RESUMO
Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Idoso , Inibidor de Quinase Dependente de Ciclina p27/genética , Análise Mutacional de DNA , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/metabolismo , Linhagem , Estudos Prospectivos , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Detecção de Cálcio/genética , Regiões não Traduzidas , Adulto JovemRESUMO
BACKGROUND: There is no consensus regarding the use of perioperative steroids for transsphenoidal pituitary surgery. We audited the effectiveness and safety of our selective perioperative steroid supplementation protocol in patients with pituitary adenomas. METHODS: Two hundred ninety-seven patients underwent 306 endoscopic transsphenoidal surgeries for removal of their pituitary tumors. Steroids were given to those with an impaired hypothalamic-pituitary-adrenal (HPA) axis, age ≥ 60 years, clinical apoplexy, hyponatremia, or if the pituitary gland was not preserved at surgery. We excluded 111 patients in whom the integrity of the HPA axis could not be determined. We compared the incidence of early postoperative adrenal insufficiency and complications in 135 patients with intact HPA axes who underwent surgery without steroids (group A) with 60 patients who had compromised preoperative HPA axes and received perioperative steroids (group B). In addition, we audited the total number of protocol violations during this period. RESULTS: Five patients (3.7%) in group A developed postoperative hypocortisolemia. There was no significant difference in the incidence of cerebrospinal fluid leak, diabetes insipidus, or hyponatremia between both groups. There were protocol deviations in 47 (15.4%) patients. Twenty one of these patients did not receive perioperative steroids in violation of the protocol, of whom 4 (19%) developed postoperative hypocortisolemia. CONCLUSIONS: Our steroid sparing protocol was both safe and effective. The 15% incidence of protocol deviations is a reminder that the rigorous usage of checklists is mandatory for successful clinical practice.
Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/cirurgia , Esteroides/uso terapêutico , Adulto , Idoso , Vazamento de Líquido Cefalorraquidiano , Feminino , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/deficiência , Sistema Hipotálamo-Hipofisário , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Sistema Hipófise-Suprarrenal , Estudos Retrospectivos , Osso Esfenoide/cirurgiaRESUMO
OBJECTIVE: Ectopic adrenocorticotropic hormone (ACTH) secretion is a less common cause of Cushing syndrome and is seen in 5 to 10% of cases with endogenous hypercortisolemia. We hereby describe our experience of patients with ectopic ACTH syndrome, who have been managed over the past 10 years at a tertiary care center in Southern India. METHODS: The inpatient and outpatient records of patients from 2006 to 2015 were retrospectively reviewed. The clinical features, clinical history, biochemical values, imaging features, including radiologic findings and positron emission tomography scans, management, details of follow-up, and outcomes, were documented. We compared the biochemical findings in these patients with 20 consecutive patients with Cushing disease (Cushing syndrome of pituitary origin). RESULTS: A total of 21 patients were studied. The median age at presentation was 34 years (range, 19 to 55 years). Seven patients had thymic carcinoid, 7 had bronchial carcinoid, 3 had lung malignancies, 2 had medullary carcinoma thyroid, 1 patient had a pancreatic neuroendocrine tumor, and 1 patient had an occult source of ACTH. The most common clinical features at presentation were muscle weakness (95%), hyperpigmentation (90%), facial puffiness (76%), easy bruising (61%), edema (57%), and striae (52%). Extensive acne was seen in a large number of patients (43%). Only 3 patients (14%) had central obesity. The median 8 am cortisol was 55.5 µg/dL (range, 3.8 to 131 µg/dL), median 8 am ACTH was 207 pg/mL (range, 31.1 to 703 pg/mL), and the median 24-hour urinary free cortisol was 2,484 µg (range, 248 to 25,438 µg). Basal cortisol and ACTH, as well as midnight cortisol and ACTH level, were markedly higher in patients with ectopic Cushing syndrome as compared to patients with Cushing disease. Twelve of 21 patients had developed life-threatening infections by follow-up. Nine patients had undergone surgical intervention to address the primary tumor. However, only 1 patient exhibited a complete cure on follow-up. CONCLUSION: In our series, ectopic Cushing syndrome was most commonly seen in association with intrathoracic tumors such as bronchial or thymic carcinoid. Hyperpigmentation and proximal myopathy were frequent, while central obesity was uncommon. Early and rapid control of hypercortisolemia was important in order to prevent life-threatening infections and metabolic complications. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CT = computed tomography DOTATATE = 68Ga-DOTA-Tyr3-octreotate ECS = ectopic Cushing syndrome FDG = fluorodeoxyglucose MTC = medullary thyroid cancer NET = neuroendocrine tumor PET = positron emission tomography.
