Endocrinology

• Decreases the secretion of GnRH, which leads to reduced levels of LH and FSH and their target organ functions:
• Men -- impotence and hypogonadism
• Women -- oligomenorrhea or amenorrhea, hirutism, galactorrhea

• Reglan
• Antidopaminergics
• Cimetidine
• Verapamil
• Risperidone
• Haldol
• Higher doses of estrogen

• PRL > 100
• If PRL > 20 but < 100, look for other causes of hyperprolactinemia
• PRL levels are especially elevated with macroadenomas, so suspect another tumor type when > 1 cmm and PRL < 200

• Transsphenoidal surgery
• Cabergoline and bromocriptine

• Valvular heart disease
• -- although unlikely at the doses used to treat hyperprolactinemia, and more likely when used at the higher doses to treat Parkinson's

• If there is marked mass effect or poor response from drugs
• Elevated PRL levels often return after surgery, so follow for an extended period of time.

No

She may ovulate during therapy, and thus need to take precaution against pregnancy

• Bromocriptine is not proven safe in pregnancy, not FDA approved, and should be discontinued unless:
• -- Current evidence of mass effect
• -- h/o a very large tumor, which greatly shrunk with treatment before pregnancy

• Do not follow prolactin levels (it is always elevated during pregnancy)
• Follow clinically depending on tumor size
• -- Microprolactinomas - 3-5% will enlarge significantly during pregnancy. Follow q 3 months and check for symptoms
• -- Macroprolactinomas - about 20-30% will enlarge during pregnancy. Follow q 1-2 months for symptoms and check visual fields

• Order MRI without contrast
• May need surgery if substantial enlargement
• Otherwise, medical treatment is preferred
• If medical therapy is reinstated, use bromocriptine at the lowest dose that provides sufficient improvement.

• Oral contraceptives are okay in women with microprolactinomas, but remember that estrogen stimulates prolactin secretion so PRL levels may rise a little.
• Avoid oral contraceptives in any woman with a macroprolactinoma

• Stimulates production of insulin-like growth factors in the liver.
• Main IGF is IGF-1
• Stimulates hepatic glucose production and inhibits peripheral action of insulin

• Acromegaly
• DM
• Hypothyroidism

• Low glucose stimulates GH secretion
• High glucose suppresses GH secretion
• GH secretion is pulsatile
• Random level of GH not usually helpful

• Order IGF-1.
• If elevated, must confirm GH. Do not order GH randomly
• Check GH only while glucose is high -- check 1 hour and 2 hours after 100 g glucose tolerance test
• While glucose is elevated, GH should be suppressed to < 5 ng/mll.
• In acromegaly, GH > 5 ng/ml

• Resection of pituitary tumor
• Consider radiation therapy, but this take years to be effective
• Medical therapy
• -- somatostatin analogues (ocreotide, lanreotide)
• -- hGHR blockers (pegvisomant)

• If patient is asymptomatic, test for:
• -- prolactin
• -- 24-hour urine cortisol or dexamethasone suppression test
• -- IGF-1
• If inactive, repeat CT/MRI in 6 months, then annually for several years to watch for growth.

• Usually seen in multiparous women
• Weakened diaphragm at top of sella invaginates and pushes the pituitary tissue to the sides of the sella.
• Pituitary still functions
• Ignore

• Löss of blood flow to the pituitary during or shortly after delivery
• May cause panhypopituitarism, or may cause loss of only one or a few hormones
• May also cause loss of posterior function with resultant diabetes insipidus

Hemorrhagic infarction of a pituitary tumor

• Severe HA with variable onset
• n/v
• Meningismus
• Vertigo
• +/- visual field defects
• +/- altered consciousness

• CT/MRI will show high-density mass within the pituitary due to blood
• Must differentiate from a leaking aneurysm

• DM with microvascular changes
• Radiotherapy to the pituitary
• Warfarin use

• Neurosurgical emergency -- may need decompression
• Mild cases can be treated with steroids

• Central DI can be caused by trauma or surgery. There are three phases:
• Phase I -- occur secondary to injury to axons. The nerve axons can be intact or severed. If injured but still intact, ADH may not be secreted and Phase I starts. This is characterized by high volume urine, serum hypernatremia, and increased osmolality. This is treated with fluids and desmopressin. If the axons are not severed, then normal function slowly resume and Phase 2 and 3 will not occur.
• Phase 2 -- occurs when the severed axons begin to decay. The stored ADH vesicles are released into the circulation. Large volume urine stops, Serum Na decreases. This is treated with fluid restriction and d/c desmopressin.
• Phase 3 -- occurs after the axons have decayed and all the stored ADH have been released. Large volume urine recur, serum Na again rises. This is treated with lifelong desmopressin, and fluid replacement. Patient now has DI for life.

Testing for diabetes insipidus involves a water deprivation test, as long as the baseline serum osmolality is not substantially elevated. Patient weight and urine and serum osmolalities are obtained every 2 hours until the urine and serum osmolalities have stabilized (serum osmolality >295 mosm/kg) and the patient has lost no more than 3% of body weight. The patient is then given 5 µg of desmopressin intranasally; urine osmolality continues to be measured hourly for the next 2 to 3 hours. During water deprivation and before desmopressin administration, healthy persons will increase their urine osmolality to greater than 800 mosm/kg, but those with diabetes insipidus will not increase theirs above 300 mosm/kg. In response to desmopressin, patients with central diabetes insipidus will increase their urine osmolality by at least 50%, but those with nephrogenic diabetes insipidus will not respond appreciably to desmopressin administration. Patients with partial diabetes insipidus will increase their urine osmolality to 300 to 500 mosm/kg with dehydration and by at least another 9% with desmopressin.

• A low plasma sodium concentration (less than 137 meq/L) with a low urine osmolality (eg, less than one-half the plasma osmolality) is usually indicative of water overload due to primary polydipsia.
• A high-normal plasma sodium concentration (greater than 142 meq/L, due to water loss) points toward DI, particularly if the urine osmolality is less than the plasma osmolality [1].
• A normal plasma sodium concentration is not helpful in diagnosis but, if associated with a urine osmolality more than 600 mosmol/kg, excludes a diagnosis of DI.

