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Endocrinology II Thyroid Pituitary Adrenal Gonads Bone

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1 Endocrinology II Thyroid Pituitary Adrenal Gonads Bone
Sarah E. French, MD July 19, 2014 Thyroid Pituitary Adrenal Gonads Bone

2 Medical-Content Category
Relative Percentage Cardiovascular Disease 14% Pulmonary Disease 10% Gastroenterology 9% Infectious Disease Rheumatology/Orthopedics 8% Endocrinology Medical Oncology 7% Hematology 6% Nephrology/Urology Psychiatry 4% Neurology Allergy/Immunology 3% Dermatology Miscellaneous Obstetrics/Gynecology 2% Ophthalmology Otorhinolaryngology

3 Endocrinology (8%) 17–19 questions
Diabetes mellitus 5–8 Thyroid disorders 2–4 Lipid disorders 2–3 Calcium metabolism and bone 1–5 Male reproductive health 1–2 Adrenal disorders 0–2 Hypertension 0–1 Female reproductive health Hypothalamic disorders Anterior pituitary disorders Posterior pituitary/water metabolism Endocrine tumors and endocrine manifestations of tumors Hypoglycemia not due to insulinoma Polyglandular disorders Nutritional disorders Women’s health endocrine issues Miscellaneous endocrine disorders

4 Thyroid

5 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

6 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

7 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

8 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

9 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.


11 What 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 biopsy Methimazole Serum thyroglobulin measurement 24-hour radioactive iodine uptake test

12 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 Subacute Thyroiditis Silent/post-partum thyroiditis Thyrotoxicosis factitia Struma ovarii

13 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

14 Graves disease Proptosis Acropachy

15 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

16 Amiodarone and the thyroid
Euthyroid hyperthyroxinemia 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

17 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

18 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

19 Cancer derived from follicles
Papillary thyroid cancer Most common Grows slowly Lymphangetic spread Follicular thyroid cancer Hematogenous spread Anaplastic thyroid cancer Extremely poor prognosis

20 Medullary thyroid cancer
Most are sporadic but often familial (MEN II) Calcitonin levels helpful Genetic tests available (RET oncogene)

21 Thyroid storm Severe hyperthyroidism Decreased mental status and fever
Give PTU first!! Then iodine, beta blockers, and glucocorticoids

22 Thyroid cases Young patient with soft goiter, bruit, weight loss
Grave’s Disease  RAI ablation Patient with sore throat, fever, painful goiter Subacute thyroiditis  Supportive care +/- steroids Patient with hepatitis C on a-INF. Mildly thyrotoxic, non-tender goiter Silent thyroiditis  Supportive care

23 Thyroid cases Old pt. with weakness, weight loss, atrial fibrillation, goiter Apathetic hyperthyroidism (Toxic MNG) Young woman with molar pregnancy, hyperthyroid Very High hCG acts 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

24 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!!

25 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

26 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 ( ng/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.

27 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.

28 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)

29 Adrenal

30 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

31 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

32 Primary aldosteronism
If age <40, CT may be sufficient for localization If age >60, do bilateral adrenal vein sampling GOLD STANDARD

33 Pheochromocytoma Symptoms due to catecholamine excess Blood pressure
Perspiration Palpitation Pallor Pain Blood pressure Sustained hypertension in 1/2 Paroxysmal hypertension in 1/3 Normal blood pressure in 1/5

34 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

Kronenberg, et al. Williams Textbook of Endocrinology. 2008

36 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

37 What 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 mass Right adrenalectomy Serum aldosterone to plasma renin activity ratio determination 24-hour measurement of urine cortisol excretion

38 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

39 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

40 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)


42 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 Cosyntropin stim test Cortisol >18 at any time rules out primary adrenal insufficiency

43 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.

