone is responsible for most if not all metabolic aspects of hypopituitary patients receiving conventional replacement therapy, regardless of age of onset or aetiology. As a consequence, GH replacement therapy not only has potential benefit in GHD patients with additional hormonal deficits, but also the indication of treatment must be extended to patients with isolated GHD.

Adenoma↗
PubMed2005

The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD.

OBJECTIVE: Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after stopping GH treatment. SUBJECTS AND METHODS: Twenty-six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty-six healthy subjects acted as age-, gender- and body mass index (BMI)-matched controls. RESULTS: The patients who did not have persistent GHD had significantly lower IGF-I values and whole-body, femoral neck and lumbar spine BMD compared to controls [0.994 +/- 0.10 vs. 1.114 +/- 0.11 g/cm2 (P = 0.003), 0.842 +/- 0.12 vs. 0.962 +/- 0.11 g/cm2 (P = 0.006) and 1.026 +/- 0.14 vs. 1.127 +/- 0.13 g/cm2 (P = 0.004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0.842 +/- 0.09 vs. 0.938 +/- 0.11, P = 0.04). Significant correlations were observed between all bone variables and IGF-I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients. CONCLUSION: In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF-I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH-IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF-I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary.

Absorptiometry, Photon↗
PubMed2005

Discontinuation of estrogen replacement therapy in GH-treated hypopituitary women alters androgen status and IGF-I.

OBJECTIVE AND DESIGN: Compared with their male counterparts, healthy females secrete more growth hormone (GH) and those with GH-deficiency have lower insulin-like growth factor I (IGF-I) levels and are less responsive to GH substitution. To test whether this gender difference is related to sex hormones we measured androgen status and IGF-I related parameters in 38 hypopituitary women (mean (range) age 41.5 (20-58) years) during continued GH substitution as compared with a control group of 38 healthy women matched for age and menopausal status. Twenty six patients were studied twice: with estrogen replacement and after 28 days of estrogen discontinuation in a randomised design. RESULTS: The patients were androgen deficient compared with controls (median, range), dehydroepiandrosterone sulphate (DHEAS): 185 (99-7800) nmol/l vs 4400 (820-13,000) nmol/l, P=or<0.001; androstenedione: 0.5 (0.1-7.1) nmol/l vs 4.3 (1.6-8.8) nmol/l, P=or<0.001; dihydrotestosterone (DHT): 0.13 (0.09-0.54) nmol/l vs 0.55 (0.09-0.89) nmol/l, P=or<0.001; testosterone: 0.28 (0.09-1.56) nmol/l vs 1.1 (0.71-2.24) nmol/l, (P=or<0.001); free testosterone: 0.004 (0.001-0.030) nmol/l vs 0.016 (0.001-0.030) nmol/l, P=or<0.001. The circulating levels of IGF-I, IGF-II, IGF-binding protein 1 (IGFBP-1), and IGFBP-3 did not differ between patients and controls. The subgroup of patients receiving hydrocortisone (HC) replacement (n=24) had significantly lower levels of androgens (suppressed by 80-100%) as well as IGF-I and IGFBP-3 as compared with the patients not receiving HC. IGF-I was correlated to free testosterone in patients (r=0.57, P=0.0005) as well as controls (r=0.43, P=0.008), and free testosterone was a significant positive predictor of IGF-I. Estrogen discontinuation induced an increase in IGF-I (167+/-15 vs 206+/-14 microg/l, P=0.005 and IGFBP-3 (3887+/-139 vs 4309+/-138 microg/l, P=0.0005). Estrogen discontinuation was associated with a significant increase in median (range) free testosterone (0.004 (0-0.02) vs 0.0065 (0-0.03) nmol/l, P=0.001) and a significant decrease in median (range) sex-hormone binding globulin (SHBG; 93 (11-278) vs 55.5 (20-142) nmol/l, P=0.001). DeltaIGF-I correlated with DeltaSHBG (r=-0.45 P=0.033) and DeltaIGFBP-3 (r=0.67 P=or<0.001). In a regression model DeltaE2, Deltatestosterone, DeltaSHBG and DeltaIGFBP-3 explained 93% of the variation in DeltaIGF-I. CONCLUSIONS: Androgen levels are low in hypopituitary women and free testosterone correlates with IGF-I. Discontinuation of estrogen replacement in these patients induces elevations in IGF-I as well as free testosterone, and DeltaIGF-I correlated positively with Deltafree testosterone. These effects may contribute to the gender differences observed in the GH-IGF axis in healthy adults as well as in the responsiveness of hypopituitary patients to GH substitution.

Adult↗
PubMed2004

Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults.

