5Thyroid function tests (TFTs) TSHIf ↓ TSH → hyperthyroidismIf ↑ TSH → hypothyroidismUse to screen and follow thyroid replacementTotal T4All T4 (but 99.98% protein-bound)↑TBG , ↑ total T4, normal free T4Pregnancy, estrogens, tamoxifen, HIV, phenothiazines↓ TBG , ↓ total T4, normal free T4Androgens, glucocorticoids, nephrotic syndrome, cirrhosis
6Thyroid function tests (TFTs) Free T4Key in diagnosis of central hypothyroidismEvaluate degree of hypothyroidismDiagnosis and response to therapy in hyperthyroidismTotal/free T3Check if suspect T3 toxicosisThyroglobulinLow in factitious thyrotoxicosisUsed to monitor thyroid cancer
8Euthyroid sick syndrome Seen in critically ill patientsImpairs body’s ability to peripherally convert T4 to T3T4 converts to reverse T3See normal TSH, normal T4, and free T3As disease severity progresses, free T3 and T4 decreasesDON’T CHECK TFTs IN SICK PATIENTS unless you think it’s thyroid storm or myxedema comaDON’T GIVE THYROID REPLACEMENT
9QuestionA 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-depressantsBegin stimulantsOrder TSH and Free T4Refer her to a psychiatrist for evaluation.
11What is most appropriate next step in management? 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 tachycardia.Thyroid gland slightly enlarged and tender with no nodules. No thyroid bruit. No cervical lymphadenopathy. No eye findings or pretibial myxedema is noted. + fine bilateral hand tremor.Lab: sed rate 45, TSH <0.01, free T4 4.1, T Doppler thyroid ultrasound showed enlarged thyroid with heterogenous echotexture. No significant vascular flow is evident.What is most appropriate next step in management?Bilateral fine-needle aspiration biopsyMethimazoleSerum thyroglobulin measurement24-hour radioactive iodine uptake test
12Causes of hyperthyroidism Increased Production of Thyroid HormonesGraves diseaseToxic multinodular goiterMolar Pregnancy (hCG)Iodine-induced (Jod-Basedow)TSH-pituitary adenomaLeakage or Extra- Thyroidal SourcesSubacute ThyroiditisSilent/post-partum thyroiditisThyrotoxicosis factitiaStruma ovarii
13Hyperthyroidism Patient < 40 yrs—#1 Graves, #2 toxic adenoma Patient > 60 yrs—#1 multinodular goiter, #2 Grave, #3 toxic adenomaWill increase metabolism of many drugsWarfarin may need LOWER dose due to increased metabolism of clotting factorsApathetic hyperthyroidism in elderlyMay only present with weight loss and fatigue
15Therapy for hyperthyroidism Immediate effectBeta blockerIodineSurgeryLatent effect—begins at 2-3 wks, full effect at 6 wksPropylthiouracil—pregnant patients (1st trimester), thyroid stormMonitor for hepatitis, agranulocytosisMethimazole—everybody elseMonitor for cholestasis, agranulocytosisLater effectRadioactive iodine—takes 2-3 months
16Amiodarone and the thyroid Euthyroid hyperthyroxinemiaSeen in < 3 months of therapyObserveAmiodarone-induced thyrotoxicosisType 1: iodine induced. + underlying goiterType 2: destructive thyroiditisDx: Doppler ultrasound (low flow in type 2)Both have low RAI uptakeAmiodarone-induced hypothyroidismUnderlying + TPO antibodiesGive levothyroxine
17Risk factors for thyroid cancer Family historyHistory of head/neck radiationNew nodule in patient <20 or >60 years oldNodule that is firm, fixed and growingNodule with regional cervical LAD or Horner’s syndromeCold nodule on scanMicrocalcifications ± central bloodflow on USDysphagia, hoarseness, respiratory obstruction, pain
18Evaluation to thyroid nodule Obtain TSH.If hyperthyroid, get thyroid scanIf hot nodule, treat with RAI ablationDo NOT biopsy a hot nodule! They’re benign.If euthyroid or hypothyroid and >1 cm, perform FNASmaller lesions with concerning features may be considered for biopsy
20Medullary thyroid cancer Most are sporadic but often familial (MEN II)Calcitonin levels helpfulGenetic tests available (RET oncogene)
21Thyroid storm Severe hyperthyroidism Decreased mental status and fever Give PTU first!!Then iodine, beta blockers, and glucocorticoids
22Thyroid cases Young patient with soft goiter, bruit, weight loss Grave’s Disease RAI ablationPatient with sore throat, fever, painful goiterSubacute thyroiditis Supportive care +/- steroidsPatient with hepatitis C on a-INF. Mildly thyrotoxic, non-tender goiterSilent thyroiditis Supportive care
