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Presentation on theme: "Endocrinology."— Presentation transcript:

1 Endocrinology

2 Regrowth of the adenoma
A 54-year-old man is evaluated for increasing fatigue and loss of libido. He reports no headache, diplopia, visual loss, rhinorrhea, or changes in thirst, urination, or weight. The patient underwent transsphenoidal surgery 6 years ago to remove a nonfunctioning pituitary adenoma; results of postoperative pituitary testing were normal. He had stereotactic irradiation to treat the residual tumor 3 months after surgery. He has no pertinent family history and takes no medications. An MRI performed 18 months ago showed no growth of the residual pituitary tumor. Physical examination reveals a pale man. Blood pressure is 106/70 mm Hg, pulse rate is 60/min, respiration rate is 14/min, and BMI is Other findings are unremarkable. Results of routine hematologic and serum chemistry studies are normal, except for a hemoglobin level of 11.8 g/dL (118 g/L). Which of the following is the most likely diagnosis? Risk factor: raidation therapy DI:hypernatremia, usually 24 hours after surgery Surgery + irradiation: very effective > 90% 20% of these patients have hypopituitarism Diabetes insipidus Hydrocephalus Hypopituitarism Regrowth of the adenoma


4 Hypopituitarism Genetic defects Hypothalamic hormone gene defects
Hypothalamic hormone receptor gene defects Pituitary hormone gene defects Pituitary hormone receptor gene defects Transcription factor gene defects (affecting multiple pituitary hormones) Embryopathies Anencephaly Midline cleft defects Pituitary aplasia Kallmann syndrome (anosmin gene defect) Acquired defects Tumors (pituitary adenomas, craniopharyngiomas, dysgerminomas, meningiomas, gliomas, metastatic tumors, Rathke cleft cysts) Irradiation Trauma (neurosurgery, external blunt trauma) Infiltrative disease (sarcoidosis, Langerhans cell histiocytosis, tuberculosis) Empty sella syndrome Vascular (apoplexy, Sheehan syndrome, subarachnoid hemorrhage) Lymphocytic hypophysitis Metabolic causes (hemochromatosis, critical illness, malnutrition, anorexia nervosa, psychosocial deprivation) Idiopathic causes

5 Hormone Treatment TSH Levothyroxine, mg/d; adjust by measuring free T4 levels. ACTH Hydrocortisone, mg in AM and 5-10 mg in PM, or prednisone, mg in AM and 2.5 mg in PM; adjust clinically. Stress dosage, hydrocortisone, mg IV every 8 hours. LH/FSH Men Testosterone: 1% gel, 1-2 packets (5-10 g) daily; transdermal patch, 5 g daily; or testosterone enanthate or cypionate, mg IM every 1-3 weeks. Adjust by measuring testosterone levels. May need injectable gonadotropins (LH, FSH) or GnRH (if a primary hypothalamic lesion) for spermatogenesis. Women Cyclic conjugated estrogens ( mg) and medroxyprogesterone acetate (5-10 mg) or low-dose oral contraceptive pills. Estrogen patches also available. May need injectable gonadotropins (LH, FSH) for ovulation or in vitro fertilization techniques. GH Adults start at µg subcutaneously daily and increment by 200 µg at monthly intervals. Adjust to maintain IGF-1 levels in the midnormal range. Women receiving oral estrogens require higher doses. Vasopressin Desmopressin: metered nasal spray, µg once or twice daily; or tablets, mg every 8-12 h; or injected, 1-2 µg SC or IV, every 6-12 h.

