Bartter Syndrome Presenting as Arginine-Vasopressin Resistance: A Report of 2 Cases.

BACKGROUND Bartter syndrome is a rare, inherited salt-wasting tubulopathy caused by mutations in 1 of 6 genes that express ion transport channels in the thick ascending limb of nephrons. Excessive prostaglandin E2 and associated hyperreninemic hyperaldosteronism occurs, causing polyhydramnios, polyuria, prematurity, failure to thrive, and characteristic physical features. Hypokalemia, hypochloremic metabolic alkalosis, and, depending on the affected gene, hypercalciuria and nephrocalcinosis are hallmarks of Bartter syndrome. CASE REPORT A 9-month-old male infant, born prematurely due to polyhydramnios, presented in the Emergency Department with dehydration due to incoercible vomiting and significant polyuria. A 6-year-old male infant with a previous history of prematurity due to polyhydramnios was referred to the Pediatric Endocrinology Department due to short stature and notable polydipsia and polyuria. Considering these marked symptoms, both cases triggered suspicion and started workup for arginine-vasopressin insufficiency/resistance. However, during the investigations, a broader clinical revision revealed that both had dysmorphic physical features (triangularly shaped face, prominent forehead, protruding ears, drooping mouth), poor growth, impaired weight gain, and typical biochemical findings (hypokalemic metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism) of Bartter syndrome. Genetic testing confirmed the diagnosis of Bartter syndrome types 1 and type 2, respectively, and this diagnosis allowed proper treatment and significant clinical improvements, personalized follow-up, and genetic counseling for parents desiring further healthy pregnancies. CONCLUSIONS Here, we present clinical and follow-up findings of 2 patients with Bartter syndrome types 1 and 2 discovered upon a broader clinical revision of suspected arginine-vasopressin insufficiency/resistance. We also review pertinent data on diagnosis and management of this challenging syndrome.

A case report of multiple endocrine neoplasia type 1 and autoimmune disease: Coincidence or correlation?

RATIONALE: Multiple Endocrine Neoplasia type 1 (MEN1) is a familial syndrome that results from the disruption of a tumor suppressor protein called MENIN. Its management is challenging, as MEN1 affects different endocrine tissues and predisposes to both benign and malignant tumors. MENIN-deficient cells have recently been recognized to play a role in triggering autoimmunity. Herein, we present a case of MEN1 with multiple endocrine and autoimmune disorders. PATIENT CONCERNS: A 50 years old female with a 25 years history of complicated nephrolithiasis presented with primary hyperparathyroidism. DIAGNOSES: Over several decades, she was diagnosed with recurrent primary hyperparathyroidism, autoimmune thyroiditis, multinodular goiter, pernicious anemia, metastatic gastric type 1 neuroendocrine tumor, macroprolactinemia, gonadotropin deficiency, mucosa-associated lymphoid tissue lymphoma of the thyroid gland, positive anti-calcium sensor receptor antibodies, and BRCA 1/2-negative invasive breast cancer. The autoimmune regulator gene was sequenced, but no pathogenic variants were found. Next-generation sequencing revealed both a pathogenic MEN1 mutation and a benign CDC73 gene variant. Familial genetic screening revealed a large kindred with multiple carriers of one or both genetic variants (MEN1 = 19; CDC73 = 7). INTERVENTIONS: The patient underwent surgical excision of three parathyroid glands, total thyroidectomy and breast tumorectomy plus tamoxifen, and monthly injections of octreotide. The patient and family members with the MEN1 mutation are under a life-long surveillance program for MEN1 prototypic tumors. OUTCOMES: The patient was stable and alive during a 24-years follow-up period. LESSONS: With the present case, the authors highlight a new interplay between MENIN and the immune system, which may have implications for future targeted life-long surveillance and treatment of MEN1 patients.

Arrested Puberty in an Adolescent Male with Anorexia Nervosa Successfully Resumed with Multidisciplinary Care.