• IGF-1
• PRL
• 24-hour urine cortisol

• Low uptake:
• -- Thryroiditis
• -- Suppression (iodine, PTU/methimazole, T4/T3)
• -- Iodine excess (kelp, contrast dye, amiodarone)

• High uptake:
• -- Graves disease
• -- Iodine deficiency
• -- Really high levels of B-HCG

Dementia, CHF, pericardial effusions, pleural effusions, respiratory depression, chronic constipation, ascites, irregular menses, galactorrhea, muscle cramps, weakness, fatigue, hyperlipidemia, anemia, depression, joint discomfort, dry skin, hair loss, HTN, coarse hair, periorbital swelling, hoarse voice, large tongue

• Thyroiditis
• Loss of gland (surgery or ablation)
• Antithyroid agents
• Iodine deficiency
• Recent Iodine load
• Pituitary disorders

• it is most often due to aery, mild Hashimoto's disease
• -- check anti-TPO antibodies
• -- if elevated
• -- high risk of overt hypothyroidism
• -- follow regularly, consider treatment

• T4 (levothyroxine)
• -- if you suspect cardiac disease, start low and titrate low

• Cholestyramine
• FeSO₄
• Al(OH)₃
• Sucralfate
• CaCO₃
• Soy protein dietary supplements

*Take LT4 several hours before or after

• When taking meds that can accelerate metabolism of T4
• -- Rifampin and anticonvulsants

• Any tacharrhythmia (not just a-fib)
• Chronic diarrhea
• CHF
• Depression
• Osteopenia
• Increased ALP
• Irregular menses
• gynecomastia
• weakness
• fatigue
• hair loss
• conjunctivitis
• diplopia

• Graves disease
• Exogenous T4/T3
• Toxic multinodular goiter
• Autonomous (hot) nodule
• Excessive iodine

• Classically, goiter and ophthalmopathy
• Elevated nuclear medicine uptake

• No goiter
• Increased FT4 and/or T3
• Low uptake

• Lumpy/bumpy, patchy scan
• Uptake may be high, low, or normal

• Thionamides
• -- PTU and menthimazole
• - inhibit synthesis of thyroid hormone
• - watch out for fetal malformations
• Iodine
• B-blockers
• Radioablation

• PTU preferred in pregnancy (but not FDA approved).
• Both methimazole and PTU can cause fetal malformations, but methimazole > PTU

• Hepatic toxicity
• Aganulocytols
• -- both are very rare, unpredictable. Do not screen or routinely check LFT or CBC. Follow clinically instead.

• Delayed effect, so not useful for acute symptoms
• Transient worsening of hyperthyroidism may occur
• May initially need to continue antithyroid medication
• -- resume PTU or methimazole
• May become hypothyroid later on
• Goal of treatment is hypothyroid. They may be euthyroid initially

• It will destroy the thyroid gland of the fetus resulting in cretinism.
• Patients undergoing radioablation need to avoid pregnancy for at least 6 months.
• Oral contraceptives are less effective in hyperthyroidism
• Use at least two methods of contraception

• If patient with Graves disease also has a cold nodule. Otherwise, radioablation is preferred if problem is only hyperthyroidism.
• Potential complications for surgery are:
• -- recurrent laryngeal nerve damage
• -- temporary or permanent hypoparathyroidism

• also known as non-thyroidal illness
• Usual labs: TSH mildly low or low-normal, FT4 mildly low or low normal
• T3 very low
• rT3 high (hallmark)
• Thyroid is not the problem, treat the underlying illness

• May be hypothyroid because the gland is sick, not making enough thyroid hormone
• Or hyperthyroid because the gland is inflamed and some thyroid hormone may leak out
• May even be euthyroid

• may follow a viral illness, most often URI
• Usually a diffuse, symmetric goiter
• Very tender gland ( hallmark sign)
• Disease is self-limited
• Sed rate elevated
• Thyroid uptake is suppressed
• This is a self-limited disease
• Treat with ASA and / or glucocorticoids, if at all

Thyroid uptake

• Hashitoxicosis if hyperthyroid
• May imitate Graves disease
• -- Both may have goiter plus hyperthyroidism
• -- Thyroid uptake will differentiate

• Thyroid uptake will differentiate:
• - Grave's disease if the uptake is high
• - Hashitoxicosis if the uptake is low.

• Treat symptomatically
• -- if hypothyroid, LT4
• -- if hyperthyroid, thionamide

• Nuclear medicine thyroid scan -- if hot or warm, then it's probably a high functioning thyroid adenoma. If cold, look at cancer risk.
• If the patient is euthyroid on presentation and has a single palplable nodule, many endocrinologist will bypass the nuclear medicine thyroid scan and proceed diretly to the FNA since this is the most cost-effective workup.

biopsy the biggest cold nodule

refer to an endocrinologist

• most common
• Usually grows slowly
• Lymphatic spread

• Papillary cancer
• Follicular cancer
• Anaplastic cancer
• Medullary

• Thyroidectomy
• High-dose radioactive iodine while TSH is markedly elevated

TSH must be markedly elevated for total body scans and radioablation. TSH should be greater than 30.

Aim for low TSH (0.2 -- 0.4, not <0.01)

• Thyroid storm
• Myxedema coma

• Preexisting hyperthyroidism
• Mental status change
• Increased temp

• Glucocorticoids -- patient will have high cortisol but this is not enough for what they need.
• Beta-blockers
• PTU or methimazole
• Iodine

• Clinical presentation is decreased mentation, hypothermia, hyponatremia, hypoventilation.
• Treat aggressively, but exercise caution if heart disease suspected
• IV T4 used frequently. Oral drug is poorly absorbed.
• IV T3 not usually used due to cardiac side effects

• There is risk of underlying cardiac dysfunction
• Surgery may precipitate thyroid storm
• If surgery is not urgent, make the patient euthyroid first
• If surgery is urgent but can be postponed for a few days, start treatment

• Load with Beta-blockers and steroids (IV)
• Start thionamide (PTU, methimazole) as soon as possible after surgery

• Risk of underlying cardiac dysfunction plus fluid and electrolyte abnormalities
• Be suspicious of possible adrenal insufficiency
• Replace thyroid hormones carefully and slowly if any suspicion of heart problems
• If surgery is not urgent, make patient euthyroid first

Increased binding globulins result in increased TT4 even if euthyroid, so always check FT4.

• Grave's disease may become symptomatic only during pregnancy, resolve once deliver
• Don't rush to treat
• Beta-blocker if necessary
• PTU if necessary
• Treatment goal is FT4 and pulse rate that are high-normal or mildly elevated.

