Progress, challenges and perspectives in the management of hypopituitarism.

Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.Diagnosis typically involves a thorough clinical evaluation, hormone level assessments, and neuroimaging studies to identify underlying causes. Treatment aims to replace deficient hormones and address the underlying cause and related complications when possible. In this special issue we address diagnosis, comorbidities, and management of hypopituitarism. We hope that it will help healthcare professionals to manage their patients.

Update on the use of long-acting growth hormone in children.

PURPOSE OF REVIEW: After extensive research and many years of waiting, long-acting growth hormone (LAGH) formulations have finally become a reality in clinical practice and emerge as a potential solution to address the challenges of daily injections of recombinant human GH (rhGH). In this review, we present a brief history of the development of LAGH and provide a critical analysis of the existing literature on the five LAGH available and approved to date for treatment in children. RECENT FINDINGS: In clinical trials, LAGH therapy has shown noninferiority compared with daily rhGH therapy in promoting linear growth in children with GH deficiency, with similar rates of adverse events. SUMMARY: In the real world, many questions still need to be answered, such as whether a specific group of patients will benefit most from the weekly injection, whether compliance will be better compared with daily rhGH, whether long-term efficacy, monitoring and safety profile will be the same for the different LAGH compounds, and whether the cost-effectiveness will justify their use in different settings.

Growth hormone (GH) deficiency and GH replacement therapy in patients previously treated for Cushing's disease.

Several complications associated with active Cushing's disease may persist even years after complete and successful therapeutic remission of hypercortisolism. Growth hormone deficiency (GHD) shares many clinical features seen in patients with Cushing's disease, and its presence after disease remission (GHD-CR) might negatively influence and potentially worsen the systemic complications caused by previous hypercortisolism. GHD-CR is more prevalent in women, and compared to other causes of GHD, patients are younger at the onset of the pituitary disease, at diagnosis of GHD-CR and at start of GH therapy; prevalence of pituitary macroadenomas and visual abnormalities are lower, while prevalence of diabetes, hypertension, low bone mass, fractures, and worst quality of life, are higher. Serum IGF-1 levels are not useful for the diagnosis of GHD-CR and the application of GH stimulating tests requires some special attention in addition to the general recommendations for detecting GHD from other etiologies. In patients with active hypercortisolism, GH secretion is completely suppressed, but it may spontaneously and progressively recover over the years following successful therapy, meaning that GH testing may be performed at an appropriate time after remission for the correct diagnosis. Moreover, if the patient presents concomitant adrenal insufficiency, GH testing should only be carried out under adequate cortisol replacement therapy. GH therapy in children with GHD-CR improves adult height in the majority of patients, while GH therapy in adults has been associated with improvements in body composition, lipid profile and quality of life, but also with worsening of glucose metabolism.

Acromegaly and pregnancy: a systematic review and meta-analysis.

PURPOSE: To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. METHODS: This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17. RESULTS: Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%). CONCLUSION: Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.

Treatment of non-functioning pituitary adenoma with cabergoline: a systematic review and meta-analysis.

PURPOSE: To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. RESULTS: Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). CONCLUSIONS: Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020206778.

Individual sensitivity to growth hormone replacement in adults.

The metabolic actions of growth hormone (GH) last a lifetime and involve several physiological functions associated with the control of body composition, energy metabolism, water regulation, immune response, cardiovascular performance, physical and mental work. Adult patients with GH deficiency (GHD) present a constellation of clinical findings, which include increased total and visceral body fat, low bone and muscle mass, reduced muscle strength, impaired anaerobic physical capacity, unfavorable cardiovascular profile, and poor quality of life. Recombinant human GH (rhGH) therapy has been proved to reverse or improve many abnormalities associated with GHD in adult life, but the therapeutic response is highly variable among patients and influenced by multiple factors, which are the main focus of this narrative review. Given the individual sensitivity of adult GHD patients to rhGH replacement, dose regimens evolved from weight-based to individualized dose-titration strategies, which improved efficacy and reduced the frequency of adverse events. Individual tailoring and maintenance doses of rhGH are mainly influenced by age, age at GHD onset, sex, body mass index, baseline GH status, quality of life and other pituitary hormone replacements. In addition, genetic background and poor adherence due to patient or product-related factors might play a role in the responsiveness to rhGH therapy. There have been attempts to develop predictive mathematical models to distinguish good and poor responders to rhGH therapy, but thus far none of them have been prospectively tested and validated in a large cohort of adult GHD individuals.

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

Personality type, eating behaviour and suicide risk in women in treatment for obesity.

