Endocrine Disorders

Chapter 22 Endocrine Disorders



I. Overview of Endocrine Disease

A. Negative feedback loops

1. Control an increase or decrease in hormone production


Negative feedback: ↑ calcium, ↓ PTH; ↓ calcium, ↑ PTH



2. Example—increased calcium decreases parathyroid hormone (PTH).

B. Stimulation tests

1. Evaluate hypofunctioning disorders

• Example—adrenocorticotropic hormone (ACTH) stimulation test is used in the workup of hypocortisolism.


Endocrine gland hypofunction: use stimulation tests


2. Causes of hypofunction

a. Autoimmune destruction


Endocrine gland hypofunction: most common cause is autoimmune disease


• Examples—Addison’s disease, Hashimoto’s thyroiditis

b. Infarction

• Example—Sheehan’s postpartum necrosis, Waterhouse-Friderichsen syndrome

c. Decreased hormone stimulation

• Example—decreased thyroid-stimulating hormone in hypopituitarism

d. Enzyme deficiency, infection, neoplasia, congenital disorder

C. Suppression tests

1. Evaluate hyperfunctioning disorders

• Example—dexamethasone suppression test evaluates hypercortisolism.


Endocrine gland hyperfunction: use suppression tests


2. Most hyperfunctioning disorders cannot be suppressed.

• Notable exceptions are prolactinoma and pituitary Cushing syndrome.


Endocrine gland hyperfunction: pituitary Cushing syndrome and prolactinoma can be suppressed


3. Causes of hyperfunction

• Adenoma, acute inflammation, hyperplasia, cancer


Endocrine gland hyperfunction: most common cause is a benign adenoma


II. Hypothalamus Disorders

A. Tumors altering hypothalamic function

1. Pituitary adenoma (see section IV)

• Most common tumor affecting the hypothalamus

2. Craniopharyngioma (see section IV)

3. Midline hamartoma

• Not a neoplasm

4. Langerhans histiocytosis (refer to Chapter 13)

B. Inflammatory disorders altering hypothalamic function

1. Sarcoidosis (refer to Chapter 16)

• Produces granulomatous inflammation

2. Meningitis (refer to Chapter 25)

C. Clinical findings of hypothalamic dysfunction

Hypothalamic dysfunction: secondary hypopituitarism, CDI, ↑ prolactin; precocious puberty, visual field defects, mass effects (hydrocephalus)


1. Secondary hypopituitarism

• No releasing hormones to stimulate the anterior pituitary

2. Central diabetes inspidus (CDI)

• Antidiuretic hormone (ADH) is synthesized in the hypothalamus.

3. Hyperprolactinemia

• Loss of dopamine inhibition causes galactorrhea.

4. Precocious puberty

• Most common cause in boys is a midline hamartoma.


“True” precocious puberty implies a central nervous system (CNS) origin for the disorder, but pseudo-precocious puberty implies a peripheral cause (e.g., adrenogenital syndrome). True precocious puberty in boys is the onset of puberty before 9 years of age. The most common cause is a midline hamartoma in the hypothalamus. True precocious puberty in girls is the onset of puberty before 8 years of age. In most cases, it is idiopathic and less likely to be caused by a midline hamartoma.



Precocious puberty: true if CNS origin, pseudo if peripheral cause


5. Visual field disturbances

• Usually bitemporal hemianopia

6. Mass effects

• Produces obstructive hydrocephalus (refer to Chapter 25)

7. Growth disorders

• Dwarfism in children

8. Kallmann’s syndrome (refer to Chapter 20)

III. Pineal Gland Disorders

A. Clinical anatomy

1. Midline location above the quadrigeminal plate


Pineal gland: midline above quadrigeminal plate


2. Site for melatonin production

a. Superior cervical sympathetic ganglia stimulates receptors on pinealocytes.

