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Advances in technology, methodology, and deep phenotyping are increasingly driving the understanding of the pathologic basis of disease. Improvements in patient identification and treatment are impacting survival. This is true in endocrinology and inborn errors of metabolism, where disease-modifying therapies are developing. Inherent to this evolution is the increasing awareness of the respiratory manifestations of these rare diseases. This review updates clinicians, stratifying diseases spirometerically; pulmonary hypertension and diseases with a predisposition to recurrent pulmonary infection are discussed. This division is artificial; many diseases have multiple pathologic effects on respiration. This review does not cover the impact of obesity., Competing Interests: Disclosure The authors have nothing to disclose., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

A number of chemical messengers, such as various hormones and hormone-like substances, along with neurotransmitters, such as serotonin, dopamine, and norepinephrine, are directly or indirectly linked with the encoding of social behavior via their action at the amygdala, hippocampus, and other related brain structures known to be involved in different aspects of social development. It is thought that any imbalance in the secretion and action of these chemicals may lead to defective or abnormal social behaviors that are the hallmarks of Autism Spectrum Disorders (ASDs). Many of the studies have described an association between ASDs and endocrine dysfunction, but have failed to establish a cause-effect connection between these 2 conditions. All together, the literature regarding the role of endocrine-related factors and ASDs is sparse and remains somewhat preliminary, controversial, and inconclusive. Thus, more research is needed in the future to shed more light on this topic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To review the available data on endocrine disorders and recurrent pregnancy loss., Findings: Our group found that most endocrine disorders do not seem to be correlated with a diagnosis of recurrent pregnancy loss (RPL). The exception to this is testing for thyroid stimulating hormone and thyroid antibodies, which is recommended due to a strong correlation with recurrent pregnancy loss and positive anti-thyroid peroxidase antibodies., Conclusion: The available literature supports testing thyroid function and antibodies in women with RPL. Testing for other endocrine disorders is only warranted if otherwise clinically indicated, independent from a history of recurrent pregnancy loss., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To investigate medical complications (MCs) occurring within 6 months postinjury in brain-injured patients with prolonged disorders of consciousness (DoC) and to evaluate impact of MC on mortality and long-term clinical outcomes., Design: Prospective observational cohort study., Setting: Rehabilitation unit for acquired DoC., Participants: Patients (N=194) with DoC (142 in vegetative state [VS], 52 in minimally conscious state; traumatic etiology 43, anoxic 69, vascular 82) consecutively admitted to a neurorehabilitation unit within 1-3 months postonset., Interventions: Not applicable., Main Outcome Measures: Mortality and improvements in clinical diagnosis and functional disability level (assessed by Coma Recovery Scale-Revised [CRS-R] and Disability Rating Scale) at 12, 24, and 36 months postonset., Results: Within 6 months postinjury, 188 of 194 patients (>95%) developed at least 1 MC and 142 of them (73%) showed at least 1 severe MC. Respiratory and musculoskeletal-cutaneous MCs were the most frequent, followed by endocrino-metabolic abnormalities. Follow-up, complete in 189 of 194 patients, showed that male sex and endocrine-metabolic MCs were associated with higher risk of mortality at all timepoints. Old age, anoxic etiology, lower CRS-R total scores, and diagnosis of VS at study entry predicted no clinical and functional improvements at most timepoints; however, epilepsy predicted no improvement in diagnosis at 24 months postonset only., Conclusions: MCs are very frequent in patients with DoC within at least 6 months after brain injury, regardless of clinical diagnosis, etiology, and age. Endocrino-metabolic MCs are independent predictors of mortality at all timepoints; however,epilepsy predicted poor long-term outcome. Occurrence and severity of MCs in patients with DoC call for long-term appropriate levels of care after the postacute phase., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Antiseizure medications and dietary therapies have associated effects on the endocrine system. We provided an overview of the relationship between epilepsy treatment and bone health in children with epilepsy. Additionally, we discussed the effects of epilepsy treatment on other endocrine systems including thyroid function, growth, reproduction, and weight. The effect of epilepsy on bone health is multifactorial; there are direct and indirect effects of medication and dietary treatments as well as a decrease in physical activity, decreased sunlight exposure, decreased vitamin D levels, and additional comorbidities. Some medications have a greater effect on vitamin D and bone health than others, however all