Endocrine Society Clinical Guideline Research Articles

PS-R07-8: A CASE OF PRIMARY ALDOSTERONISM CAUSED BY BILATERAL ALDOSTERONE-PRODUCING MICROTUMORS WITH A UNILATERAL ADRENAL MASS

Introduction: Primary aldosteronism (PA) is defined as a disease in which overproduction of aldosterone causes various complications such as hypertension, cardiovascular disorder and kidney disease. We herein report a case of PA caused by bilateral aldosterone-producing microtumors with a unilateral adrenal mass. Case presentation: A 54-year-old man was referred to our hospital with a clinical suspicion of PA. He had a history of hypertension and chronic kidney disease for 10 years and had experienced paresthesia that was caused by putaminal hemorrhage in the past. In the initial examination, he exhibited hypertension (150/90 mmHg), high aldosterone (pg/mL)-to-renin (ng/mL/h) ratio (1,744), and overt hypokalemia (K, 2.9 mEq/L). The serum creatinine level was 1.89 mg/dL. The captopril challenge test showed no changes in his blood pressure or plasma aldosterone concentration. These results led to a clinical diagnosis of PA. Computed tomography (CT) revealed the presence of left adrenal mass, so that we suspected that the mass should be responsible for overproduction of aldosterone. We performed adrenal venous sampling. Unexpectedly, the adrenal venous sampling highly suggested the presence of aldosterone-producing microtumors in bilateral adrenal glands (lateralized ratio, 1.3; left contralateral ratio, 0.2). After evaluation, we decided that there was no indication for the removal of left adrenal mass. Then, a low dose of a mineralocorticoid receptor (MR) antagonist was started. Although the dose of an MR antagonist could not be increased sufficiently due to poor renal function, he exhibited an improved control of blood pressure and was followed up thereafter. Discussion and Conclusion: Although PA is one of the most common causes of secondary hypertension, making an accurate diagnosis and appropriate treatment is sometimes problematic due to the difficulty in assessing the site of aldosterone overproduction. The Japanese Endocrine Society clinical guideline states that PA with unilateral adrenal tumor in young patients may not require adrenal venous sampling. From the current case, however, we should always consider the possibility of bilateral microtumors or hyperplasia even in the presence of a unilateral adrenal mass.

Prostate-Specific Antigen Concentrations in Response to Testosterone Treatment of Severely Hypogonadal Men.

ContextClinical guidelines recommend measurement of the serum prostate-specific antigen (PSA) concentration during testosterone treatment of hypogonadal men to determine whether the increase is sufficiently high to warrant urologic referral. Prior studies of the effect of testosterone treatment on PSA concentrations have been conducted in men who were mildly to moderately hypogonadal.ObjectiveThe objective of this work is to determine the PSA response to testosterone treatment of men who are severely hypogonadal.Design and SettingThis retrospective cohort study was conducted at a single academic medical center.ParticipantsEighty-five men participated who were severely hypogonadal as a result hypothalamic-pituitary or testicular disease.Main Outcome MeasureChanges in serum PSA concentrations were measured during testosterone treatment for up to 18 months.ResultsTestosterone treatment increased the median serum testosterone concentration from 36 ng/dL (interquartile range [IQR], 20-91 ng/dL) at baseline to 395 ng/dL (IQR, 266-542 ng/dL) at 6 to 18 months. This treatment resulted in a median increment in PSA above baseline of 0.70 ng/mL (IQR, 0.10-1.85 ng/mL) at 6 to 18 months. Apropos current Endocrine Society clinical guidelines, 31% of the men experienced a PSA increase above baseline greater than 1.4 ng/mL, and 13% reached an absolute PSA concentration of greater than 4.0 ng/mL. Four men were diagnosed with prostate cancer.ConclusionsThe PSA response to testosterone replacement in men who are severely hypogonadal as a result of pituitary or testicular disease is greater than that previously reported in men with mild to moderate hypogonadism. These results suggest the magnitude of the PSA response to testosterone replacement is related to the degree of hypogonadism.