23Thyroid casesOld pt. with weakness, weight loss, atrial fibrillation, goiterApathetic hyperthyroidism (Toxic MNG)Young woman with molar pregnancy, hyperthyroidVery High hCG acts as TSH analogPatient with h/o goiter s/p contrasted CT scan, hyperthyroid sx.Job-Basedow’s Disease (iodine induced)Nurse with hyperthyroidism, no goiter, low RAIUFacticious (taking synthroid) Check thyroglobulin
24Primary vs Secondary Hypothyroidism Primary hypothyroidismProblem is the gland itselfWill see ↑TSH and ↓free T4Secondary hypothyroidismProblem is outside the gland (ie pituitary, etc)Will see ↓ or ↔TSH and ↓free T4Remember inappropriate normals!!
25QuestionAn 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 D50Levothyroxine 300mcg IVLevothyroxine 300mcg IV and hydrocortisone 100mg IVLevothyroxine 300mcg IV and one amp of D50 IVLevothyroxine 200mcg PO
26QuestionA 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 ( ng/dL). She obviously has severe hypothyroidism.Which of the following should you do next?Administer thyroxine 500mcg IV daily for 5 dosesAdminister thyroxine 500mcg IV and triiodothyronine 20mcg IV daily for three days.Begin levothyroxine 300mcg PO dailyBegin levothyroxine 100mcg PO dailyBegin levothyroxine 25mcg PO dailyReplace levothyroxine slowly in elderly or cardiac patientsThere is no scenario where you should need to pick T3 over T4.
27Hypothyroidism 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.
28Hypothyroidism cases27 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 T4Estrogens increase TBG, so increase levothyroxine dose by 30-50% during pregnancyThyroid Lymphoma - FNA diagnosis and irradiateIncreased TBG due to heroin (also seen with methadone)
30Primary aldosteronism ScreeningHypertension with hypokalemiaRefractory hypertension (>3 BP meds)Even if normal KWork-upCalculate aldosterone/renin activity ratioRatio >20 with aldo >15 ng/dL → high likelihoodConfirmationUrine 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
31Primary aldosteronism ClassificationAldosterone-producing adenomaBilateral zone glomerulosa hyperplasiaAdrenal carcinoma (rare)Glucocorticoid-remediable aldosteronism (rare)TreatmentAdenoma: medically or surgeryHyperplasia: only medically, spironolactoneIf gynecomastia, switch to eplerenone
32Primary aldosteronism If age <40, CT may be sufficient for localizationIf age >60, do bilateral adrenal vein samplingGOLD STANDARD
33Pheochromocytoma Symptoms due to catecholamine excess Blood pressure PerspirationPalpitationPallorPainBlood pressureSustained hypertension in 1/2Paroxysmal hypertension in 1/3Normal blood pressure in 1/5
34Diagnosing pheochromocytoma Plasma metanephrinesStart with this99% sensitive—good for ruling out pheoFalse (+)—stress, tobacco, coffee, Tylenol, TCAs24-hr urine for metanephrines and catecholaminesCheck if plasma metanephrines are positiveIf >2-fold increase, 99% specific
35NEVER BIOPSY AN ANDRENAL MASS WITHOUT RULING OUT PHEO FIRST!! Kronenberg, et al. Williams Textbook of Endocrinology. 2008
36Treatment of pheochromocytoma Surgery is treatment of choiceLaproscopic surgery is an optionPreparation for surgeryAlpha blockade with phenoxybenzamine (alternative: terazosin)Titrate until patient is orthostatic or patient is at maximum doseThen start beta blockerIf surgery is not an option (ie metastatic tumor)MetyrosineChemotherapy and radiation
37What is most appropriate management? 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 massRight adrenalectomySerum aldosterone to plasma renin activity ratio determination24-hour measurement of urine cortisol excretion
38Adrenal incidentaloma Only 15% functionalCushing’s > pheochromocytoma > primary aldoWork-upAll: 1 mg dex suppression test and plasma metanephrinesIf HTN: renin and aldosteronismRemove if functional or >6 cmIf non-functional and 4-6 cm, monitor very closelyRemove if necrosis, hemorrhage, irregular marginsIf non-functional <4 cm, re-evaluate in 6 months
