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1.
Exp Clin Endocrinol Diabetes ; 128(12): 827-834, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31634962

ABSTRACT

OBJECTIVE: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing's syndrome (CS). The aim of the current article is to define the role of unilateral adrenalectomy (UA) in treating patients with CS related to PBMAH. METHODS: A PubMed database search was conducted to identify articles reporting UA to treat PBMAH. We also report cases of PBMAH from our medical center treated by UA. RESULTS: A total number of 71 cases of PBMAH (62 cases reported in the literature and 9 cases from our center) are presented. Most patients were women (73.2%) and most UA involved the left side (64.3%). In most cases, the resected gland was the larger one. Following UA, 94.4% of cases had remission of hypercortisolism. Recurrence rate of CS was 19.4% and hypoadrenalism occurred in 29.6%. After UA, when the size of the remained adrenal gland was equal or greater than 3.5 cm, CS persisted in 21.4% of cases, and recurrence occurred in 27.3% of cases (after 20±9.2 months). However, when the size of the remained gland was less than 3.5 cm, CS resolved in all cases and recurrence occurred in 21.2% of cases after a long period (65.6±52.1 months). High levels of urinary free cortisol (UFC) were not correlated with post-surgical CS recurrence or persistence. CONCLUSIONS: UA leads to beneficial outcomes in patients with CS related to PBMAH, also in cases with pre-surgical elevated UFC or contralateral large gland.


Subject(s)
Adrenalectomy , Cushing Syndrome/pathology , Cushing Syndrome/surgery , Outcome Assessment, Health Care , Adult , Aged , Cushing Syndrome/urine , Female , Humans , Hydrocortisone/urine , Male , Middle Aged , Recurrence
2.
Ann Endocrinol (Paris) ; 80(5-6): 324-328, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31703800

ABSTRACT

AIM: Some resected adrenal-confined adrenocortical carcinomas metastasize and others not. The present study was designed to evaluate the expression of metallothionein protein (MT) and minichromosome maintenance protein-2 (MCM2) in adrenocortical carcinomas and adrenocortical adenomas, and to test the correlation between this and adrenocortical carcinoma aggressiveness. MATERIALS AND METHODS: The study comprised 14 patients operated on for adrenocortical carcinoma, 15 operated on for adrenocortical adenoma and 2 with normal adrenals. Hematoxylin-eosin staining was used for histological evaluation under light microscopy, and sequential sections were used for MCM2 and MT staining. RESULTS: In normal adrenals, positive staining was weak for MT and zero for MCM2. Rates of positive staining for MT and MCM2 were significantly higher in adrenocortical carcinomas than in adrenocortical adenomas (P=0.008 and P<0.001, respectively). In adrenocortical carcinomas, a significant positive correlation was found between MCM2 staining and Weiss revisited score (P=0.022) but not for Weiss score, and a significant positive correlation was found between MCM2 and mitotic rate on histology (P=0.033). MCM2 but not MT staining was also shown to correlate significantly with stage IV carcinoma (P=0.008 and P=0.165, respectively). CONCLUSION: MCM2 and MT are overexpressed in adrenocortical carcinoma, and MCM2 expression correlates significantly with metastatic disease.


Subject(s)
Adrenal Cortex Neoplasms/chemistry , Adrenocortical Adenoma/chemistry , Adrenocortical Carcinoma/chemistry , Metallothionein/analysis , Minichromosome Maintenance Complex Component 2/analysis , Adrenal Cortex Neoplasms/pathology , Adrenal Glands/chemistry , Adrenocortical Adenoma/pathology , Adrenocortical Carcinoma/pathology , Adult , Aged , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Metastasis/pathology , Retrospective Studies
3.
Harefuah ; 158(9): 568-570, 2019 Sep.
Article in Hebrew | MEDLINE | ID: mdl-31507105

ABSTRACT

AIMS: To examine statistical correlation between mSASSS and serum levels of testosterone in males suffering from AS. BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory rheumatic disease primarily involving sacroiliac joints and spine. Structural damage, caused by AS, manifests with development of vertebral syndesmophytes and can be calculated as units of modified Spinal Ankylosing Spondylitis Syndesmophyte Score (mSASSS). The rate of growth of spinal syndesmophytes differs among individual AS patients, while male patients develop significantly more structural damage compared to females in general. METHODS: Twenty males with AS known for at least 5 years (average disease duration 12.8 years) and aged between 25 to 40 years donated 5 ml of peripheral blood for serum testosterone assay, and underwent X-ray films of cervical and lumbar spine. The mSASSS was calculated and correlation with serum testosterone levels was examined using Pearson correlation test. RESULTS: The mSASSS values of patients included in the final analysis ranged from 0-14 units and testosterone levels ranged from 8.4-25.5 nmol/L. No significant correlation was found between mSASSS values and testosterone levels in this cohort. CONCLUSIONS: This study did not find statistical correlation between mSASSS and serum levels of testosterone in males suffering from AS.


