ABSTRACT. Background. Premature adrenarche refers to the early maturation of the adrenal zona reticularis such that the resultant modest hyperandrogenism causes the early appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The precise etiology of premature adrenarche is not known. However, recent studies indicate that certain girls with premature adrenarche are at risk of developing functional ovarian hyperandrogenism, polycystic ovarian syndrome, and hyperinsulinism. Caribbean Hispanic women in general are at increased risk of developing polycystic ovarian syndrome, and African-Americans are at increased risk of developing the complications of hyperinsulinism. Previously, girls with premature adrenarche were reported to have androgens in the range found in normal children in the early stages of puberty. We noted that many of our African-American and Caribbean Hispanic patients with premature adrenarche had androgens that were much higher than what has been reported previously.Objective. This retrospective study was performed to characterize the adrenocorticotropin-stimulated androgen response in an African-American and Caribbean Hispanic population of girls with premature adrenarche.Methodology. The androgen response to adrenocorticotropin stimulation in 72 African-American and Caribbean Hispanic girls with premature adrenarche was compared with those reported for normal girls in early puberty (Tanner stages II and III). The mean age was 6.8 ؎ 0.8 years, bone age was 8 ؎ 1.5 years, pubic hair was Tanner stages II and III, and body mass index was 18.6 ؎ 4.Results. Of the girls, 28% were found to have elevated stimulated 17OHPregnenolone (17OHPreg) levels that were >2 SD units above the mean for normal early pubertal children. The stimulated ratio of 17OHPreg/ 17OHProgesterone also was elevated in 18% of the girls and showed a modest correlation with body mass index.Conclusion. In contrast to previous studies of girls of mixed ethnic backgrounds with premature adrenarche, 28% of the 72 African-American and Caribbean Hispanic girls with premature adrenarche had adrenocorticotropin-stimulated 17OHPreg levels that were significantly higher than those seen in early pubertal girls. Because 17OHPreg hyperresponsiveness has been described previously in women with hirsutism or polycystic ovarian syndrome, the similar finding in many African-American and Caribbean Hispanic girls with premature adrenarche

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from ∼5 to ∼12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.

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Introduction Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi Fujimoto disease, is a disorder of unknown etiology. Diagnosis is made only with histological examination and is frequently misdiagnosed as lymphoma. Our objective is to maintain high index of suspicion to diagnose HNL and to emphasize on the role of hydroxychloroquine (HCQ) for management of complicated cases. Case 48 year old male with a past medical history of ankylosing spondylitis, uveitis, and hypothyroidism initially presented 4 years ago with fever, night sweats, vomiting and weight loss of 10 pounds over the past 1 month. The physical exam was significant for tender, mobile left supraclavicular lymphadenopathy with no hepatosplenomegaly. Laboratory findings revealed leukopenia, anemia and elevated liver enzymes, lactate dehydrogenase, erythrocyte sedimentation rate and C-reactive protein. He was given broad spectrum antibiotics with no improvement. Computed tomography of the chest/abdomen demonstrated mediastinal, hilar and abdominal lymphadenopathy. Further infectious and autoimmune workup was negative. The patient then underwent a left supraclavicular lymph node excision which was consistent with HNL (Figure 1). Flow cytometry of the lymph node revealed no diagnostic evidence of a lymphoproliferative disorder. He was started on prednisone and his symptoms resolved. He had multiple episodes of recurrence in the last 4 years, manifesting as high grade fever, fatigue and lymphadenopathy. He was treated each time with prednisone. No provoking factors including viral infection or flare of uveitis was evidenced. Most recently, he had 3 episodes within 12 month span. Eventually he was treated with HCQ and since, has had no recurrence. Discussion HNL is most commonly reported among young Asian females. The exact entity of this disease is unclear including its pathogenesis and treatment. No signs or symptoms are pathognomonic, making it a difficult diagnosis. Awareness of this disorder by clinicians would help prevent unnecessary treatment with antibiotics and allow earlier initiation of HCQ. Characteristic histopathologic findings of HNL include irregular paracortical areas of coagulative necrosis with karyorrhectic focus, distorting the nodal architecture. The foci are formed by predominantly histiocytes and plasmacytoid monocytes, also immunoblasts and lymphocytes. Neutrophils are absent and plasma cells are either absent or scarce. The histiocytes express antigens such as CD163 and CD68. Most cases of HNL have a self-limited clinical course, although 3-7% of patients experience recurrent episodes. Treatment is generally directed towards symptomatic relief. Use of short term administration of corticosteroids and nonsteroidal anti-inflammatory drugs may be effective. However preventing recurrence has been a challenge. Several reports have proposed a close association between HNL and autoimmune disorders. Therefore, it has been speculated that HCQ would be useful for treating HNL. Our patient had 3 recurrences within 4 years and with the use of HCQ, remission was finally achieved. Conclusion In past 1 year, two articles discussed the use of HCQ in HNL. Lin et al. presented a retrospective review of 40 children diagnosed with HNL over approximately 15 years. Corticosteroids and HCQ were administered in 15.6% of patients. There were neither recurrences nor relevant major adverse effects in cases treated with HCQ. Honda et al. reported a case of a 42 year old female with multiple recurrences following tapering dose of prednisone. Continuous remission was achieved by concomitant use of HCQ with prednisolone. Several other cases have been reported suggesting that HCQ is effective for treating HNL patients with Systemic lupus erythematosus (SLE). Despite our patient not meeting the American College of Rheumatology criteria of SLE, he still responded to HCQ and has been able to avoid unnecessary use of steroids. Further research is needed regarding management of HNL flares which do not present with obvious autoimmune symptoms. Lin, YC et al., Pediatric Kikuchi-Fujimoto disease: A clinicopathologic study and the therapeutic effects of hydroxychloroquine; https://doi.org/10.1016/j.jmii.2017.08.023 Honda et al; Recurrent Kikuchi-Fujimoto Disease Successfully Treated by the Concomitant Use of Hydroxychloroquine and Corticosteroids; Intern Med. 2017 Dec 15; 56(24): 3373-3377. Disclosures No relevant conflicts of interest to declare.