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Pituitary Gland System – “Paracrine”

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Pituitary Gland System – “Paracrine” Endocrine-related Problems Pathology of the Endocrine System • Overproduction of a hormone • Underproduction of a hormone • Nonfunctional receptors that cause target cells to become insensitive to hormones ผูชวยศาสตราจารย แพทยหญิง จุลินทร สําราญ ภาควิชาพยาธิวิทยา คณะแพทยศาสตร Endocrine system 1. Endocrine organs Hypothalamus 2. Endocrine components in mixed and organs 3. Diffuse endocrine Pituitary gland system – “paracrine” 1 Hypothalamus – Pituitary gland Pituitary gland Pituitary gland Pituitary Hormones Adenohypophysis Neurohypophysis Roof of mouth – Rathke’s pouch Floor of diencephalon 2 Clinical Manifestations Hypopituitarism of Pituitary Disease • Hyperpituitarism • Deficient secretion of one or more of pituitary hormones • Hypopituitarism – Pituitary tumor compressing normal tissue • Local mass effects – Sheehan Syndrome: ischemic injury from PPH • Diseases of the posterior pituitary: – Pituitary apoplexy: hemorrhage or infarct in normal tissue or inactive adenoma Increased or decreased ADH – Trauma, surgery or radiation – Infiltrative disease including infection, inflammation, and some tumors – Genetic abnormalities of pituitary development – Empty sella syndrome Hyperpituitarism Local mass effects • Increased secretion of one or more of pituitary hormones • Headaches: Increase intracranial pressure – Pituitary adenoma – streching of dura – Pituitary hyperplasia • Visual field defect: – Pituitary carcinoma Nasal retinal fiber compression – Secretion of hormones by nonpituitary • Cranial nerve palsies tumors (III, IV, V, and VI): – Hypothalamic disorder Lateral extension of the tumor 3 Pituitary adenoma and Hyperpituitarism The most common and important diseases of the pituitary gland - Pituitary adenoma • The most common cause of hyperpituitarism is an adenoma arising Functioning adenoma in the anterior lobe • Overproduction of hormones: common GH • Pituitary adenomas: functional or silent and Prolactin and few , and usually composed of a single cell ACTH type and produce a single predominant Non-functioning adenoma hormone • Mass effect: Bitemporal • Pituitary adenomas may be hormone- hemianopia and negative hypopituitarism Bitemporal Hemianopsia • Incidence: about 10% of intracranial neoplasms (discovered incidentally in up to 25% of routine autopsies) • usually found in adults, with a peak incidence from the thirties to the fifties • Most pituitary adenomas occur as isolated lesions. In about 3% of cases associated with multiple endocrine neoplasia (MEN) type 1 4 Growth Hormone from Somatotroph The second most common type of functioning pituitary adenoma Gigantism in children before closure of epiphyses - a generalized increase in body size with disproportionately long arms and legs Acromegaly in adult or after closure of epiphyses - Enlargement of the jaw , hands, feet, and visceral organs (thyroid, heart, liver, and adrenals) Prolactinoma from Lactotroph The most frequent type of hyperfunctioning pituitary adenoma -Galactorrhea, amenorrhea, infertility Acromegaly 5 Corticotroph cell adenoma The clinical manifestations Depend on the specific hormone lacking Hypercortisolism • Growth hormone deficiency in children by pituitary adenoma develop growth failure (pituitary dwarfism) Hyperpigmentation • Gonadotropin (GnRH) deficiency leads to amenorrhea and infertility in women and decreased libido, impotence, and loss of pubic and axillary hair in men. • TSH and ACTH deficiencies result in Cushing disease symptoms of hypothyroidism and hypoadrenalism, respectively • Prolactin deficiency results in failure of postpartum lactation Hypopituitarism Sheehan syndrome 70-90% (≥75%) parenchymal loss Postpartum necrosis of anterior pituitary Congenital (rare): Mutation Pit-1 Pregnancy Acquired Hypertrophy/Hyperplasia of Lactotroph – Tumor or Other mass lesion: Non-functioning Not increase blood supply adenoma, metastatic tumor, cyst etc. – Ablation by surgery or radiation Blood loss during delivery – Ischemic necrosis and Sheehan syndrome Agalactia, amenorrhea, hypothyroidism, – Empty sella syndrome: Primary & Secondary adrenocortical insufficiency – Pituitary apoplexy – Inflammatory lesion 6 Posterior Pituitary Syndromes Diabetes insipidus Clinically significant: • The clinical manifestations of DI • Diabetes insipidus • SIADH – excretion of large volumes of dilute urine with an inappropriately low specific gravity. – Serum sodium and osmolality are increased owing to excessive renal loss of free water, resulting in thirst and polydipsia. – Life-threatening dehydration: Patients who can not drink adequate water to compensate for urinary losses Diabetes insipidus Syndrome of inappropriate ADH secretion: SIADH • ADH deficiency Æ Excessive