antiseizure medical treatments are associated with lower vitamin D levels in pediatric patients. We have provided practical suggestions for vitamin D surveillance in children with epilepsy as well as replacement strategies. Children with epilepsy have an increased likelihood of additional endocrine disorders including subclinical hypothyroidism, decreased growth, weight abnormalities, reproductive and sexual dysfunction. To a great extent, this is medication specific. Though more studies are needed to elucidate optimal treatment and monitoring of bone health and other endocrinopathies in children with epilepsy, it is critical that caregivers pay close attention to these issues to provide optimal comprehensive care to their patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Postoperative nonunion is not uncommon in the lower extremity, and significant morbidity can be associated with nonunion of the foot and ankle after surgical reconstruction. For the purposes of the present study, we retrospectively reviewed and compared a cohort of patients who had undergone elective foot and ankle reconstruction to better assess the modifiable risk factors associated with postoperative nonunion. We hypothesized that the presence of endocrine and metabolic abnormalities are often associated with nonunion after foot and ankle surgical reconstruction. We formulated a matched case-control study that included 29 patients with nonunion and a control group of 29 patients with successful fusion to assess the prevalence of certain modifiable risk factors known to have an association with nonunion after foot and ankle arthrodesis. The modifiable risk factors assessed included body mass index, tobacco use, diabetes mellitus, vitamin D abnormality, thyroid dysfunction, and parathyroid disease. A statistically significant (p < .05) difference was found between the 2 groups for endocrine and metabolic disease diagnoses in the medical records of the 58 patients identified. Thus, 76% versus 26% (p < .05) of patients experienced nonunion in the endocrine disease group versus the nonendocrine disease group, respectively. Patients with vitamin D deficiency or insufficiency were 8.1 times more likely to experience nonunion (95% confidence interval 1.996 to 32.787). No statistically significant differences were found between the groups in terms of age, sex, tobacco use, body mass index, or procedure selection (p = .56, p = .43, p = .81, p = .28, and p = 1.0, respectively). A greater prevalence of endocrine abnormalities, in particular, vitamin D deficiency and insufficiency, was associated with nonunion after elective foot and ankle reconstruction. Patients with such abnormalities appear to have a greater risk of developing nonunion after arthrodesis procedures., (Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The endocrine system is a complex group of organs and glands that relates to multiple other organs and systems in the body with the ultimate goal of maintaining homeostasis. This complex network functions through hormones excreted by several glands and released in the blood, targeting different body tissues and modulating their function. Any primary disorders affecting the endocrine glands and altering the amount of hormones synthesized and released will lead to disruption in the functions of multiple organs. The central nervous system of a developing child is particularly sensitive to endocrine disorders. A variety of neurological manifestations have been described as features of several endocrine diseases in childhood. Their knowledge may contribute to an early diagnosis of a particular endocrine condition, especially when more typical features are not present yet. In this article, we discuss specific neurological manifestations found in various endocrine disorders in children., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Endocrine diseases, such as equine metabolic syndrome and pituitary pars intermedia dysfunction, are common in domesticated horse populations, and the frequency with which these diseases are encountered and managed by equine veterinary practitioners is expected to increase as the population ages. As clinicians learn more about the effects of these diseases on equine reproductive physiology and efficiency (including effects on reproductive seasonality, ovulation efficiency, implantation, early pregnancy loss, duration of pregnancy, and lactation), strategies and guidelines for improving fertility in affected animals continue to evolve. It is hoped that further research will establish these recommendations more firmly., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The cardiovascular system is affected by a multitude of endocrine disorders, including dysfunction of the thyroid, calcium, glucocorticoids, insulin/glucose, and growth hormone axes. Since most of these changes in the cardiovascular system are reversible when treated, early diagnosis is important, as if left untreated, they may become fatal. This review focuses on the pathophysiology, clinical presentation, pathology, and treatment of patients with these endocrine diseases who present with a variety of cardiovascular manifestations. Neuroendocrine tumors presenting with the carcinoid syndrome and their cardiovascular manifestations are also discussed., (© 2013 Elsevier Inc. All rights reserved.)