OBJECTIVES: To determine the personality types of women in treatment for obesity and the associations among their personality characteristics, eating behaviour and suicide risk. SUBJECTS: Sixty women in pharmacological treatment for obesity (clinical group: CG) and 60 women post-bariatric gastric bypass surgery (surgical group: SG) were evaluated. METHODS: This was an observational and transversal study conducted in a specialized outpatient unit. Personality types were evaluated through the Myers-Briggs Type Indicator (MBTI) test. A semi-structured questionnaire that investigated sociodemographic and lifestyle characteristics was applied, along with the Binge Eating Scale (BES) and the Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Among the 16 possible personality types, the ISFJ (Introversion, Sensing, Feeling, Judging) and ESFJ (Extraversion, Sensing, Feeling, Judging) types were more frequent. In the SG, 32% of the participants presented with the ISFJ type, and 18.3% presented with the ESFJ type. In the CG, 33% presented with the ISFJ type and 25% presented with the ESFJ type. There was a higher prevalence of binge eating behaviour in the CG (Cohen's d: - 0.47; p < 0.0001) and a higher tendency to graze in the SG (p = 0.005). Participants with introverted attitudes showed a higher prevalence of severe binging (13.3% vs 3.3%, p = 0.07), suicidal thoughts throughout life (STTL) (69.5% vs 45.1%, p = 0.007), and recent suicidal thoughts (RSTs) (30.4% vs 11.7%, p = 0.01) in comparison to extraverted participants. BMI was associated with a higher chance of STTL (37.96 ± 6.41 kg/m2 with STTL vs 33.92 ± 4.68 kg/m2 without STTL; p = 0.01) in the CG compared to the SG. RSTs were associated with BMI in the SG (34.47 ± 3.86 kg/m2 with RSTs vs 30.61 ± 5.72 kg/m2 without RSTs; p = 0.01). In the multivariable analysis, personality type (ISFJ) was an independent predictor of STTL (OR: 3.6; CI 1.3-10.2; p = 0.01) and Suicidal Behaviour (SB) (OR: 9.7; CI 2.44-38.9; p = 0.001). Conversely, while BMI was an independent factor associated with binge eating, personality type was not. CONCLUSIONS: Women who were in pharmacological treatment for obesity or were post-bariatric surgery present specific types of personality. Introversion was associated with a higher BMI and a higher risk of suicidal thoughts. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Fertility issues in aggressive pituitary tumors.

The management of aggressive pituitary adenomas represents a special clinical challenge, and usually involves a combination of surgery, radiotherapy and pharmacological agents to control tumor growth and hormone abnormalities. Fertility is commonly affected in these patients due to compressive effects of the tumor, pituitary hormone dysfunction or as a result of the multiple therapies. The initial approach to restore fertility involves the reduction of tumor volume by the use of dopamine agonists in prolactinomas and by surgery in other pituitary adenomas. Somatostatin analogues are alternative options for GH, ACTH and TSH-secreting tumors. When present, pituitary deficiencies should be appropriately treated, particularly GH deficiency that has been associated with poor pregnancy rates in hypopituitary patients. Other therapies for aggressive pituitary tumors, such as invasive surgery, radiotherapy and temozolamide, may lead to infertility. In such cases, fertility preservation strategies might be considered and discussed with the patient desiring conception before or during treatment. In men and women with hypogonadotropic hypogonadism, administration of gonadotropins or pulse GnRH has resulted in satisfactory pregnancy rates. If spontaneous gestation is not achieved, assisted reproduction techniques can be employed as the last line of treatment. In any context, pre-conception counseling and care are essential as pregnancies in women with aggressive pituitary tumors should always be considered high risk.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

Metabolic syndrome and its components in adult hypopituitary patients.

PURPOSE: To evaluate the prevalence of metabolic syndrome (MetS) and its components in adult hypopituitary patients. PATIENTS AND METHODS: Retrospective, cross-sectional analysis of a cohort of hypopituitary adult patients followed in a single reference center for pituitary diseases. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Patients with 18 years or older, presenting two or more anterior pituitary deficiencies associated or not with diabetes insipidus (DI), were included, while patients with hypopituitarism due to Acromegaly or Cushing's disease were excluded. RESULTS: We studied 99 hypopituitary patients (52 males, mean age 50.1 ± 16.3 years, mean age at diagnosis 33.7 ± 17.6 years) who have been followed for a mean time of 15.9 ± 10.1 years. Hypothalamic-pituitary tumors and non-tumoral etiologies were observed in 53.4% and 46.6% of the cases, respectively. FSH/LH, GH, TSH, ACTH deficiency and DI was present in 99%, 98.6%, 96%, 81.8%, and 23.2%, respectively. The prevalence of MetS was 39.4% and was significantly higher in patients older than 50 years (p = 0.02), overweight/obese (p < 0.001), with hypopituitarism diagnosed in adult life (p = 0.02), who did not replace GH (p = 0.004) and in smokers (p = 0.007). In the logistic regression model, body mass index (BMI) and GH replacement were significantly associated with the presence of MetS. Reduced HDL cholesterol was the most prevalent component of MetS in hypopituitary patients. CONCLUSIONS: MetS is a common finding in adult hypopituitary patients, which is mainly influenced by increased BMI and untreated GH deficiency. Trial Registration number (Plataforma Brasil): CAAE 51008815.2.0000.0096 (May 31, 2017) .