39Congenital adrenal hyperplasia (CAH) 21-hydroxylase is most commonAccumulation of 17-OH progesterone →androgensClassical form (complete deficiency)Starts in infancySalt-wasting, hypotension, virilizationSometimes ambiguous genitalia at birthPartial deficiencyYoung adulthoodHirsutism, menstral irregularitiesMimics PCOSTreatment: prednisone+ fludrocortisone if needed
40Adrenal insufficiency SymptomsWeakness, fatigue, abdominal pain, nausea, vomitingSignsHyponatremia, hypotension, hypoglycemiaWomen have loss of axillary and pubic hairDue to loss of adrenal androgensPrimary adrenal insufficiencyHyperpigmentation (↑ ACTH)Hyperkalemia (mineralocorticoid deficiency)
42Primary adrenal insufficiency Addison’s diseaseOccurs when 90% of gland destroyedInvolves all 3 layers of glandMost common cause in US: autoimmune adrenalitisMost common cause worldwide: TBOther causes: histoplasmosis, HIV, metastatses, adrenal hemorrhage, Waterhouse-Friderichsen syndromeDiagnosis with Cosyntropin stim testCortisol >18 at any time rules out primary adrenal insufficiency
43Adrenal cases60 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 HyperaldosteronismSalt load and then 24 hour urine aldo >12 OR2 liter NS bolus with plasma aldo >10.Bilateral adrenal vein sampling first.
44Adrenal cases24 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 highLicorice (glycyrrhizic acid) inhibits conversion of hydrocortisone to cortisoneRenin low, Aldosterone low
46Anterior pituitary hormones Adrenocorticotropic hormone (ACTH)CRH stimulates release of ACTHGrowth hormone (GH)GHRH stimulates release of GHThyroid stimulating hormone (TSH)TRH stimulates release of TSHLuteinizing hormone (LH)GnRH stimulates release of LHFollicle-stimulating hormone (FSH)ProlactinUnder continuous hypothalamic inhibition by dopamine
47Pituitary tumors Is it hormonally active? Is there any mass effect? PRL > GH > ACTH > LH/FSH >> TSHAlpha chain tumors not biologically activeIs there any mass effect?Bitemporal hemianopsia, headache, seizuresIs it affecting normal production of pituitary hormones?Most critical: ACTH and TSHBeware low free T4 but “normal” TSH!Remember inappropriate normals!!
48Prolactinoma Most common pituitary tumor Women: secondary amenorrhea and galactorrheaMen: hypogonadismTreatment: dopamine agonistBromocriptine or carbegolineNOT SURGERY!!Suspect another tumor if tumor > 1 cm and PRL < 200Severe-long standing primary hypothyroidism will ↑ TRH →↑PRL and ↑growth of thyrotrophs → pituitary mass → give levothyroxine
49Patient had menarche at 13 and has irregular periods since then. 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 testRandom growth hormone measurementSerum cortisolVisual field testing
50Other causes of hyperprolactinemia PregnancyExogenous estrogensPrimary hypothyroidismDrugs: metoclopramide, amytriptyline, phenothiazines, antidopaminergicsOther tumors that compress pituitary stalk
51Acromegaly Diagnosis often overlooked and late (>10 years) Often macroadenoma (>1 cm)Frontal bossing, enlarging hands and feetSleep apnea, HTN, carpal tunnel, skin tags, colon polypsScreening: ↑ IGF-1GH too pulsatile!Confirmation: GH does not suppress 1 hour after glucose load (remains >1)Treatment: surgery
52Acromegaly Use medical therapy if incomplete control after surgery Somatostatin analogues: octreotide, lanreotideGH receptor antagonist: pegvisomantUsually added to somatostatin analogueGoal: normal IGF-1 and normal GH suppression after glucose load
54Cushing’s syndrome Make diagnosis Localize site of problem Overnight 1 mg dexamethasone suppression testElevated urinary free cortisol in 24-hour urineElevated midnight salivary cortisolLocalize site of problemACTH-producing pituitary tumor (70%)Ectopic ACTH (15%)Most common—bronchial carcinoidAdrenal adenoma or carcinoma (15%)
55Cushing’s syndrome Check ACTH Primary versus ectopic ACTH < 5—adrenal adenoma or carcinoma>20—pituitary or ectopic ACTH>200—most likely ectopic ACTHPrimary versus ectopic ACTHHigh dose dexamethasone suppression testNot so good as some ectopics will suppressInferior petrosal sinus samplingGOLD STANDARD
56Cushing’s syndrome Visualize lesion Cushing’s disease—MRI pituitaryEctopic—CT chest/abdomen/pelvisAdrenal—CT or MRI adrenalRemember pituitary or adrenal mass may be just an incidentaloma!
