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Hypothalamus and Pituitary Gland

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