Diazoxide-Induced Neutropenia and Long-Term Follow-up in a Patient with Hyperinsulinemia-Hyperammonemia due to GLUD1 Mutation.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

Acquired resistance to pamidronate treated effectively with zoledronate in juvenile Paget's disease.

Juvenile Paget's disease (JPD) is a rare autosomal recessive osteopathy. There is still a question about the most effective treatment modality in long-term prognosis. A 9-month-old boy who suffered from bone pain and deformities with a very high alkaline phosphatase level was diagnosed as JPD by radiographic findings. Genetic analysis showed a homozygous large deletion in TNFRSF11B gene encoding osteoprotegerin. Clinical improvement was observed with intravenous pamidronate therapy. However, the effect of drug reduced in time so the annual dose per kilogram body weight was increased after 2 years. Despite this increment, bone fractures developed and bone pain recurred with high-ALP levels, which suggested resistance to pamidronate. Switching to zoledronate resulted a significant improvement in bone findings radiographically and ALP level. Severe hypocalcemia requiring intravenous calcium treatment complicated the first dose of zoledronate, but not recurred thereafter. Intravenous pamidronate therapy is effective in reducing bone pain, improving bone deformities and motor development in infantile onset JPD. However, this effect can be transient. Switching to another bisphosphonate like zoledronate may provide long-term clinical and biochemical improvement as an alternative treatment in case of resistance to pamidronate therapy.

The efficacy of greater occipital nerve blockade in chronic migraine: A placebo-controlled study.

OBJECTIVE: GON blockade with local anesthetics is an effective treatment for a group of headaches, such as cervicogenic headache, cluster headache, occipital neuralgia, migraine. Our aim was to evaluate the efficacy of greater occipital nerve (GON) blockade in patients with chronic migraine (CM) by using a control group. MATERIALS AND METHODS: We included 44 CM patients and randomly divide the patients into two groups, as group A (bupivacaine) and group B (placebo) to our study. GON blockade was administered four times (once per week) with bupivacaine or saline. After 4 weeks of treatment, patients were followed up for 3 months, and findings were recorded once every month for comparing each month's values with the pretreatment values. The primary endpoint was the difference in the frequency of headache (headache days/month). VAS pain scores were also recorded. RESULTS: A total of 44 patients had completed the study; no severe adverse effects had occurred. Group A showed a significant decrease in the frequency of headache and VAS scores at the first, second, and third months of follow-up. Similarly, group B showed a significant decrease in the frequency of headache and VAS scores at the first month of follow-up, but second and third months of follow-up showed no significant difference. CONCLUSION: Our results suggest that GON blockade with bupivacaine was superior to placebo, has long-lasting effect than placebo, and was found to be effective for the treatment of CM. More studies are needed to better define the safety and cost-effectiveness of GON blockade in CM.

Greater occipital nerve block in the treatment of triptan-overuse headache: A randomized comparative study.

OBJECTIVES: This study aims to investigate the efficiency of a single and repeated greater occipital nerve (GON) block using lidocaine in the treatment of triptan-overuse headache (TOH), whose importance has increased lately. MATERIALS AND METHODS: In the study, 105 consecutive subjects diagnosed with TOH were evaluated. The subjects were randomized into three groups. In Group 1 (n=35), only triptan was abruptly withdrawn. In Group 2 (n=35), triptan was abruptly withdrawn and single GON block was performed. In Group 3 (n=35), triptan was abruptly withdrawn and three-stage GON block was performed. All patients were injected bilaterally with a total amount of 5 cc 1% lidocaine in each stage. During follow-up, the number of headache days per month, the severity of pain (VAS), the number of triptans used, and hsCRP and IL-6 levels were recorded three times; in the pretreatment period, in the second month post-treatment, and in the fourth month post-treatment. They were then compared. RESULTS: There was a statistically significant difference in the post-treatment fourth month in comparison with the pretreatment period in Group 3 (P<.05). Compared to Group 1, the number of headache days, VAS, and decrease in triptan need in Group 3 was statistically significant compared to Group 2 (P<.05). Compared to pretreatment, in the fourth month post-treatment, both hsCRP and IL-6 levels were lower only in Group 3 (P<.05). CONCLUSIONS: We are of the opinion that repeated GON block in addition to the discontinuation of medication has significant efficacy for TOH cases.

