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Pituitary Physiology and Deficiencies

Pituitary Physiology and Deficiencies. Heidi Chamberlain Shea, MD Endocrine Associates of Dallas. Pituitary. Pituitary “Master” gland Most of the pituitary hormones control other endocrine glands. Goals of Discussion. Review pituitary anatomy Understand pituitary physiology

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Pituitary Physiology and Deficiencies

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  1. Pituitary Physiology and Deficiencies Heidi Chamberlain Shea, MD Endocrine Associates of Dallas

  2. Pituitary • Pituitary • “Master” gland • Most of the pituitary hormones control other endocrine glands

  3. Goals of Discussion • Review pituitary anatomy • Understand pituitary physiology • Discuss pituitary hormone deficiencies

  4. Nomenclature • Pituitary • Greek • ptuo (to spit) • Latin • Pituita (mucus) • Mucus was produced by the brain and was excreted through the nose by the pituitary

  5. Pituitary Development • Evagination of the stromodeal ectoderm from buccal cavity • Infundibulum, neural stalk and posterior lobe from diencephalon • Development 3rd to the 15th week gestation

  6. Pituitary Anatomy Gross • Sits in sella turcica • Surrounded by dura • Sphenoid • Lateral and inferior • Lateral • Cavernous sinus • Internal carotid artery • CN III, IV, VI, V1 and V2

  7. Pituitary AnatomyGross • Symmetrical bean shaped • Brownish red • 13 mm transverse • 9 mm AP • 6 mm height • Adult • 0.4-0.9 grams • Larger in women • Larger in multiparous women • During pregnancy increases to 0.9-1 grams

  8. Pituitary AnatomyMicroscopic • Anterior lobe • 80% of gland • Brown color • Posterior lobe • Gray/brown color

  9. Pituitary AnatomyMicroscopic • Anterior lobe 3 divisions • Pars distalis • Largest • Hormone producing cells • Pars intermedia • Poorly defined in the human • Pars tuberalis • Upward extension to the anterior lobe and attached to pituitary stalk • Posterior lobe • Pars nervosa

  10. Pituitary GlandMicroscopic • Pars distalis • Pink acidophils • Growth hormone • Prolactin • Dark purple basophils • Corticotropin (ACTH) • Thyroid stimulating hormone (TSH) • Follicle stimulating hormone (FSH) • Luteinizing hormone (LH)

  11. PituitaryPortal System • Hypophyseal arteries • From carotid • Superior • 80-90% to adenophysis • Inferior • Posterior pituitary • Posterior lobe • Rich nerve supply • Unmyelinated nerves

  12. Goals of Discussion • Review pituitary anatomy • Understand pituitary physiology • Discuss pituitary hormone deficiencies

  13. Hormones Of The Anterior Pituitary • 6 main hormones secreted by the adenohypophysis: • Growth hormone • Somatotropin • Thyroid-stimulating hormone • Thyrotropin • Adrenocorticotropic hormone • Corticotropin • Prolactin • Follicle-stimulating hormone • Luteinizing hormone

  14. Anterior pituitary Hypothalamic Pituitary Target Hormone product product organ product CRH ACTH Adrenal Cortisol cortex TRH TSH Thyroid T4, T3 GHRH (+) GH Liver; IGF-I (systemic) SRIH (-) Tissues IGF-I (local) PRIH PRL Breast [Lactation] (dopamine) GnRH LH, Gonad Sex hormones (LHRH) FSH

  15. Hormone Structure Amino acids/Source • Polypeptide/proteins • ACTH Polypeptide 39 Corticotroph • GH Protein 191 Somatotroph • PRL Protein 199 Lactotroph • Glycoproteins • TSH Alpha* / TSH-beta 110 Thyrotroph • LH Alpha / LH-beta 115 Gonadotroph • FSH Alpha / FSH-beta 115 Gonadotroph • [hCG Alpha / beta-hCG] 147 [Placenta] • * 92 amino acids

  16. GH_AXIS_ (-) HYPOTHALAMIC- SRIH PITUITARY (-) PORTAL SYSTEM GHRH (+) DIRECT GH INCR. [FFA] TISSUES INSULIN RESISTANCE EFFECTS IGF-I GROWTH IGFBP-3 HYPOTHALAMUS POSTERIOR PITUITARY ANTERIOR PITUITARY

  17. HYPOTHALAMUS (-) HYPOTHALAMIC- PITUITARY PORTAL SYSTEM (-) CRH POSTERIOR PITUITARY ACTH ADRENAL Fasiculata CORTISOL (+) ANTERIOR PITUITARY

  18. HYPOTHALAMUS (-) HYPOTHALAMIC- PITUITARY PORTAL SYSTEM (-) TRH (+) POSTERIOR ANTERIOR PITUITARY PITUITARY TSH THYROID GLAND T4, T3 (T4 --> T3)

  19. HYPOTHALAMUS PRIH (DOPAMINE) (-) ANTERIOR PITUITARY PRL BREAST POSTERIOR PITUITARY

  20. HYPOTHALAMUS (-) HYPOTHALAMIC- PITUITARY PORTAL SYSTEM (-) GnRH (LHRH) (+) LH, FSH GONAD SEX HORMONES, INHIBIN POSTERIOR ANTERIOR PITUITARY PITUITARY