6 Pituitary Tumors Micro < 10mm Macroadenomas > 10mm
Goals of therapy reduce tumor mass Prevent tumor recurrence Correct any hormone oversecretion witout damaging normal pituitary All surgery is primary mode of therapy EXCEPT prolactinoma Radiation is adjunctive therapy for residual tumor and or continued hormone hypersecretion

7 Pituitary Surgery via a craniotomy Radiation therapy
A 34-year-old man is evaluated for a 1-year history of impotence. He reports mild fatigue but no headaches or visual symptoms. Personal and family medical histories are noncontributory. He takes no medications. Physical examination reveals an obese man. Blood pressure in 132/80 mm Hg, pulse rate is 80/min, respiration rate is 16/min, and BMI is He has normal secondary sexual characteristics. Labs: Prolactin: 11,420, Testosterone: 134, TSH: 0.6, Thyroxine Free: 0.52, Cortisol: 4.3. An MRI shows a 3.2 x 1.7 x2.8cm macroadenoma invading the cavernous sinus and wrapping around the right carotid artery. Results of visual field testing are normal. In addition to treating the hypopituitarism, which of the following is the most appropriate initial therapy for this patient? Hypogonadism common presenting symptom of hyperprolactinemia Additional hormone deficiency may be the result of mass effect Dopamine agonists are very effective Causes normalization of prolactin levels is greater than 90% of patients Surgery and radiation are reserved for people who cannot tolerate dopamine agonists Surgery not an option for tumor wrapped around the carotid artery Cabergoline Pituitary Surgery via a craniotomy Radiation therapy Somatostatin analogue Transsphenoidal surgery

8 Prolactinoma/Hyperprolactinemia
Most common type of pituitary adenoma hyperprolactinemia caused by drugs and other non-prolactinoma causes level is usually < 150ng/mL Drugs that block dopamine release or action will often cause increased prolactin: Antipsychotics Verapamil Metoclopramide Dopamine can also be decreased by compression of the hypothalams or pituitary stalk Pregnancy causes hyperprolactinemia by estrogen causing lactotroph hyperplasia Idiopathic hyperprolactinemia

9 Hyperprolactinemia Symptoms: galactorrhea, oligomenorrhea, amenorrhea in women, ED in men, in both sexes: decrease libido, infertility, and osteopenia Treatment: dopamine agonist (Carbegoline or Bromocriptine), in idopathic hyperprolactinemia you can try OCPs in women not interested in being fertile. Dopamine agonists can decrease size of tumor by 50% so ok to use in patients with visual symptoms

10 Occurs before epiphyseal closure gigantism
After epiphyseal closureacromegaly Prognathism, enlargement of nose, lips, and tongue, frotnal bossing, malocclusion, sleep apnea, enlargemtn of hands and feet, arthritis, carpal tunnel 2-3 fold increase in mortality because of CV and CVA IGF1 levels Tx: surgery, adjunctive radiation or medical therapy Acromegaly and GH excess Cushing Disease and ACTH excess: discuss in adrenal disorders Both present with local mass effects Treatment is surgery Gonadotropin-Producing adenomas and nonfunctionign adenomas Screen for hormone overproduction (prolactin, IgF 1, overnight dexamethasone suppresion test Treatment indicated for hormone over or underproduction or visual fielf defects Periodic monitoring is appropriate if no symtpoms and normal hormones Incidentalomas Rare Somatostatin analogues are effective as adjunctive treatment of patients with TSH secreting adenomas TSH excess

11 Disorders of the Thyroid

12 Free T4 and T 3 are active Thyroid produces mostly T4 and most T3 comes from peripheral conversion Inactive bound to albumin, prealbumin, or TBG

