What cells are found in the Thyroid Gland?
Follicular (epithelial) cells - thyroid hormone synthesis
Parafollicular Cells or C- Cells = make Calcitonin
Describe the Biosynthetic pathway of Thyroid Hormone Synthesis.
ACtive Uptake of Iodide --> Oxidation of I to I2
Organification of Tyr --> Conversion to MIT and DIT
MIT + DIT = T3
DITx2 = T4
Exocytosis and transport w/ TBG (T4 3x more exported than T3 so that can control w/ peripheral metabolism of T4 to T3 in tissues where you need it)
What converts Thyroxine in the periphery?
D2 converts T4 to T3 as does D1 in the periphery
D3 converts T4 to rT3 (inactive) which is the direct deactivation pathway and can be seen in severe stress
Describe Thyroid Hormone action on bone, CV, Liver, Fat, Brain, and GI.
Bone: Activation of Osteoclasts
CV: Increases CO and Blood Volume; Decreases Systemic vascular resistance
Liver: Regulates lipid metabolism
Fat: Lipid storage, lipolysis, adipocyte proliferation
Brain: Stimulates Axonal growth and development
GI: Bowel irregularity
Clinical Presentation of Hypothyroidism?
Variable presentation from asymptomatic to Comatose - Myxedema Coma !!!
Hypothermia, slowed speech and movements
fatigue, weight gain, pallor, yellowing of skin, dry skin and hair loss
joint pain, Macroglossia, edema
Decreased SBP and Increased DBP
Bradycardia and Pericardial Effusion
Hyporeflexia w/ delayed relaxation
Primary Hypothyroidism - Labs? Causes of Primary Hypothyroidism?
Labs: low or normal low T4/T3 and elevated TSH due to loss of negative feedback
Acquired Etiologies: Hashimoto's Thyroiditis, post-Ablative, Iodine Deficiency - endemic goiter, Transient post-thyroiditis, Drug induced (amiodarone or sunitinib), or drugs block synth/release T4 (Lithium, sulfonamides, Amiodarone), Infiltrative diseasese
Congenital Etiologies: Thyroid agenesis/dysplasia, TSH receptor defects, Iodide Transport or utilization defect - Pendre's Syndrome etc
What is Pendred's Syndrome?
Iodide tranpsort or utilization defect (NIS or pendrin mutations) that causes Primary Hypothyroidism and Sensorineural Deafness
Hashimoto's - who gets it? What causes it/what do you see? What are you at increased risk for? What's it associated w/?
Autoimmune destruction of Thyroid gland w/ Lymphocytic infiltration and fibrosis
Women > ME, Familial predisposition
Thyroid Autoantibodies - TPO and Thyroglobulin Antipodies
Association/Component of APS-2
5% risk of Thryoid Cancer
What are some causes of central aka secondary Hypothyroidism? What Labs would you see? Test to determine source?
Labs: Low TSH bc pathology of Hypothal or Pituit and Low T4/T3
Acquired causes: Pituitary or hypothalamic disorders, Da problems, Bexarotene (retinoid X receptor Agonist)
Congenital Causes: TSH deficiency or receptor defect
TRH stimulation test can determine between Pituitary or Hypothalamic
Another cause of Hypothyroidism can be resistance to TH. What happens here? Manifestations?
TR-Beta gene mutation and so can't respond to T3
Clinical Manifestations: Goiter, Tachycardia, Elevated levels of hormones - can be confused w/ TSH producing tumor
Labs: Elevated TSH and variable T3/4
What tumors can cause consumptive hypothyroidism?
Hemangiomas or Hemangioendotheliomas
- rapid destruction of thyroid hormone due to D3 over-expression in tumors to use all available thyroxine
What is Myxedema Coma? Who gets it? Precipitating Factors?
Endocrine Emergency - severe long-standing hypothyroidism leading to depressed mental state
- Occurs in old women in winter? Accompanied by Hypothermia
Precipitating Factors: Loss of adaptive mechanisms to maintain homeostasis in the face of CVA, Trauma, Infection, CNS depressants, Raw Bock Choy?, Cold
*Hypothermia can mask infection!
What are the Signs and Symptoms of Myxedema Coma?
ALTERED MENTAL STATUS - Hallmark Feature: Disorientation, paranoia, depression, hallucination
Bradycardia, Heartblock, prolonged QT
Hyponatremia - increase ADH
Hypoventilation - Hypoxia and Hypercapnse
Seizures due to resulting hyponatremia, hypoglycemia or hypoxemia
What are labs you can get for all causes of hypothyroidism?
