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Anterior Pituitary Disease Adenohypophysis Disease Department of Endocrinology and Metabolism West China Hospital Sichuan University 余叶蓉.

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Presentation on theme: "Anterior Pituitary Disease Adenohypophysis Disease Department of Endocrinology and Metabolism West China Hospital Sichuan University 余叶蓉."— Presentation transcript:

1 Anterior Pituitary Disease Adenohypophysis Disease Department of Endocrinology and Metabolism West China Hospital Sichuan University 余叶蓉

2 主要内容  下丘 脑 - 垂体相关基 础 知 识  腺垂体疾病的分类  腺垂体疾病的 诊 断思路  腺垂体疾病的治 疗 原 则  病例 讨论: 垂体前叶功能减退症 1

3 The pituitary gland is located within the sella turcica ventral to the diaphragma sella 1-1

4 1-2 The hypothalamus - pituitary complex is the “master gland”,it orchestrates the regulatory functions of multiple other endocrine glands.

5 Vascular and Neural Connections Between the Hypothalamus and Pituitary  The hypothalamic nuclei produce hormones that traverse the portal system and impinge on anterior pituitary cells to regulate pituitary hormone secretion.  Posterior pituitary hormones are derived from direct neural extensions 1-3

6 HYPOTHALAMUS–PITUITARY HORMONES Two major groups of hormones secreted: Inhibiting and Releasing 1-4 Hypothalamic Hormone Target Cell (Hormone) GHRH Somatotrope (+) GH Somatostatin Somatotrope (-) GH Thyrotrope (-) TSH Dapamine Lactotrope (-) PRL TRH Thyrotrope (+) TSH Lactotrope (+) PRL GnRH Gonadotrope (+) FSH Gonadotrope (+) LH CRH Corticotrope (+) ACTH

7 HYPOTHALAMUS–PITUITARY HORMONES Feedback Regulation 1-5

8 Normal Range Primary Failure of target Endo. Organ Trophic H. Failure Autonomous Secretion of Trophic H. or …… Autonomous Secretion of Target Endo. Organ Low Normal High Target Gland Hormone Level Trophic Hormone Level HORMONAL FEEDBACK REGULATION 1-6

9 Case Study 38 岁女性,因闭经半年就诊。 1-7 血 E2 水平降低 FSH/LH 水平增高 闭经的原因? 血 E2 水平降低 FSH/LH 水平正常 闭经的原因? 血 E2 水平正常 FSH/LH 水平正常 闭经的原因?

10 DISORDERS OF ANTERIOR PITUITARY DISEASE 2

11 Anterior pituitary diseases can be divided into three major types of conditions (1) Hormone overproduction(Excess): Hyperfunction disorder (2) Hormone underproduction(Deficiency): Hypofunction disorder (3) Altered tissue response to hormone: hormone resistance 2-1

12 1. ANTERIOR PITUITARY HYPERFUNCTION DISORDERS 2-2 GH-cell adenoma Prolactin-Secreting Adenomas TSH-Secreting Tumors ACTH-Secreting Tumors  What happens if:  TOO MUCH Prolactin secretion?

13 2. ANTERIOR PITUITARY HYPOFUNCTION DISORDERS  Most examples of hormone deficiency states can be attributed to anterior pituitary destruction caused by: Surgery Tumor infiltration Infarction Inflammation Infection Autoimmunity Hemorrhage Genetic abnormalities 2-5

14 3. HORMONE RESISTANCE SYNDROME  Glucocorticoid Resistance  What happens if generalized GC resistance? 2-6

15 Approach to the Patients with Suspected Pituitary Disease

16 Symptoms, signs, others. H.measurement & endo. test CT, MRI, and others Suggestion of pituitary disease Functional evaluating of pituitary.G. No Yes Etiological diagnosis Hyper/hypo -function Localization of the lesion DIAGNOSIS of PITUITARY DISEASE 3-1