Background & Aims: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency., Methods: We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins., Results: We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears., Conclusions: In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

It is possible that autism spectrum disorders (ASDs) have a multifactorial cause along with more than one predisposing and perpetuating factor, all of which culminate in expression of these disorders. Endocrine and neuropeptide factors are among the list of possible etiologic or predisposing contenders. The search for an endocrine model to explain the etiopathogenesis of ASD is a new endeavor. In this article, the authors look at some of the emerging literature that is available regarding any possible relationship between the endocrine hormones and factors and whether it can possibly be etiologic or merely coincidental with autism and ASDs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

As survival rates continue to increase after allogeneic stem cell transplant (allo-SCT), the associated long-term complications of transplant need to be taken into consideration. Here, we review the endocrine and metabolic complications associated with transplant survivors, including diabetes, dyslipidemia, hypertension, cardiovascular disease, hypogonadism, vitamin D deficiency, osteoporosis, thyroid disease, adrenal dysfunction, and pituitary disorders, and provide a brief summary of evaluation and treatment of these conditions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Childhood obesity is a profoundly complex problem and serves as an example of a biospsychosocial issue. Scientific inquiry has provided incredible insight into the complex etiology of weight gain but must be viewed as an interaction between a human's propensity to conserve calories for survival in a world with an abundance of it. This article provides a brief overview divided between biological (nature) and psychosocial and behavioral (nurture) factors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Clinical guidelines and consensus statements serve to summarize and organize current knowledge on diverse subjects and provide practical guidelines for proper clinical management. Recommendations should be based on research and evidence derived from appropriate sources. In 2008, more than 20 consensus statements were published in the pediatric literature alone. This article summarizes the salient points of the latest consensus statements jointly developed by multiple endocrine societies including the Lawson Wilkins Society for Pediatric Endocrinology and the European Society for Pediatric Endocrinology. As much as possible, the original intent and language of the statements was respected and paraphrased., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This article reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Most of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long-term strategies for management. The foundation for all treatments for pediatric obesity remains restriction of energy intake with lifestyle modification. There are few long-term studies of pharmacotherapeutic interventions for pediatric obesity. Bariatric surgical approaches are the most efficacious treatment but, because of their potential risks, are reserved for those with the most significant complications of obesity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Whether for the prepubertal or pubertal child, the goal of fertility preservation is to obtain cells or tissues to be used to produce future children. For the prepubertal child, preservation efforts involve germ cells, earlier forms of sperm, and immature follicles, rather than mature spermatozoa or follicles. Options for prepubertal children include for boys freezing testicular tissue and extracting testicular sperm or for girls obtaining ovarian cortical or follicular tissue for storage. These procedures involve extraction and storage of immature gametes for subsequent in vitro maturation, although attempts for sperm currently involve only animal studies. For adolescent subjects who have sufficient gonadal development and reserve, sperm, oocytes, and ovarian cortex can be retrieved as among adults., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In laminitis occurring in the field, as opposed to laminitis occurring during hospitalization or severe illness, endocrinopathic laminitis is the predominant form of laminitis. Prevalent causes of endocrinopathic laminitis are ECS and EMS. Exclusion of inflammatory or weight bearing causes of laminitis and focussing on the identification and treatment of underlying endocrine conditions will improve laminitis management strategies., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Endocrinopathic laminitis in horses and ponies has the potential to cause extensive damage to the feet before clinical signs of laminitis are apparent. Early diagnosis and intervention based on the detection and control of hyperinsulinemia are critical if the crippling changes that are seen in the disease are to be avoided. Preventing endocrinopathic laminitis, rather than treating it, is good practice management benefiting not only equine patients but also their owners., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

CD is an immune-mediated enteropathy caused by genetically predisposed individuals eating gluten-containing foods (Catassi et al., 2007; Celiac Working Group et al., 2008; Green & Cellier, 2007; Hill et al., 2005). There are several endocrine disorders that are associated with CD. In many of these cases, CD does not present with the typical gastrointestinal symptoms. Nurses working with children who have endocrine conditions need to consider CD as part of the differential and follow-up care plan. This awareness will facilitate more efficient diagnosis and minimize the risk of conditions associated with untreated CD.

