Feedback control Endocrinology Update Robert J. Rushakoff, MD Professor of Medicine University of California, San Francisco robert.rushakoff@ucsf.edu Golden Rule of Endocrinology If overproduction is suspected, try to suppress production. If underproduction is suspected, try to stimulate production. 1
- Hormone Action Hypothalamus - SOMATOSTATIN Thyroid TSH (+) TRH + PITUITARY - PIT T 4 , T 3 (-) TSH + T 4 , T 3 (+) Thyroid T 4 Hormone T 3 Action Hormone Action Hormone Action Primary Hyperthyroidism Thyroid Failure Thyroid Thyroid ↓ ↓ TSH ↑↑ TSH (+) PITUITARY (+) X PITUITARY (+) T 4 , T 3 (-) ↑ T 4 , T 3 T 4 , T 3 ↑ T 4 , T 3 (-) Thyroid Excess Thyroid Hormone Hormone Action Action 2
Thyroid Function Tests � Total Thyroid Hormone � T 4 � T 3 TSH � Free Thyroid Hormone � direct and indirect measurement � FT 4, FT 3 normal � Tests for Thyroid hormone binding protein � T 3 U � TBG Primary Primary Euthyroid Hypothyroid Hyperthyroid Radioactive Iodine Uptake Radioactive Iodine Scanning � 123 I given orally � Image of thyroid obtained after the administration of RAI � Gamma counter over area of thyroid measures radioactivity at 24 hours � NOT A TEST FOR ASSESSMENT OF THYROID FUNCTION � Useful for differential diagnosis of thyrotoxicosis � Useful for when thyrotoxic nodular disease is suspected. � NOT A TEST FOR ASSESSMENT OF THYROID FUNCTION � Dependent on iodine intake 3
Thyroid Function and Oral Patient ASBP Contraceptives Patient TDF Hyperthyroid Euthyroid Euthyroid Serum T 4 Serum T 4 T 3 Uptake T 3 Uptake Anabolic Steroids TSH Free T 4 Free T 4 TSH Patient SF Patient SF FH + for mother with thyroid disease Medications: none Neck: thyroid enlarged 2X, beefy, no nodules Exam: Thin female, hyperactive Heart: + Means-Lerman systolic scratch (rubbing together of normal pleural and Pulse regular at 120. BP: 98/60 pericardial surfaces) HEENT: + stare, + lid lag Ext: fine tremor, no rash at 98mm measure 17mm bilat 4
Symptoms of Hyperthyroidism Do you suspect � Palpitations � Heat intolerance that the patient � nervousness � weight loss (with increased appetite) � fatigue has � Neck swelling � hyperkinesia � Neck pain � hyperdefication hyperthyroidism? � Changes in eyes � sweating � decrease in menstrual periods Symptoms of Hyperthyroidism Signs of Hyperthyroidism � Palpitations � Heat intolerance � Tachycardia � Onycholysis (separation of the nail � nervousness � weight loss (with � Lid lag from its bed) increased appetite) � fatigue � Stare � brisk reflexes � Neck swelling � hyperkinesia � exophthalmus � Dermopathy � Neck pain (Graves’ disease) � hyperdefication (thickened skin, most � Changes in eyes � Tremor � sweating often pretibial) � decrease in � Thyroid enlargement menstrual periods Patient SF 5
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Laboratory Tests for Thyrotoxicosis Is the patient TSH Primary FT 4 thyrotoxic? thyrotoxicosis TSH Secondary FT 4 is 36 (nl 12-24) thyrotoxicosis FT 4 TSH is 0 (nl 0.5-5) Laboratory Tests for Laboratory Tests Not Usually Needed for Diagnosis Thyrotoxicosis TSH ? T 3 toxicosis FT 4 � TSI � Thyroid Antibodies TSH T 3 toxicosis FT 4 FT 3 7
Causes of Thyrotoxicosis Causes of Thyrotoxicosis � Common Causes � Common Causes � Graves’ Disease � Toxic Nodule (Plummer’s Nodule) autoimmune disease - B lymphocytes produce TSI Single autonomous nodule (>3cm) Female:Male 5:1 Age usually > 40 Peak age 20-40 � Subacute thyroiditis � Toxic Multinodular Goiter (TMNG) � Young patient � older patients with history of multinodular goiter � history of malaise, neck pain, viral infection � may be precipitated by iodine � thyroid may be slightly large and tender Causes of Thyrotoxicosis Causes of Thyrotoxicosis � Less Common Causes � hypothalamic-pituitary � Less Common Causes � Jod Basedow � post-partum iodine induced (usually in patient with underlying goiter) “postpartum depression” � Silent Thyroiditis followed by hypothyroidism � factitious � molar pregnancy � excessive thyroid hormone ingested, usually for weight high levels of hCG control � Most often someone in medical field � Struma Ovarii teratoma of ovary containing thyroid tissue 8
