Endocrinology II Sarah E. French, MD July 19, 2014 Thyroid Pituitary Adrenal Gonads Bone
Thyroid function tests (TFTs) • TSH • If ↓ TSH → hyperthyroidism • If ↑ TSH → hypothyroidism • Use to screen and follow thyroid replacement • Total T4 • All T4 (but 99.98% protein-bound) • ↑TBG , ↑ total T4, normal free T4 • Pregnancy, estrogens, tamoxifen, HIV, phenothiazines • ↓ TBG , ↓ total T4, normal free T4 • Androgens, glucocorticoids, nephrotic syndrome, cirrhosis
Thyroid function tests (TFTs) • Free T4 • Key in diagnosis of central hypothyroidism • Evaluate degree of hypothyroidism • Diagnosis and response to therapy in hyperthyroidism • Total/free T3 • Check if suspect T3 toxicosis • Thyroglobulin • Low in factitious thyrotoxicosis • Used to monitor thyroid cancer
Thyroid function tests (TFTs) • Thyroid uptake • Normal uptake 10-15% • ↑uptake: Graves, toxic multinodular goiter, solitary toxic adenoma • ↓uptake: thyroiditis, factitious hyperthyroidism • Thyroid scan • Hot nodule = benign • Cold nodule > 1 cm needs FNA
Euthyroid sick syndrome • Seen in critically ill patients • Impairs body’s ability to peripherally convert T4 to T3 • T4 converts to reverse T3 • See normal TSH, normal T4, and free T3 • As disease severity progresses, free T3 and T4 decreases • DON’T CHECK TFTs IN SICK PATIENTS unless you think it’s thyroid storm or myxedema coma • DON’T GIVE THYROID REPLACEMENT
Question A patient of yours comes to see you and complains about being tired. She gave birth to a healthy child about 6 months ago and tells you that the baby is doing fine. Her obstetrician reported to you that the pregnancy and delivery were uneventful. At first everything was perfect. She had plenty of energy and lost the baby weight without difficulty and had no difficulty staying up late at night to take care of the baby. After about two months she began to feel more tired and her fatigue steadily worsened such that now she can barely function. She is having difficulty with nursing. She blames herself for everything that’s wrong and begins to cry. Which of the following should you do next? • Tell her that the symptoms of her “post-partum blues” will soon pass. • Begin anti-depressants • Begin stimulants • Order TSH and Free T4 • Refer her to a psychiatrist for evaluation.
24 yo woman evaluated for 1 week history of neck discomfort that radiates to jaw, palpitations, fast heart rate, anxiety and fever. Reports having sore throat 4 weeks ago that resolved after a few days. No other symptoms. No personal history of thyroid or other endocrine disorders. • On physical exam, she appears anxious. Temperature 37.5 C (99.5F), BP 140/60, pulse 110. + tachycardia. • Thyroid gland slightly enlarged and tender with no nodules. No thyroid bruit. No cervical lymphadenopathy. No eye findings or pretibialmyxedema is noted. + fine bilateral hand tremor. • Lab: sed rate 45, TSH <0.01, free T4 4.1, T3 300. Doppler thyroid ultrasound showed enlarged thyroid with heterogenousechotexture. No significant vascular flow is evident. • What is most appropriate next step in management? • Bilateral fine-needle aspiration biopsy • Methimazole • Serum thyroglobulin measurement • 24-hour radioactive iodine uptake test
Causes of hyperthyroidism Increased Production of Thyroid Hormones • Graves disease • Toxic multinodular goiter • Molar Pregnancy (hCG) • Iodine-induced (Jod-Basedow) • TSH-pituitary adenoma Leakage or Extra-Thyroidal Sources • SubacuteThyroiditis • Silent/post-partum thyroiditis • Thyrotoxicosisfactitia • Struma ovarii
Hyperthyroidism • Patient < 40 yrs—#1 Graves, #2 toxic adenoma • Patient > 60 yrs—#1 multinodular goiter, #2 Grave, #3 toxic adenoma • Will increase metabolism of many drugs • Warfarin may need LOWER dose due to increased metabolism of clotting factors • Apathetic hyperthyroidism in elderly • May only present with weight loss and fatigue
Graves disease Proptosis Acropachy
Therapy for hyperthyroidism • Immediate effect • Beta blocker • Iodine • Surgery • Latent effect—begins at 2-3 wks, full effect at 6 wks • Propylthiouracil—pregnant patients (1st trimester), thyroid storm • Monitor for hepatitis, agranulocytosis • Methimazole—everybody else • Monitor for cholestasis, agranulocytosis • Later effect • Radioactive iodine—takes 2-3 months
