Endocrinology Review I

1. Endocrinology Review I Olivia Baugh MD Chief Resident

2. A 44 yo woman requests thyroid testing. She has chronic fatigue, which she attributes the stress of being a single mother and having two jobs. Her medical history is notable for depression which is now controlled. Her mother has hypothyroidism and her father has coronary artery disease. Her only medication is fluoxetine. On exam her blood pressure is 135/85, pulse 64/min, and BMI 26.1. Her thyroid gland is not enlarged but is firm in consistency. Her skin is dry. Her reflexes are normal. Labs: CBC nl, BMP nl, cholesterol 235, triglycerides 118, HDL 45, LDL 166, TSH 13 mU/L, repeat TSH after 6 weeks 14 mU/L, free T4 1.0 ng/dL. Which of the following clinical benefits will she likely experience in response to starting thyroid hormone replacement therapy? A. Weight Loss B. Reduced blood pressure C. Increased HDL D. Decreased LDL E. Increased lean body mass

3. Answer D This patient has subclinical hypothyroidism. Her TSH is elevated and T4 is still within the normal reference range. Patients with a TSH above 10 mU/L experience a decrease in their LDL cholesterol with thyroid hormone replacement therapy. The other answer choices in this question did not show any significant change after treatment and if the TSH is below 10, there is no significant change in the LDL after starting thyroid hormone replacement.

5. Thyroid gland tests TSH (0.5-5 mU/L) main test for thyroid function, misleading results in some pituitary diseases (require MRI if TSH too low) Free thyroxine (0.8-1.8 ng/dL) use to evaluate thyroid function Tree T3 (1.5-7 pmol/L) if suspect T3 thyrotoxocosis serum thyroid stimulating immunoglobulin (expensive test) used to diagnose Graves disease but usually not needed

6. Functional disorders Hyperthyroidism (thyrotoxicosis) Graves disease Toxic adenoma Toxic multinodular goiter Thyroiditis Exogenous T4, T3 TSH mediated Hypothyroidism Hashimotos disease Postoperative/post-ablative Iodine deficiency

7. Evaluation of thyroid function Thyrotoxicosis: check TSH and T4, usually see a supressed TSH if primary thyroid gland overproduction See normal or elevated TSH if primary pituitary tumor If TSH is undetectable and T4 is normal, check T3 as can have T3-thyrotoxicosis Next test is the nuclear medicine 24 hour RAIU and thyroid scan Shows where the thyroid gland uptake is occuring Contraindicated in pregnancy and breast feeding

8. Thyrotoxicosis causes Graves disease Most common cause in the US Have unregulated production of T3 and T4 due to autoantibodies to the TSH receptor. Treat with antithyroid drugs: methimazole 20-30mg daily, propylthiouracil 200 to 300 mg divided 3 times daily (only 50% cure rate after 1 year of therapy) These medications can cause agranulocytosis, hepatic necrosis or vasculitis but rare (<0.5%) Radioactive iodine ablation: do not use with severe ophthalmopathy as this worsens for 2-3 months after treatment Surgical resection

10. Ophthalmoplegia Exophthalmic ophthalmoplegia also is known as Graves ophthalmopathy and infiltrative ophthalmopathy. This refers to weakness of external ocular muscles and exophthalmos from Graves disease. Strabismus and diplopia may be present, as well as pain and lid retraction. The term infiltrative ophthalmopathy refers to ocular muscle histology that suggests an autoimmune process: prominent fibroblastic tissue, degenerated fibers, and infiltration of lymphocytes, mononuclear leukocytes, and lipocytes.

11. Thyrotoxicosis causes Toxic multinodular goiter Thyroid scan shows areas of suppressed activity and multiple areas of increased uptake Treat with antithyroid medications but never get remission after the medications are stopped Treatment of choice is RAIU, usually the non-nodular thyroid tissue recovers normal function but sometimes patients become hypothyroid Treat with thyroidectomy if large goiter that is compressive, see suspicious �cold� nodules, patient intolerant to antithyroid meds or refuses radioiodine treatment

12. Thyroiditis with autonomous nodule

13. Thyrotoxicosis causes Toxic adenoma or �hot� nodules Amount of thyroid hormone produced correlates to the adenoma size, do not see hyperthyroidism until nodule is >3cm in size Treat with hemithyroidectomy or radioiodine Thyroiditis See low RAIU due to transient thyroid damage Postpartum thyroiditis occurs in 10% of pregnancies 9 different types recognized

15. Types of thyroiditis Acute (suppurative, thyroid abscess) infectious causes Subacute (granulomatous, de Quervians) possibly post-viral, see thyrotoxicosis then hypothyroidism and finally euthyroid (pain in thyroid bed radiating to the ears) Postpartum (painless) autoimmune (anti-TPO antibodies) same pattern as subacute Silent (painless) autoimmune Drug-induced caused by amiodarone, lithium, alpha-interferon, interleukin-2 Traumatic, rare (palpation, radiation) seat belt injury, choking injury Hashimotos (chronic lymphocytic) autoimmune anti-TPO Riedels (fibrous) rare sclerosing disease

17. Subclinical hyperthyroidism Suppressed serum TSH from increased T4 or T3 that is still in the normal range, but this lab finding can be due to other causes: Meds (steroids), non-thyroidal illness, transitional thyroid state, central hypothyroidism, excessive thyroid hormone intake If TSH persistently suppressed, perform thyroid scan with RAIU If TSH <0.1 mU/L cardiac arrhythmia risk is high so treat when TSH at this level