• Treatment of hypothyroidism during pregnancy may help the child's neuropsychological development
• May need a higher dose due to greater levels of binding globulins
• Follow TSH and FT4
• If they are already on thyroxine before they became pregnant, may have to increase the dose

• Somewhat common
• Usually early hyperthyroid stage (about 1 month)
• Followed by a long hypothyroid period (up to a year)
• Self-limited, but treat the hypothyroidism

Never order a thyroid scan or give radioactive iodine for any reason to a woman who might be pregnant or nursing

17-OH progesterone

• Low cortisol
• Low mineralocrticoids -- hypotension, salt-wasting, hyperkalemia
• High Androgens -- virilization, hirsutism, menstrual irregularities

Adrenal carcinoma usually also secrete DHEA and/or testosterone, may be palpable, much more symptomatic, progress more readily

• First, verify hypercortisolism
• 24-hour urine for cortisol
• Normal: 20-90 ug/day
• Cushing syndrome: > 150 ug/day
• Second, check for normal suppression
• Use low-dose dexamethasone suppression
• If adequate suppression
• Normal HPA axis
• Pseudo-Cushing's
• Inadequate suppression indicates disorder
• Third, check for pituitary disease
• Use high-dose dexamethasone suppression
• Adequate suppression indicates pituitary source (Cushing disease)
• Inadequate suppression indicates non-pituitary cause

• 1 mg dexamethason suppression test
• give 1mg of dexamethason at 11:00 pm
• draw blood at 8:00 am
• Cortisol
• -- Normal post-suppression: < 5 ug/dL
• -- Cushing syndrome: > 10 ug/dL

• 8 mg dexamethasone suppression test
• give dose at 2300
• draw blood at 0800
• Check cortisol
• < 50% of baseline suggests pituitary ACTH-dependent (Cushing's) disease
• > 50% of baseline suggests wither exotic ACTH disease or ACTH-indpendent cause

• Malignant adrenal tumor
• Adrenal cyst
• Pheochromocytoma

• Surgery if it's a tumor
• Other options are not very good.

• Primary symptoms: Fatigue, nausea, anorexia, weight loss, abdominal pain, arthralgia, low-grade fever; salt craving, postural dizziness; decreased libido
• Central symptoms: Same symptoms as primary insufficiency but no salt craving and postural dizziness

• Primary signs: Hyperpigmentation, Dehydration, Hypotension, Decreased pubic/axillary hair in women
• Central signs: Normal pigmentation, Normal volume, Slight decrease in blood pressure, Decreased pubic/axillary hair in women

• When primary adrenal insufficiency is present, plasma ACTH levels are increased and serum cortisol and aldosterone levels are low. A minimal or no increase in serum cortisol level in response to cosyntropin stimulation confirms the diagnosis. In normal persons, serum cortisol levels increase to 18.5 µg/dL (510.6 nmol/L) or greater 60 minutes after 250 µg of cosyntropin is administered intravenously (mean response, 28 µg/dL [772.8 nmol/L]).
• Patients with central adrenal insufficiency have low or low-normal plasma ACTH levels and normal plasma aldosterone levels. Although patients with central adrenal insufficiency usually have a subnormal response to cosyntropin, some with partial deficiency display normal responses; in such patients, using a lower dose of cosyntropin (1 µg instead of 250 µg) improves the diagnostic accuracy of the test. Serum levels of DHEA and DHEA-S are low in both primary and central adrenal insufficiency.

fludrocortisone, 0.05 to 0.1 mg/d

• Patients with primary adrenal insufficiency require corticosteroid therapy and mineralocorticoid replacemen
• Whereas those with central disease need corticosteroid therapy only

• Primary: Low basal serum cortisol level (<5.0 µg/dL [138 nmol/L]) with a suboptimal response (<18.5 µg/dL [510.6 nmol/L]) to cosyntropin; low serum DHEA and DHEA-S levels but high plasma renin activity and ACTH level
• Secondary: Same cortisol findings as primary insufficiency except low or inappropriately normal ACTH level; normal aldosterone and plasma renin activity

• Usual findings with low cortisol
• Weakness and fatigue
• Sparse body hair
• Low or low-normal glucose
• Anorexia
• Nausea
• Diarrhea
• Abdominal pain

• Autoimmune destruction (Addison disease)
• Surgery or trauma
• Infectious destruction
• Hemorrhagic destruction ( i.e., Waterhhouse-Friderichson syndrome of meningococcemia, purpura, and acute adrenal hemorrhage)

• Pituitary insufficiency secondary to inadequate ACTH production
• Withdrawal of exogenous glucocorticoids (common)

Giving it in the morning makes it less likely to suppress ACTH, which can happen if dose is given at night.

• Synthetic ACTH (cosyntropin)
• 1 amp (250 ug) given IM or IV
• Draw blood before the ACTH is given and 30 to 60 minutes afterwards
• Measure serum cortisol
• Normal is any cortisol > 20 ug/dL

150-200 mg/d IV in four divided doses

100-150 mg/d IV in four divided doses

30-50 mg/d PO in three divided doses

15-25 mg PO in three divided doses,^a at 8:00 AM (7.5-12.5 mg), 12:00 noon (5.0-7.5 mg), and 6:00 PM (2.5-5.0 mg)

^aFor twice daily dosing, the morning dose is 10-15 mg PO, and the late afternoon dose is 5-10 mg PO.

• The only treatment is glucorticoids
• Typically hydrocortisone BID
• Hydrocortisone also has some mineralocoticoid effects, which are useful if primary adrenal insufficiency

Replace glucocorticoids before starting on thyroxine replacement

• Hyperkalemia
• Metabolic acidosis
• Hypotension

• Hypokalemia
• Metabolic alkalosis
• HTN
• Often without edema

• First, try to suppress aldosterone
• Saline load
• Supine for several hours while fully hydrated
• Check aldosterone and renin
• High aldosterone and low renin indicates primary hyperaldosteronism
• High aldosterone and high renin indicates secondary hyperaldosteronism

• Presentation similar to primary hyperaldosteronism
• - hypokalemia
• - alkalosis
• - hypertension
• - low renin
• But low aldosterone
• High levels of deoxycorticosterone (DOC)
• - can be from DOC-secreting tumor
• Ingestion of natural licorice
• - has metabolite which inhibit 11β-hydroxysteroid dehydrogenase type 2 (converts cortisol into cortisone) and raises cortisol levels within the kidney.