13 Repeat measurement of TSH and free T 4 levels
A 26-year-old woman is evaluated for a 5-day history of constipation, fatigue, and weight gain. Two months ago, she began experiencing nervousness, heat intolerance, and weight loss but says these symptoms abated after 6 weeks. The patient delivered a healthy infant 14 weeks ago. After thyroid function tests performed 8 weeks postpartum revealed a thyroid-stimulating hormone (TSH) level of 0.02 µU/mL (0.02 mU/L) and a free thyroxine (T4) level of 3.5 ng/dL (45.2 pmol/L), she was placed on atenolol, 25 mg/d. On physical examination, blood pressure is 115/70 mm Hg, pulse rate is 50/min, respiration rate is 14/min, and BMI is No proptosis or inflammatory changes are noted on ocular examination. Examination of the neck reveals no tenderness or bruits; the thyroid gland cannot be palpated. Which of the following is the best next step in management? Postpartum thyroiditis, occurs in 5% of wormen Painless Transient thyrotoxicosis, trasient hypothyroidism or thyrotoxicosis Radioactive iodine uptake will be low during thyrotoxic phase and then elevated during the hypothyroid phase Methimazole Repeat measurement of TSH and free T 4 levels Thyroid scan and 24 hour radioactive iodine uptake test Thyroid ultrasound

14 Thyrotoxicosis Encompasses all forms of thyroid hormone excess
Where as hyperthyroidism refers to thyroid gland over activity

15 TSH Nml/ FT4 FT3 TPO Ab +/- - TG Ab TSI + TB II TG RAIU <5% Graves
Toxic Adenoma/MNG Subactue thyroiditis Thyrotoxic Phase Postpartum Thyroiditis Exogenous T4 Exogenous T3 TSH-secreting pituitary Tumor TSH Nml/ FT4 FT3 TPO Ab +/- - TG Ab TSI + TB II TG RAIU <5% TBII: thyrotropin-binding inhibitory immunoglobulin RAIU: radioactive iodine uptake

16 Atenolol and Methimazole Radioactive iodine and methimazole
An 18-year-old woman is evaluated for tachycardia, nervousness, decreased exercise tolerance, and weight loss of 6 months’ duration. She has otherwise been healthy. Her sister has Graves disease. She takes no medications. On physical examination, blood pressure is 128/78 mm Hg, pulse rate is 124/min, respiration rate is 16/min, and BMI is There is no proptosis. An examination of the neck reveals a smooth thyroid gland that is greater than 1.5 times the normal size. Cardiac examination reveals regular tachycardia with a grade 2/6 early systolic murmur at the base. Her lungs are clear to auscultation. Labs: HCG: negative, TSH: <0.01, Free T4: 5.5, Free T3: 9.1 Which of the following is the most appropriate treatment regiment at this time? Make the diagnosis of graves disease Beta blocker indicated for tachycardia MTX or PTU MTX generally has less side efects RAIU is generally reserved for patient with severe thyrotoxicosis or comorbidities Beware of agranulocytosis Atenolol Methimazole Atenolol and Methimazole Radioactive iodine and methimazole

17 Graves Disease Autoimmune process with production of antibodies against TSH receptor Treatment: Antithyroid Drugs PTU Methimazole Side effects: hepatotoxicity, agranulocytosis Use PTU first line only in pregnancy Radioactive iodoine (131-I) Usually hypothyroid after administration Thyroid Surgery Reserved for concurrent nodules, goiters or opthalmopathy in whom radiactive iodine has aggraved

18 Toxic Multinodular Goiter and Toxic Adneoma
TMG: thyroid scan reveals patchy uptake of radioactive iodine Adenoma: thyroid scan reveals “hot” nodule Treatment: 131I Destructive Thyroiditis Subacute, silent, postpartum Transient destruction of thyroid tissue Drug Induced Thyrotoxicosis Lithium, interferon alpha, IL2, amiodarone, Iodine loads Twp types with amiodarne: type 1 (iodine induced) type 2 (destructive) Subclinical Hyperthyroid Treat when TSH < 0.1 or symptoms Start with antithyroid medications

19 Hashimoto Thyroiditis
Subclinical Hypothyroidism SAT Recovery Phase Postpartum Thyroiditis Hypothyroid Phase Central Hypothyroidism TSH Nml/ FT4 Nml FT3 TPO Ab+ + +/- - TG Ab +/-