Assuntos
Síndrome de ACTH Ectópico/fisiopatologia , Síndrome de Cushing/fisiopatologia , Neoplasias/metabolismo , Síndrome de ACTH Ectópico/complicações , Síndrome de ACTH Ectópico/diagnóstico por imagem , Síndrome de ACTH Ectópico/metabolismo , Acne Vulgar/etiologia , Adulto , Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/metabolismo , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/metabolismo , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/metabolismo , Síndrome de Cushing/etiologia , Síndrome de Cushing/metabolismo , Edema/epidemiologia , Feminino , Humanos , Hidrocortisona/metabolismo , Hiperpigmentação/etiologia , Índia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Neoplasias/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Obesidade Abdominal/etiologia , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Centros de Atenção Terciária , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Adulto JovemRESUMO
BACKGROUND: This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing's disease (CD). METHOD: We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 µg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery. RESULTS: Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n = 15), enlarged adenomectomy (n = 21) and subtotal/hemihypophysectomy (n = 17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 µg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6-18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 µg/dl in the 1st week after surgery was highly predictive of remission (p = 0.001). CONCLUSION: ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.
Assuntos
Endoscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/cirurgia , Osso Esfenoide/cirurgia , Adulto , Idoso , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Vazamento de Líquido Cefalorraquidiano/etiologia , Dexametasona/farmacologia , Feminino , Seguimentos , Humanos , Hidrocortisona/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Hipofisárias/patologia , Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Postoperative diabetes insipidus (DI) is a significant cause of morbidity in craniopharyngiomas (CP) and its effective management improves outcome. OBJECTIVE: The objective was to determine the efficacy of a treatment protocol in the management of early postoperative DI in CP. MATERIALS AND METHODS: The quality of postoperative DI control in a prospective cohort of 26 patients treated utilizing a strict protocol (Group 1) was compared with a retrospective cohort of 34 patients (Group 2) managed without a protocol. A 6-h urine output more than 4 ml/kg/h or serum sodium (Na+) more than 145 mEq/L was diagnosed as DI. The quality of DI control was assessed by determining the incidence of serum Na+ values above 150 mEq/L or below 130 mEq/L and the incidence of wide (>10 mEq/L) intra-day fluctuations of serum Na+ levels. RESULTS: The occurrence of high and low serum Na+ levels was significantly lower in Group 1(P = 0.032). The incidence of serum Na+ exceeding 150 mEq/L on postoperative days 2 and 3 was significantly higher in Group 2 as compared with those in Group 1 (25% vs. 7.6%, P = 0.0008). Hyponatremia was more frequent in Group 2 and tended to occur on postoperative days 6, 7, and 8 (14.2% vs. 3.2%; P = 0.004). The same patients who had hypernatremia in the early part of the week later developed hyponatremia. Although the incidence of wide intra-day fluctuations (>10 mEq/L) was higher in Group 2, it did not reach statistical significance. CONCLUSION: A strict protocol based management results in better control of postoperative DI in CP.
RESUMO
We report the rare occurrence of an opticochiasmatic glioblastoma multiforme 6 years following conventional radiotherapy for Cushing's disease. This article highlights the risks of collateral damage to the optic apparatus when irradiating the sellar region.
Assuntos
Neoplasias Encefálicas/cirurgia , Síndrome de Cushing/radioterapia , Glioblastoma/etiologia , Glioblastoma/cirurgia , Neoplasias Induzidas por Radiação/cirurgia , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etiologia , Feminino , Glioblastoma/diagnóstico , Humanos , Neoplasias Induzidas por Radiação/diagnóstico , Radioterapia/efeitos adversos , Resultado do TratamentoRESUMO
Snake venom can cause local tissue damage and lead to coagulopathy, shock, neurotoxicity and acute kidney injury. Hypopituitarism is a rare complication following snake bite. It has been described following Russell's viper bite from Burma and South India. Herein we describe a patient who presented with severe thyrotoxicosis and partial hypopituitarism following snake bite.