Subject(s)
Spondylitis, Ankylosing/blood , Testosterone/blood , Adult , Disease Progression , Female , Humans , Lumbar Vertebrae , Male , Radiography , Severity of Illness Index , Spine
4.
Minerva Endocrinol ; 44(3): 241-245, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30256074

ABSTRACT

BACKGROUND: Earlier research on 1 µg low-dose test (LDT) performed using 20.3 cm plastic IV tubing on healthy volunteers, has shown that afternoon testing was associated with a sevenfold increased likelihood of failing the test. Nevertheless, it has been claimed that subnormal cortisol response using plastic tubes might have resulted from cosyntropin adherence to the tube and, thus, loss of the delivered dosage. Following from our previous study, which showed that using a short (2.5 cm) plastic tube does not alter in-vitro-cosyntropin dosage delivery or healthy-volunteers' morning cortisol responses, we predicted that, when using the same short plastic tube, LDT would show comparable morning and afternoon cortisol stimulation. The current study was designed to investigate this prediction by comparing morning and afternoon cortisol responses in healthy volunteers during LDT, using a short plastic tube. METHODS: Thirteen healthy adult volunteers were recruited for the study. Each subject underwent morning and afternoon LDT via 25 mm plastic intravenous line tube. Baseline serum cortisol (SC) in addition to SC and salivary free cortisol (SFC) 30-minute responses were determined. RESULTS: Mean baseline morning SC concentration was higher in the morning than in the afternoon (13.63±3.42 and 9.18±2.78 µg/dL, respectively; P<0.001); however, mean absolute SC-concentration increment between baseline and 30-minute time point was higher in the afternoon than in the morning (11.89±3.50 and 7.71±3.12 µg/dL, respectively; P=0.002). Subsequently, LDT resulted in comparable morning and afternoon 30-minute SC (21.33±3.08 and 21.08±3.43 µg/dL, respectively; P=0.782) and SFC concentration (0.939±0.256 and 1.036±0.372 µg/dL, respectively; P=0.463). CONCLUSIONS: In healthy volunteers, using a 2.5 cm plastic tube, LDT provides comparable morning and afternoon 30-minute stimulated SC and SFC concentration.


Subject(s)
Adrenal Insufficiency/diagnosis , Cosyntropin/pharmacology , Adult , Female , Healthy Volunteers , Humans , Hydrocortisone/blood , Hydrocortisone/metabolism , Male , Middle Aged , Saliva/chemistry , Time Factors
5.
Endocrine ; 62(2): 448-455, 2018 11.
Article in English | MEDLINE | ID: mdl-30051198

ABSTRACT

INTRODUCTION: Pasireotide, a multi-somatostatin receptor (SSTR)-ligand with high affinity for SSTR5 was recently approved for acromegaly treatment. PATIENTS AND METHODS: A retrospective multicenter study investigating the efficacy and safety of long-acting (LAR) pasireotide treatment in 35 patients (20 males) with active acromegaly (28 macroadenomas). RESULTS: Mean baseline insulin-like growth factor-1 (IGF-1) at diagnosis was 3.1 ± 1.3 × ULN. All but five patients have undergone pituitary surgery and six received sellar radiotherapy. All remained with active acromegaly despite first-generation somatostatin analogue (SSA) treatment. Immediately before pasireotide-LAR initiation, eighteen patients were under SSA monotherapy and one with pegvisomant. The remaining patients received combination therapy with SSA and pegvisomant, n = 9 (two received cabergoline also); SSA and cabergoline, n = 4; pegvisomant and cabergoline, n = 1. Two were untreated. Mean IGF-1 was 1.76 ± 0.9 ULN before pasireotide. Pasireotide-LAR starting dose was 40 mg/4 weeks in most patients. IGF-1 normalized in 19 patients, IGF-1 between 1-1.2 × ULN was reached in five, and in additional two patients IGF-1 was significantly suppressed. No effect was seen in nine patients. Pasireotide dose was reduced by 20 mg in six patients with excellent response, with preserved IGF-1 control in five. Severe headaches in six patients disappeared or improved with pasireotide. Side effects consisted of symptomatic cholelithiasis in one patient and deterioration of glucose control in 22 patients, requiring initiation or intensification of antidiabetic treatment in seventeen. One patient developed diabetic ketoacidosis. CONCLUSIONS: In the real-life scenario ~54% of patients with acromegaly resistant to first-generation SSA, may normalize IGF-1 with pasireotide; however, 63% experienced glucose control deterioration.


