Pituitary Physiology and Deficiencies Heidi Chamberlain Shea MD
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 • Discuss pituitary hormone deficiencies
Nomenclature • Pituitary – Greek • ptuo (to spit) – Latin • Pituita (mucus) – Mucus was produced by the brain and was excreted through the nose by the pituitary
Pituitary Development • Evagination of the stromodeal ectoderm from buccal cavity • Infundibulum, neural stalk and posterior lobe from diencephalon • Development 3 rd to the 15 th week gestation
Pituitary Anatomy Gross • Sits in sella turcica • Surrounded by dura • Sphenoid – Lateral and inferior • Lateral – Cavernous sinus • Internal carotid artery • CN III, IV, VI, V 1 and V 2
Pituitary Anatomy Gross • 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
Pituitary Anatomy Microscopic • Anterior lobe – 80% of gland – Brown color • Posterior lobe – Gray/brown color
Pituitary Anatomy Microscopic • 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
Pituitary Gland Microscopic • Pars distalis – Pink acidophils • Growth hormone • Prolactin – Dark purple basophils • Corticotropin (ACTH) • Thyroid stimulating hormone (TSH) • Follicle stimulating hormone (FSH) • Luteinizing hormone (LH)
Pituitary Portal System • Hypophyseal arteries – From carotid – Superior • 80 -90% to adenophysis – Inferior • Posterior pituitary • Posterior lobe – Rich nerve supply – Unmyelinated nerves
Goals of Discussion • Review pituitary anatomy • Understand pituitary physiology • Discuss pituitary hormone deficiencies
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
Anterior pituitary Hypothalamic product Pituitary product Target organ Hormone product CRH ACTH Adrenal cortex Cortisol TRH TSH Thyroid T 4, T 3 GHRH (+) SRIH (-) GH Liver; Tissues IGF-I (systemic) IGF-I (local) PRIH (dopamine) PRL Breast [Lactation] Gn. RH LH, FSH Gonad Sex hormones (LHRH)
Hormone Structure Polypeptide/proteins ACTH Polypeptide GH Protein PRL Protein Amino acids/Source 39 191 199 Corticotroph Somatotroph Lactotroph Glycoproteins TSH Alpha* / TSH-beta 110 LH Alpha / LH-beta 115 FSH Alpha / FSH-beta 115 Thyrotroph Gonadotroph [h. CG Alpha / beta-h. CG] * 92 amino acids 147 [Placenta]
GH_AXIS_ HYPOTHALAMUS (-) HYPOTHALAMICPITUITARY PORTAL SYSTEM SRIH (-) POSTERIOR PITUITARY GHRH (+) ANTERIOR PITUITARY INCR. [FFA] DIRECT INSULIN RESISTANCE EFFECTS GH TISSUES IGFBP-3 IGF-I GROWTH
HYPOTHALAMUS (-) HYPOTHALAMICPITUITARY PORTAL SYSTEM (-) CRH (+) ANTERIOR PITUITARY POSTERIOR PITUITARY ACTH ADRENAL Fasiculata CORTISOL
HYPOTHALAMUS (-) HYPOTHALAMICPITUITARY PORTAL SYSTEM (-) TRH (+) ANTERIOR PITUITARY POSTERIOR PITUITARY TSH THYROID GLAND T 4, T 3 (T 4 --> T 3)
HYPOTHALAMUS PRIH (DOPAMINE) (-) POSTERIOR PITUITARY ANTERIOR PITUITARY PRL BREAST
HYPOTHALAMUS (-) HYPOTHALAMICPITUITARY PORTAL SYSTEM Gn. RH (-) (LHRH) (+) ANTERIOR PITUITARY POSTERIOR PITUITARY LH, FSH GONAD SEX HORMONES, INHIBIN
Posterior pituitary Hypothalamic source (cell body) Target Effect ADH Collecting duct H 2 O retention Oxytocin Breast Uterus Milk let down Smooth muscle Contraction
Goals of Discussion • Review pituitary anatomy • Understand pituitary physiology • Discuss pituitary hormone deficiencies
History • 15 yr 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
History • Drinks 32 oz water Q 34 hrs during the day • Drinks and urinates Q 23 hrs at night • ROS: occasional headaches, fatigue and difficulty losing weight
Physical Exam • • • Wt 62. 9 kg (75%) Ht 5 ft 3. 5 in (50%) BMI 24. 2 kg/m 2 HR 80 B/P 117/86 • General: nondysmorphic, wellnourished • HEENT: visual fields intact, no thyromegaly • Breast: no discharge, Tanner V • GU: Tanner V
Differential Diagnosis Hypopituitarism • 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 Diagnosis Hypopituitarism • Vascular disease – Sheehan’s postpartum necrosis – Carotid aneurysm • Destructive – Surgery – Radiation – Trauma • Infiltration – Hemochromatosis – Amyloidosis
Hypopituitary Presentation • 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
Hypopituitary Presentation • Growth hormone deficiency – Children • Short stature – Adults • Non specific • Fine wrinkling around the face • Improved insulin sensitivity
Hypopituitary Presentation • Gonadotropin deficiency – Women • Amenorrhea – Primary or secondary • Infertility – Men • Decreased libido • Decreased beard and body hair
Hypopituitary Presentation • 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
Hypopituitary Presentation • Hypothryoidism – – Fatigue Cold intolerance Puffy skin Absence of goiter • Diabetes Insipidus – Polyuria – Polydipsia
Evaluation • What testing? – Polydipsia and polyuria • Water deprivation test – Secondary amenorrhea • Prolactin • Gonadotropins • Thyroid function
Laboratory • Water deprivation test reveals diabetes insipidus • MRI – pituitary seen, no masses, subtle thickening of 3 rd ventricle floor and no hyperintense neurohypophysis in sella noted • TSH 1. 61 ug/dl (0. 35 -5. 54) • T 4 8. 4 u. IU/ml (4. 0 -12. 8)
Laboratory • • • Cortisol 0800 15. 5 ug/dl (5 -25) ACTH 14 pg/ml BHCG <5 m. IU/ml Prolactin 5 ng/ml (3 -27) Estradiol 1. 3 ng/dl (3. 4 -17) ESR 101
Laboratory • • FSH 6. 9 m. IU/ml (Tanner V 1. 0 -9. 2) LH 7. 1 m. IU/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 <5 ng/ml
Treatment • Growth hormone therapy • Estrogen and progesterone – Birth control pills • Testosterone – Cypianate or enanthate • 200 mg IM Q 2 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 • Cortisol – Hydrocortisone • 10 mg AM and 5 mg PM • 6 -8 mg/m 2/day • Stress dosing – – Fever, illness, surgery 20 mg/m 2/day Double or triple daily dose 100 mg x 1 then 25 -50 mg Q 6 -8 hrs • All hypopituitary patients need a medic alert bracelet
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
Treatment • DDAVP nasal spray 10 mcg QD • Ortho-novum 777 • Growth hormone therapy
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