Transcript Endocrinology II (French)

ENDOCRINOLOGY II
Sarah E. French, MD
July 19, 2014
Thyroid
Pituitary
Adrenal
Gonads
Bone
Medical-Content Category
Relative Percentage
Cardiovascular Disease
14%
Pulmonary Disease
10%
Gastroenterology
9%
Infectious Disease
9%
Rheumatology/Orthopedics
8%
Endocrinology
8%
Medical Oncology
7%
Hematology
6%
Nephrology/Urology
6%
Psychiatry
4%
Neurology
4%
Allergy/Immunology
3%
Dermatology
3%
Miscellaneous
3%
Obstetrics/Gynecology
2%
Ophthalmology
2%
Otorhinolaryngology
2%
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
0–1
Hypothalamic disorders
0–1
Anterior pituitary disorders
0–1
Posterior pituitary/water metabolism
0–1
Endocrine tumors and endocrine
manifestations of tumors
0–1
Hypoglycemia not due to insulinoma
0–1
Polyglandular disorders
0–1
Nutritional disorders
0–1
Women’s health endocrine issues
0–1
Miscellaneous endocrine disorders
0–1
THYROID
Thyroid function tests (TFTs)
• TSH
• If ↓ TSH → hyperthyroidism
• If ↑ TSH → hypothyroidism
• Use to screen and follow thyroid replacement
• Total T4
• All T4 (but 99.98% protein-bound)
• ↑TBG , ↑ total T4, normal free T4
• Pregnancy, estrogens, tamoxifen, HIV, phenothiazines
• ↓ TBG , ↓ total T4, normal free T4
• Androgens, glucocorticoids, nephrotic syndrome, cirrhosis
Thyroid function tests (TFTs)
• Free T4
• Key in diagnosis of central hypothyroidism
• Evaluate degree of hypothyroidism
• Diagnosis and response to therapy in hyperthyroidism
• Total/free T3
• Check if suspect T3 toxicosis
• Thyroglobulin
• Low in factitious thyrotoxicosis
• Used to monitor thyroid cancer
Thyroid function tests (TFTs)
• Thyroid uptake
• Normal uptake 10-15%
• ↑uptake: Graves, toxic multinodular goiter, solitary toxic adenoma
• ↓uptake: thyroiditis, factitious hyperthyroidism
• Thyroid scan
• Hot nodule = benign
• Cold nodule > 1 cm needs FNA
Euthyroid sick syndrome
• Seen in critically ill patients
• Impairs body’s ability to peripherally convert T4 to T3
• T4 converts to reverse T3
• See normal TSH, normal T4, and free T3
As disease severity progresses, free T3 and T4
decreases
• DON’T CHECK TFTs IN SICK PATIENTS unless you think
it’s thyroid storm or myxedema coma
•
• DON’T GIVE THYROID REPLACEMENT
Question
A patient of yours comes to see you and complains about being tired. She
gave birth to a healthy child about 6 months ago and tells you that the
baby is doing fine. Her obstetrician reported to you that the pregnancy
and delivery were uneventful. At first everything was perfect. She had
plenty of energy and lost the baby weight without difficulty and had no
difficulty staying up late at night to take care of the baby. After about two
months she began to feel more tired and her fatigue steadily worsened
such that now she can barely function. She is having difficulty with
nursing. She blames herself for everything that’s wrong and begins to
cry.
Which of the following should you do next?
1.
Tell her that the symptoms of her “post-partum blues” will soon pass.
2.
Begin anti-depressants
3.
Begin stimulants
4.
Order TSH and Free T4
5.
Refer her to a psychiatrist for evaluation.
• 24 yo woman evaluated for 1 week history of neck discomfort
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that radiates to jaw, palpitations, fast heart rate, anxiety and
fever. Reports having sore throat 4 weeks ago that resolved
after a few days. No other symptoms. No personal history of
thyroid or other endocrine disorders.
On physical exam, she appears anxious. Temperature 37.5 C
(99.5F), BP 140/60, pulse 110. + tachycardia.
Thyroid gland slightly enlarged and tender with no nodules. No
thyroid bruit. No cervical lymphadenopathy. No eye findings or
pretibial myxedema is noted. + fine bilateral hand tremor.