Although the treatment and management of laminitis in the horse requires a holistic and often multidisciplinary approach from the veterinarian, farrier, and nutritionist, this review focuses on pharmacologic interventions that might have prophylactic benefit, specifically in the horse with laminitis as a result of pituitary pars intermedia dysfunction and equine metabolic syndrome., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Medication-related problems are common in hemodialysis (HD) patients. These patients often require 12 medications to treat 5 to 6 comorbid conditions. Medication-related problem research reports cannot be generalized to the entire HD population because data are obtained from single centers and limited numbers of patients. We conducted a pooled analysis to gain additional insight into the frequency, type, and severity of medication-related problems and extrapolated the data to the entire US HD population., Methods: Articles were identified through a MEDLINE search (1962 to March 2004). Seven studies were included in the analysis. Medication-related problems were categorized into the following 9 categories: indication without drug therapy, drug without indication, improper drug selection, subtherapeutic dosage, overdosage, adverse drug reaction, drug interaction, failure to receive drug, and inappropriate laboratory monitoring. A medication-related problem appearance rate was determined., Results: We identified 1,593 medication-related problems in 395 patients (51.2% men; age, 52.4 +/- 8.2 years; 42.7% with diabetes). The most common medication-related problems found were inappropriate laboratory monitoring (23.5%) and indication without drug therapy (16.9%). Dosing errors accounted for 20.4% of medication-related problems (subtherapeutic dosage, 11.2%; overdosage, 9.2%). The medication-related problem appearance rate was 5.75e(-0.37x), where x equals number of months of follow-up (P = 0.02)., Conclusion: HD patients experience ongoing medication-related problems. Reduction in medication-related problems in dialysis patients may improve quality of life and result in decreased morbidity and mortality. Pharmacists are uniquely trained to detect and manage medication-related problems. Pharmacists should be an integral member of the dialysis health care team.

Both obesity and the polycystic ovary syndrome (PCOS) are commonly seen in women of reproductive age. Fifty percent of all patients with PCOS are obese, and the presence of obesity affects the clinical manifestations of PCOS. The underlying pathogenetic mechanisms appear to involve insulin resistance and hyperinsulinemia, the magnitude of which is greater in obese than in non-obese women with PCOS. Specific effects of obesity on the manifestations of PCOS, underlying mechanisms of the interactions between obesity and PCOS, and therapeutic implications of these interactions are discussed in this article.

Diabetes remains the most commonly encountered endocrinopathy with the incidence of type 2 doubling in the past decade. The prevalence of diabetes is projected to continue to increase dramatically over the next several decades unless major public health initiatives are successful in stemming this growth. Both type I and 2 diabetics more frequently require surgical and critical care than their non-diabetic counterparts. Type 1 and 2 diabetics also sustain greater peri-operative morbidity and mortality. Careful preoperative assessment and appropriate perioperative intervention may limit this. There is increasing evidence that maintenance of normal blood glucose in the perioperative period and during critical illness is beneficial for diabetic and non-diabetic patients. More data will hopefully be forthcoming to substantiate recent reports and identify the mechanisms of improved outcome. Thyroid disease remains a commonly encountered pathology that is more readily identified and controlled in the modern era of radioimmune assays of thyroid hormone and successful medical and surgical therapies. Severe hypothyroidism and thyroid storm are associated with significant increases in perioperative morbidity and mortality. Recognition of these entities or those at risk for developing them post operatively is crucial in initiating timely and effective therapy. Primary Al is uncommon, but results in glucocorticoid and mineralocorticoid deficiency. Tertiary Al is far more common, most often secondary to iatrogenic therapy with exogenous glucocorticoids for the management of chronic diseases such as connective tissue disorders, anti-rejection regimes, and severe asthma. Glucocorticoid replacement or supplementation is needed on a case-by-case basis and should be individualized based on chronic steroid dose, duration, and stress of the surgical procedure. Perioperative steroid dosing regimes now recommend lower doses for shorter periods than previously suggested. More recently Al has been recognized in two populations, elderly patients undergoing major surgery and a subgroup of patients with septic shock. Timely diagnosis using synthetic ACTH stimulation testing and stress glucocorticoid, and possibly mineralocorticoid therapy, seems to reverse these processes and improve recovery. Although uncommon, patients with pheochromocytoma who undergo open or laparoscopic resections remain diagnostic and therapeutic challenges. Perioperative outcome seems to have improved, in part, related to newer therapies and less invasive surgeries when indicated. The appropriate preoperative assessment and management of patients with various endocrinopathies is important to optimize outcome and limit avoidable complications. Hopefully additional evidence based guidelines will be forth-coming particularly in caring for the ever increasingly encountered perioperative diabetic.