• Causes release of melatonin into spinal fluid and blood

b. Melatonin functions


Melatonin: chemical messenger of darkness


(1) Important in sleep/moods and circadian rhythms

• Released at night

(2) Used in the treatment of sleep and mood disorders

B. Disorders

1. Dystrophic calcification of the pineal gland begins in childhood.


Pineal gland: commonly undergoes dystrophic calcification


a. Useful in showing shifts due to mass lesions in the brain

b. Approximately 80% are calcified between 70 and 80 years old.

2. Pineal tumors

a. Majority are germ cell tumors resembling seminomas.


Pineal gland: majority are germ cell tumors


b. Minority of tumors are teratomas.

C. Clinical findings

1. Visual disturbances

• Paralysis of upward conjugate gaze (Parinaud’s syndrome; see Fig. 25-5)


Pineal gland tumors: paralysis of upward gaze (“setting sun” sign)


2. Obstructive hydrocephalus

• Due to compression of the aqueduct of Sylvius in the third ventricle

IV. Pituitary Gland Disorders

A. Anterior pituitary hypofunction

1. Epidemiology

a. Partial or complete loss of secretion of one or more hormones

• Infarctions of the pituitary invariably lead to panhypopituitarism


Pituitary infarction: invariably produces panhypopituitarism


b. Increased incidence of vascular or cerebrovascular disease

c. Types of pituitary dysfunction

(1) Primary hypopituitarism (pituitary dysfunction)

• Approximately 75% of the gland must be destroyed.

(2) Secondary hypopituitarism (hypothalamic dysfunction)

• Decreased hypothalamic releasing factors

2. Causes of hypopituitarism

a. Nonfunctioning (null) pituitary adenoma (Fig. 22-1)

image

22-1: Pituitary adenoma. The interrupted arrow shows a well-circumscribed mass that has almost completely replaced the pituitary gland. A thin rim of sella turcica is present at the base of the tumor. The solid arrow shows the optic nerve and its proximity to the sella turcica.


(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 444, Fig. 9-20.)



Hypopituitarism in adults: most common cause is nonfunctioning adenoma


(1) Most common cause

(2) Microadenoma < 10 mm; macroadenoma > 10 mm

(3) Association with multiple endocrine neoplasia (MEN) I syndrome


MEN I: pituitary adenoma, hyperparathyroidism, pancreatic tumor


(4) MEN I syndrome findings include pituitary adenoma, hyperparathyroidism, pancreatic tumor (Zollinger-Ellison syndrome or insulinoma).

b. Craniopharyngioma

(1) Most common cause of hypopituitarism in children


Hypopituitarism in children: most common cause is craniopharyngioma


(2) Benign pituitary tumor derived from Rathke’s pouch remnants


Rathke’s pouch is an ectodermal derivative derived from the oral cavity. It develops into the anterior lobe of the pituitary gland.


(3) Located above the sella turcica


Rathke’s pouch: develops anterior pituitary


• Extends into sella turcica and destroys the gland

(4) Cystic tumor with hemorrhage and calcification

(5) Commonly causes bitemporal hemianopia

(6) May produce central diabetes insipidus

c. Sheehan’s postpartum necrosis


Sheehan’s postpartum necrosis: sudden cessation of lactation; pituitary infarction secondary to shock


(1) Hypovolemic shock (e.g., blood loss) causes infarction.

(2) Sudden cessation of lactation due to loss of prolactin

• Eventual development of hypopituitarism


The pituitary gland doubles in size during pregnancy due to synthesis of prolactin. Prolactin release is inhibited by estrogen and progesterone during pregnancy.


d. Pituitary apoplexy

(1) Term “apoplexy” refers to a sudden onset of neurologic dysfunction

(2) Most often due to hemorrhage/infarction of preexisting pituitary adenoma

(3) Predisposing factors

• Trauma, pregnancy (Sheehan’s postpartum necrosis, a nontumorous cause), treatment of a prolactinoma with bromocriptine

(4) Clinical findings; sudden onset of

(a) Headache, mental status dysfunction, visual disturbances

(b) Hormone dysfunction


Pituitary apoplexy: hemorrhage into preexisting adenoma


e. Sickle cell anemia

• Pituitary infarction from vascular occlusion by irreversibly sickled cells

f. Lymphocytic hypophysitis

(1) Female dominant autoimmune destruction of the pituitary gland

(2) Occurs during or after pregnancy


Lymphocytic hypophysitis: autoimmune destruction; occurs during or after pregnancy


g. Empty sella syndrome

(1) Epidemiology

(a) Radiologic studies show an empty sella turcica.