[What does a thorough personality questionnaire, the MMPI-2, tell us about psychological aspects of recurrent miscarriage?]. / Étude des aspects psychologiques des fausses couches à répétition à l'aide d'un questionnaire de personnalité approfondi : le MMPI-2.

OBJECTIVES: Try to analyse the experience of couples undergoing repeated miscarriages by answering the following questions: what can we learn from these men and women who suffered from repeated miscarriages? PATIENTS AND METHODS: A thorough personality questionnaire, the MMPI-2, presented to 50 couples who have had repeated miscarriages. RESULTS: Through a hierarchical classification, different profiles appear in the men's group as well as in the women's group, revealing a somatization of psychological suffering. It is also revealing acute defensive personality profiles showing restricted affects in a lot of these men whose partners have suffered from multiple procreation failures. Such a narrower range of emotions can be a cause of additional pain for their partner and for themselves. DISCUSSION AND CONCLUSION: We can therefore establish that, in these circumstances, the medical and/or psychological treatment should include both couple members to improve the marital adjustment and ease the couple towards another pregnancy which is always apprehended with the fear of another failure. A few etiological hypothesis may be evoked.

Anemia and neutropenic fever with high dose diazoxide treatment in a case with hyperinsulinism due to Munchausen by proxy.

BACKGROUND: The etiology of hyperinsulinemic hypoglycemia in adolescents is similar to that of adults. Patients resistant to medical treatment may undergo pancreatectomy. Diazoxide is the mainstay of medical treatment. Rarely bone marrow suppression is reported due to diazoxide. PATIENT: An adolescent with severe hyperinsulinemic hypoglycemia was referred for pancreatectomy after she was treated with high doses of diazoxide, octreotide and glucose. She developed anemia and febrile neutropenia in the course of diazoxide treatment that resolved with cessation of medication. The cause of the hyperinsulinemia proved to be classical Munchausen by proxy. CONCLUSION: This is the first report of bone marrow suppression involving erythroid series by diazoxide. Follow-up of blood count may be considered in patients on high dosages since anemia may be dose dependent. Munchausen by proxy poses a serious threat to children with significant morbidity and mortality. Awareness and a high index of suspicion in clinical settings with unusual causes are the mainstay for the diagnosis.

Assessment of thyroid function during the long course of Hashimoto's thyroiditis in children and adolescents.

CONTEXT: The prognosis of Hashimoto's thyroiditis (HT) in children and adolescents is not well known and studies reporting long-term outcome of the disease are scarce. OBJECTIVE: To assess the thyroid hormone status during long-term follow-up and to establish the prognosis of children and adolescents with HT. PATIENTS: One hundred and twenty-nine patients with HT were re-evaluated for thyroid hormone status after a mean follow-up period of 50 months. RESULTS: Seventy-seven per cent of the euthyroid patients were still euthyroid, while 21.1% of these patients became hypothyroid at the time of re-evaluation. However, 69.5% of hypothyroid patients remained hypothyroid (overt or subclinical) and 30.5% recovered. CONCLUSION: HT is a dynamic process. Thyroid functions can show variation during follow-up. Therefore, thyroid function tests should be repeated periodically to detect progression to hypothyroidism in initially euthyroid patients as well as reversibility of hypothyroidism.

Hashimoto's thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease.

UNLABELLED: Hashimoto's thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents in iodine replete areas. To find out the clinical, epidemiological and laboratory characteristics of the disease in childhood, we reviewed files of 162 children and adolescents with HT followed in the Department of Pediatric Endocrinology, Hacettepe University Faculty of Medicine. RESULTS: Female patients constituted 86.4% (n = 140) of all patients with a female:male ratio of 6.4. Mean age at diagnosis was 11.4 +/- 2.97 years (age range 4.4-16.5 years). At the time of diagnosis 43.2% of the patients (n = 70) were euthyroid, 24.1% (n = 39) had subclinical hypothyroidism, 21% (n = 34) had overt hypothyroidism, and 8.6% (n = 14) had overt and 3.1% (n = 5) subclinical hyperthyroidism. CONCLUSIONS: Autoimmune thyroiditis is more frequent in females, and increases in frequency over age during childhood and adolescence. At the time of diagnosis, frequency of overt and subclinical hypothyroidism is similar to that of euthyroid goiter.

