ABSTRACT
Levothyroxine therapy in management of diferentiated thyroid carcinoma (DTC) has been common practice for decades. Levothyroxine is being administered to patiens with DTC after total thyreoidectomy (with or without postopreative radioiodine treatment) not only to restore euthyroidism but to suppress the production of thyroid-stimulating hormone (TSH) as well because TSH is considered as a growth factor for thyroid follicular cells. However there has been a downside to this threatment recently. The main concerns are the known risks related to iatrogenic subclinical or even mild but clinicaly overt iatrogenic hyperthyroidism. Therefore individualized treatment approach aiming to balance between the risk of tumor recurence and the risks related to hypertyhroidism in view of pateints age, risk factors and comorbidities is essential. Close folow-up is therefore necessary with frequent dose adjustments according to target TSH values published in American Thyroid Association guidelines.
Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Humans , Thyroxine/therapeutic use , Iodine Radioisotopes/therapeutic use , Thyroid Neoplasms/drug therapy , Thyrotropin/therapeutic useABSTRACT
Enlargement of the pituitary gland is heterogenous in the etiology. Common causes of pituitary enlargement are physiological hypertrophy during pregnancy, primary and secondary tumors, autoimmune hypophysitis including side effects of anticancer therapy with check-point inhibitors. Terms like hypertrophy, hyperplasia, sellar expansion and hypophysitis are commonly used to describe enlargement of the pituitary gland on MR scan regardless its etiology. The most common pathology causing pituitary gland enlargement is pituitary adenoma. Magnetic resonance imaging can differentiate pituitary tumors from diffuse enlargement due to hypophysitis in most but not all cases. Changes on imaging during time or response to pharmacotherapy might help determine the final diagnosis in uncertain cases. We present a case report of a young woman with sellar expansion due to prolonged untreated peripheral hypothyroidism mimicking pituitary adenoma. Interdisciplinary cooperation of endocrinologist, radiologist and neurosurgeon is crucial in determining the diagnosis.
Subject(s)
Adenoma , Hypophysitis , Hypothyroidism , Pituitary Diseases , Pituitary Neoplasms , Adenoma/complications , Adenoma/diagnosis , Diagnosis, Differential , Female , Humans , Hypertrophy , Hypothyroidism/complications , Magnetic Resonance Imaging , Pituitary Diseases/complications , Pituitary Diseases/diagnosis , Pituitary Gland/diagnostic imaging , Pituitary Gland/pathology , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnosis , PregnancyABSTRACT
PURPOSE: Surgical resection is the first line treatment for growth hormone (GH) secreting tumors. Stereotactic radiosurgery (SRS) is recommended for patients who do not achieve endocrine remission after resection. The purpose of this study was to evaluate safety and efficacy of repeat radiosurgery for acromegaly. METHODS: Three hundred and ninety-eight patients with acromegaly treated with the Gamma Knife radiosurgery (Elekta AB, Stockholm) were identified from the International Gamma Knife Research Foundation database. Among these, 21 patients underwent repeated SRS with sufficient endocrine follow-up and 18 patients had sufficient imaging follow-up. Tumor control was defined as lack of adenoma progression on imaging. Endocrine remission was defined as a normal IGF-1 concentration while off medical therapy. RESULTS: Median time from initial SRS to repeat SRS was 5.0 years. The median imaging and endocrine follow-up duration after repeat SRS was 3.4 and 3.8 years, respectively. The median initial marginal dose was 17 Gy, and the median repeat marginal dose was 23 Gy. Of the 18 patients with adequate imaging follow up, 15 (83.3%) patients had tumor control and of 21 patients with endocrine follow-up, 9 (42.9%) patients had endocrine remission at last follow-up visit. Four patients (19.0%) developed new deficits after repeat radiosurgery. Of these, 3 patients had neurologic deficits and 1 patient had endocrine deficit. CONCLUSIONS: Repeat radiosurgery for persistent acromegaly offers a reasonable benefit to risk profile for this challenging patient cohort. Further studies are needed to identify patients best suited for this type of approach.