Lab: sed rate 45, TSH <0.01, free T4 4.1, T3 300. Doppler
thyroid ultrasound showed enlarged thyroid with 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
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 ExtraThyroidal Sources
- Subacute Thyroiditis
- Silent/post-partum
thyroiditis
- Thyrotoxicosis factitia
- Struma ovarii
Hyperthyroidism
• Patient < 40 yrs—#1 Graves, #2 toxic adenoma
• Patient > 60 yrs—#1 multinodular goiter, #2 Grave, #3
toxic adenoma
• Will increase metabolism of many drugs
• Warfarin  may need LOWER dose due to increased metabolism
of clotting factors
• Apathetic hyperthyroidism in elderly
• May only present with weight loss and fatigue
Graves disease
Proptosis
Acropachy
Therapy for hyperthyroidism
• Immediate effect
• Beta blocker
• Iodine
• Surgery
• Latent effect—begins at 2-3 wks, full effect at 6 wks
• Propylthiouracil—pregnant patients (1st trimester), thyroid storm
• Monitor for hepatitis, agranulocytosis
• Methimazole—everybody else
• Monitor for cholestasis, agranulocytosis
• Later effect
• Radioactive iodine—takes 2-3 months
Amiodarone and the thyroid
• 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
Risk factors for thyroid cancer
• Family history
• History of head/neck radiation
• New nodule in patient <20 or >60 years old
• Nodule that is firm, fixed and growing
• Nodule with regional cervical LAD or Horner’s syndrome
• Cold nodule on scan
• Microcalcifications ± central bloodflow on US
• Dysphagia, hoarseness, respiratory obstruction, pain
Evaluation to thyroid nodule
• Obtain TSH.
• If hyperthyroid, get thyroid scan
• If hot nodule, treat with RAI ablation
• Do NOT biopsy a hot nodule! They’re benign.
• If euthyroid or hypothyroid and >1 cm, perform FNA
• Smaller lesions with concerning features may be considered for
biopsy
Cancer derived from follicles
• Papillary thyroid cancer
• Most common
• Grows slowly
• Lymphangetic spread
• Follicular thyroid cancer
• Hematogenous spread
• Anaplastic thyroid cancer
• Extremely poor prognosis
Medullary thyroid cancer
• Most are sporadic but often familial (MEN II)
• Calcitonin levels helpful
• Genetic tests available (RET oncogene)
Thyroid storm
• Severe hyperthyroidism
• Decreased mental status and fever
• Give PTU first!!
• Then iodine, beta blockers, and glucocorticoids
Thyroid cases
Young patient with soft goiter, bruit, weight loss
Grave’s Disease  RAI ablation
Patient with sore throat, fever, painful goiter
Subacute thyroiditis
 Supportive care +/- steroids
Patient with hepatitis C on a-INF. Mildly thyrotoxic, non-tender goiter
Silent thyroiditis
 Supportive care
Thyroid cases
• Old pt. with weakness, weight loss, atrial fibrillation, goiter
– Apathetic hyperthyroidism (Toxic MNG)
• Young woman with molar pregnancy, hyperthyroid
– Very High 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
Primary vs Secondary Hypothyroidism
• Primary hypothyroidism
• Problem is the gland itself
• Will see ↑TSH and ↓free T4
• Secondary hypothyroidism
• Problem is outside the gland (ie pituitary, etc)
• Will see ↓ or ↔TSH and ↓free T4
• Remember inappropriate normals!!
Question
An 84 yo lady with a history of dementia and no other medical problems
presents from the nursing home with altered mental status. She is
on no medications. She is unable to provide any history but on your
examination of her you find that she has a well healed transverse
scar across her neck. She is hypothermic, bradycardic, has doughy
skin and brittle hair. Labs are pending, but you find a fingerstick
glucose of 52.
Which of the following is the most reasonable next step in her
care?
1.
Give her one amp of D50
2.
Levothyroxine 300mcg IV
3.
Levothyroxine 300mcg IV and hydrocortisone 100mg IV
4.
Levothyroxine 300mcg IV and one amp of D50 IV
5.
Levothyroxine 200mcg PO
Question
A psychiatrist in your community refers an 80 year old woman being
treated for depression. She reports generalized weakness, fatigue,
dry skin, weight gain and constipation. Her past medical history
includes CHF and stable angina. Your examination reveals periorbital edema, skin that is cool and dry, loss of the lateral third of her
eyebrow, mild bradycardia and a slow relaxation phase of her deep
tendon reflexes. You strongly suspect hypothyroidism and check
TSH and Free T4. The TSH is 95 units/mL and Free T4 is 0.1ng/dL
(0.7-1.5ng/dL). She obviously has severe hypothyroidism.
