Pituitary Gland (2) - Medical Lecture - PDF

Academy Of Engineering And Medical Sciences Department of medical sciences Pituitary Gland (2) Dr.kerollos M.Rezk Phoniatric lecture at military medical complex MBA hospital management AAST  Intended Learning Outcomes (I...

Academy Of Engineering And Medical Sciences Department of medical sciences Pituitary Gland (2) 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:  Describe pituitary gland related hormonal disorders  Investigate hypothalamo-hypophyseal axis  Diagnose a patient with hypopituitarism  Diagnose a patient with short stature  Diagnose a patient with posterior pituitary disorders (DI, SIADH) Hypothalamus and Pituitary Gland  Functional anatomy and physiology The pituitary gland is enclosed in the sella turcica and bridged over by a fold of dura mater called the diaphragma sellae, with the sphenoidal air sinuses below and the optic chiasm above. The cavernous sinuses are lateral to the pituitary fossa and contain the 3rd, 4th and 6th cranial nerves and the internal carotid arteries. Anatomy of Pituitary and Hypothalamus A  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. 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. Hypopituitarism  Hypopituitarism  Hypopituitarism is manifested by diminished or absent secretion of one or more pituitary hormones.  In general, acquired loss of anterior pituitary function follows the sequence of GH, LH/FSH, TSH, ACTH, and PRL.  Treatment and prognosis depend on the extent of hypofunction, the underlying cause, and the location of the lesion in the hypothalamic- pituitary axis.  Etiology Infiltrative / Inflammatory / Invasive (Neoplastic) Immunology Infarction / Vascular Iatrogenic / Injury  Manifestations  The presentation of hypopituitarism can be considered as the presentation of deficiency of each anterior pituitary hormone.  Patients in whom the hypopituitarism is due to a sellar mass may also have symptoms related to the mass, such as headache, visual loss, or diplopia.  Manifestations The clinical presentation of anterior pituitary hormone deficiencies varies, depending upon:  The rapidity with which a disease affects anterior pituitary cells ( e.g. pituitary apoplexy lead to sudden onset of manifestations however radiation therapy, usually act slowly, causing symptoms many months or, more likely, years later.  The severity of the hormonal deficiency.  The types of cells affected, leading to impairment in the secretion of one, a few, or all the pituitary hormones (called panhypopituitarism). Clinical presentation of Hypopituitarism The presentation is highly variable. With progressive lesions of the pituitary there is a characteristic sequence of loss of pituitary hormone secretion. Growth hormone secretion is often the earliest to be lost. In adults, this produces lethargy, muscle weakness and increased fat mass, but these features are not obvious in isolation. Next, gonadotrophin (LH and FSH) secretion becomes impaired with, in the male, loss of libido and, in the female, oligomenorrhoea or amenorrhoea. Later, in the male there may be gynaecomastia and decreased frequency of Clinical presentation of Hypopituitarism In both sexes axillary and pubic hair eventually become sparse or even absent and the skin becomes characteristically finer and wrinkled. Chronic anemia may also occur. The next hormone to be lost is usually TSH, resulting in secondary HYPOTHYROIDISM, This contributes further to apathy and cold intolerance. In contrast to primary hypothyroidism, frank myxoedema is rare, presumably because the thyroid retains some autonomous function. Clinical presentation of Hypopituitarism Finally, ACTH is lost, resulting in symptoms of cortisol insufficiency. HYPOPIGMENTATION is characteristic In contrast to the pigmentation of Addison's disease, a striking degree of pallor is usually present, principally because of lack of stimulation of melanocytes by β-lipotrophic hormone (β- LPH, a fragment of the ACTH precursor peptide) in the skin. Clinical presentation of Hypopituitarism The onset of all previous symptoms is obvious insidious. However, patients sometimes present acutely unwell with glucocorticoid deficiency. This may be precipitated by a mild infection or injury, or may occur secondary to pituitary apoplexy.  Hormone Deficiencies ACTH GH  Secondary adrenal  In children - short stature. insufficiency  In adults  Intact mineralocorticoids: - Changes in body - No salt wasting composition - No volume - Increased fat mass contraction - Decrease lean ‫نحيف‬body - No hyperkalemia mass  No Hyperpigmentation - Decreased bone mineral TSH Prolactin density.  Secondary  Inability to lactate after hypothyroidism delivery.  Isolated deficiency is rare  Gonadotropins  Deficient secretion of FSH and LH results in hypogonadotropic hypogonadism (secondary hypogonadism) in both women and men. In women,  It means ovarian hypofunction, which results in decreased estradiol secretion.  In premenopausal women include amenorrhea, anovulatory infertility, vaginal atrophy, and hot flashes.  Breast tissue decreases and bone mineral density declines. In men,  It means testicular hypofunction, which results in infertility and decreased testosterone secretion.  Testosterone deficiency causes decreased energy and libido, and hot flashes if sufficiently severe, within weeks to months, but does not cause decreased muscle mass (and perhaps strength) for several years. Testosterone deficiency also causes decreased bone mineral dens  Sheehan’s Syndrome  Infarction of the pituitary gland after postpartum hemorrhage  Clinical Features: 1. A history of postpartum hemorrhage so severe as to cause hypotension and require transfusion of multiple units of blood. 