Subject(s)
Acromegaly/radiotherapy , Radiosurgery , Acromegaly/blood , Adolescent , Adult , Aged , Female , Human Growth Hormone/blood , Humans , Insulin-Like Growth Factor I/metabolism , Male , Middle Aged , Reoperation , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS. METHODS: Twenty-eight patients were followed-up after GKRS for 26-195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients). RESULTS: After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient. CONCLUSIONS: GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.
Subject(s)
Prolactinoma/radiotherapy , Radiosurgery/methods , Adult , Dopamine Agonists/therapeutic use , Female , Hemianopsia/radiotherapy , Humans , Hypopituitarism/radiotherapy , Male , Middle Aged , Prolactinoma/drug therapy , Treatment Outcome , Young AdultABSTRACT
AIM OF THE STUDY: Angiopoietin-like protein 6 (ANGPTL6) is a circulating protein with a potential role in energy homeostasis. The aim of the study was to explore the changes in ANGPTL6 levels in patients with obesity (Body mass index, BMI > 40 kg/m2) with and without type 2 diabetes mellitus (T2DM) undergoing dietary intervention (very low calorie diet - VLCD) and in a subgroup of T2DM patients after bariatric surgery. Additionally, we examined changes in ANGPTL6 in anorexia nervosa (AN) patients at baseline and after partial realimentation. We also explored the changes in ANGPTL6 mRNA expression in subcutaneous adipose tissue (SAT) of obese subjects. MATERIALS AND METHODS: The study included 23 non-diabetic obese patients, 40 obese patients with T2DM (27 underwent VLCD and 13 underwent bariatric surgery), 22 patients with AN, and 37 healthy control subjects. RESULTS: ANGPTL6 levels of AN patients were increased relative to the control group (68.6 ± 9.9 ng/ml) and decreased from 110.2 ± 13.3 to 73.6 ± 7.1 ng/ml (p = 0.004) after partial realimentation. Baseline ANGPTL6 levels in patients with obesity and T2DM did not differ from the control group. VLCD decreased ANGPTL6 levels only in obese patients with T2DM. Bariatric surgery induced a transient elevation of ANGPTL6 levels with a subsequent decrease to baseline levels. ANGPTL6 mRNA expression transiently increased after bariatric surgery and returned to baseline levels after 12 months. CONCLUSIONS: Collectively, our data suggest that serum ANGPTL6 levels and ANGPTL6 mRNA expression in SAT are affected by metabolic disorders and their treatment but do not appear to directly reflect nutritional status.
Subject(s)
Angiopoietins/blood , Anorexia Nervosa/blood , Diabetes Mellitus, Type 2/blood , Obesity/blood , Angiopoietin-Like Protein 6 , Angiopoietin-like Proteins , Anorexia Nervosa/diet therapy , Anorexia Nervosa/metabolism , Bariatric Surgery , Caloric Restriction , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/surgery , Humans , Middle Aged , Obesity/diet therapy , Obesity/surgery , Treatment OutcomeABSTRACT
INTRODUCTION: We continuously look for new techniques to improve the radicality of resection and to eliminate the negative effects of surgery. One of the methods that has been implemented in the perioperative management of Cushing's disease was the combination of three magnetic resonance imaging (MRI) sequences: SE, SPGR and fSPGR. MATERIAL AND METHODS: We enrolled 41 patients (11 males, 30 females) diagnosed with Cushing's disease. A 3D tumour model with a navigation console was developed using each SPGR, fSPGR and SE sequence. The largest model was then used. In all cases, a standard four-handed, bi-nostril endoscopic endonasal technique was used. Endocrinological follow-up evaluation using morning cortisol sampling was performed for 6-34 months in our study. RESULTS: In total, 36 patients (88%) were disease-free following surgery. Our results indicate we achieved 100% sensitivity of MR. Overall, the conformity of at least one donor site, as compared with the places designated on MR, was in 78% of patients. We searched the place of compliance in individual locations. There is a consensus in individual locations in 63 of the 123 cases (or 56%). The correlation gamma function at a 5% significance level was then 0.27. DISCUSSION: The combination of MR sequences (SE, SPGR, fSPGR), neuronavigation system and iMRI led to increased sensitivity of up to 100%. Specificity reached 56% in our study. CONCLUSION: We found a high success rate in surgical procedure in terms of the correlation between MR findings and histology, which leads to remission of Cushing's disease.
