Disorders of the hypothalamus and pituitary: acromegaly, diabetes insipidus. Endocrine and metabolic emergencies.

Transcription

1 Disorders of the hypothalamus and pituitary: acromegaly, diabetes insipidus. Endocrine and metabolic emergencies. Dr. Lakatos Péter Semmelweis Egyetem I. Belgyógyászati Klinika

2 Disorders of the hypothalamus and pituitary: acromegaly, diabetes insipidus.

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5 Hypothalamus diseases Hypothalamic, pituitary and other masses Pituitary adenomas Prolactinoma Acromegaly Hypopytuitarism Cushing disease Neurohypophysis Diabetes insipidus

6 Hypothalamus diseases see Causes of hypopituitarism Kallmann syndrome KAL gene Xp22.3 GnRH deficiency + anosmia (deafness, blindness, renal, neurological signs) Bardet-Biedl syndrome obesity, mental ret, renal dis., fingers, GnRH (75%) retinal deg., diabetes insipidus Prader-Willi syndrome SNRP, NECIDIN genes hypogonadotrop hypogonadism, hyperphagia-obesity, ment. ret., muscl. hypotonia DM, somatic defects Leptin receptor mutations hyperphagia, obesity, central hypogonadism

7 Hypothalamic, pituitary and other masses Hypothalamic masses meningeomas, germonomas, histiocitosis X, hamartomas, gliomas Craniopharyngeomas benign, suprasellar cystis mass derived from Rathke pouch arise near the pituitary stalk, locally invasive intracranial presure signs, hypopituitarism and diabetes insip

8 Empty sella enlarged sella obes, multipara women Primary ESS is associated with obesity high blood pressure in women. idiopatic intracranial hipertension Endocrine disorders usually no hyperprolactinemia early onset of puberty GH reserv

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10 All pituitary adenomas 4.0/ in Finland Lactotroph adenomas 2.2 Clinically nonfunctioning adenomas 1.0 Somatotroph adenomas 0.34 Corticotroph adenomas 0.17 All adenomas 77.6 / in England Lactotroph adenomas 44.4 Nonfunctioning adenomas 22.2 Somatotroph adenomas 8.6 Corticotroph adenomas 1.2 1/3 is non-functioning adenomas!

11 Pituitary adenomas I. Pathophysiology: G protein mutation, ras mutation Classification: Based on staining: (hem eos) basophilic, acidophilic, chromophobic, (ACTH) (prolactin) (prolactin, GH, TSH, LH, FSH) Based on immunohistochemistry: Corticotrop (ACTH and POMC), somatotrop (GH), thyreotop(tsh), gonadotrop (LH,FSH and subunits), lactotrop (prol) and null cell Based on size: microadenoma < 10 mm, macroadenoma > 10 mm invasiv tumors are rare

12 Pituitary adenomas II. Pressure signs Headache Visual loss homonym hemianopsia blindness (8%) one eye blindness (9%) Ocolomotorius paresis Hormonal effects prolactin increasing others decreasing Hormonal signs see at diseases 15% of adenomas produce more than one hormon

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14 Prolactinoma I. most common pituitary adenoma (40%) 3/ tipically: women micro-, males macroadenoma Clinical signs: A, Direct hormone effects: B, : Tumor mass effect galactorrohea (30% pituitary adenoma) amenorrhea infertility decreased libido, impotence (8% of men with impotence) During pregnancy it is growing but usually it has no clinical consequence

15 Prolactinoma II. Diagnosis Laboratory measurement (10-25 ug/l ng/ml; miu/l) repeated, morning time, fasting, no stress situation MRI Ophthalmological examination Treatment most of the microadenomas will not become macro microadenoma: in case of clinical signs (?!) macroadenoma: in all cases Medical treatment: dopamine agonists (bromocriptine 0, mg/die quinagolid ug/die) Surgical: transspenoidal approach recurrence rate 40 % in micro, 80 % in macro Irradiation radiation, gamma knife, proton beam

16 Hyperprolactinemia prolactinoma Physiological Pregnancy, stress, irritation of nipples, sex, sleep, digestion Drugs Dopamine receptor antagonists: metoclopramid, butyrophenon Dopamine-blockers: metyldopa, estrogens, opiates, verapamil Diseases Pituitary adenoma Hypothalamic diseases Primary hypothyroidism Chr. kidney failure Cirrhosis hepatis Chest trauma 30 %