5967 yo man evaluated in ER for explosive headache and blurred vision that began 4 hours ago. Reports 3 month history of fatigue, 10 lb weight gain and erectile dysfunction.Physical exam shows pale man who appears uncomfortable. BP 88/56. Visual field exam reveals bitemporal hemianopia. Other than neck stiffness, rest of exam is normal.Sodium 128. CT shows heterogenous sellar mass with suprasellar extension and bowing of optic chiasm.In addition to neurosurgical consult, what is most appropriate initial management?Glucocorticoid administrationInsulin tolerance testLumbar punctureSerum prolactin measurement
60Pituitary apoplexy Hemorrhagic infarction of pituitary Severe headache, altered mental status, ophthalmoplegiaCT/MRI: high density mass within pituitaryAdminister stress doses of steroidsContact neurosurgery for possible decompression
61Diabetes insipidus Problem with ADH Central—no ADH productionNephrogenic—no ADH actionRemember that hypokalemia and hypercalcemia can cause nephrogenic DIPersistent non-concentrated polyuria with dehydrationHypernatremia, hyperosmolarity (>295), low urine osmolarity (<300)Confirm with water deprivation test
62Diabetes insipidusDistinguish central from nephrogenic diabetes insipidus with 1 mcg desmopressinCentral: increases urine osmolarity >50%Nephrogenic: no responseTreatmentCentral: DDAVPNephrogenic: thiazide diuretics
63SIADH Too much ADH Retain too much free water → hyponatremia Hyponatremia, low serum osmolarity (<275), inappropriately urine osmolarity (>100), high urine sodium (>30)Rule out dehydrationCheck renal, adrenal and thyroid functionTreatmentWater restrictionConivaptan—ADH receptor antagonist; acute txDemeclocycline—blocks ADH at collecting tubal, chronic tx
64Excess Insufficiency ACTH GH ACTH GH TSH FSH/LH TSH FSH/LH Acromegaly Cushing’s DiseaseSlow onsetClassic phenotypeHTN/diabetesosteoporosisSkin thinning, ecchymosesGHAcromegalySlow OnsetSleep apneaCarpal TunnelHTN/DiabetesColon polypsSkin tagsACTHSalt craving, nausea, “vague abdominal pain”, FeverHYPOGLYCEMIA Weight lossPubertal hair lossGHYoungShort statureOlder“Decreased Vigor”TSHRare.Hyperthyroidism with “normal” or increased TSHFSH/LHAmazingly rarePrecocious pubertyMcCune Albright SyndromeTSHRare.Hypothyroidism with “normal” or decreased TSHFSH/LHVERY COMMONHypogonadism with atrophic gonads and “normal” or low FSH/LH
65Complications of pituitary irradiation HypopituitarismLow prolactin supports diagnosisCan see hypothyroidism and adrenal insufficiencyCan develop years after radiation treatmentVisual defectsDue to damage to optic chiasmSecond tumor development
66Pituitary cases32 yo ♂ with severe HA’s, double vision, 2.5cm pituitary mass compressing the optic chiasm, prolactin level 3,215. Cause and Treatment?Prolactinoma (PRL > 200). Medical therapy first: Try dopamine receptor agonist (cabergoline, bromocriptine). If fails, surgery.22 yo ♂ with HA’s, 1.5cm cystic-solid sellar mass with calcification. PRL 70. Cause?Craniopharyngioma with Stalk effect Interruption of hypothalamic inhibition.32 yo with low energy, missed menstrual cycle, PRL 68Pregnant (check HCG)
67Bronchial carcinoid. ACTH > 200. IPSS/periphery ACTH ratio < 2 Pituitary cases32 yo woman with Cushingoid features. Serum K 4.0.MRI: 0.8 cm pituitary mass. IPSS/Periphery ratio >242 yo woman with Cushingoid features. Serum K 3.0. CT chest: lung nodule. Nonsmoker. MRI pituitary: normal. IPSS/Periphery ratio <23. 69 yo man, smoker. Weight loss, hyperpigmentation, new onset DM and HTN. No Cushingoid features. Serum K 2.3. CT chest: RUL mass with adenopathies IPSS/Periphery ratio <2. ACTH >200Cushing’s disease (pituitary). ACTH < 200Next Step ----> Surgery.Bronchial carcinoid. ACTH > 200.IPSS/periphery ACTH ratio < 2Small cell lung cancer
