Plasma aldosterone level in a female case of pseudohyperaldosteronism (Liddle's syndrome)

A 22-yr-old female suffering from hypertension, hypokalemic alkalosis and suppressed plasma renin activity was studied. The plasma aldosterone concentration (PAC) ranged between subnormal and normal levels while the other adrenal mineralocorticoids were normal. Examinations through computed tomography and ultrasonography showed no abnormal findings. For differential diagnosis, dexamethasone, spironolactone and triamterene were administered. Triamterene alone corrected the abnormalities in this case, and the therapeutic effect was further enhanced by sodium restriction. Therefore, the present case is strongly suggested to be one of Liddle's syndrome, which is characterized by a primary defect in renal tubular sodium handling and can be corrected with triamterene. However, the patient in our study is different from the first reported case in which aldosterone secretion was estimated to be low. Analysis of the changes in PAC has shown that PAC is parallel with the level of plasma progesterone in accordance with the rhythm of the menstrual cycle and, in the follicular phase, PAC is rather low. It is concluded that the patient was suffering from Liddle's syndrome, and it is assumed that PAC is not always subnormal and, as same as in normal females, PAC may change in accordance with the rhythm of the menstrual cycle in a female case of Liddle's syndrome.     

Peritoneal carcinomatosis following laparoscopic resection of an adrenocortical tumor causing primary hyperaldosteronism

A clinical syndrome combining hypertension and hypokalemic alkalosis led to the diagnosis of primary hyperaldosteronism, caused by a right-sided, 2 cm large, apparently benign aldosterone-producing adenoma. The adrenal tumor was completely resected by laparoscopic adrenalectomy. Six months after surgery, the patient exhibited a severe relapse of hyperaldosteronism. Extensive peritoneal metastases of a mixed aldosterone- and cortisol-secreting adrenocortical carcinoma were found at abdominal laparotomy. In the light of this case report, we discuss the possibility that laparoscopic resection of adrenocortical tumors might contribute to their subsequent peritoneal dissemination.     

Hypertension, hypokalemia and hypoaldosteronism with suppressed renin: a clinical study of a patient with Liddle's syndrome

A 24-yr-old woman with hypertension, hypokalemic alkalosis, low plasma renin and hypoaldosteronism was studied. Plasma aldosterone, renin and potassium returned to normal and blood pressure fell after sodium restriction or the administration of triamterene. Thiazide therapy also normalized her blood pressure while dexamethasone, spironolactone and furosemide did not improve her symptoms. Plasma aldosterone levels were low and responded poorly to a short term ACTH injection, but responded well to the maximal adrenal stimulation by ACTH-Z. Plasma levels of cortisol, corticosterone and deoxycorticosterone were within the normal range. Adrenal scintigram with 131I-adosterol and abdominal computed axial tomography did not reveal the presence of a sizeable adrenal tumor. In addition, the urinary kallikrein excretion was low after sodium restriction and showed no response to saline infusion. These findings suggest that the excessive secretion of unusual mineralocorticoids may not exist in this case. From these observations and the results of the therapeutic responses to the diuretic agents, we conclude that the primary cause of the disorder of this patient seems to be a renal defect in the distal tubule in handling sodium and potassium which is similar to that in Liddle's syndrome.     

Severe Ectopic Cushing Syndrome Caused by Adenoid Cystic Carcinoma of a Salivary Gland

ObjectiveWe present a rare case of Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS). To our knowledge only two similar cases have been previously reported.MethodsThis is a case report of EAS by a metastatic lingual adenoid cystic carcinoma (ACC).ResultsThe patient was diagnosed of a Cushing syndrome caused by tumoral EAS two years after initial cancer diagnosis. Clinical presentation included asthenia, insomnia, hypertension, acne, and hyperpigmentation developing in a period of two months. Laboratory and imaging testing revealed hypokalemic metabolic alkalosis, hypercortisole- mia, high ACTH, nonsuppresion by 8 mg dexamethasone, and a normal pituitary magnetic resonance imaging (MRI). With a high clinical suspicion of EAS, combined medical treatment was started but was unsuccessful. Bilateral adrenalectomy could not be performed given the patient’s rapid deterioration. Immunostained tissue from the original tumor was positive for synaptophysin.ConclusionThis rare case of EAS illustrates the challenge that this condition may confer regarding diagnosis and management. (Endocr. Pract. 2013;19:e118-e121)     