44 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

45 Pituitary

46 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) Prolactin Under continuous hypothalamic inhibition by dopamine

47 Pituitary tumors Is it hormonally active? Is there any mass effect?
PRL > GH > ACTH > LH/FSH >> TSH Alpha chain tumors not biologically active Is there any mass effect? Bitemporal hemianopsia, 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!!

48 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 →↑PRL and ↑growth of thyrotrophs → pituitary mass → give levothyroxine

49 Patient 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 test Random growth hormone measurement Serum cortisol Visual field testing

50 Other causes of hyperprolactinemia
Pregnancy Exogenous estrogens Primary hypothyroidism Drugs: metoclopramide, amytriptyline, phenothiazines, antidopaminergics Other tumors that compress pituitary stalk

51 Acromegaly Diagnosis often overlooked and late (>10 years)
Often macroadenoma (>1 cm) Frontal bossing, enlarging hands and feet Sleep apnea, HTN, carpal tunnel, skin tags, colon polyps Screening: ↑ IGF-1 GH too pulsatile! Confirmation: GH does not suppress 1 hour after glucose load (remains >1) Treatment: surgery

52 Acromegaly Use medical therapy if incomplete control after surgery
Somatostatin analogues: octreotide, lanreotide GH receptor antagonist: pegvisomant Usually added to somatostatin analogue Goal: normal IGF-1 and normal GH suppression after glucose load

53 Growth Hormone Excess

54 Cushing’s syndrome Make diagnosis Localize site of problem
Overnight 1 mg dexamethasone suppression test Elevated urinary free cortisol in 24-hour urine Elevated midnight salivary cortisol Localize site of problem ACTH-producing pituitary tumor (70%) Ectopic ACTH (15%) Most common—bronchial carcinoid Adrenal adenoma or carcinoma (15%)

55 Cushing’s syndrome Check ACTH Primary versus ectopic ACTH
< 5—adrenal adenoma or carcinoma >20—pituitary or ectopic ACTH >200—most likely ectopic ACTH Primary versus ectopic ACTH High dose dexamethasone suppression test Not so good as some ectopics will suppress Inferior petrosal sinus sampling GOLD STANDARD

56 Cushing’s syndrome Visualize lesion
Cushing’s disease—MRI pituitary Ectopic—CT chest/abdomen/pelvis Adrenal—CT or MRI adrenal Remember pituitary or adrenal mass may be just an incidentaloma!

57 Cushing’s Syndrome


59 67 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 administration Insulin tolerance test Lumbar puncture Serum prolactin measurement

60 Pituitary apoplexy Hemorrhagic infarction of pituitary
Severe headache, altered mental status, ophthalmoplegia CT/MRI: high density mass within pituitary Administer stress doses of steroids Contact neurosurgery for possible decompression

61 Diabetes insipidus Problem with ADH
Central—no ADH production Nephrogenic—no ADH action Remember that hypokalemia and hypercalcemia can cause nephrogenic DI Persistent non-concentrated polyuria with dehydration Hypernatremia, hyperosmolarity (>295), low urine osmolarity (<300) Confirm with water deprivation test

62 Diabetes insipidus Distinguish central from nephrogenic diabetes insipidus with 1 mcg desmopressin Central: increases urine osmolarity >50% Nephrogenic: no response Treatment Central: DDAVP Nephrogenic: thiazide diuretics

63 SIADH Too much ADH Retain too much free water → hyponatremia
Hyponatremia, low serum osmolarity (<275), inappropriately urine osmolarity (>100), high urine sodium (>30) Rule out dehydration Check renal, adrenal and thyroid function Treatment Water restriction Conivaptan—ADH receptor antagonist; acute tx Demeclocycline—blocks ADH at collecting tubal, chronic tx

