Pituitary Gland (Hyper) PDF

Academy Of Engineering And Medical Sciences Department of medical sciences Pituitary Gland Dr.kerollos M.Rezk Phoniatric lecture at military medical complex MBA hospital management AAST  Intended Learning Outcomes (ILOs) By the end of this lec...

Academy Of Engineering And Medical Sciences Department of medical sciences Pituitary Gland Dr.kerollos M.Rezk Phoniatric lecture at military medical complex MBA hospital management AAST  Intended Learning Outcomes (ILOs) By the end of this lecture the student will be able to:  Define pituitary adenomas.  Classify pituitary adenomas.  Diagnose a patient with acromegaly.  Diagnose a patient with hyperprolactinemia.  Diagnose a patient with gynaecomastia. Hypothalamus and Pituitary Gland  FUNCTIONAL ANATOMY The gland is composed of two lobes, anterior and posterior, and is connected to the hypothalamus by the infundibular stalk, which has portal vessels carrying blood from the median eminence of the hypothalamus to the anterior lobe and nerve fibres to the posterior lobe. The supraoptic and paraventricular nuclei synthesize ADH (vasopressin) and send it via their axons to be stored in posterior pituitary. Pituitary – Target organ hormone axis Stimulatory Anterior lobe of Pituitary Gland Hypothalamic Pituitary target cell Pituitary hormone Peripheral target Peripheral hormone affected gland hormone affected TRH Thyrotroph TSH Thyroid gland T4, T3 GHRH Somatotroph GH Liver IGF-1 GnRH Gonadotroph LH, FSH Ovary / testis Progesterone / Testosterone / Inhibin CRH Corticotroph ACTH Adrenal gland Cortisol Posterior lobe of pituitary Vasopressin Kidney Oxytocin Uterus, breast Inhibitory Somatostatin Somatotroph GH Liver Thyrotroph TSH Thyroid Dopamine Lactotroph Prolactin Breast Common symptoms and signs in Pituitary disease  Investigation of patients with pituitary disease  Direct measurement of hormone levels (non-dynamic tests) are used for: PRL, LH, FSH (and sex steroids), TSH (and free T4/T3)  Dynamic tests are mainly used for Cortisol and Growth Hormone measurements.  EXCESS HORMONE suspected = use a SUPPRESSION test  Hypersecretion of cortisol = dexamethasone suppression test  Hypersecretion of GH = oral glucose tolerance test (OGTT)  DEFICIENCY suspected = use a STIMULATION test  Deficiency of Cortisol = Insulin stress test / short synACTHen test.  Deficiency of GH = Insulin stress test / glucagon test.  Pituitary adenomas Adenoma = a benign epithelial tumour in which the cells form recognizable glandular structures or in which the cells are derived from glandular epithelium. Pituitary adenomas have effects on the gland causing symptoms of hypOfunction, hypERfunction or mass/pressure effects (non-functioning/non- secretory). They are always benign. Pituitary tumours (almost always benign adenomas) account for ~ 10% of intracranial tumours.  PITUITARY ADENOMAS A pituitary adenoma may be classified as either a macroadenoma (> 10 mm diameter) or a microadenoma (< 10 mm diameter). Microadenomas are not associated with hypopituitarism or compression of local structures and are only treated if they are secreting excess hormones. Features of Sellar Mass Lesions MRI of the pituitary. A, Coronal section of a normal pituitary gland. ----------------------------------------- B, Sagittal view of a large pituitary adenoma lifting and distorting the optic chiasm and invading the sphenoid sinus and impinging the frontal lobe. ------------------------------------------ C, Coronal view of a large macroadenoma elevating the optic chiasm and invading the right cavernous sinus.  Non-functioning/Non-secretory pituitary adenomas The commonest pituitary tumour does not secrete known active hormones and is called a ‘non-secretory’ adenoma. HYPOPITUITARISM and/or MASS EFFECTS are the main consequences. Effects of non-functioni ng adenomas: Mass effects: - Headache - Optic Chiasm compression causing visual field defects – bitemporal hemianopia: - Cranial Nerve palsies (due to pressure or invasion of the cavernous sinus) (3rd nerve palsy = most common) - CSF rhinorrhoea, due to erosion through the floor of the sella turcica Neuroendocrine effects: - Hypopituitarism (damage to other anterior pituitary cells or interruption of their control) - Hyperprolactinaemia (pituitary stalk disruption interrupting inhibitory effect of hypothalamic dopamine) - Disturbances of temperature, sleep, appetite. - Hypothalamic and/or posterior pituitary damage: Diabetes Insipidus The main hypERfunctioning pituitary adenomas GH Hyper-secretion -Acromegaly-  Growth Hormone  Postnatal & through Puberty: GH and IGF-1 are critical in determining longitudinal skeletal growth and maturation.  