3 The pituitary gland is located within the sella turcica ventral to the diaphragma sella
4 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
6 HYPOTHALAMUS–PITUITARY HORMONES Two major groups of hormones secreted: Inhibiting and Releasing Hypothalamic Hormone Target Cell (Hormone)GHRH Somatotrope (+) GHSomatostatin Somatotrope (-) GHThyrotrope (-) TSHDapamine Lactotrope (-) PRLTRH Thyrotrope (+) TSHLactotrope (+) PRLGnRH Gonadotrope (+) FSHGonadotrope (+) LHCRH Corticotrope (+) ACTH
8 HORMONAL FEEDBACK REGULATION Autonomous Secretion of Trophic H. or ……Primary Failure of target Endo. OrganHighNormalRangeTrophic Hormone LevelNormalAutonomous Secretion of Target Endo. OrganTrophic H. FailureLowLowNormalHighTarget Gland Hormone Level
9 Case Study 38岁女性，因闭经半年就诊。 血E2水平降低 FSH/LH水平增高 闭经的原因？ 血E2水平降低
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
12 1. ANTERIOR PITUITARY HYPERFUNCTION DISORDERS What happens if:TOO MUCH Prolactin secretion?Prolactin-Secreting AdenomasGH-cell adenomaACTH-Secreting TumorsTSH-Secreting Tumors
13 2. ANTERIOR PITUITARY HYPOFUNCTION DISORDERS Most examples of hormone deficiency states can be attributed to anterior pituitary destruction caused by:Surgery Tumor infiltrationInfarction InflammationInfection AutoimmunityHemorrhage Genetic abnormalities
15 Approach to the Patients with Suspected Pituitary Disease
16 DIAGNOSIS of PITUITARY DISEASE Suggestion of pituitary diseaseSymptoms, signs, others.H.measurement & endo. testFunctional evaluating of pituitary.G.Hyper/hypo-functionNoYesLocalization of the lesionEtiology study◆ Cytologic studies as semen analysis forhypogonadism/ or infertility ; fine needlebiopsy for thyroid nodule .◆ Genetic studies as karyotype exmination forKlinefilter Syndrome (47,XXY ) . genomemapping , microarray for G , mutation◆ Immunologic studiesInvestigation of antithyroid globulin Ab ＆antithyroid peroxidase Ab in Hashimoto’sthyroiditis .◆ GAD-Ab for LADA .CT, MRI, and othersEtiological diagnosis
17 DIAGNOSIS of PITUITARY DISEASE HORMONE MEASUREMENTSSimultaneous measurement of H./effector pairs is necessary for assessment pituitary function.LH/FSH --- E2 / TTSH --- T4ACTH --- CortisolThe 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
18 Hypothalamus–Pituitary Hormones Biorhythms 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 DIAGNOSIS of PITUITARY DISEASE DYNAMIC ENDOCRINE TESTSDynamic test involve the stimulation or suppression of H. productionDynamic 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
21 THERAPEUTIC STRATEGIES OF ANTERIOR PITUIATRY DISEASE
22 THERAPEUTIC STRATEGIES OF ANTERIOR PITUIATRY DISEASES Treatment of hyperfunctionTumor:Remove a tumor by surgeryDestroy a tumor by radiation (radiotherapy)Medication: Use chemical agents to block or inhibit the excessive biosynthesis or release of the hormone
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.
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。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 Major causes Mass lesions - pituitary adenomas, other benign tumors, cystsPituitary surgeryPituitary radiationInfiltrative lesions - lymphocytic hypophysitis, hemochromatosisInfarction - Sheehan syndromeApoplexyGenetic diseasesDefinitionHypopituitarism refers to decreased secretion of pituitary hormonesHypopituitarism can result from diseases of the pituitary gland or from diseases of the hypothalamus.Major causesPituitary diseasesHypothalamic diseasesMass lesions - benign and malignant tumorsRadiation - for CNS and nasopharyngealmalignancies Infiltrative lesions - Langerhans cell histiocytosisTrauma - fracture of skullbaseInfections - 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 systemThe pituitary gland is enlarged in pregnancy and prone to infarction from hypovolemic shock
29 CLINICAL MANIFESTATIONS OF HYPOPITUITARISM The clinical manifestations of hypopituitarism depend on the following factors:The rapidity with which a disease affects anterior pituitary cellsThe 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.
30 CLINICAL MANIFESTATIONS OF HYPOPITUITARISM ACTH Deficiency Symptoms/signsFrequency,percentWeakness, tiredness, fatigue100AnorexiaGastrointestinal symptoms92Nausea86Vomiting75Constipation33Abdominal pain31Diarrhea16Muscle or joint pains6-13Weight loss or Weight gain The presentation of ACTH deficiency is that of the resulting cortisol deficiencyWhat differences between ACTH deficiency and primary adrenal insufficiency?Salt wasting, volume contraction, hyperkalemiaHyperpigmentationHypoglycemia
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:Nausea and vomiting with a history of weakness, tiredness, fatigueand anorexiaAbdominal pain, so-called "acute abdomen"Unexplained hypoglycemiaUnexplained feverHyponatremia
32 Clinical Manifestations of Hypopituitarism TSH Deficiency Similar to but sometimes milder than those of primary hypothyroidismCommon symptoms: fatigue, cold intolerance, muscle cramps, headache, weight gainMechanismSymptomsSignsSlowing of metabolic processesFatigue and weaknessCold intolerance,Dyspnea on exertionWeight gainCognitive dysfunctionConstipationSlow movement and slow speechDelayed relaxation of tendon reflexesBradycardiaCarotenemiaAccumulation of matrix substancesDry skinHoarsenessEdemaCoarse skinPuffy facies and loss of eyebrowsPeriorbital edemaEnlargement of the tongueOtherDecreased hearingMyalgia and paresthesiaDepressionMenorrhagiaArthralgiaPubertal delayDiastolic hypertensionPleural 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:Decreased mental statusHypothermiaBradycardiaHyponatremiaHypoglycemiaHypotensionPrecipitating illnessHallmarks of myxedema coma
34 Clinical Manifestations of Hypopituitarism Gonadotropin Deficiency In women: ovarian hypofunction--- decreased E2 secretionIrregular periods or amenorrhea, anovulatory infertility, vaginal atrophyAfter several years, breast tissue decreases, bone mineral density declinesIn men: testicular hypofunction---infertility , decreased T secretiondecreased energy and libidodecreased bone mineral densityProlactin 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
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.
37 DIAGNOSIS OF HYPOPITUIATROSM Biochemical diagnosis is made by demonstrating low levels of trophic hormones in the setting of low target hormone levelsEach pituitary hormone must be tested separately.ACTH:Basal ACTH-Cortisol secretion (8:00Am-9:00Am)ACTH reserve: Stimulating TestTSH-T4LH/FSH – E2/T(8:00Am-10:00Am)Basal GH – IGF-1, Stimulating test
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 glandsTreatment 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.
40 Hormone Replacement Therapy Trophic Hormone DeficitHormone ReplacementACTHHydrocortisone (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 gonadotropinsGHAdults: Somatotropin (0.3–1.0 mg SC qd) Children: Somatotropin [0.02–0.05 (mg/kg/d)]All doses shown should be individualized for specific patients and should be reassessed during stress, surgery, or pregnancy
41 The management of this patient 1st and 2nd day:Fluid therapyHydrocortisone 100mg iv.3rd and 4th day:Hydrocortisone 50mg ivL-Thyroxine 25g/d, po5 day later:Prednisone 5mg/d, poThe patient discharged one week later and follow up regularly at outpatient department.