69HirsutismDevelopment of androgen-dependent terminal body hair in a woman in places not usually foundVariation in different ethnic groupsAffects 5-10% of women of reproductive age2 most common causes are idiopathic hirsutism and PCOS
71Red flags for tumors Recent onset and/or rapid progression Late onset (ie post-menopausal)Virilization—voice change, clitomegalyTotal testosterone >200 ng/dL
72PCOS Usually evident at puberty Anovulatory cycles with continuous stimulation of ovary by LHOligomenorrhea or amenorrheaHyperandrogenismTotal testosterone elevated but <200 ng/dLLH:FSH ratio usually >2:1Lacks sensitivity and specificity
74Hypogonadism Low sex hormone levels Primary hypogonadism—problem with gonadNormal pituitary →↑FSH (women) and ↑LH (men)Secondary—problem with pituitaryTertiary—problem with hypothalamusSecondary and tertiary may have inappropriately normal LH and FSH levelsRemember inappropriate normals!!
75Causes of hypogonadism in women PrimarySecondaryTurner syndromeRadiationChemotherapyAutoimmune destruction of ovaries (APS)Kallman syndromeHyperprolactinemiaAnorexia nervosaStrenuous exercise trainingStressHypothalamic/pituitary disease
76Turner syndrome Primary amenorrhea with ↑FSH and ↑LH Incidence 1:2000 (>50% mosaicism)Karyotype 45 XOLymphocytes may be normal. Need fibroblast.If any Y present, ↑gonadoblastoma →prophylactic oophorectomyPhysical exam: short stature, webbed neck, broad chest with widely spaced nipples, little breast development↑ risk of aortic stenosis, aortic coarctation (10%), renal abnormalities (50%)Hypothyroidism from Hashimoto’s thyroditisOsteoporos from hypogonadismTreatmentEstrogen replacementGH for short stature
77What is most appropriate next diagnostic step? 18 yo woman with 6 month history of amenorrhea. Menarche at 13 and had normal cycles until 6 months ago. No hot flushes, night sweats, weight changes or cold/heat intolerance. No uterine procedures. No family history of thyroid disease or primary ovarian insufficiency.Vital signs normal. BMI 22. No hirsutism, acne, alopecia, clitoromegaly or galactorrhea.Lab results are normal, including FSH, hCG, prolactin, free T4 and TSH.What is most appropriate next diagnostic step?Measure total testosterone and DHEAMRI of pituitaryPelvic ultrasoundProgesterone challenge testing
78Amenorrhea Rule out pregnancy Check hCGRule out pituitary disease or ovarian failureCheck prolactin and FSHProgestrin challenge (Provera 10mg x 10 days)If bleeding, anovulatory cycles (PCOS)If no bleeding, anatomic defect
79Klinefelter syndrome Form of primary male hypogonadism Incidence 1:1000 live birthsKaryotype 47 XXYPre-puberal failure with small, firm testesGynecomastiaSometimes decreased intellectual development
80Kallman syndrome Form of primary hypogonadism Normal karyotype (46 XY) Due to abnormal development of GnRH producing neuronsAlso close to olfactory systemGet isolated hypogonadotrophic hypogonadism with anosmiaNormal karyotype (46 XY)Small testes (but larger than Klinefelter)Infertility treated with LHRH infusion pump
82Erectile dysfunction Start with TSH and testosterone level If ↓ testosterone, get prolactin and LHDrugs associated with ED (without hypogonadism): thiazide, beta blockers, anticholinergics, SSRIs, clonidine, morphine