血浆FA、ET-1、Hcy、VEGF水平与妊娠高血压综合征的相关性研究

目的:研究叶酸(FA)、内皮素(ET-1)、同型半胱氨酸(Hcy)和血管内皮生长因子(VEGF)与妊娠高血压综合征的相关性。方法:选择2013年1月~2016年9月在我院进行诊治的妊娠高血压综合征患者80例,分为妊娠期高血压组即A组(40例)以及子痫前期、子痫组即B组(40例),60例正常晚期孕妇为C组,60例正常非孕妇为D组,分别检测各组的血浆FA、ET-1、Hcy和VEGF水平,并进行相关性分析。结果:四组间血浆FA、ET-1和Hcy水平相比,B组的血浆FA和VEGF水平最低(P0.05),ET-1和Hcy水平最高(P0.05);妊娠高血压综合征的妇女血浆FA和VEGF水平均低于正常晚期孕妇,ET-1和Hcy水平明显高于正常晚期孕妇(P0.05);多因素logistic回归分析显示FA、ET-1、Hcy、VEGF水平是妊娠高血压综合征的危险因素。结论:妊娠期FA缺乏引起血浆Hcy水平的升高可能与妊娠高血压综合征的发病及病情发展有关,VEGF可能是妊娠高血压综合征发生、发展的一个重要危险因素。     

Ionenkanalerkrankungen der Niere und Nebenniere

Genetic kidney diseases represent a significant proportion of kidney diseases manifesting in childhood and adolescence, but are also gaining importance in slowly progressive or late-onset adult diseases. A significant portion of kidney diseases particularly in childhood are associated with end stage renal disease and/or other relevant morbidity. An early (molecular) diagnosis can be a prerequisite for a better prognostic assessment and provides opportunities in terms of optimized symptomatic therapy. Mechanistically speaking, mutations in ion channel-associated nephropathy represent—in addition to structural defects of the glomerular filter (e.g., COL4A3, LAMB2, nephrin) and disorders of signaling pathways that are relevant for the development of the urogenital tract (e.g., HNF1B, WT1)—a significant proportion of the group with respect to number and prototypes. Determination of the molecular genetics of (hypokalemic) salt-losing tubulopathies has contributed significantly to our understanding of the central role of the kidney in salt balance. The spectrum of renal ion channelopathies is shown using the example of classical salt-losing tubulopathies (Bartter syndrome and Gitelman syndrome), the transient receptor potential (TRP) channel group and the role of channel changes in aldosteronism and congenital hypertension.     

Licorice reduces serum testosterone in healthy women

Licorice has been considered a medicinal plant for thousands of years. The most common side effect is hypokalemic hypertension, which is secondary to a block of 11beta-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid effect of cortisol. We have investigated the effect of licorice on androgen metabolism in nine healthy women 22-26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6% W.W. of glycyrrhizic acid) daily for two cycles. They were not on any other treatment. Plasma renin activity, serum adrenal and gonadal androgens, aldosterone, and cortisol were measured by radioimmunoassay. Total serum testosterone decreased from 27.8+/-8.2 to 19.0+/-9.4 in the first month and to 17.5+/-6.4 ng/dL in the second month of therapy (p<0.05). It returned to pre-treatment levels after discontinuation. Androstenedione, 17OH-progesterone, and LH levels did not change significantly during treatment. Plasma renin activity and aldosterone were depressed during therapy, while blood pressure and cortisol remained unchanged. CONCLUSIONS: Licorice can reduce serum testosterone probably due to the block of 17-hydroxysteroid dehydrogenase and 17-20 lyase. Licorice could be considered an adjuvant therapy of hirsutism and polycystic ovary syndrome.     

Adrenocortical Hyperfunction Associated with Bronchogenic Carcinoma: Report of Five Cases

Five patients with bronchogenic carcinoma associated with adrenocortical hyperfunction are described. The clinical features, laboratory studies and autopsy findings are discussed and compared with previously reported cases. Four patients presented most of the typical features of this disorder as previously described, whereas the fifth was atypical in some respects. Typical features included: acute onset of adrenocortical hyperfunction in a middle-aged male, rapid downhill course, slight or absent physical signs of Cushing''s syndrome, frequently impaired glucose tolerance, markedly elevated plasma and urinary 17-hydroxycorticosteroids not suppressed by exogenous steroids, absent diurnal variation of plasma corticoids, hypokalemic alkalosis with normal aldosterone excretion, and tumour histology of the oat cell variety. The adrenal glands of two patients were of normal or slightly increased weight, and mean 17-ketosteroid excretion values were normal in three; this contrasts with the marked increase in adrenal weight and 17-ketosteroid excretion in most reported cases.     

