Endocrine Pathology Lecture

EndocrinologyPathology Part 1

Big Sib Lecture 2014

Topics

• Pituitary• Thyroid• MEN syndromes

Pituitary Pathology

Anatomy

• Lies in the sella turcica

• Outside the blood brain barrier

• Posterior to optic chiasm

• Medial to cavernous sinuses, internal carotids, several cranial nerves

• Anterior to sphenoid sinus

Physiology

Anterior (Adenohypophysis)

• Produces AND Releases hormones

• Controlled by hypothalamus via releasing factors and inhibitory factors delivered via a venous system.

Posterior (Neurohypophysis)

• Stores and releases hormones but does NOT produce them

• Arises from the floor of the hypothalamus

• Connected to the hypothalamus via the pituitary stalko axons with cell bodies in the

supraoptic and paraventricular

nuclei

Hormones

Anterior (Adenohypophysis)

• Somatotrophs (GH) - 50%

• Gonadotrophs (FSH/LH) - 10%

• Lactotrophs (prolactin) - 15-20%o controlled by DA!

• Corticotrophs (ACTH) - 15-20%

• Thyrotrophs (TSH) - 5%

Posterior (Neurohypophysis)

• Oxytocin

• Vasopressin

Tumors• Majority in ANTERIOR

• Most common intracranial tumor of adolescents and young adults

• Symptomso hyperpituitarism → prolactin, GH, ACTHo hypopituitarism → decreased TSH, ACTH, LH/FSHo mass effect → bitemporal hemianopsia, cavernous sinus invasion, high

ICP, stalk compression (disinhibition of prolactin)● Adenomas (common) vs Carcinomas (rare)

○ Invasive adenoma (NOT carcinoma) = ·invasion of dura, sphenoid bone, cavernous sinus, or nasopharynx

○ Carcinoma = <1%, CSF spread, non-contiguous parenchymal spread, mets● Micro (<10mm) vs Macro (>10mm)

Type % Symptoms Histology Treatment

prolactinoma 30-50% Women - amenhorrea, galactorrhea, infertilityMen - impotence, low libido, infertility

95% - sparsely granulated, 5% - dense, misplaced exocytosis (away from vascular pole)

bromocriptine (DA agonist), surgery

growth hormone 25% - can be pure, mixed, plurihormonal

Child - giantism Adult - acromegaly, HTN, CAD

surgery

ACTH 15% Cushing’s Syndrome - weight gain, buffalo hump, moon facies, striae

Most are microadenomas, basophilic, densely granulated

Previously → B/L adrenalectomy lead to Nelson’s syndromeCurrent → tumor resection

Glycoprotein 10% Typically silent due to biologically inactive hormone

TSH, LH, FSH surgery

Null Cell 25-30% Mass effect, no hormones produced

IHC stains chromogranin,oncocytoma variant is pink due to mitochondria

surgery

Infarction • Ischemic → Sheehan’s syndrome

o postpartum necrosis of anterior pituitary o AP increases 2x during pregnancy but blood supply does not

increase (PP not as susceptible)o hemorrhage or shock during delivery o ischemic injury also caused by DIC, trauma, sickle cell, etc.

• Hemorrhagic → Pituitary Apoplexy o sudden hemorrhagic infarction of adenomao Symptoms → headache, diplopia, ocular nerve palsy,

hypopituitarism

Posterior Pituitary Pathology• Granular cell tumor

o arises from astrocytes within the PPo pink + granular → looks like oncocytic null cell adenoma

• Diabetes Insipitus o central (ADH deficiency) vs nephrogenic (inappropriate response to

ADH)o trauma, tumors, inflammation, spontaneous o excessive dilute urine → kidney unable to reabsorb H2Oo Serum hypernatremia, hyperosmolality

• SIADHo High ADH = excessive absorption of free H2Oo ectopic ADH from tumor (SCC of lung), drugs, infection, traumao Serum hyponatremia, cerebral edema, NO peripheral edema

Other Stuff• Giant Cell Granuloma

o inflammatory process that destroys the glando clinical and radiological appearance of null cell adenomao 3rd trimester/post-partum period in womeno mononuclear cells forming giant cells, edema, destruction of normal

endocrine cells

• Rathke’s Cleft Cysto embryological remnants destroy normal cells by accumulating

protienacious fluid causing expansion o pseudostratified columnar epithelial cells lining cyst that may also

contain apical cilia and goblet cells

ThyroidNormal Thyroid, notice follicles filled w/ colloid

Parafollicular C cells are stained here

makes thyroid hormone Makes calcitonin

Clinical presentation: Hypothyroidism vs

HyperthyroidismCold intoleranceWeight gain, decreased appetiteHypoactivity, lethargy, fatigue, weaknessConstipationDecreased reflexesMyxedema Dry, cool skin, coarse hairBradycardia, dyspnea on exertionsHyperprolactinemia

• Heat intolerance• Weight loss, increased appetite• Hyperactivity• Diarrhea• Increased reflexes• Pretibial myxedma• Warm, moist skin, fine hair• Chest pain, palpations arrhythmias

Hypothyroidism• Primary causes: developmental,

Thyroid hormone resistance syndrome, Postablative, Autoimmune, Iodine deficiency, Drugs (lithium, iodides), Congenital, thyroditis