Adulthood: maintain skeletal architecture and bone mass.  GH also has effects on the metabolism of carbohydrates, lipids, and proteins by antagonizing insulin action, increasing lipolysis and free fatty acid production, and increasing protein synthesis.  GH hyper-secretion / Acromegaly Definition and epidemiology  Acromegaly is literally translated as abnormal enlargement of the extremities of the skeleton. It is caused by hyper-secretion of GH in adulthood.  Gigantism is excessive GH secretion before closure of the epiphyseal growth plate.  The cause is almost always a GH-secreting pituitary adenoma.  30% are plurihormonal and also secrete prolactin.  Clinical Presentation  The rate of change of symptoms and signs is slow and insidious.  The usual period from earliest onset of symptoms and signs to diagnosis is 8 to 10 years. Bone - Soft tissue - Endocrine - Metabolic abnormalities  Clinical Presentation Changes Manifestations Somatic changes Acral changes Enlarged hands and feet Muscloskeletal changes Arthralgias ‫الم في المفاصل‬ Malocclusion Carpal tunnel syndrome Proximal myopathy Skin changes Swaeting Colon changes Polyps Carcinoma Cardiovascular Cardiomegaly Hypertension Pulmonary Sleep disturbance – sleep apnea Viceromegaly Tongue, Thyroid, Liver  Clinical Presentation Changes Manifestations Endocrine-Metabolic changes Reproductive Menstrual abnormalities Galactorrhea Decrease Libido Carbohydrates metabolism IGT DM Lipids Hypertriglyceridemia Local Tumor effect Pituitary enlargement Visual field defect Cranial nerve palsy Headache Markedly increased soft tissue bulk and blunt fingers in a middle-aged man with acromegaly Radiologic signs in acromegaly. Left: Skull with enlarged sella turcica and frontal sinuses, thickening of the calvarium, and enlargement of the mandible. Center: Hand with enlarged sesamoid bone and increased soft tissue shadows. Right : Thickened heel pad.  Key Summary of Diagnosis  Acromegaly is a clinical syndrome that does not manifest with clear diagnostic features.  Serum GH assays are not standardized.  The GH after administration of 75 g of glucose orally (OGTT) should be less than 1.0 ng/mL to define normal.  Serum IGF-I assays, Assess integrated GH secretion and are excellent for diagnosis, monitoring, and screening.  The diagnosis of acromegaly depends on clinical, laboratory and imaging features. Hyperprolactinemia REGULATION OF PROLACTIN SECRETION  Hyperprolactinemia, causes  PHYSIOLOGICAL:  Pregnancy  Nursing  Physical and psychological stress  Sleep  PHARMACOLOGICAL:  Estrogens  Metoclopramide  Verapamil  SSRI  Methyldopa  Opioids  TUMOURS: Prolactinoma, Pituitary stalk compression by tumor Craniophyrangiomas.  OTHERS: Primary hypothyroidism, Chest wall lesion, Chronic renal failure, Empty sellasyndrome.  IDIOPATHIC A Prolactinoma is classified as: Microprolactinoma (< 10 mm diameter) OR Macroprolactinoma (>10 mm diameter).  60% of the Men present withmacroprolactinomas.  90% of the females present withmicroprolactinomas.  Clinical manifestations  Hormonal Effect :  Women : infertility, oligomenorrhea, amenorrhea or rarely galactorrhea.  Men : decreased libido, impotence, infertility, gynecomastia, very rarely galactorrhea. Increased body weight – associated withprolactin- secreting tumor Osteopenia – patients with associatedhypogonadism Degree of bone loss  Clinical presentation of hyperprolactinemia Mass Effect : headache ,CSF rhinorrhea , compression of optic chiasma & cranial nerve.  Diagnosis and testing  Based on clinical evaluation, biochemical testing and imaging  History: drugs, amenorrhoea, galactorrhoea  Physical examination: visual field defects, breast discharge.  Laboratory investigations: pregnancy test, TSH, free T4, creatinine, anterior pituitary function assay  MRI of the pituitary: pituitarytumour  Presence of Pituitary mass on MRI  Serum prolactin level: normal range 5-25ng/ml.  