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Concept: Gigantism


Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

Concepts: Human, Africa, Sub-Saharan Africa, North Africa, Human height, Netherlands, Cold War, Gigantism


Acromegaly results from the overproduction of growth hormone in adulthood and is characterised by overgrowth of soft tissue and/or bone as well as insulin resistance. There are few data indicating the risk factors associated with this disease in dogs or its clinicopathological features and sequelae. The objective of this retrospective study was to catalogue and assess these aspects of the disease in German shepherd dogs (GSDs) which were found to be over-represented among acromegalic dogs attending two veterinary referral clinics over a period of 7 years. Each acromegalic dog (AD) was compared with two breed/age/sex matched controls. Clinical signs of acromegaly included panting, polyuria/polydipsia, widened interdental spaces, weakness, inspiratory stridor, macroglossia, weight gain, redundant skin folds, thick coat, exophthalmos and mammary masses. Serum alkaline phosphatase, creatine-kinase, glucose, triglyceride, phosphate ion, and ‘calcium per phosphate product’ concentrations were significantly higher in acromegalic animals while haemoglobin concentration, blood urea nitrogen, sodium and chloride ion concentrations, and urinary specific gravity, osmolality and fractional excretion of phosphate were significantly lower. Although, in the majority of cases clinicopathological abnormalities resolved following ovariohysterectomy, in one dog, acromegalic signs abated and insulin-like growth factor-1 concentrations normalised only following the surgical excision of mammary tumours carried out 2 months after ovariohysterectomy. The findings of this study indicate that GSDs are predisposed to the development of acromegaly with a suspected inherited susceptibility.

Concepts: Epidemiology, Metabolism, Blood, Blood urea nitrogen, Insulin-like growth factor 1, Growth hormone, Gigantism, German Shepherd Dog


This study investigated the association between the frequency of growth hormone receptor (GHR) exon 3 polymorphism (exon 3 deletion; d3-GHR) and metabolic factors in patients with acromegaly in Korea.

Concepts: Immune system, Protein, Hormone, Growth hormone, Peptide hormone, Carpal tunnel syndrome, Growth hormone receptor, Gigantism


The Dutch are the tallest people on earth. Over the last 200 years, they have grown 20 cm in height: a rapid rate of increase that points to environmental causes. This secular trend in height is echoed across all Western populations, but came to an end, or at least levelled off, much earlier than in The Netherlands. One possibility, then, is that natural selection acted congruently with these environmentally induced changes to further promote tall stature among the people of the lowlands. Using data from the LifeLines study, which follows a large sample of the population of the north of The Netherlands (n = 94 516), we examined how height was related to measures of reproductive success (as a proxy for fitness). Across three decades (1935-1967), height was consistently related to reproductive output (number of children born and number of surviving children), favouring taller men and average height women. This was despite a later age at first birth for taller individuals. Furthermore, even in this low-mortality population, taller women experienced higher child survival, which contributed positively to their increased reproductive success. Thus, natural selection in addition to good environmental conditions may help explain why the Dutch are so tall.

Concepts: Human, Natural selection, Human height, Netherlands, Gigantism, Heightism


We investigated the incidence of stroke and stroke subtypes in a population-based cohort of patients in France treated with growth hormone (GH) for short stature in childhood.

Concepts: Immune system, Growth hormone, Turner syndrome, Endocrine gland, Growth hormone deficiency, Coming of age, Gigantism, Idiopathic short stature


The advancement of “human growth hormone (hGH)-for-height” - increasing height attainment in children short for reasons other than GH deficiency - arose from intuitive, deep-seated assumptions about the disability of short stature, its improvement with hGH-mediated height gain, and the safety of escalating dosages of hGH in healthy children. Evidence challenging these assumptions now strengthens criticism of hGH-for-height as cosmetic endocrinology. To counter this characterization, collective acceptance of guidelines is needed that advise nontreatment of the vast majority of short children, support strategies that minimize treatment duration and dosage, and restrain enhancement of normal adult stature. Through a clinical case analysis, ethical issues underlying these recommendations are explored. These include duties to provide informed assent and re-assent, protect children from unnecessary treatment, consider fairness to nontreated children, and allocate healthcare resources responsibly. Informed assent for hGH-for-height should ensure awareness of modest, variable height gain expectations, limited evidence for psychosocial benefit, ongoing studies for potential posttreatment adverse effects, and options for less expensive/invasive approaches, including nontreatment and counseling. Approaching growth pro-motion in this way fosters therapeutic restraint, resists the al lure of enhancement therapy, and minimizes contributions to society’s perception that to be taller is to be better.