17 DIAGNOSIS of PITUITARY DISEASE HORMONE MEASUREMENTS  Simultaneous measurement of H./effector pairs is necessary for assessment pituitary function. LH/FSH --- E2 / T TSH --- T4 ACTH --- Cortisol  The biorhythms of hormones, and factors that can affect their secretion such as sleep, meals, and medications, must be considered. ACTH / Cortiso, GH / IGF-1, PRL 3-2

18 Hypothalamus–Pituitary Hormones Biorhythms 3-3 Pituitary hormones are secreted in a pulsatile manner and entrained to sleep and the circadian cycle. Recognition of these rhythms is important for endocrine testing and treatment.

19 DYNAMIC ENDOCRINE TESTS  Dynamic test involve the stimulation or suppression of H. production  Dynamic test are useful for detecting subtle endocrine dysfunction and for localizing the site of the defect.  Stimulation tests are used when hypofunction is suspected and are designed to assess the reserve capacity to form and secrete H.  Suppression test are used when hyperfunction is suspected and are designed to determine whether negative feedback control is intact DIAGNOSIS of PITUITARY DISEASE 3-4

20 Case Study - 2  28 岁 女性患者 , 因近 2 年体 重逐 渐 增加 , 伴双下肢凹陷 性水 肿 及月 经 紊乱就 诊。  查 体 : 血 压 140/98mmHg , 满 月面 , 上唇可 见 小 须。 向 心性肥胖 。 下腹部皮肤可 见 粗大紫 纹。  疑 诊 “ 库 欣 综 合征 ” ,查 PTC ( 8Am ) 520 nmol/L ( Ref nmol/L ) 3-7 Anterior pituitary ACTH Adrenal gland Cortisol Targets tissue Dexamethasone -   Dexamethasone Suppression Tests

21 THERAPEUTIC STRATEGIES OF ANTERIOR PITUIATRY DISEASE 4

22 THERAPEUTIC STRATEGIES OF ANTERIOR PITUIATRY DISEASES  Treatment of hyperfunction  Tumor:  Remove a tumor by surgery  Destroy a tumor by radiation (radiotherapy)  Medication: Use chemical agents to block or inhibit the excessive biosynthesis or release of the hormone 4-1

23 THERAPEUTIC STRATEGIES OF ANTERIOR PITUIATRY DISEASES  Treatment of hypofunction ◇ The basic form of remedy is replacement therapy by using a hormone defected. ◇ Ablation of a tumor which destroys or compresses the endocrine tissue. 4-2

24 HYPOPITUITARISM Case Study 5

25 病 历 摘要  65 岁 女性 , 因 闭经、 乏力 、 脱 发、 怕冷 30 年 ,发热、 咳嗽 伴 头 昏 、 口 齿 不清 1 周入院 。  入院前 30 年 , 患者分娩 时难产 大出血 , 昏迷 ,经抢 救后好 转。 但 产 后无乳汁分泌 ,闭经, 逐 渐 出 现 阴毛 、 腋毛脱落 , 性欲减退 , 乏力 、纳 差 、 怕冷 , 易感冒 ,记忆 力下降 。  入院前 10 年 渐 出 现 全身浮 肿, 以 胫 前及 颜 面部明 显。  入院前 1 周因受凉感冒后出 现头 昏 、发热( T 38.5 )、 咽痛 、 咳嗽 , 伴乏力 、纳 差及怕冷加重 , 在当地医院予抗感染治 疗 后咽痛 、 咳嗽 渐缓 解 , 但乏力加重 , 伴 恶 心呕吐 , 不能 进 食 。  4 小 时 前出 现 心悸 、视 物模糊 、 嗜睡 , 当地医院 转诊 至我院 。  患病以来 , 患者体重增加 10Kg 。 5-1