Subject(s)
Magnetic Resonance Imaging/methods , Neuronavigation/methods , Pituitary ACTH Hypersecretion/diagnostic imaging , Pituitary ACTH Hypersecretion/surgery , Transanal Endoscopic Surgery/methods , Adolescent , Adult , Aged , Child , Female , Humans , Magnetic Resonance Imaging/standards , Male , Middle Aged , Sensitivity and Specificity , Young AdultABSTRACT
Male hypogonadism can be of various etiology and that reflects its clinical manifestation, diagnostics and treatment. Male hypogonadism leads not only to decreased fertility, but influences the cardiovascular system, mood changes, bone fragility, lipids and other metabolic functions. Diagnosis of hypogonadism can be cumbersome, as well as the choice of optimal hormonal supplementation. The aim of this article is to summarize the basics from symptoms, diagnosis and treatment of male hypogonadism.
Subject(s)
Hypogonadism , Testosterone , Humans , Hypogonadism/therapy , MaleABSTRACT
INTRODUCTION: To increase radicality and avoid surgical complications new treatment options are under investigation. One of the promising possibilities is to assess early morning cortisol levels on the first and second postoperative day. MATERIAL AND METHODS: We enrolled 34 patients (9 males, 25 females) diagnosed with Cushing's disease. Blood samples to determine cortisol level were taken always at 06:00 and sent to the lab. The samples were taken on the first and second postoperative day. For all patients, standard four-handed, a bi-nostril endoscopic endonasal technique was used. Endocrinological follow-up (6-34 months) was performed using morning cortisol sampling. RESULTS: In total, 36 patients (88%) were disease-free post-surgery. In the group with early postoperative levels of morning cortisol of less than 463 nmol/L, only 2 of 29 patients (7%) exceeded the final morning level of cortisol at follow-up. In patients with early postoperative cortisol levels between 17 nmol/l and 234 nmol/l all subjects showed normal postoperative cortisol levels. DISCUSSION: In 30 of 34 patients (88%), the level of cortisol was within normal limits. The prediction importance of early measurement of cortisol is 93% for patients with early postoperative cortisol levels of less than 463 nmol/L. The prediction importance of early measurement of cortisol is 100% for patients with early postoperative cortisol levels from 17 to 234 nmol/L. CONCLUSION: The monitoring of early morning cortisol levels seems to be an important tool in the management of central Cushing's disease.
Subject(s)
Hydrocortisone/blood , Neurosurgical Procedures/methods , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/surgery , Adolescent , Adult , Aged , Child , Endoscopy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Monitoring, Physiologic , Pituitary Gland/surgery , Postoperative Complications/epidemiology , Postoperative Period , Treatment Outcome , Young AdultABSTRACT
Studies on the time course of ACTH- or insulin-induced hypoglycemia stimulating adrenal androgens are usually limited to dehydroepiandrosterone and/or its sulphate. Our data on dehydroepiandrosterone (DHEA) and its hydroxylated metabolites clearly show that measurements of DHEA and its sulphate (DHEAS) are valuable markers of the integrity of the HPA (hypothalamus-pituitary-adrenal) axis. Assessments of HPA function should rely on measurements of baseline and/or stimulated serum cortisol concentrations, and C19 Δ5-steroids may provide additional information. The art of stimulation of 7- and 16-hydroxylated metabolites of DHEA can help our understanding of the formation sequence of these compounds.
Subject(s)
ACTH-Secreting Pituitary Adenoma/diagnosis , Adrenal Insufficiency/diagnosis , Dehydroepiandrosterone Sulfate/blood , Hydrocortisone/blood , ACTH-Secreting Pituitary Adenoma/blood , Adrenal Insufficiency/blood , Adult , Dehydroepiandrosterone/administration & dosage , Diagnostic Techniques, Endocrine , Female , Humans , Hypoglycemia/chemically induced , Middle AgedABSTRACT
Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 µg, 10 µg, and 250 µg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 µg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.
Subject(s)
Adrenal Insufficiency/diagnosis , Cosyntropin/pharmacology , Dehydroepiandrosterone/analysis , Hydrocortisone/analysis , Pregnenolone/analysis , Saliva/metabolism , Adrenal Insufficiency/metabolism , Adult , Chromatography, Liquid/methods , Diagnostic Tests, Routine/methods , Healthy Volunteers , Hormones/pharmacology , Humans , Hypothalamo-Hypophyseal System/metabolism , Male , Pituitary-Adrenal System/metabolismABSTRACT
Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.