Comparación alejada (más de 5 años) de la radioterapia externa y la prostatectomía radical en cáncer localizado de próstata / Distant comparison (more than 5 years) of external beam radiation and radical prostatectomy for localized prostate cancer

Objetivo: Comaparar la evolución de pacientes con cáncer clinicamente localizado de próstata tratados con prostatectomía radical (PR) o radioterapia externa (RT) luego de más de cinco años fr tratamiento. Material y Métodos: Revisamos las historias clínicas de pacientes tratados con PR o RT entre 4/1992 y 12/1998 con cáncer localizado de próstata. La dosis de RT fue de 65GY. Se registraron tacto rectal+ APE previo al tratamiento, biopsias y evolución: progresión, morbomortalidad. Resultados: Se evaluaron 84 pacientes. 35 tratados con RT, Tacto + en 21, APE entre 5,6 y 38,2 mg/ml y Gleason (SG) 3-7; 49 pacientes tratados con PR, tacto + en 17, APE 4,2 a 43 ng, SG 3-9.Se halló perforación capsular en 20 (40,8 pòr ciento), 8 además con vesículas seminales infiltradas; 4 presentaron metástasis en ganglios. El AP >10 en 18 de 20 pacientes hallados con pT3. De 29 pacientes con pT1-2, 18 tenían APE <10 y 1 solo >20. Dos pacientes requirieron esfínter urinario artificial y otros cuatro continuaron con incontinencia leve. Lurgo de 5 años el 77 por ciento de pacientes irradiados presentaron progresión; 24 tratados con PR progresaron (48,9 por ciento), 5 de ellos eran pT2. Conclusiones: La PR mostró resultados superiores a la RT para el tratamiento del cáncer clínicamente localizado de próstata, aunque con mayor morbilidad. La RT con dosis de 65Gy parece insuficiente para obtener resultados curativos. La PR permitió la curación de más del 80 por ciento con estadio clínico T1c y APE<10, pero los resultados son pobres en pacientes con tacto rectal + y APE>20

Supresión versus modificación del antiandrógenos ciproterona en la progresión del cáncer de próstata / Antiandrogen withdrawal versus change of ciproterone in relapse prostate cancer

Objetivo: Analizar las respuestas en la concentración del antígeno prostático específico (APE) y en la clínica. en pacientes hormorrefractarios al bloqueo androgénico con ciproterona más aginistas LHRH, que hubieran tenido una respuesta positiva de al menos 6 meses con la primer línea terapéutica, al suprimir la ciproterona o bien reemplazarla por bicalutamida. Material y Métodos: Se randomizaron 12 pacientes para suprimir en 6 de ellos la ciproterona o reemplazarla con bicalutamida en los otros 6., determinándose entonces la concentración sérica mensual de APE y la respuesta clínica subjetiva. Resultados: en 7 pacientes (4 del grupo que suprimió ciproterona y 3 del que reemplazó con bicalutamida) la concentración sérica del APE se redujo entre 38,4 y 82,2 por ciento, observándose una respuesta clínica satisfactoria en los 5 pacientes de este grupo que eran sintomáticos. Tres de los pacientes continuaron progresando (2 del grupo con bicalutamida) tanto en valores de de APE cuanto en la evaluación del dolor. Los pacientes con respuestas favorables habian tenido una respuesta a la primera línea del tratamiento entre 17 y 58 meses (media 37,8 meses) y el Gleason promedio fue 5,1 (rango 3 a 7). Los pacientes en los que observamos progresión tuvieron una respuesta positiva a la primera línea del tratamiento entre 10 y 15 meses (p`romedio 12,3 meses) y el Gleason promedio fue de 8,66 (rango 8 a 9). Conclusiones: Hemos observado respuestas en pacientes con cáncer de próstata refractario a la terapia combinada con agonistas LHRH más ciproterona tanto en los que se suprimió la coproterona como en los que se reemplazó al antiandrógeno por bicalutamida. La respuesta positiva parece estar ligadaal Gleason inicial y al tiempo de respuesta a la primeralinea terapéutica en menos de 15 meses y con Gleason mayor de 8 no respondieron a ninguna de las variantes de supresión o remplazo. Al momento, no podemos determinar cuál de las 2 ramas de tratamiento (remplazo o supresión) resulta más eficaz