(b) Primary and secondary types

(2) Primary type

(a) Anatomic defect above pituitary


Empty sella syndrome: subarachnoid space extends into sella; ↑ CSF pressure compresses gland


(b) Subarachnoid space extends into sella turcica and fills up with cerebrospinal fluid (CSF).

(c) Increase in pressure on the pituitary gland causes it to flatten out.

(d) Often associated with women who are obese and have high blood pressure


Empty sella syndrome: obese with hypertension


(3) Secondary type

• Regression in size due to radiation, trauma, surgery

h. Hypothalamic dysfunction (see section II)

3. Clinical and laboratory findings of pituitary hypofunction (Table 22-1 and Fig. 22-2)

4. Diagnosis

a. CT scan or MRI (better test) of sella turcica

b. Stimulation tests for the various deficiencies

5. Treatment

a. Surgery for tumors (usually transsphenoidal)

b. Hormone replacement for deficiencies

B. Posterior pituitary hypofunction

1. Normal function of posterior pituitary

a. Stores ADH

(1) Controls total body water

(2) Presence of ADH produces concentration of urine.

(3) Absence of ADH produces dilution of urine.


Table 22-1 Clinical Findings in Hypopituitarism

image

image

22-2: Schematic of the metyrapone test: a normal response (A) and the response expected in hypopituitarism (B). See text for discussion. ACTH, adrenocorticotropic hormone.



Posterior pituitary: storage of ADH and release of oxytocin


b. Releases oxytocin

• Produces milk ejection and uterine contractions

2. Refer to Chapter 4 for discussion of diabetes insipidus

C. Pituitary hyperfunction disorders

1. Prolactinoma

a. Epidemiology

(1) Benign adenoma


Prolactinoma: most common pituitary tumor


(2) Overall most common pituitary tumor (35%)

(3) Secrete growth hormone as well in 7% of cases

b. Clinical and laboratory findings


Prolactinoma: secondary amenorrhea + galactorrhea


(1) Women

(a) Secondary amenorrhea

• Prolactin inhibits gonadotropin-releasing hormone (GnRH).

(b) Galactorrhea (see Fig. 21-34)

(2) Men


Prolactinoma in men: impotence due to loss of libido; headache


(a) Impotence

• Loss of libido due to decrease in testosterone

(b) Headache

• Tumors tend to be larger than in women.

(c) Not enough estrogen-dependent breast tissue to produce galactorrhea

(3) Serum prolactin level is usually >200 ng/mL.

(4) Decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

• Due to decreased GnRH

c. Other causes of galactorrhea (refer to Chapter 21)

d. Treatment


Rx prolactinoma: dopamine analogues; surgery


(1) Dopamine analogues (e.g., cabergoline)

(a) Tumor does respond to suppression.

• Shrinks in <50% of cases

(b) Restores gonadal function in 70% to 90% of cases

(2) Surgery if macroadenomas

2. Growth hormone (GH) adenoma

a. Epidemiology

(1) Accounts for 20% of all pituitary adenomas

(2) Functions of GH


GH: gluconeogenesis; ↑ amino acid uptake in muscle; stimulate IGF-1 in liver


(a) Stimulates liver synthesis/release of insulin growth factor (IGF)-1

(b) Stimulates gluconeogenesis and amino acid uptake in muscle

(c) Negative feedback relationship with glucose and IGF-1

(d) Antinatriuretic action (retains sodium)

(3) Functions of IGF-1


IGF-1: stimulates bone, cartilage, soft tissue growth


• Stimulates growth of bone (linear and lateral), cartilage, soft tissue

b. Clinical and laboratory findings


Gigantism: ↑ linear/lateral bone growth in children; epiphyses not fused


(1) Children develop gigantism.