SAT-315 SDHC Germline Mutation Carrier with Primary Paraganglioma of the Thyroid Gland

Background Thyroid paragangliomas(PGLs) are less than 0.1% of all thyroid neoplasms. They represent a subset of inferior laryngeal PGL and can be located adjacent to or inside the gland. About 30% of paragangliomas are genetically determined, and 40% of those are succinate dehydrogenase (SDH) related. SDHD and SDHB are more frequently detected than SDHC and SDHA [1]. To date, thyroid paraganglioma has been reported in SDHA and B germline mutation carriers, but there is no case reported with thyroid paraganglioma related to SDHC and D mutations[2]. Clinical case A 50 year old female self-detected a nodularity on her neck. Fine needle aspiration biopsy of the nodule was suspicious for thyroid cancer. She had total thyroidectomy followed by radioactive iodine treatment. Five years after treatment, surgical specimen of thyroid slides were reviewed again upon relocation. Surprisingly, distinct pathologic changes of nodule with characteristic nesting pattern (zellaballen) was noted. On immunohistochemistry study, the cells of the lesion were positive for synaptophysin, chromogranin and S-100, and negative for keratin, CEA, thyroglobulin, TTF-1, calcitonin, EMA and Congo red stain. Based on the histologic feature and immunohistochemistry finding, right lobe paraganglioma was diagnosed retrospectively. When she was 67 years old, she developed symptoms of intermittent flushing, diarrhea, dizziness, and nausea. Her chromogranin A increased from 210 ng/mL to 3413 ng/mL in 6 months. Further pertinent laboratory work-up results included but not all: cortisol 15 mcg/dL, ACTH 35.7pg/mL(7.2-63.3 pg/mL), 24 hour urine free cortisol 17mcg (ref. range <= 176 mcg/24hr), dopamine 133pg/mL (0-20pg/mL), norepinephrine 725 pg/mL (80-520 pg/mL), epinephrine 48 pg/mL (10-200 pg/mL), normetanephrine 0.82 nmol/L (0.00-0.89 nmol/L). This was suggestive of functioning paraganglioma. The patient was evaluated by medical genetics, and a heterozygous germline pathologic variant, NM_003001.3(SDHC):c.43C>T (p.Arg15Ter) was identified. Galium-68-Dotatate scan showed a glomus tumor jugulare. Due to the location of the tumor, the patient was referred for radiation therapy (not yet completed). She was started on monthly octreotide injection and symptoms improved. Her chromogranin A decreased to 70 ng/mL ( 0-95 ng/mL) and dopamine reduced to 76 pg/mL( 0-20pg/mL). Conclusion This is the first case report of a primary paraganglioma of the thyroid gland in an SDHC mutation carrier. The Endocrine Society Clinical Guidelines Subcommittee recommends all patients with PPGLs to be engaged in shared decision making for germline genetic testing. This information can be important for future cancer screening for the patient and family cascade testing and counseling. Reference 1.Hereditary paraganlioma-Pheochromocytoma syndrome, GeneReviews, L Fishbein et al.2.Endocr Relat Cancer. 2015 Apr;22(2):191-204

Improvement of bone turnover markers and bone mineral density following treatment of primary aldosteronism.