Comparación alejada (más de 5 años) de la radioterapia externa y la prostatectomía radical en cáncer localizado de próstata / Distant comparison (more than 5 years) of external beam radiation and radical prostatectomy for localized prostate cancer

Objetivo: Comaparar la evolución de pacientes con cáncer clinicamente localizado de próstata tratados con prostatectomía radical (PR) o radioterapia externa (RT) luego de más de cinco años fr tratamiento. Material y Métodos: Revisamos las historias clínicas de pacientes tratados con PR o RT entre 4/1992 y 12/1998 con cáncer localizado de próstata. La dosis de RT fue de 65GY. Se registraron tacto rectal+ APE previo al tratamiento, biopsias y evolución: progresión, morbomortalidad. Resultados: Se evaluaron 84 pacientes. 35 tratados con RT, Tacto + en 21, APE entre 5,6 y 38,2 mg/ml y Gleason (SG) 3-7; 49 pacientes tratados con PR, tacto + en 17, APE 4,2 a 43 ng, SG 3-9.Se halló perforación capsular en 20 (40,8 pòr ciento), 8 además con vesículas seminales infiltradas; 4 presentaron metástasis en ganglios. El AP >10 en 18 de 20 pacientes hallados con pT3. De 29 pacientes con pT1-2, 18 tenían APE <10 y 1 solo >20. Dos pacientes requirieron esfínter urinario artificial y otros cuatro continuaron con incontinencia leve. Lurgo de 5 años el 77 por ciento de pacientes irradiados presentaron progresión; 24 tratados con PR progresaron (48,9 por ciento), 5 de ellos eran pT2. Conclusiones: La PR mostró resultados superiores a la RT para el tratamiento del cáncer clínicamente localizado de próstata, aunque con mayor morbilidad. La RT con dosis de 65Gy parece insuficiente para obtener resultados curativos. La PR permitió la curación de más del 80 por ciento con estadio clínico T1c y APE<10, pero los resultados son pobres en pacientes con tacto rectal + y APE>20(AU)

Supresión versus modificación del antiandrógenos ciproterona en la progresión del cáncer de próstata / Antiandrogen withdrawal versus change of ciproterone in relapse prostate cancer

Objetivo: Analizar las respuestas en la concentración del antígeno prostático específico (APE) y en la clínica. en pacientes hormorrefractarios al bloqueo androgénico con ciproterona más aginistas LHRH, que hubieran tenido una respuesta positiva de al menos 6 meses con la primer línea terapéutica, al suprimir la ciproterona o bien reemplazarla por bicalutamida. Material y Métodos: Se randomizaron 12 pacientes para suprimir en 6 de ellos la ciproterona o reemplazarla con bicalutamida en los otros 6., determinándose entonces la concentración sérica mensual de APE y la respuesta clínica subjetiva. Resultados: en 7 pacientes (4 del grupo que suprimió ciproterona y 3 del que reemplazó con bicalutamida) la concentración sérica del APE se redujo entre 38,4 y 82,2 por ciento, observándose una respuesta clínica satisfactoria en los 5 pacientes de este grupo que eran sintomáticos. Tres de los pacientes continuaron progresando (2 del grupo con bicalutamida) tanto en valores de de APE cuanto en la evaluación del dolor. Los pacientes con respuestas favorables habian tenido una respuesta a la primera línea del tratamiento entre 17 y 58 meses (media 37,8 meses) y el Gleason promedio fue 5,1 (rango 3 a 7). Los pacientes en los que observamos progresión tuvieron una respuesta positiva a la primera línea del tratamiento entre 10 y 15 meses (p`romedio 12,3 meses) y el Gleason promedio fue de 8,66 (rango 8 a 9). Conclusiones: Hemos observado respuestas en pacientes con cáncer de próstata refractario a la terapia combinada con agonistas LHRH más ciproterona tanto en los que se suprimió la coproterona como en los que se reemplazó al antiandrógeno por bicalutamida. La respuesta positiva parece estar ligadaal Gleason inicial y al tiempo de respuesta a la primeralinea terapéutica en menos de 15 meses y con Gleason mayor de 8 no respondieron a ninguna de las variantes de supresión o remplazo. Al momento, no podemos determinar cuál de las 2 ramas de tratamiento (remplazo o supresión) resulta más eficaz(AU)