20 Measure her free triiodothyronine (T3) level
A 23-year-old woman comes to the office for follow-up. The patient has a 5-year history of hypothyroidism and has been on a stable dose of levothyroxine for the past 3 years. She is now 6 weeks pregnant with her first child. Physical examination findings are noncontributory. Results of laboratory studies 1 month ago showed a serum thyroid-stimulating hormone (TSH) level of 2.9 µU/mL (2.9 mU/L) and a free thyroxine level of 1.4 ng/dL (18.1 pmol/L). Which of the following is the most appropriate management? Add iodine therapy Measure her free triiodothyronine (T3) level Recheck her serum TSH level Continue current managment Fetus depends on materal thyroid hormone for the first 10 to 12 weeks of gestation, thyorid levels during pregnancy mus tbe followed closely TSH and total Thyroxine followed (free not as accurate) Total T4 level should be kept stable at 1.5 tims the normal range, TSh should e kept lower than normal Because of estogen elevation during pregnancy, TBG increased

21 Hypothyroidism Hashimoto thyroiditis most frequent cause
Iatrogenic second most frequent (post radiation, post radioactive iodide, post surgical) Treat with levothyroxine therapy Always take on empty stomach, 1 hour before or 2-3 hours after intake of food Goal TSH of 1-2.5 Subclinical Hypothyroidism: don’t treat unless TSH > 10

22 A 35-year-old woman comes to the office for her annual physical examination. The patient says she feel well. She has no pertinent personal or family medical history and takes no medications. On physical examination, vital signs are normal. Palpation of the thyroid gland suggests the presence of a nodule. All other findings of the general physical examination are normal. Laboratory studies show a thyroid-stimulating hormone level of 1.3 µU/mL (1.3 mU/L) and a free thyroxine (T4) level of 1.3 ng/dL (16.8 pmol/L). An ultrasound of the thyroid gland reveals a normal-sized gland with a 2-cm hypoechoic right midpole nodule. Which of the following is the most appropriate next step in management? Fine needle aspiration is the mainstay in evaluation of a nontoxic thyroid nodule Fine needle aspiration biopsy of the nodule Measurement of anti-thyroperoxidase and anti-thyroglobulin antibody titers Neck CT with contrast Thyroid scan with technetium Trial of levothyroxine therapy

23 Structural Thyroid Disease
Factors associated with increased cancer risk: <20, or >60, male, history of H/N irradiation, family history of thyroid cancer, rapid nodule growth, hoarseness, hard nodule, local lymphadenopathy, fixation to adjacent tissue and vocal cord paralysis Don’t need to measure antibodies Ultrasound characteristics: > 3 cm, speckled calcification, high intravascular flow Biopsy all nodules > 1cm or with worrisome US feaures

24 Propanolol, prophylthiouracil, and hydrocortisone
A 55-year-old woman is evaluated for new-onset fever, productive cough, palpitations, and hyperdefecation. The patient has Graves disease treated with methimazole. She has been nonadherent to her medication regimen, not having refilled her methimazole prescription 6 weeks ago. On physical examination, temperature is 39.4 °C (102.9 °F), blood pressure is 140/85 mm Hg, pulse rate is 138/min, and respiration rate is 16/min. Examination of the neck reveals a smoothly symmetrical thyroid gland that is three time its normal size. Auscultation of the lungs reveals crackles in the left lower lobe. Cardiac examination shows tachycardia and a regular rhythm. Labs: WBC: 14,300, ALT: 100, AST: 75, Alk Phos: 135, TSH: <0.1, Free T4: 4.4, Free T3: 7.8 A chest radiograph shows a left lower lobe infiltrate. Electrocardiography reveals sinus tachycardia. Ceftriaxone and azithromycin are begun. Which of the following is the most appropriate next step in management? Clinical diagnosis Don’t us RAIA since it can acutely exacerbate thyrotoxic state Atenolol Propanolol, prophylthiouracil, and hydrocortisone Thyroid ablation with radioactive iodine Thyroid scan with a radioactive iodine uptake test