2. Lethargy, anorexia, weight loss, and inability to lactate. 3. Loss of axillary and pubic hair. 4. A small pituitary within a sella of normal size, sometimes read as an "empty sella" on MRI  Pituitary apoplexy  Sudden hemorrhage into the pituitary gland is called pituitary apoplexy.  Hemorrhage often occurs into a pituitary adenoma. In its most dramatic presentation, apoplexy causes the sudden onset of sever headache, diplopia and hypopituitarism.  All pituitary hormonal deficiencies can occur, but the sudden onset of ACTH and therefore cortisol deficiency is the most serious because it can cause life-threatening hypotension.  Empty Sella Syndrome An empty sella can develop as a consequence of a primary congenital weakness of the diaphragm Damage to the sellar diaphragm can lead to arachnoid herniation into the sella. Usually have normal pituitary function(incidental finding) Implying that the surrounding rim of pituitary tissue is fully functional Hypopituitarism may develop insidiously. Rarely, functional pituitary adenomas may arise within the rim of pituitary tissue, and these are not always visible on MRI. Aetiology:- 1.Congenital 2.Primary hypophisitis  Clinical Presentation Can present with features of deficiency of one or more anterior pituitary hormones. Up to 50% of patients with primary empty sella have associated benign intracranial hypertension Clinical presentation depends on: Age at onset Hormone affected, extent Speed of onset Duration of the deficiency  Empty Sella Syndrome MRI brain(sagittal Specimen showing section) empty pit fossa  Investigations for Hypopituitarism Measure serum levels where appropriate / STIMULATION TEST Thyroid (TSH & T4), Gonadotrophin (LH & FSH) and Prolactin hormone secretion are adequately assessed by measuring basal serum levels to see if deficient. Prolactin may be ↑ due to loss of dopamine from the hypothalamus (dopamine inhibits PRL release, so if it doesn’t reach the pituitary, prolactin levels are not inhibited so levels rise).  Investigations for Hypopituitarism GH & Adrenal axes – IGF-1 can be used to roughly measure GH axis (screening test) & Cortisol levels (↓) for adrenal axis.  INSULIN STRESS TEST / insulin tolerance test (ITT) (stimulation test) = More accurate test for GH and adrenal axes. INSULIN STRESS TEST= Give IV insulin to make patient hypoglycaemic (essentially stressed). Their glucose must ↓ to 20 mU/L and >550mmol/L respectively. GH and cortisol do not increase above these levels if the patient is hypocortisolaemic (cortisol deficient) and Growth Hormone deficient.  Investigations for Hypopituitarism MRI to look for pituitary or hypothalamic lesion.  Short Stature Height below 3rd centile or more than 2 standard deviations below the median height for age & sex  Causes of Short Stature Physiological:  Familial  Constitutional Pathological:  Undernutrition  Chronic systemic diseases  Endocrine Causes  Psychosocial dwarfism  Skeletal dysplasias  Genetic syndromes Non- endocrine causes: Constitutional Genetic Chronic diseases Malnutrition Intrauterine growth retardation Skeletal dysplasias Genetic syndromes Drugs Endocrine causes: Growth hormone deficiency Psychosocial dwarfism Hypothyroidism Cushing’s syndrome Psudohypoparathyroidism Diabetes mellitus Disorders of vitamin D Diabetes insipidus  Assessment of child with Short Stature Accurate height assessment Assessment of body proportions Comparison with population norms Comparison with child’s own genetic potential Sexual maturity rating  Investigations Level One: Complete blood count with ESR Bone Age Urinalysis Stool examination RFT LFT FBS  Investigations cont. Level Two: TFT Karyotying Level Three: GH stimulation tests Posterior pituitary  Posterior pituitary Vasopressin (AVP or antidiuretic hormone) and oxytocin, neurohypophyseal hormones, are synthesized by the supraoptic and paraventricular nuclei of the hypothalamus. Transported to the posterior lobe in neurosecretory granules along the supraopticohypophyseal tract. ADH (VASSOPRESSIN)  Diabetes insipidus (DI) Uncommon disorder is characterised by the excretion of excessive dilute urine and by thirst. Classified as cranial diabetes insipidus (deficient ADH production by hypothalamus) or nephrogenic DI (renal tubules unresponsive to ADH).  CAUSES OF DIABETES INSIPIDUS CENTRAL NEPHROGENIC  Idiopathic  Idiopathic  Familial  Familial V2 receptor gene  Hypophysectomy mutation Aquaporin-2 gene  mutation Infiltration of  Chronic renal disease. hypothalamus and medullary cystic disease) posterior pituitary  Langerhans cell  Hypokalemia  Hypercalcemia histiocytosis  Granulomas Infection  Sickle cell anemia  Tumors (intrasellar and  Drugs: Lithium ,Fluoride, Demeclocycline & suprasellar) Colchicine Autoimmune  DI, CLINICAL FEATURES Clinical features : Polyuria (5–20 L/24 hrs) and polydipsia. Urine is of low specific gravity ( 300 mOsm/ kg), either undetectable serum ADH or urine is not maximally concentrated (i.e. < 600 mOsm/kg). IF NOT water deprivation test is required  No fluids are allowed for 8 hrs  Body weight, plasma and urine osmolality are measured every 2 hrs.  Stop test if > 3% of body weight is lost.  DI is confirmed by plasma osmolality > 300 mOsm/kg with urine osmolality < 600 mOsm/kg.  SIADH Syndrome of inappropriate antidiuretic hormone secretion (SIADH):  Continued secretion or action of arginine vasopressin (AVP) despite normal or increased plasma volume.  Resulting in impairment of water secretion and consequent water retention →hyponatremia (ie, serum Na+ < 135 mmol/L) with concomitant hypo-osmolality (serum osmolality < 280 mOsm/kg) and high urine osmolality (hallmark of SIADH).  Hyponatremia results from an excess of water rather than a deficiency of sodium. Thank You