(a) Due to increased linear bone growth (epiphyses have not fused)

(b) Lateral bone growth also increased

(2) Adults develop acromegaly (Fig. 22-3)

image

22-3: Acromegaly showing the patient before development of the tumor (left) and after development of the tumor (right). Note the coarse facial features and enlargement of the jaw and lips.


(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 407.)



Acromegaly: ↑ lateral bone growth only (epiphyses not fused), organomegaly, hyperglycemia


(a) Increased lateral bone growth (e.g., hands, feet, jaw)

• No linear growth because epiphyses are fused

(b) Prominent jaw

• Spacing between the teeth


Acromegaly: comparing old versus new photograph is valuable diagnostic tool


(c) Frontal bossing

• Enlarged frontal sinus increases the hat size.

(d) Macroglossia, cardiomyopathy (cause of death)

(3) Increased GH and IGF-1 (more sensitive test than GH)

• Hormones are not suppressed by glucose administration.

(4) Hyperglycemia

• Due to increase in gluconeogenesis

(5) Hypertension

• Sodium retention related to increased GH and insulin (hyperglycemia increases its release)


Acromegaly: heart failure from cardiomyopathy is a common cause of death


(6) Visceral organomegaly with dysfunction

• Heart, liver, kidneys, thyroid

(7) Muscle weakness (myopathy); cardiomyopathy

(8) Headache and visual field defects

• Enlarged sella turcica

c. Diagnosis

(1) Imaging with CT scan, MRI (best study)

(2) Suppression tests

d. Treatment

(1) Transsphenoidal surgery

(2) If surgery does not correct

• Somatostatin and dopamine analogues; GH receptor antagonists

3. Syndrome of inappropriate ADH (SIADH)

• Refer to Chapter 4 for complete discussion of SIADH

V. Thyroid Gland Disorders

A. Steps in thyroid hormone synthesis

1. Trapping of iodide is thyroid-stimulating hormone (TSH)–mediated.

2. Oxidation of iodides to iodine is peroxidase-mediated.

3. Organification

a. Iodine is incorporated into tyrosine to form MIT (monoiodotyrosine) and DIT (diiodotyrosine).

b. It is TSH-mediated.

4. Coupling of MIT with DIT produces triiodothyronine (T3).


Thyroid hormone: iodide attached to tyrosine


5. Coupling of DIT with DIT produces thyroxine (T4).

6. Hormones are stored as colloid.

7. Proteolysis of colloid by lysosomal proteases is TSH-mediated.


TSH: mediates trapping, organification, and proteolysis


8. T4 and T3 bind to thyroid-binding globulin (TBG).

• One third of TBG binding sites are normally occupied.

9. Free T4 (FT4) is peripherally converted to free T3 (FT3) by an outer ring deiodinase.


FT4: prohormone; rendered metabolically active by outer ring deiodinase (FT3)


a. FT3 is a metabolically active hormone.

b. FT4 is considered a prohormone.

c. FT4 and FT3 have a negative feedback relationship with TSH.


FT4/FT3: negative feedback with TSH


(1) An increase in FT4/FT3 should produce a decrease in TSH.

(2) A decrease in FT4/FT3 should produce an increase in TSH.

B. Functions of thyroid hormone

1. Control of total energy expenditure

2. Growth and maturation of tissue

3. Turnover of hormones and vitamins

4. Cell regeneration

C. Thyroid function tests

1. Total serum T4 (Fig. 22-4A)

a. Represents T4 bound to TBG and free (unbound) T4 (FT4)

image

22-4: Schematic of total serum thyroxine (T4) in a normal individual (A) and an individual with an increase in thyroid-binding globulin (TBG) (B). The actual numbers do not represent the true concentration of T4 and free T4 (FT4). The bars represent TBG and the circles are T4 bound to TBG and T4 that is free (FT4). FT4 normally has a negative feedback with thyroid-stimulating hormone (TSH). Refer to the text for a complete discussion.


(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 19-1.)



