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