Serum prolactin valuesabove 200 ng/mL usually indicate the presence of a lactotroph adenoma. Gynecomastia  Definition  Gynecomastia is benign enlargement of the male breast caused by proliferation of glandular breast tissue. Pseudogynecomastia: Enlargement of the male breast, as a result of increased fat deposition is called Pseudogynecomastia. synonymous terms are used like Adipomastia, or lipomastia.  Pathophysiology  Gynecomastia results from an imbalance between the stimulatory effect of estrogen on ductal proliferation and the inhibitory effect of androgen on breast development.  The imbalance is most commonly caused by increased production of estrogens, decreased production of testosterone, or increased conversion of androgens to estrogens in peripheral tissue.  Disorders of sex hormone–binding globulin or with androgen receptor binding and function can also result in gynecomastia.  Causes of Gynecomastia  Persistent pubertal gynecomastia  Drugs : Common drugs includes Spironolactone, Cimetidine, Ketoconazole, Estrogens and estrogen agonists, human chorionic gonadotropin hCG), antiandrogens, gonadotropin-releasing hormone (GnRH) agonists, and 5- alpha-reductase inhibitors.  No detectable abnormality (idiopathic).  Cirrhosis or malnutrition.  Hypogonadism.  Testicular tumors.  Hyperthyroidism.  Chronic renal insufficiency. Other endocrine causes: Hyperprolactinemia, Acromegaly, Androgen receptor disorder, Excessive Aromatase activity.  Clinical manifestation  Gynecomastia usually manifests as a palpable, discrete button of tissue radiating from beneath the nipple and areola.  Gynecomastia feels “gritty” when the breast is pinched between the thumb and forefinger.  Fatty tissue (Pseudogynecomastia), unlike gynecomastia, will not cause resistance until the nipple is reached. (Difference in clinical examination).  Examination Findings  The examination is performed by having the patient lie on his back with his hands behind his head. The examiner then places his or her thumb and forefinger on each side of the breast and slowly brings them together  Gynecomastia is appreciated as a concentric, rubbery-to-firm disk of tissue, often mobile, located directly beneath the areolar area.  Pseudogynecomastia presents no discrete mass,  Other masses due to disorders such as cancer tend to be eccentrically positioned (insert) Source: uptodate.com  Evaluation HISTORY:  Age  Duration of the gynaecomastia  Presence of pain.  Use of drugs including recreation drugs e.g. Alcohol  Presence of symptoms suggestive of pathological cause.  Symptome of hypogonadism - reduced libido, erectile dysfunction. Systemic disease: Hepatic, Renal, Endocrine disease. (Thyrotoxicosis, Cushing syndrome).  Physical examination:  Breasts: Pinch breast tissue between thumb and forefinger—distinguish from fat. (Method Previously Described) Measure glandular tissue diameter. Look for galactorrhea.  Testiculr palpation: Exclude tumour. Assess testicular size—?atrophy.  2° sex characteristics.  Look for evidence of systemic disease e.g. chronic liver or renal disease, thyrotoxicosis, Cushing's syndrome, chronic cardiac or pulmonary disease.  Baseline investigations  Serum testosterone.  Serum estradiol.  LH and FSH.  Prolactin.  SHBG.  hCG.  Liver function tests.  Additional investigations  If testicular tumour is suspected, e.g. raised estradiol/hCG: testicular USG.  If adrenal tumour is suspected, e.g. markedly raised estradiol: abdominal CT or MRI scan.  If breast malignancy is suspected: mammography; FNAC/tissue biopsy.  If lung cancer is suspected, e.g. raised hCG: chest radiograph.  Other investigations, depending on clinical suspicion, e.g. renal or thyroid function.  Lecture Quiz A 56-year-old male presents with a 5 year history of increased sweats and change in shoe size. Examination reveals prognathism and macroglossia, with large hands. Blood pressure is 180/94 mmHg but visual field examination is full to confrontation. Which of the following tests would be diagnostic? A. Oral glucose tolerance test B. TRH test C. Insulin tolerance test D. Pituitary MRI E. IGF-1 concentration  Lecture Quiz The diagnosis of acromegaly is confirmed with a failure of GH suppression during an oral glucose tolerance test. Though a pituitary adenoma may be present it is not diagnostic of acromegaly.