Amiodarone and the thyroid • Euthyroidhyperthyroxinemia • Seen in < 3 months of therapy • Observe • Amiodarone-induced thyrotoxicosis • Type 1: iodine induced. + underlying goiter • Type 2: destructive thyroiditis • Dx: Doppler ultrasound (low flow in type 2) • Both have low RAI uptake • Amiodarone-induced hypothyroidism • Underlying + TPO antibodies • Give levothyroxine
Risk factors for thyroid cancer • Family history • History of head/neck radiation • New nodule in patient <20 or >60 years old • Nodule that is firm, fixed and growing • Nodule with regional cervical LAD or Horner’s syndrome • Cold nodule on scan • Microcalcifications± central bloodflow on US • Dysphagia, hoarseness, respiratory obstruction, pain
Evaluation to thyroid nodule • Obtain TSH. • If hyperthyroid, get thyroid scan • If hot nodule, treat with RAI ablation • Do NOT biopsy a hot nodule! They’re benign. • If euthyroid or hypothyroid and >1 cm, perform FNA • Smaller lesions with concerning features may be considered for biopsy
Cancer derived from follicles • Papillary thyroid cancer • Most common • Grows slowly • Lymphangetic spread • Follicular thyroid cancer • Hematogenous spread • Anaplastic thyroid cancer • Extremely poor prognosis
Medullary thyroid cancer • Most are sporadic but often familial (MEN II) • Calcitonin levels helpful • Genetic tests available (RET oncogene)
Thyroid storm • Severe hyperthyroidism • Decreased mental status and fever • Give PTU first!! • Then iodine, beta blockers, and glucocorticoids
Thyroid cases Young patient with soft goiter, bruit, weight loss Grave’s Disease RAI ablation Patient with sore throat, fever, painful goiter Subacutethyroiditis Supportive care +/- steroids Patient with hepatitis C on a-INF. Mildly thyrotoxic, non-tender goiter Silent thyroiditis Supportive care
Thyroid cases • Old pt. with weakness, weight loss, atrial fibrillation, goiter • Apathetic hyperthyroidism (Toxic MNG) • Young woman with molar pregnancy, hyperthyroid • Very High hCGacts as TSH analog • Patient with h/o goiter s/p contrasted CT scan, hyperthyroid sx. • Job-Basedow’s Disease (iodine induced) • Nurse with hyperthyroidism, no goiter, low RAIU • Facticious (taking synthroid) Check thyroglobulin
Primary vs Secondary Hypothyroidism • Primary hypothyroidism • Problem is the gland itself • Will see ↑TSH and ↓free T4 • Secondary hypothyroidism • Problem is outside the gland (ie pituitary, etc) • Will see ↓ or ↔TSH and ↓free T4 • Remember inappropriate normals!!
Question An 84 yo lady with a history of dementia and no other medical problems presents from the nursing home with altered mental status. She is on no medications. She is unable to provide any history but on your examination of her you find that she has a well healed transverse scar across her neck. She is hypothermic, bradycardic, has doughy skin and brittle hair. Labs are pending, but you find a fingerstick glucose of 52. Which of the following is the most reasonable next step in her care? • Give her one amp of D50 • Levothyroxine 300mcg IV • Levothyroxine 300mcg IV and hydrocortisone 100mg IV • Levothyroxine 300mcg IV and one amp of D50 IV • Levothyroxine 200mcg PO
Question A psychiatrist in your community refers an 80 year old woman being treated for depression. She reports generalized weakness, fatigue, dry skin, weight gain and constipation. Her past medical history includes CHF and stable angina. Your examination reveals peri-orbital edema, skin that is cool and dry, loss of the lateral third of her eyebrow, mild bradycardia and a slow relaxation phase of her deep tendon reflexes. You strongly suspect hypothyroidism and check TSH and Free T4. The TSH is 95 units/mL and Free T4 is 0.1ng/dL (0.7-1.5ng/dL). She obviously has severe hypothyroidism. Which of the following should you do next? • Administer thyroxine 500mcg IV daily for 5 doses • Administer thyroxine 500mcg IV and triiodothyronine 20mcg IV daily for three days. • Begin levothyroxine 300mcg PO daily • Begin levothyroxine 100mcg PO daily • Begin levothyroxine 25mcg PO daily Replace levothyroxine slowly in elderly or cardiac patients There is no scenario where you should need to pick T3 over T4.