Assuntos
Daboia , Hipopituitarismo/etiologia , Mordeduras de Serpentes/complicações , Tireoidite Autoimune/etiologia , Venenos de Víboras/intoxicação , Animais , Feminino , Humanos , Hipopituitarismo/diagnóstico , Tireoidite Autoimune/diagnóstico , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: To report a case of primary amenorrhoea and to describe an approach to evaluation. METHODS: Primary amenorrhoea can be due to diverse causes and needs detailed and astute evaluation. We report the case of a 17 years old individual born and brought up as a female, who was brought to us with primary amenorrhoea. Approach to such a patient with a review of available published literature is described. RESULTS: After detailed history, biochemical testing, imaging and karyotyping, we found that this patient had a XY karyotype with normal uterus, fallopian tubes and vagina, but streak gonads. CONCLUSION: Swyer syndrome (46,XY gonadal dysgenesis), a sex reversal disorder characterized by a phenotypic female with non-functional streak gonads, poorly developed secondary sexual characters, primary amenorrhoea and 46,XY karyotype was diagnosed. This patient was treated with gonadectomy and sex hormone replacement.
Assuntos
Amenorreia/diagnóstico , Disgenesia Gonadal 46 XY/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Cariotipagem , Adulto JovemRESUMO
The aim of this study was to determine the factors influencing the use of a transcranial (TC) approach in pituitary adenomas and suggest a decision-making tree for the surgical strategy. The data for 23 (4.6%) patients who underwent TC surgery from amongst 494 pituitary adenomas were retrospectively analyzed. Eight factors on magnetic resonance imaging (MRI) that could predict a difficult transsphenoidal (TS) surgery were noted. Adverse findings at TS surgery leading to a 2nd stage TC surgery were documented. Eighteen of the 23 cases were giant adenomas. Thirteen patients underwent TC surgery alone or as an initial approach when combined with TS while 10 underwent 2nd stage TC surgery following a TS approach. Most cases in the first group had 3 or more radiological factors in combination with a small sella. The 2nd group had higher sellar tumor volumes and fewer unfavourable radiological factors that led to the initial use of the TS approach. A hard, fibrous consistency or a significant residue obscured from the surgeon's view, and difficulty in hemostasis were additional factors prompting the use of a TC approach. Tumor excision ≥90% could be achieved in 13 cases (56.5%). Post-operative RT was administered in 12 patients. There were 2 deaths (8.7%) and the major morbidity rate was 43 %. Despite advances in endoscopic surgery the TC approach may be required in 5% of cases. A study of the preoperative MRI for factors that predict difficulty with the TS approach might encourage the surgeon to consider a TC surgery either as an initial approach or combined with a TS surgery.
Assuntos
Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND & OBJECTIVES: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. METHODS: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. RESULTS: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 µg/day had a low sensitivity and uNMN >600 µg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. INTERPRETATION & CONCLUSIONS: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.
Assuntos
Neoplasias das Glândulas Suprarrenais/urina , Metanefrina/urina , Normetanefrina/urina , Feocromocitoma/urina , Neoplasias das Glândulas Suprarrenais/sangue , Adulto , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Metanefrina/sangue , Pessoa de Meia-Idade , Normetanefrina/sangue , Feocromocitoma/sangue , Curva ROC , Sensibilidade e EspecificidadeRESUMO
PURPOSE: This study aims to determine the incidence, predictors, early post-operative course of diabetes insipidus (DI) in paediatric craniopharyngiomas(CP) and compare the findings with adults. METHODS: Retrospective analysis of clinical, biochemical, radiological and operative data for 102 consecutive CP surgeries (45 paediatric and 57 adult cases) was done. Bivariate and multivariate analyses were done to determine the predictors of DI. The incidence of the triphasic response and electrolyte abnormalities in the first post-operative week was compared between children and adults. RESULTS: Children had larger tumours and higher incidence of cystic tumours and hydrocephalus. Preoperative DI was close to 15 % in both the age groups. Radical/subtotal excision was achieved in 58 % of children and 53 % of adults. The incidence of post-operative DI was 80 % and 63 % in children and adults, respectively. Children had significantly higher incidence of permanent DI (55.6 %). Radical excision in children (p = 0.000); previous tumour surgery (p = 0.014) and new onset hypopituitarism (p = 0.019) in adults were associated with permanent DI. The triphasic response (23 %), wide intra-day serum sodium fluctuations and hyponatraemia were more common in children. CONCLUSIONS: Post-operative DI is a frequent and significant cause of morbidity in children undergoing surgery for CP. Children have a higher incidence of permanent DI. Radical excision is a predictor of permanent DI in children, whereas previous tumour excision and new onset hypopituitarism were predictors of permanent DI among adults. The management of post-operative DI is more difficult in children and the treating physician needs to be alert to detect the triphasic response.
