Neuroendocrine tumors (NET) of the thymus are rare, usually aggressive, and prone to metastatic lesion. Ectopic adrenocorticotropic hormone (ACTH) secretion in thymic NET (TNEN) is associated with ...poor prognosis. Most of TNET express somatostatin receptors, it allows the use of somatostatin receptor scintigraphy (SRS) and SPECT/CT or PET/CT with 68Ga-labeled peptides for diagnosis and staging of the disease. Surgery (macroscopic-complete resection) is the mainstay treatment for TNET. Now, there are no unequivocal data in adjuvant therapy and its effectiveness. We present a case report of the pediatric patient with well differentiated atypical ACTH-producing thymic carcinoid. This localization was verified by whole body somatostatin receptor scintigraphy with 111In-DTPA-octreotide (Octreoscan). The patient proceeded with the surgical treatment followed by remission of hypercorticism without adjuvant chemotherapy. Tumor recurrence with redevelopment of ACTH-ectopic syndrome was detected after 67 months of observation.
This review provides the main results of clinical trials and the literature on the experience of using pegvisomant, the first drug from the class of growth hormone receptor antagonists. The mechanism ...of action of the drug, its effectiveness with respect to disease control and its effect on complications, information on adverse events, and brief information on the experience of use during pregnancy are discussed in detail. In conclusion, a clinical observation of successful use of pegvisomant in resistant to standart treatment acromegaly is given. A discussion of the available literature data, the results of clinical studies and practical experience allows us to conclude that the drug is highly effective in terms of achieving biochemical remission of acromegaly, and also has a number of additional valuable properties: it is capable of improvement of patients' glucose metabolism and quality of life and has a minimal amount of adverse events. Pegvisomant is currently registered in the Russian Federation only for use in monotherapy; the possibility of combination therapy with somatostatin analogues will additionally allow to reliably control the growth of the pituitary adenoma and significantly cut treatment costs by reducing the dose of pegvisomant. These features of the drug make it very relevant when discussing issues related to drug therapy of acromegaly, and suggest a good prospect for use in clinical practice.
We do not recommend population screening for diabetes insipidus (DI) (B3). We recommend to perform diagnostic testing for central diabetes insipidus (CDI) in patients who underwent neurosurgery, ...after skull and brain trauma, subarchnoid hemorrhage (B3). We recommend excluding thirst impairment during all stages of diagnostic assessment (С3).
We recommend excluding DI in cases of persistent hypotonic polyuria: excretion of more than 3 L. or more than 40 mL/kg of urine daily; urine osmolality less than 300 mOsm/kg or urinary specific gravity less than 1004 g/L in all urine samples or during Zimnitsky test (В3). After hypotonic polyuria is confirmed, we recommend excluding of the main causes of nephrogenic diabetes insipidus (NDI) (B3). We recommend simultaneous measurement of urine osmolality and blood osmolality/sodium level in order to confirm DI. Blood hyperosmolality (more than 300 mOsm/kg) and/or hypernatremia with low urine osmolality (less than 300 mOsm/kg) confirms DI (B2). If testing does not reveal these findings, we recommend performing a fluid deprivation test to exclude primary polydipsia (PP) (B2). Desmopressin test is recommended to distinguish CDI and NDI (B2).
In cases of CDI we recommend to perform head MRI with contrast (B3). In cases of NDI we recommend assessing renal structure and function and possible electrolyte disturbances (C3). In cases of PP we recommend to refer a patient to psychiatrist (B3).
We recommend treating CDI with synthetic vasopressin analogue desmopressin (B1). We recommend an individual approach in choosing desmopressin dosage form (B2). As the initial dose is difficult to predict when starting desmopressin treatment, we recommend titrating the dosage using two approaches: the average dose and as required (C4). We recommend educating the patients to ensure knowledge of the features of various desmopressin dosage forms (C4). To decrease the risk of water intoxication, we recommend educating the patients to the water intake regimen adherence (С4). When CDI is accompanied by thirst impairment, we recommend titrating the dose in a clinical setting, with assessment of blood sodium, bodyweight and/or urine volume (C4).
Акромегалия — нейроэндокринное заболевание, возникающее вследствие избыточной продукции гормона роста (соматотропного гормона, СТГ). В большинстве случаев причиной акромегалии являются аденомы ...гипофиза, продуцирующие СТГ. Гораздо реже встречаются случаи эктопической акромегалии. Последняя возникает вследствие опухолей, продуцирующих гормон роста-рилизинг гормон (ГРРГ), или опухолей внегипофизарной локализации, продуцирующих СТГ. Основными источниками секреции ГРРГ являются нейроэндокринные опухоли (НЭО) легких и поджелудочной железы. Лечение эктопической акромегалии заключается в хирургическом удалении источника гиперпродукции ГРРГ, а в случае невозможности радикального удаления используют аналоги соматостатина длительного действия, пэгвисомант, химиотерапию, иммунотерапию, лучевую терапию.