OBJECTIVE: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes. METHODS: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy. RESULTS: In the placebo-controlled trial, the FT(3) levels increased after 6 months in the GH-treated group, and in the open study the FT(3) levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction. CONCLUSION: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients.

Adult↗
PubMed2004

Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats.

Patients with growth hormone deficiency (GHD) have an increased risk of bone fractures. In these patients, the well-described decrease in bone mineral density (BMD) and content (BMC) may, however, not alone explain the increase in fracture rate. Accordingly, the aim of this study was to evaluate collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try to clarify the explanation for the increased fracture rate. The Dw-4 rat was used as a model for GHD. This strain of rats has an autosomal recessive disorder, reducing GH synthesis to approximately 10% and growth rate to approximately 40-50% when compared to normal control rats. Five male Dw-4 rats were examined at age 12 weeks and five healthy Lewis rats served as age-matched controls. The animals were examined for (1) bone mineral status by dual energy X-ray absorptometry (DXA) and ash weight/bone volume, (2) biomechanical properties, (3) serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and (4) collagen morphology of cortical bone from the right femurs was examined by scanning and transmission electron microscopy. A significant decrease was found in serum IGF-I, IGFBP-3 and biomechanical properties in GHD rats compared to controls (P < 0.009). While DXA-derived BMD was decreased, no significant difference was found in ash weight/bone volume. Electron microscopy showed a significant decrease in the number and a significant increase in the diameter of collagen microfibrils in GHD rats as compared to their controls (P < 0.009). In conclusion, we report for the first time that collagen morphology in bone is markedly altered in rats with isolated GHD. Whether similar conditions are present in GHD patients need further investigations. The changes described, however, may provide a co-explanation for the increased fracture rate in GHD.

Absorptiometry, Photon↗
PubMed2004

Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults.

Normal ageing is associated with a decline in spontaneous growth hormone (GH) secretion, and although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of GH responsiveness on dynamic testing, there are few data available on the response to GH replacement in older subjects. We have studied the baseline characteristics of 295 patients (173 males and 122 females) aged >65 years of age who began GH replacement therapy at the time of entry into the KIMS program (Pfizer International Metabolic Database) and the effects of GH replacement in 125 patients who completed at least 12 months of GH replacement therapy. Data were compared with those of 2469 (1249 males and 1220 females) patients aged <65 years with adult-onset GH deficiency (GHD). The patients were selected using strict criteria in accordance with the recommendations from the Growth Hormone Research Society. There was a higher proportion of pituitary adenoma relative to craniopharyngioma in the older age group (P<0.001), but there was no difference between groups in the degree of hypopituitarism (number of additional hormone deficiencies). Blood pressure, cholesterol and low-density lipoprotein (LDL) cholesterol levels were positively correlated with age, and older patients had a predictably higher prevalence of diabetes mellitus, coronary heart disease, stroke and history of hypertension. Quality of life (Assessment of Growth Hormone Deficiency in Adults (AGHDA) score) was impaired in both groups before the start of GH therapy. GH replacement doses were lower in older patients with GHD as compared with patients <65 years old. After 12 months of GH replacement, significant improvements were evident in waist circumference, waist/hip ratio, lean body mass, diastolic blood pressure, total and LDL cholesterol levels and AGHDA scores in patients aged <65 years. Similar significant reductions were evidenced in patients >65 years old compared with those observed in younger patients. The total number of adverse events was similar in younger and older patients with GHD. However, younger patients had more fluid retention-related adverse events such as headache, oedema and arthralgia; whereas, older patients with GHD had more adverse events related to glucose metabolism, cardiovascular events and neoplasms. These data indicate a positive benefit from GH replacement in older patients with hypopituitarism - particularly in relation to quality of life - using a lower dose of GH for replacement and with appropriate age-related safety controls.

Adenoma↗
PubMed2004

Combined dietary and pharmacological weight management in obese hypopituitary patients.

OBJECTIVE: The high prevalence of obesity and cardiovascular risk factors in hypopituitarism affirms the need for effective weight loss intervention. In this study, we investigated the combined effect of sibutramine, diet, and exercise in obese hypopituitary patients (HPs). RESEARCH METHODS AND PROCEDURES: In an open-label prospective intervention trial, 14 obese well-substituted nondiabetic HPs and 14 matched simple obese controls were allocated to 11-month treatment with sibutramine (10 to 15 mg), diet (600 kcal/d deficit), and exercise. Anthropometric indices and body composition (obtained from DXA scan) were assessed monthly for the first 5 months and thereafter every second month for the next 6 months. RESULTS: Mean (+/-SD) weight loss at 11 months was 11.3 +/- 4.8 kg in patients vs. 10.7 +/- 4.7 kg in controls. The HPs exhibited the same improvements in body composition, waist circumference, blood lipids, and fasting glucose as the simple obese. In a multivariate model, baseline weight, duration of growth hormone replacement therapy, and duration of pituitary disease explained 79% (p = 0.001) of the variation in weight loss at 4 months in the HPs. Only baseline weight and waist circumference could predict weight loss at 11 months. DISCUSSION: HPs are not resistant to weight loss therapy. Almost all will achieve at least 5% weight loss, and 60% can lose >10% weight within 11 months. However, the long-term effect on risk factors associated with type 2 diabetes and cardiovascular disease as well as on mortality needs to be established.