Recent studies showed association between hyperaldosteronism and low bone density among patients with primary aldosteronism (PA) due to secondary hyperparathyroidism. Our objective is to assess bone turnover markers (BTM) and bone mineral density (BMD) of PA patients compared to essential hypertension. This was an open-label, prospective, case-controlled study, conducted over 12 months. Fifty-two consecutive patients referred for secondary hypertension were screened. Eighteen patients with confirmed PA (diagnosis based on the Endocrine Society clinical guideline) and seventeen matched controls with essential hypertension were recruited. BTM (CTX and P1NP), BMD, intact parathyroid hormone (iPTH), and bone profile were assessed at baseline and three months following treatment among the PA patients. Calcium intake was assessed using a validated questionnaire. Primary outcomes were the changes of bone markers and BMD following treatment of PA, and their relation to other parameters. PA patients had significantly lower serum calcium and higher iPTH despite comparable vitamin D levels with control group. Both BTM were significantly higher among the PA group. BMD of lumbar spine, neck of femur and distal radius did not differ between groups. Three months following treatment, there were significant: 1) reduction in BTM; 2) improvement in the lumbar spine BMD; 3) reduction in iPTH level; and 4) increment of serum 25-OH vitamin D level. Our findings support that bone loss and potential fracture risk among PA patients are likely a result of aldosterone-mediated secondary hyperparathyroidism. Patients with early PA may already exhibit increased bone turnover despite no significant changes in BMD.

The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

To develop clinical practice guidelines for the management of patients with primary aldosteronism. The Task Force included a chair, selected by the Clinical Guidelines Subcommittee of the Endocrine Society, six additional experts, a methodologist, and a medical writer. The guideline was cosponsored by American Heart Association, American Association of Endocrine Surgeons, European Society of Endocrinology, European Society of Hypertension, International Association of Endocrine Surgeons, International Society of Endocrinology, International Society of Hypertension, Japan Endocrine Society, and The Japanese Society of Hypertension. The Task Force received no corporate funding or remuneration. We searched for systematic reviews and primary studies to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations and "suggest" for weak recommendations. We achieved consensus by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. With the help of a medical writer, the Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and Council successfully reviewed the drafts prepared by the Task Force. We placed the version approved by the Clinical Guidelines Subcommittee and Clinical Affairs Core Committee on the Endocrine Society's website for comments by members. At each stage of review, the Task Force received written comments and incorporated necessary changes. For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist.

Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline

This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 μg) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (∼8 mg/m(2)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.

Expert interview: New ENDO guidelines.

Expert interview: New ENDO guidelines.

Acromegaly: an endocrine society clinical practice guideline.

The aim was to formulate clinical practice guidelines for acromegaly. The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.

Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.

The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. We suggest personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.

The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC-MS/MS method in routine clinical practice.

The Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The LC-MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls. Sensitivity and specificity were determined in the combined groups of non-CS patients, healthy controls, and CD in remission. UFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity for de novo CS, while sensitivity was 80% for recurrent CD patients, who were characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and UFF:UFE levels, which were normal in the CD remission patients and in those receiving medical therapy. Our data suggest high diagnostic performance of UFF excretion measured using LC-MS/MS, in detecting de novo CS. UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis, although high levels were found to be indicative of ectopic CS.

Safety of hormonal treatment in transgenders

Discussion of short and long-term issues of cross-hormone treatment of transgender individuals in the light of recent literature. Gender nonconformity has been depathologized and replaced by gender dysphoria in the Diagnostic and Statistical Manual of Mental Disorders version V.Safety of cross-sex hormone treatment is still a matter of debate, but the latest findings in literature are quite reassuring about short-term and long-term effects. No dramatic changes in recommendations for treatment have emerged in the past years, and for the most part, clinical work is based on Endocrine Society Clinical Guidelines published in 2009. Most recent findings agreed on the importance of maintaining cross-sex hormone serum concentration within the physiological range, avoiding or limiting maximum peaks and troughs.Treatment must be highly individualized and transitioning patients need to be engaged in a 'clinical contract' with the physician in order to ensure compliance with prescribed treatments.Although overall mortality appears to be higher among transgender individuals, this in not attributed to hormonal treatment but to other causes mostly related to lifestyle habits.

Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline

The aim was to develop clinical practice guidelines on hypertriglyceridemia. The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. The Task Force recommends that the diagnosis of hypertriglyceridemia be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150-999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of > 1000 mg/dl) be considered a risk for pancreatitis. The Task Force also recommends that patients with hypertriglyceridemia be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease. The Task Force recommends that the treatment goal in patients with moderate hypertriglyceridemia be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate should be used as a first-line agent.

Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline

The aim was to formulate practice guidelines for management of osteoporosis in men. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and evidence quality. Consensus was guided by systematic evidence reviews, one in-person meeting, and multiple conference calls and e-mails. Task Force drafts were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee; representatives of ASBMR, ECTS, ESE, ISCD; and members at large. At each stage, the Task Force received written comments and incorporated needed changes. The reviewed document was approved by The Endocrine Society Council before submission for peer review. Osteoporosis in men causes significant morbidity and mortality. We recommend testing higher risk men [aged ≥70 and men aged 50-69 who have risk factors (e.g. low body weight, prior fracture as an adult, smoking, etc.)] using central dual-energy x-ray absorptiometry. Laboratory testing should be done to detect contributing causes. Adequate calcium and vitamin D and weight-bearing exercise should be encouraged; smoking and excessive alcohol should be avoided. Pharmacological treatment is recommended for men aged 50 or older who have had spine or hip fractures, those with T-scores of -2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors. Treatment should be monitored with serial dual-energy x-ray absorptiometry testing.

The D‐Lightful Vitamin D for Child Health

Vitamin D deficiency and insufficiency is common in children. Vitamin D deficiency is defined as a 25-hydroxyvitamin D <20 ng/mL and insufficiency as 21-29 ng/mL. The major sources of vitamin D are sun exposure, diet, and supplements. In young children, vitamin D deficiency causes a mineralization defect of the skeleton, resulting in rickets. Vitamin D deficiency has been linked to many chronic diseases, including multiple sclerosis, type 1 diabetes, infectious diseases, heart disease, and type 2 diabetes. In utero vitamin D deficiency increases risk for preeclampsia and the need for a cesarean section. Children living at higher latitudes and who are presumed to be at increased risk for vitamin D deficiency are at higher risk for developing type 1 diabetes and multiple sclerosis later in life. The Institute of Medicine recommends that children 0-1 year and 1-18 years need 400 and 600 IU/d, respectively, of vitamin D for maximal skeletal health. The Endocrine Society's Clinical Guidelines recommended that to prevent and treat vitamin D deficiency, children 0-1 year and 1-18 years need 400-1000 and 600-1000 IU/d, respectively.

Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline

We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing's syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients' quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.

A detour guide to the Endocrine Society Clinical Practice Guideline on case detection, diagnosis and treatment of patients with primary aldosteronism

The Endocrine Society (USA) commissions clinical practice guidelines that address topics of major interest to the endocrine community and for which international consensus is urgently needed. As a reflection of the important contributions of European endocrinologists to the field, the Endocrine Society Clinical Guidelines Subcommittee has selected more and more European experts to join their American colleagues and help compiling and reviewing the guidelines before they are issued. However, a mid-term goal of transatlantic collaboration would certainly be the joint release of guidelines that appear concurrently in the Journal of Clinical Endocrinology & Metabolism and the European Journal of Endocrinology. Until this is achieved, we have actually decided to release a series of invited ‘European perspective’ commentaries on recently published guidelines and in this issue we will make a start with this commentary on the Clinical Practice Guideline on diagnosis and treatment of primary aldosteronism (1). Why do we need a clinical practice guideline on primary aldosteronism? Usually guidelines are needed when there have been important changes, primarily in the way we perceive the significance of a disease or when research has gained novel insights into pathogenesis and opens up new options for treatment. Primary aldosteronism has made it into the headlines over the last few years mainly due to the notion that it might be more frequent than previously assumed, possibly affecting up to 10% of all hypertensive patients (2, 3), with a recent large European trial reporting a prevalence of 4.8% (4). Thus, previous diagnosis rates would not reflect the entirety of a very rare disease but perhaps only the ‘tip of iceberg’, with many others also affected, but currently undiagnosed. With this perceived paradigm change came a change in attitude towards screening for primary aldosteronism. While we previously aimed to establish this diagnosis mainly in patients presenting with hypokalaemic hypertension, more and more physicians took to actively screening their hypertensive patients for the presence of primary hyperaldosteronism. However, given that in western countries currently about 10% of the population suffers from hypertension, these changes in diagnostic strategy represent a significant risk for our health care systems, potentially generating huge costs with insufficiently assessed gain. Thus, a level-headed look at our management strategy for primary hyperaldosteronism, based on systematic review of available evidence was urgently needed, and this is exactly what these guidelines set out to achieve.