18. Were they mentally disabled�hobbits? No, just hypothyroid

19. Thyroid function Hypothyroidism, most common cause is Hashimotos disease (in the US) Subclinical hypothyroidism: elevation of serum TSH level caused by decrease in serum T4 but within the normal range. Most of these patients have Hashimotos thyroiditis, but not all: Same causes as for subclinical hyperthyroidism (see previous slide) Consensus is to treat with TSH >10 due to lipid improvement, and possibly bone density improvement Goal is to treat to prevent progression to overt disease and not to overtreat (esp older patients)

21. The pregnant thyroid Thyroid binding globulin doubles due to estrogen increase Women with normal thyroid glands incrase T4 and T3 production to maintain normal free T4 levels but hypothyroid women cannot so replacement needs to be increased 50% to 75% and after delivery the dose can be decreased to the pre-pregnancy level Poorly controlled hyperthyroidism in pregnancy leads to pre-eclampsia, CHF in mother, fetal death and low infant birth weight, monitor regularly in pregnancy Graves disease is most common cause of hyperthyroidism in pregnancy but b-hcg can also stimulate the thyroid so this is when the Ig test is done as radioiodine is contraindicated TSH is suppressed in first and second trimesters, no treatment needed

22. Thyroid canundrums? Huh? Patient compliant with medication and despite increased doses of thyroid still not therapeutic consider malabsorption (e.g. celiac disease) Pendreds syndrome: autosomal recessive condition accounting for up to 10% of hereditary deafness. Pt�s have sensorineural hearing loss that occurs as children due to dysplasia of the cochlea. Pt�s also have goiter associated with the disorder, occuring in late childhood. MRI or CT shows a cochlea with too few turns or large vestibular aqueducts Mccune �Albright syndrome-hyperthyroidism, caf�-au-lait spots, and polyostotic fibrous dysplasia

23. Structural thyroid disorders Thyroid nodules detected in up to 25% of adults by high-resolution ultrasound Evaluate thyroid nodules with TSH, T4 and FNA biopsy Multinodular goiter may extend substernally compressing trachea, esophagus, and great vessels of the neck

24. Structural thyroid disorders Thyroid cancers-�cold� nodules Papillary (75%-80%), marker is thyroglobulin, lymphatic spread, 98% 10-year survival Follicular (15%-20%), marker is thyroglobulin, hematogenous spread, 92% 10-year survival Medullary (<5%), markers calcitonin and CEA, lymphatic and hematogenous spread, 80% 10-year survival Anaplastic (<5%), no marker, direct extension, 13% 10-year survival MEN type 2a: medullary thyroid cancer, hyperparathyroidism, pheochromocytoma MEN type 2b: medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid body habitus

25. Structural thyroid disorders Treatment Papillary and follicular thyroid cancers are treated with thyroidectomy followed by ablation with radioactive iodine Medullary thyroid cancer is made up of C-cells so does not take up iodine, treat with resection Anaplastic thyroid cancer needs to be resected

26. Thyroid storm The mortality rate of thyroid storm can be as high as 20-40%. The symptoms usually are exaggerated manifestations of the symptoms seen in hyperthyroidism; a superimposed infection and the stress associated with it would exacerbate the symptoms. Fever, abdominal pain, delirium, and psychosis can occur. The patient may become obtunded. Thyroid storm should be suspected in any patient with severe hyperpyrexia, tachycardia, and a goiter.

27. Precipitants of thyroid storm Thyroid surgery Withdrawal of antithyroid meds Radioiodine therapy Thyroid palpation Iodinated contrast dyes Massive thyroid hormone overdose

28. Symptoms of thyroid storm Constitutional: Hyperpyrexia Cardiac: tachycardia, hypertension, high-output cardiac failure, and a propensity to develop cardiac arrhythmias. Neuro: irritability and restlessness in thyrotoxicosis progress to severe agitation, delirium, seizures, and coma. GI: diarrhea, vomiting, jaundice, and abdominal pain,

30. Treatment of thyroid storm Propylthiouracil: blocks new hormone synthesis and blocks T4 to T3 conversion (may also use methimazole but does not inhibit conversion) Propranolol: blocks T4 to T3 conversion at 60-80mg q4h (may also use esmolol) Iodine solution: start 1 hour after antithyroid drugs, blocks new hormone synthesis and hormone release (can use lithium carbonate if pt allergic to iodine) Hydrocortisone: blocks T4 to T3 conversion, prophylaxis against adrenal insufficiency (may also use dexamethasone)

32. Myxedema coma Obtundation and hypothermia Precipitating event: Infection Trauma Cold exposure Sedative use Exam: peripheral vasoconstriction, decreased heart rate, decreased cardiac output, pericardial effusion may precipitate tamponade

33. Myxedema coma treatment: IV thyroid hormone due to impaired oral absorption Initial dose 200-500 ug followed by 50-100ug daily Give corticosteroids because restoration of thyroid hormone levels can precipitate adrenal crisis Intubation usually needed due to hypoxia and CO2 retention Lots of fluids Avoid aggressive rewarming due to vasodilation that could worsen hypotension Culture blood, sputum and urine Broad spectrum antibiotics until cultures negative