高血压患者胰岛素抵抗与代谢综合征及心血管事件的发生情况的相关性分析

目的:分析高血压患者胰岛素抵抗与代谢综合征及心血管事件的发生情况及其影响因素。方法:选择2014年6月至2017年9月解放军113医院及河南大学附属医院收治的382例高血压患者,根据是否存在胰岛素抵抗将其分为单纯高血压(对照组,n=212)和高血压伴胰岛素抵抗(实验组,n=170)。根据国际糖尿病联盟代谢综合征的相关定义将患者分为A组(代谢综合征,n=202)和B组(非代谢综合征,n=180)。比较患者的身高、体质量并计算其体质量指数(BMI)、收缩压(SBP)、舒张压(DBP),检测两组受试者空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、肌酐(SCr)、血尿素氮(BUN)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、采用酶联免疫法测定高敏C反应蛋白(hs-CRP)、脂联素(APN)、空腹胰岛素(FINS)水平。随访1年并记录患者心血管事件发生情况。结果:实验组血清APN、FPG、FINS、HOMA-IR、hs-CRP水平与对照组比较,差异具有统计学意义(P0.05)。A组患者SBP、DBP、BUN、APN、FPG、HOMA-IR、hs-CRP水平明显高于B组,HDL-C水平明显低于B组,差异具有统计学意义(P0.05)。BUN、HDL-C、HOMA-IR、hs-CRP水平升高为高血压患者发生代谢综合征独立危险因素(P0.05)。随访1年后,对照组患者发生心血管事件72例,实验组144例。进一步采用多因素Logistic回归分析显示,血清TG、HDL-C、HOMA-IR、hs-CRP水平升高为高血压患者发生心血管事件的危险因素(P0.05)。结论:高血压伴胰岛素抵抗患者其胰岛素抵抗程度高于单纯高血压患者;胰岛素抵抗与代谢综合征显著相关,为高血压患者发生心血管事件的危险因素。     

A case of hypokalemic myopathy associated with transient hypothyroidism

A case of transient hypothyroidism in the course of hypokalemic myopathy is reported. A 69-year-old woman had severe muscle weakness and marked potassium deficiency associated with alkalosis during treatment with thiazide diuretics. The cause of muscle weakness proved to be hypokalemic myopathy confirmed by clinical findings and muscle biopsy. After the episode of hypokalemic myopathy, serum levels of thyroid hormone were lowered (T4; 3.8 micrograms/dl, T3; 54 ng/dl) and that of TSH was elevated (25.1 microU/ml). Antithyroid microsomal antibody was positive (1:25600) and anti-thyroglobulin antibody was negative. About one month after potassium supplement, her thyroid functions returned to normal, along with normalization of serum potassium level. This is the first documented case report of hypokalemic myopathy accompanied by transient hypothyroidism in a patient with autoimmune thyroiditis. We suggest that this transient hypothyroidism might be induced by hypokalemia during the course of autoimmune thyroiditis.     

P450C17 (CYP17) Deficiency in Native Mexican Patient with a Novel CYP17A1 Mutation

ObjectiveTo report a case of congenital adrenal hyperplasia due to CYP17 deficiency caused by a novel CYP17A1 mutation.MethodsWe describe the clinical, biochemical, genetic, and radiologic findings of a sporadic case of congenital adrenal hyperplasia due to CYP17 deficiency in a young patient.ResultsAn 18-year-old woman presented with hypogonadism and progressive muscle weakness and had not yet undergone thelarche, adrenarche, and menarche. Blood pressure was 155/90 mm Hg, she had no axillary or pubic hair, breasts were Tanner stage 1, and female genitalia were Tanner stage 1. Further laboratory studies showed hypokalemia with metabolic alkalosis, hypergonadotropic hypogonadism, a 46,XY karyotype, a low 17-hydroxyprogesterone level, and a high deoxycorticosterone level. Sequencing of the CYP17A1 gene demonstrated homozygous transversion of cytosine to adenine (TCAàTAA) in exon 5, which causes a premature stop codon at position 288 (Ser288X). Imaging studies showed large adrenal glands, cystic picture in the inguinal canal (suggestive of intra-abdominal testes), and absent Müllerian structures. Exploratory laparotomy was performed to remove the remaining gonads, and the final histologic examination showed atrophic testes.ConclusionsCongenital adrenal hyperplasia due to CYP17 deficiency should be suspected in patients with hypertension, hypokalemic alkalosis, and hypogonadism. In such cases, it is mandatory to assess the karyotype and perform hormonal and molecular genetic studies. (Endocr Pract. 2011;17:99-103)     