Which of the following should you do next?
1.
Administer thyroxine 500mcg IV daily for 5 doses
2.
Administer thyroxine 500mcg IV and triiodothyronine 20mcg IV
daily for three days.
3.
Begin levothyroxine 300mcg PO daily
4.
Begin levothyroxine 100mcg PO daily
5.
Begin levothyroxine 25mcg PO daily
Replace levothyroxine slowly in elderly or cardiac patients
There is no scenario where you should need to pick T3 over T4.
Hypothyroidism Scenarios
83 yo woman with depression, clearly hypothyroid. Otherwise getting
along okay. Therapy?
Low dose levothyroxine therapy (25mcg/day) and advance slowly to reach goal.
47 yo man with CABG 8 months ago, hypothyroid. Treatment?
Low dose levothyroxine therapy (25mcg/day) and advance slowly to reach goal.
74 yo NH resident with thyroidectomy scar, on no meds comes in with
altered mental status, severe hypothyroidism. Glucose is 56.
Treatment?
Hydrocortisone 100mg IV and Levothyroxine IV.
Hypothyroidism cases
27 year old woman with Hashimotos on levothyroxine
75mcg daily, 2 weeks pregnant.
Estrogens increase TBG, so increase levothyroxine dose by 30-50% during
pregnancy
45 year old woman with Hashimotos has a rapidly
enlarging goiter
Thyroid Lymphoma - FNA diagnosis and irradiate
32 year old man begins abusing heroin, has high Total T4
Increased TBG due to heroin (also seen with methadone)
ADRENAL
Primary aldosteronism
• Screening
• Hypertension with hypokalemia
• Refractory hypertension (>3 BP meds)
• Even if normal K
• Work-up
• Calculate aldosterone/renin activity ratio
• Ratio >20 with aldo >15 ng/dL → high likelihood
• Confirmation
• Urine aldo > 12 mcg/24 hrs while on high salt diet (urine Na >200
mEq)
• Plasma aldo > 10mg/dL after 2 L of saline over 4 hours
Primary aldosteronism
• Classification
• Aldosterone-producing adenoma
• Bilateral zone glomerulosa hyperplasia
• Adrenal carcinoma (rare)
• Glucocorticoid-remediable aldosteronism (rare)
• Treatment
• Adenoma: medically or surgery
• Hyperplasia: only medically, spironolactone
• If gynecomastia, switch to eplerenone
Primary aldosteronism
• If age <40, CT may be sufficient for localization
• If age >60, do bilateral adrenal vein sampling
• GOLD STANDARD
Pheochromocytoma
• Symptoms due to catecholamine excess
• Pressure
• Perspiration
• Palpitation
• Pallor
• Pain
• Blood pressure
• Sustained hypertension in 1/2
• Paroxysmal hypertension in 1/3
• Normal blood pressure in 1/5
Diagnosing pheochromocytoma
• Plasma metanephrines
• Start with this
• 99% sensitive—good for ruling out pheo
• False (+)—stress, tobacco, coffee, Tylenol, TCAs
• 24-hr urine for metanephrines and catecholamines
• Check if plasma metanephrines are positive
• If >2-fold increase, 99% specific
NEVER
BIOPSY AN
ANDRENAL
MASS
WITHOUT
RULING
OUT PHEO
FIRST!!
Kronenberg, et al. Williams Textbook of Endocrinology. 2008
Treatment of pheochromocytoma
• Surgery is treatment of choice
• Laproscopic surgery is an option
• Preparation for surgery
• Alpha blockade with phenoxybenzamine (alternative: terazosin)
• Titrate until patient is orthostatic or patient is at maximum dose
• Then start beta blocker
• If surgery is not an option (ie metastatic tumor)
• Metyrosine
• Chemotherapy and radiation
• 61 yo man with epigastric pain found to have 7 cm R
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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 24hr urine metanephrines. Dexamethasone suppression
test normal.
CT scan showed 7cm R adrenal mass with 77 Hounsfield
units. Normal L adrenal gland. No lymphadenopathy.
What is most appropriate management?