  21. Posterior pituitary • Hypothalamic • source (cell body) Target Effect • ADH Collecting H2O retention • duct • Oxytocin Breast Milk let down • Uterus Smooth muscle • Contraction

  22. Goals of Discussion • Review pituitary anatomy • Understand pituitary physiology • Discuss pituitary hormone deficiencies

  23. History • 15yr old WF presents with secondary amenorrhea, polydipsia and polyuria • Normal growth and development • Menarche at 11 years of age • Qmonth menses until 12 years of age • Withdrawal bleeding only with OCP’s

  24. History • Drinks 32 oz water Q3-4hrs during the day • Drinks and urinates Q2-3hrs at night • ROS: occasional headaches, fatigue and difficulty losing weight

  25. Wt 62.9kg (75%) Ht 5ft 3.5in (50%) BMI 24.2 kg/m2 HR 80 B/P 117/86 General: nondysmorphic, well-nourished HEENT: visual fields intact, no thyromegaly Breast: no discharge, Tanner V GU: Tanner V Physical Exam

  26. Isolated hormone deficiencies Acquired or congenital Tumors Pituitary adenomas Pituitary apoplexy Hypothalamic tumors Metastatic carcinoma Inflammatory Granulomatous disease Sarcoidosis, TB and syphilis Eosinophilic granuloma Lymphocytic hypophysitis Differential DiagnosisHypopituitarism

  27. Vascular disease Sheehan’s postpartum necrosis Carotid aneurysm Destructive Surgery Radiation Trauma Infiltration Hemochromatosis Amyloidosis Differential DiagnosisHypopituitarism

  28. Growth hormone production First hormone to be disrupted Gonadotropin deficiency Easily disrupted Corticotropin Less frequently affected Thyrotropin Rarely affected Anti-diuretic hormone Deficiency usually due to tumor Craniopharyngioma HypopituitaryPresentation

  29. HypopituitaryPresentation • Growth hormone deficiency • Children • Short stature • Adults • Non specific • Fine wrinkling around the face • Improved insulin sensitivity

  30. HypopituitaryPresentation • Gonadotropin deficiency • Women • Amenorrhea • Primary or secondary • Infertility • Men • Decreased libido • Decreased beard and body hair

  31. Corticotropin deficiency Fatigue Decreased appetite Weight loss Decreased pigmentation Abnormal response to stress Hypotension Hyponatremia Fever Primary Adrenal Insufficiency Addison’s disease Fatigue Decreased appetite Weight loss Increased pigmentation Hyperkalemia Abnormal response to stress Hypotension Hyponatremia Fever HypopituitaryPresentation

  32. Hypothryoidism Fatigue Cold intolerance Puffy skin Absence of goiter Diabetes Insipidus Polyuria Polydipsia HypopituitaryPresentation

  33. Evaluation • What testing? • Polydipsia and polyuria • Water deprivation test • Secondary amenorrhea • Prolactin • Gonadotropins • Thyroid function

  34. Laboratory • Water deprivation test reveals diabetes insipidus • MRI – pituitary seen, no masses, subtle thickening of 3rd ventricle floor and no hyperintense neurohypophysis in sella noted • TSH 1.61 ug/dl (0.35-5.54) • T4 8.4 uIU/ml (4.0-12.8)

  35. Laboratory • Cortisol 0800 15.5 ug/dl (5-25) • ACTH 14 pg/ml • BHCG <5 mIU/ml • Prolactin 5 ng/ml (3-27) • Estradiol 1.3 ng/dl (3.4-17) • ESR 101

  36. Laboratory • FSH 6.9 mIU/ml (Tanner V 1.0-9.2) • LH 7.1 mIU/ml (Tanner V 0.4-11.7) • IGF-1 207 ng/ml (217-589) • Skeletal Xray: no lesions and epiphyses closed. • Dopamine arginine GH stimulation test <5ng/ml

  37. Growth hormone therapy Estrogen and progesterone Birth control pills Testosterone Cypianate or enanthate 200 mg IM Q2 weeks Gels 5-10 gram per day Fertility Refer to Reproductive Endocrinologist Thyroid Levothyroxine (generic) Synthroid Levoxyl Unithroid Dose ranges 75-150 mcg per day Treatment

  38. Treatment • Cortisol • Hydrocortisone • 10mg AM and 5 mg PM • 6-8 mg/m2/day • Stress dosing • Fever, illness, surgery • 20 mg/m2/day • Double or triple daily dose • 100 mg x1 then 25-50 mg Q6-8hrs • All hypopituitary patients need a medic alert bracelet

  39. Treatment • Desmopressin (DDAVP) • Nasal spray • 10 mcg QD-BID • Tablets • 0.1 to 0.2 mg QD-BID • SQ injection • 1-2 ug QD-BID

  40. Treatment • DDAVP nasal spray 10mcg QD • Ortho-novum 777 • Growth hormone therapy

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