Hypothyroidism Scenarios 83 yo woman with depression, clearly hypothyroid. Otherwise getting along okay. Therapy? 47 yo man with CABG 8 months ago, hypothyroid. Treatment? 74 yo NH resident with thyroidectomy scar, on no meds comes in with altered mental status, severe hypothyroidism. Glucose is 56. Treatment? Low dose levothyroxine therapy (25mcg/day) and advance slowly to reach goal. Low dose levothyroxine therapy (25mcg/day) and advance slowly to reach goal. Hydrocortisone 100mg IV and Levothyroxine IV.
Hypothyroidism cases 27 year old woman with Hashimotos on levothyroxine 75mcg daily, 2 weeks pregnant. 45 year old woman with Hashimotos has a rapidly enlarging goiter 32 year old man begins abusing heroin, has high Total T4 Estrogens increase TBG, so increase levothyroxine dose by 30-50% during pregnancy Thyroid Lymphoma - FNA diagnosis and irradiate Increased TBG due to heroin (also seen with methadone)
Primary aldosteronism • Screening • Hypertension with hypokalemia • Refractory hypertension (>3 BP meds) • Even if normal K • Work-up • Calculate aldosterone/renin activity ratio • Ratio >20 with aldo >15 ng/dL→ high likelihood • Confirmation • Urine aldo > 12 mcg/24 hrs while on high salt diet (urine Na >200 mEq) • Plasma aldo > 10mg/dL after 2 L of saline over 4 hours
Primary aldosteronism • Classification • Aldosterone-producing adenoma • Bilateral zone glomerulosa hyperplasia • Adrenal carcinoma (rare) • Glucocorticoid-remediable aldosteronism (rare) • Treatment • Adenoma: medically or surgery • Hyperplasia: only medically, spironolactone • If gynecomastia, switch to eplerenone
Primary aldosteronism • If age <40, CT may be sufficient for localization • If age >60, do bilateral adrenal vein sampling • GOLD STANDARD
Pheochromocytoma • Symptoms due to catecholamine excess • Pressure • Perspiration • Palpitation • Pallor • Pain • Blood pressure • Sustained hypertension in 1/2 • Paroxysmal hypertension in 1/3 • Normal blood pressure in 1/5
Diagnosing pheochromocytoma • Plasma metanephrines • Start with this • 99% sensitive—good for ruling out pheo • False (+)—stress, tobacco, coffee, Tylenol, TCAs • 24-hr urine for metanephrines and catecholamines • Check if plasma metanephrines are positive • If >2-fold increase, 99% specific
NEVER BIOPSY AN ANDRENAL MASS WITHOUT RULING OUT PHEO FIRST!! Kronenberg, et al. Williams Textbook of Endocrinology. 2008
Treatment of pheochromocytoma • Surgery is treatment of choice • Laproscopic surgery is an option • Preparation for surgery • Alpha blockade with phenoxybenzamine (alternative: terazosin) • Titrate until patient is orthostatic or patient is at maximum dose • Then start beta blocker • If surgery is not an option (ie metastatic tumor) • Metyrosine • Chemotherapy and radiation
61 yo man with epigastric pain found to have 7 cm R adrenal mass. No change in weight. No history of HTN, palpitations, headaches or excessive sweating. • Physical exam shows normal features. BP 122/76 and pulse 74. No plethora, muscle wasting, weakness or ecchymosis. • Labs: normal serum electrolytes, cortisol, ACTH, and 24-hr urine metanephrines. Dexamethasone suppression test normal. • CT scan showed 7cm R adrenal mass with 77 Hounsfield units. Normal L adrenal gland. No lymphadenopathy. • What is most appropriate management? • Biopsy of adrenal mass • Right adrenalectomy • Serum aldosterone to plasma renin activity ratio determination • 24-hour measurement of urine cortisol excretion
Adrenal incidentaloma • Only 15% functional • Cushing’s > pheochromocytoma > primary aldo • Work-up • All: 1 mg dex suppression test and plasma metanephrines • If HTN: renin and aldosteronism • Remove if functional or >6 cm • If non-functional and 4-6 cm, monitor very closely • Remove if necrosis, hemorrhage, irregular margins • If non-functional <4 cm, re-evaluate in 6 months