64 Excess Insufficiency ACTH GH ACTH GH TSH FSH/LH TSH FSH/LH Acromegaly
Cushing’s Disease Slow onset Classic phenotype HTN/diabetes osteoporosis Skin thinning, ecchymoses GH Acromegaly Slow Onset Sleep apnea Carpal Tunnel HTN/Diabetes Colon polyps Skin tags ACTH Salt craving, nausea, “vague abdominal pain”, Fever HYPOGLYCEMIA Weight loss Pubertal hair loss GH Young Short stature Older “Decreased Vigor” TSH Rare. Hyperthyroidism with “normal” or increased TSH FSH/LH Amazingly rare Precocious puberty McCune Albright Syndrome TSH Rare. Hypothyroidism with “normal” or decreased TSH FSH/LH VERY COMMON Hypogonadism with atrophic gonads and “normal” or low FSH/LH

65 Complications of pituitary irradiation
Hypopituitarism Low prolactin supports diagnosis Can see hypothyroidism and adrenal insufficiency Can develop years after radiation treatment Visual defects Due to damage to optic chiasm Second tumor development

66 Pituitary cases 32 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 68 Pregnant (check HCG)

67 Bronchial carcinoid. ACTH > 200. IPSS/periphery ACTH ratio < 2
Pituitary cases 32 yo woman with Cushingoid features. Serum K 4.0. MRI: 0.8 cm pituitary mass. IPSS/Periphery ratio >2 42 yo woman with Cushingoid features. Serum K 3.0. CT chest: lung nodule. Nonsmoker. MRI pituitary: normal. IPSS/Periphery ratio <2 3. 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 >200 Cushing’s disease (pituitary). ACTH < 200 Next Step ----> Surgery. Bronchial carcinoid. ACTH > 200. IPSS/periphery ACTH ratio < 2 Small cell lung cancer

68 Gonads

69 Hirsutism Development of androgen-dependent terminal body hair in a woman in places not usually found Variation in different ethnic groups Affects 5-10% of women of reproductive age 2 most common causes are idiopathic hirsutism and PCOS


71 Red flags for tumors Recent onset and/or rapid progression
Late onset (ie post-menopausal) Virilization—voice change, clitomegaly Total testosterone >200 ng/dL

72 PCOS Usually evident at puberty
Anovulatory cycles with continuous stimulation of ovary by LH Oligomenorrhea or amenorrhea Hyperandrogenism Total testosterone elevated but <200 ng/dL LH:FSH ratio usually >2:1 Lacks sensitivity and specificity

73 PCOS treatment Hirustism Infertility Mechanical hair removal
OCPs + spironolactone (anti-androgen) Weight loss Infertility Clomiphene Metformin

74 Hypogonadism Low sex hormone levels
Primary hypogonadism—problem with gonad Normal pituitary →↑FSH (women) and ↑LH (men) Secondary—problem with pituitary Tertiary—problem with hypothalamus Secondary and tertiary may have inappropriately normal LH and FSH levels Remember inappropriate normals!!

75 Causes of hypogonadism in women
Primary Secondary Turner syndrome Radiation Chemotherapy Autoimmune destruction of ovaries (APS) Kallman syndrome Hyperprolactinemia Anorexia nervosa Strenuous exercise training Stress Hypothalamic/pituitary disease

76 Turner syndrome Primary amenorrhea with ↑FSH and ↑LH
Incidence 1:2000 (>50% mosaicism) Karyotype 45 XO Lymphocytes may be normal. Need fibroblast. If any Y present, ↑gonadoblastoma →prophylactic oophorectomy Physical 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 thyroditis Osteoporos from hypogonadism Treatment Estrogen replacement GH for short stature

77 What 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 DHEA MRI of pituitary Pelvic ultrasound Progesterone challenge testing

78 Amenorrhea Rule out pregnancy
Check hCG Rule out pituitary disease or ovarian failure Check prolactin and FSH Progestrin challenge (Provera 10mg x 10 days) If bleeding, anovulatory cycles (PCOS) If no bleeding, anatomic defect

79 Klinefelter syndrome Form of primary male hypogonadism
Incidence 1:1000 live births Karyotype 47 XXY Pre-puberal failure with small, firm testes Gynecomastia Sometimes decreased intellectual development