Subject(s)
Acromegaly/drug therapy , Somatostatin/analogs & derivatives , Somatostatin/therapeutic use , Acromegaly/etiology , Adenoma/complications , Adenoma/drug therapy , Adult , Delayed-Action Preparations/therapeutic use , Drug Resistance, Neoplasm/drug effects , Female , Growth Hormone-Secreting Pituitary Adenoma/complications , Growth Hormone-Secreting Pituitary Adenoma/drug therapy , Humans , Male , Middle Aged , Retrospective Studies , Treatment Failure , Treatment Outcome
6.
Endocrine ; 57(1): 46-50, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28530018

ABSTRACT

PURPOSE: Studies on 1 µg low-dose test showed that among 1 µg cosyntropin samples pushed through long IV plastic tubing, some adrenocorticotropic hormone dosage was not recovered, and in healthy volunteers it provided subnormal cortisol responses. The aim of the current study is to assess whether there is any loss in adrenocorticotropic hormone 1-24 concentration when pushed through a short plastic tube, and to assess serum and salivary cortisol responses in low-dose test among healthy volunteers, using a similar short plastic tube vs. direct intravenous consyntropin injection. METHODS: We evaluated in vitro if adrenocorticotropic hormone was absorbed in a 2.5 cm plastic tube by measuring adrenocorticotropic hormone 1-24 concentration in a 1 µg/ml adrenocorticotropic hormone aliquot solution before and after being flushed through the plastic tube. For the in vivo study, we recruited 20 healthy adult volunteers. Each subject underwent low-dose test via 2.5 cm plastic tube via plastic tube and via direct intravenous injection by a metal syringe via direct intravenous injection, and cortisol responses were determined. RESULTS: Mean adrenocorticotropic hormone 1-24 concentration did not differ significantly when flushed via plastic tube or measured in the aliquot solution (P = 0.25). In vivo, mean 30-min serum cortisol concentrations were 20.47 ± 2.87 and 21.62 ± 3.89 µg/dl in via plastic tube and in via direct intravenous injection tests, respectively, and did not show a significant difference (P = 0.16). CONCLUSIONS: In low-dose test, using a 2.5 cm plastic tube ensures completeness of the intravenous adrenocorticotropic hormone injection dosage and provides equivalent cortisol responses.


Subject(s)
Adrenal Insufficiency/diagnosis , Adrenocorticotropic Hormone/analysis , Cosyntropin , Hydrocortisone/analysis , Adult , Diagnostic Tests, Routine , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Saliva/chemistry , Sensitivity and Specificity , Young Adult
7.
Hormones (Athens) ; 15(3): 453-458, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27394707

ABSTRACT

OBJECTIVE: Cushing's disease during pregnancy is associated with an increased risk for maternal and fetal complications. In recurrent Cushing`s disease following transsphenoidal surgery, and when re-operation is not feasible, medical treatment is usually considered. Cabergoline was found to be effective in reducing hypercortisolism in Cushing's disease. Evolving data concerning the safety of cabergoline use during pregnancy show no significant increase in the rate of complications during pregnancy or the postnatal period. METHODS: We report a 29-year-old woman, gravida 0, para 0, with recurrent Cushing`s disease, three years after transsphenoidal resection of pituitary ACTH-secreting macroadenoma. Repeated MRI revealed an empty sella with a small gadolinium-enhancing lesion, suspected to be an adenoma remnant on the medial wall of the right cavernous sinus. As the patient was not willing to undergo repeat surgical intervention, treatment with cabergoline was initiated, with a gradual dose titration up to 3.5 mg/week. Clinical improvement ensued, and 4 months later, she conceived spontaneously. After discussing treatment options with the patient, cabergoline treatment at a dose of 2 mg/week was continued throughout pregnancy. RESULTS: The patient showed complete clinical remission during pregnancy. Consecutive tests of 24-h urinary free cortisol concentration were not found to be elevated. Pregnancy and delivery were uneventful except for mild hypothyroidism observed during the second trimester. At full term the patient delivered a healthy female infant, by an elective cesarean section. CONCLUSION: This case report demonstrates that cabergoline may be an effective and safe therapeutic option for the treatment of Cushing's disease during pregnancy.


