PITUITARY HORMON ANTERIOR LOBE: Growth hormon (GH) Prolactin (PRL) Adrenocorticotropic hormone (ACTH) Thyroid stimulating hormone

ormone (TSH) Luteinizing hormon (LH) Follicle stimulating hormone (FSH)

POSTERIOR LOBE: Arginine vasopressin (AVP)/ Antidiuretic hormone (ADH) Oxytocin

HYPOTHALAMUS HORMON GHRH (GH Releasing factor) PIF (Prolactin inhibiting factor) ACTH RH (ACTH Releasing factor) TSHRH (TSH Releasing factor) LHRH (RH Releasing factor) FSHRH (FSH Releasing factor) MIF (MSH Inhibiting factor)

HYPOPITUITARISM HYPOTHALAMIC OR PITUITARY DYSFUNCTION HORMON DEFICIENCY SINGLE OR MULTIPLE ETIOLOGY OF HYPOPITUITARISM

= Mass lesions metastatic Ca, adenoma, granuloma, craniopharyngioma, meningioma, chondrosarcoma, germinoma, glioma, chordoma of the clivus, Rathkes cleft cyst, apoplexy, Langerhans cell histiocytosis, MEN 1 (multiple endocrine neoplasia type 1/ pituitary & parathyroid & pancreas tumors) = Diseases Sheehans syndrome, autoimmune hypophysitis, encephalitis eclampsia, sickle cell anaemia, African Tripanosoma = Genetic Kallmanns syndrome: isolated gonadotropin deficiency + unilateral agenesis renal + cryptorchidism, nystagmus, cleft lip, bilateral synkinesis, high arched palate

= Physiologic isolated hypogonadotrophic hypogonadism severe illness, malnutrition, extreme prolonged exercise, obese DM type 2, longterm intrathecal opioid, methadone = Hypopituitarism without mass lesions idiopathic, trauma, surgery, radiation, hemochromatosis, stroke, CABG, aneurysma subarachnoid hemorrhage GROWTH HORMON EXCESSIVE GH SECRETION Disease : Acromegaly/Gigantism

Essential marker Dx: - Excessive growth of external organ : jaw, hand, feet or gigantism if occur before epiphysis closed - Excessive growth of internal organ - Headache, loss of visual field, asthenia, amenorrhea, sweaty & soft handshake - Insulin like growth hormon (IGF-I) increased - GH not severe decreased after 1 hour OGTT AETHIOLOGY Mostly macroadenoma May be associated MEN 1 Part of Mc Cune Albraight Syndrome Part of Carney syndrome (atrial myxoma, acoustic neuroma, lentigines, adrenal hypercortisolism) Ectopic secretion GHRH/GH by lymphoma, hypothalamic tumor, ca bronchial, pancreatic tumor

CLINICAL SIGN Acromegaly : = Extremity enlargement growth developed after closer of epiphysis finger widen, carpal tunnel syndrome, feet growth = Facial bone, sinus, mandibulae & skull enlarge, teeth space wider =Macroglossia, hypertrophy pharynx & larynx tissue deep voice, hoarseness, sleep apnea

=Enlargement of the internal organ & skin : goiter, cardiomegaly & heart failure, muscle & fat & bone, enlarge, weight gain, DM, arthralgia, vertebrae overgrowth & spinal stenosis, hepatomegaly, colon polyps, skin papilloma, cystic acne, acanthosis nigricans = Supra sella tursica growth tumor : chronic & severe headacne, Chiasma n.optici suppressed can cause hemianopia = Hypertension LABORATORY IGF-I Increased up to 5 x PRL/ prolactin mostly increase OGTT IGT, DM SGOT/SGPT mostly increased Ureum & creatinine mostly increased Ca serum (hyperparathyroidism) Anorganic P increased TSH increased , free T4 decreased

RADIOLOGY & IMAGING X Ray finger & toes (tufting of terminal phalanges & foot (thickening hell pad), skull (enlarge sella & thickening skull) CT Scan, showed the pituitary tumor MRI, showed the pituitary tumor, more superior then CT Scan

MANAGEMENT Micro surgery operation : endoscopic transnasal transsphenoidal pituitary operation Adenoma extirpation & removing Difficult technic for Mc Cune Albright syndrome, because of fibrous dysplasia of skull base Cabergoline drug Pegvisomant (GH block/GH receptor agonist) Octreotide injection SC Lanreotide injection SC

GH DEFICIENCY Central obesity mild to moderate Increased systolic BP Increased LDL-cholesterol

Small heart and reduction cardiac output Asthenia May occur combine pituitary hormon deficiency Panhypopituitarism