Adult↗
PubMed2004

Unsuccessful radioiodine treatment of a non-toxic goiter: a case report.

A middle-aged woman with a large right-sided, non-toxic goiter with low iodine uptake was admitted to the Department of Endocrinology with the purpose of volume reduction of the goiter. Thyroid pertechnetate scintigraphy showed homogenous and diffuse uptake in both lobes. Initially thyroxine treatment was given without volume-reducing effect. Radioiodine was administered twice to deliver a total radiation dose of 70 mCi iodine (I)-131. Subsequent pertechnetate scintigraphy showed that the normal-sized, normally functioning left lobe had disappeared after radioiodine, whereas the enlarged right lobe appeared unchanged. During the following years the size of the right lobe increased, and compression symptoms developed. The thyroid gland finally had to be removed by surgery. A large solitary thyroid nodule was removed, but no left lobe was identified. After surgery the patient had no thyroid tissue and had to be substituted by thyroid hormones. Despite good results of iodine treatment of non-toxic goiters, this case describes an unintended outcome leaving a patient without thyroid tissue, and a protracted course could have been avoided if the patient had undergone surgery earlier. However, this reported case should not discredit the use of radioiodine treatment of non-toxic goiters, but focus on patients with a single large solitary adenoma in whom this treatment may be inappropriate.

Denmark↗
PubMed2003

Thyrotropin-releasing hormone stimulation test in patients with pituitary pathology.

OBJECTIVES: To evaluate the value of the thyrotropin-releasing hormone (TRH) stimulation test in the diagnostic work-up of the thyroid function in patients with pituitary pathology. METHODS: To compare the thyrotropin (TSH) response and the absolute and fold changes after TRH administration in 35 patients with pituitary pathology and 26 normal subjects. RESULTS: Nine of the patients and 2 of the normal subjects had a pathological response. No difference in the thyrotropic response to TRH was found either for the actual values, or for the absolute or fold changes of TSH between the groups. CONCLUSION: The role of the TRH test in the evaluation of thyroid function in patients with pituitary pathology is modest. The best variables for evaluation of the presence of central hypothyroidism are still a free thyroxine estimate combined with an inappropriately low TSH.

Adolescent↗
PubMed2003

Ultrasonically measured horizontal eye muscle thickness in thyroid associated orbitopathy: cross-sectional and longitudinal aspects in a Danish series.

PURPOSE: To analyse horizontal extraocular muscle findings by ultrasound and exophthalmometry in a tertiary endocrinology centre series of patients with thyroid associated orbitopathy (TAO). METHODS: The 90 thyroid patients included underwent ultrasonic measurement of horizontal eye muscle thickness by a B-scan based technique carried out in addition to their general ophthalmic evaluation. As an indicator of mainly advanced TAO, longterm prednisone or cyclosporine A was given to many of the patients, and drug-resistant visual loss indicated decompression surgery in four of the 90 patients. Thirty-four patients underwent repeated muscle recordings over 15-49 months; this allowed for cross-sectional analysis and the outlining of longitudinal trends. RESULTS AND CONCLUSIONS: (A) Although marginally overlapping, all four muscle groups were significantly thicker in the study group than in normal control subjects. The mean of the sum of all four muscles was 16.8 mm (range 13.6-21.7 mm) in the control group versus 22.6 mm (range 15.5-36.4 mm) in the thyroid group. (B) Using the clinical NOSPECS grading, more advanced eye involvement was found to generally result in a higher exophthalmometric measurement of protrusion and eye muscle thickness. However, slender rectus muscles and/or normal exophthalmometric values might occur even in advanced orbitopathy. (C) Over a period of 2-4 years, only a few of 34 patients with satisfactory serial ultrasonic measurements returned to their premorbid ophthalmic status. Typically, the extraocular muscles kept their abnormal size after having become clinically quiescent (fibrotic). (D) We found no safe indication regarding disease stage, active or late, from the ultrasonic appearance of the muscle tissue. (E) Discrepancies between various normative eye muscle studies are discussed with regard to computer tomography and magnetic resonance imaging.