Neonatal thyroid screening: methods-efficiency-failures.

Newborn screening for congenital hypothyroidism (CH) is one of the major achievements of preventive medicine, as the condition occurs frequently (1/4000 newborns) and results in brain damage if not detected and treated in the first few days of life. Measurement of T4 and/or TSH in dried blood spots collected on the second through fifth days of life are the most widely used methods in screening programs for CH currently. Some children with the disease may be missd in any screening program, however, owing to factors related to the disease itself and the methods employed in its detection, as well as factors ascribed to the element of human error, ie screening errors. The methods employed in newborn screening programs for CH, their efficiency in disease detecetion, and biological factors as well as screening errors leading to missed cases are discussed.

Langerhans' cell histiocytosis: report of an atypical case.

A patient is described with Langerhans' cell histiocytosis and polyneuropathy diagnosed 12 years after the development of diabetes insipidus after head trauma.

Iodine deficiency in Turkey.

UNLABELLED: Turkey is an iodine deficiency area. The overall goitre prevalence is thought to be 30%, and most epidemiological studies give figures compatible with mild to moderate iodine deficiency. However, it is suspected that there are regions where iodine deficiency might be more severe than previously known. In this study the goitre prevalence and iodine status in a mountain village in Central Anatolia were investigated and the results compared to those of an urban area with mild iodine deficiency. Parameters of iodine status in the mountainous region showed severe iodine deficiency comparable to that in Central Africa. It seems that there are regions in Turkey where current programmes of salt iodization will be inadequate to correct the problem of iodine deficiency. CONCLUSIONS: Our observations suggest that regional variations in iodine status may impede the success of salt iodization programmes, which alone may not be adequate for correction of the problem country-wide. Alternative sources of iodine should be considered in addition to expanded and more efficient salt iodization programmes.

Disminución de la indicación quirúrgica en la hipertrofia prostática benigna por la utilización de nuevas terapias farmacológicas / Reduction in single prostatectomy by the use of new pharmacologic agents

La hipertrofia benigna de próstata es el tumor benigno más frecuente en el hombre. La resolución quirúrgica es el mejor tratamiento para resolver los fenómenos obstructivos originados. La utilización de nuevos agentes medicamentosos que actúan sobre la hiperplasia glandular (finasteride y Serenoa repens) y el tono muscular alfa-adrenérgico (terazosina y otros) plantea una alternativa. Habiéndose mantenido los mismos criterios para la indicación quirúrgica investigamos el total de pacientes operados en el servicio de urología del Hospital Israelita durante períodos de 18 meses a partir de enero de 1986, 1990 y 1995 para observar la influencia de los nuevos tratamientos en el último de los tres períodos estudiados. La reducción de las indicaciones quirúrgicas por hiperplasia benigna de próstata resultó estadísticamente significativa en el último período, por lo que concluimos que la utilización de agentes farmacológicos que actúan sobre la hiperplasia glandular y sobre el tono muscular alfa-adrenérgico ha permitido tal modificación en la indicación quirúrgica

Disminución de la indicación quirúrgica en la hipertrofia prostática benigna por la utilización de nuevas terapias farmacológicas / Reduction in single prostatectomy by the use of new pharmacologic agents

