Hypothyroidism incidence in and around pregnancy: a Danish nationwide study.

OBJECTIVE: Immunological changes in and after a pregnancy may influence the onset of autoimmune diseases. An increased incidence of hyperthyroidism has been observed both in early pregnancy and postpartum, but it remains to be studied if the incidence of hypothyroidism varies in a similar way. DESIGN: Population-based cohort study using Danish nationwide registers. METHOD: All women who gave birth to a singleton live-born child in Denmark from 1999 to 2008 (n = 403 958) were identified, and data on hospital diagnosis of hypothyroidism and redeemed prescriptions of thyroid hormone were extracted. The overall incidence rate (IR) of hypothyroidism during 1997-2010 and the IR in three-month intervals before, during and after the woman's first pregnancy in the study period were calculated and compared with the IR of hyperthyroidism. RESULTS: Altogether 5220 women were identified with onset of hypothyroidism from 1997 to 2010 (overall IR 92.3/100 000/year) and 1572 women developed hypothyroidism in the period from 2 years before to 2 years after birth of the first child in the study period. The incidence of hypothyroidism decreased during the pregnancy (incidence rate ratio (IRR) vs overall IR in the rest of the study period: first trimester: 0.89 (95% CI: 0.66-1.19), second trimester: 0.71 (0.52-0.97), third trimester: 0.29 (0.19-0.45)) and increased after birth with the highest level at 4-6 months postpartum (IRR 3.62 (2.85-4.60)). CONCLUSION: These are the first population-based data on the incidence of hypothyroidism in and around pregnancy. The incidence declined during pregnancy followed by a sharp increase postpartum. Notably, hypothyroidism as opposed to hyperthyroidism showed no early pregnancy increase.

Vitamin D-rich marine Inuit diet and markers of inflammation - a population-based survey in Greenland.

The traditional Inuit diet in Greenland consists mainly of fish and marine mammals, rich in vitamin D. Vitamin D has anti-inflammatory capacity but markers of inflammation have been found to be high in Inuit living on a marine diet. Yet, the effect of vitamin D on inflammation in Inuit remains unsettled. This led us to investigate the association between vitamin D and markers of inflammation in a population with a high intake of a marine diet. We studied 535 Inuit and non-Inuit living in West and East Greenland. Information concerning dietary habits was obtained by interview-based FFQ. Blood samples were drawn for analysis of 25-hydroxyvitamin D, high-sensitivity C-reactive protein (hsCRP) and chitinase-3-like protein 1(YKL-40). Participants were divided into three groups based on degree of intake of the traditional Inuit diet. The diet groups (Inuit diet/mixed diet/imported foods) were associated with vitamin D levels in serum (74·2, 69·8 and 52·9 nm; P < 0·001), hsCRP (1·6, 1·4 and 1·3 mg/l; P = 0·002) and YKL-40 (130, 95 and 61 ng/ml; P < 0·001), respectively. YKL-40 level decreased with rising vitamin D level in Inuit (Inuit diet P = 0·002; mixed diet P = 0·011). YKL-40 was lower in groups with higher vitamin D levels after adjusting for other factors known to influence inflammation (P < 0·001). This was not seen for hsCRP. In conclusion, vitamin D and markers of inflammation vary in parallel with the intake of the marine Inuit diet. Vitamin D levels were inversely associated with YKL-40 levels, but no association with hsCRP was found. The hypothesised anti-inflammatory effect of vitamin D was not supported. Other factors in the marine diet may be speculated to influence inflammation.

Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics.

Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X-chromosome inactivation and parent-of-origin of the extra X-chromosome have been suggested to influence cognitive function and psychological traits. These issues have not been clarified for KS patients. We studied X-chromosome inactivation pattern, CAG repeat length and parent-of-origin in relation to educational and cohabitation status, personality and autism traits, psychological distress, cognitive function and brain volumes in 73 KS patients and 73 controls. Grey matter (GM) volume of left insula was significantly decreased in KS patients with skewed X-inactivation (z = 5.78) and we observed a borderline significant difference in global brain matter volume where KS patients with skewed X-chromosome inactivation tended to have smaller brains. Skewed X-inactivation, CAG repeat length and parent-of-origin were not correlated with educational and marital status, personality traits, autism traits, and psychological distress, prevalence of depression and anxiety or cognitive function. Interestingly our results regarding brain volumes indicate that X-inactivation has an influence on GM volume in left insula and might also be related to global GM volume, indicating a possible effect of X-linked genes on the development of GM volume in KS patient. Skewed X-inactivation, CAG repeat length and parent-of-origin have no impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov (Clinical trial NCT00999310)).

Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study.

OBJECTIVE: To examine the association between maternal hyper- and hypothyroidism and the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in the child. DESIGN: A population-based cohort study. SETTING: Singletons liveborn in Denmark between 1991 and 2004. POPULATION: A total of 857 014 singletons alive and living in Denmark at the age of 3 years. METHODS: Information on the diagnosis and/or treatment of maternal thyroid disease and the neurodevelopmental disorders ADHD and ASD in the child was obtained from Danish nationwide registers. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence interval (95% CI) for risk of ADHD and ASD in children born to mothers with thyroid dysfunction, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: ADHD and ASD in the child. RESULTS: Altogether, 30,295 singletons (3.5%) were born to mothers with thyroid dysfunction. Maternal hyperthyroidism diagnosed and treated for the first time after the birth of the child increased the risk of ADHD in the child (adjusted HR 1.23; 95% CI 1.05-1.44), whereas hypothyroidism increased the risk of ASD (adjusted HR 1.34; 95% CI 1.14-1.59). No significant association was seen for maternal diagnosis and treatment prior to the birth of the child. CONCLUSIONS: Children born to mothers diagnosed and treated for the first time for thyroid dysfunction after their birth may have been exposed to abnormal levels of maternal thyroid hormone already present during the pregnancy, and this untreated condition could increase the risk of specific neurodevelopmental disorders in the child.

Intake of traditional Inuit diet vary in parallel with inflammation as estimated from YKL-40 and hsCRP in Inuit and non-Inuit in Greenland.

BACKGROUND: Chronic low-grade inflammation is involved in the initiation and progression of atherosclerosis and ischemic heart disease. This was rare in pre-western Inuit who lived on a diet that consisted mainly of marine mammals rich in n-3 fatty acids. OBJECTIVES: To assess the association between biomarkers of inflammation and the intake of traditional Inuit diet in addition to Inuit ethnicity. METHODS: YKL-40 and hsCRP were measured in serum from 535 Inuit and non-Inuit living in the capital city Nuuk in West Greenland or in the main town or a settlement in rural East Greenland. Dietary habits were assessed by an interview-based food frequency questionnaire. RESULTS: The participation rate was 95%. YKL-40 was higher in Inuit than in non-Inuit (p < 0.001), in Inuit with a higher intake of traditional Inuit diet (p < 0.001), and in Inuit from rural compared to urban areas (p < 0.001). It also rose with age (p < 0.001), alcohol intake (0.019) and smoking (p < 0.001). Inuit had higher hsCRP compared to non-Inuit (p = 0.003) and hsCRP increased in parallel with intake of traditional Inuit foods (p < 0.001). Alcohol associated with a decrease in hsCRP in Inuit (p = 0.004). YKL-40 and hsCRP increased with higher intakes of traditional Inuit diet after adjusting for ethnicity, gender, age, smoking, alcohol intake and BMI. CONCLUSIONS: Biomarkers of inflammation vary in parallel with the intake of traditional Inuit diet. A diet based on marine mammals from the Arctic does not reduce inflammatory activity and it may be speculated that markers of inflammation reflect the disease rather than the cause of the disease.

Acute presentation of craniopharyngioma in children and adults in a Danish national cohort.