Assuntos
Craniofaringioma , Diabetes Insípido/epidemiologia , Diabetes Insípido/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Neoplasias Hipofisárias , Complicações Pós-Operatórias/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Craniofaringioma/diagnóstico , Craniofaringioma/epidemiologia , Craniofaringioma/cirurgia , Eletrólitos/metabolismo , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Phaeochromocytomas may be discovered incidentally when patients present with hypertensive crisis during general anaesthesia. A 49-year-old man underwent thyroidectomy 25 years ago and was diagnosed to have spindle cell carcinoma of the thyroid. He presented with recent onset of hoarseness of voice and was found to have a vocal cord nodule. He developed a hypertensive crisis during surgery. He was subsequently evaluated and found to have bilateral phaeochromocytoma. Further evaluation revealed a RET proto-oncogene mutation at codon 634 consistent with multiple endocrine neoplasia (MEN)-2A.
Assuntos
Hipertensão/complicações , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Neoplasias da Glândula Tireoide/complicações , Prega Vocal , Neoplasias das Glândulas Suprarrenais/complicações , Anestesia Geral , Carcinoma/cirurgia , Humanos , Doenças da Laringe/complicações , Masculino , Pessoa de Meia-Idade , Feocromocitoma/complicações , Proto-Oncogene Mas , Neoplasias da Glândula Tireoide/cirurgia , Tomografia Computadorizada por Raios XRESUMO
We describe an endoscopic transsphenoidal excision of a GH-PRL-secreting pituitary adenoma and remodeling of frontotemporal fibrous dysplasia in a patient with McCune-Albright syndrome. Sphenoid dysplasia rendered transsphenoidal surgery challenging, but a study of the radiological anatomy and good surgical planning made this feasible. Medical therapy and radiation was required for persistent acromegaly after surgery.
Assuntos
Endoscopia/métodos , Displasia Fibrosa Poliostótica/complicações , Neoplasias Hipofisárias/cirurgia , Prolactinoma/cirurgia , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To estimate the prevalence of USP8, USP48, and BRAF mutations in patients with Cushing's disease (CD) from the Indian subcontinent, and determine their genotype-phenotype correlation. METHODS: We prospectively recruited 46 patients with CD who underwent surgery between September 2015 and July 2019 at our institute. Fresh frozen tumour tissue was obtained in all patients. Using Sanger sequencing, the presence of somatic USP8 mutations was documented and the frequency of USP48 and BRAF mutations in USP8 wild-type corticotroph adenomas was determined. Clinical, hormonal, and surgical data were then compared between USP8-, USP48- and BRAF-variant carriers and patients with wild-type tumours. RESULTS: Signature USP8 mutations were detected in 17 (37%) patients. Of the 29 USP8 wild-type adenomas, 4 (13.8%) harboured USP48 mutations, one of them being a splice-site mutation that has previously not been described. BRAF mutations were not found in any of the 29 patients. Corticotroph adenomas with USP8 mutations had a higher incidence of Crooke's hyaline change than wild-type tumours (70.6 vs. 37.9%, p = 0.032). Adenomas with USP48 mutations had a higher rate of cavernous sinus invasion than their wild-type counterparts (50 vs. 4%, p = 0.042). No other significant phenotypic difference could be established between mutant and wild-type tumours. CONCLUSIONS: The prevalence of USP8 mutations in our series of patients with CD was 37%. The prevalence of USP48 mutations in USP8 wild-type adenomas was 13.8%, including a novel splice-site mutation. BRAF mutations were not found in any USP8 wild-type tumour. USP8-mutants showed significantly more Crooke's hyaline change and USP48-mutants were more likely to demonstrate cavernous sinus invasion.
Assuntos
Adenoma , Hipersecreção Hipofisária de ACTH , Adenoma/genética , Endopeptidases/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Estudos de Associação Genética , Humanos , Índia , Mutação , Hipersecreção Hipofisária de ACTH/genética , Proteínas Proto-Oncogênicas B-raf/genética , Ubiquitina Tiolesterase/genética , Proteases Específicas de Ubiquitina/genéticaRESUMO
Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.
Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Alelos , Feminino , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Índia , Masculino , Mutação/genética , Fenótipo , Reação em Cadeia da Polimerase/métodos , Esteroide 21-Hidroxilase/genéticaRESUMO
BACKGROUND: Delayed hyponatremia is a serious complication seen after pituitary surgery. We document the incidence, presentation, outcome and risk factors for this condition. MATERIALS AND METHODS: This was a retrospective study involving 222 patients operated for nonfunctioning pituitary macroadenomas between 2007-2016. Delayed hyponatremia was defined as serum sodium <135 mmol/L, occurring after the third post-operative day. Hyponatremia was categorized as mild (134-130 mmol/L), moderate (129-125 mmol/L) and severe (<125 mmol/L). All patients received intravenous (0.9%) saline, intravenous hydrocortisone and 12g oral salt over 24 hours. Patients with severe hyponatremia were given 3% saline. RESULTS: Fifty eight patients (26%) developed delayed hyponatremia; thirty (13.5%) had severe hyponatremia. Delayed hyponatremia usually (43.1%) occurred on the seventh post-operative day (range, 3-15 days). Most patients (81%) remained asymptomatic; 11 patients developed vomiting (5), seizures (3), lethargy (1), fever (1) and paralytic ileus (1). One patient developed status epilepticus. Patients who manifest symptoms had lower sodium levels as compared to those who did not have symptoms (mean 117.7 mmol/L vs. 123 mmol/L; P < 0.01). Male gender (P = 0.002) and intra-operative CSF leak (P = 0.003) were risk factors for developing delayed hyponatremia. Other factors like, age, pre-operative cortisol levels, extent of resection and post-operative diabetes insipidus did not correlate with the occurrence of delayed hyponatremia. Patients who maintained their mean serum sodium levels >138 mmol/L (day 1-day 3) were unlikely to develop delayed hyponatremia (sensitivity, 55.2% and specificity, 83.9%), positive predictive value, 63.2% [confidence interval (CI) 48, 76.7%] and negative predictive value, 78.8% (CI 70.6, 85.5%). In most patients (57%) hyponatremia was corrected within 48 hours (h). CONCLUSIONS: We recommend routine serum sodium testing on the seventh post-operative day for all patients undergoing pituitary surgery. Most patients remain asymptomatic and unless they are detected early they can go on to develop serious complications.
Assuntos
Adenoma/cirurgia , Hiponatremia/epidemiologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Doenças Assintomáticas , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Feminino , Hidratação , Humanos , Hiponatremia/fisiopatologia , Hiponatremia/terapia , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de Risco , Solução Salina Hipertônica/uso terapêutico , Convulsões/fisiopatologia , Índice de Gravidade de Doença , Fatores Sexuais , Cloreto de Sódio/uso terapêutico , Seio Esfenoidal , Fatores de Tempo , Vômito/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE AND AIMS: To study hormonal axis (HA) dysfunction pre-operatively and at three months after surgery in patients with large (>3 cms) (Hardy's grade C) and giant (>4 cms) nonfunctioning pituitary adenomas (NFPA). METHODS: One hundred thirty nine patients operated between 2006 and 2017, with 3 months post-operative hormonal evaluation, were included in this retrospective study. HA damage was categorized as 0 to 3 based on number of axes (thyrotroph, corticotroph and gonadotroph) that were affected. Risk factors studied for HA dysfunction before and after surgery included duration of symptoms, size of tumor, diabetes mellitus, hypertension and extent of resection. RESULTS: Preoperatively 45 (32.3%) had no axis involvement, 34 (24.4%), 36 (25.8%) and 24 (17.2%) had one, two and three axes involvement respectively. Thyrotroph axis was affected in most patients. Tumor volume had significant correlation with preoperative pituitary dysfunction (P < 0.000). Post-operatively HA function remained same in 100 (72%), improved in only 7 (5%) and worsened in 32 (23%) of the patients. Of the 3 HA, corticotroph function worsened in most patients. None of the patients who had dysfunction in all three axes had improvement after surgery. No significant risk factors were associated with post-operative pituitary function outcomes. Persistent diabetes insipidus was noted in six (4.3%) patients. CONCLUSION: Pre-operatively anterior pituitary dysfunction is noted in nearly two-thirds of patients with large and giant NFA. Tumor volume >15 cc had significant correlation with pre-operative panhypopituitarism. Post-operatively, pituitary function remains the same in nearly three quarters of the patients. No significant risk factors were found for post-operative hormonal outcomes.
