Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach

Since normocalcemic primary hyperparathyroidism (NHPT) was first defined at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008, many papers have been published describing its prevalence and possible complications. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. Recent studies have shown that intermittent oscillations of serum calcium just below and slightly above the normal limits are very frequent, therefore challenging the assumption that serum calcium must be consistently normal to make the diagnosis. There is debate if these variations in serum calcium outside the normal range should be included under the rubric of NHPT or, rather, a milder form of classical primary hyperparathyroidism. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. New associations between parathyroid hormone (PTH) and several other comorbidities have also been reported from observational studies, suggesting that excessive PTH secretion might cause tissue dysfunction independent of serum calcium. Heterogeneous studies using different definitions of NHPT, however, make it difficult to draw definitive conclusions regarding the role of PTH excess when complications other than osteoporosis or kidney stones are described. This review will focus on clinical aspects and suggest an approach to NHPT

Retrospective assessment of fracture risk through opportunistic radiological screening in a large modern cohort of liver transplant recipients

Objective: Liver transplantation has been associated with a high prevalence of osteoporosis, although most data rely on single-center studies with limited sample size, with most of them dating back to late 1990s and early 2000s. The present thesis aims to assess the prevalence of fragility fractures and contributing factors in a large modern cohort of liver transplant recipients managed in a referral Italian Liver Transplant Center. Design and Methods: Paper and electronic medical records of 429 consecutive patients receiving liver transplantation from 1/1/2010 to 31/12/2015 were reviewed, and 366 patients were selected. Clinically obtained electronic radiological images within 6 months from the date of liver transplant surgery, such as lateral views of spine X-rays or CT abdominal scans, were opportunistically reviewed in a blinded fashion to screen for morphometric vertebral fractures. Clinical fragility fractures reported in the medical records, along with information on etiology of cirrhosis and biochemistries at the time of liver surgery were also recorded. Results: Prevalence of fragility fractures in the whole cohort was 155/366 (42.3%), with no significant differences between sexes. Of patients with fractures, most sustained vertebral fractures (145/155, 93.5%), the majority of which were mild or moderate wedges. Multiple vertebral fractures were common (41.3%). Fracture rates were similar across different etiologies of cirrhosis and were also comparable in patients with diabetes or exposed to glucocorticoids. Kidney function was significantly worse in women with fractures. Independent of age, sex, alcohol use, eGFR, etiology of liver disease, lower BMI was the only independent risk factor for fractures (adjusted OR 1,058, 95%CI 1,001-1,118, P=0.046) in this study population. Conclusions: A considerable fracture burden was shown in a large and modern cohort of liver transplant recipients. Given the remarkably high prevalence of fractures, a metabolic bone disease screening should be implemented in every patient awaiting liver transplantation

Sclerosing Angiomatoid Nodular Transformation of the Adrenal Gland: A Case Report of a Novel Histopathological Entity

The finding of an indeterminate adrenal mass at radiological investigations is a challenge for physicians. Complex diagnostic work-up, periodic follow-up, or surgical intervention are therefore needed to rule out malignant lesions. Tertiary care hospitals are provided with F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET) and F-18-dihydroxyphenylalanine (F-18-DOPA) PET, which aid in the characterization of indeterminate adrenal masses. Nevertheless, the histopathological examination may be required to exclude malignancy or rare etiologies. A 54-year-old woman presented to our clinic 6 months after a cerebral hemorrhage. She was hypertensive and had recently discovered a left adrenal mass of 15 mm during an abdominal ultrasound. Contrast-enhanced CT, following adrenal protocol, revealed a 14-mm adrenal mass without characteristics suggestive of an adrenal adenoma. Tumor markers were negative. Functional tests excluded hormone hypersecretion. An F-18-DOPA PET was negative. An F-18-FDG PET showed mild uptake of both the adrenal glands, with a more circumscribed pattern in the left one (maximum standardized uptake value 5 4). As the clinical diagnosis was still indeterminate, we performed laparoscopic left adrenalectomy. The histopathological examination described a sclerosing angiomatoid nodular transformation (SANT) of the adrenal gland, a benign lesion already described as a rare occurrence only in the spleen. IgG4 levels were reduced. In conclusion, this is a report of a SANT of the adrenal gland, a novel entity that should be taken into consideration in the differential diagnosis of indeterminate adrenal masses at CT scan. Copyright (C) 2019 Endocrine Societ