25 Thyroid Storm Thyroid Storm Cardiovascular (tachycardia, Afib, CHF)
Gastrointestinal-Hepatic (Diarrhea, abdominal pain, jaundice) CNS (agitationseizure/coma) Precipitant History (storm previously) Thermoregulatory Dysfunction (temperature) Scores Totaled Thyroid Storm: >45 Impending Storm: 25-44 Storm unlikely: < 25 Medication Comment Inhibit hormone production PTU, MTX Inhibits T4-T3 conversion Inhibition of hormone release Iodine-potassium solutions (SSKI) Begun >1 h after first antithyroid drug B blockers propanolol Inhibits T4-T3 conversion at higher doses, also blocks beta adrenergic receptors Supportive therapies hydrocortisone Inhibtis T4 to T3 conversion; used with possible adrenal insufficiency for hypotension

26 Intravenous Levothyroxine
A homeless man is brought by ambulance to the emergency department. He was found unconscious in an abandoned, unheated house by city workers. The temperature has been below freezing for the past 24 hours. No medications were found on the patient. Physical examination reveals an obese, poorly arousable older man. Temperature is 33.3 °C (92.0 °F), blood pressure is 120/90 mm Hg, pulse rate is 50/min, and BMI is 34. His pupils are equal, round, and reactive to light. Examination of the neck reveals a well-healed surgical scar at the base. His lungs are clear to auscultation. Distant heart sounds are heard on cardiac examination. There is 2+ edema bilaterally in the lower legs. Neurologic examination shows bilateral ankle jerk reflexes with delayed tendon relaxation recovery. Labs: Creatinine: 1.5, Sodium: 130, Potassium: 3.8, Cl: 101, Bicarb: 27, TSH: pending, free T4: pending, ABG: pH: 7.31, Pco2: 55, Po2: 60, Oxygen Saturation: 90% Blood, urine, and sputum cultures are obtained. Findings on chest radiography are within normal limits. Electrocardiography reveals sinus bradycardia with low voltage throughout. In addition to beginning intravenous normal saline and passively warming the patient, which of the following is the most appropriate next step in management? In patients will myxedema coma, immediate therapy should be instituted until thyroid hormone levels can be normalized, and potential underlying precipitants should be identified and addressed Intravenous Levothyroxine Intravenous Levothyroxine and intravenous hydrocortisone Intravenous levothyroxine, intravenous hydrocortisone, and empiric antibiotics Review of results of TSH and free T4 level measurements

27 Myxedema Coma Extreme manifestation of hypothyroidism systemic decompensation Common precipitating factors: hypothermia, stroke, heart failure, infection, metabolic disturbances, trauma, GI bleeding, acidosis, hypoglycemia, hypercalcemia Hallmark findings: hypothermia and mental status changes, hypoventilation and hyponatremia Treatment: IV levothyroxine, liothyronine (oral of IV) ** more controversial

28 Cosyntropin stimulation test Insulin-induced hypoglycemia test
A 32-year-old woman is evaluated for a 3-month history of fatigue, nausea, poor appetite, and salt craving. She also reports a 6.0-kg (13.2-lb) weight loss over this same period. On physical examination, temperature is normal, blood pressure is 92/62 mm Hg supine and 78/58 mm Hg sitting, pulse rate is 88/min supine and 110/min sitting, respiration rate is 16/min, and BMI is 25. Her skin is tanned, and hyperpigmentation is noted in the gum line. Labs: Na: 127, K: 5.9, Chloride: 101, Bicarb: 24, ACTH: 155, Cortisol (8am): 8ug/dl (normal 5-25) Which of the following is the most appropriate next diagnostic test? Primary adrenal insufficiency Dark pigmentation <3 am cortisol is diagnostic 3-10 suggestive Confirmed by cosyntopin and cortisol < 18 Insulin induced hypoglycemia test: give insulin  hypoglycemia stimulates ACTH secretion adrenal glands cortisol (only done by endocrinologists…. High adverse effects) Cosyntropin stimulation test Insulin-induced hypoglycemia test Measurement of morning salivary cortisol level 24 hour urine free cortisol measurement