Update in Primary Aldosteronism

It is now widely recognized that primary aldosteronism (PA) is much more common than previously thought, accounting for up to 5-10% of hypertensives, and that aldosterone excess has adverse cardiovascular consequences that go above and beyond hypertension development. These findings have precipitated a marked resurgence of research activity, most of which has supported the concept that PA plays an important role in cardiovascular disease states and should be systematically sought and specifically treated, and the development of an Endocrine Society clinical guideline for the case detection, diagnosis, and management of this common, specifically treatable, and potentially curable condition. Areas of recent, topical research include: 1) the demonstration of excess morbidity in patients with PA compared with other forms of hypertension, confirming the clinical relevance of non-blood pressure-dependent adverse effects of aldosterone excess; 2) the further demonstration that this excess morbidity and mortality are ameliorated with specific (but not nonspecific antihypertensive) therapy directed against aldosterone excess, confirming the importance of detection and diagnosis of PA to enable optimal specific management; 3) the development of new treatment strategies; 4) an ongoing appraisal and refinement of diagnostic approaches including screening, subtype differentiation, and new assay development; and 5) further insights into the importance and nature of genetic factors related to the development of PA.

COMMENTARY: Are the Endocrine Society's Clinical Practice Guidelines on Androgen Therapy in Women Misguided? A Commentary

The Endocrine Society Clinical Guidelines on Androgen Therapy in Women (henceforth referred to as the Guidelines) do not necessarily represent the opinion held by the many health-care professionals and clinicians who are specialized in the evaluation, diagnosis, and treatment of women's health in androgen insufficiency states. The recommendations provided in the published Guidelines are neither accurate nor complete. We disagree with the therapeutic nihilism promoted by these Guidelines. The members of the Guidelines Panel (henceforth referred to as the Panel), in their own disclaimer, stated that the Guidelines do not establish a standard of care. Based on data available in the contemporary literature, on the role of androgens in women's health, we provide in this commentary a point-by-point discussion of the arguments made by the Panel in arriving at their recommendations. It is our view that the Guidelines are not based on the preponderance of scientific evidence. Health-care professionals, physicians, and scientists often disagree when determining how best to address and manage new and emerging clinical issues. This is where we stand now as we endeavor to understand the role of androgens in a woman's health and welfare. Indeed, some basic facts are not in contention. All agree that dehydroepiandrosterone sulfate (DHEA-S) production from the adrenal gland begins during the preteen years, peaks in the mid 20s, then declines progressively over time. In contrast, ovarian androgen (i.e., testosterone) secretion commences at puberty, is sustained during a woman's peak reproductive years and declines as a woman ages, with a more rapid and steep decrease after surgical menopause. However, there are ample data to suggest that adrenal androgens play a role in the development of axillary and pubic hair, and that testosterone is critical for women's libido and sexual function. We take this opportunity to invite members of the Panel on Androgen Therapy in Women to discuss, clarify, comment, or rebut any of the points made in this Commentary. It is our goal to elevate this debate in order to provide women who are afflicted with androgen insufficiency and sexual disorders with the highest quality health care and to relieve their distress and suffering, as well as to improve their quality of life.