Endocrinology

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 27.4. 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?

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1. Diabetes insipidus2. Hydrocephalus3. Hypopituitarism4. Regrowth of the adenoma

HypopituitarismGenetic 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

Hormone Treatment

TSH Levothyroxine, 50-200 mg/d; adjust by measuring free T4 levels.

ACTH Hydrocortisone, 10-20 mg in AM and 5-10 mg in PM, or prednisone, 2.5-5.0 mg in AM and 2.5 mg in PM; adjust clinically. Stress dosage, hydrocortisone, 50-75 mg IV every 8 hours.

LH/FSHMen Testosterone: 1% gel, 1-2 packets (5-10 g) daily; transdermal patch, 5 g

daily; or testosterone enanthate or cypionate, 100-300 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 (0.3-0.625 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 200-300 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, 10-20 µg once or twice daily; or tablets, 0.1-0.4 mg every 8-12 h; or injected, 1-2 µg SC or IV, every 6-12 h.

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

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 32.3. 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?

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1. Cabergoline2. Pituitary Surgery via a craniotomy3. Radiation therapy4. Somatostatin analogue5. Transsphenoidal surgery

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

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

• Occurs before epiphyseal closure gigantism• After epiphyseal closureacromegaly• 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

Disorders of the Thyroid

• 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

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 23.3. 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?

1. Methimazole2. Repeat measurement of TSH and free T 4 levels3. Thyroid scan and 24 hour radioactive iodine uptake test4. Thyroid ultrasound

Thyrotoxicosis

Hyperthyroidism Other TSH Mediated Thyroiditis

Graves DiseaseToxic MNGToxic Adenoma

AcuteSubacutePostpartumSilentHashimotoDrug-inducedTraumaticRiedel

TSH secretingThyroid Hormone Resistance

Exogenous T4/T3Iodine Load

• Encompasses all forms of thyroid hormone excess

• Where as hyperthyroidism refers to thyroid gland over activity

Graves Toxic Adenoma/MNG

Subactue thyroiditis Thyrotoxic Phase

Postpartum Thyroiditis

Exogenous T4

Exogenous T3

TSH-secreting pituitary Tumor

TSH Nml/

FT4 Nml/ Nml/ Nml/ Nml/ Nml/ Nml/ Nml/

FT3 Nml/ Nml/ Nml/ Nml/ Nml/ Nml/

TPO Ab +/- +/- +/- +/- - - -

TG Ab +/- +/- +/- +/- - - -

TSI + - - - - - -

TB II + - - - - - -

TG

RAIU Nml/ Nml/ <5% <5% <5% <5% Nml/

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 19.5. 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: 9.1Which of the following is the most appropriate treatment regiment at this time?

1. Atenolol2. Methimazole3. Atenolol and Methimazole4. Radioactive iodine and methimazole

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

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

Hashimoto Thyroiditis

Subclinical Hypothyroidism

SAT Recovery Phase

Postpartum Thyroiditis Hypothyroid Phase

Central Hypothyroidism

TSH Nml/

FT4 Nml/ Nml Nml/ Nml/ Nml/

FT3 Nml/ Nml Nml/ Nml/ Nml/

TPO Ab+ + +/- - + -

TG Ab +/- +/- +/- +/- +/- -

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?

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1. Add iodine therapy2. Measure her free triiodothyronine (T3) level3. Recheck her serum TSH level4. Continue current managment

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

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?

1. Fine needle aspiration biopsy of the nodule2. Measurement of anti-thyroperoxidase and anti-thyroglobulin antibody titers3. Neck CT with contrast4. Thyroid scan with technetium5. Trial of levothyroxine therapy

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

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?

1. Atenolol2. Propanolol, prophylthiouracil, and hydrocortisone3. Thyroid ablation with radioactive iodine4. Thyroid scan with a radioactive iodine uptake test

Thyroid Storm

Cardiovascular (tachycardia, Afib, CHF)

Gastrointestinal-Hepatic (Diarrhea, abdominal pain, jaundice)

CNS (agitationseizure/coma)

Precipitant History (storm previously)

Thermoregulatory Dysfunction (temperature)

Scores TotaledThyroid Storm: >45Impending Storm: 25-44Storm unlikely: < 25

Medication CommentInhibit 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

Thyroid Storm

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?

1. Intravenous Levothyroxine2. Intravenous Levothyroxine and intravenous hydrocortisone3. Intravenous levothyroxine, intravenous hydrocortisone, and empiric antibiotics4. Review of results of TSH and free T4 level measurements

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

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?

1. Cosyntropin stimulation test2. Insulin-induced hypoglycemia test3. Measurement of morning salivary cortisol level4. 24 hour urine free cortisol measurement

Disorders of the Adrenal Glands

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

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 HyperpigmentationDehydrationHypotensionDecreased pubic/axillary hair in women

Normal pigmentationNormal volumeSlight decrease in blood pressureDecreased pubic/axillary hair in women

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

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?

1. Cosynthropin stimulation test2. High-dose dexamethasone suppression test3. Measurement of morning serum cortisol level4. Measurement of 24 hour urine free cortisol excretion

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

Step 1 and 2

Step 3

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, 18-25 mL) bilaterally. The penis appears normal. LabsFSH: < 0.1, LH: <0.1, Prolactin: 12, Total Test: < 50MRI of the pituitary gland shows normal findings.Which is the most likely diagnosis?

1. Anabolic Steroid Abuse2. Nonfunctioning Pituitary macroadenoma3. Primary Testicular Failure4. Prolactinoma

Male Reproductive DisordersPrimary 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 20-30 minute intervals)Random Testosterone> 350ng/dL excludes hypogonadism, <200ng/dL confirms hypogonadismIf low testosterone, will need to check bioavailable testosterone

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?

1. Hysterosalpingography2. Measurement of serum follicle-stimulating hormone and prolactin levels3. Measurement of total serum testosterone level4. Pelvic Ultrasound

Female Reproductive DisordersPrimary 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 firstReproductive axis is particularly vulnerable to disruption by systemic illness and weight lossFirst Step: Test: FSH, prolactin, TSH, free thyroxine levelsSecond 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

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?

1. Alendronate2. Calcitonin3. Teriparatide4. Testosterone

Metabolic Bone Disease• Osteoporosis

– T score of 2.5 SDs below the peak values– Severe: if < -2.5 with history of fragility

fracture– Osteopenia: -1.0- -2.5– Normal: >-1.0– Treatment: (anyone with <-1.0)

• Vit D: >50 years old 800-1000U/d• Vit D: <50 years old 400-800 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 1200-1500mg/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

Diabetes

Diabetic Complications• Acute:

– DKA– Hyperglycemic Hyperosmolar Syndrome– Hypoglycemia

• Chronic:– Microvascular

• Diabetic nephropathy• Diabetic neuropathy• Diabetic retinopathy

– Macrovascular• CAD• Carotid artery disease• CVA