Subject(s)
Carcinoma, Neuroendocrine , Neuroendocrine Tumors , Paraganglioma , Humans , Immunohistochemistry , Neuroendocrine Tumors/pathology , Transcription Factors/metabolism , Paraganglioma/diagnosis , Paraganglioma/pathology , Carcinoma, Neuroendocrine/pathologyABSTRACT
Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to understand variance in practice management of pituitary tumors amongst neurosurgical centers. A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, "mainly endoscopic/mainly microscopic practice" and geographical regions. Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1-5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.
Subject(s)
Adenoma , Pituitary Neoplasms , Prolactinoma , Adenoma/pathology , Adenoma/surgery , Adrenocorticotropic Hormone , Humans , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Prolactinoma/pathology , Prolactinoma/surgery , Retrospective StudiesABSTRACT
A number of endocrine abnormalities develop in patients with HIV infection, although many are likely responses to infection, stress, and malnutrition. Others are due to infiltration of endocrine glands by tumor or infection. This article reviews adrenal, testicular, resp.gonadal, pancreatic, calcium and thyroid abnormalities in HIV infected patients.
Subject(s)
Endocrine System Diseases/complications , HIV Infections/complications , Acquired Immunodeficiency Syndrome/complications , HumansABSTRACT
BACKGROUND: Targeted stereotactic radiosurgery (SRS) with sparing of the residual pituitary is the traditional radiosurgical method for pituitary adenomas. Whole-sella SRS is an alternative choice for radiologically indeterminate or large adenomas, the safety and efficacy of which has yet to be determined. OBJECTIVE: To determine if whole-sella SRS in acromegaly would have comparable radiographic and biochemical control to targeted SRS. We performed a multicenter, retrospective matched cohort study to compare outcomes between groups. METHODS: We conducted a retrospective review of acromegalic patients who underwent SRS from 1990 to 2016 at 10 centers participating in the International Radiosurgery Research Foundation. Whole-sella and targeted SRS patients were then matched in a 1:1 ratio. RESULTS: A total of 128 patients were eligible for inclusion. Whole-sella patients had a higher pre-SRS random serum growth hormone, larger treatment volume, and higher maximum point dose to the optic apparatus. The rates of initial/durable endocrine remission, new loss of pituitary function, and new cranial neuropathy were similar between groups. Mortality and new visual deficit were higher in the whole-sella cohort, though not statistically significant. CONCLUSION: There was no difference in biochemical remission or recurrence between treatment groups. Although not statistically significant, the higher rates of tumor regression and lower rates of mortality and new visual deficit may suggest consideration of targeted SRS over whole-sella SRS in acromegaly treatment. Further research is needed to determine the association between visual deficits and mortality with whole-sella SRS.
Subject(s)
Adenoma/surgery , Pituitary Neoplasms/surgery , Radiosurgery/methods , Acromegaly/etiology , Acromegaly/surgery , Adenoma/complications , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Pituitary Neoplasms/complications , Radiation Injuries/epidemiology , Radiation Injuries/etiology , Radiosurgery/adverse effects , Retrospective Studies , Young AdultABSTRACT
CONTEXT: Improvement of imaging methods has led to more incidental adrenal tumor findings, especially adenomas. Routine hormonal evaluation uses only a few steroids to evaluate possible hormonal hypersecretion of these adenomas, but a wide spectrum of serum steroid hormone changes has not been published. OBJECTIVE: To measure the serum levels of 83 steroids from patients with unilateral and bilateral adrenal incidentalomas to uncover full steroid profile changes in patients with subclinical hypercortisolism (SH). DESIGN: Cross-sectional study. SETTING: The study was conducted at a tertiary inpatient clinic. PATIENTS: Fifty-two patients with adrenal incidentalomas (unilateral, n = 29; bilateral, n = 23), including nonfunctioning (n = 11) vs SH (n = 41), and 26 age- and sex-matched controls from the general population were included. MAIN OUTCOME MEASURES: Eighty-three serum steroids were measured by gas chromatography-tandem mass spectrometry (GC-MS/MS) before and after 1 mg dexamethasone, ACTH, midnight serum cortisol, and urinary free cortisol/24 hour. RESULTS: Of 83 measured steroids, 10 were significantly decreased in patients with SH, including dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate, epiandrosterone sulfate, androstenediol sulfate, conjugated 5α-androstane-3ß,17ß-diol, and conjugated 5α-androstane-3α,17ß-diol. This finding was observed even when unilateral, bilateral, male, and female subgroups were analyzed separately. When we compared routine clinical methods and GC-MS/MSâmeasured steroids, the most discriminatory was DHEAS followed by midnight serum cortisol, epiandrosterone sulfate, androsterone sulfate, ACTH, and 16α-hydroxypregnenolone. CONCLUSIONS: SH was associated with decreased levels of adrenal androgens, their metabolites, and pregnenolone metabolite. GC-MS/MS is a powerful tool for measuring serum levels of these undescribed changes in steroid metabolism, which are characteristic of SH in adrenal incidentalomas.
Subject(s)
Adrenal Gland Neoplasms/blood , Adrenocortical Hyperfunction/diagnosis , Gas Chromatography-Mass Spectrometry/methods , Steroids/blood , Tandem Mass Spectrometry/methods , Adrenal Gland Neoplasms/etiology , Adrenocortical Hyperfunction/complications , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
CONTEXT: Cushing's syndrome is caused by increased exposure to cortisol. Discrimination of different causes of endogenous hypercortisolism can make a diagnostic dilemma. PATIENTS AND METHODS: In serum samples from patients with Cushing's syndrome (47 with Cushing's disease, 6 with ectopic ACTH-dependent Cushing's syndrome, 16 with adrenal adenoma, 7 bilateral adrenal hyperplasia (BMAH) with overt Cushing's syndrome, 42 controls from the general population) using novel method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) we measured 94 serum steroids to search for steroid fingerprint of each subtype. RESULTS: Patients with Cushing's disease and ectopic ACTH producing tumors showed elevated levels of androgens and their metabolites when compared with healthy controls. Mineralocorticoid precursors were also elevated in ectopic ACTH syndrome. The levels of androgens were decreased in adrenal adenomas and BMAH. ROC analysis showed 100% sensitivity and 93.6% specificity for 11ß-hydroxyepiandrosterone sulfate for discrimination of Cushing's disease from ectopic ACTH secretion. We didn't find any significant (pâ¯<â¯0.05) difference in steroids that would discriminate BMAH from unilateral adenomas causing Cushing's syndrome. CONCLUSION: Various causes of Cushing's syndrome show particular steroid fingerprints that can be used to discriminate and may help to achieve appropriate clinical diagnosis.
Subject(s)
ACTH Syndrome, Ectopic/diagnosis , Adenoma/diagnosis , Adrenal Hyperplasia, Congenital/diagnosis , Adrenocorticotropic Hormone/blood , Cushing Syndrome/diagnosis , Disorder of Sex Development, 46,XY/diagnosis , Hydrocortisone/blood , Steroids/blood , ACTH Syndrome, Ectopic/blood , Adenoma/blood , Adrenal Hyperplasia, Congenital/blood , Adult , Aged , Biomarkers/blood , Case-Control Studies , Cushing Syndrome/blood , Disorder of Sex Development, 46,XY/blood , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
OBJECTIVE: Pituitary adenomas comprise about 3% of all intracranial tumors in pediatric patients. This study examines the role of stereotactic radiosurgery in the management of pediatric acromegaly or patients with Cushing disease (CD). METHODS: From an international consortium, we retrospectively collected treatment and outcome data on pediatric adrenocorticotrophic hormone and growth hormone-secreting pituitary adenomas treated with Gamma Knife radiosurgery (GKRS). There were a total of 36 patients including 24 with CD and 12 with acromegaly. The data were analyzed to assess outcomes including tumor control, endocrine remission, and adverse effects. Statistical analysis was performed to determine correlation between clinical/treatment parameters and outcomes. RESULTS: At the last follow-up after GKRS, endocrine remission rates for CD and acromegaly were 80% and 42%, respectively. Tumor control was achieved in 87.5% of patients with CD and in 42% of patients with acromegaly. New pituitary hormone deficiency occurred in 7 of the 36 patients at a median time of 18 months after GKRS (range, 12-81 months). The predictive factors for endocrine remission were age <15 years (P = 0.015) and margin dose (P = 0.042). The median endocrine follow-up was 63.7 months (range, 7-246 months). CONCLUSIONS: GKRS affords reasonable rates of endocrine remission and tumor control in most pediatric patients with functioning adenomas. The most common post-GKRS complication was hypopituitarism, although this occurred in only a few patients. Given the larger at-risk period for pediatric patients, further study is required to evaluate for delayed recurrences and hypopituitarism.
