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Chapter 20 Endocrine Disease Physical Signs of Endocrinopathy 1) Weakness (most frequent complaint).

With weight loss: adrenal insufficiency, hyperthyroidism, and diabetes mellitus Without weight loss -hypothyroidism, hypopituitarism, hyperparathyroidism, hyperaldosteronism. 2) Menstrual irregularities - hypothyroidism, adrenogenital syndrome, and ovarian neoplasm. 3) Hirsutism - adrenal dysfunction 4) Loss of hair - Cushing, hypothyroidism, and hypopituitarism 5) Loss of libido - usually associate with anterior pituitary disease. Also seen in diabetes mellitus. 6) Obesity - diabetes mellitus, hypothyroidism, hypopituitarism, and Cushing. 7) Gynecomastia - adrenal tumors 8) Hypertension - hyperaldosteronism, hyperparathyroidism, pheochromocytoma 9) Polyuria & polydipsia - diabetes mellitus

I(a) ANTERIOR PITUITARY: Hyperfunction - Most common causes are tumors (prolactinoma most common 20-30%)

Growth Hormone producing tumors are the second most common hormone producing tumor that results in pituitary hyperfunction. In adults it is seen as acromegaly (growth only occurs where growth centers remain - jaw, finger and toe joints. In children, where growth centers are still active, increased growth hormone causes Gigantism.

Increased activity of the adrenal cortex causes hypercortisolism. Hypercortisolism is Cushings Syndrome. There are other causes of Cushings Syndrome. When it is caused by increased production of ACTH in the pituitary it is caused Cushings Disease.

HypofunctionMost cases of anterior pituitary hypofunction are due to: --- adenomas (non-secretory)

Disease States: Endocrine disease can be broadly classified ashyperfunction hypofunction neoplasia - micro (<3mm) - and macroadenomas (>3mm)

---ischemic necrosis of the pituitaryrequires 75% destruction ---destruction of the gland by surgery or radiation

Clinical manifestations of ant pituitary hypofnctn depends on the specific hormones lacking:

-- In children: dwarfism(pituitary dwarfs differ from achondroplastic dwarfs) -- In adults: decreased prolactin--- lactation failure Decreased ACTH--- hypoadrenalism Decreased TSH---- hypothyroidism

I (b): POSTERIOR PITUITARY: Axon terminals in the neurohypophysis store two hormones: ADH and oxytocin. As a practical matter, only decreased ADH production causes clinical problems-Diabetes insipidus - lack of ADH, frequent urination, dehydration.

2.Hypothyroid - 4 types: caused by anything that interferes with thyroid hormone prod. 1) Developmental - (congenital - cretinism),

In older children and adults the condition is called myexedema.

II. THYROID Gland Disease: see table 20-2

1.Hyperthyroid - thyrotoxicosis. A hypermetabolic state with increased stimulation of the sympathetic system. Diagnosed by measuring serum TSH(!) and T4(^) levels. Most associated with autoimmune diseases.

2) Goiter- enlargement of the thyroid gland. Impaired thyroid hormone production. The most common thyroid disease. Typically, in the USA, goiter is sporadic and for unknown reasons.
Endemic goiter - lack of iodine in diet due to environmental factors Nodular & multinodular goiters - asymmetrical, irregular enlargement. Persons with nodular goiters may be euthyroid.

Signs: heat intolerance, muscle weakness, ocular protrusion, tachycardia.

The most notable hyper thyroid state is Graves Disease.

Graves disease - triad of a) thyrotoxicosis (100%), b) exophthalmia (40%), and c) myxedema (~20%) - (pretibial classic). 20-40 years of age and females 7X > males. Etiology - autoimmune disorder (but not to one specific antigen). Predominately caused by antibodies binding the TSH receptor and turning on adenylate cyclase (kicks hormone production into high gear). Cause of exophthalmia is not clear. Testing - Elevated T3 and T4 levels AND depressed TSH.

3) Thyroiditis - Inflammation. Many causes- most common is Hashimoto thyroiditis.

Hashimoto - Most common thyroiditis. Autoimmune disease at the other end of the spectrum from Graves disease---- most common cause of hypothyroidism. B-cells produce antibodies that block the action of TSH. 45-65 years of age. Females 1020 times more frequently. Diffuse, symmetrical enlargement. May start with thyrotoxicosis. Increased risk of B cell lymphomas (remember most lymphomas are B cell type).

