Thyrotoxic Periodic Paralysis and Complicated Thyrotoxicosis, Two Presentations of Hyperthyroidism with Notable Differences in their Clinical Manifestations: An Experience from a Tertiary Care Hospital in the United States.

OBJECTIVE: Thyrotoxic periodic paralysis (TPP) is a muscular disorder characterized by sudden episodes of muscle weakness and hypokalemia in the setting of thyrotoxicosis. We aimed to report our experience with TPP in West Texas and compare its clinical presentation to that of patients admitted for complicated thyrotoxicosis. METHODS: Retrospective review of records of adult patients with admission diagnosis of hyperthyroidism, thyrotoxicosis, and/or discharge diagnosis of periodic paralysis seen at our institution in a 6-year period. RESULTS: Patients admitted for complicated thyrotoxicosis were more commonly females of a mean age of 44 years. Patients with TPP were more commonly Hispanic males of a mean age of 27 years. Despite no significantly different thyroid hormone levels, patients with TPP presented with less-severe signs and symptoms of hyperthyroidism, as reflected by lower Burch-Wartofsky score on admission (19 vs. 35; P<.001) and lower occurrence of atrial fibrillation in the TPP group (0% vs. 36%; P<.001). Finally, 89% of TPP patients presented with corrected QT (QTc) prolongation, whereas only 19% of thyrotoxic patient presented with a prolonged QTc. CONCLUSION: Hispanic patients with TTP seems to have relative resistance to the actions of thyroid hormones and commonly present with QTc prolongation, a risk factor for cardiac arrhythmias. ABBREVIATIONS: BWS = Burch-Wartofsky point scale; EKG = electrocardiogram; FT3 = free triiodothyronine; FT4 = free thyroxine; ICD = International Classification of Diseases; QTc = corrected QT; TPP = thyrotoxic periodic paralysis.

Lipopolysaccharide (LPS)-induced septic shock causes profound changes in myocardial energy metabolites in pigs.

INTRODUCTION: Energy deficiency is a cause for myocardial dysfunction during septic shock. In rodents, septic shock decreases the oxidation of long-chain fatty acids and glucose in the myocardium causing energy deficiency. However, the effect of septic shock on myocardial energy metabolites in large animals and human is unknown. OBJECTIVES: Investigate the effects of septic shock on myocardial energy metabolites in domestic pigs. METHODS: Seventeen female pigs divided into control and lipopolysaccharide (LPS)-induced septic shock groups. Myocardial metabolites were analyzed ex vivo by 1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. Gene and protein expression analysis were analyzed by real-time PCR and western blot. RESULTS: Septic shock was associated with an increase in myocardial levels of short- and medium-chain acylcarnitines, lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression. COX-2 and prostaglandin E4 receptor gene expression also increased in the septic myocardium, although the only elevated eicosanoid in the septic animals was thromboxane B2. Myocardial levels of niacin, taurine, glutamate, glutamine, and glutathione were higher, and hypoxanthine levels lower in septic pigs than controls. CONCLUSIONS: In pigs, septic shock induced by LPS caused myocardial changes directed to decrease the oxidation of medium- and short-chain fatty acid without an effect on long-chain fatty acid oxidation. The increase in myocardial levels of lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression suggest that septic shock decreases pyruvate dehydrogenase complex activity and glucose oxidation. Homeostasis of niacin, taurine, glutamate, glutamine, glutathione, hypoxanthine and thromboxane B2 is also affected in the septic myocardium.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

OBJECTIVE: Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. DESIGN: A prospective, observational study of patients receiving GH replacement as part of routine clinical care. PATIENTS: Twenty adult hypopituitary men. MEASUREMENTS: Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. RESULTS: The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. CONCLUSIONS: In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle.

Thyroid hormones are needed to sustain "inappropriately" normal TSH during non-thyroidal illness syndrome: a clinical observation in severely ill patients with primary hypothyroidism.