• Biopsy of adrenal mass
• Right adrenalectomy
• Serum aldosterone to plasma renin activity ratio determination
• 24-hour measurement of urine cortisol excretion
Adrenal incidentaloma
• Only 15% functional
• Cushing’s > pheochromocytoma > primary aldo
• Work-up
• All: 1 mg dex suppression test and plasma metanephrines
• If HTN: renin and aldosteronism
• Remove if functional or >6 cm
• If non-functional and 4-6 cm, monitor very closely
• Remove if necrosis, hemorrhage, irregular margins
• If non-functional <4 cm, re-evaluate in 6 months
Congenital adrenal hyperplasia (CAH)
• 21-hydroxylase is most common
• Accumulation of 17-OH progesterone →androgens
• Classical form (complete deficiency)
• Starts in infancy
• Salt-wasting, hypotension, virilization
• Sometimes ambiguous genitalia at birth
• Partial deficiency
• Young adulthood
• Hirsutism, menstral irregularities
• Mimics PCOS
• Treatment: prednisone
• + fludrocortisone if needed
Adrenal insufficiency
• Symptoms
• Weakness, fatigue, abdominal pain, nausea, vomiting
• Signs
• Hyponatremia, hypotension, hypoglycemia
• Women have loss of axillary and pubic hair
• Due to loss of adrenal androgens
• Primary adrenal insufficiency
• Hyperpigmentation (↑ ACTH)
• Hyperkalemia (mineralocorticoid deficiency)
BEFORE
AFTER
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
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?
Renin/Aldosterone ratio >20 with Aldo >15  Primary Hyperaldosteronism
Confirmatory Test?
Salt load and then 24 hour urine aldo >12 OR
2 liter NS bolus with plasma aldo >10.
Electrolytes corrected and he feels better. Ready for
surgery now?
Bilateral adrenal vein sampling first.
Adrenal cases
24 yo man with resistant HTN, short stature, history of
genitourinary surgeries as a child, low potassium. Likely
diagnosis?
Congenital Adrenal Hyperplasia (17-alpha hydroxylase deficiency)
Renin low, aldosterone low, deoxycorticosterone high
45 yo farmer who dips tobacco, has resistant HTN with
hypokalemia.
Licorice (glycyrrhizic acid) inhibits conversion of hydrocortisone to cortisone
Renin low, Aldosterone low
PITUITARY
Anterior pituitary hormones
• Adrenocorticotropic hormone (ACTH)
• CRH stimulates release of ACTH
• Growth hormone (GH)
• GHRH stimulates release of GH
• Thyroid stimulating hormone (TSH)
• TRH stimulates release of TSH
• Luteinizing hormone (LH)
• GnRH stimulates release of LH
• Follicle-stimulating hormone (FSH)
• GnRH stimulates release of LH
• Prolactin
• Under continuous hypothalamic inhibition by dopamine
Pituitary tumors
• Is it hormonally active?
• PRL > GH > ACTH > LH/FSH >> TSH
• Alpha chain tumors not biologically active
• Is there any mass effect?
• 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!!
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
• 26 yo woman evaluated for hyperprolactinemia after
recent labwork showed serum prolactin of 55 (normal 1026). Mild hyperprolactinemia was detected 6 years ago
during evaluation for irregular menstrual cycles. MRI at
that time showed pituitary microadenoma. Was treated
with dopamine agonist and subsequent serum prolactins
were normal until this reading.
• Patient had menarche at 13 and has irregular periods
since then.
• Vitals normal. Breast development normal but there is
breast tenderness present. No galactorrhea, acne,
hirsutism, or striae are present.
• What is most appropriate next diagnostic test?
• Pregnancy test
• Random growth hormone measurement
• Serum cortisol
• Visual field testing
Other causes of hyperprolactinemia
• Pregnancy
• Exogenous estrogens
• Primary hypothyroidism
• Drugs: metoclopramide, amytriptyline, phenothiazines,
antidopaminergics
• Other tumors that compress pituitary stalk
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
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
Growth Hormone Excess
Cushing’s syndrome
• Make diagnosis
• 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%)
Cushing’s syndrome
• Check 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
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!
Cushing’s Syndrome
• 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
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
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
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
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
Excess
Insufficiency
ACTH
GH
ACTH
GH
Cushing’s Disease
Slow onset
Classic phenotype
HTN/diabetes
osteoporosis
Skin thinning,
ecchymoses
Acromegaly
Slow Onset
Sleep apnea
Carpal Tunnel
HTN/Diabetes
Colon polyps
Skin tags
Salt craving,
nausea, “vague
abdominal pain”,
Fever
HYPOGLYCEMIA
Weight loss
Pubertal hair loss
Young
Short stature
TSH
FSH/LH
TSH
FSH/LH
Rare.