26 病 历 摘要  查 体 : T 36.0 , P 78 次 / 分 , R 16 次 / 分 , BP 100/60mmHg  慢性重病容 ,贫 血貌 , 表情淡漠 , 神志恍惚 , 不 语。  全身皮肤 苍 黄 、 干燥 , 四肢皮温低 ,颜 面浮 肿, 阴毛 、 腋毛脱落 。 5-2  甲状腺不大 , 双肺叩 诊 清音 , 双下肺可 闻 及 细 湿 罗 音 。 叩 诊 心界不大 , 心率 78 次 / 分 , 律 齐, 各瓣膜区未 闻 及病理性 杂 音 。 腹部 查 体无阳性 发现。  双下肢非凹陷性水 肿 伴 胫 前色 素沉着 。

27 Hypopituitarism  Definition  Hypopituitarism refers to decreased secretion of pituitary hormones  Hypopituitarism can result from diseases of the pituitary gland or from diseases of the hypothalamus.  Major causes  Pituitary diseases  Hypothalamic diseases 5-3  Mass lesions - pituitary adenomas, other benign tumors, cysts  Pituitary surgery  Pituitary radiation  Infiltrative lesions - lymphocytic hypophysitis, hemochromatosis  Infarction - Sheehan syndrome  Apoplexy  Genetic diseases  Mass lesions - benign and malignant tumors  Radiation - for CNS and nasopharyngeal  malignancies Infiltrative lesions - Langerhans cell histiocytosis  Trauma - fracture of skull  baseInfections - TB meningitis

28 Anterior Pituitary Infarction – Sheehan syndrome  The anterior pituitary lacks a major direct arterial blood supply; it is bathed in a dense capillary network : hypothalamic- hypophyseal portal venous system  The pituitary gland is enlarged in pregnancy and prone to infarction from hypovolemic shock 5-5

29 CLINICAL MANIFESTATIONS OF HYPOPITUITARISM  The clinical manifestations of hypopituitarism depend on the following factors:  The rapidity with which a disease affects anterior pituitary cells  The severity of the hormonal deficiency.  The number of different anterior pituitary cells that are affected, leading to impairment in the secretion of one, a few, or all the pituitary hormones. 5-6

30 CLINICAL MANIFESTATIONS OF HYPOPITUITARISM ACTH Deficiency  The presentation of ACTH deficiency is that of the resulting cortisol deficiency  What differences between ACTH deficiency and primary adrenal insufficiency?  Salt wasting, volume contraction, hyperkalemia  Hyperpigmentation  Hypoglycemia 5-7 Symptoms/signs Frequency, percent Weakness, tiredness, fatigue 100 Anorexia100 Gastrointestinal symptoms 92 Nausea86 Vomiting75 Constipation33 Abdominal pain31 Diarrhea16 Muscle or joint pains6-13 Weight loss or Weight gain

31 Pituitary-Adrenal Crisis  The syndrome of adrenal crisis may occur in the following situations:  In a previously undiagnosed patient with pituitary of adrenal insufficiency who has been subjected to serious infection or other acute, major stress.  In a patient with known pituitary or adrenal insufficiency who does not take more glucocorticoid during an infection or other major illness.  Clinical and laboratory findings suggesting adrenal crisis: 1 Nausea and vomiting with a history of weakness, tiredness, fatigue and anorexia Abdominal pain, so-called "acute abdomen" Unexplained hypoglycemia Unexplained fever Hyponatremia

32 Clinical Manifestations of Hypopituitarism TSH Deficiency  Similar to but sometimes milder than those of primary hypothyroidism  Common symptoms: fatigue, cold intolerance, muscle cramps, headache, weight gain 5-8 MechanismSymptomsSigns Slowing of metabolic processes Fatigue and weakness Cold intolerance, Dyspnea on exertion Weight gain Cognitive dysfunction Constipation Slow movement and slow speech Delayed relaxation of tendon reflexes Bradycardia Carotenemia Accumulation of matrix substances Dry skin Hoarseness Edema Coarse skin Puffy facies and loss of eyebrows Periorbital edema Enlargement of the tongue OtherDecreased hearing Myalgia and paresthesia Depression Menorrhagia Arthralgia Pubertal delay Diastolic hypertension Pleural and pericardial effusions