Congenital adrenal hyperplasia (CAH) • 21-hydroxylase is most common • Accumulation of 17-OH progesterone →androgens • Classical form (complete deficiency) • Starts in infancy • Salt-wasting, hypotension, virilization • Sometimes ambiguous genitalia at birth • Partial deficiency • Young adulthood • Hirsutism, menstral irregularities • Mimics PCOS • Treatment: prednisone • + fludrocortisone if needed
Adrenal insufficiency • Symptoms • Weakness, fatigue, abdominal pain, nausea, vomiting • Signs • Hyponatremia, hypotension, hypoglycemia • Women have loss of axillary and pubic hair • Due to loss of adrenal androgens • Primary adrenal insufficiency • Hyperpigmentation (↑ ACTH) • Hyperkalemia (mineralocorticoid deficiency)
Primary adrenal insufficiency • Addison’s disease • Occurs when 90% of gland destroyed • Involves all 3 layers of gland • Most common cause in US: autoimmune adrenalitis • Most common cause worldwide: TB • Other causes: histoplasmosis, HIV, metastatses, adrenal hemorrhage, Waterhouse-Friderichsen syndrome • Diagnosis with Cosyntropinstim test • Cortisol >18 at any time rules out primary adrenal insufficiency
Adrenal cases 60 yo man with hypokalemia, U waves on EKG, HTN (190/120), weakness, extreme thirst and polyuria. Normal glucose. CT scan shows 1cm nodule on right adrenal gland. First diagnostic step? Confirmatory Test? Electrolytes corrected and he feels better. Ready for surgery now? Renin/Aldosterone ratio >20 with Aldo >15 Primary Hyperaldosteronism Salt load and then 24 hour urine aldo >12 OR 2 liter NS bolus with plasma aldo >10. Bilateral adrenal vein sampling first.
Adrenal cases 24 yo man with resistant HTN, short stature, history of genitourinary surgeries as a child, low potassium. Likely diagnosis? 45 yo farmer who dips tobacco, has resistant HTN with hypokalemia. Congenital Adrenal Hyperplasia (17-alpha hydroxylase deficiency) Renin low, aldosterone low, deoxycorticosterone high Licorice (glycyrrhizic acid) inhibits conversion of hydrocortisone to cortisone Renin low, Aldosterone low
Anterior pituitary hormones • Adrenocorticotropic hormone (ACTH) • CRH stimulates release of ACTH • Growth hormone (GH) • GHRH stimulates release of GH • Thyroid stimulating hormone (TSH) • TRH stimulates release of TSH • Luteinizing hormone (LH) • GnRH stimulates release of LH • Follicle-stimulating hormone (FSH) • GnRH stimulates release of LH • Prolactin • Under continuous hypothalamic inhibition by dopamine
Pituitary tumors • Is it hormonally active? • PRL > GH > ACTH > LH/FSH >> TSH • Alpha chain tumors not biologically active • Is there any mass effect? • Bitemporalhemianopsia, headache, seizures • Is it affecting normal production of pituitary hormones? • Most critical: ACTH and TSH • Beware low free T4 but “normal” TSH! • Remember inappropriate normals!!
Prolactinoma • Most common pituitary tumor • Women: secondary amenorrhea and galactorrhea • Men: hypogonadism • Treatment: dopamine agonist • Bromocriptine or carbegoline • NOT SURGERY!! • Suspect another tumor if tumor > 1 cm and PRL < 200 • Severe-long standing primary hypothyroidism will ↑ TRH →↑PRLand ↑growth of thyrotrophs → pituitary mass → give levothyroxine
26 yo woman evaluated for hyperprolactinemia after recent labwork showed serum prolactin of 55 (normal 10-26). Mild hyperprolactinemia was detected 6 years ago during evaluation for irregular menstrual cycles. MRI at that time showed pituitary microadenoma. Was treated with dopamine agonist and subsequent serum prolactins were normal until this reading. • Patient had menarche at 13 and has irregular periods since then. • Vitals normal. Breast development normal but there is breast tenderness present. No galactorrhea, acne, hirsutism, or striae are present. • What is most appropriate next diagnostic test? • Pregnancy test • Random growth hormone measurement • Serum cortisol • Visual field testing
Other causes of hyperprolactinemia • Pregnancy • Exogenous estrogens • Primary hypothyroidism • Drugs: metoclopramide, amytriptyline, phenothiazines, antidopaminergics • Other tumors that compress pituitary stalk