В данной статье приведено описание трех клинических случаев эктопической акромегалии вследствие ГРРГ-продуцирующих НЭО легких, каждый из которых примечателен рядом особенностей. В первых двух случаях акромегалия имела мягкое течение и неяркие клинические проявления, при этом во 2 случае имелось сочетание эктопической акромегалии и первичного гиперпаратиреоза. В 3 случае эктопическая акромегалия сочеталась с макроаденомой гипофиза, и после хирургического лечения НЭО ремиссия акромегалии не наступила. Во всех трех случаях НЭО легких были обнаружены случайно при проведении рентгенологического обследовании грудной клетки по поводу других состояний.
ОБОСНОВАНИЕ. Нейрохирургическое лечение является наиболее эффективным методом терапии акромегалии. Учитывая преобладающую долю макроаденом у пациентов с акромегалией, оперативное лечение не всегда ...является успешным, даже при экспертном уровне нейрохирурга. Определение частоты ремиссии акромегалии после хирургического лечения и поиск дооперативных предикторов эффективности являются актуальными задачами современных исследований.ЦЕЛЬ. Оценить краткосрочную и долгосрочную ремиссию акромегалии после эндоскопической трансназальной аденомэктомии в условиях высокоспециализированного стационара и определить предикторы эффективности нейро хирургического вмешательства.МАТЕРИАЛЫ И МЕТОДЫ. Проведено одноцентровое проспективное неконтролируемое исследование. В выборку включались пациенты с активной стадией акромегалии, не получавшие медикаментозную терапию аналогами соматостатина, направленные на эндоскопическую транссфеноидальную аденомэктомию. Экспрессия микроРНК плазмы проведена методом количественной ПЦР с обратной транскрипцией. Послеоперационные образцы аденом направлены на иммуногистохимическое исследование с определением морфологического варианта и экспрессии рецепторов соматостатина 2 и 5 подтипов.РЕЗУЛЬТАТЫ. В исследование включены 44 пациента, из них 32,8% мужчин, медиана возраста составила 47,0 34,0; 55,0, уровень инсулиноподобного фактора роста 1-го типа (ИФР-1) — 744,75 нг/мл 548,83; 889,85, соматотропного гормона (СТГ) — 9,5 нг/мл 4,94; 17,07, объем опухоли — 832 мм3 419,25; 2532,38. Ранняя послеоперационная ремиссия достигнута у 35 больных (79,5%). Пациенты, достигшие кратковременной ремиссии, имели более высокий уровень ИФР-1 и базальный СТГ. Медиана наблюдения составил 19,0 мес 12,5; 29,0. Длительная ремиссия достигнута у 61,4% (27 больных), ремиссии не было у 9 (20,5%), рецидив выявлен у 2 пациентов (4,5%), 6 потеряны для наблюдения (13,6%). У пациентов с долгосрочной ремиссией отмечались более низкие базальные уровни СТГ и ИФР-1. Различий по уровням исследованных микроРНК не выявлено. Проведена оценка прогностической ценности базального СТГ до операции в определении долгосрочной ремиссии: площадь под кривой 0,811 (95% ДИ 0,649; 0,973). Пороговое значение 15,55 нг/мл соответствовало чувствительности 70,0 (34,8; 93,3)%, специфичности — 85,7 (67,3; 96,0)%, точности — 81,6 (65,7; 92,3)%, прогностической ценности положительного результата — 63,6 (39,3; 82,5)%, прогностической ценности отрицательного результата — 88,9 (75,4; 95,4)%.ЗАКЛЮЧЕНИЕ. Частота краткосрочной и долгосрочной ремиссии после эндоскопической транссфеноидальной аденомэктомии в изученной когорте составила 79,5 и 61,4% соответственно и сравнима с литературными данными нейрохирургических центров экспертного уровня. Базальный СТГ демонстрирует потенциальную ценность в прогнозировании долгосрочной ремиссии акромегалии, однако для получения более точных отрезных значений необходимы дальнейшие исследования на расширенной выборке.
Abstract
Introduction Thyrotropin-secreting pituitary adenoma (TSH-oma) is a rare cause of thyrotoxicosis and represents 0.5-3% of all pituitary adenomas. Given the rarity of the disease and the lack ...of extensive clinical experience in world practice, the analysis of each case of TSH-secreting pituitary tumors is extremely relevant.