33 Hypothyroidism Crisis--- myxedema coma  Myxedema coma is defined as severe hypothyroidism leading to symptoms related to slowing of function in multiple organs.  Clinical features of myxedema coma: 1 Decreased mental status Hypothermia Bradycardia Hyponatremia Hypoglycemia Hypotension Precipitating illness Hallmarks of myxedema coma

34 Clinical Manifestations of Hypopituitarism Gonadotropin Deficiency  In women: ovarian hypofunction--- decreased E 2 secretion  Irregular periods or amenorrhea, anovulatory infertility, vaginal atrophy  After several years, breast tissue decreases, bone mineral density declines  In men: testicular hypofunction--- infertility, decreased T secretion  decreased energy and libido  decreased bone mineral density 5-9 Prolactin Deficiency  The only known presentation of prolactin deficiency is the inability to lactate after delivery.

35 Clinical Manifestations of Hypopituitarism GH deficiency  In children: growth retardation ( short stature)  In adults: Changes in body composition: increased fat mass with a decrease in lean body mass 5-10

36 Clinical features of Sheehan's syndrome  A history of postpartum hemorrhage so severe as to cause hypotension and require transfusion of multiple units of blood.  In severe cases, lethargy, anorexia, weight loss, and inability to lactate developed during the first days or weeks after delivery.  In less severe cases, failure of postpartum lactation and failure to resume menses in the weeks and months after delivery, and loss of sexual hair, as well as milder degrees of fatigue, anorexia, and weight loss.  In mild cases, possible delay in recognition for many years after the inciting event.  Eventual development of a small pituitary within a sella of normal size, sometimes read as an "empty sella" on MRI. 5-11

37 DIAGNOSIS OF HYPOPITUIATROSM  Biochemical diagnosis is made by demonstrating low levels of trophic hormones in the setting of low target hormone levels  Each pituitary hormone must be tested separately.  ACTH:  Basal ACTH-Cortisol secretion (8:00Am-9:00Am)  ACTH reserve: Stimulating Test  TSH-T 4  LH/FSH – E 2 /T(8:00Am-10:00Am)  Basal GH – IGF-1, Stimulating test 5-14

38 Case Study-Labs.  ACTH(8:00Am) : 15.1 ng/L (Ref ng/L),  PTC: 84nmol/L (Ref nmol/L)  TSH : 2.91mU/L (Ref mU/L),  FT4: 3.40pmol/L (Ref.12-24pmol/L)  LH: <0.1mU/L (Ref ), FSH0.487mU/ml(Ref )  E2: < 5.0pg/ml(Ref. 5-54),  GH: 0.92ng/ml (Ref ) Final Diagnosis:  Hypopituitarism or Sheehan's syndrome 5-15

39 TREATMENT OF HYPOPITUITARISM  The treatments of ACTH, TSH, and LH /FSH deficiencies are the same as the treatments of primary deficiencies of the respective target glands  Treatment regimens that mimic physiologic hormone production allow for maintenance of satisfactory clinical homeostasis.  Hormone replacement therapy, including glucocorticoids, thyroid hormone, sex steroids, and growth hormone, is usually free of complications. 5-16

40 Hormone Replacement Therapy Trophic Hormone Deficit Hormone Replacement ACTHHydrocortisone (10–25 mg /d.) or Prednisone (2.5mg - 5 mg A.M.) TSHL-Thyroxine (75  g –150  g daily) LH / FSHMales: Testosterone Undecanoate Capsule ( mg/d) Females: Estradiol (1mg–2mg qd  21d ) Progesterone (5–10 mg qd) on days 14–21 For fertility: human chorionic gonadotropins GHAdults: Somatotropin (0.3–1.0 mg SC qd) Children: Somatotropin [0.02–0.05 (mg/kg/d)] 5-17 All doses shown should be individualized for specific patients and should be reassessed during stress, surgery, or pregnancy