29 Disorders of the Adrenal Glands

30 Adrenal Insufficiency
Primary Adrenal Insufficiency Impaired secretion of ALL adrenal hormones Causes: autoimmune adrenalitis, infection (TB, fungal, bacterial, HIV), Metastatic disease, Medications, Hemorrhage Central Adrenal Insufficiency Impaired production of ACTH-dependent corticosteroids (cortisol, DHEA, and DHEA sulfate) Causes: exogenous steroid use, pituitary cysts, hypothalamic tumors, sarcoidosis, cranial irradiation, drugs, megace

31 Characteristic Primary Adrenal Insufficiency Central Adrenal Insufficiency Symptoms Fatgiue, nausea, anorexia, weight loss, abdominal pain, arthralgia, low-grade fever; salt craving, postural dizziness, decreased libido Same symptoms as primary insufficiency but no salt craving and postural dizziness Signs Hyperpigmentation Dehydration Hypotension Decreased pubic/axillary hair in women Normal pigmentation Normal volume Slight decrease in blood pressure Major Lab Findings Low basal serum cortisol level (< 5.0) with a uboptimal response to cosyntropin, low serum CHEA and DHEA-S levels but high plasma renin activitiy and ACTH level Same cortisol findings as primary insufficency except low or inappropriately normal ACTH level; normal aldosterone and plasma renin activity Other Lab Findings Hyponatremia, high potassium level, azotemia, anemia, hypglycemia, and leukopenia (with a high % of eosinophils and lymphocytes) Same findings as primary insufficency but also normal potassium level

32 A 45-year-old woman is evaluated for a 6-month history of weakness, menstrual irregularities, hirsutism, insomnia, and emotional lability. She also reports an 8.0-kg (17.6-lb) weight gain during this period. She was previously healthy. She takes no medications. On physical examination, temperature is 36.0 °C (96.8 °F), blood pressure is 172/90 mm Hg, pulse rate is 78/min, respiration rate is 16/min, and BMI is 32. The patient has a rounded, plethoric face with increased supraclavicular and dorsal fat pads. There are areas of unexplained ecchymoses over the upper and lower extremities. Abdominal examination reveals purple striae. She has proximal muscle weakness. Results of routine laboratory studies are normal except for a serum potassium level of 3.4 meq/L (3.4 mmol/L). Which of the following is the most appropriate next test for this patient? Best two screening tests for cushing syndrome are 24 hour urine free cortisol excretion and the 1mg overnight dexamethasone suppression test Cosynthropin stimulation test High-dose dexamethasone suppression test Measurement of morning serum cortisol level Measurement of 24 hour urine free cortisol excretion

33 Cushing Syndrome Syndrome: collection of signs and symptoms occur after prolonged exposure to supraphysiologic doses of corticosteroids Most commonly, exogenous corticosteroid use First Step: Screen for hypercortisolism 24 hour urine free cortisol secretion Loss of normal diurnal variation in cortisol secretion (late night, salivary cortisol level) Loss of feedback inhibition (dexamethasone suppression) Second Step: Confirmation when screening tests are equivocal 24 hour urine cortisol Dexamethasone +CRH Low dose Dexamethasone Suppression Third Step: Determine the cause Determine ACTH dependent vs ACTH independent High dose dexamethasone differentiates pituitary from ectopic sources Fourth Step: Imaging after biochemical confirmation MRI sella tursica: may be normal because often adenomas are too small to be picked up Consider petrosal sinus catheterization with measurements of ACTH levels after CRH CT of adrenal glands if ACTH indepednent: adenoma vs. carcinoma