80 Kallman syndrome Form of primary hypogonadism Normal karyotype (46 XY)
Due to abnormal development of GnRH producing neurons Also close to olfactory system Get isolated hypogonadotrophic hypogonadism with anosmia Normal karyotype (46 XY) Small testes (but larger than Klinefelter) Infertility treated with LHRH infusion pump

81 Gynecomastia Occurs when estrogen/androgen balance favors estrogen
↑ estrogens: cirrhosis, hyperthyroidism, β-hCG/estrogen-secreting tumors ↓androgens: testicular surgery/trauma, renal failure, hyperprolactinemia, drugs drugs: spironolactone, ketoconazole, calcium channel blockers, phenothiazines, TCAs

82 Erectile dysfunction Start with TSH and testosterone level
If ↓ testosterone, get prolactin and LH Drugs associated with ED (without hypogonadism): thiazide, beta blockers, anticholinergics, SSRIs, clonidine, morphine

83 Anabolic steroid abuse
Men Small testicles, gynecomastia, low sperm count Women Hirsutism, small breast, enlarged clitoris, deepening voice Both HTN, increased CVD, acne, male-pattern baldness, irritability, psychosis

84 Hypogonadism cases 25 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 hypogonadism Suppresses GnRH release and reverses with removal of steroids. Hyperprolactinemia Check prolactin level to confirm

85 Hypogonadism cases 18 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 scan High risk for osteoporosis! Kallman Syndrome – Neuronal Migration disorder – also associated with anosmia Exercise-Induced Amenorrhea – Mediated by low GnRH Also seen with anorexia, low body fat

86 Bone

87 Risk factors for osteoporosis
Thin Caucasian Female gender First degree relative with osteoporosis Alcohol Smoking Rheumatoid arthritis Use of glucocorticoids

88 Indications for bone mineral density
Female > 65 years old Post-menopausal female <65 years if: 1st degree relative, smoker, weight < 127 lbs Male >70 years old Fragility fracture Glucocorticoids >3 months Medical condition associated with osteoporosis Hyperparathyroidism, Cushing’s disease, etc

89 Interpreting DEXA results
T-score compares patient to 30-year woman Z-score compares patient to age-related controls Normal—T-score > -1 Osteopenia—T-score > -1 but < -2.5 Use FRAX score to determine who to treat If risk >3% hip and >20% any, treat patient Osteoporosis—T-score < -2.5

90 What 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 D Measure 25-hydroxyvitamin D Parathyroidectomy Repeat DEXA scan in 1 year

91 Stop use after 2 years → risk of osteosarcoma.
Osteoporosis therapy Drug Spine Hip Bisphosphonates + Raloxifene - Tamoxifen Calcitonin Teriparatide Stop use after 2 years → risk of osteosarcoma. Useful for bone pain. Tachyphylaxis limits use.

92 Paget’s Disease Disease of increased bone turnover
Bone pain with elevated alkaline phosphatase Bone scan: focal uptake with no evidence of cancer. If affecting skull  osteoporosis circumscripta Risk of cranial nerve palsies, particularly CN VIII Risk of fracture at site of bone turnover Therapy–pamidronate or alendronate daily

93 Osteoporosis circumscripta

94 Osteomalacia Also see ↓ Ca, ↓ PO4, ↑ alk phos, ↑ PTH
Decreased bone mineralization usually from vitamin D deficiency In kids, we call it ricketts Typically older patient with bone pain and proximal muscle weakness “bilateral symmetric pseudofractures” Check 25-OH vitamin D and replace to >30 Also see ↓ Ca, ↓ PO4, ↑ alk phos, ↑ PTH Work-up vitamin D deficiency

95 Psuedofracture of Looser’s zone

96 Miscellaneous

97 Nutritional deficiencies after bariatric surgery
Iron Vitamin D B12 Folic acid Thiamine (B1) Vitamin A Zinc

98 Good luck on the boards!

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