urination (polyuria) owing to an inability of the Water retention, hyponatremia, hypotonicity kidney to resorb water properly from the Excess ADH: urine • Etiology: a variety of processes, including Paraneoplastic secretion: Small cell lung CA – Head trauma Tumor trauma inflammation – Tumors – Inflammatory disorders of the Pulmonary lesion hypothalamus and pituitary Brain lesion – Effect from Brain surgery Drugs 7 Thyroid gland: two cell types Thyroid follicular cells – forming follicles: converting thyroglobulin into thyroxine (T4) and Thyroid gland triiodothyronine (T3) and releasing into the systemic circulation Parafollicular cell (C-cell) – minor population arranging in small clusters in the interstitium: producing calcitonin Ectopic thyroid gland most commonly located at the base of the tongue (lingual thyroid) or at other sites abnormally high : consists of two bulky lateral lobes connected in the neck by a relatively thin isthmus, usually located below and anterior to the larynx +/- presence of a pyramidal lobe 8 Thyroglossal Duct Cyst What is “Goiter” ? • Goiter – enlargement of thyroid gland (not specific term, not specific etiology and associated with decreased or increased hormone output) – Toxic goiter: thyroid enlargement associated with increase thyroid hormone output – Non-toxic goiter: thyroid enlargement •Remnant of thyroglossal duct with normal hormonal level •Midline of neck •Move related to tongue movement Thyroid enlargement: diffuse or nodular Cystic lesion is lined • Irregular multinodular enlargement of the by squamous or entire thyroid: Multinodular goiter in elderly respiratory • Focal nodular enlargement within the epithelium and thyroid: Thyroid tumor presence of thyroid follicles at the cystic • Symmetrical slightly nodular firm wall enlargement of the whole thyroid: Hashimoto’s thyroiditis • Symmetrical enlargement of the thyroid: Graves’ disease or in puberty/ pregnancy 9 Thyrotoxicosis vs Hyperthyroidism Disorders Associated with Thyrotoxicosis • Thyrotoxicosis - hypermetabolic state Secondary hyperthyroidism caused by elevated circulating levels of • TSH-secreting pituitary adenoma (rare) free T3 and T4 Not Associated with Hyperthyroidism • Hyperthyroidism - hyperfunction of the • Subacute granulomatous thyroiditis thyroid gland (painful) • Most of thyrotoxicosis caused by • Subacute lymphocytic thyroiditis (painless) hyperthyroidism • Struma ovarii (ovarian teratoma with • Hyperthyroidism: Primary or Secondary ectopic thyroid) • Factitious thyrotoxicosis (exogenous thyroxine intake) Disorders Associated with Clinical manifestations of Thyrotoxicosis thyrotoxicosis Primary hyperthyroidism • excess thyroid hormone and overactivity of sympathetic nervous system • Diffuse toxic hyperplasia (Graves disease) – Increase in the basal metabolic rate: soft and • Hyperfunctioning ("toxic") multinodular warm and flushed skin, heat intolerance with goiter increased sweating and weight loss (despite • Hyperfunctioning ("toxic") adenoma increased appetite) • Hyperfunctioning thyroid carcinoma • Iodine-induced hyperthyroidism – Cardiac manifestations are among the earliest and most consistent features of • Neonatal thyrotoxicosis associated with maternal Graves disease hyperthyroidism: Tachycardia, palpitations, and cardiomegaly 10 – Overactivity of the sympathetic nervous system produces tremor, hyperactivity, Hypothyroidism emotional lability, anxiety, inability to concentrate, and insomnia and Proximal • Disease effect structure or function muscle weakness (thyroid myopathy) derangement that interferes with the – Ocular changes: wide, staring gaze and lid production of adequate levels of thyroid lag and thyroid ophthalmopathy associated hormone. with proptosis in Graves disease • Divided into: primary and secondary – Sympathetic hyperstimulation of the gut categories, depending on intrinsic results in hypermotility, malabsorption, and abnormality in the thyroid or occurs as a diarrhea result of pituitary disease; rarely, hypothalamic failure is a cause of tertiary – Osteoporosis: Thyroid hormone stimulates hypothyroidism bone resorption Cause of Hypothyroidism Primary • Thyroid storm: abrupt onset of severe • Developmental (thyroid dysgenesis: PAX-8, TTF-2, hyperthyroidism. TSH-receptor mutations) • Apathetic hyperthyroidism refers to • Thyroid hormone resistance syndrome (TRβmutations) thyrotoxicosis occurring in the elderly • Surgery, radioiodine therapy, or external radiation • Diagnosis of hyperthyroidism: Clinical and • Autoimmune hypothyroidism: Hashimoto lab such as TSH, T3 and T4 thyroiditis* • Iodine deficiency* – Primary hyperthyroidism: decrease TSH, • Drugs (lithium, iodides, p-aminosalicylic acid)* Increase T3 and T4 • Congenital biosynthetic defect (dyshormonogenetic goiter)* Secondary: Pituitary failure Tertiary: Hypothalamic failure
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