• HTN
• Sudden, severe throbbing HA
• Profuse sweating
• Palpitations
• Anxiety or a sense of doom
• Skin pallor
• Nausea

• 24-hour urine for catecholamines, metanephrines, VMA
• Consider serum catecholamines while patient is symptomatic
• Plasma free metanephrines -- high sensitivity, but has high false positive

• Diuretics
• Vasodilators (hydralazine, minoxidil)
• CCB
• ACE-I

• Surgical recetion of tumor, but patient must first be treated with an a-adrenergic receptor blocker (phenoxybenzamine)
• Never block B-receptores without first blocking a-receptors; otherwise unopposed a-stimulation worsens vasoconstriction
• Give large volume during surgery

• Check the ff:
• - Blood pressure
• - Serum potassium
• - 24-hour urine dor catecholamines, metanephrines, and VMA

• *If you suspect cortisol excess, order 24-hour urine cortisol or overnight dexamethasone suppression test
• *If suspect mineralocorticoid excess, order supine aldosterone and renin activity
• *Women with hirsutism, check testosterone
• *Man with gynecomastia, check testosterone and estradiol

• If (+) secretion or if tumor is > 5 cm, need surgical resection
• Otherwise, consider referral for CT-guided biopsy (first rule out pheo)
• Remaining option is to repeat CT in 3 months and look for evidence of growth
• If growing, refer for surgical resection

• Same symptoms as primary insufficiency but no salt craving and postural dizziness
• Normal pigmentation
• Normal volume
• Slight decrease in blood pressure
• Decreased pubic/axillary hair in women
• Same cortisol findings as primary insufficiency except low or inappropriately normal ACTH level; normal aldosterone and plasma renin activity
• Same findings as primary insufficiency but also normal potassium level

• Fatigue, nausea, anorexia, weight loss, abdominal pain, arthralgia, low-grade fever; salt craving, postural dizziness; decreased
• libido
• Hyperpigmentation
• Dehydration
• Hypotension
• Decreased pubic/axillary hair in women
• Low basal serum cortisol level (<5.0 µg/dL [138 nmol/L]) with a suboptimal response (<18.5 µg/dL [510.6 nmol/L]) to cosyntropin; low serum DHEA and DHEA-S levels but high plasma renin activity and ACTH level
• Hyponatremia, high potassium level, azotemia, anemia, hypoglycemia, and leukopenia (with a high % of eosinophils and lymphocytes)

• Turner syndrome
• Destruction of the ovaries
• - Radiation or chemotherapy
• - Autoimmune

• Kallman's syndrome
• Hypothalamic and pituitary disease
• Uremia and chronic renal failure
• Anorexia nervosa
• Strenuous weight bearing exercise (swimmers not affected)
• Stress

• Gonadotropins (LH, FSH) are elevated
• Karyotype to verify (Some women will have Y chromosome). This points to a high risk of gonadoblastoma. Need referral to surgery to remove all the tissue around where the ovaries would be.

• HTN
• Heart murmur, often aortic stenosis
• Coarctation of the aorta
• Renal abnormalities
• Increased risk of:
• Hashimoto's thyroiditis
• Osteoporosis
• DM
• Aortic dissection

• Begin exogenous estrogen at expected time of puberty and later add periodic progesterone
• Estrogen to help bone density
• Progesterone to induce menses and protect the endometrium
• Eche q 3-5 years (due to high risk of aortic dissection)
• Excision of gonadal area if Y chromosome is present.

• No history of any menses by age 16
• No secondary sex characteristics by age 14

• Past history of menses
• No menses for 3 months

• Pregnancy test
• Prolactin and TSH
• Ovarian axis (FSH, LH)
• - Elevated implies ovarian failure
• - Decreased or inappropriately normal implies CNS or pituitary dysfunction
• Assess endogenous estrogens
• - Check estradiol
• - Induce withdrawal bleeding

Anovulatory with continuous stimulation of the ovary by LH

• Infertility
• Hirsutism
• Amenorrhea
• Obesity
• Virilization
• Ovary thickened, enlarged, with multiple follicles at different levels of maturation

• Increased risk of endometrial hyperplasia and cancer from unopposed estrogens
• Insulin resistance
• Increased risk of coronary artery disease

• LH (elevated)
• FSH (often normal)
• LH/FSH ratio (usually > 3)
• Testosterone (elevated)
• Estrogens (elevated)
• Check PRL and TSH

Clomiphine citrate

Metformin (not FDA approved for this), less effective than clomiphene

18 +/- 4.8 ml

• 1. Klinefilter
• 2. low gonadotropins
• 3. postpuberal atrophy

• Trauma, torsion
• Infection (mumps, leprosy)
• Cryptorchidism
• Klinefilter's syndrome
• Radiation or chemo
• Autoimmune destruction

Klinefilter

• 47 XXy (Barr body is present)
• Onset is prepubertal
• Testes small and firm, often < 2.5 cm (4 ml), smaller than prepubertal size
• Increased length of lower body segment
• Arm span not increased (unexpected)
• Gynecomastia
• Testosterone low or low-normal
• Gonadotropins elevated

• Can occur in both men and women
• 46, XY (or XX)
• Testes small, but larger than in Klinefelter -- 3-4 cm, normal prepubertal size
• Eunochoid proportions -- lower body segment and arm span
• Normal mental development
• Anosmia or hyposmia (olfactory bulb neuron migrationd defect)
• Basal FSH and LH low or undetectable
• Low testosterone
• Do not order karyotype to verify

Kallman syndrome

• Androgen replacement does not address infertility
• Fertility treament
• -- hCG (LH replacement) to stimulate Leydig cells
• -- Once testosterone levels are normal, begin rhFSH for spermatogenesis
• - - alternatively LHRH pulsatile infusion pump

• Nitrates are contraindicated
• LV outflow obstruction (i.e., aortic stenosis, idiopathic hypertrophic subaortic stenosis)
• Concomitant use of alpha-blockers

unilateral, hard contender, irregular mass

Testosterone, LH, FSH, β-hCG, TSH, estradiol, prolactin

• Hereditary angioneurotic edema
• -- Danazol stimulates C1q production
• Hypogonadism
• -- titrate dose based on subjective response. Do not measure testosterone

• Hepatotoxicity, including liver cancer
• Decreases fertility and testicular sizes
• Cardiomyopathy
• Thrombosis
• Gynecomastia
• Behavioral disturbances
• In women: hirsutism and virilization