PANHYPOPITUITARISM Several pituitary hormon deficiency Developed due to PROP 1 gene mutation, infiltration to sella tursica for example : adenoma chromophob/acidophile, craniopharyngioma, aneurisma a.carotis interna, TBC/fungal meningeal spreading to pituitary, Sheehans syndrome, cerebrovascular bleeding. Deficiency : GH, TSH, FSH, LH, ACTH Clinical sign depend on the pituitary hormon deficiency GH deficiency syndrome Gonadotropin deficiency FSH, LH deficiency androgen & estrogen deficiency lack of libido, DE, amenorrea ACTH deficiency cortisol/adrenal hormon deficiency symptom & sign like Addisons diseases TSH deficiency hypothyroidism symptom & sign cretin, mixoedem PRL deficiency lactation disorder MSH deficiency look pale

RADIOLOGY - CT Scan hypophysis tumor, others SOL (Space occupying lesion) in supra seller - MRI supra seller mass/sol/tumor etc MANAGEMENT a. Transsphenoidal operation : removing pituitary tumor b. Hormon substitution therapy - rhGH injection - DHEA (dehydroepiandrosterone) - Levothyroxine tablet - Hydrocortisone tablet - Estrogen tablet/cap Etc.

INTRODUCTION Insufficiency adrenal produced Deficiency adrenal hormon Primary (adrenal gland) Secondary (pituitary gland) Tertiary (hypothalamus)

INCIDENCE & PREVALENCE Estimate incidence in the developed world 0.8 cases per 100.000 & prevalence 4-8 cases 100.000 population (Stewart, 2003) Incidence Primary adrenocortical insufficiency (Pai) UA western population nearly 50 cases per 1 million. Pai due to steroid withdrawal much more, occur approximately 6 million in the USA (Kevin k.2007) Pai has multiple etiologies, however 80% caused by autoimmune adrenal destruction in USA (kevin K. 2007)

ADRENAL HORMON A. CORTEX : -CORTISOL -ALDOSTERONE -ANDROGEN B. MEDULLA : -EPINEPHRINE -NOREPINEPHRINE GLUCOCORTICOID PHYSIOLOGIC EFFECT Stimulate gluconeogenesis & decrease cellular glucose use Mobilize amino acid & fatty acids Inhibit the effects of insulin Give rise to ketone bodies in metabolism (ketogenesis) Elevated RBC & platelet level Exhibit anti inflamatory effects e.g. vascular response to vasoconstrictor, increases capillary permeability, inhibit IL2, stimulate PMN, reduction adherence of macrophage to endothelium, depletion eosinophils & lymphocytes, reduction circulating lymphocytes (>T cell)

MINERALOCORTICOID PHYSIOLOGIC EFFECT Primary action aldosteron : to renal, gut, salivary & sweat gland Kidney : stimulate reabsorption Na, secretion K & H ion Aldosterone excess : retension Na, hypo K & alkalosis Aldosteron deficiency : increase Na loss, hyper K & acidosis

ADRENAL ANDROGEN HORMON ANDROSTENADIONE DEHYDROEPIANDROSTERONE (DHEA)

ETIOLOGY INSUFFICIENCY ADRENAL A. PRIMARY: ADDISONS DISEASE 1. Autoimmune polyendocrine syndrome I (APS I) (Addisons, mucocutaneus candidiasis, dental enamel hypoplasia, alopecia, gonadal failure) 2. Autoimmune polyendocrine syndrome II (APS II): Addisons, hypothyroidisme, vitiligo, hypogonadism, IDDM, pernicious anaemia 3. INFECTIONS: tbc, fungal, CMV, HIV 4. METASTASIS TUMOR 5. INFILTRATION: Amyloid, hemochromatosis 6. ADRENAL HEMORRHAGE (Waterhouse Friderichsen syndrome) meningococcus septicemia 7. ADRENOLEUCODYSTROPHIES 8. CONGENITAL ADRENAL HYPOPLASIA 9. ACTH RESISTANCE SYNDROME 10. BILATERAL ADRENECTOMY B. SECONDARY ETIOLOGY Exogenous glucocorticoic therapy Hypopituitarism Removal ACTH secreting pituitary adenoma Pituitary tumor surgery, craniopharyngiomas Pituitary apoplexy Granulomatous diseases (Tbc, sarcoid, eosinophilic granulomas) Secondary tumor (breast, bronchus) Sheehans syndrome Pituitary irradiation Idiopathic

Lymphocytic hyphophysitis POMC processing defects POMC gene mutation

PRIMARY ADRENAL INSUFFICIENCY SYMPTOM WEAKNESS, TIREDNESS, FATIGUE ANOREXIA GASTROINTESTINAL SYMPTOM Vomiting Nausea Constipation Abdominal pain Diarrhea SALT CRAVING Postural dizziness Muscle & joint pain 100% 100% 92% 86% 75% 31% 31% 16% 16% 12% 6-13%