La hipertrofia benigna de próstata es el tumor benigno más frecuente en el hombre. La resolución quirúrgica es el mejor tratamiento para resolver los fenómenos obstructivos originados. La utilización de nuevos agentes medicamentosos que actúan sobre la hiperplasia glandular (finasteride y Serenoa repens) y el tono muscular alfa-adrenérgico (terazosina y otros) plantea una alternativa. Habiéndose mantenido los mismos criterios para la indicación quirúrgica investigamos el total de pacientes operados en el servicio de urología del Hospital Israelita durante períodos de 18 meses a partir de enero de 1986, 1990 y 1995 para observar la influencia de los nuevos tratamientos en el último de los tres períodos estudiados. La reducción de las indicaciones quirúrgicas por hiperplasia benigna de próstata resultó estadísticamente significativa en el último período, por lo que concluimos que la utilización de agentes farmacológicos que actúan sobre la hiperplasia glandular y sobre el tono muscular alfa-adrenérgico ha permitido tal modificación en la indicación quirúrgica(AU)

Intravenous immunoglobulin treatment in children with Guillain-Barré syndrome.

We have retrospectively reviewed the data of 75 consecutive children diagnosed with Guillain-Barré syndrome (GBS) and hospitalized in two centres. There were 51 children with GBS treated in Ankara, Turkey and 24 patients treated in Toronto, Canada. To evaluate the effect of intravenous immunoglobulin (IVIG) treatment, the patients were divided into three groups. All 24 Canadian patients received IVIG in a dose of 1 g/kg/day for 2 days. In the Ankara group 23 children received 0.4 g/kg/day for 5 days and the remaining 28 patients in that group received supportive treatment only. In all but two patients IVIG was started within the first 2 weeks of neuropathic symptoms. The patients' data, including mean functional grades, frequency of bulbar signs and autonomic dysfunction and age were similar in all three groups. Analysis of the short-term outcome demonstrated that the patients treated with IVIG had a significantly faster rate of recovery. Mean time-lapse until improvement of one functional grade was 17.4 days in the IVIG group from Toronto, and 20.8 days in the IVIG group and 62.4 days in the non-IVIG group of patients from Ankara. We conclude that IVIG has considerable efficacy in the treatment of children with GBS. Furthermore, we have also demonstrated a faster rate of recovery in patients who received a total dose of IVIG in 2 days as opposed to 5 days.

Cockayne syndrome: review of 25 cases.

Clinical and laboratory findings of 25 patients with classical Cockayne syndrome (CS) are reviewed. A history of consanguinity was present in 21 patients, and 15 patients had at least 1 affected sibling. Apart from the cardinal features of dwarfism, microcephaly, and mental retardation, the most consistent clinical features included photosensitivity (84%), gait disturbances (84%), progeroid appearance (84%), and ocular abnormalities (88%). The most consistent laboratory findings comprised abnormal nerve conduction (slowed conduction in 13 of the 16 cases with an ENMG), and an abnormal brainstem auditory evoked response (BAER) and/or audiometry (abnormal in 13 of the 17 cases in whom either one of them were available). Cerebral atrophy and calcification of the basal ganglia were the next more common laboratory findings. Clinical criteria are useful in most instances in the diagnosis of CS. In patients in whom the clinical features are controversial for a diagnosis of Cockayne syndrome, studies directed to disorders of myelination involving both peripheral and central nervous systems in conjunction with audiometry may aid in the diagnosis.

Acute ascending myelitis and encephalopathy after intrathecal cytosine arabinoside and methotrexate in an adolescent boy with acute lymphoblastic leukemia.

A 14-year-old boy with acute lymphoblastic leukemia developed acute ascending myelitis followed by encephalopathy after intrathecal administration of methotrexate 15 mg and cytosine arabinoside 50 mg. The patient had none of the risk factors noted previously in other patients with intrathecal therapy (IT) induced neurotoxicity. The doses administered were within the standard scales, and toxicity developed in the second boost of IT 20 days after the first one. There may not be any parameters to predict the occurrence of such severe and rare form of CNS neurotoxicity attributed to IT.