Robbins Flashcards
What gene mutations have been identified as causes of familial pituitary adenomas?
MEN 1
CDKNIB
PRKARIA
AIP–> develops GH secreting adenoma @ young age
Cellular monomorphism, absence of Reticulin network?
Pituitary adenoma
Macroadenomas in pituitary gland lead to mass effect causing?
Visual disturbances
What mutation is one of the more come genetic alterations in Pituitary adenomas?
GNAS I mutation–> constitutively active Gs protein
What is the MC type of hyperfunctioning pituitary adenomas?
Prolactinomas
What are the consequences of Prolactinomas?
Amenorrhea
Galactorrhea
Libido
Infertility
Persistent hypersecretion of GH stimulates secretion of what?
IGF-I (somatomedin C) from Liver
Enlargement of jaw + hands + feet + separation of teeth?
Acromegaly from GH excess in adults
**Children get Gigantism
What is GH excess associated with causing?
Acromegaly/ Gigantism Glucose intolerance DB mellitus Muscle weakness HTN + CHF Arthritis Osteoporosis
What type of pituitary adenoma stains Positively with PAS?
Corticotroph cell Adenoma (ACTH releasing)
Corticotroph cell adenomas can clinically present with?
Cushing syndrome
Hyperpigmention due to MSH accompanying ACTH release
What is the typical presentation of nonfunctioning pituitary adenomas and Most other pituitary adenomas?
Mass effect
Possible Hypopituitarism
What are the necessary condition to get clinical signs of Hypopituitarism?
75% loss or absence of Pituitary gland
Hypopituitarism with evidence of posterior pituitary dysfunction will clinically present as what?
Diabetes Insipidus –> almost always Hypothalamic in orgin
Sheehan syndrome is?
Postpartum Ischemic necrosis of anterior pituitary gland.
What happens to Anterior Pituitary gland during pregnancy?
Enlarges–> increased size/# of prolactin secreting cells but NOT accompanied by increased Blood supply–> susceptible to necrosis
What are some (other than pregnancy) conditions associated with Significant pituitary necrosis?
DIC SCD Elevated intracranial pressures Traumatic injury Shock
What are some other conditions associated with Anterior pituitary hypo function?
Sarcoidosis
TB
Metastasis
What are some of the clinical signs/symptoms of Hypopituitarism?
Dwarfism (GH) Amenorrhea + infertility in women (GnRH) Decreased Libido, impotence, Loss of pubic hair Hypothyroidism Hypoadrenalism Failure of postpartum lactation Pallor of skin (ACTH/ MSH)
Nonapeptide hormone synthesized in the Supraoptic nucleus?
ADH
What is the most useful screening test for Hyper or hypo thyroidism?
TSH
Increased Radioactive Iodide uptake is seen in what conditions?
Graves
Solitary nodule in toxic adenoma
Decreased Radioactive iodide uptake is seen in what condition?
Thyroditis
MCC of Hypothyroidism?
Ww–> Iodine deficiency
Developed worlds–> Autoimmune
Hypothyroidism in infant or child?
Cretinism
Signs and symptoms of Cretinism?
Mental retardation Short stature Coarse Facial Features Protruding tongue Umbilical Hernia
Hypothyroidism in adults?
Myxoedema
Signs and symptoms of Myxoedema?
Mentally sluggish cold intolerant Myxoedema--> mucopolysaccharide edema Broadening and coarsening of facial features Tongue enlargement Deepening of VOICE Constipation CHF
Condition associated with acute illness and sever thyroid pain?
Infectious thyroiditis
Granulomatous Thyroiditis
Disorders manifested by thyroid dysfunction and little inflammation?
Subacute lymphocytic thyroditis (PAINLESS)
Fibrous [Reidel] Thyroditis
2nd MCC of Hypothyroidism characterized by glandular thyroid failure secondary to Autoimmune destruction of thyroid gland?
Hashimoto Thyroditis
Pg of Hashimoto thyroiditis?
CD8 mediated cell death
Cytokine mediated cell death–>IFN gamma= macs
Antithyroid Abs mediate cytotoxicity
Hashimoto Thyroiditis has what genetic association?
CTLA4–> encodes for Treg cells
Biopsy showing widespread infiltration of Lymphocytes, plasma cells, Well developed Germinal Centers?
Hashimoto
What are Hurthle or Oxyphil cells?
Follicular cells with:
Abundantly eosinophilic
Granular cytoplasm
Numerous mitochondria
Painless enlargement of thyroid, associated with Hypothyroidism in middle age women?
Hashimoto
People with Hashimoto are at increased RISK for what?
Non-Hodgkin B cell Lymphoma within Thyroid gland
Characterized by Transient Hyperthyroidism and longterm Hypothyroidism?
Hashimoto
Patient with Hx of URTi just before onset of Thyroditis?
Subacute Granulomatous Thyroiditis–> Follows viral infections
Firm thyroid, intact capsule, and PMN infiltration followed by lymphocytes, macs, plasma cells provoking a granulomatous reaction with giant cells inside Colloid?