TSH or T4
- Total T4 = Free and Protein bound (TBG, albumin, transthyretin)
MEasurement of Thyroid Antibodies - TPO and TgAb
Thyroid Function tests in Primary vs Central Hypothyroidism vs REsistance?
Primary: Elevated TSH, Low/Normal T4/T3, TPO/TBAg positive in Hashimotos
Central: TSH Low/Normal, T4/T3 Low
TH Resistance: TSH high and T4/T3 high
TSH Normally .5-4.5
What is the goal of medical management in Hypothyroidism? How do you achieve that? What do you use?
Goal: Normalize serum TSH levels so treat w/ Thyroid hormone replacement
Drugs: Levothyroxine (T4 Analogue AKA Synthroid, Levoxyl etc)
or can give Liothyronine (cytomel) which is T3
What is Subcliical Hypothyroidism?
Elevated TSH (between 5-10) and normal T4/T3
What are some complications to mom and baby when have Hypothyroidism in pregnancy?
Danger in Hashimotos?
MAternal - preeclampsia, anemia, hemorrhage, Central Ventricular dysfunction, abortion, abruption
Fetal - low birth weight, impaired cognitive development, fetal mortality
High TPO titers confer higher risk of Abortion in Hashimotos
What is the treatment goal for hypothyroidism in pregnancy? What if not enough TH?
GOAL TSH 0.2-3.5 mlU/L
NEED enough in the first trimester or else Cretinism
What are most common causes of Hyperthyroidism? Who gets them?
GRAVES DISEASE MOST COMMON - peak incidence 20s-40s
Toxic Multinodular Goiter (MNG) - peak incidence > 50 yo
Toxic Adenoma - peak incidence 30-40
Females > MAles
How do symptoms of Hyperthyroidism manifest differently in older vs younger patients?
Young PAtients - symptoms of sympathetic activation, anxiety, hyperactivity, tremor
Older Patients - manifest CV symptoms like Dyspnea, AFIB w/ unexplained weight loss
What are the symptoms and signs of Hyperthyroidism?
Symptoms: Anxiety, sweating, tremor, heat intolerance, weakness, Diarrhea, hyperactivity, palpitations, weight loss, dyspnea, insomnia, menstraul abnormalities
Signs: hyperactivity, weight loss, hair loss, Tachycardia or Atrial Arrhtyhmia, Systolic HTN, Warm - smooth skin, Proximal Myopathy, Exophthalmos, Emotional Lability, Hyperactive reflexes
Labs in Primary Hyperparathyroidism?
Overproduction of T4/T3 w/ low levels of TSH
Causes of Hyperthyroidism that lead to Low TSH and HIGH RAIU
TSH receptor mutations
causes of hyperthyroidism that lead to Low TSH and LOW RAIU
Amiodarine associated - due to excess iodine release
Teratoma that has functional Thyroid carcinoma
What is the most common cause of Thyrotoxicosis? What are the signs/symptoms/associations? What do you see on RAIU?
Thyroid-Stimulating Immunoglobulin (TSI)- antibodes that bind TSH receptor resulting in growth of thyroid cells and increased function
RAIU: Diffuse Increased uptake!
Signs/Symptoms: - Pretibial Myxedema - swelling over anterir shin
- Thyroid Eye disease
- Increased pigmentation and Vitiligo
Another cause of primary hyperthyroidism is Multinodular Goiter. Desecribe what's happening there and where you see it? Presentaiton?
2 or more thyroid nodules secreting excess TH
- RAUI shows multiple hyperfuncitoning nodules
- Potentiated by drugs w/ Iodine - Radiocontrast or Amiodarone
- can have insidious onset and present in older patients as Apathetic Hyperthyroidism: WEight loss, AFIB, Depression
What is a Toxic Adenoma? Who gets it? Treatment?
Single Hyper-functioning nodule
seen in pts 30-40 yo
RAIU shows 1 nodule uptake and remainder or thyroid gland is suppressed
Treatment is RAdioablation or surgery
What is the relationship between Beta-HCG and TSH? Why is this good normally? and When/why is it bad?