34 Step 1 and 2

35 Step 3


37 A 25-year-old man is evaluated for a 2-year history of infertility
A 25-year-old man is evaluated for a 2-year history of infertility. He and his wife have been unable to conceive since marrying 2 years ago. Analysis of a semen sample provided 3 weeks ago during an infertility evaluation showed azoospermia. The patient has a strong libido and no history of erectile dysfunction. He has no other medical problems and exercises regularly. There is no family history of delayed puberty or endocrine tumors. On physical examination, the patient appears very muscular. Temperature is normal, blood pressure is 142/85 mm Hg, pulse rate is 55/min, respiration rate is 14/min, and BMI is 22. Visual fields are full to confrontation. There is extensive acne but no gynecomastia or galactorrhea. Testes volume is 4 mL (normal, mL) bilaterally. The penis appears normal. Labs FSH: < 0.1, LH: <0.1, Prolactin: 12, Total Test: < 50 MRI of the pituitary gland shows normal findings. Which is the most likely diagnosis? Normal libido Normal erectile function Atrophic testes Infertility Low gonadotropin an dtestosterone levels Anabolic Steroid Abuse Nonfunctioning Pituitary macroadenoma Primary Testicular Failure Prolactinoma

38 Male Reproductive Disorders
Primary Hypogonadism Almost always causes infertility Chromosomal, congenital, toxic/traumatic, infiltrative Toxic exposures such as alkylating agents Suggested by high serum FSH level and confirmed by inhibin B level < 100 Secondary Hypogonadism Hypothalamic and/or pituitary dysfunction Careful work up in younger men Prolactin suppresses gonadotropins directly Drugs, malnutrition, obesity, aging, anabolic steroids Androgen deficiency in aging male Testosterone production declines at 1%/year after age 25 ADAM (adrogen deficiency in the aging male) Fatigue, muscular loss, poor libido, hot flushes, sexual dysfunction,depression Normal prolactin, normal LH, low testonerone, men >60 y/o Best screening test: total serum testosterone before 10:00AM (ideally, three pooled specimens drawn at minute intervals) Random Testosterone> 350ng/dL excludes hypogonadism, <200ng/dL confirms hypogonadism If low testosterone, will need to check bioavailable testosterone

39 Hysterosalpingography
A 23-year-old woman is evaluated after having no menses for 6 months. She began menstruating at age 12 years, and menses have always been regular. The patient reports no recent weight gain, voice change, or facial hair growth; she says she may even have lost some weight recently and tends to feel warm. She is not sexually active. There is no family history of infertility or premature menopause. On physical examination, temperature is normal, blood pressure is 115/72 mm Hg, pulse rate is 66/min, respiration rate is 14/min, and BMI is 22. She has no acne, hirsutism, or galactorrhea. Her thyroid gland is slightly enlarged. Visual field testing yields normal results. Results of standard laboratory studies are normal, including thyroid-stimulating hormone and free thyroxine (T4) levels; a human chorionic gonadotropin level is negative for pregnancy. Which of the following is the most appropriate first step in evaluation? Absences of menses for 3 or more consecutive months Exclude pregnancy PCOS is the most common cause FSH, TSH, prolactin FSH > 20 suggests ovarian failure If < 30 years old obtain a karotype for turners Then if normal, next step is progestin withdrawal challenge If negative, then need to look at anatomy Hysterosalpingography Measurement of serum follicle-stimulating hormone and prolactin levels Measurement of total serum testosterone level Pelvic Ultrasound