Total serum T4: T4 bound to TBG + FT4


• Note: the values used in the schematic do not represent true values for each of the components.

(1) Figure 22-2A shows one third of TBG binding sites on two TBGs occupied by T4.

• Total of 6 T4 bound to TBG

(2) There are 4 FT4.

(3) The total serum T4 is 10.

(4) TSH is normal, because FT4 is normal.

b. Increase in TBG synthesis increases total serum T4 (Fig. 22-4B).


Estrogen: ↑ TBG which ↑ total serum T4 but not FT4


(1) Estrogen increases the synthesis of TBG.

• Pregnancy, oral contraceptive pill, hormone replacement

(2) Extra TBG automatically has one third of its binding sites occupied by T4.

• Total of 9 T4 bound to TBG

(3) The 3 T4 used to bind to the extra TBG are replaced by 3 T4 released from the thyroid gland.

(4) FT4 remains normal (4).

(5) Total serum T4 is increased (9 + 4 = 13).

(6) TSH is normal, because FT4 is normal.

(7) No signs of thyrotoxicosis are present.

c. Decrease in TBG synthesis decreases total serum T4.


↓ TBG: ↓ total serum T4 but not FT4


(1) Causes of a decreased TBG

• Anabolic steroids, nephrotic syndrome (urinary loss)

(2) Total serum T4 is decreased.

(3) FT4 and TSH remain normal.

(4) No signs of hypothyroidism


Alterations in TBG: alter total serum T4; no effect on FT4 and TSH


d. Normal TBG with increase or decrease in total serum T4

(1) Increase or decrease in FT4 must be present.

(2) Increased FT4—Graves’ disease, thyroiditis

(3) Decreased FT4—hypothyroidism

2. Serum TSH

a. Best overall screening test for thyroid dysfunction


Serum TSH: best screening test for thyroid dysfunction


b. Increased TSH

• Primary hypothyroidism

c. Decreased TSH

(1) Thyrotoxicosis (e.g., Graves’ disease)

(2) Hypopituitarism/hypothalamic dysfunction

• Causes secondary/tertiary hypothyroidism, respectively

3. 123I radioactive uptake

a. Evaluates synthetic activity of the thyroid gland


123I uptake: evaluates synthetic activity of thyroid gland


• Iodide is used to synthesize thyroid hormone.

b. Increased uptake indicates increased synthesis of T4.


↑ 123I uptake: increased synthesis of thyroid hormone; Graves’ disease


• Examples—Graves’ disease, toxic nodular goiter

c. Decreased uptake of 123I

(1) Inactivity of the gland

• Example—patient taking thyroid hormone

(2) Inflammation of the gland

• Example—acute/subacute/chronic thyroiditis


↓ 123I uptake: thyroiditis; patient taking excess thyroid hormone


d. Evaluates functional status of thyroid nodules

(1) Decreased uptake in a nodule

• “Cold” nodule—cyst, adenoma, cancer (Fig. 22-5)

image

22-5: Nuclear scan of thyroid showing “cold” nodules (lack of uptake or radioactive iodine) in both lobes of the thyroid (arrows).


(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 531, Fig. 2.)



Cold nodule: ↓ 123I uptake


(2) Increased uptake in a nodule

• “Hot” nodule—toxic nodular goiter


Hot nodule: ↑ 123I uptake


4. Thyroglobulin

• Marker for thyroid cancer

D. Lingual thyroid

1. Failed descent of thyroid anlage from the base of the tongue


Mass at base of the tongue: lingual thyroid


• Usually represents all of the thyroid tissue

2. Clinical findings

a. Dysphagia for solids

b. Mass lesion

3. 123I scan locates the lesion

• Also identifies any other thyroid tissue that is present

4. Treatment

a. Suppression with thyroxine

• Lingual thyroids are usually hypofunctional.

b. Ablation with radioactive iodine

c. Surgery if obstructive

E. Thyroglossal duct cyst

1. Cystic midline mass that is close to or within the hyoid bone (Fig. 22-6)

image

22-6: Patient with a midline thyroglossal duct cyst.