TSH and BETA-HCG have Alpha Subunit Homology and so B-HCG acts on the TSH receptor to stimulate TH production
Normally occurs in pregnancy bc need increased TH; resolves in normal pregnancy by 14 weeks and associated w/ Hyperemesis Gravidarum or Twins
Bad when seen w/ Trophoblastic or germ cell tumors, familial gestational hyperthyroidism
Clinical Symptoms of Thyroid Storm?
FEVER and profuse sweating
Altered MS - agitation, delirium, psychosos, coma
Tachyarrthythmia - sinus, AFIB, Tachypnea
GI dysfunction and Jaundice
When is Thyroid storm seen? What are some precipitating factors?
Graves and TMG
- surgery or trauma
INFECTION MOST COMMON
Iodine load - like CT scan w/ IV contrast
What is the cause of SEcondary Hyperthyroidism? What labs do you see? PResentation? RAIU scan? Treatment?
TSH-Producing Pituitary Adenoma
Labs: Normal/elevated TSH and Elevated T3/T4 (similar to TH resistance)
Presentation: Bitemporal Hemianopsia, HA, Goiter, Hyperthyroid
Majority are MACROADENOMAs and 25% co-secrete GH and Prolactin!!!
High uptake on RAIU scan!
Treatment: surgery and somatostatin analogues
What can cause transient TH excess and what do you see? Treatment?
Thyroiditis - inflammation causes release of a bunch of TH all at once
Low TSH and Low Uptake on Scans
Following viral illness get Painful Thyroid + Hyperthyroidism as it gets inflamed and just dumps all stored colloid
Tx: Beta Blockers, NSAIDS, Prednisolone but no need for antithyroid drugs
What do you see in Post-Partum Thyroiditis?
several weeks after delivery get transient thyrotoxicosis followed by hypothyroidism and recover
RAIU uptake low bc destruction of gland
What is Subclinical Hyperthyroidism and who gets treated for it?
Low/Suppressed TSH w/ normal T4/T3 - assays for TSH more sensitive than for normal T4/T3
No symptoms but higher incidence low bone density
should really be named Mild Hyperthyroidism
TREAT IN POST-MENOPAUSAL WOMEN - improves bone density and cardiac function
Low or suppressed TSH < 0.4 mIU/L
Lab testing for All hyperthyroidism? differences in etiologies and labs?
TSH, T4 and T3
*High T3 suggestive of Grave's Disease
TSI and TSH receptor Antibody (TRAb)
Hyperthyroidism: Low TSH, T4 and/or T3 elevated, and can have Antibodies
TSH-Producing Pituitary Adneoma: TSH normal or elevated, T4 and/or T3 elevated
TH resistance: TSH high and T3/T4 high
Imaging for Thyroid diseases - what do you use?
Thyroid US - for nodules, drug induced, or increased Vascularity seen in Grave's
MRI Brain for pituitary lesions
Thyroid Uptake and Scan:
- high uptake = Graves (diffuse), Toxic MNG, Toxic Adenoma
- Low uptake = Thyroiditis, Iodine-induced hyperthyroidism
How id Thyroid Scintigraphy used? Relation to TSH?
Used to determine etiology of Hyperthyroidism by using radioisotopes of Iodine (I-123) or Tech-99 which are taken up by the Follicular cells
Thyroid takes up Iodine under influsence of TSH
Graves: whole thyroid dark bc TSH stimulation to take up everywhere
Toxic MNG/Adenoma: nodules or adenoma dark and then rest is light bc no TSH to the rest of the thyroid
Thyroiditis: no TSH bc suppressed so less uptake
What are the management goals and treatments used for Hyperthyroidism?
GOAL: Normalize serum TSH
Beta Blockers (non-selective) to help w/ symptoms - Propanolol (blocks peripheral T4 to T3 conversion)
Antithyroid Drugs inhibit synthesis of TH: Methimazoe and TPU
Radio-Ablation w/ I-133
Surgery to take out and then use Levothyroxine replacement
Grave's Disease and Hyperthyroidism need to be treated in pregnancy or else get what maternal/fetal complications?
Complications of treatment?
Maternal - preeclampsia, anemia, hemorrhage, spontaneous abortion
Fetal - low birth weight, fetal goiter, fetal neonatal hyperthyroidism or hypothyroidism, and death
Treatment can cause liver disease so need to monitor LFTs and TFTs every 2 weeks!
What are complications of Untreated Hyperthyroidism?
AFIB and Stroke
Osteoporosis and broken hip
Maternal/Fetal Complications in pregnancy