Assuntos
Adenoma/cirurgia , Hormônio Adrenocorticotrópico/sangue , Hormônio Foliculoestimulante/sangue , Hormônio do Crescimento Humano/sangue , Hormônio Luteinizante/sangue , Neoplasias Hipofisárias/cirurgia , Prolactina/sangue , Tireotropina/sangue , Adenoma/sangue , Adulto , Feminino , Humanos , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroendoscopia , Neoplasias Hipofisárias/sangue , Período Pós-Operatório , Estudos Retrospectivos , Testosterona/sangue , Hormônios Tireóideos/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: The global prevalence of obesity is increasing and has nearly doubled in the last decade, disproportionately impacting less-developed countries. The aim of this cross-sectional study was to analyse health-related quality of life (HRQOL) in morbidly obese women attending a bariatric clinic in India, and assess potential obesity indicators that can be utilised in under-resourced settings, to better understand HRQOL of individual patients. METHODS: Anthropometric measurements were collected, including waist circumference, hip circumference, waist-hip ratio, waist-height ratio and body mass index (BMI). HRQOL was assessed using an obesity-related quality-of-life questionnaire focused on the impact of obesity on physical distress, self-esteem, sexual life and work life. RESULTS: The average BMI of study participants was 39.6 kg/m2, with an average HRQOL of 40.2%. The strongest correlation was noted between BMI and HRQOL (R2=0.16). Exploratory analyses demonstrated that patients with higher BMI quartiles had lower scores for physical impact and psychosocial impact, and higher scores for sexual health, comfort with food, and experience with dieting compared to patients in lower quartiles. CONCLUSION: In South Indian, middle-aged, morbidly obese women, HRQOL is lower than average and is highly correlated with BMI, with different BMI levels having higher impacts in different subcategories, supporting the need for an individualised therapeutic focus for each patient.
RESUMO
CONTEXT: The size and morphology of the adrenal glands are affected by several physiological and pathological conditions. Radiologists need to be aware of the normal thickness of adrenal gland to accurately assess patients with suspected adrenal pathology. However, there is limited data on the normal size of the adrenal glands. Moreover, this has not been studied in our population. AIMS: To study the normal thickness of adrenal gland on computerized tomography (CT) in Indian adult population. SETTINGS AND DESIGN: Retrospective study in a tertiary care hospital in Southern India. SUBJECTS AND METHODS: Our study included 586 adults who underwent a CT abdominal angiogram over 15 months, and excluding patients with clinical or imaging evidence of adrenal disease. The measurements made included: the maximum thickness of the body, medial and lateral limbs, measured perpendicular to the long axis. RESULTS: The median age was 51 (range: 18-85) years. The mean maximum thickness of the adrenal body, medial, and lateral limbs were 7.2 ± 1.8, 4.1 ± 1.1, and 4.3 ± 1.1 mm on the right side and 8.8 ± 1.9, 4.7 ± 1.1, and 4.9 ± 1.3 mm on the left. The cumulative thickness of the body and the limbs were 15.6 ± 3.7 mm and 18.4 ± 3.8 mm on the right and left sides, respectively. There was a statistically significant difference in all the measurements between the right and left adrenal glands (all P values = 0.000) and between men and women, being larger in men (P value <0.05). Among our patients 27% had at least one adrenal gland body measuring ≥10 mm in thickness. CONCLUSIONS: Our study has defined the normal range of adrenal gland thickness in an Asian Indian adult population, which may be used as a baseline reference for future research and as a reference for radiological reporting.
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Re-operative adrenal surgery for recurrent pheochromocytoma/paraganglioma (PCC/PGL) is a therapeutic situation not commonly encountered. The recurrence rate of pheochromocytoma is estimated to be 6.1-16.5% of patients from published retrospective series; there are no reports from the Asian continent. A retrospective analysis of the departmental database was performed on patients who had undergone surgery for PCC/PGL from January 2004 to December 2014 at the Christian Medical College Hospital, Vellore, India. Among 99 patients identified during the study period, there were 14 recurrent tumours and 13 patients underwent re-operative surgery. We located eight recurrences on the right side, three on the left side and three in the midline. All 14 recurrences were functioning, and the biochemical analysis as well as imaging studies were positive in 13 of them. The mean duration to recurrence from the time of the primary surgery was 76.3 months (range 6-180 months). Of the 89 patients who underwent their first operation at our centre, 67.4% reported for follow-up for a mean period of 25 months (range 4-132 months). Four of these required re-operation with a recurrence rate of 4.5% (4/89). The open approach was used for all but one of the recurrent tumours. Recurrence following surgery for PCC/PGL is a rarely studied though significant problem. Right adrenal tumour recurrences were most common, and all these recurrences were in the retrocaval region; this typical phenomenon may be dubbed the 'right retrocaval trap'. The reason for this was presumably due to difficult access and inadequate exposure of this area in open and laparoscopic surgery, resulting in incomplete dissection.