(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 52, Fig. 103.)



Thyroglossal duct cyst: cystic midline mass


2. Surgery with removal of the proximal duct and hyoid bone


Branchial cleft cyst: located in the anterolateral neck


F. Thyroiditis

1. Acute thyroiditis

a. Bacterial infection (e.g., Staphylococcus aureus)

b. Clinical findings

(1) Fever


Acute thyroiditis: thyrotoxicosis; ↓ 123I uptake


(2) Tender gland with painful cervical adenopathy

(3) Initial thyrotoxicosis from gland destruction

• Increased serum T4, decreased serum TSH

(4) Permanent hypothyroidism is uncommon.

c. Decreased 123I uptake

d. Treatment

• Penicillin or ampicillin

2. Subacute granulomatous thyroiditis

a. Viral infection (e.g., coxsackievirus, mumps)

b. Occurs most often in women 40 to 50 years old

c. Granulomatous inflammation with multinucleated giant cells

d. Clinical findings

(1) Most common cause of a painful thyroid gland


Subacute granulomatous thyroiditis: most common cause of painful thyroid; virus induced; no adenopathy


(2) Often preceded by an upper respiratory infection

(3) Cervical adenopathy is not prominent.

(4) Initial thyrotoxicosis from gland destruction

• Increased serum T4, decreased serum TSH

(5) Permanent hypothyroidism is uncommon.

e. Decreased 123I uptake

f. Self-limited; does not require treatment

3. Hashimoto’s thyroiditis

a. Epidemiology

(1) Autoimmune thyroiditis


Hashimoto’s thyroiditis: autoimmune thyroiditis


(2) Incidence increases with age

(3) More common in women than men

(4) Human leukocyte antigen (HLA)-Dr3 and -Dr5 associations

(5) Increased incidence in:

• Turner’s syndrome, Down syndrome, Klinefelter’s syndrome

(6) Increased incidence of other autoimmune diseases (e.g., pernicious anemia)


Hashimoto’s thyroiditis: type IV (mainly) and type II hypersensitivity


b. Pathogenesis (multifactorial)

(1) Cytotoxic T cells destroy parenchyma (type IV hypersensitivity reaction, HSR)

• Initial thyrotoxicosis, eventual hypothyroidism

(2) Blocking antibodies against TSH receptor (type II HSR)

• Decrease hormone synthesis; type II hypersensitivity

(3) Helper T cells release cytokines attracting macrophages that damage tissue (type IV HSR)

(4) Antimicrosomal and thyroglobulin antibodies destroy parenchyma (type II HSR)

c. Gross and microscopic

(1) Enlarged, gray gland

(2) Lymphocytic infiltrate with prominent germinal follicles (Fig. 22-7)

d. Clinical findings

(1) Most common cause of primary hypothyroidism

image

22-7: Microscopic section of Hashimoto’s thyroiditis. Note the prominent germinal follicle and heavy infiltrate of lymphocytes throughout the gland with destruction of the thyroid follicles.


(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 522, Fig. 9-10.)



Hashimoto’s thyroiditis: most common cause of hypothyroidism


(2) Initial thyrotoxicosis from gland destruction

• Known as hashitoxicosis

(3) Signs of hypothyroidism (see later discussion)

(4) Risk factor for primary B-cell malignant lymphoma of the thyroid

4. Reidel’s thyroiditis

a. Fibrous tissue replacement of the gland

b. Extension of fibrosis into surrounding tissue


Reidel’s thyroiditis: fibrous tissue replacement of gland and surrounding tissue


• Can produce tracheal obstruction

c. Associated with other sclerosing conditions

• Example—sclerosing mediastinitis

d. Hypothyroidism may occur.

e. Treatment

(1) Initial treatment with corticosteroids

(2) Tamoxifen

• First-line therapy or if corticosteroids are unsuccessful

(3) Surgery

5. Subacute painless lymphocytic thyroiditis

a. Autoimmune disease that develops post partum


Subacute painless lymphocytic thyroiditis: develops post partum; progression to hypothyroidism


b. Gland lacks germinal follicles.

c. Clinical findings

(1) Abrupt onset of thyrotoxicosis due to gland destruction

(2) Gland is slightly enlarged and painless.