Diagnosis of obstructive sleep apnea syndrome]

Symptoms and signs in 12 patients with severe obstructive sleep apnea (OSA) syndrome have been presented. The most common symptoms were snoring , increased motor activity during sleep and excessive daytime somnolence. The factors predisposing to OSA syndrome were obesity and anatomic abnormalities of the upper airway structure. In some cases the signs of OSA syndrome included hypertension, right heart failure, chronic alveolar hypoventilation and polycythemia. Polysomnography showed sleep fragmentation and the prevalence of light sleep stages. Obstructive sleep apneas repeated 73 +/- 23 times per hour of sleep. The mean apnea duration was 19 +/- 8 s. The mean arterial oxygen saturation during apnea was 72 +/- 14%.     

Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies

Hereditary muscle channelopathies are caused by dominant mutations in the genes encoding for subunits of muscle voltage-gated ion channels. Point mutations on the human skeletal muscle Na+ channel (Nav1.4) give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2. Point mutations on the human skeletal muscle Ca2+ channel give rise to hypokalemic periodic paralysis and malignant hyperthermia. Point mutations in the human skeletal chloride channel CIC-1 give rise to myotonia congenita. Point mutations in the inwardly rectifying K+ channel Kir2.1 give rise to a syndrome characterized by periodic paralysis, severe cardiac arrhythmias and skeletal alterations (Andersen's syndrome). Involvement of the same ion channel can thus give rise to different phenotypes. In addition, the same mutation can lead to different phenotypes or similar phenotypes can be caused by different mutations on the same or on different channel subtypes. Bearing in mind, the complexity of this field, the growing number of potential channelopathies (such as the myotonic dystrophies), and the time and cost of the genetic procedures, before a biomolecular approach is addressed, it is mandatory to apply strict diagnostic protocols to screen the patients. In this study we propose a protocol to be applied in the diagnosis of the hereditary muscle channelopathies and we demonstrate that muscle biopsy studies and muscle cell cultures may significantly contribute towards the correct diagnosis of the channel involved. DNA-based diagnosis is now a reality for many of the channelopathies. This has obvious genetic counselling, prognostic and therapeutic implications.     

Ion channels-related diseases

There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia may result from dysfunction of voltage-gated sodium, potassium and calcium channels, or acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's syndrome, policystic kidney disease and Dent's disease, secretion disorders, e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision disorders, e.g., congenital stationary night blindness and total colour-blindness may also be linked to mutations in ion channels.     

Linkage of infantile Bartter syndrome with sensorineural deafness to chromosome 1p.

Bartter syndrome (BS) is a family of disorders manifested by hypokalemic hypochloremic metabolic alkalosis with normotensive hyperreninemic hyperaldosteronism. We evaluated a unique, inbred Bedouin kindred in which sensorineural deafness (SND) cosegregates with an infantile variant of the BS phenotype. Using a DNA-pooling strategy, we screened the human genome and successfully demonstrated linkage of this unique syndrome to chromosome 1p31. The genes for two kidney-specific chloride channels and a sodium/hydrogen antiporter, located near this region, were excluded as candidate genes. Although the search for the disease-causing gene in this family continues, this linkage further demonstrates the genetic heterogeneity of BS. In addition, the cosegregation of these phenotypes allows us to postulate that a single genetic alteration may be responsible for the SND and the BS phenotype. The identification and characterization of this gene would lead to a better understanding of the normal physiology of the kidney and the inner ear.     