CLINICAL SIGN Weight loss Hyperpigmentation Hypotension (<110mm Hg systolic) Vitiligo Auricular calcification 100% 94% 88-94% 10-20% 5%

CLINICAL & LABORATORY ADRENAL CRISIS Dehydration, hypotension or shock Nausea, vomiting, history weight loss & anorexia Acute abdomen/pain Unexplain hypoglicemia Hypo Na, hyper K, hyper Ca, azotemia, eosinophilia Hyperpigmentation or vitiligo Other autoimmune endocrine deficiency

LABORATORY FINDING IN PRIMARY ADRENAL INSUFFICIENCY ANEMIA EOSINOPHILIA AZOTEMIA HYPONATREMIA 40% 17% 55% 88%

HYPERKALEMIA HYPERCALCEMIA HYPOGLICEMIA

64% 6% <3%

LABORATORY TEST (PRIMARY ADRENAL INSUFFICIENCY) Basal plasma & urine cortisol low ACTH stimulation test (tetracosactrin iv/im) Prolonged ACTH Stimulation test (differ primary & secondary adrenal insuff.) Low dose ACTH stimulation test Overnight metyrapone test CRH test Auto AB-21 hydroxylase THORN Test Insuline tolerance test Glucose tolerance test

RADIOLOGY COMPUTED TOMOGRAPHY SCANS MAGNETIC RESONANCE IMAGING ULTRASONOGRAPHY

Other Tests Adrenocorticotropic hormone stimulation test Note: Inemergent situations, do not delay treatment of presumed adrenal insufficiency during diagnostic testing. Treatment with dexamethasone allows ACTH stimulation testing without affecting or interfering with the measurement of serum cortisol levels. Obtain baseline serum cortisol and ACTH levels Administer 0.25 mg (250 mcg) of cosyntropin (synthetic ACTH) IV/IM. Repeat cortisol levels every 30 minutes (some authors recommend 60 min) and 6 hours after ACTH administration Normal response is indicated when the cortisol level doubles in response to ACTH stimulation In adrenal insufficiency, serum cortisol levels fail to rise after ACTH administration Electrocardiograph (ECG): Elevated peaked T waves may indicate hyperkalemia 24-hour urinary cortisol: Use only in nonemergent situations

TREATMENT : ACUTE ADRENAL INSUFFICIENCY CRISIS SHOULD NOT BE DELAYED WHILE WAITING FOR DEFINITIVE PROOF OF DIAGNOSIS BASED ON CLINICAL & LABORATORY FEATURE OF AN ADRENAL CRISIS Emergency Department Care (KevinM Klauer, Ohio UC Osteopa.m, 2007) Maintain airway, breathing and circulation Employ coma protocol (ie, glucose, thiamine, naloxone) Use aggressive volume replacement therapy (dextrose 5% in normal saline solution [D5NS]) Correct electrolyte abnormalities as follows: Hypoglycemia (67%) Hyponatremia (88%) Hyperkalemia (64%) Hypercalcemia (6-33%) Use dextrose 40% as needed for hypoglycemia Administer hydrocortisone 100 mg IVP q6h. During ACTH stimulation testing, dexamethasone (4 mg IV) can be used instead of hydrocortisone to avoid interference with testing of cortisol levels Administer fludrocortisone acetate (mineralocorticoid) 0.1 mg qd Always treat the underlying problem that precipitated the crisis

Imaging Studies Chest radiograph CT scan A CT scan of the abdomen may slow hemorrhage in the adrenals, calcification of the adrenals (seen with TB), or metastasis In cases of secondary adrenal insufficiency, a head CT scan may show destruction of the pituitary (ie, empty sella syndrome) or a pituitary mass lesion

TREATMENT: CHRONIC ADRENOCORTICAL INSUFFICIENCY SUBSTITUTION TREATMENT - hydrocortison 12,5 mg/2 3x/day -deoxycorticosterone trimethylacetate 1 cc im every week -DOCA (Deoxycorticosterone acetate) 25 mg/mouth -Fludrocortison 0,05 0,2 mg/day replacement mineralocorticoid

Consultations Endocrine consultation following admission is beneficial. If no endocrinologist is available, a general internist can manage the process. Emergency management should be implemented in the ED prior to consultation when sufficient clinical suspicion for this diagnosis exists ICU admission is necessary fo most patients with acute adrenal insufficiency and adrenal crisis CONCLUSION Incidence Primary adrenocortical insufficiency (Pai) 50 per 1 million, prevalence 4 to 11 cases per 100.000 (Western), secondary: steroid withdrawl approximately 6 million in USA Pai has multiple etiologies, however 80% cases are caused by auto immune adrenal destruction Awarenss to clinical & laboratory Pai & secondary adrenocortical insufficiency is very important, otherwise we are loosing a golden periode of treatment