We aimed to study the occurrence of acute-onset symptoms at initial presentation in a national Danish cohort of patients with childhood- or adult-onset craniopharyngioma, and to investigate potential risk factors for acute presentation. Medical records of 189 consecutive patients (39 children, 150 adults) presenting with craniopharyngioma during the period 1985-2004 were reviewed, and data regarding initial symptoms, neuroimaging results, vision and pituitary function were systematically collected. Acute symptoms preceding hospital admission were noted. Subgroup analyses were based on age, gender and calendar year period. Potential risk factors for acute presentation were analysed through uni- and multivariate analyses. Acute symptoms were reported in 24 (13%) patients. Acute visual symptoms, headache, nausea or vomiting were most frequently reported, and acute symptoms were more frequent among children (28%) than among adults (9%) (P < 0.01). There were no differences according to sex or calendar year period. Hydrocephalus was present in half of childhood cases and one-fifth of adult patients (P < 0.001). Intra-tumour haemorrhage was seen in two cases. Acute symptoms were more frequent among patients with tumours occupying the third ventricle (P < 0.01), radiologic signs of calcification (P < 0.05) or hydrocephalus (P < 0.01). In multivariate analysis, however, only childhood onset (P < 0.05) and calcification (P < 0.05) were independent risk factors for acute presentation. Craniopharyngioma presented with acute symptoms in 13% of patients. Childhood onset and radiologic signs of calcification were independent risk factors for acute presentation. Intra-tumour haemorrhage was rare.

Hypothyroidism and thyroid substitution: historical aspects.

The last part of the 19th century was a period of great achievements in medicine and endocrinology. The thyroid gland evolved from being considered a rudimentary structure to an organ related to specific diseases. The singular importance of iodine became acknowledged. Graves-Basedow's disease was described. Surgical treatment evolved with extraordinary speed. Theodor Kocher observed that the clinical picture in patients after total thyroidectomy was similar to the one seen in cretinism. In 1850, the first case of hypothyroidism or myxedema was described. Less than 50 years later, effective treatment was introduced. Another 50 years later, autoimmune thyroiditis was ascertained as the most frequent cause of hypothyroidism (in areas with no iodine deficiency). This paper gives a short survey of the history of hypothyroidism and its treatment.

Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults.

We studied the incidence of craniopharyngioma in Denmark during the period 1985-2004 and estimated worldwide incidence rates (IR) of craniopharyngioma based on a literature review. Craniopharyngioma patients diagnosed during the period 1985-2004 were identified from the Danish National Patient Registry, the Danish Cancer Registry and regional registries. Medical records were reviewed. Danish population data were obtained from Statistics Denmark. European and World population data were obtained from EU and WHO homepages. Prior studies providing data on craniopharyngioma IRs were identified via PubMed and, if appropriate, were included in a weighted analysis estimating overall and children's IRs of craniopharyngioma. IRs are given as new cases per million per year. We identified 189 patients with new verified (162) or probable craniopharyngioma. The overall WHO World-standardised incidence rate was 1.86 (1.60-2.14) for all ages and 2.14 (1.53-2.92) for children (age <15 years). Peak incidence rates were observed in age groups 5-9 and 40-44 years. Fifteen prior studies (including 1,232 craniopharyngioma cases) were identified. Seven and 11 studies, respectively, were eligible for weighted all-ages and childhood population IR analyses, yielding summary IRs of 1.34 (1.24-1.46) (all ages) and 1.44 (1.33-1.56) (children). We have provided a detailed survey of the incidence of craniopharyngioma in Denmark during a recent 20-year period. Overall IR of craniopharyngioma in Denmark was 1.86 (1.60-2.14) as compared to 2.14 (1.53-2.92) among children. Weighted estimates of craniopharyngioma world IRs were 1.34 (1.24-1.46) in all ages and 1.44 (1.33-1.56) among children.

Excess mortality in women with pituitary disease: a meta-analysis.