Materials and methods: We enrolled consecutive patients with TSH secreting pituitary adenoma. TSH (0,25-3,5 mIU/L), FT4 (9-20 pmol/l) FT3 (2,5-5,5 pmol/l) were measured by Architect i2000SR (Abbott Laboratories, Abbott Park, Illinois, U.S.A). An octreotide test consisted of injecting short-acting somatostatin analogue (SSA) at a dose of 100 μg 3 times a day subcutaneously during 3 days or long-acting SSA 20 mg in 28 days minimum for two months and measuring thyroid profile blood tests before and at the end of the test. MRI was performed on GE Optima MR450w 1.5T.
Results: We present 28 case series with TSH-omas followed in our center from 2010 to 2019, the median age - 46 (from 10 to 71 years) with a predominance of a female (21 cases) over a male (7 cases). Clinical manifestations included cardiac arrhythmias (82.1%), neurological changes (60.7%), visual impairment (39.3%), osteoporosis (28.6%), hypopituitarism (7.1%).
At first admission, 17 patients had increased TSH, FT3 and FT4; in 7 patients - FT3 and FT4 only, and in 4 - an increase was in one of the hormones; mean value of TSH was 5,04 mIU/L, FT4 - 24,46 pmol/l, FT3 - 8,9 pmol/l. SSBG, CTx, osteocalcin were elevated in 60.9%, 57.9% and 31.6% of cases, respectively. In 88.5% of cases octreotide test led to thyroid hormones normalization. On MRI macroadenomas was registered in 67.9%. In 12 patients, diagnosis was confirmed by immunohistochemical examination. In 12 patients, the diagnosis verification was based on remission after surgical and medical treatment. In the remaining four cases, the diagnosis was made on clinical and laboratory data, however, confirmation was inconceivable due to inefficacy of medical treatment.
Remission was achieved in 23 patients: 17 of 21 after neurosurgery (81%), 3 of 7 after primary administration of SSA, and 3 after administration of SSA after surgery (100% remission in cases of combined treatment and 42.9% of monotherapy); 3 out of 5 patients who did not achieve remission were lost for observation. Two patients died: in one case due to the brain herniation and cachexia in active thyrotoxicosis. In second case, the patient developed a mental disorder (catatonia) after the second transphenoidal adenomectomy, which led to death.
Conclusion The diagnosis of TSH-oma should be based on all thyroid hormones assessment, since biochemical thyrotoxicosis can manifest itself in various ways. The most effective treatment is transphenoidal adenomectomy. If a neurosurgery is not effective or contraindicative, preoperative preparations SSA can be used.
We do not recommend population screening for diabetes insipidus (DI) (B3). We recommend to perform diagnostic testing for central diabetes insipidus (CDI) in patients who underwent neurosurgery, ...after skull and brain trauma, subarchnoid hemorrhage (B3). We recommend excluding thirst impairment during all stages of diagnostic assessment (С3).
We recommend excluding DI in cases of persistent hypotonic polyuria: excretion of more than 3 L. or more than 40 mL/kg of urine daily; urine osmolality less than 300 mOsm/kg or urinary specific gravity less than 1004 g/L in all urine samples or during Zimnitsky test (В3). After hypotonic polyuria is confirmed, we recommend excluding of the main causes of nephrogenic diabetes insipidus (NDI) (B3). We recommend simultaneous measurement of urine osmolality and blood osmolality/sodium level in order to confirm DI. Blood hyperosmolality (more than 300 mOsm/kg) and/or hypernatremia with low urine osmolality (less than 300 mOsm/kg) confirms DI (B2). If testing does not reveal these findings, we recommend performing a fluid deprivation test to exclude primary polydipsia (PP) (B2). Desmopressin test is recommended to distinguish CDI and NDI (B2).
In cases of CDI we recommend to perform head MRI with contrast (B3). In cases of NDI we recommend assessing renal structure and function and possible electrolyte disturbances (C3). In cases of PP we recommend to refer a patient to psychiatrist (B3).
We recommend treating CDI with synthetic vasopressin analogue – desmopressin (B1). We recommend an individual approach in choosing desmopressin dosage form (B2). As the initial dose is difficult to predict when starting desmopressin treatment, we recommend titrating the dosage using two approaches: “the average dose” and “as required” (C4). We recommend educating the patients to ensure knowledge of the features of various desmopressin dosage forms (C4). To decrease the risk of water intoxication, we recommend educating the patients to the water intake regimen adherence (С4). When CDI is accompanied by thirst impairment, we recommend titrating the dose in a clinical setting, with assessment of blood sodium, bodyweight and/or urine volume (C4).
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