40 Female Reproductive Disorders
Primary Amenorrhea Absence of spontaneous menses by 16 or age 14 in the absence of secondary sexual characteristics Anatomic defects, ovarian failure, chronic anovulation with normal estrogen, chronic anovulation with low estrogen Turners, mullerian duct agenesis, congenital hypopituitarism, anorexia nervosa, systemic illness Requires thorough evaluation by gynecologist Secondary and Hypothalamic Amenorrhea Absence of menses for 3 or more consecutive months in woman who previously menstruated Oligomenorrhea (irregular and infrequent) is more common than complete amenorrhea Women who do not resume their menstrual cycle after OCPs should be evaluated as spontaneous amenorrhea Causes: PCOS,Asherman Syndrome, Elevated prolactin, mosaic Turners, autoimmune oophoritis, hypothalamic amenorrhea Hirsutism and PCOS PCOS: chronic anovulation with normal estrogen levels Ovulator dysfunction, laboratory evidence of hyperandrogenism, ultrasound evidence of polycystic ovaries Most common cause of secondary amenorrhea or oligomenorrhea Serum total testosterone level > 150 suggests an androgen-producing ovarian or adrenal tumor (requires further work up) Treatment: spironolactone + OCP or metformin or clomiphene Check pregnancy test first Reproductive axis is particularly vulnerable to disruption by systemic illness and weight loss First Step: Test: FSH, prolactin, TSH, free thyroxine levels Second Step: progestin withdrawla challenge with medroxyprogesterone acetate for 10 days. Menstruation= normal estrogen levels, absense= low estrogen or anatomic defect review pelvic anatomy with US, MRI or hysteroslpingography

41 Alendronate Calcitonin Teriparatide Testosterone
A 72-year-old man is evaluated for a 2-week history of low back pain. The patient has a history of alcoholism but stopped drinking alcohol 10 years ago. He also has stage 3 chronic kidney disease and a 50-pack-year smoking history. Current medications are hydrochlorothiazide, ramipril, and a multivitamin. On physical examination, vital signs are normal. Lumbar lordosis, decreased mobility and spasm of the paravertebral muscles, and tenderness to palpation at L4-L5 are noted. Neurologic screening examination findings are normal. Labs: Calcium: 9.0, creatinine: 2.1, Phos: 2.1, PTH: 50, Testosterone: 400, 25 hydroxy vitamin D: 34, eGFR: 40 A radiograph of the lumbosacral spine shows a compression fracture of L4. A dual-energy x-ray absorptiometry scan shows a T-score of –3.0 in the lumbosacral spine and –3.2 in the left hip. Which of the following is the best treatment for this patient? T scores of -3.0 and -3.2 Osteoporosis is present and needs to be treated Bisphophanates and teriparatide are approved for men Risk factors: prolonged exposures to steroids, chronic dseases, smoking, excessive alcohol use, low calicu, olderage, hypogonadism, hereditary, race Alendronate Calcitonin Teriparatide Testosterone

42 Metabolic Bone Disease
Osteoporosis T score of 2.5 SDs below the peak values Severe: if < -2.5 with history of fragility fracture Osteopenia: Normal: >-1.0 Treatment: (anyone with <-1.0) Vit D: >50 years old U/d Vit D: <50 years old U/d Severe Vit D deficiency: 50K U three times weekly for 5 weeks Calcium: age related dose Ca: < 50 years old 1000mg/day >50 years old mg/day Bisphosphanates Raloxifene (SERM) Teriparatide (recombinant human parathryoid hormone) Paget Disease of Bone Localized disorder of osteoclast overactivitiy Leads to formation of mechanically ineffective woven or repaired, rather than lamellar, bone. Results in bending and periosteal expansion and cortical thickening Progressive Treatment if symtpoms are present or if lytic involvement of the vertebrae, skull, weight-bearing bones, or areas adjacent to major joints occur bisophosphanates

43 Diabetes Screening for Diabetes: USPSTF: BP > 135/80
ADA: q3yrs > 45 yo

44 Biguanides (metformin): diarrhea, abdominal discomfort
Sulfonylureas: hypoglycemia, weight gain Thiazolidinediones (rosigligtazone, pioglitazone): weight gain; concern with heart failure Alpha Glucosidease inhibitors (acarbose): abdominal discomfort

45 Diabetic Complications
Acute: DKA Hyperglycemic Hyperosmolar Syndrome Hypoglycemia Chronic: Microvascular Diabetic nephropathy Diabetic neuropathy Diabetic retinopathy Macrovascular CAD Carotid artery disease CVA

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