Recent Advances on Subclinical Hypercortisolism

During the last 20 years, a significant body of literature has accumulated regarding subclinical hypercortisolism in patients with adrenal incidentalomas. Retrospective studies have indicated these patients have an increase in cardiovascular events and mortality. Current recommendations for patients with adrenal incidentalomas include an overnight low-dose dexamethasone suppression test and a thorough evaluation of cardiovascular and metabolic risk factors. Further hormonal testing and close monitoring are necessary in patients with incomplete suppression. Unilateral adrenalectomy may be beneficial in cases with abnormal suppression and comorbidities related to hypercortisolemia. Prospective studies are need for a better risk stratification and tailored therapy

Review of bone health in women with estrogen receptor–positive breast cancer receiving endocrine therapy

In estrogen-receptor-positive tumors, adjuvant endocrine therapy has been shown to be highly beneficial for both overall and disease-free survival. Estradiol is key in regulating bone and mineral physiology, and several studies found a strong correlation between these therapies and the risk of fractures. Since these therapies are often given for 5 through 10 years, the timing for bisphosphonates or denosumab initiation seems essential to managing bone metabolism. However, gray zones and discrepancies between guidelines remain as to the best threshold when to start antiresorptive treatment, or whether antiresorptive treatment should be administered to every woman undergoing adjuvant endocrine therapy, independent of their risk factors for fractures. Treatment options and strategies should be discussed at the start of hormone adjuvant therapy to come to a shared decision with the patient, with the final aim of reducing the risk of future fractures as much as possible. This review will cover present guidelines and literature on antiresorptive treatment in this setting, to provide clinicians with useful clues for managing these patients

Glucocorticoid- and Transplantation-Induced Osteoporosis

Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis; nonetheless, it remains an undertreated condition. Transplantation-induced osteoporosis encompasses a broad range of unique pathogenetic features with distinct characteristics dependent on the transplanted organ. Understanding the pathogenesis of bone loss is key to recommending osteoporosis therapy in these patients. This review summarizes recent advances and addresses current issues in these fields

Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

Normocalcemic primary hyperparathyroidism (NHPT) was first described over 10\u2009years ago, but uncertainties still remain about its definition, prevalence, and rates of complications. As a result, consensus management guidelines for this condition have not yet been published. Several hypotheses have been proposed for the pathophysiology of NHPT, but it may be a heterogeneous disorder with multiple causes, rather than a single etiology that explains this biochemical phenotype. A common clinical concern is whether NHPT should be treated surgically when complications are already present at first recognition of the disorder, rather than following patients clinically over time. The literature on NHPT is based mostly on larger studies of population\u2010based cohorts and smaller studies from referral centers. Lack of rigorous diagnostic criteria and selection bias inherent in populations seen at tertiary referral centers may explain the heterogeneity of reported rates of bone and renal complications in relation to consistently mild laboratory alterations. Unresolved questions remain about the significance of NHPT when it is diagnosed biochemically without evident bone or kidney complications. Moreover, its natural history remains to be elucidated because a proportion of what is classified as NHPT may revert to normal spontaneously, thus revealing previously unrecognized secondary hyperparathyroidism. These issues indicate that caution should be used in recommending surgery for NHPT. This review will focus on recent issues regarding the pathophysiology, evaluation, and management of NHPT. \ua9 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Challenges in the management of chronic hypoparathyroidism

The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1\u201384) (rhPTH(1\u201384)) was approved by the FDA in January 2015. Since the approval of rhPTH(1\u201384), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in the quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism