Carmen A. Carrasco

Sequential hormonal changes in 21 patients with recurrent Cushing's disease after successful pituitary surgery

OBJECTIVEnTo describe the sequence of hormonal changes during recurrence of Cushings disease (CD) after successful transsphenoidal surgery (TSS).nnnDESIGNnRetrospective study in a single center.nnnPATIENTS AND METHODSnWe studied 101 of the 127 patients treated by TSS for CD between 1996 and 2009, who had hypocortisolism or eucortisolism for at least 3 months post-TSS. We arbitrarily defined overt recurrence, as presence of two classical parameters of excess cortisol (increased midnight--either serum or salivary--and 24u200a h urinary cortisol (UC)), leading to further specific therapeutic action, and mild recurrence, as presence of a single classical parameter, leading to simple surveillance.nnnRESULTSnOf the 101 patients, 21 (20.8%) presented with recurrence, mild or overt, during long-term follow-up (median 50.4 months, range 7-99). Recurrence occurred less frequently (16.8 vs 50%, P=0.02), and later (mean 44.7 months, median 43, range 7-94 vs mean 21.5 months, median 17, range 3-61, P=0.05), in patients with early post-TSS hypocortisolism compared with those with eucortisolism. Increase in midnight cortisol occurred in a mean time of 38.2 months, while UC elevation was observed at 50.6 months. Vasopressin analogs and CRH tests were eventually positive in 85 and 93% of all patients respectively; a positive response to one of the two dynamic tests preceded the increase in midnight cortisol or UC in 71 and 64% of the patients respectively.nnnCONCLUSIONnA positive response to vasopressin analogs and/or CRH tests occurs early in recurrence, followed by an increase in midnight cortisol, while UC elevation is at a later stage.

Reproducibility and performance of one or two samples of salivary cortisol in the diagnosis of Cushing’s syndrome using an automated immunoassay system

The purpose of this article is to evaluate the variability and reproducibility of late night salivary cortisol (LNSC) using electrochemiluminescence immunoassay (ECLIA) and compare the accuracy of one or two samples in diagnosis of Cushing’s syndrome (CS). We prospectively included 64 healthy volunteers (HV), 35 patients with clinically suspected CS (S), and 26 patients with confirmed CS. Nine patients in the CS group had 24-h urinary free cortisol (UFC) less than two times the upper limit of normal (mild CS). UFC and two consecutive LNSC (LNSC1, LNSC2) were collected at home. All patients in the S group had normal UFC and low-dose dexamethasone suppression test. No differences were found between the HV and S groups in UFC, LNSC1, and LNSC2. Intra-individual variability between the two samples of LNSC was 22% in HV (1.6−91%), 32% in the S group (1.6−144%), and 51% (1.6−156%) in the CS group. Variability was higher in CS patients than those in the HV (Pxa0<xa00.001) and S groups (Pxa0=xa00.05). The AUC of LNSC1 was 0.945 (IC 95% 0.880–1.004); when considering the highest LNSC, the AUC was 0.980 (IC 95% 0.954–1.007) (Pxa0<xa00.01). We found 23% of discordant LNSC in the S group and 11% in the CS group. Three patients with CS had only one elevated LNSC, all of them with mild CS. Our results suggest that LNSC is variable, and reproducibility is affected in both CS and S patients. We found significant improvements in the diagnostic accuracy of the LNSC measurement by obtaining two samples.

Primary pituitary lymphoma in immunocompetent patient: diagnostic problems and prolonged follow-up

Primary pituitary lymphoma in immunocompetent patients is a rare disease and has been described in less than 20 cases. Moreover, low-grade lymphomas constitute only 3% of all primary central nervous system lymphoma. The objective of this report is to report a low-grade primary pituitary lymphoma, diagnostic problems and to give more evidence about the evolution of this rare disease. A 49 y.o. woman was referred to our clinic with symptoms of hypopituitarism. A diagnostic work-up showed mild anemia, an erythrocyte sedimentation rate of 122xa0mm/h and a negative Elisa test for HIV. Panhypopituitarism was confirmed and the MRI showed a 20xa0mm sellar and suprasellar enhancing mass with a thickening of the pituitary stalk, chiasmal compression and bitemporal hemianopsia. She underwent transsphenoidal resection only 10xa0months later for non medical reasons. During this period she was clinically asymptomatic on hormonal replacement therapy. A new MRI showed regression of the suprasellar extension and invasion to the left cavernous sinus. A firm and infiltrative mass was found during transsphenoidal surgery, and only partial resection was performed. Biopsy showed a low-grade lymphoplasmacytic lymphoma. Staging was negative for other localizations. She was given chemotherapy and localized radiotherapy. Four years after surgery, the sellar MRI showed a 10xa0mm residual sellar mass with the persistence of a cavernous sinus invasion and she is considered to be in remission. The neurosurgeon and clinician should consider primary pituitary lymphoma as a potential cause of a sellar mass, especially in the presence of diabetes insipidus and an enhancing invasive mass. Neurosurgical biopsy is crucial for a correct diagnosis and prognosis could be better than classic CNS primary lymphomas.

MELANOTIC NONPSAMMOMATOUS TRIGEMINAL SCHWANNOMA AS THE FIRST MANIFESTATION OF CARNEY COMPLEX: CASE REPORT

OBJECTIVEMelanotic schwannoma is a rare neoplasm, classifiable as a peripheral nerve sheath tumor, and differentiated from a typical schwannoma by heavy pigmentation. Psammoma bodies can be visualized in more than 50% of melanotic schwannomas. Half of patients with such “psammomatous melanotic schwannomas” have Carney complex, a dominantly transmitted autosomal disorder. Most recently, the tumor suppressor gene, PRKAR1A, coding for the Type 1α regulatory subunit of protein kinase A was found to be mutated in approximately half of the known Carney complex families. Although cranial schwannomas have been described in patients with Carney complex, their numbers are too small to be considered a definite part of the syndrome. Furthermore, only melanotic schwannomas with psammoma bodies are included as diagnostic criteria for Carney complex. The objective of this report is to communicate a case of trigeminal nonpsammomatous melanotic schwannoma as the first manifestation of Carney complex. CLINICAL PRESENTATIONA 34-year-old woman presented with odontalgia, right V3 hypoesthesia, V2 paresthesia, and diplopia. Magnetic resonance imaging scans of the brain revealed a small tumor with homogenous contrast in the right trigeminal pathway. INTERVENTIONWe performed an extradural approach to the right cavernous sinus by a middle fossa approach. The lateral wall was opened between the cranial nerves, and a soft and black tumor was resected in a piecemeal fashion. Histology and immunohistochemical analysis of the tumor were compatible with melanotic schwannoma, but no psammomatous bodies were identified. Endocrine evaluation showed that this patients symptoms fulfilled the diagnostic criteria of Carney complex, with lentiginosis, multiple breast ductal adenomas, multiple hypoechoic nodules on thyroid ultrasonography, and a 4 × 5-cm asymptomatic atrial cardiac myxoma, which was removed 15 days after the neurosurgery. Three months later, a recurrence of melanotic schwannoma was identified. Molecular analyses of genomic and somatic deoxyribonucleic acid from the patient found a 578 to 579delTG mutation of PRKAR1A. CONCLUSIONWe present the unusual case of a nonpsammomatous trigeminal melanotic schwannoma associated with Carney complex, with confirmed PRKAR1A gene mutation. Our case highlights that neurosurgeons, in the presence of a melanotic schwannoma, should be aware of the features of the Carney complex because, in such cases, pre- and postoperative management is significantly affected. We also postulate that the absence of psammoma bodies or cranial localization do not exclude this diagnosis.

Hormonal, Radiological, NP-59 Scintigraphy, and Pathological Correlations in Patients With Cushing's Syndrome Due to Primary Pigmented Nodular Adrenocortical Disease (PPNAD)

CONTEXTnPrimary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushings syndrome that may occur in an isolated form or as part of Carney complex. The diagnosis of this disease can be difficult preoperatively because computed tomography (CT) scan can be normal or suggest unilateral adrenal lesion, which can impede the correct diagnosis of bilateral adrenal disease.nnnOBJECTIVEnThe aim of our study was to describe the results of preoperative imaging (adrenal [6β-(131)I]iodomethyl-19-norcholesterol] [NP-59] scintigraphy and standard adrenal CT scan) and their correlations with clinical, pathological, and genetics investigations in patients with PPNAD.nnnPATIENTS AND METHODSnSeventeen patients with ACTH-independent syndrome due to PPNAD were investigated with a standard adrenal CT scan and NP-59 scintigraphy. Hormonal, pathological, and genetics data were analyzed.nnnRESULTSnFour males and 13 females (median age, 27 y) were included. PPNAD was isolated in 11 patients (with PRKAR1A mutation, n = 7; and without PRKAR1A mutation, n = 4) and was associated with extra-adrenal manifestations of Carney complex in six patients (with PRKAR1A mutation, n = 4; and without PRKAR1A mutation, n = 2). Standard adrenal CT scan revealed micronodules in 11 patients, macronodules in three patients, and was normal in three patients. All patients demonstrated bilateral adrenal radiocholesterol uptake. Adrenal uptake was asymmetrical in 10 of 17 patients (59%). Asymmetrical uptake correlated with the presence of macronodules at pathological analysis (P = .03).nnnCONCLUSIONnStandard adrenal CT scan most often reveals micronodules but there is no specific CT imaging. NP-59 scintigraphy always shows a bilateral adrenal uptake confirming the bilateral nature of the disease, but asymmetrical scintigraphic uptake can be observed in patients with macronodules.

The Expression of RAC1 and Mineralocorticoid Pathway- Dependent Genes are Associated With Different Responses to Salt Intake

BACKGROUNDnRac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO-1) or nuclear factor-B (NF-κB), and the expression of neutrophil gelatinase-associated lipocalin (NGAL), a cytokine upregulated upon MR activation.nnnAIMnWe evaluated RAC1 expression in relation of high salt intake and association with MR, NGAL, HO-1, and NF-κB expression, mineralo- and glucocorticoids levels, and inflammatory parameters.nnnSUBJECTS AND METHODSnWe studied 147 adult subjects. A food survey identified the dietary sodium (Na) intake. RAC1 expression was considered high or low according to the value found in normotensive subjects with low salt intake. We determined the gene expression of RAC1, MR, NGAL, HO-1, NF-κB, and 18S, isolated from peripheral leukocytes. We measured aldosterone, cortisol, sodium, potassium excretion, metalloproteinase (MMP9 y MMP2), and C-reactive protein.nnnRESULTSnWe identified 126 subjects with high Na-intake, 18 subjects had high, and 108 low-RAC1 expression. The subjects with high-RAC1 expression showed a significant increase in MR (P = 0.0002), NGAL (P < 0.0001) HO-1 (P = 0.0004), and NF-κB (P < 0.0001) gene expression. We demonstrated an association between RAC1 expression and MR (R sp 0.64; P < 0.0001), NGAL (R sp 0.48; P < 0.0001), HO-1 (R sp 0.53; P < 0.0001), and NF-κB (R sp0.52; P < 0.0001). We did not identify any association between RAC1 and clinical or biochemical variables.nnnCONCLUSIONSnRAC1 expression was associated with an increase in MR, NGAL, NF-κB, and HO-1 expression, suggesting that RAC1 could be a mediator of cardiovascular damage induced by sodium, and may also useful to identify subjects with different responses to salt intake.

The role of primary pharmacological therapy in acromegaly

Background and objectivesPrimary pharmacological therapy may be the only viable treatment option for many patients with acromegaly, especially those presenting with advanced disease with large inoperable tumors. Long-acting somatostatin analogs are currently the first-line treatment of choice in this setting, where they provide biochemical control and reduce tumor size in a significant proportion of patients. We herein present a brief overview of the role of primary pharmacological therapy in the treatment of acromegaly within the context of Latin America and support this with a representative case study.Case descriptionA 20xa0year old male presented with clinical and biochemical evidence of acromegaly. The glucose-suppressed growth hormone (GH) was 5.3 μg/L, his insulin-like growth factor-1(IGF-1) was 3.5 times the ULN and serum prolactin greater than 4,000 μg/L. Pituitary MRI revealed a large and invasive mass, extending superiorly into the optic chiasm and laterally into the left cavernous sinus. He was treated with a combination of octreotide and cabergoline with remarkable clinical improvement, normalization of GH and IGF-1 values and striking shrinkage of the adenoma.ConclusionThis case illustrates how effective the pharmacological therapy of acromegaly can be and yet at the same time, raises several important issues such as the need for life-long treatment with costly medications such as the somatostatin analogs. Access to these agents may be limited in regions where resources are restricted and clinicians face challenges in order to make the most efficient use of available options.

Aggressive tumors and difficult choices in acromegaly.

PurposeThe current article looks at some of the factors associated with pituitary adenomas displaying unusually aggressive biological and clinical behaviour in patients with acromegaly.MethodsThis was a retrospective, narrative review of previously published evidence chosen at the authors’ discretion and presented from the perspective of a Latin American case study.Findings and ConclusionsAlthough most pituitary tumors in acromegalic patients are benign and non-aggressive many can behave more aggressively, compromising local surrounding structures. These lesions tend to respond poorly to somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a worse prognosis. Patients with more aggressive tumors constitute a particular challenge, as they often require several therapeutic approaches and may be difficult to manage, especially when options are restricted due to limited resources.

Criterios para la indicación selectiva de glucocorticoides en pacientes con tumores hipofisiarios sometidos a cirugía transesfenoidal

BACKGROUNDnThere is consensus in promoting the selective use of glucocorticoids (GC) in the peri-operative period of transsphenoidal surgery (TE) for pituitary adenomas (PA).nnnAIMnTo evaluate the safety of a selective glucocorticoid administration protocol and the usefulness of immediate postoperative cortisol levels as a predictor of final eucortisolism.nnnPATIENTS AND METHODSnClinical and biochemical data from 40 patients aged 27 to 78 years (65% males) were prospectively collected. Exclusion criteria were previous use of GC, apoplexy and Cushing disease. Patients with pre-operative short synthetic ACTH test (SST) > 18 µg/dl or basal cortisol > 15 µg/dl did not receive GC. A morning serum cortisol (SC) threshold of 10 µg/dl in postoperative days one to three was used to decide a discharge without GC. Hypotension, dizziness or nausea, requirement of increased dose of corticosteroids, hospitalizations and emergency service visits were investigated, as well as surgical and endocrinological complications. Corticotropic status was evaluated three months after surgery.nnnRESULTSnMacroadenomas were present in 87% of patients. Median hospital stay was 4 days and follow up lasted 9 months. No differences were found in gender, age or tumor size between patients who received or not GC (35 and 65% respectively). Eighty five percent of patients were discharged without GC and all of them had normal corticotropic function three months after surgery. A SC ≥ 15 µg/dl had 100% specificity to predict eucortisolism.nnnCONCLUSIONSnSelective glucocorticoid administration is safe. A normal corticotropic function before surgery and in the immediate postoperative period are useful to identify patients who do not need GC.

Usefulness and Pitfalls in Sodium Intake Estimation: Comparison of Dietary Assessment and Urinary Excretion in Chilean Children and Adults

BACKGROUNDnHigh sodium intake has been associated with various noncommunicable disease like hypertension, cardiovascular disease, or stroke. To estimate accurately sodium intake is challenging in clinical practice. We investigate the usefulness and limitations of assessing sodium intake simultaneously by dietary assessment and urinary samples in both children and adults.nnnMETHODSnWe used a cross-sectional study design inviting 298 Chilean subjects (74 children and 222 adults) aged between 9 and 66 years of both genders. Sodium intake by dietary assessment was obtained from Chilean food composition data, based on FAO tables. Sodium and creatinine excretion were measured in 24-hour urine samples, in all participants.nnnRESULTSnAdequate urinary collection was obtained in 81% of children (59/74) and 61% of adults (135/222). The mean sodium intake by dietary assessment was similar to the sodium excretion in 24 hours (3,121±1,153mg/d vs. 3,114±1,353mg/24h, P = nonsignificant) in children but was significantly lower (3,208±1,284mg/d vs. 4,160±1,651mg/24h, P < 0.001) in adults. In both children and adults, sodium intake correlated with urinary sodium excretion (r = 0.456, P < 0.003 and r = 0.390, P < 0.001, respectively). Secondary analyses also suggested that the dietary assessment was more inaccurate in overweight adult subjects.nnnCONCLUSIONSnOur results showed that average sodium intake was higher than recommended in both children and adults (WHO ≤2,000mg/d). The sodium intake estimated by dietary assessment correlated with urinary excretion in all subjects, but in obese adults was more inaccurate than in children. Future studies to validate the appropriate test to assess sodium intake by age and nutritional status are warranted.