The normal development of puberty depends on the specific pulsatility of gonadorelin, which is finely regulated by genetic and environmental factors. In the published literature, eating disorders figure as a cause of pubertal delay/arrest in females but are rarely considered in males with disordered puberty. A 16.7-year-old male was referred to the Department of Pediatrics with arrested puberty due to severe malnutrition in the context of food restriction. Past medical history was relevant for asthma. Generalized cachexia, facial lanugo hair, cutaneous xerosis, and Russell's sign were noted; he had a height of 155.5 cm (-2.5 SD; target height: 168 cm, -1.1 SD) and a BMI of 12.4 kg/m2 (-6.8 SD); left and right testicular volumes were 8 mL and 10 mL, respectively. He had a twin brother who had normal auxological/pubertal development (height: 167 cm, -1.05 SD; testicular volumes: 20 mL). Anorexia nervosa was diagnosed, and he was enrolled in a personalized treatment and surveillance program. "Nonthyroid illness" resembling secondary hypothyroidism was noted, as was low bone mineral density. Clinical and biochemical follow-up showed significant improvements in BMI (16.2 kg/m2, -2.55 SD), completion of puberty (testicular volumes: 25 mL), and reversion of main neuroendocrine abnormalities. Herein, we present an adolescent male with arrested puberty in the context of anorexia nervosa. The recognition of this rare condition in males allows a personalized approach to disordered puberty, with resumption of normal function of the hypothalamic-pituitary-gonadal axis and achievement of pubertal milestones.

Orthorexia nervosa and comorbid depression successfully treated with mirtazapine: a case report.

Orthorexia nervosa (ON) is a recently proposed eating disordered behaviour characterized by an obsessional or exaggerated fixation on healthy eating. The published literature is scarce regarding its classification, clinical presentation, management and long-term outcomes. Herein, we present the clinical and follow-up findings of an 18-year-old woman with ON comorbid with depression, successfully treated with mirtazapine. The patient had a 12-month history of obsessional behaviours for "healthy food", characterized by suppression of sugar and fat from her diet, tightly counted meal calorie content, eating only self-made meals, avoidance of eating in public, unacceptance of other person's opinions on diet, social isolation and a weight loss of 15 kg (body mass index of 16.2 kg/m2). A score of 19-points was initially obtained on the ORTO-15 questionnaire, suggesting the presence of orthorexic tendencies and behaviours. The patient also reported a 1-month history of depressed mood, anxiety, anhedonia, fatigue, insomnia with early morning waking, leading to the presumptive diagnosis of ON with comorbid depression. Treatment with mirtazapine for 11 months resulted in the remission of the disordered eating behaviour, a sustained regain of weight, a score of 41-points on the ORTO-15, and to the resolution of depressive symptomatology (including insomnia). To our knowledge, this is the first description of ON with comorbid depression successfully treated with mirtazapine. This case highlights the possible usefulness of mirtazapine as a treatment option for patients with ON. However, randomized controlled studies are warranted to confirm the current findings.

A Clinical Roadmap to Investigate the Genetic Basis of Pediatric Pheochromocytoma: Which Genes Should Physicians Think About?

Pheochromocytoma is very rare at a pediatric age, and when it is present, the probability of a causative genetic mutation is high. Due to high costs of genetic surveys and an increasing number of genes associated with pheochromocytoma, a sequential genetic analysis driven by clinical and biochemical phenotypes is advised. The published literature regarding the genetic landscape of pediatric pheochromocytoma is scarce, which may hinder the establishment of genotype-phenotype correlations and the selection of appropriate genetic testing at this population. In the present review, we focus on the clinical phenotypes of pediatric patients with pheochromocytoma in an attempt to contribute to an optimized genetic testing in this clinical context. We describe epidemiological data on the prevalence of pheochromocytoma susceptibility genes, including new genes that are expanding the genetic etiology of this neuroendocrine tumor in pediatric patients. The clinical phenotypes associated with a higher pretest probability for hereditary pheochromocytoma are presented, focusing on differences between pediatric and adult patients. We also describe new syndromes, as well as rates of malignancy and multifocal disease associated with these syndromes and pheochromocytoma susceptibility genes published more recently. Finally, we discuss new tools for genetic screening of patients with pheochromocytoma, with an emphasis on its applicability in a pediatric population.