Concepts: Immune system, Hypothalamus, Insulin-like growth factor 1, Growth hormone, Growth hormone deficiency, Gigantism, Idiopathic short stature


This article reviews evaluation of short stature in childhood and options for management of idiopathic cases (e.g., familial short stature or constitutional delay of growth and puberty), including observation and reassurance, growth hormone treatment, and low-dose oral oxandrolone in boys.

Concepts: Immune system, Hypothalamus, Growth hormone, Anabolic steroid, Growth hormone deficiency, Gigantism, Idiopathic short stature, Short stature


Recently, in a cohort study with “overgrowth syndrome with intellectual disability,” five subjects were reported to have de novo heterozygous truncating variants in HIST1H1E, which encodes linker histone H 1.4. However, their growth pattern appeared complex that four out of five patients had a decreasing height percentile over time, and three of these patients began with above-average heights but exhibited reductions to average heights or below when they were older. Herein, we report a female patient with intellectual disability and distinctive facial features including a wide nasal bridge and prominent cheek bones. She did not exhibit skeletal overgrowth, but she had a short stature at 21 years of age. An exome analysis identified a de novo heterozygous 1-bp duplication in HIST1H1E, that is, c.433dup p.(Ala145Glyfs*51). The physical features of the proposita were essentially the same as those observed in patients with the aforementioned HIST1H1E-related overgrowth syndrome. Our review of the growth trajectories in seven patients showed that five of seven patients did not exhibit skeletal overgrowth. This “lack of overgrowth in overgrowth syndrome” is reminiscent of a subset of patients with a short stature who have Sotos syndrome, a prototypic overgrowth syndrome. Considering this complexity in growth, this newly identified condition should be referred to as Rahman syndrome.

Concepts: Cohort study, Patient, Human height, Down syndrome, Facial features, Human variability, Gigantism, Idiopathic short stature


Acromegaly is a rare disease associated with an increased risk of prostate enlargement. Severe prostate enlargement with severe lower urinary tract symptoms (LUTS) in an acromegalic patient is even more uncommon. Herein we report on a 55-year-old man who was diagnosed with acromegaly and prostate enlargement at 40 years of age. Transsphenoidal surgery, postoperative radiotherapy, and octreotide medical therapy failed to control the acromegaly, and growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels remained elevated. When the patient was 53 years of age, severe LUTS and prostate enlargement (prostate volume = 128 mL) were noted. However, LUTS improved and prostate volume decreased markedly after 5α-reductase inhibitors were used, despite the poorly controlled acromegaly (elevated GH and IGF-1 levels). This is the first long-term observation of LUTS and prostate enlargement in a poorly controlled acromegalic patient. Although the GH-IGF-1 axis was a factor contributing to prostate enlargement, the present case suggests that androgens may still play an essential role in prostate enlargement and symptoms in active acromegalic patients >50 years of age. Indeed, we should be aware that suppressing the GH-IGF-1 axis is not the only treatment choice for prostate enlargement in acromegalic patients, and even in poorly controlled acromegalic patients in whom suppression of the GH-IGF-1 axis is difficult. Symptomatic prostate enlargement in cases of active acromegaly can be treated with 5α-reductase inhibitors, as in general benign prostate hyperplasia populations.

Concepts: Prostate cancer, Urinary bladder, Insulin-like growth factor 1, Growth hormone, Benign prostatic hyperplasia, Prostate, Prostatic stent, Gigantism


To describe the course of growth hormone response to growth hormone releasing hormone (GHRH) plus arginine provocative test in children with idiopathic short stature (ISS) and to evaluate the role of peak time.

Concepts: Immune system, Growth hormone, Human height, Arginine, Gigantism, Idiopathic short stature, Growth hormone releasing hormone, Short stature