Adolescent↗
PubMed2003

High risk of adrenal insufficiency in adults previously treated for idiopathic childhood onset growth hormone deficiency.

The aim was to reevaluate a group of adults treated for idiopathic childhood onset GH deficiency (GHD) after 18 yr without GH treatment. Twenty-six (11 females) patients participated. All but two had isolated GHD. Childhood diagnosis was established by insulin tolerance test (ITT). The patients were retested with an ITT to evaluate adult GH status. In five patients, an arginine and a synacthen test were performed instead of an ITT. Eleven of 25 patients had a subnormal cortisol response to ITT or synacthen. Ten patients had a GH peak less than 3.0 microg/liter (0.5. +/- 0.5 microg/liter), whereas 16 patients displayed a normal GH response (12.3 +/- 10.6 microg/liter) after ITT. IGF-I values were decreased in the patients with a pathological retest as well as in patients with a normal GH response compared with controls (P < 0.005). In 26 idiopathic childhood onset GHD patients, 44% of the patients had developed adrenal insufficiency; 38.5% had persistent GHD in adulthood, using the same test in both childhood and adulthood. Patients having a normal GH test had decreased IGF-I levels, compared with controls, indicating impaired function of a seemingly normal GH axis. It is imperative that pituitary axes other than the GH axis are tested at regular intervals, even in the absence of GHD in adulthood.

Adrenal Insufficiency↗
PubMed2003

Abnormal sympathoadrenal activity, but normal energy expenditure in hypopituitarism.

In this study of 23 hypopituitary patients and 26 healthy controls, we have addressed whether the obese state of substituted hypopituitary patients is facilitated by abnormal sympathoadrenal activity or energy expenditure (EE). All patients received adequate substitution therapy including GH therapy. The investigation program included assessment of sympathoadrenal activity (urinary catecholamines), body composition (dual-energy x-ray absorptiometry), appetite sensations (visual analog scale), and EE (indirect calorimetry in respiration chamber). Twenty-four-hour urinary epinephrine adjusted for lean body mass and fat mass was significantly lower in patients compared with controls. GH and hydrocortisone were single negative predictors of urinary epinephrine. The major determinants of EE in patients were lean body mass and fat mass, explaining 96, 95, and 80% of the variance in 24-h EE, sleeping EE, and basal metabolic rate, respectively. Addition of urinary catecholamines explained another 1-4% of the variance in 24-h EE and basal metabolic rate, respectively. Lean patients exhibited significantly more hunger than obese patients and lean controls. In conclusion, hypopituitary patients have lower sympathoadrenal activity but normal EE, compared with healthy controls. This may reflect a central defect in hypopituitarism, however the possible impact of long-term GH and hydrocortisone treatment requires further attention.

Adrenal Glands↗
PubMed2003

Circulating leptin and thyroid dysfunction.

The identification and sequencing of the ob gene and its product, leptin, in 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. Since its discovery, leptin has been the subject of an enormous amount of work especially within the fields of nutrition, metabolism and endocrinology. Leptin is accepted as an adipose signal, and even though the underlying mechanisms are not fully clarified, leptin, in addition to the thyroid hormones, is believed to be involved in regulation during the switch from the fed to the starved state. It is not clear whether leptin and the melanocortin pathways interact with the thyroid axis under physiological conditions other than during starvation or in response to severe illness, both states in which the hypothalamo-pituitary-thyroid axis may be severely suppressed. In addition to the suggested central relationship between leptin and thyroid hormones, there might also be a peripheral relationship although this effect is not clear. Both thyroid hormones and leptin might be involved in the adaptive thermogenesis through mitochondrial uncoupling proteins and heat production because both thyroxine and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid hormone involvement in thermogenesis and regulation of uncoupling proteins. In this review, we have focused on leptin in relation to thyroid pathophysiology.

Animals↗
PubMed2002

Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, double-blind study.

OBJECTIVE: To characterise the effect of long-term low-dose growth hormone (GH) treatment on cardiac anatomy and function. METHODS: 20 patients with multiple pituitary hormone deficiencies, including severe acquired GH deficiency (GHD), were randomly assigned to GH or placebo (P) for 18 months. Echocardiographic measurements were performed at baseline and after 6, 12 and 18 months. RESULTS: At baseline, 8 of 20 patients had diastolic dysfunction (6 severe and 2 borderline), while only 1 had systolic dysfunction. None of the investigated parameters of diastolic or systolic function changed during treatment. CONCLUSION: In adult onset GHD, diastolic dysfunction was present in 40% of the patients. None of the investigated values were different after 18 months of GH compared to placebo.

Adenoma↗