41 The management of this patient  1 st and 2 nd day:  Fluid therapy  Hydrocortisone 100mg iv.  3 rd and 4 th day:  Hydrocortisone 50mg iv  L-Thyroxine 25g/d, po  5 day later:  Prednisone 5mg/d, po  L-Thyroxine 25g/d, po  The patient discharged one week later and follow up regularly at outpatient department. 5-18

42 小 结 -1 : 腺垂体疾病  下丘 脑 - 腺垂体是内分泌系 统 的中枢器官 。  下丘 脑 - 腺垂体激素的分泌具有 节 律性  下丘 脑 - 垂体 - 靶腺激素通 过 正 负 反 馈调节 而 维 持体内激素水平 于生理范 围。  腺垂体疾病可大致分 为 三大类 : 激素分泌增多 、 激素分泌减 少 、 激素抵抗 。  腺垂体激素分泌增多的主要原因是相关内分泌 细 胞 肿 瘤  腺垂体激素分泌减少的主要原因包括鞍区 肿 瘤 、 手 术、 放射 性治 疗、 梗死 、 浸 润 性病 变、 感染 、 炎症 、 基因突 变 等 。  腺垂体疾病 诊 断步 骤为:详细 收集病史 、查 体 、检测 相关激 素水平及功能 试验( 功能 诊 断 )、 定位 诊 断 ( 病因 诊 断 )。  腺垂体疾病的治 疗 原 则: 1 ) 去除病因 ; 2 ) “ 削峰填谷 ” 6-1

43 小 结 -2 : 垂体前叶功能低下  定 义: 垂体前叶一 项 或多 项 激素分泌不足  病因 : 垂体或下丘 脑 区域的 肿 瘤 、 手 术、 放射性治 疗、 梗 死 、 浸 润 性病 变、 感染 、 炎症 、 基因突 变 等 。  因 产 后大出血 诱发 腺垂体 组织 梗死者特称 为 席 汉综 合征  临 床表 现: 主要 为 各相关靶激素缺乏的症状与体征  临 床 诊 断 : 靶激素水平降低而相关促激素水平正常或降低  治 疗 原 则: 去除病因 ,长 期激素替代治 疗,终 身随 访 6-2

44 Case Study  17 岁女性,因身材矮小、原发性闭经就诊。  自幼生长缓慢,智力较差。  当地医院头颅 CT 发现垂体体积增大,疑 “ 垂体肿 瘤 ”  查体:面容虚浮,皮肤干燥脱屑,乳腺发育差, 积压乳房可见少量乳汁溢出。外阴呈幼女型,未 见阴毛。 Division of Endocrinology and Metabolism West China Hospital, SCU

45 Case Study  该病例存在的问题:  原发性闭经伴第二性征不发育  智力差,生长迟缓,皮肤干燥,面容虚浮  溢乳,垂体体积增大,疑占位性病变  哪些疾病可出现上述表现?  进一步需作哪些检查?

46 Case Study  患者相关激素检测结果:  HPG axis: E 2 : 1.8 pg/ml; (Ref. 5-54) ; P: 0.08ng/ml (Ref ); FSH: 2.9 mU/L (Ref ); LH: 3.4 mU/L(Ref )  PRL: 42.8 ng/ml (Ref. 6-29)  HPT axis:FT 3 : 2.1pmol/L (Ref ); FT 4 : 5.2pmol/L (Ref ); TSH:  100 mU/ L (Ref ).  HPA axis:PTC(8Am): 414 nmol/L (Ref ); ACTH: 35 pmol/L (Ref ).  GH: 1.2ng/ml (Ref )

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