• Lactescent serum
• Eruptive xanthoma
• Lipemia retinalis
• - retinal vessels are white
• Abdominal findings
• - pain
• - acute pancreatitis
• - hepatosplenomegaly

• Ethanol abuse
• Insulin resistance
• Obesity
• Hypothyroidism
• Nephrotic Syndrome
• Medications

• Antiretroviral therapy (not atazanavir)
• Estrogens (oral > patch)
• Tamoxifen
• Glucocorticoids
• Non-selective beta blockers
• 13-cis-retinoic acid
• HCTZ (> 50 mg/day)

• DM
• Hypothyrodism
• Nephrotic syndrome
• CRF
• Obstructive liver disease
• Glucocorticoids
• Anabolic steroids
• Progestins

• diet high in trans-fatty acids
• Beta-blockers (except labetalol)

• Uncommon
• LDL typically > 250 mg/dL
• First line treatment -- statins

• Common
• Most common cause of lactescent plasma
• High LDL and VLDL
• Increased production of VLDL, which leads to high LDL (VLDL gets converted into LDL)
• LDL typically 190-230
• Treat with statin

• High TG (from VLDL)
• Treatment:
• -- First choice: niacin (inhibits hepatic syntheses of VLDL)
• -- 2^nd choice: fibrates (increase activity of LPL, which removes TG from VLDL)

• High IDL
• Familial but usually in conduction with DM, obesity, hypothyroidism, or alcohol abuse
• Characteristic finding is yellow palmar crease
• Treatment:
• -- Nicotinic acid
• -- Low-fat diet

LDL

TG

TG

LDL + TG

IDL

• Age
• -- Men > 45 years
• -- Women > 55 years

• Family history if premature CHD in first degree relatives
• -- male < 55 years
• -- female < 65 years

Current cigarette smoking

DM

• Non-CHD atherosclerotic disease
• -- peripheral arterial disease
• -- abdominal aortic aneurysm
• -- symptomatic carotid artery disease

Multiple risk factors conferring 10-year risk of CHD > 20%

• LDL goal is < 100
• Begin drugs if LDL > 130

• LDL goal < 130
• Begin drugs if LDL > 160

• LDL goal < 160
• Begin drugs if LDL > 190

• Check baseline LFTs and repeat in 12 weeks after starting or increasing the dose
• If ALT > 3X ULN, reduce dose or switch statins

• Decrease VLDL
• May raise LDL
• Increase HDL
• No effect on chylomicrons

Fenofibric acid (Trilipix)

• Inhibits intestinal absorption of dietary and biliary cholesterol
• Effect on lipids:
• -- reduces TC and LDL
• -- Increases HDL
• Small risk of myopathy and elevated transaminases, mostly in combination with a statin

• Examples include Cholestyramine and Colestipol
• Decrease LDL
• No effect on HDL
• May increase production of VLDL (TG)
• -- avoid if TG elevated
• -- avoid in dysbetalipoproteinemia because VLDL gets converted into IDL
• Do not take within 4 hours of other drugs
• Side effects include N/V, constipation, bloating

Bile acid sequestrates (cholestyramine, colestipol)

• Inhibits hepatic production of VLDL
• Lowers TG, LDL
• Raises HDL

statin

Nicotinic acid

• Other choices:
• Fibrates (but may raise LDL)
• Statin with fibrate
• Ezetimibe

Nicotinic acid or fibrate

Active or Chronic liver diease

Active of chronic liver disease

• Dysbetalipoproteinemia
• TG > 400 mg/dL

Severe kidney or liver disease

• Chronic liver disease
• Severe gout

• Symptoms plus casual glucose ≥ 200 mg/dL
• or fasting glucose ≥ 126 mg/dL
• or 2-hour glucose ≥ 200 mg/dL during a 75 g OGTT

• 100-125 mg/dL
• 140-199 mg/dL two hours after 75 g OGTT

Acanthosis nigricans

• Usual onset is 10-15 years after developing diabetes.
• Type 1 diabetics do not need to be screened for microvascular complications for the first five years.

• duloxetine
• pregabalin

• screen every 6 months
• Random urine for albumin and creatinine:
• Normal: < 30 mg albumin/g Cr
• Microalbuminuria: 30-300 mg albumin/g Cr
• Macroalbuminuria: > 300 mg albumin/g Cr

If very acidotic (pH < 7.1) and discontinue when it reaches 7.2

• Latent Autoimmune Diabetes of Adults
• Type 2 DM but with autoantibodies
• -- Anti-GAD (Glutamic Acid Decarboxylase)
• -- Anti-islet cell
• Antibodies will convert type 2 into type 1
• May respond to oral treatment initially, but will soon require insulin

• Glucose levels often rise just before we wake up
• Minimal increase
• Due to early morning rise in growth hormone levels
• Not associated with preceding hypoglycemia

• Early morning rise in glucose caused by nocturnal hypoglycemia
• Need to decrease the evening insulin
• Look for evidence of nocturnal hypoglycemia
• -- sweating during the night
• -- restless sleeping
• -- waking up feeling tired and drained
• -- bad nightmares

• Glipizide
• Glyburide
• Glimepiride

• Meglitinides
• "Immediate" release of insulin
• Very short half-life
• Available agents are -- Repaglinide, Nateglinide
• Avoid if with significant liver disease
• Use low dose in mild hepatic dysfunction
• Safe in renal failure -- no dose adjustment needed
• Nateglinide is not indicated if patient failed other oral secretagogues

• Only metformin is available
• Reduce insulin resistance primarily at the level of the liver
• Reduce hepatic glucose production

Creatinine ≥ 1.5 in men and ≥ 1.4 in women

• Improve insulin resistance at the level of the adipocytes and muscles
• No adjustment needed for renal failure
• May cause or worsen edema
• May reduce Hgb levels
• Examples are: Rosiglitazone, Pioglitazone
• Risk of hepatic dysfunction
• -- check ALT before initiation and periodically thereafter
• -- Hold if ALT ≥ 2.5 x ULN
• Cardiac risk is suspected with rosiglitazone
• May cause/worsen heart failure
• -- do not use in class III or IV CHF
• -- Risk is greater when used in combination with insulin
• -- avoid highest dose if also on insulin

• Currently available -- Acarbose, Miglitol
• Work in GI tract wo slow the digestion of complex COOH
• Little or no systemic drug levels