Subject(s)
Acromegaly/radiotherapy , Pituitary ACTH Hypersecretion/radiotherapy , Pituitary Neoplasms/complications , Radiosurgery , Acromegaly/complications , Acromegaly/diagnosis , Adolescent , Adult , Child , Female , Humans , Kaplan-Meier Estimate , Male , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/diagnosis , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: The role of primary stereotactic radiosurgery (SRS) in patients with medically refractory acromegaly who are not operative candidates or who refuse resection is poorly understood. The aim of this multicenter, matched cohort study was to compare the outcomes of primary versus postoperative SRS for acromegaly. METHODS: The authors reviewed an International Radiosurgery Research Foundation database of 398 patients with acromegaly who underwent SRS and categorized them into primary or postoperative cohorts. Patients in the primary SRS cohort were matched, in a 1:2 ratio, to those in the postoperative SRS cohort, and the outcomes of the 2 matched cohorts were compared. RESULTS: The study cohort comprised 78 patients (median follow-up 66.4 months), including 26 and 52 in the matched primary and postoperative SRS cohorts, respectively. In the primary SRS cohort, the actuarial endocrine remission rates at 2 and 5 years were 20% and 42%, respectively. The Cox proportional hazards model showed that a lower pre-SRS insulin-like growth factor-1 level was predictive of initial endocrine remission (p = 0.03), whereas a lower SRS margin dose was predictive of biochemical recurrence after initial remission (p = 0.01). There were no differences in the rates of radiological tumor control (p = 0.34), initial endocrine remission (p = 0.23), biochemical recurrence after initial remission (p = 0.33), recurrence-free survival (p = 0.32), or hypopituitarism (p = 0.67) between the 2 matched cohorts. CONCLUSIONS: Primary SRS has a reasonable benefit-to-risk profile for patients with acromegaly in whom resection is not possible, and it has similar outcomes to endocrinologically comparable patients who undergo postoperative SRS. SRS with medical therapy in the latent period can be used as an alternative to surgery in selected patients who cannot or do not wish to undergo resection.
ABSTRACT
BACKGROUND: Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined. OBJECTIVE: To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors. METHODS: We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo. RESULTS: The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%. CONCLUSION: SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission.
Subject(s)
Acromegaly/surgery , Adenoma/surgery , Growth Hormone-Secreting Pituitary Adenoma/surgery , Radiosurgery/methods , Acromegaly/etiology , Adenoma/complications , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Growth Hormone-Secreting Pituitary Adenoma/complications , Humans , Male , Middle Aged , Radiosurgery/adverse effects , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is a controversial topic; it remains unclear if HT acts as a risk factor of TC. The aim of our study was to compare the presence of HT and thyroid function in patients with TC and benign nodules. We analyzed 2571 patients after fine needle aspiration biopsy of thyroid nodule. Totally, 91 patients with primary TC and 182 sex- and age-matched controls were included. Positive antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies were associated with TC (anti-TPO 44% in TC vs. 27% in controls, P = 0.005, anti-TG 35% in TC group vs. 21% in controls, P = 0.018), and the TC group had significantly higher TSH (median 1.88 mIU/l vs. 1.21 mIU/l, P < 0.001). Using multiple logistic regression, positive anti-TPO was identified as an independent risk factor (OR 2.21, P = 0.018), while spontaneously suppressed TSH < 0.5 mIU/l was a protective factor (OR 0.3, P = 0.01) against TC. In conclusion, nodules in subjects with positive antithyroid antibodies could be considered to have a higher risk of malignancy. However, based on our results, it is not possible to declare that TC is triggered by HT.