Should we suspect primary aldosteronism in patients with hypokalaemic rhabdomyolysis? A systematic review.

Severe hypokalaemia causing rhabdomyolysis (RML) in primary aldosteronism (PA) is a rare entity, and only a few cases have been reported over the last four decades. This systematic review and case report aims to gather all published data regarding a hypokalaemic RML as presentation of PA in order to contribute to the early diagnosis of this extremely rare presentation. With the use of PubMed Central, EMBASE, and Google Scholar, a thorough internet-based search of the literature was conducted to identify articles and cases with RML secondary to hypokalaemia due to PA between June 1976 and July 2023. The case study concerns a 68-year-old male patient with hypokalaemic RML at presentation of PA. In the systematic review of the literature, 37 cases of RML secondary to hypokalaemia due to PA have been reported to date. In summary, the median age was 47.5 years, the male/female ratio was 17/21, all patients presented symptoms (weakness and/or myalgia), all the patients were hypertensive, and only four patients had complications with acute kidney injury (AKI). Although PA rarely presents with RML, it should be suspected when marked hypokalaemia and hypertension are also present. Early detection and management are essential to reduce the frequency of manifestations such as AKI.

Conversion from Duodenal Switch to Single Anastomosis Duodenal Switch to Deal with Postoperative Malnutrition.

BACKGROUND: Duodenal switch (DS) is considered one of the most effective bariatric techniques for long-term weight and comorbidity control. After these operations, some patients may get severe complications related to malnutrition and a few of them may need surgical revision. Lengthening the common channel (CC) is usually the solution: changing the Roux anastomosis or with a side-to-side anastomosis (kissing X). We propose that when simplified construction of the DS is used, conversion to single anastomosis DS (SADI-S/OADS) is an easy and safe choice. OBJECTIVES: To evaluate the safety and effectiveness of conversion from DS to SADI-S in cases of malnutrition. METHODS: We report three patients with severe malnutrition after a DS at 9, 74, and 84 months. One of them had also liver failure related to alcohol abuse and malnutrition. Laparoscopic reoperations included a new ileo-ileal anastomosis and takedown of the Roux-en-Y anastomosis with the aim of lengthening the CC. RESULTS: All three patients were successfully converted by laparoscopy. After a median follow-up of 54.6 months [32-76 months], all of them had moderate weight regain and returned to normal biochemical nutritional parameters. Two patients with type 2 diabetes (T2DM) before DS had complete remission before conversion; one of them had recurrence of T2DM after conversion. The patient with liver failure improved significantly after conversion. CONCLUSIONS: Conversion from DS to SADI-S/OADS is a simple operation with excellent results in resolving malnutrition in those patients. However, weight regain and recurrence of comorbidities may arise.

Intestinal absorption and pancreatic function are preserved in anorexia nervosa patients in both a severely malnourished state and after recovery.

INTRODUCTION: Anorexia nervosa (AN) is characterised by a refusal to normal body weight accompanied by a marked restriction of food intake, frequently leading to severe malnutrition. In severe malnutrition and wasting syndromes, mucosal atrophy, altered gastrointestinal motility and pancreatic atrophy, which alter digestive function and can exacerbate malnutrition, have been described. The objective of this work was to determine intestinal absorption and pancreatic function in severely malnourished AN patients before and after recovery. METHODS: Ten severely malnourished AN women were studied at hospital admittance (body mass index = 11.44-16.16 kg/m(2)) and after weight recovery with artificial nutrition (body mass index ≥ 20 kg/m(2)). A (13)C-labelled triglycerides digestion test, faecal elastase test and d-xylose absorption test were performed. RESULTS: In nine patients, (13)C-labelled triglycerides digestion tests and the faecal elastase and d-xylose tests were normal both before and after weight recovery. In one patient, the results were abnormal, and they led to the detection of a previously undiagnosed celiac disease in addition to her AN. CONCLUSION: In this series, there was neither intestinal absorption nor pancreatic function disturbances in severely malnourished AN patients either before or after weight recovery. The usefulness of these tests in the differentiation of functional versus structural changes needs further studies.

Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas / Clinical and molecular study of five families with resistance to thyroid hormones

Fundamento y objetivo: La resistencia a la acción de las hormonas tiroideas (SRHT) es un síndrome causado mayoritariamente por mutaciones en el gen receptor beta de las hormonas tiroideas (THRB). Se estudian cinco familias con fenotipo de SRHT. Pacientes y método: Se realizó secuenciación de THRB. Se evaluó la respuesta a triyodotironina (T3) y efecto dominante negativo de los mutantes in vitro y se estudiaron los mecanismos de resistencia en sujetos sin mutación THRB cuantificando en cultivos de fibroblastos cambios de expresión en los genes regulator of calcineurin 2 (ZAKI4) y Kruppel-like factor 9 (BTEB). Resultados: Tres casos presentaron mutaciones en THRB: R243Q, R320C, R429Q, dando lugar a receptores TRβ con menor respuesta a T3. R243Q y R320C ejercen efecto dominante negativo. Un sujeto sin mutación THRB presentó cambios de expresión en ZAKI4 y BTEB similar a R230C, mientras que el otro mostró niveles de expresión superiores a los controles. Conclusiones: Mutaciones heterocigotas en THRB causaron tres de los casos de SRHT estudiados. Uno de los casos con SRHT sin mutación se comporta a nivel molecular como los portadores de mutación, mientras que en el otro la resistencia no está mediada por TRβ (AU)

Background and objective: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. Patients and methods:THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures.Results: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. Conclusions:Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRβ independent (AU)

[Clinical and molecular study of five families with resistance to thyroid hormones]. / Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas.