OFF-LABEL USE AND MISUSE OF TESTOSTERONE, GROWTH HORMONE, THYROID HORMONE, AND ADRENAL SUPPLEMENTS: RISKS AND COSTS OF A GROWING PROBLEM.

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to "adrenal fatigue," an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Novel SUZ12 mutations in Weaver-like syndrome.

SUZ12 is a core component of polycomb repressive complex 2 (PRC2) along with EZH2 and EED. Recently, germline mutations in the SUZ12, EZH2 and EED genes have been reported in Weaver syndrome (WS) or Weaver-like syndrome, suggesting a functional link between PRC2 deficits and WS. However, only one case of a SUZ12 mutation presenting with Weaver-like syndrome has been reported. Here, we report a missense and a frameshift mutation in SUZ12 (c.1797A>C; p.Gln599His and c.844_845del; p.Ala282Glnfs*7), both of which are novel, in two individuals. Their clinical features included postnatal overgrowth, increased bifrontal diameter, large ears, round face, horizontal chin crease and skeletal anomalies, but did not fulfill the WS diagnostic criteria. These data provide strong evidence that SUZ12 mutations cause Weaver-like syndrome.

Different Cerebellar Ataxia Phenotypes Associated with Mutations of the PNPLA6 Gene in Brazilian Patients with Recessive Ataxias.

Autosomal recessive cerebellar ataxias (ARCAs) represent a heterogeneous group of inherited disorders. The association of early-onset cerebellar ataxia with hypogonadotropic hypogonadism is related to two syndromes, known as Gordon Holmes syndrome (GHS-ataxia and pyramidal signs with hypogonadotropic hypogonadism) and Boucher-Neuhäuser syndrome (BNS-ataxia with chorioretinal dystrophy). Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations. We reported two Brazilian patients with sporadic, progressive cerebellar ataxia, associated with hypogonadotropic hypogonadism, in whom the GHS and BNS were confirmed by the demonstration of compound heterozygote mutations in the PNPLA6 gene. Genetic analysis of the patient 1 revealed compound heterozygous mutations, one allele in exon 34 and the other allele in exon 29. Genetic exam of the patient 2 also demonstrated compound heterozygous mutations. Three were novel mutations. The missense mutation c.3373G> A, found in the BNS patient, was previously related to Oliver-McFarlane syndrome. These different mutations in this gene suggest a complex phenotype associated disease spectrum.

Challenges in the diagnosis and management of acromegaly: a focus on comorbidities.

INTRODUCTION: Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. METHODS: We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. FINDINGS AND CONCLUSIONS: Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.

Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management.

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.

Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine.

CONTEXT: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. OBJECTIVE: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). METHODS: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had insulin-like growth factor I (IGF-I) ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0×ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary (ASD) score, and maintenance of mean 5-sample growth hormone (GH) <1.0 ng/mL. RESULTS: The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0×ULN (odds ratio: 126.53; 95% CI: 13.73, >999.99; P<.0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (±SE) change in IGF-I of 0.04±0.09×ULN versus 0.83±0.1×ULN (P<.0001); mean (±SE) change in ASD score of -0.6±1.5 versus 4.6±1.6 (P=.02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) versus 5/18 (27.8%) patients (odds ratio: 16.61; 95% CI: 2.86, 181.36; P=.0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. CONCLUSION: Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

Safety of long-term use of daily and long-acting growth hormone in growth hormone-deficient adults on cancer risk.

Daily injections of recombinant human growth hormone (rhGH) have been used in clinical practice for almost four decades as a replacement therapy in adult patients with GH deficiency (GHD). Long-term adherence to daily injections of rhGH is a clinical concern that may result in reduced therapeutic efficacy, and long-acting GH (LAGH) formulations have been developed in an attempt of overcoming this problem. Long-term safety issues of rhGH are the other side of the coin that has been carefully monitored over the years, particularly related to the proliferative actions of GH that could increase the risk of tumor recurrence or induce the development of new benign and malignant tumors. In this review, we present what is currently known about the cancer risk in GHD adults treated with daily rhGH injections and we discuss the major concerns and responses needed from future surveillance studies regarding the safety of LAGH preparations.

The science behind the relations among cancer, height, growth patterns, and growth hormone axis.

The association between growth hormone (GH) and carcinogenesis has long been postulated. The rationale for this association is that several components of the GH axis play an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis and have been tested as targets for cancer therapy. Epidemiological and clinical studies have examined the association between height, growth patterns, and insulin-like growth factor 1 (IGF1) levels with the most common types of malignancies, while genome-wide association studies have revealed several height-associated genes linked to cancer and/or metastasis-driving pathways. In this context, a permissive role of the GH-IGF signaling system in the link between height and cancer risk has also been investigated. In animal and human models, genetic defects associated with GH deficiency or resistance are associated with protection from tumor development, while the risk of malignancies in acromegaly or in patients exposed to recombinant GH therapy has long been a matter of concern and scrutiny. In this review, we present a narrative and historical review covering the potential relations among height, growth patterns, GH axis, and cancer.