OBJECTIVES: Non-thyroidal illness syndrome (NTIS) is a form of hypothyroidism that occurs during illness. NTIS is characterized by low thyroid hormones (TH) level in the serum and tissues, with normal serum TSH levels that are considered "inappropriately" normal. The mechanisms responsible for a lack of increase in serum TSH during NTIS are unknown. However, a decreased expression of hypothalamic TRH has been documented in deceased humans with NTIS. It has been suggested that pro-inflammatory cytokines are responsible for the inhibition of TRH release. If a similar TSH response occurs in severely ill patients with primary hypothyroidism has not been reported. DESIGN: Seven severely ill patients with unknown or poorly treated primary hypothyroidism are presented. Serum TSH and TH were measured at admission and during TH replacement. SETTING: Tertiary university hospital. RESULTS: Besides suffering severe illness, patient's serum TSH was high and decreased once TH replacement was given. Levothyroxine administration was enough to down regulate TSH secretion. Serum reverse T3 (rT3) was normal or high and showed further elevation with stepwise increase in levothyroxine doses. CONCLUSIONS: The thyroid axis inhibitory feedback system is fully preserved in primary hypothyroidism during severe illness. In NTIS, serum TSH levels remain within normal limits because the supply of TH to TRH neurons is sustained normally. Pro-inflammatory cytokines does not play a major role inhibiting TRH release during NTIS associated to primary hypothyroidism. D3 activity increases in humans with severe illness, a mechanism behind the increased requirements in TH replacement to achieve normal serum TH.

Mutations in SECISBP2 result in abnormal thyroid hormone metabolism.

Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins. Mice lacking tRNA(Sec) die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans. Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. We identified three of seven siblings with clinical evidence of abnormal thyroid hormone metabolism. Their fibroblasts showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. Systematic linkage analysis of genes involved in DIO2 synthesis and degradation led to the identification of an inherited Sec incorporation defect, caused by a homozygous missense mutation in SECISBP2 (also called SBP2). An unrelated child with a similar phenotype was compound heterozygous with respect to mutations in SECISBP2. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.

Adrenal Medullary Hyperplasia: An Under the Radar Cause of Endocrine Hypertension.

Adrenal medullary hyperplasia is a cause of increased secretion of catecholamines by the adrenal gland that is rarely considered among the differential diagnoses of endocrine hypertension. We report the case of a 48-year-old Hispanic woman who presented for evaluation of resistant hypertension with several episodes of hypertensive crisis. The clinical presentation, biochemical results, and abdominal computed tomography scan suggested the possibility of a pheochromocytoma; however, an iodine-123-meta-iodobenzylguanidine (123I-MIBG) uptake study combined with single-photon emission computed tomography (SPECT) and computed tomography (CT) scan showed diffusely increased metabolic activity in both adrenal glands. The patient underwent left adrenalectomy, and the pathology study revealed the presence of adrenal medullary hyperplasia. After surgery, blood pressure control was achieved with one antihypertensive drug, and the patient did not have recurrent hypertensive crisis. Relevant findings obtained from a whole genomic sequence done on a whole blood DNA sample from the patient are discussed.

Non-thyroidal illness syndrome, the hidden player in the septic shock induced myocardial contractile depression.

Septic shock causes high mortality in hospitalized patients, especially in those that develop myocardial dysfunction as an early complication. The myocardial dysfunction of septic shock is characterized by a decrease in ventricular relaxation (diastolic dysfunction) and reduced ventricular ejection fraction (systolic dysfunction). Most patients with septic shock have low serum thyroid hormone levels, a condition known as non-thyroidal illness syndrome. Thyroid hormones sustain myocardial contractility and energy metabolism. Septic shock non-thyroidal illness syndrome causes myocardial hypothyroidism, and hypothyroidism causes myocardial dysfunction that resembles the myocardial depression of septic shock. We hypothesize that the myocardial hypothyroidism that occurs during septic shock has a causal role in the pathogenesis of septic shock-induced myocardial dysfunction. Thyroid hormones regulate the calcium cycle, the phenotype of contractile proteins, adrenergic response, and fatty acid transport and oxidation in the cardiomyocytes. Therefore, the administration of levothyroxine and liothyronine to normalize thyroid hormones level within the myocardium will improve the myocardial function. The hypothesis will be tested in humans with septic shock by performing a prospective, randomized, placebo-controlled study to compare the effect of thyroid hormone administration with placebo on myocardial function. The proposed hypothesis challenges the idea that non-thyroidal illness syndrome is a beneficial response of the thyroid hormone axis to illness and that thyroid hormone replacement is detrimental. The administration of thyroid hormone in order to prevent and reverse myocardial hypothyroidism during septic shock is a new theoretical concept on thyroid hormone metabolism and action at the tissue level during non-thyroidal illness syndrome. If the hypothesis is correct, clinicians should consider cardiac hypothyroidism as a central player in myocardial dysfunction caused by sepsis. Thyroid hormone replacement should be incorporated into the armamentarium of septic shock treatment.

Usefulness of plasmapheresis in patients with severe complicated thyrotoxicosis.

The standard treatment of complicated thyrotoxicosis and thyroid storm with the concomitant use of antithyroid medication, iodine, beta-blockers, and corticosteroids is successful in most cases. However, treatment options are limited when antithyroidal drugs cannot be used or in cases that are refractory to standard treatment. Plasmapheresis provides a safe and effective strategy when initial treatment fails, facilitating the transition to definitive treatments such as thyroidectomy. We present two adults with complicated thyrotoxicosis successfully treated with plasmapheresis as a bridge therapy to thyroidectomy or as an alternative to drug-induced toxicity.

Effect of chemoradiation on the size of the thyroid gland.

We aimed to evaluate changes in thyroid gland size during the treatment of malignancies outside the head and neck with chemotherapy and/or external beam radiation. We performed a retrospective review of records of adult patients treated at our institution with external beam radiation to the chest and/or chemotherapy with taxanes, alkylating agents, and/or a topoisomerase II inhibitor. Neck and chest computed tomography (CT) images were used to calculate thyroid gland volume before and after therapy, using Vitrea® software or the volumetric ellipsoid method. Thirty-seven patients were included. After treatment, there was a significant reduction in thyroid gland volume of 14.0% (P < 0.01) using Vitrea and 17.1% (P < 0.05) using the volumetric ellipsoid method. Exposure to radiation or chemotherapy was not found to be associated with the degree of thyroid gland reduction, nor was the number of days between CT scans or the stage of the malignancy being treated. Finally, the degree of thyroid gland size reduction did not predict mortality. Our results showed that the treatment of malignancies outside the head and neck with chemotherapy and/or external beam radiation results in a reduction in thyroid gland size. The impact on thyroid gland function remains unknown.

High prevalence of non-thyroidal illness syndrome in patients at long-term care facilities.

PURPOSE: Patients in acute care hospitals are often transferred to long-term care (LTC) when there is an expectation for a lengthy recovery. Prolonged non-thyroidal illness syndrome (NTIS) creates a state of hypothyroidism. We aimed to investigate the prevalence of NTIS in patients at LTC facilities. METHODS: A cross-sectional study at University Hospitals and Rehabilitation and Skilled Nursing facility was performed. Four groups: control (n:33), intensive care unit (ICU) (n:34), long-term care hospital (LTCH) (n:50), and long-term care on chronic ventilatory support (LTCVS) (n:30). Serum levels of TSH, free T4 (FT4), free T3 (FT3), and interleukin 6 (IL6) measured at admission day in controls, within 48 h of admission in the intensive care group, between days 31 and 120 in the LTC hospital group and days 31 and 6 years in the LTC on chronic ventilatory support group. RESULTS: Serum FT3 levels were lower in groups intensive care unit ICU, LTCH, and LTCVS than control. Low serum FT3 levels were observed in 80% ICU, 54% LTCH, 37% LTCVS, and 6% control patients. Low serum FT4 levels were observed in 32% ICU, 16% LTCH, and 20% LTCVS patients. Both low serum FT4 and FT3 levels were observed in 32% ICU, 16% LTCH, and 13% LTCVS patients. Serum IL6 and FT3 levels showed a negative correlation. CONCLUSIONS: NTIS is highly prevalent in patients in LTC, creating a state of persistent hypothyroidism. The effects of thyroid hormone replacement in patients at LTC with non-thyroidal illness deserve further investigation.

Prevalence and functional analysis of the S107P polymorphism (rs6647476) of the monocarboxylate transporter 8 (SLC16A2) gene in the male population of north-west Spain (Galicia).

OBJECTIVE: Mutations in SLC16A2, the gene encoding the thyroid hormone (TH)-specific transporter monocarboxylate transporter 8 (MCT8), result in a thyroid phenotype and severe mental retardation caused by neuronal TH deficiency. These mutational effects raise the question of whether polymorphic variation in SLC16A2 may also be associated with differences in serum levels of TH and/or TSH. DESIGN: This is the first major study of the frequency of the SLC16A2 rs6647476 single nucleotide polymorphism (SNP) (amino acid change Ser107Pro). We also studied the relationships of SLC16A2 genetic variants with serum levels of TSH, T4 and T3, with their mRNA expression and with expression of the TH-responsive genes ZAKI-4 and BTEB in white blood cells. Experiments in cultured fibroblasts were carried out to ascertain the dynamics of the T3 response. METHODS: A total of 276 men were studied. Genotyping of the S107P SNP was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP); serum hormone levels were determined by chemiluminescence; expression of mRNA was quantified by real-time PCR. RESULTS: The SLC16A2 S107P SNP was found in 36% of Galician males. With the present sample size we did not find any association of this polymorphism with variability in serum levels of TSH, free T4 (fT4) or fT3, or with basal expression of mRNA for SLC16A2 or the two TH-responsive genes ZAKI-4 and BTEB, either in white blood cells or in cultured human fibroblasts from either Ser107 or Pro107 genotypes under T3 stimulation. CONCLUSIONS: The S107P change in MCT8 is frequent in the male population in Galicia. In the population studied in this report an association with a thyroid phenotype was not demonstrated, even though the S107P SNP causes an important amino acid change.

Bilateral adrenal myelolipomas presenting as acute adrenal insufficiency in an adult with congenital adrenal hyperplasia.

Adrenal myelolipomas are relatively rare tumours composed of adipocytes and myeloid cells that arise in response to chronic adrenocorticotropic hormone stimulation. We present the case of bilateral adrenal myelolipomas in a 39-year-old man with untreated congenital adrenal hyperplasia (CAH) presenting with acute adrenal insufficiency and severe virilisation. Phenotypically, he is a man of short stature and has hyperpigmentation of the skin, gingiva and nail beds. Genital examination revealed micropenis and no palpable testes. Laboratory testing was consistent with primary adrenal insufficiency. An abdominal CT showed bilateral adrenal myelolipomas. An MRI of the pelvis revealed female reproductive organs. Chromosome study showed a karyotype of 46,XX. A CYP21A2 gene mutation confirmed diagnosis of CAH with 21-hydroxylase deficiency. The patient was treated with stress dose corticosteroids, subsequently tapered to physiological doses. We review previously reported cases and discussed diagnosis and treatment, including hormonal therapy and psychological approach.

Unfavorable Socioeconomic Factors Underlie High Rates of Hospitalization for Complicated Thyrotoxicosis in Some Regions of the United States.

OBJECTIVE: The authors' institution-a safety net, university, and tertiary-care hospital located in West Texas-has a high number of hospital admissions for complicated thyrotoxicosis. It was hypothesized that unfavorable socioeconomic conditions result in increased risk of poor outcomes in hyperthyroid patients, and increased rates of hospitalization for thyrotoxicosis in West Texas. The primary aim of this study was to identify factors associated with admission for complicated thyrotoxicosis in patients living in the Panhandle and Llano Estacado of Texas. METHOD: A retrospective chart review of patients aged ≥18 years with a diagnosis of thyrotoxicosis evaluated at the authors' institution from January 2011 to January 2017. Patients were divided into two groups: a hospitalized group, consisting of patients who required hospitalization for complicated thyrotoxicosis, and an outpatient group. Demographics, clinical, and biochemical data were reviewed to identify factors associated with hospitalization for complicated thyrotoxicosis. RESULTS: The hospitalized group consisted of 80 patients, and the outpatient group consisted of 294 patients. Thyrotoxicosis accounted for 0.05% of all-cause hospital admissions during the study period. Patients with thyrotoxicosis and a lack of health insurance had 12 times higher odds of being hospitalized for complicated thyrotoxicosis compared to patients with commercial insurance. Conversely, the odds of hospitalization for complicated thyrotoxicosis were reduced by 63% in patients with a higher median income, and by 33% in those with college or university studies versus high school studies. Thirty-two percent of patients hospitalized for complicated thyrotoxicosis presented with thyroid storm, and this accounted for 7% of the studied cohort. CONCLUSION: Socioeconomic conditions are the main factors associated with the odds of being admitted to a hospital in West Texas for complicated thyrotoxicosis, including thyroid storm. Patients without healthcare insurance have higher odds of admission, while patients with higher education and living in areas of higher income have lower odds of hospital admission due to thyrotoxicosis.

Duodenal somatostatinoma presenting as obstructive jaundice with the coexistence of a gastrointestinal stromal tumour in neurofibromatosis type 1: a case with review of the literature.

Somatostatinomas are rare neuroendocrine tumours, mostly located in the pancreas or duodenum, with an estimated incidence of 1 in 40 million. Duodenal somatostatinomas (DSs) are usually found in association with neurofibromatosis type 1 (NF1), tuberous sclerosis and Von Hippel-Lindau syndrome. Gastrointestinal stromal tumours (GIST) have also been described in NF1, but the association with somatostatinoma is very uncommon. We report the case of a patient with NF1 who presented with obstructive jaundice due to multiple firm nodules around the ampulla of Vater. A pancreaticoduodenectomy was performed and revealed a 1 cm duodenal/ampullary mass which stained positive for somatostatin, together with a GIST also found on the duodenal wall. Despite its rarity, ampullary somatostatinomas should be considered in the differential diagnosis of biliary tract dilation in patients with NF1.

Pendred syndrome in two Galician families: insights into clinical phenotypes through cellular, genetic, and molecular studies.

CONTEXT: We studied two families from Galicia (northwest Spain) with Pendred syndrome (PS) and unusual thyroid phenotypes. In family A, the proposita had a large goiter and hypothyroxinemia but normal TSH and free T3 (FT3). In family B, some affected members showed deafness but not goiter. OBJECTIVE: Our objective was to identify the mutations causing PS and molecular mechanisms underlying the thyroid phenotypes. INTERVENTIONS: Interventions included extraction of DNA and of thyroid tissue. PATIENTS: Propositi and 10 members of the two families participated in the study. MAIN OUTCOME MEASURES: Main outcome measures included SLC26A4 gene analysis, deiodinase activities in thyroid tissue, and c.416-1G-->A effects on SLC26A4 splicing. In addition, a primary PS thyrocyte culture, T-PS2, was obtained from propositus B and compared with another culture of normal human thyrocytes, NT, by Western blotting, confocal microscopy, and iodine uptake kinetics. RESULTS: Proposita A was heterozygous for c.578C-->T and c.279delT, presented with goiter, and had normal TSH and FT3 but low FT4 attributable to high type 1 and type 2 iodothyronine deiodinase activities in the goiter. Propositus B bore c.279delT and a novel mutation c.416-1G-->A; some deaf relatives were homozygous for c.416-1G-->A but did not present goiter. The c.279delT mutation was associated with identical haplotype in the two families. T-PS2 showed truncated pendrin retained intracellularly and high iodine uptake with low efflux leading to iodine retention. CONCLUSIONS: c.279delT is a founder mutation in Galicia. Proposita A adapted to poor organification by increasing deiodinase activities in the goiter, avoiding hypothyroidism. Lack of goiter in subjects homozygous for c.416-1G-->A was due to incomplete penetrance allowing synthesis of some wild-type pendrin. Intracellular iodine retention, as seen in T-PS2, could play a role in thyroid alterations in PS.

Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock.

OBJECTIVE: Septic shock is one of various causes of nonthyroidal illness syndrome (NTIS). In humans, the molecular mechanisms involved in NTIS are mostly unknown. The aim of this study was to investigate, in patients with NTIS secondary to septic shock, changes in the expression of genes involved in the actions of thyroid hormones and in the activity of deiodinase enzymes, in two tissues important for protein and energy metabolism, skeletal muscle (SM) and subcutaneous adipose tissue (SAT). DESIGN: Hospitalized patients were divided into a control and a septic shock NTIS group. MEASUREMENT: Serum collection for biochemical measurements, and SM and SAT biopsies for mRNA expression analysis of thyroid hormone receptors (THRB1, THRA1), retinoid X receptors (RXRA, RXRB, RXRG), nuclear receptor corepressor (NCOR1), silencing mediator of retinoid and thyroid hormone receptor (SMRT), steroid receptor coactivator (SRC1), type 1 and 2 deiodinases (D1, D2), monocarboxylate transporter 8 (MCT8), SECIS binding protein 2 (SBP2) and uncoupling protein 3 (UCP3) as well as D1, D2 and D3 enzyme activity measurements. RESULTS: The NTIS group had lower serum TSH, and free T3 and higher rT3 than controls. D1 and D3 were detected in SAT, with no differences found between the two groups; SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls. SM expression of THRB1, RXRG and D2 was lower and RXRA higher in NTIS than controls. SAT from NTIS patients had lower MCT8, THRB1, THRA1, RXRG and SMRT, and higher UCP3 expression than controls. CONCLUSIONS: In patients with septic shock NTIS tissue responses are orientated to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3, as well as to decrease thyroid hormone actions.

A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin resistance, aortic stenosis and hypertrophic cardiomyopathy.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by abnormal fat distribution. Familial partial lipodystrophy 2 (FPLD2) is due to mutations in the LMNA gene. Previous studies have suggested that LMNA mutations 5' to the nuclear localization signal (NLS) are more likely to underlie laminopathies with cardiac or skeletal muscle involvement, while mutations 3' to the NLS are more likely to underlie lipodystrophy and progeroid syndromes. OBJECTIVE: To study the clinical and molecular features of a subject with FPLD. SUBJECTS AND METHODS: We carried out mutational analysis of LMNA gene in a woman with FPLD phenotype and in her relatives. Insulin resistance was evaluated by minimal model. Body composition was evaluated by dual-energy X-ray absorptiometry (DEXA). Echocardiography was done in affected subjects. 3T3-L1 preadipocytes were transfected with wild-type or mutant prelamin A constructs. In transfected cells, lamin A was detected using a Cy3-conjugated monoclonal anti-FLAG antibody. RESULTS: The patient showed atypical fat distribution, insulin resistance, severe aortic stenosis and hypertrophic cardiomyopathy. She has an affected 11-year-old son, not yet lipodystrophic but with an incipient aortic disease. LMNA sequencing showed that mother and son were both heterozygous for a novel c.1772G > T missense mutation in exon 11, which causes the substitution of the cysteine at residue 591 by a phenylalanine (C591F). In mouse preadipocytes transfected with the mutant human LMNA gene, the mutant lamin A isoform was mislocated in the nucleus. CONCLUSIONS: This patient shows a novel clinical form of FPLD2, due to a mutation affecting lamin A only, with cardiac involvement.

Genetic bases of benign thyroid processes.

The advances made in the last decade in gene analysis techniques have greatly simplified the study of the genetic bases of disease, hastening identification of the genes causing or involved in disease development. Rapid and low-cost genome sequencing in all individuals may become a reality. The genetic bases of defects in thyroid hormone formation have been well defined, and those of defects in thyroid ontogeny have been partially defined; in the last 4 years, the genes responsible for 2 new syndromes causing reduced sensitivity of the action of thyroid hormone and affecting thyroid hormone transport (MCT8 mutations) and intracellular metabolism (SECISBP2 mutations) have been discovered. The genetic bases of toxic adenomas and toxic multinodular goiters have been determined and several genes involved in the development of follicular thyroid adenomas have been identified. However, not all the genes involved in thyroid ontogeny have been identified and the genetic bases of multinodular hyperplastic goiter, highly prevalent in some regions of Spain, as well as those of most autoimmune thyroid disorders, are unknown. Major challenges remain in the characterization of the genetic bases of benign thyroid processes, which, together with their high prevalence and the current and future potential of technology, suggest a promising and exciting future in this field of research.

Pneumocephalus as a Complication of Transsphenoidal Surgery for Pituitary Adenoma: A Case Report.

Pneumocephalus (PNC) is a rare complication of transsphenoidal surgery that can result from cerebrospinal fluid (CSF) leak, allowing air entry into the CSF. We report the case of a 49-year-old female patient who presented to the emergency department three weeks after a transsphenoidal pituitary tumor resection, with symptoms of generalized throbbing headache associated with nausea. The patient was alert and oriented without any focal neurological deficit. A head computed tomography (CT) scan showed air in the subarachnoid space and ventricles. She was admitted to the hospital and was initially treated conservatively. However, her symptoms persisted, and a repeat head CT scan demonstrated worsening PNC. She then underwent lumbar drain placement and sellar floor repair. Her symptoms resolved postoperatively. When PNC results in intracranial hypertension, it is referred to as tension PNC, a complication that can be fatal. Conservative treatment involves analgesics and therapy for intracranial hypertension. Surgical intervention to decrease intracranial hypertension and repair the CSF leakage may also be necessary.

Thyroid hormone resistance and its management.

The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Patients can present with symptoms of hyperthyroidism or hypothyroidism. They usually have elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone level. Due to their nonspecific symptomatic presentation, these patients can be misdiagnosed if the primary care physician is not familiar with the condition. This can result in frustration for the patient and sometimes unnecessary invasive treatment such as radioactive iodine ablation, as in the case presented herein.