4) Thyroid Neoplasia Benign Adenomas - Most follicular, usually solitary, most are cold. Adenomas rarely undergo malignant transformation. Males>females, younger>older.

IV. ADRENAL CORTEX DISEASE: Disease related to hyper & hypofuction & Mass affects A. Cortical hyperfunction Hyperfunction produces syndromes related to the overproduction of 3 classes of hormones: 1. Increased Cortisol (Cushing Syndrome)

Malignant Uncommon in USA. Most common is papillary carcinoma. Papillary Carcinoma - Most common malig neoplasm (~80%). predom in females. History or thyroid irradiation increases risk. . ~80% 5 year survival rate

2. Increased Mineralcorticoids (Hyperaldosteronism) 3. Increased Androgens (Virilizing Syndromes) 1.Cushing syndrome: most cases caused by the administration of exogenous adrenocortical hormones. The rest are caused as seen in Figure 20-35.

Medullary carcinoma represents about 5% of thyroid cancers.80% are spontaneous; HOWEVER, the rest are assoc w/ MEN syndr (MEN II & III - AKA Features - hypertension, weight gain early on then moon facies, buffalo hump, IIa & IIb). Of C cell origin. 50% five year survival. They produce a variety of truncal obesity, weakness, cutaneous striae, osteoporosis, hirsutism, and mental hormones & symptoms are related to which hormones are produced. distrubances. Suppression of immune responses. Since glucocorticoids induce gluconeogenesis, hyperglycemia and other indicators of diabetes mellitus are seen. III. PARATHYROID GLAND DISEASE. Hyperfunction - Activity of the parathyroids are affected by serum calcium levels and 2. Hyperaldosteronism: Excessive levels of aldosterone causes Na retention & K+ not a hypothalamic feedback loop. excretion leading to hypertension. Caused by a neoplasm or cortical hyperplasia. 2 forms: Primary: usually caused by an adenoma. Causes hypercalcemia via increased 3. Adrenogenital Syndromes: Excess androgens caused by adrenal disorders and parathyroid hormone. May be sporadic or be associated with a MEN syndrome. Clinical gonadal disorders. Tumors are often the cause of adrenal cortical increased production findings include osteoporosis, renal stones, depression and muscular weakness. of androgens. Clinical problems include masculinization in the female and enlargement of external genitalia and precocious puberty. Secondary: often do to renal disease. Causes bone lesion called Brown tumor of hyperparathyroidism.

B. Adrenal Cortical Hypofunction: As with hyper, hypofunction can be caused primarily by adrenal disease or b/c of secondary diseases. See Table 20-8. Addison disease: Results from progressive destruction of the adrenal cortex. About 90% of cortex has to become nonfunctional before symptoms arise. Causes ACUTE DISEASE: sudden withdrawal of steroid therapy. CHRONIC DISEASE: autoimmune disease (90% of cases) and infections. SYMPTOMS, chronic disease: progressive weakness, easy fatigability, nausea and weight loss, hyperpigmentation, hypotension and hypoglycemia. SYMPTOMS, acute disease: adrenal crisis, which consists of severe hypotension, shock and coma from sudden decreases in aldosterone. Most important disease:

C. Adrenal Neoplasms: Adrenal cortex may have functional or nonfunctional adenomas and carcinomas. The adrenal medulla is the site of the pheochromocytoma. Pheochromocytoma - rare but these are significant because they secrete epinephrine & norepinephrin (catecholamines are strong vasopressors - increase BP). Rule of 10s: 10% associated w/MEN syndrome, 10% malignant, 10% bilateral, & 10% extra-adrenal. Features - HT w/associated tachycardia, headache, palpitations, tremor, diaphoresis. Elevated vanillylmandelic acid, a catecholamine metabolite found in the urine.

MEN SYNDROMES - MEN IIa and IIb (II and III) most significant for us as dentists. MEN IIa (II) - Sipple syndr. Pheochromocytoma, thyroid medullary carcinoma & primary hyperparathyroidism. MEN IIb (III) William syndr. Like IIa - also have neuromas of skin & mucous membr.