Subacute Granulomatous Thyroiditis
Thyroid pain in young patient vs. old patient?
Young–> Hashimoto
Old–> Subacute granulomatous
Painless thyroiditis following pregnancy, normal appearing thyroid, lymphocytic infiltration + hyperplastic germinal center formation caused by Autoimmunity?
Subacute Lymphocytic Thyroiditis
Autoimmune condition causing Extensive fibrosis of thyroid and neck structures producing a HARD and fixed thyroid mass that may stimulate a neoplasm? Other consequences?
Riedel Thyroiditis–> associated with retroperitoneal fibrosis in some cases
Causes Thyrotoxicosis, Ophthalmopathy, Dermopathy (Pretibial Myxedema)?
GRAVES
What are some of the genetic association with Graves disease?
HLA-DR3
CLTA4
PTPN22
Autoimmune disease characterized by thyroid stimulating Igs, Thyroid growth stimulating Igs, TSH binding inhibitor Igs?
Graves disease
What is the Pg of Ophthalamopathy in Graves disease?
- T cell infiltration
- Inflammation + swelling of extraocular muscles
- Glycosaminoglycan (Hyaluronic acid chondroitin sulfate) accumulation
- Increased Adipocyte #
Microscopic appearance of Graves disease?
Diffuse hypertrophy/ hyperplasia
Scalloped colloid in Follicular margins
Germinal center formation
Characteristically causes increased blood flow to the thyroid with audible bruits, wide gaze and lid lag patient?
Graves disease
Typical characteristics of neoplastic thyroid nodules?
Solitary Younger patient Males History of Radiation NOT "Hot" (take up radioactive Iodine)
What genetics is associated with thyroid adenomas?
TSH receptor mutations
GNAS–> allows follicular cells to secrete Thyroid hormone independent of TSH (autonomy)
Painless Solitary nodule with Well-defined, Intact capsule, that compresses adjacent thyroid parenchyma?
Adenoma
What is the scanning radionuclide description for a thyroid adenoma?
Cold–> less likely to be neoplastic
**some are HOT–> Toxic and most turn malignant
Types of Thyroid Carcinomas in incidence order?
Papillary
Follicular
Anaplastic
Medullary
Genetics associated with Papillary thyroid carcinoma?
MAP kinase activation: RET or NTRKI + BRAF
Genetics associated with Follicular thyroid carcinoma?
PI-3K/AKT signaling pathway mutation
Genetics associated with Medullary thyroid carcinoma?
MEN-2 and RET oncogene mutations
Vast majority of Thyroid cancers are associated with Hx of?
Radiation
Cells with finely dispersed chromatin, imparting an optically clear appearance of a Ground glass Nuclei?
Papillary thyroid carcinoma–> “Orphan Annie eye” nuclei
Neoplastic growth with cells showing invaginations, pseudoinclusions, concentrically calcified structures (Psammoma bodies) with in papillae?
Papillary thyroid carcinoma–> metastasis to near by lymph nodes 50%
Thyroid carcinoma associated with 40-60 yo women in Iodine deficient areas?
Follicular Thyroid carcinoma
What is the important difference between follicular adenoma and follicular carcinoma?
Invasion of the CAPSULE or Vessel
Solitary Cold nodule, that Hematogenously spreads to Lungs, bone, or liver?
Follicular thyroid carcinoma–> NO LYMPH node metastasis
Undifferentiated tumor of thyroid follicular epithelium, in >60yo, aggressive with nearly 100% mortality rate?
Anaplastic carcinoma
Bulky mass that typically grows rapidly beyond thyroid capsule into adjacent neck structures, with large pleomorphic giant cells, spindle cells?
Anaplastic carcinoma
Neuroendocrine neoplasm derived from parafollicular cells or C cells, secrete Calcitonin, in CHILD is associated with what genetics?
Medullary carcinoma–> MEN 2a or 2b
Altered calcitonin molecules in adjacent stroma of medullary carcinoma leads to deposition of what?
AMYLOID
Multicentric C cell hyperplasia with amyloid deposition usually presents with what clinical symptoms?
Medullary carcinoma–> Dysphagia or hoarseness
Familial medullary carcinoma is associated with what mutation?
RET–> Prophylactic Thyroidectomy
Radioactive Iodine uptake shows Homogenous image with HIGH uptake?
Graves
Radioactive iodine uptake shows no image or Low uptake?
Subacute thyroiditis
PPT
Pt taking EXCESS thyroid hormone
Radioactive Iodine uptake shows Multiple Hot spots with high uptake?
Toxic multinodular goiter
Radioactive iodine uptake shows Single High Uptake hot spot with rest of gland suppressed?
Toxic adenoma
RAI uptake image shows Single focal COLD spot in otherwise normal gland?
Benign/ colloid cyst
Bengin/malignant tumor
RAI uptake showing patchiness without hotter or colder spots?
Multinodular non-toxic goiter