(3) Progresses to primary hypothyroidism in 40% to 50% of cases

(4) Antimicrosomal antibodies (50–80%)

d. Treatment

• Levothyroxine in the hypothyroid stage

G. Hypothyroidism

1. Reduced secretion of thyroid hormone


Hypothyroidism: hypometabolic


a. Patients are hypometabolic.

b. ↓ Basal metabolic rate; ↓ β-receptor/low density lipoprotein receptor synthesis

2. Causes

a. Hashimoto’s thyroiditis (90% of cases)

b. Subacute painless lymphocytic thyroiditis

c. Hypopituitarism, iodine deficiency, enzyme deficiency

d. Drugs

• Amiodarone, lithium, sulfonamides, phenylbutazone

e. Hypothalamic dysfunction/hypopituitarism (see sections II and IV, respectively)

f. Congenital (see later discussion)

3. Cretinism

a. Hypothyroidism in infancy or early childhood

b. Brain requires thyroxine for its maturation.


Brain: requires thyroxine for maturation


c. Causes

(1) Maternal hypothyroidism


Cretinism: most often caused by maternal hypothyroidism before fetal thyroid is developed


• Before the fetal thyroid is developed

(2) Enzyme or iodine deficiency

d. Clinical findings

(1) Severe mental retardation

(2) Increased weight and short stature


Cretinism: severe mental retardation


• Pituitary dwarfism—decreased weight and short stature

e. Treatment is thyroid hormone replacement.

4. Clinical findings in adult hypothyroidism

a. Proximal muscle myopathy

(1) Very common finding

(2) Increased serum creatine kinase


Hashimoto’s thyroiditis: muscle weakness common complaint; weight gain; dry, brittle hair


b. Weight gain

• Due to hypometabolic state with retention of water and salt

c. Dry and brittle hair; loss of outer one-third of eyebrow

d. Bradycardia (slow heart rate)

e. Coarse yellow skin

• Yellow skin due to less conversion of β-carotenes into retinoic acid

f. Periorbital puffiness, hoarse voice


Hashimoto’s thyroiditis: periorbital puffiness, hoarse voice; signs of myxedema


(1) Both of these are due to myxedema (Fig. 22-8)

(2) Increased hyaluronic acid in interstitial tissue

(3) Nonpitting edema

g. Fatigue, cold intolerance, constipation

image

22-8: Primary hypothyroidism in a patient with Hashimoto’s thyroiditis. The patient has a puffy face, particularly around the eyes, and coarse hair.


(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 325, Fig. 7-72.)



Hashimoto’s thyroiditis: cold intolerance, constipation


h. Menstrual irregularities

• Most often menorrhagia

i. Diastolic hypertension


Hashimoto’s thyroiditis: hypertension from sodium retention; delayed reflexes


• Due to retention of sodium and water

j. Congestive (dilated) cardiomyopathy with biventricular heart failure

k. Atherosclerotic coronary artery disease

l. Delayed recovery of Achilles reflex, mental slowness, dementia

5. Laboratory findings

a. Decreased serum T4, increased serum TSH


Primary hypothyroidism: ↓ serum T4/FT4; ↑ serum TSH, cholesterol


b. Antimicrosomal, antiperoxidase, and antithyroglobulin antibodies

• Hashimoto’s thyroiditis; subacute painless lymphocytic thyroiditis

c. Hypercholesterolemia

• Due to decreased synthesis of low-density lipoprotein (LDL) receptors

6. Treatment

a. Levothyroxine in small increments every 6–8 weeks

b. Bring serum TSH into the normal range (euthyroid state)

7. Myxedema coma

a. Causes

(1) Idiopathic; cold exposure

(2) Use of sedatives/opiates

(3) Acute illness

b. Clinical findings


Myxedema coma: stupor, hypothermia, hypoventilation; IV levothyroxine, corticosteroids


(1) Progressive stupor

(2) Hypothermia

(3) Bradycardia; hypoventilation

(4) Hypoglycemia, hypocortisolism, SIADH

c. Treatment

(1) Ventilatory support

(2) Treat hypothermia

(3) IV levothyroxine

(4) High doses of corticosteroids

d. Mortality rate is 20% to 50%.