Subject(s)
Antineoplastic Agents/therapeutic use , Ergolines/therapeutic use , Neoplasm Recurrence, Local , Pituitary ACTH Hypersecretion/drug therapy , Pregnancy Complications/drug therapy , Adult , Biomarkers/blood , Cabergoline , Female , Humans , Hydrocortisone/blood , Live Birth , Magnetic Resonance Imaging , Neoplasm, Residual , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/diagnosis , Pituitary ACTH Hypersecretion/surgery , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/diagnosis , Pregnancy Complications/surgery , Remission Induction , Treatment Outcome
8.
Obes Res Clin Pract ; 10(3): 275-82, 2016.
Article in English | MEDLINE | ID: mdl-26277697

ABSTRACT

PURPOSE: In order to differentiate between Cushing's syndrome (CS) and Pseudo-Cushing's syndrome, it is customary to use a test that is conducted by cortisol suppression with low-dose dexamethasone, followed by the administration of corticotropin releasing hormone (Dex-CRH test). In children with severe obesity, Dex-CRH test has shown a specificity of 55%. The aim of current study was to evaluate the specificity of Dex-CRH test in morbid obese adults. METHODS: The study included a total of 19 subjects with a body mass index (BMI) equal or higher than 40kg/m(2). In all subjects Dex-CRH test was performed, and 24h urinary free cortisol was collected prior the test and during the second day of dexamethasone administration (2nd-day-UFC). RESULTS: BMI was 45.1±4.6kg/m(2) and 45.7±3.3kg/m(2) in women and men, respectively. 14 subjects underwent bariatric surgery. No subject had surgical or perioperative complications and surgically treated subjects had mean body weight loss of 46.5±16.6kg. All except for 2 subjects had normal Dex-CRH test, as 15-min cortisol falling below 1.4µg/dl. During follow-up, no subject gained additional weight, neither developed signs of CS. 15-min-cortisol concentration of 1.4µg/dl revealed a specificity of 89% and 2nd-day-UFC of 16µg/24h showed a specificity of 100%. CONCLUSIONS: Morbid obesity in adults seems not to comprise a significant confounder in Dex-CRH test, and 15-min-cortisol concentration of 1.4µg/dl had a higher specificity than previously reported in obese children.


Subject(s)
Body Mass Index , Corticotropin-Releasing Hormone , Cushing Syndrome/diagnosis , Dexamethasone , Hydrocortisone/urine , Obesity, Morbid/complications , Adult , Bariatric Surgery , Corticotropin-Releasing Hormone/administration & dosage , Cushing Syndrome/complications , Cushing Syndrome/urine , Dexamethasone/administration & dosage , Female , Humans , Male , Middle Aged , Obesity, Morbid/surgery , Sensitivity and Specificity , Young Adult
9.
Harefuah ; 154(12): 791-4, 803, 2015 Dec.
Article in Hebrew | MEDLINE | ID: mdl-26897783

ABSTRACT

Cushing's syndrome results from prolonged and excessive exposure to medically prescribed corticosteroids, or from excess endogenous cortisol secretion. When endogenous cortisol secretion is suspected, several screening tests are conducted in order to confirm or to rule out the diagnosis. In recent years, as the cut-off point of cortisol concentration on the 1 mg overnight dexamethasone suppression test was lowered, the prevalence of Cushing's syndrome has increased, and more cases of mild syndromes, with negative results on one or more screening tests, have increasingly been reported. In this paper, we will describe the various screening tests used for Cushing's syndrome, and will discuss their degree of sensitivity in the diagnosis of mild cases. We conclude that, in cases of mild syndromes, the sensitivity of some tests appears to be notably lower than has been reported. Until recently, the major challenge has been to distinguish between pseudo-Cushing's states and Cushing's syndrome. Today, however, the challenge has become to avoid misdiagnosis of mild cases, presenting with normal results on some screening tests. The sensitivity of urinary free cortisol seems to be lower than previously reported. Therefore, we recommend not to rely solely on this test in ruling out Cushing's syndrome.


Subject(s)
Cushing Syndrome/diagnosis , Hydrocortisone/metabolism , Cushing Syndrome/physiopathology , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Humans , Sensitivity and Specificity
10.
Ann Clin Biochem ; 51(Pt 4): 490-4, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24518530

ABSTRACT

Heterophilic antibodies are well described, but poorly appreciated interferents and is often not a recognized problem affecting most immunoassays. We report a patient presented with ectopic Cushing's syndrome (CS), but repeated plasma adrenocorticotropic hormone (ACTH) concentrations conducted by immunoassay were inappropriately within the reference range and not elevated, most probably as a result of antibody interference. A 36-year-old woman, presented with large gastric neuroendocrine carcinoma and severe ectopic CS, while repeated plasma ACTH concentrations conducted by immunoassay were inappropriately within the reference range. As we expected ACTH concentration to be higher, we performed several tests to evaluate whether there was any assay interference causing falsely lower than expected ACTH results. We measured ACTH using a different immunoassay, assayed the sample in dilution, assayed the sample after being incubated in heterophilic antibody blocking agent tube and performed recovery studies. Tests indicated the presence of interfering compounds, most probably heterophilic antibodies. When clinicians find ACTH concentrations to be lower than expected, we recommend the laboratory investigate antibody interference.