THE RELATIONSHIP OF THE REFERRING PHYSICIAN TO THE PSYCHIATRIST

Tumors of the adrenal glands produce hormones which cause a variety of symptoms and signs including high blood pressure, excessive growth of hair on the body and precocious sexual development. By recently developed tests, it has been possible to differentiate high blood pressure due to these tumors from hypertension due to other causes. Removal of these tumors will often alleviate changes caused by them. Localization of the tumor and appraisal of the condition of the contralateral gland should be carried out preoperatively if possible. In this, several kinds of roentgen studies are helpful. Infusions of drugs during operation can be used to control the blood pressure which otherwise would vary widely. During a ten-year period (1942 to 1951) there were observed at the Los Angeles County General Hospital 100 proved cases of non-secreting and secreting primary neoplasms of the adrenal glands. In addition, there were three cases of Cushing's syndrome due to bilateral adrenal cortical hyperplasia, and ten probable cases (four, pheochromocytomas; five, Cushing's syndrome; one, adrenogenital syndrome) in which operation was not done.     

Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome.

Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13 families and have performed SSCP analysis of the coding sequence and the exon-intron boundaries of the NKCC2 gene; and we report 14 novel mutations in patients with antenatal Bartter syndrome, as well as the identification of three isoforms of human NKCC2 that arise from alternative splicing.     

Diabetic Ketoacidosis—A Review of Cases at a University Medical Center

Twenty-five cases of diabetic ketoacidosis were studied retrospectively with respect to clinical characteristics and results of therapy. In this series (as with all 88 patients admitted in the last five years with a diagnosis of diabetic ketoacidosis) there were no deaths. Infection was found to be the most common precipitating event, documented by physical findings and cultures in one-third of these cases.In about two-thirds of the cases, electrocardiograms which were read as abnormal on admission reverted to normal after therapy.In all patients serum potassium levels decreased from admission values; one patient became symptomatically hypokalemic.Low serum potassium levels on admission and early vigorous bicarbonate therapy are emphasized as major predisposing factors of symptomatic hypokalemia. None of the patients had overt hyperosmolar coma, lactic acidosis or cerebral edema during therapy.     

Clinical, biochemical and molecular genetic data in five children with Gitelman's syndrome.

Gitelman's variant of Bartter's syndrome, inherited hypokalemic alkalosis, is caused by mutation in the thiazide-sensitive NaCl co-transporter (NCCT). The main clinical symptoms are: muscular weakness, carpopedal spasm, constipation and short stature. The diagnosis was suspected in five children according to clinical criteria. All patients exhibited carpopedal spasm during febrile illness, three patients had short stature. Biochemical features were: metabolic alkalosis, hypokalemia, hypomagnesemia, low IGF-I levels, hyperkaliuria, hypernatriuria, hypocalciuria and normoprostaglandinuria. Three patients had elevated plasma renin activity and hyperaldosteronism. Mutational analysis of the NCCT gene confirmed the diagnosis in all five patients. Different forms of therapy, potassium and magnesium substitution, spironolactone and indomethacin failed to fully correct hypokalemia and hypomagnesemia, but markedly improved growth velocity and normalized IGF-I levels in the three patients with short stature. During therapy, clinical symptoms disappeared. We conclude that Gitelman's syndrome is a disorder with a variable symptom profile, but can be suspected on clinical signs already in early childhood. The early diagnosis is essential in preventing complications.     

Hyperthyroidism with Periodic Paralysis

Hyperthyroidism may be associated with hypokalemic periodic paralysis. Two cases are presented demonstrating intermittent attacks of flaccid paralysis associated with clinical symptoms, signs and laboratory findings of hyperthyroidism. During an attack, one patient had a serum potassium of 2.1 mEq. per litre.Various factors such as trauma, exposure to cold, excessive carbohydrate ingestion and certain medications have been stated to precipitate an episode of paralysis. Attacks may range from mild weakness to generalized flaccid paralysis with loss of deep tendon reflexes. Several reported patients have died owing to cardiac arrest or respiratory paralysis.During attacks, the serum potassium is usually in the range of 2.2 to 3.2 mEq. per litre. It is postulated that a metabolic abnormality affecting the muscle-cell membrane can occur in the hyperthyroid state resulting in a shift of potassium to the intracellular position, thus producing a situation of hyperpolarization of the muscle-cell membrane which in turn alters the muscle contractibility.The importance of recognizing the unusual association of hypokalemic periodic paralysis with hyperthyroidism is stressed because, with successful treatment of the hyperthyroidism, the episodes of paralysis disappear.