H. Thyroid hormone excess

1. Classification

a. Thyrotoxicosis

• Describes hormone excess regardless of cause


Thyrotoxicosis: hormone excess from any cause


b. Hyperthyroidism

(1) Describes hormone excess due to increased synthesis


Hyperthyroidism: thyrotoxicosis due to excess synthesis of thyroid hormone


(2) Examples—Graves’ disease, toxic nodular goiter

2. Patients are hypermetabolic.

• Increase in the basal metabolic rate

3. Graves’ disease

a. Epidemiology

(1) Most common cause of hyperthyroidism and thyrotoxicosis


Graves’ disease: most common cause of hyperthyroidism and thyrotoxicosis


(2) Female dominant autoimmune disease

(3) HLA-B8 and HLA-Dr3 association

b. Pathogenesis

(1) T cells induce specific B cells to produce IgG antibodies against the TSH-receptor

(a) Stimulating type of antibody as opposed to a blocking antibody


Graves’ disease: anti-TSH receptor antibody, type II hypersensitivity


(b) Type II hypersensitivity reaction

(2) Antimicrosomal and thyroglobulin antibodies are present.

(3) Inciting events that may initiate onset of the disease

• Infection, withdrawal of steroids, iodide excess, post partum

c. Symmetrical, nontender thyromegaly

(1) Scant colloid

(2) Papillary infolding of the glands

d. Clinical features unique to Graves’ disease

(1) Infiltrative ophthalmopathy (exophthalmos; 50%)


Unique to Graves’: exophthalmos, pretibial myxedema, thyroid acropachy


(a) Proptosis and muscle weakness of the eye (Figs. 22-9 and 22-10)

(b) Due to adipose and glycosaminoglycans deposited in orbital tissue

image

22-9: Graves’ disease. The patient has exophthalmos and a diffuse enlargement of the thyroid gland (goiter).


(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 323, Fig. 7-61.)


image

22-10: Severe exophthalmos in Graves’ disease. Note the proptosis of the eye, increased vascularity of the conjunctiva, and the enlarged lacrimal gland.


(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 232, Fig. 10-35.)



Transient hyperthyroidism in fetus


(2) IgG-TSH receptor antibodies can cross placenta and produce transient hyperthyroidism in fetus

(3) Pretibial myxedema (1–2%; Fig. 22-11)

• Due to excess glycosaminoglycans (hyaluronic acid) in the dermis

(4) Thyroid acropachy

image

22-11: Pretibial myxedema in Graves’ disease. Note the thickened area of erythema involving the pretibial area and dorsum of the foot.


(Courtesy of R.A. Marsden, MD, St. George’s Hospital, Lodon.)



Thyroid acropathy: digital swelling and clubbing


(a) Digital swelling and clubbing of fingers

(b) Nails separate from nail bed (lifted up)

(c) Exophthalmos and pretibial myxedema usually present

4. Graves’ disease in the elderly (apathetic hyperthyroidism)


Graves’ disease in elderly: cardiac and muscle findings predominate; apathetic appearing


a. Cardiac abnormalities

• Atrial fibrillation, congestive heart failure

b. Muscle weakness, apathy

c. Thyromegaly

5. Toxic multinodular goiter (Plummer’s disease)


Toxic multinodular goiter: one or more nodules in a multinodular goiter becomes TSH-independent


a. One or more nodules in a multinodular goiter become TSH-independent.

b. See “hot” nodules with 123I scan

c. Distinctions from Graves’ disease

• Lack exophthalmos and pretibial myxedema

d. Treatment is surgery.

6. Clinical findings in all causes of thyrotoxicosis

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Jun 25, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Endocrine Disorders

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