17 Blick diagnosis

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19 General Skin Head-neck Circulation Sexuality CNS Muscles Joints Acromegaly I. after the closing of the epiphyseal line ~4/million w/m 1:1; middle age Clinical signs weakness, sweating, weight gain Decreased life expectency hand and acras growing, hypertrichosis headache, visual loss, sinus disease enlarged tongue, changing voice, heart failure, hypertension, pulm disease libido, impotence, infertilities paresthesia, hypersomnolence weakness, proximal myopathy pain, osteoarthrosis

20 Acromegaly II. Laboratory hgh. IGF-I, IGF-BP3 glucose-suppression test: 100 (75) g glucose per os GH measurement 0, 30, 60 and 120 min normal value: 0 < 5 ug/l, 60 and 120 < 2 ug/l IGF-1: norm dep. on age; screening marker IGF-BP3: best marker could be : insulin resistance (80%), hypercalciuria (25%), hyperphosphatemia (50%), hyperprolactinemia (50%) Radiologic investigation: MRI, sella turcica X-ray 90 % abnormal bone x-rays /enlarged vertebral bodis, increased thickness of ribs/ colonoscopy

21 Therapy target: Acromegaly III. GH and IGF-1 to normalize tumor size shrinking Surgery: transphenoidal operation 20-40% possible (depends on tumor size) Irradiation: slow effect (hypofunction) proton irradiation (rare cyclotron) X-ray gamma knife cobalt 60 Drugs: bromocriptine per os mg/die only 20 % GH<5 ug/l octreotide SANDOSTATIN sc. 4* ug, LAR 4 weeks/20-40 mg pegvisomant SOMAVERTsc mg/die long term control needed

22 Hypopytuitarism

23 Causes of hypopituitarism Congenital diseases Hypophysis dysplasia Septo-optico dysplasia Pit-1; Prop-1 mutation Kallmann syndrome KAL gene Xp22.3 GnRH deficiency + anosmia (deafness, blindness, renal neurological signs) Bardet-Biedl syndrome obesitas, mental ret, renal disease, fingers, GnRH Prader-Willi syndrome SNRP, NECIDIN gén hypogonadotrop hypogonadizmus, hyperphagia-obesitas, ment. ret.,muscl. hypotonia DM, somaticus defects

24 Causes of hypopituitarism Acquired diseases Trauma accidental, surgery, radiation, birth trauma Tumors adenoma, craniopharyngioma, brain tumors metastasis, lymphoma Infiltration limfocytic hypophysitis, hemochromatosis, histocytosis X, sarcoidosis Infection hystoplasmosis, toxoplasmosis, tuberculosis, pneumocystitis carinii Vascular causes hypophysis apoplexia, Sheehan postpartum necrosis sickle cell anemia

25 Clinical signs of hypopituitarism GH>LH/FSH>TSH>ACTH>prol GH growing disorders in childhood adult: wrinkled, more subcutaneous fat tissue, less muscle, higher mortality rate LH/FSH amenorrhea, infertility, decreased libido and hair TSH hypothyroidism (TSH ; ft3, ft4 ) ACTH cortisol deficiency (Not ADDISON disease!!!) Prolactin breast-feeding problems

26 Diabetes insipidus = lack of vasopressin effects Diff. dg.: central nephrogen psychogen (primary)

27 Acquired: Trauma Tumor Granuloma histiocytosis, xanthoma disseminate Infection meningitis, encephalitis, toxoplasmosis, CMV, herpes Inflammation SLE, Wegener, scleroderma Toxins snake toxin Circulation Sheehan, aneurism, hypoxia Idiopathic Diabetes Insipidus Central causes: Congenital: X chromosome AD AR AVP neurophysin gene, Wolfram gene congenital malformation

28 Diabetes Insipidus Nephrogen causes: Congenital: Aquaporin-2 gene mutation Acquired: Drugs lithium, amphotericin B, cytostatics Metabolic hypercalcemia, hypokalemia, Ishemia acute tubular necrosis Tumor Gravidity Idiopathic

29 Diabetes Insipidus Clinical manifestations Polyuria (> 50 ml/bwkg >3500 ml/die) Polydipsy Excessive thirst Mild elevation in the se-na In case of severe dehydration: weakness, fever, psychic disturb., hypotension - tachycardia, death, Diagnosis Polyuria > 3,5 l 50 ml/bwkg Urine specific gravity < 1010 (1005) Urine osmolality < 300 mosmol X-ray, MRI, ophtalmologic examinations, Tests: thirsting test Carter-Robbins test