BACKGROUND AND OBJECTIVE: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. PATIENTS AND METHODS: THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures. RESULTS: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. CONCLUSIONS: Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRß independent.

Pituitary stalk dysgenesis-induced hypopituitarism in adult patients: prevalence, evolution of hormone dysfunction and genetic analysis.

OBJECTIVES: To investigate the prevalence of pituitary stalk dysgenesis (PSD) in adult hypopituitary patients by describing the chronology of hormone deficiencies and their potential correlation with traumatic delivery, mutations in genes required for pituitary development and function and pituitary stalk visibility on MRI. DESIGN: Retrospective and prospective study involving 231 hypopituitary patients, including 26 diagnosed with PSD. Clinical, biochemical and radiological studies were reviewed. Molecular analyses of HESX1, LHX4,PROP1 and POU1F1 genes were performed prospectively. RESULTS: PSD was present in 11.2% of hypopituitary patients. PSD was diagnosed before 14 years of age in 46.2% of cases, between 14 and 18 years of age in 23%, and in adulthood in 30.8%. Perinatal complications or gene mutations were present in 26.9 and 4.3% of patients, respectively. At first assessment, 92.3% of patients had growth hormone (GH) deficiency. 26.9% presented as combined pituitary deficiencies and 7.6% as panhypopituitarism. Hormone deficiencies were progressive during follow-up in 84.6%. 96% progressed to multiple deficiencies and 46% to panhypopituitarism. No significant association was found between hormonal dysfunction and previous perinatal damage or breech delivery (p = 0.17), PROP1 mutations (p = 0.26) or pituitary stalk visibility on MRI (p = 0.52). No mutations in POU1F1, HESX1 and LHX-4 genes were detected. CONCLUSION: In this study, PSD prevalence in adult hypopituitary patients was 11.2%. Typical clinical presentation includes isolated or combined pituitary hormone deficiencies during the pediatric age, which usually progress to combined or complete hypopituitarism in adulthood. Phenotype is highly variable depending on hormone profile and age at onset.

Hypopituitarism and growth hormone deficiency in adult subjects after traumatic brain injury: who and when to test.

Traumatic brain injury (TBI) was traditionally considered an infrequent cause of hypopituitarism. However recent reports strongly suggest that TBI-mediated pituitary hormones deficiency may well be more frequent than previously thought. As the prevalence of hypopituitarism is not dependent on the severity of the trauma and considering the high number of TBI events in all industrialized countries a screening procedure for detecting hormone deficiencies in all TBI patients is not possible. In the present work a suggestion for screening a subgroup of TBI patients is discussed in order to increase the effectiveness of the whole procedure.

Effect of acute reduction of free fatty acids by acipimox on growth hormone-releasing hormone-induced GH secretion in type 1 diabetic patients.

BACKGROUND: In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with acipimox, alone or in combination with GHRH, on GH secretion in DM1. METHODS: Six type 1 diabetic patients were studied (three women, three men), mean age of 30 +/- 2.1 years, body mass index (BMI) 23.1 +/- 1.5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 microg/kg intravenously (i.v.) at min 180], acipimox (250 mg orally at min 0 and 120) and GHRH plus acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose. RESULT: In control subjects, the GH area under the curve (AUC; microg/l x 120 min) was for acipimox-treated 1339 +/- 292 and 1528 +/- 330 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus acipimox was 3031 +/- 669, significantly greater than the response after acipimox alone (P<0.05) or GHRH alone (P<0.05). In diabetic patients, the GH AUC was for acipimox-treated 2516 +/- 606 and 1821 +/- 311 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus acipimox was 7311 +/- 1154, significantly greater than the response after acipimox alone (P<0.05) or GHRH alone (P<0.05). The GH response after acipimox was increased in diabetic when compared with normal (P<0.05), with a GH AUC of 1339 +/- 292 and 2515 +/- 606 for normal subjects and diabetic patients, respectively. The GH response after acipimox plus GHRH was increased in diabetic when compared with normal (P<0.05), with a GH AUC of 3031 +/- 669 and 7311 +/- 1154 for normal subjects and diabetic patients, respectively. The administration of acipimox induced a FFA reduction during the entire test. CONCLUSIONS: Reduction of free fatty acids with acipimox is a stimulus for GH secretion in DM1. The combined administration of GHRH plus acipimox induces a markedly increased GH secretion in type 1 diabetic patients when compared with normal subjects. These data suggest that patients with DM1 exhibit a greater GH secretory capacity than control subjects, despite the fact that endogenous FFA levels seems to exert a greater inhibitory effect on GH secretion in these patients.