• Normally secreted by β-cells along with insulin
• Suppresses postprandial rise in glucagon, thus decrease hepatic gluconeogenesis
• Slows gastric emptying
• Decreases appetite

• Can be used with insulin in type 1 or 2
• Injectable only -- cannot be mixed with insulin
• Associated with weight loss
• Most common side effect is nausea, hypoglycemia
• Initially reduce insulin dose by 50% if taking it with Pramlintide

• Normally secreted bu certain intestinal cells in response to a meal
• Suppresses postprandial rise in glucagon
• Stimulates glucose-dependent insulin secretion
• Stimulates increase in beta cells
• Slows gastric emptying
• Decreases appetite

• Approved for DM-2, not type 1
• Approved for use with sulfonylurea, metformin, or TZD
• Cannot be mixed with insulin

• Oral
• Inhibits breakdown of GLP-1

• low carbohydrate diet
• multiple small meals

• 72-hour fast
• Terminate 72-hour fast if with 2 or more glucose levels < 40 mg/dL and neuroglycopenic signs
• Detectable levels of insulin and C-peptide
• No evidence of surreptitious insulin secretagogues
• Refer for localization of islet cell tumor and surgical excision
• Screen for sulfonylurea also

• Confusion
• Lightheadedness
• Aberrant behavior
• Blurred vision
• Loss of consciousness
• Seizures

1,25(OH)₂ Vit D

• Apathy, drowsiness, depression, obtundation, coma
• Muscle weakness
• Bowel hypomotility
• Shortening of QTc time interval
• Decreased GFR, impaired concentrating ability, nephrolithiasis, nephrocalcinosis

• Salt-and-pepper appearance of skull
• Resorption of distal phalanges
• Tapering of distal clavicle
• Bone cysts (osteitis fibrosa cystica)
• Osteopenia

• Measure _iPTH
• Elevated _iPTH (or even WNL) with high Ca⁺⁺
• Usually low phosphate levels

Surgical exploration and resection if indicated.

• Serum Ca ≥ 1 mg/dL over ULN
• Urine calcium > 400 mg/day
• Symptomatic
• Low bone density (t score < -2.5)
• Age < 50 years
• Cr Cl reduced by ≥ 30%

• Apathy, drowsiness, drowsiness, depression, obtundation, coma
• Muscle weakness
• Bowel hypomotility
• Shortening of QTc time interval
• Decreased GFR, impaired concentrating ability, nephrolithiasis, nephrocalcinosis

• Primary hyperparathyroidism
• Malignancy related
• Medications
• Granulomatous disease
• Immobilization
• Milk-alkali syndrome

• Measure intact PTH (iPTH)
• Elevated iPTH (or even WNL) with high Ca++
• Usually low phosphate levels (PTH stimulates renal excretion of phosphate)

Surgical exploration and resection if indicated

• Mild is Ca < 12 mg/dL with no or mild symptoms
• Encourage hydration
• Avoid thiazides, high calcium diet, bed rest

• Severe is Ca++ > 14 mg/dL
• IV hydration
• IV calcitonin (if responsive, works in hours)
• IV bisphosphonate (works in a few days)
• -- Pamidronate
• -- Zoledronic acid -- more efficacious, faster infusion, but higher risk of jaw osteonecrosis

• Carpal spasm with pressure-- ischemia or upper arm nerves (Trosseau sign)
• Twitch with tapping of facial nerve (Chvosted sign)
• Prolongation of QTc interval
• Circumoral numbness, cramps, fatigue, irritability, anxiety, depression

• Insufficient exposure to sunlight
• Inadequate vitamin D intake
• Malabsorption
• Measure 25(OH) Vit D for (vitamin D stores)

• Seen in patients with prolonged primary hyperparathyroidism
• Bones become very deficient in calcium
• Following parathyroid adenoma resection, PTH levels drop and the bones avidly take up calcium
• May require calcium and Vit D supplements for a limited time

Corrected calcium = measure calcium + (4-albumin) x 0.8

• It is a genetic disorder that results from impaired PTH receptor
• Main characteristic is shortened 4th and 5th metacarpals and metatarsals (watch for picture of hand with short 4th and 5th fingers)
• Round faces
• Short stature
• Obesity
• 

No!

• Family must have adenomas of at least 2 of the following organs:
• - Pituitary
• - Pancreas -- Gastrinoma, Insulinoma, Glucagon, serotonin, VIP
• - Parathyroid

• Medullary thyroid cancer
• Pheochromocytoma
• Two "flavors" of MEN 2 based on other tumors

2A: Parathyroid adenoma

2B: Ganglioneuroma phenotype -- Thickened lips, Multiple small bumps of the tip of the tongue

• Arises from the calcitonin-secreting C cells
• Occurs in 4 settings:
• - Sporadic
• - Component of MEN 2A
• - Component of MEN 2B
• - Familial non-MEN medullary thyroid cancer
• Fatal if not treated early
• Requires early thyroidectomy at an early age.
• But must be sure before you send a child for a total thyroidectomy antis possible complications

• Check for RET proto-oncogene mutations
• If index cases has a detectable mutation:
• - Check all primary relatives for the same mutation
• - If found, refer for cervical exploration and total thyroidectomy (even if very young) after screenig for pheochromocytoma
• If relative does not have the mutation, then no risl

24-hour urine 5-HIAA

• Hyperaldosteronism
• Order saline suppression test with aldosterone and renin while supine

• It is useful when investigating the possibility of excessive glucocorticoid secretion
• Not helpful in diagnosing adrenal insufficiency because of the wide range of normal values

• used as the gold standard to investigate the integrity of the hypothalamic-pituitary-adrenal axis.
• hypoglycemia stimulates ACTH secretion from the pituitary gland, which in turn stimulates the adrenal glands to secrete cortisol.

*Given its serious potential adverse effects, the insulin-induced hypoglycemia test should be performed only by experienced endocrinologists and should not be pursued as a routine diagnostic test in this patient.

• DM
• Hypogonadotropic hypogonadism
• Adrenal insufficiency

Mental status changes and hypothermia

1.0 to 2.5 µU/mL (1.0 to 2.5 mU/L).

The presence of anti–thyroid peroxidase antibodies

Adequate iodine intake is imperative for thyroid hormone production; pregnant and lactating women require 50% or 100%, respectively, more iodine intake than the general population.