Tests for Differential Diagnosis Tests for Differential Diagnosis TSH FT 4 24h RAI uptake TSH FT 4 24h RAI uptake Graves’ Graves’ Disease Disease Subacute Subacute Thyroiditis Thyroiditis Graves’ gland “beefy” Graves’ gland “beefy” Thyroiditis gland hard Thyroiditis gland hard ESR high in Subacute thyroiditis ESR high in Subacute thyroiditis Tests for Differential Diagnosis Tests for Differential Diagnosis TSH FT 4 24h RAI uptake TSH FT 4 FT 3 24h RAI uptake TMNG Factitious Toxic Nodule Factitious: low thyroglobulin TMNG : feel a multinodular goiter, scan shows hot spots Toxic nodule : palpate a single large nodule, scan shows single hot spot 9
Treatment for Subacute Graves’ Disease Treatment Thyroiditis � Treatment of symptoms � Treat with beta blocker titrated to lower pulse Antithyroid � Antithyroid medications of no use Surgery Drugs � ASA or NSAIA for pain � toxic state should resolve in 2-3 months Radioactive iodine Treatment for Subacute Patient LL Thyroiditis � After toxic period, may have transient Patient is a 21 year old female who is hypothyroidism (in some patients preparing for finals. She complains of mild permanent). fatigue and heavy menstrual periods. She is on no medications (including birth control � May choose to just watch patient during pills). She has gained 15 lbs in past 2 this time and most will be euthyroid in years. another 2-4 months. Patient’s sister takes thyroid hormone. � May start on levothyroxine and then stop in a year to see if needed long term Physical exam is normal. 10
Symptoms of Hypothyroidism Do you suspect � Fatigue that the patient � Cold intolerance � Weight gain has � constipation � heavy, frequent menstrual periods hypothyroidism? � muscle cramps Symptoms of Hypothyroidism Signs of Hypothyroidism � Fatigue � Dry skin � Cold intolerance � puffy face and hands � Weight gain � hoarse � constipation � slow reflexes � heavy, frequent menstrual periods � muscle cramps Patient LL 11
Signs of Hypothyroidism Is the patient � Dry skin � puffy face and hands hypothyroid � hoarse � slow reflexes Patient LL ? TSH is 35 (nl .5-5). Laboratory Tests for Laboratory Tests for Hypothyroidism Hypothyroidism TSH TSH Primary Subclinical FT 4 FT 4 hypothyroidism hypothyroidism Clinical significance not clear. TSH Secondary Patients with TSH >20 or + thyroid hypothyrodism antibodies have >80% chance to FT 4 become clinically hypothyroid within 5 years 12
Etiology of Hypothyroidism Thyroid Hormone Preparations � Primary � Levothyroxine (T 4 ) � Hashimoto’s Thyroiditis � most physiologic automimmune � treatment of choice +/- goiter � daily dose � After RAI or surgery for Graves’ disease � t 1/2 1 week � subacute thyroiditis � average dose 0.125 mg/d � inborn errors of thyroid hormone synthesis – 1.6 mcg/kg Secondary � hypothalamic or hypopituitarism Thyroid Hormone Preparations Thyroid Hormone Preparations � Liothyronine (T 3 ) � Desiccated thyroid � tid dosing � potency variable � not physiologic � variable T 4 and T 3 levels � bypass normal T 4 to T 3 conversion � monitoring difficult � t 1/2 1 day � bypass normal T 4 to T 3 conversion � 80% of patients on this preparation shown not to require any thyroid hormone replacement 13
Monitoring Thyroid Hormone Monitoring Thyroid Hormone Replacement Replacement Goal is for normal TSH Minimal time after any change in thyroid hormone dose before rechecking TSH level is 6- TSH 8 weeks. It takes this long to reach steady state. Subclinical More frequent testing will be not only a waste of FT 4 hyperthyroidism money but potentially misleading. Decreased Absorption: Associated with decreased bone density. – Drugs, supplements: calcium, iron, soy, Associated with atrial arrhythmias in older patients. Cholestyramine – Decreased gastric acid: H. pylori infection , Patient needs decrease in thyroid hormone dose. omeprazole Thyroid Nodules Hypopituitarism Although primary organ failure is more � In experienced hands, thyroid US can be common, hypopituitarism is in the first diagnostic test differential diagnosis in cases of � Fine needle aspiration alternative first hypothyroidism, hypoadrenalism and diagnostic test hypogonadism � Experienced pathologist of key importance GH, gonadotrophins, TSH, ACTH, Prolactin (loss in this order) � Thyroid radioactive scans not helpful to determine if nodule is benign or malignant ADH deficiency only if posterior pituitary involved 14
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