Tremor in childhood, beginning in the neonatal period, is more common than generally appreciated. Although some tremor disorders in children (eg, essential tremor) also affect adults, others (eg, shuddering, jitteriness, spasmus nutans, and vitamin B12-deficiency tremor) are seen exclusively in children. This review covers the etiology, clinical features, and treatment of the major tremor syndromes in children, and when appropriate, makes comparisons with similar disorders in adults.

This article presents the clinical pathology and the involvement of the cardiovascular, renal, endocrine, and immunologic systems in laminitis. The data available on these systems are presented with respect to the disease phase and severity. The nutritional and metabolic alterations realized in the chronically affected horse are also presented. In this discussion, the origins and clinical implications of these systemic findings are discussed.

Hypertension is a common medical disorder in pregnancy that may predate or first appear in pregnancy. Endocrine disorders rarely are the cause of the elevated blood pressure. However, it is essential to have a high index of suspicion because they carry much higher fetal and maternal morbidity and mortality risks. Endocrine disorders presenting as hypertension are primarily the result of autonomous production of renin, aldosterone, cortisol, or catecholamines. This report discusses the physiological changes in pregnancy, presentation, investigation, and management of these disorders.

Fatigue occurs in more than 70% of patients treated with interferon-alpha (IFN-alpha) and is the most problematic toxicity associated with IFN-based immunotherapy. Abundant evidence suggests that immune-mediated endocrine disease occurs during IFN-alpha therapy, which may contribute to the etiology of fatigue. Autoimmune thyroid disease is a well-recognized consequence of IFN-alpha therapy and may be mediated by the induction of IFN-gamma production by lymphocytes. Administration of exogenous IFN-gamma has been associated with upregulation of class II major histocompatibility antigens in the thyroid and the development of thyroiditis. Interferon-alpha also stimulates the production of interleukin-6; both interleukin-6 and IFN-gamma have specific effects on thyrocyte function. There also is evidence suggesting that IFN-alpha initiates a cytokine cascade that effects the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, thus affecting regulation of glucocorticoid and sex steroid hormone secretion, but the clinical significance of these observations has not been established. Although endocrine disease will not explain the occurrence of fatigue symptoms in all patients, there is clear evidence that hormonal deficiency syndromes occur in a relatively large portion of patients receiving systemic IFN-alpha therapy. Most importantly, the possibility of hypothyroidism must be considered; however, diagnosis of hypothyroidism in cancer patients is complicated by the occurrence of the "sick euthyroid syndrome." Clinical recommendations for assessment and treatment of IFN-alpha-induced fatigue are offered. Most importantly, measurements of thyroid-stimulating hormone and antithyroid autoantibodies should be used to evaluate thyroid status. Acknowledging the limitations of current clinical data, adrenal- and gonadal-axis dysfunction also must be considered in patients with IFN-alpha-induced fatigue.

Skin lesions can be associated with many internal diseases. Most organ systems seem to have conditions in which skin lesions can develop. Treatment of the skin lesions in such a situation is palliative. The underlying internal disease must be addressed for resolution of the skin lesions to occur. It is important to view the skin as an integral communicating part of the body and not just as the skin.