Hyperthyroidism
with “normal” or
increased TSH
Amazingly rare
Precocious puberty
Rare.
Hypothyroidism
with “normal” or
decreased TSH
VERY COMMON
Hypogonadism
with atrophic
gonads and
“normal” or low
FSH/LH
McCune Albright
Syndrome
Older
“Decreased
Vigor”
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
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)
Pituitary cases
32 yo woman with Cushingoid features. Serum K 4.0.
MRI: 0.8 cm pituitary mass. IPSS/Periphery ratio >2
Cushing’s disease (pituitary). ACTH < 200
Next Step ----> Surgery.
42 yo woman with Cushingoid features. Serum K 3.0. CT
chest: lung nodule. Nonsmoker. MRI pituitary: normal.
IPSS/Periphery ratio <2
Bronchial carcinoid. ACTH > 200.
IPSS/periphery ACTH 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
Small cell lung cancer
GONADS
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
Red flags for tumors
• Recent onset and/or rapid progression
• Late onset (ie post-menopausal)
• Virilization—voice change, clitomegaly
• Total testosterone >200 ng/dL
PCOS
• Usually evident at puberty
• Anovulatory cycles with continuous stimulation of ovary by
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LH
Oligomenorrhea or amenorrhea
Hyperandrogenism
Total testosterone elevated but <200 ng/dL
LH:FSH ratio usually >2:1
• Lacks sensitivity and specificity
PCOS treatment
• Hirustism
• Mechanical hair removal
• OCPs + spironolactone (anti-androgen)
• Weight loss
• Infertility
• Clomiphene
• Metformin
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!!
Causes of hypogonadism in women
Primary
Secondary
• Turner syndrome
• Kallman syndrome
• Radiation
• Hyperprolactinemia
• Chemotherapy
• Anorexia nervosa
• Autoimmune destruction
• Strenuous exercise
of ovaries (APS)
training
• Stress
• Hypothalamic/pituitary
disease
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
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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
• 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
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
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
Kallman syndrome
• Form of primary hypogonadism
• 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
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
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
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
Hypogonadism cases
25 yo man with decreased libido, decreased testicular volume,
otherwise normal. AST/ALT elevated. Next Test?
Hemochromatosis - Iron saturation > 45 is quite suggestive.
May all see arthritis, risk for Type I DM.
47 yo man with rheumatoid arthritis on chronic opiate therapy
with prednisone 10mg daily; hypogonadal symptoms. Likely
diagnosis?
Glucocorticoid-induced hypogonadism
Suppresses GnRH release and reverses with removal of steroids.
37 yo man with decreased libido, develops gynecomastia and
galactorrhea. Beta-hCG normal, labs confirm low LH and low
testosterone. Next test?
Hyperprolactinemia
Check prolactin level to confirm
Hypogonadism cases
18 yo man with cryptorchidism, delayed puberty, cleft
palate, abnormal movements. Diagnosis?
Kallman Syndrome – Neuronal Migration disorder – also
associated with anosmia
27 yo female marathon runner with amenorhea.
Exercise-Induced Amenorrhea – Mediated by low GnRH
Also seen with anorexia, low body fat
Test to check in long term hypogonadism  DEXA
scan
High risk for osteoporosis!
BONE
Risk factors for osteoporosis
• Thin
• Alcohol
• Caucasian
• Smoking
• Female gender
• First degree relative
with osteoporosis
• Rheumatoid arthritis
• Use of
glucocorticoids
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
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
• 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
Osteoporosis therapy
Drug
Spine
Hip
Bisphosphonates
+
+
Raloxifene
+
-
Tamoxifen
+
+
Calcitonin
+
-
Teriparatide
+
+
Useful for bone pain.
Tachyphylaxis limits use.
Stop use after 2 years → risk
of osteosarcoma.
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
Osteoporosis circumscripta
Osteomalacia
• 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
Psuedofracture of Looser’s zone
MISCELLANEOUS
Nutritional deficiencies after bariatric surgery
• Iron
• Vitamin D
• B12
• Folic acid
• Thiamine (B1)
• Vitamin A
• Zinc
Good luck on the boards!