84Hypogonadism cases25 yo man with decreased libido, decreased testicular volume, otherwise normal. AST/ALT elevated. Next Test? 47 yo man with rheumatoid arthritis on chronic opiate therapy with prednisone 10mg daily; hypogonadal symptoms. Likely diagnosis? 37 yo man with decreased libido, develops gynecomastia and galactorrhea. Beta-hCG normal, labs confirm low LH and low testosterone. Next test?Hemochromatosis - Iron saturation > 45 is quite suggestive.May all see arthritis, risk for Type I DM.Glucocorticoid-induced hypogonadismSuppresses GnRH release and reverses with removal of steroids.HyperprolactinemiaCheck prolactin level to confirm
85Hypogonadism cases18 yo man with cryptorchidism, delayed puberty, cleft palate, abnormal movements. Diagnosis?27 yo female marathon runner with amenorhea.Test to check in long term hypogonadism DEXA scanHigh risk for osteoporosis!Kallman Syndrome – Neuronal Migration disorder – alsoassociated with anosmiaExercise-Induced Amenorrhea – Mediated by low GnRHAlso seen with anorexia, low body fat
87Risk factors for osteoporosis ThinCaucasianFemale genderFirst degree relative with osteoporosisAlcoholSmokingRheumatoid arthritisUse of glucocorticoids
88Indications for bone mineral density Female > 65 years oldPost-menopausal female <65 years if:1st degree relative, smoker, weight < 127 lbsMale >70 years oldFragility fractureGlucocorticoids >3 monthsMedical condition associated with osteoporosisHyperparathyroidism, Cushing’s disease, etc
89Interpreting DEXA results T-score compares patient to 30-year womanZ-score compares patient to age-related controlsNormal—T-score > -1Osteopenia—T-score > -1 but < -2.5Use FRAX score to determine who to treatIf risk >3% hip and >20% any, treat patientOsteoporosis—T-score < -2.5
90What is most appropriate next step in management? 66 yo woman comes for management of osteoporosis noted on screening DEXA scan. No personal history of fracture. No family history of parathyroid disease or low bone mineral density. Has HTN controlled by lisinopril. No other medications or supplements.Vital signs normal. Good dentition. Physical exam normal except for mild kyphosis.Lab: albumin 4.0, calcium 8.7, creatinine 0.7, phosphorus 2.9, PTH 176.DEXA showed T-score -2.1 in lumbar spine, -3.0 in femoral neck, and -2.5 in total hip.What is most appropriate next step in management?Measure 1,25-dihydroxyvitamin DMeasure 25-hydroxyvitamin DParathyroidectomyRepeat DEXA scan in 1 year
91Stop use after 2 years → risk of osteosarcoma. Osteoporosis therapyDrugSpineHipBisphosphonates+Raloxifene-TamoxifenCalcitoninTeriparatideStop use after 2 years → risk of osteosarcoma.Useful for bone pain. Tachyphylaxis limits use.
92Paget’s Disease Disease of increased bone turnover Bone pain with elevated alkaline phosphataseBone scan: focal uptake with no evidence of cancer.If affecting skull osteoporosis circumscriptaRisk of cranial nerve palsies, particularly CN VIIIRisk of fracture at site of bone turnoverTherapy–pamidronate or alendronate daily
94Osteomalacia Also see ↓ Ca, ↓ PO4, ↑ alk phos, ↑ PTH Decreased bone mineralization usually from vitamin D deficiencyIn kids, we call it rickettsTypically older patient with bone pain and proximal muscle weakness“bilateral symmetric pseudofractures”Check 25-OH vitamin D and replace to >30Also see ↓ Ca, ↓ PO4, ↑ alk phos, ↑ PTHWork-up vitamin D deficiency