Color-flow Doppler ultrasonography

• Graves disease
• toxic multinodular goiter
• toxic adenoma

A T3 level (total or free) should be obtained in patients with a suppressed TSH level but a normal free T4 level because some patients have T3 toxicosis

TSH receptor antibodies TSI and TBII

• an autoimmune process characterized by the production of antibodies against the TSH receptor.
• On TSH receptor binding, these antibodies stimulate autonomous thyroid gland function and lead to excess serum T4 or T3 levels.
• can present with either subclinical or overt thyrotoxicosis.

• Antithyroidal drugs
• radioactive iodine (131I)
• thyroid surgery

typically reserved for patients with ¹concurrent suspicious nodules, ²extremely large goiters, or ³ophthalmopathy in whom radioactive iodine has aggravated their eye condition.

• Propylthiouracil
• methimazole

• elevated aminotransferase levels
• higher rate of serious adverse effects on the liver than methimazole.
• Rarely, severe hepatic necrosis has been reported, predominantly with propylthiouracil

a recent advisory suggested that propylthiouracil should not be used as a first-line antithyroidal medication, with the possible exception of the first trimester of pregnancy, during which methimazole has been associated with possible teratogenicity.

Both are know to cause agranulocytosis

Radioactive iodine treatment has been associated with worsening of Graves ophthalmopathy

toxic adenoma

toxic multinodular goiter

• Good history is essential.
• Evaluate onset, rate of progression, presence of virilization, and presence of other symptoms, such as galactorrhea, bruising, or myopathy.
• Differential dx includes -- PCOS, androgen producing tumors, Cushing syndrome, and occult 21-hydroxylase deficiency, particularly when the hirsutism involves sudden onset and rapid progression
• PCOS, the most common cause of hirsutism, normally starts during pubertal development, progresses slowly, and does not cause virilization or cushingoid features.

according to the current Rotterdam criteria, requires two of the three following findings: ovulatory dysfunction, laboratory or clinical evidence of hyperandrogenism, and ultrasonographic evidence of polycystic ovaries.

• If fertility is not desired, spironolactone plus an oral contraceptive pill containing a progestin with low androgenicity (desogestrel, norgestimate, gestodene, or drospirenone) is a good first-line combination therapy.
• Metformin decreases the serum testosterone level and improves ovulation rates in women with PCOS, even in those with normal insulin sensitivity
• Clomiphene is superior to metformin for producing live births with oral therapy alone in women with PCOS who desire children, but infertility treatments such as clomiphene should be prescribed only by a reproductive endocrinologist

• Dopamine agonists (cabergoline and bromocriptine) are preferred as the initial treatment of prolactinomas because of their fery high efficacy
• Dopamine agonists are effective for patients with small and large prolactinomas, and cabergoline is more efficacious and better tolerated than bromocriptine.
• Cabergoline causes a normalization of prolactin levels in greater than 90% of patients and also a significant reduction in prolactinoma size in nearly 90%. If the large tumor has caused hypopituitarism, a restoration of normal pituitary function may also occur.

• MEN1 is characterized by tumors of the parathyroid, pituitary, and pancreatic islet cells (the three “P”s)
• MEN1 is inherited in an autosomal or sporadic manner
• The most common familial form of hyperparathyroidism is a component of MEN1.
• Primary hyperparathyroidism is almost always present in this disorder
• Pancreatic tumors, present in 30% to 80% of patients with MEN1, are islet cell tumors that most commonly secrete gastrin and cause Zollinger-Ellison syndrome
• The second most common pancreatic tumor is an insulinoma.
• Pituitary adenomas affect 15% to 50% of patients with MEN1 and are mostly prolactinomas, although tumors causing acromegaly and Cushing disease also occur.

• MEN2 is characterized by medullary carcinoma of the thyroid gland in combination with pheochromocytoma and parathyroid adenomas (MEN2a) or with a pheochromocytoma, ganglioneuromas, and a marfanoid habitus (MEN2b)
• MEN2 is inherited as an autosomal dominant trait

• An inherited autosomal recessive disorder with a 25% incidence among siblings of patients with the disease.
• Characterized by the triad of chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and adrenal insufficiency.

• or POEMS syndrome
• consists of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (M spike) on serum protein electrophoresis, and Skin abnormalities
• This syndrome is associated with several endocrinopathies in the setting of lymphoproliferative disorders and presumed B-cell dysfunction.
• Hypogonadism appears to be the most common endocrine abnormality.

• If results of the initial laboratory assessment are normal, the cornerstone of the evaluation for secondary amenorrhea rests on the results of a progestin withdrawal challenge (medroxyprogesterone acetate, 10 mg orally for 10 days).
• Menstrual flow on progestin withdrawal indicates relatively normal estrogen production and a patent outflow tract, which limits diagnostic evaluation to chronic anovulation.
• Absence of flow indicates estrogen absence and/or an anatomic defect. In patients with no flow, pelvic anatomy is assessed with ultrasonography and/or MRI. The absence of menses for several months after dilation and curettage in this patient suggests severe endometrial damage or formation of scar tissue (Asherman syndrome).

• This is due to increased 1,25-dihydroxy vitamin D production in patients with granulomatous diseases (sarcoidosis or lymphoma)
• 1. Can be treated with prednisone for 2 to 5 days.
• 2. Calcium absorption can be partially blocked by phosphate-containing drugs that form insoluble calcium phosphate complexes and prevent absorption.
• 3. Reducing calcium intake to 400 mg/d or less is also beneficial.

Pts with Ca level 14 mg/dL should be treated regardless of symptoms

Klinefilter syndrome

Papillary thyroid cancer and follicular thyroid cancer are treated with total thyroidectomy followed generally by therapy with iodine-131.

• fine-needle aspiration biopsy should be performed to establish diagnosis
• radionuclide scanning should be reserved for patients with indeterminate cytology or thyrotoxicosis

• production of calcitonin
• Serum calcitonin levels can be used to monitor disease status.

Thyroidectomy

Secondary hyperparathyroidism occurs when decreased circulating serum calcium levels stimulate secondarily increased secretion of PTH. This commonly occurs in vitamin D deficiency and chronic kidney disease. Although hypercalcemia does not occur in secondary hyperparathyroidism, patients with chronic kidney disease who have hypercalcemia can develop dysregulation of parathyroid function, which results in a condition known as tertiary hyperparathyroidism.