BACKGROUND: Increased mortality has been reported in patients with pituitary disease, with some studies showing higher standard mortality rates (SMR) in women than in men. OBJECTIVE: To assess overall SMR for men and women with benign pituitary disease without excessive ATCH or GH secretion and to investigate associations between SMR and time period of diagnosis. DESIGN: From searches in PubMed, Embase and Web of Science databases, and reference lists of major reviews and original articles, we included original studies providing SMR values and 95% confidence intervals (CI) for men and women separately. Thirty articles were studied in detail. Six studies were eligible for the meta-analysis of sex-specific mortality, and seven for the analysis of association between SMR and diagnosis period. RESULTS: Individual studies (total 5412 patients) reported total SMR values (men and women together) ranging from 1.21 to 3.80. SMR varied from 0.98 to 3.36 in men and from 2.11 to 4.54 in women. Weighted SMR values were significantly higher in women (2.80; CI 2.59-3.02) than in men (2.06; CI 1.94-2 20) (P < 0.0001). SMR was negatively correlated with first year of diagnosis in individual studies (partial correlation analysis controlling for sex, P = 0.017), and approached normal in recent studies in men but not in women. CONCLUSIONS: In our meta-analysis of patients with pituitary disease without ACTH or GH excess, SMR was significantly higher in women than in men. SMR reached normal levels in men treated in recent decades, but remained elevated in women.

Evaluating iodine deficiency in pregnant women and young infants-complex physiology with a risk of misinterpretation.

OBJECTIVE: To review methods for evaluating iodine deficiency in pregnant women and young infants and to discuss factors to be considered in the interpretation of their results. DESIGN: Review of the literature regarding the various methods available for assessing iodine status. SETTING: Population surveys and research studies. SUBJECTS: Pregnant women and young infants. RESULTS: Several factors to consider when assessing iodine status in pregnant women and young infants include: 1) the urinary iodine (UI) concentration (microg l-1) is not interchangeable with 24 h UI excretion (microg per 24 h); 2) the concentration of iodine in a spot or casual urine sample cannot be used to diagnose iodine deficiency in an individual; 3) a moderate fall in the concentration of serum free T4 during pregnancy is not a sign of maternal iodine deficiency; 4) an increase in the concentration of serum thyroglobulin (Tg) during pregnancy is not a sign of maternal iodine deficiency; 5) a higher concentration of TSH and Tg in cord blood than in maternal blood is not a sign of iodine deficiency in the mother or neonate; and 6) thyroid function in a full-term foetus, a neonate or a small child is not more sensitive to a mild iodine deficiency than in the mother. CONCLUSIONS: If the iodine status of pregnant women and small children is not to be misjudged, the above six factors need to be taken into account.

Hypopituitarism and mortality in pituitary adenoma.

BACKGROUND AND OBJECTIVE: Previous studies on hypopituitarism and mortality have concluded that insufficient pituitary function is associated with decreased survival. For several reasons the results are difficult to compare - particularly because definitions and treatment of hypopituitarism have varied and various underlying disorders have been included. The purpose was to assess the relationship between mortality and pituitary function. PATIENTS AND DESIGN: One hundred and sixty consecutive patients (99 men and 61 women) with functionless, suprasellar pituitary adenoma. All were operated on transsphenoidally during the period 1985-1996. Additional radiotherapy was given to 29 patients. Mortality was calculated 12.4 years (median, range 8.1-19.9) after operation. Postoperative hormonal deficits were treated in most, though GH substitution was given only to a minority of patients. RESULTS: Postoperatively 30% of the patients had normal pituitary function (normal adrenocortical, thyroid and gonadal function), 26% were panhypopituitary and 36% had partial pituitary insufficiency. Forty-one patients had died (34.7 expected) yielding a standard mortality ratio (SMR) of 1.18 (95% confidence limits (CI) 0.87-1.60). SMR was significantly increased in women (1.97, CI 1.20-3.21) but not in men (0.83, CI 0.55-1.26). SMR in patients with normal pituitary function, panhypopituitarism and partial insufficiency were not different from that in the general population. SMR in hypopituitary women was substantially higher than in men with pituitary insufficiency. Treatment with growth hormone in GH-deficient patients did not influence survival. CONCLUSION: Pituitary surgery for nonfunctioning adenoma and subsequent pituitary insufficiency had no effect on mortality in men, but was associated with significantly increased mortality in women. Suboptimal hormonal substitution in women may play a role.