30 Diabetes Insipidus Differential diagnosis: central diabetes insipidus - nephrogen diabetes insipidus - primary polydipsy (psychogen) anamnesis DDAVP test Treatment of diabetes insipidus Name of the drug dose effect duration Arginin vasopressin 5-10 U 3-6 h Desmopressin (1 deamino D arginin- 8 vasopressin) intranasal ug h sc. iv. 1-4 ug h Carbamazepine 3* 200 mg Thiazide diuretics mg

31 Endocrine and metabolic emergencies

32 Panhypopytuitarismus Addison crisis Pheochromocytoma Thyrotoxic crisis Myxodema coma Hypercalcaemic crisis Hypoglycemic crisis Hyperglycemic crisis

33 Adrenal crisis I. chronic adrenal insufficiency + sepsis or surgical stress bilateral adrenal hemorrhage: Waterhouse-Friderichsen sy. (pseudomonas, meningococcus) anticoagulant therapy coagulation disorders birth trauma Iatrogen causes rapid withdrawal of steroids from patient inhibiting steroid synthesis (mitotane, ketoconazole) increasing steroid metabolism (phenytoin, rifampin)

34 Adrenal crisis II. Clinical signs In untreated patient, preexisting symptoms are intensified nausea, vomiting, abdominal pain, fever, lethargy, hypotension, hypovolemic vascular collapse Previously treated patients, clinical signs come back hypotension later

35 Adrenal crisis III. 100 mg hydrocortisone iv. bolus followed by continuous infusion 10 mg/h + maybe required: hydration, vasopressor agent

36 Pheochromocytoma Crisis (paroxysmal) occurs in over half of the patients sudden onset; intervals: weeks, months; it may last from few minutes to several hours Signs: headache, profuse sweating, palpitation, pain in the chest and abdomen; vomit, pallor blood pressure is elevated, tachycardia (hypotension-adrenomedullin) Treatment: nitroprusside (Nipride) or phentolamine (Regitine) administered intravenously. 1 mg- 5mg - infusion

37 Thyrotoxic crisis Reason: hyperthyroidism + infection, radioiodine treatment, drugs contaning iodine, after surgery, trauma, delivery Signs: Severe hyperthyroidism + extreme irritability, restlessness, fever (41 C), delirium-coma, tachycardia, hypotension, vomiting, diarrhea, dehydration,

38 Thyrotoxic crisis II. Treatment: methimazol, propylthiouracil - Beta-blockers: Propranolol 1 mg/min iv. until adequate beta-blockade has been achieved or mg/ 4 hours per os Esmolol mg/kg iv. followed by ug/kg/min - Iodine: Lugol s solution 10 drops/3 times daily - Glucocorticoid: hydrocortisone 100 mg iv./3 times daily - Antipyretic: acetaminophene is preferable to aspirin

39 Myxoedema coma Cause: long-standing hypothyroidism + an acute event infection, myocardial infarction, cold exposure, or the administration of sedative drugs, especially opiates.

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41 Hypercalcemic crisis

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44 Hypercalcemic crisis Treatment treat the reason! - Volume expansion followed by a loop diuretic - Salmon calcitonin: rapid effect, short term use - Bisphosphonates pamidronate: 3*30 mg iv. zoledronate: 2,0-4,0 mg iv. - Dialysis

45 Hypoglycemic crisis - Sweating, trembling, confusion, unconsciousness - Blood glucose low - If possible oral glucose - If not possible iv glucose ml 40% glucose solution 40 g ( mg) glucose - 5 l (50x100 ml) blood in humans - mg%= mg / 50 dl = 800 mg% blood glucose = 47 mmol/l!!! - Brain edema death! - Never more than ml 40% glucose iv,! - Afterwards, 5% glucose infusion if needed

46 Hyperglycemic crisis - Red, dry skin, elevated blood glucose - Hyperosmolar hyperhycemia - Ketoacidotic hypergylcemia, coma (ph) - ph correction only < Hydration (1 liter in 30 minutes) - Small dose iv insulin (6-8 IU fast-acting) + KCl - <11 mmol/l glucose, trasition to sc 5x insulin - Antibiotics, circulation support, etc.

47 Köszönöm a figyelmet!