• Secondary: Pituitary failure, hypothalamic failure (rare)

Clinical findings• Cretinism (in children)

• short stature, coarse facial features, protruding tongue, umbilical hernia

• Diagnosis: Elevated TSH and low T4

• early dx essential for prevention of growth / mental retardation and cardiac abnormalities

• Myxedema (in adult)- fatigue, weight gain, constipation, apathy, cold intolerance, decreased exercise capacity, SOB

Hashimoto Thyroiditis• Autoimmune disease causing hypothyroidism• Monozygotic twin concordance rate of 40%• Anti-thyroglobulin and anti-thyroid peroxidase

antibodies lead to antibody-dependent cell-mediated cytotoxicity

• Extensive infiltration by mononuclear inflammatory infiltrate, germinal centers

• Epithelial cells with Eosinophilic, granular cytoplasm = Hurthle cell

• May be hyperthyroid early in course (thyrotoxicosis during follicular reupture)

hashimotos

Lymphoid follicle at right

DeQuervian• Subacute (granulomatous) thyroiditis• Self limited hypothyroidism usually following a flu-like

illness • Painful thyroid w/ transient hyperthyroidism (2-6 weeks)• Findings – Increased ESR, jaw pain, early inflammation,

very tender thyroid, no prominent cervical adenopathy

Riedel Thyroiditis• “Rock hard” Riedel• Characterized by fibrosis of thyroid• Painless, fixed, asymmetrically

enlarged• Hard and fixed mass simulated thyroid

carcinoma, normally remain euthyroid, surgery necessary if compression of airway

Hyperthyroidism• Caused by elevated levels of T3 or T4• Secondary: TSH secreting pituitary adenoma (rare)• Primary (Caused by excess production of the gland)

• Graves disease• Hyperfunctioning toxic multinodular goiter• Hyperfunctioning toxic adenoma• Iodine-induced hyperthyroidism• Neonatal thyrotoxicosis associated w/ maternal Graves

disease

Graves Disease• Autoimmune disease caused by Thyroid-stimulating

immunoglobulins (TSI) • MCC of endogenous hyperthyroidism, women > men (in

developed countries)• Genetics: concordance rate in monozygotic twins: 30-40%• Triad:

• 1. hyperthyroidism- hyperfunctional enlargement of thyroid

• 2. infiltrative ophthalmopathy w/ resultant exophthalmos• 3. localized, infiltrative dermopathy- pretibial myxedema

• Increased connective tissue deposition – proptosis and EOM swelling due to glycosaminoglycan synthesis by fibroblasts stimulated by the antibody

characterized by follicular hyperplasia, intracellular colloid droplets, cell scalloping, a reduction in follicular colloid, and a patchy (multifocal) lymphocytic infiltration. Only rarely are lymphoid germinal centers seen, although the histological picture may be greatly influenced by treatment with antithyroid drugs

Subacute Lymphocytic Thyroiditis• Painless thyroiditis- painless goiter• Most common in women, postpartum• Variant of Hashimoto- pts with anti-

thyroid peroxidase antibodies• Patients may have transient

hyperthyroidism, then euthyroid, then possible transient hypothyroidism

• treat symptomatically and follow, typically diagnosed with RAIU

Multinodular goiter• Present as enlarged thyroid• Multilobulated• Mass effects including dysphagia, superior vena cava

syndrome• Most are euthyroid or have subclinical hyperthyroidism• Toxic multinodular goiter- focal patches of hyperfunctioning

follicular cells working independently of TSH• Toxic nodular goiter – one nodule become hot• Toxix Multinodular Goiter – Plummer’s

Thyroid Storm

• Can be a complication of Graves, infection, trauma, pregnancy

• Stress-induced catecholamine surge• Arrhythmia, hyperthermia, vomiting w/

hypovolemic shock,• TX – PTU, B blockers, steriods

Follicular Adenoma• Solitary Adenoma => FNA and thyroid studies• Most common benign tumor• Hallmark- intact, well-formed capsule• Unilateral painless mass• Nonfunctioning adenomas are cold on

radionucliotide scan

Thyroid CancersPapillary - MCCFollicular - radiation (X-rays)

Hurthle cell cancerMedullary - MENAnaplastic - worst prognosis

Papillary carcinoma• Most common thyroid cancer• Mutation in RET and NTRK1• Increased risk with childhood irradiation• Ages 25-50 Most common• Great prognosis, lymphatic > hematogenous spread• Clear cytoplasm, w ground-glass or • Orphan Annie nuclei (ground glass)• Psammoma bodies, nuclear grooves

Thyroid cancer cont…• Follicular

– 2nd most common type– ½ have mutations in RAS gene– Uniform follicles– Fibrous capsule w/ invasion– Lymphatic spread is uncommon, vascular is common

• Anaplastic– Very aggressive and poor prognosis– Associated w/ p53 mutation– Older patients– Mass effect => sx like dyspnea, dysphagia– Large, pleomorphic giant cells, spindle cells, mixed spindle cells

• Medullary Thyroid Carcinoma– Arise from parafollicular C cells, produce calcitonin– Seen in MEN2– Associated with RET mutation

Questions?Alexis Nickols

alexisnickols@gmail.com

Cara SweeneyCara.Ann.Sweeney@gmail.com