Is there a need to redefine the upper normal limit of TSH?

Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been discussed as being a risk factor for the development of overt thyroid dysfunction and for a number of clinical disorders. The diagnosis critically depends on the definition of the upper normal limit of serum TSH as, by definition, free thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have been conventionally used to diagnose an elevated TSH serum concentration. Recent data from large population studies have suggested a much lower TSH cut-off with an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of subjects from the general population studies aiming at assessing TSH reference intervals (no personal or family history of thyroid disease, no thyroid antibodies and a normal thyroid on ultrasonography) did not result in an unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the available evidence for lowered upper TSH cut-off values and their potential therapeutic implications there is presently insufficient justification to lower the upper normal limit of TSH and, for practical purposes, it is still recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as intervening with thyroxine treatment in such subjects, is probably doing more harm than good.

Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma.

BACKGROUND AND OBJECTIVE: There is agreement in the literature that pituitary apoplexy is a rare disorder. As our experience differs from this view, we analysed the incidence in patients operated on for a nonfunctioning pituitary adenoma. PATIENTS AND DESIGN: One hundred ninety-two consecutive patients with a suprasellar, clinically inactive adenoma operated on during the period 1985-1996 were retrospectively reviewed. A diagnosis of pituitary apoplexy was made from relevant neurological symptoms together with pertinent findings at operation. RESULTS: Pituitary apoplexy occurred in 41 patients (21%), in 23 patients within 12 days prior to the operation. The male/female ratio was 1.9. Median follow-up time was 13.7 years (range 8.9-19.9). During this period, 12 patients had died, yielding a standard mortality ratio of 1.09 (95% CI 0.62-1.92), similar to that in the patients who had not sustained pituitary apoplexy. Postoperatively, 24% of the patients had normal pituitary function, 38% were panhypopituitary and partial pituitary insufficiency was present in 38%. Subnormal GH secretion was present in virtually all patients tested. Two patients died within 60 days of surgery and in two no or incomplete data were available, although they most likely were panhypopituitary. CONCLUSION: Most of our findings add little to what is known about pituitary apoplexy. On one point, however, they are contrary to previously presented data. We found a much higher incidence of pituitary apoplexy despite rather rigorous criteria for the diagnosis. The outcome as regards survival and endocrine function was not different from that in patients with a nonfunctioning adenoma who did not suffer pituitary apoplexy.

Cold adaptation and thyroid hormone metabolism.

Resting oxygen consumption and energy expenditure is sensitive to slight alterations in thyroid function. This means that timing and magnitude of cold adaptation would to some extent depend on thyroid function. Local thyroid hormone metabolism is important for energy expenditure and dissipation of heat in special tissues. Recruitment of brown adipocytes and upregulation of uncoupling protein 1 in mitochondria depends on high tissue T3 concentrations. Most of this T3 is derived from local 5' deiodination of T4. Brown fat is vital for cold exposed mice and rats, and may be important for temperature adaptation in human neonates. The role of thyroid hormone metabolism in adult human cold adaptation has not been finally clarified. Hypothetically, cold exposure may enhance T3 production by deiodination of T4 in skeletal muscle, which may enhance heat production in muscle via a change in muscle fiber type. Another hypothetical possibility is recruitment of brown adipocytes embedded in white adipose tissue in human adults. Understanding cold adaptation in human adults may lead to development of new drugs against obesity.

Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl.

OBJECTIVE: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. DESIGN: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. METHODS: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. RESULTS: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. CONCLUSIONS: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

Low socio-economic status and familial occurrence of goitre are associated with a high prevalence of goitre.