Subject(s)
Adrenocorticotropic Hormone/blood , Autoantibodies/blood , Carcinoma, Neuroendocrine/blood , Pituitary ACTH Hypersecretion/blood , Stomach Neoplasms/blood , Adrenocorticotropic Hormone/immunology , Adult , Autoantibodies/immunology , Carcinoma, Neuroendocrine/immunology , Female , Humans , Immunoassay , Pituitary ACTH Hypersecretion/immunology , Stomach Neoplasms/immunology
11.
Neuro Endocrinol Lett ; 34(5): 331-8, 2013.
Article in English | MEDLINE | ID: mdl-23922042

ABSTRACT

A 54-year-old woman presented with a stalk mass that was discovered incidentally with mild visual fields defect. The mass was operated surgically by the fronto-temporal approach, and histology met the diagnosis of neurohypophesial granular cell tumor (GCT). After surgery, the patient suffered from an irreversible severe bi-temporal visual deficit and an irreversible hypopituitarism. We review the literature and discuss the clinical nature of GCTs, treatment options and outcome. In an effort to avoid the severe complications that may result from surgical removal of neurohypophesial GCT, we discuss also the possibility of choosing the conservative approach with close follow-up. The tumor's firm consistency, tendency to hemorrhage, involving the pituitary stalk and lack of dissection plane from basal brain structure render surgery difficult, and maximal resection often requires sacrificing the stalk. Moreover, small asymptomatic neurohypophysial GCTs are common findings, most probably benign tumors with slow growing nature. Hence, for a neurohypophesial tumor which is suspected to be a GCT, we offer to consider the alternative approach, with close clinical, visual field and radiological study follow up.


Subject(s)
Granular Cell Tumor/pathology , Hypopituitarism/pathology , Pituitary Gland, Posterior/pathology , Pituitary Neoplasms/pathology , Female , Granular Cell Tumor/surgery , Humans , Hypopituitarism/surgery , Middle Aged , Pituitary Gland, Posterior/surgery , Pituitary Neoplasms/surgery
12.
Eur J Obstet Gynecol Reprod Biol ; 165(1): 1-7, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22698457

ABSTRACT

We present a case of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome diagnosed in a patient in the third trimester of her pregnancy, with an adrenal mass observed on imaging studies. Laparoscopic adrenalectomy was performed successfully at 32 weeks. To the best of our knowledge, this is the latest gestational age at which laparoscopic adrenalectomy has been reported. We present the various considerations for determining the surgical approach and the optimal timing for surgery. Adrenalectomy during pregnancy for the treatment of Cushing's syndrome caused by adrenocortical adenoma has been reported in 23 patients in the English-language medical literature to date and seems safe and beneficial. According to the data, surgical treatment has led to a reduction in perinatal mortality and maternal morbidity rates, but has not affected the occurrence of preterm birth and intrauterine growth restriction. The best outcome can be achieved by a multidisciplinary approach, with a team comprising a maternal-fetal medicine specialist, an endocrinologist and a surgeon. The timing of surgery and the surgical approach need to be determined according to the surgeon's expertise, the severity of the condition, the patient's preferences, and gestational age. Laparoscopy may prove to be the preferred surgical approach. The small number of cases precludes providing evidence-based recommendations.


Subject(s)
Adrenal Cortex Neoplasms/surgery , Adrenalectomy , Adrenocortical Adenoma/surgery , Cushing Syndrome/etiology , Pregnancy Complications, Neoplastic/surgery , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/physiopathology , Adrenalectomy/adverse effects , Adrenocortical Adenoma/complications , Adrenocortical Adenoma/physiopathology , Adult , Cushing Syndrome/prevention & control , Diabetes, Gestational/diet therapy , Diabetes, Gestational/prevention & control , Female , Hormone Replacement Therapy , Humans , Hydrocortisone/therapeutic use , Laparoscopy , Pregnancy , Pregnancy Complications, Neoplastic/physiopathology , Pregnancy Trimester, Third , Term Birth , Treatment Outcome
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