Hypertension is a prominent feature of various endocrine diseases including primary aldosteronism, pheochromocytoma (considered separately in this issue), Cushing's syndrome, adrenal enzymatic deficiencies like 11 beta-hydroxylase, 17 alpha-hydroxylase deficiencies, and congenital or acquired 11 beta-hydroxysteroid dehydrogenase deficiencies. Patients with 11 beta-hydroxylase deficiency cannot convert 11-deoxycortisol or deoxycorticosterone into the active glucocorticoids cortisol and corticosterone, respectively. The increase in the powerful mineralocorticoid deoxycorticosterone, resulting from the enzymatic block, promotes sodium retention, hypertension, and hypokalemia. Females who have the deficiency also show signs of virilization due to the shunting of the precursors to the synthesis of adrenal androgens. Patients with 17 alpha-hydroxylase deficiency present with hypertension and/or hypokalemia, and male members exhibit pseudohermaphroditism with no development of male sexual characteristics. The defect is due to the lack of 17-hydroxylated steroids, which are necessary precursors in the synthesis of androgens and estrogens. The hypertension is due to the accumulation of the mineralocorticoid deoxycorticosterone. The mineralocorticoid receptor derives its specificity from the co-expression of the 11 beta-hydroxysteroid dehydrogenase, which converts the active steroids corticosterone and cortisol to the inactive 11-dehydrocorticosterone and cortisone, preventing their interaction with the receptor. Congenital absence of the 11 beta-hydroxysteroid dehydrogenase or acquired deficiency induced by consuming licorice or its derivatives result in occupancy of the mineralocorticoid receptor by cortisol and corticosterone, and production of mineralocorticoid-type hypertension.

Swollen and droopy eyelids are obvious ocular findings, unlike many ocular conditions that require the use of special equipment to observe. Neither of these findings is a specific diagnosis but rather each is evidence of localized disease and often is a sign of underlying systemic disorder. Therefore, it is important for the clinician evaluating the child with a swollen or droopy lid to have a working knowledge of these diagnostic possibilities. In this article the author presents the various causes of the swollen and droopy eyelid, focus on the most relevant clinical characteristics, and emphasize systemic associations.

Hypertension in children is not a common problem. When it is found, however, a pathologic cause can often be identified. The endocrine causes of hypertension in children are generally rare. We have reviewed the diverse and rare endocrine causes of hypertension in the pediatric population. Table 3 lists features of these conditions that assist in their diagnosis. In all patients with hypertension, a thorough history and physical examination may point to the diagnosis of endocrine or other causes of secondary hypertension. For a more detailed approach to these diagnoses, other reviews may be helpful. A phased laboratory evaluation similar to that suggested by Ogborn and Crocker facilitates in the evaluation of secondary hypertension. The critical screening tests from an endocrine point of view are plasma sodium, potassium, calcium, renin activity, and thyroid function tests, including T4, T3, and thyroid stimulating hormone. Measurement of a 24-hour urine collection for aldosterone, metanephrine, and catecholamines may be warranted if the previously mentioned studies are unrevealing. More specific studies also may be suggested by these preliminary evaluations and the history and physical examination. Further investigations should be done with the additional guidance of a pediatric endocrinologist.

Routine measurement of estrogens, testosterone, T4, insulin, FSH, and LH at least four times per year (e.g., during each of the four seasons) may improve the efficiency of stallion management. Benefits may not be realized in the short term but will provide valuable historical data on individual stallions that, when added to other data, will improve ability of management personnel to initiate early treatment and delay or slow declining fertility. This ability will be greatly improved as more data and products become available. There appears to be a relationship between low total estrogen concentration/high FSH concentration and subfertility. This condition is associated with high average breedings per pregnancy. A decrease in concentration of estrogen and an increase in FSH concentration often precede a decline in fertility associated with oligospermia. Hypogonadotropic stallions have not been reported. This condition is not likely to be a cause of declining fertility in stallions and greatly limits the potential efficacy of GnRH therapy in subfertile stallions. Much research must be done to elucidate the etiology of testicular degeneration associated with increased FSH concentrations and decreased estrogen concentrations in stallions. At present, no reliable hormonal therapeutic protocols exist that will improve fertility in subfertile stallions.

Osteoporosis is a common disorder in women. Fifty percent of women more than 65 years of age have bone mineral density below the fracture threshold. Factors which accelerate bone loss include deficiency of gonadal hormones, nutritional effects, lack of exercise, smoking, alcoholism and endocrinopathies. Fractures of the hip, vertebra and radius occur much more frequently in patients with osteoporosis. Chronic pain is caused by compression fractures of vertebrae resulting in mechanical changes in the spine. The most desirable treatment is prevention. Adequate dietary intake of calcium, exercise and avoidance of excess intake of protein and phosphorus should be advised. Treatment with fluoride is promising but requires further study.