The occurrence of goitre is dependent on genetic and environmental factors, but the associations with socio-economic and life-style factors have only been examined briefly. A cohort of 4649 participants from the general population was examined with questionnaires, thyroid ultrasonography, clinical examination and blood tests. Data were analysed in linear models and logistic regression analysis. Thyroid volume and serum thyroglobulin were closely associated with educational level with higher values in the group with the lowest levels of education (p < 0.001). The same pattern applied to thyroid multinodularity at ultrasonography (p = 0.002) and palpable goitre (p = 0.01). Physical activity in leisure time was negatively associated with thyroid enlargement (p = 0.02) and serum thyroglobulin (p < 0.001). These associations diminished markedly if adjustment was made for smoking habits, alcohol consumption and iodine intake. Familial occurrence of goitre was associated with goitre prevalence (Odds Ratio 2.5, 95% CI: 1.6-3.9), but did not confound the socio-economic associations. In conclusion, social imbalances in the occurrence of goitre were identified. These imbalances could in part be explained by differences in smoking habits and iodine intake.

High occurrence of thyroid multinodularity and low occurrence of subclinical hypothyroidism among tobacco smokers in a large population study.

Tobacco smoking increases the risk of goitre and Graves' disease, but the association with thyroid nodularity and hypothyroidism has not been settled. We investigated 4649 subjects from the general population with questionnaires, thyroid ultrasonography and blood tests. The results were analysed in multivariate regression models. Tobacco smoking was associated with an increased prevalence of thyroid multinodularity (odds ratio (OR) 1.9; 95% confidence interval (CI) 1.4-2.5), but not with increased prevalence of solitary thyroid nodules. The tendency was for a stronger association in the area with the most pronounced iodine deficiency (P for interaction=0.08). Lower levels of serum TSH were found among tobacco smokers (P<0.001), but this association disappeared when adjustment was made for thyroid nodularity and thyroid Volume. The prevalence of elevated TSH levels was markedly reduced among smokers (OR 0.47; 95% CI 0.33-0.67). No association was found between smoking and hyperthyroidism. The observed associations seem to be explainable by the blocking of iodine uptake and organification in the thyroid by thiocyanate, a degradation product of cyanide in tobacco smoke.

Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly.

Lanreotide Autogel is a new long-acting aqueous preparation of lanreotide for the treatment of acromegaly and is administered by deep sc injection from a small volume, prefilled syringe. The aim of this study was to evaluate the efficacy and safety of this new long-acting formulation in a large population of acromegalic patients previously responsive to lanreotide 30 mg, im (sustained release microparticle formulation). Lanreotide Autogel was administered by deep sc injection every 28 d to 107 patients (54 males and 53 females; mean age, 54 +/- 1.2 yr). All patients had been treated with lanreotide (30 mg) for at least 3 months before study entry and had a mean GH level less than 10 ng/ml after at least 4 subsequent im injections every 14 d (48%), 10 d (32%), or 7 d (20%). Treatment was switched from lanreotide 30 mg injected every 14, 10, or 7 d to 60, 90, or 120 mg lanreotide Autogel, respectively, every 28 d. After three fixed dose injections of lanreotide Autogel, mean lanreotide levels were similar to those obtained at steady state with lanreotide 30 mg. During lanreotide Autogel treatment, the control of acromegalic symptoms was comparable with that previously achieved during lanreotide 30 mg treatment. After 3 injections of lanreotide Autogel, mean GH (2.87 +/- 0.22 ng/ml) and IGF-I (317 +/- 15 ng/ml) values were comparable with those recorded at the end of lanreotide 30 mg treatment (GH, 2.82 +/- 0.19 ng/ml; IGF-I, 323 +/- 16 ng/ml). GH levels below 2.5 ng/ml and age-/sex-normalized IGF-I were achieved in 33% and 39% of patients during lanreotide 30 mg and lanreotide Autogel treatment, respectively. Diarrhea, abdominal pain, and nausea were reported by 38%, 22%, and 18% of patients during lanreotide 30 mg treatment and by 29%, 17%, and 9% of patients, respectively, during lanreotide Autogel treatment. In conclusion, this clinical study shows that lanreotide Autogel is at least as efficacious and well tolerated as lanreotide 30 mg. This new long-acting lanreotide formulation, lanreotide Autogel, which is administered from a small volume, prefilled syringe by deep sc injection, is therefore likely to improve the acceptability of medical treatment for patients requiring long-term somatostatin analog therapy.