A 52-yr-old woman developed exudative ascites 2 yr after the onset of peripheral neuropathy. Extensive evaluation revealed that the patient had no underlying liver disease, malignancy, infection, or cardiac or renal disease. The ascites initially responded to high-dose corticosteroid therapy. The patient had many clinical features of the recently described POEMS syndrome, including a persistent IgA lambda-paraprotein. Initially, her ascites responded to treatment with steroids. This is characteristic of the syndrome and should be considered in patients with POEMS syndrome and refractory ascites.

Having seen five patients with both SLE and thyroid disease (case reports available on request) in a short period of time, we have undertaken a survey of the association between the ARD and endocrine disorders. On the basis of a literature review and our own reported study, it is apparent that an association between these major groups of disorders is well established with some individual diseases, though much more dubious in others (Table 3). The possibility of coexistent endocrine disease in a patient with a multisystem ARD should be carefully considered throughout the course of the patient's follow-up.

Hypoglycemia of infancy and childhood represents a treatable cause of mental retardation and seizures. Most neonates with hypoglycemia have transient disorders, but with persistent hypoglycemia one must consider hyperinsulinism, hypopituitarism, or hereditary hepatic enzyme deficiencies. Outside of the neonatal period, ketotic hypoglycemia is the most common cause of hypoglycemia in childhood. One cannot overemphasize the value of obtaining certain diagnostic tests at the presentation of spontaneous hypoglycemia, including blood for insulin, cortisol, growth hormone, and urine for ketone bodies. Supportive treatment with intravenous glucose to maintain the blood glucose greater than 50 mg/dl is important until a diagnosis is established allowing specific therapy aimed at the underlying disorder.

In summary, the diagnostic tools are now available to ascertain whether elevated levels of androgens underlie some cases of acne vulgaris. Awareness of androgen excess as a contributing factor in acne may help to identify patients who would benefit from endocrine evaluation and, possibly, from hormonal therapy.

Short stature is a common pediatric problem that requires us to decide whether a child's small size represents only normal variation or indicates the presence of an underlying disease. In a population of children two standard deviations (SD) below the mean for height (below the third percentile), about 20 per cent may be expected to have pathologic short stature with the remaining 80 per cent about equally divided between familial short stature and constitutional growth delay. In contrast, most children three SD below the mean for height have pathologic short stature. Set forth in this article is an orderly approach to identify normal variants of short stature and to investigate the causes of pathologic short stature.

It is not widely appreciated that endocrine disease may present primarily as rheumatic syndromes, sometimes spectacular in onset, more commonly insidious and subtle, making their true recognition difficult. The underlying hormonal, biochemical, and metabolic events have understandable reflection in the structure and function of bone, joint, and muscle.

Reviewing the chronological evolution of our understanding of why some children fail to thrive without obvious organic cause permits us to develop a rational contemporary approach to diagnosis and management. Originally recognized as a phenomenon of children living in institutions, it later became clear that it could occur in children living with their families. While emotional deprivation was at first emphasized as the principal determinant of growth failure, it is now apparent that the major mediating mechanism is insufficient caloric intake. Thus prior to nutritional recovery it may be difficult to segregate whether emotional symptoms in the child reflect the causes or effects of malnutrition. With rare exceptions, an etiologic diagnosis can be suspected on the basis of history, physical examination, and family assessment. Nonspecific investigative screening of such children has proved to be without value. Successful management depends on recognition of the supernormal caloric intake required to induce rapid catch-up growth. Aggressive hyperalimentation combined with intensive emotional stimulation and often with active family participation offer the best chances of a successful outcome.

As the presenting complaint in 7 per cent of pediatrician visits, pain in the limbs is a common problem in childhood. It is important that the diagnosis be made expeditiously. The authors review the possible organic cause of limb pain, as well as limb pain from conversion reactions and from growing pains, giving special attention to the differential diagnosis so that appropriate treatment for the pain can be initiated.

None of the previously described treatments for idiopathic infertility have been shown to be effective (Table). Controlled clinical trials may indicate that certain treatments are effective in carefully selected subsets of infertile men. The key to rational therapy will be basic research leading to the elucidation of the pathophysiology of what is presently "idiopathic infertility." Our policy is to present the facts honestly and invite our patients to participate in controlled clinical trials with therapies of uncertain value.