More advanced forms of hyperparathyroid bone disease, such as osteitis fibrosa cystica, also can rarely occur; radiographic manifestations of osteitis fibrosa cystica include periosteal resorption of the digits, irregular demineralization of the skull, and brown tumors of the long bones.

initiate therapy with an α-blocker, either a long-acting, noncompetitive antagonist, such as phenoxybenzamine, or a short-acting antagonist, such as prazosin, doxazosin, or terazosin. Recent data indicate that many centers use a short-acting α-blocker instead of phenoxybenzamine because the latter can be associated with more prolonged postoperative hypotension. Preoperative preparation with α-adrenergic blockade reduces the incidence of intraoperative hypertensive crisis and postoperative hypotension. The primary goal is to maintain blood pressure in the range of 140 to 150/90 mm Hg. Preoperative medical therapy should be instituted once the diagnosis is reached and before surgical resection.

A low radioactive iodine uptake in a patient with symptoms of thyrotoxicosis suggests thyroiditis or exogenous thyroid hormone exposure; the erythrocyte sedimentation rate and thyroglobulin level are low in patients taking exogenous thyroid hormone and elevated in those with thyroiditis.

Paget disease is a focal disorder of bone remodeling that leads to greatly accelerated rates of bone turnover, disruption of the normal architecture of bone, and sometimes gross deformities of bone (such as enlargement of the skull and bowing of the femur or tibia). Most patients with Paget disease are asymptomatic. The diagnosis is often suspected from radiographs obtained for other reasons or from an isolated elevation of the serum alkaline phosphatase level. There is no cure for Paget disease, but bisphosphonates (such as alendronate, risedronate, tiludronate, pamidronate, zoledronate, and etidronate) decrease the accelerated rate of osteoclastic bone resorption.

BMI ≥40 or ≥35 with medical comorbidities such as sleep apnea, obesity-related cardiomyopathy, severe arthritis, hyperlipidemia, diabetes, or glucose intolerance

In lymphocytic hypophysitis, a pituitary mass that mimics an adenoma is typically seen on an MRI. Diffuse enhancement of a symmetrically enlarged pituitary gland on MRI is also characteristic. This disorder, which usually develops intrapartum, is a destructive process thought to have an autoimmune basis. Adrenocorticotropic hormone (ACTH) deficiency occurs in two thirds of patients with such lesions and is a major cause of death in patients with lymphocytic hypophysitis.

Pituitary tumor apoplexy, which is usually due to hemorrhage into a prior tumor, has a dramatic presentation, with sudden onset of severe headache, stiff neck, and (often) a decreased level of consciousness.

The evaluation of unexplained hypertension and unprovoked hypokalemia begins with measurement of the plasma renin activity and aldosterone level. A serum aldosterone to plasma renin activity ratio greater than 20 and a serum aldosterone level greater than 15 ng/dL (414 pmol/L) strongly suggest primary hyperaldosteronism. After hyperaldosteronism is confirmed, a search for the anatomic or pathologic cause should begin. CT of the adrenal glands is the appropriate initial step in identifying the anatomic cause of the disease.

• When aldosterone is secreted excessively, the expected outcome is hypertension, hypokalemia, and metabolic alkalosis. For these reasons, patients with hypertension should be screened for primary hyperaldosteronism, especially when the hypertension is difficult to control or associated with hypokalemia.
• Screening of patients for primary hyperaldosteronism focuses on the physiologic changes (namely, suppressed renin activity) and thus involves the simultaneous measurements of the plasma aldosterone level and plasma renin activity. A ratio of plasma aldosterone (measured in ng/dL) to plasma renin activity (measured in ng/mL/h) of greater than 20 is highly suggestive of primary hyperaldosteronism, especially when the plasma aldosterone level is greater than 15 ng/dL (414 pmol/L). This ratio is particularly helpful in patients taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs), in whom plasma renin activity is expected to be generally high but plasma aldosterone levels are usually low. In a patient receiving an ACE inhibitor or an ARB, one would expect the plasma aldosterone level to be lower than 10 ng/dL (276 pmol/L) and the plasma renin activity to be greater than 3 ng/mL/h (3 µg/L/h) with an aldosterone-to-renin ratio of less than 5. Thus, in a patient receiving an ACE inhibitor or ARB, an aldosterone-to-renin ratio of 10 or more would be highly suggestive of hyperaldosteronism.
• The screening tests can be performed on random blood samples, even in patients on antihypertensive medications (except the aldosterone receptor antagonists spironolactone and eplerenone). Confirmation of the biochemical diagnosis involves showing persistent elevation (poor suppressibility) of plasma aldosterone in response to a high salt load. Salt can be given orally (sodium chloride, 2 g three times daily for 3 days) or intravenously (with normal saline, 500 mL/h for 3 hours). During either method of salt loading, plasma aldosterone levels are suppressed to less than 5 ng/dL (138 pmol/L) in normal subjects but remain elevated (often greater than 10 ng/dL [276 pmol/L]) in patients with primary hyperaldosteronism.

• The goal of treatment in patients with acromegaly is to normalize anterior pituitary function and GH secretion, control tumor growth, and treat systemic complications. Transsphenoidal surgical resection is typically the treatment of choice. Medical treatment is often also required because many of these tumors are too large at presentation to be completely excised by surgery. In patients with such tumors, medical therapy is indicated.
• Examples of somatostatin analogues are octreotide or lanreotide.

Diagnosis requires two of the three following features: (1) ovulatory dysfunction, (2) laboratory or clinical evidence of hyperandrogenism, and (3) ultrasonographic evidence of polycystic ovaries.

In patients with hirsutism and polycystic ovary syndrome who do not wish to become pregnant, the most appropriate initial therapy is spironolactone and an oral contraceptive pill.

• Metformin decreases the serum testosterone level and improves ovulation rates in women with PCOS, even in those with normal insulin sensitivity. Although metformin is effective and does not appear to be teratogenic, patients should be counseled that the treatment of PCOS with metformin is an off-label indication and that ovulation and pregnancy may occur. Given the favorable effect of metformin on lipid profiles and progression to diabetes in selected populations, chronic metformin therapy offers many advantages and should be considered, either alone or in combination with other agents, a first-line therapy when metabolic abnormalities are significant.
• Clomiphene is superior to metformin for producing live births with oral therapy alone in women with PCOS who desire children

a rare familial condition caused by inactivating mutations of the calcium-sensing receptor, which has a major function in regulating calcium metabolism through parathyroid tissue and renal calcium. The disorder is autosomal dominant with high penetrance. There is decreased sensitivity of the calcium-sensing receptor to calcium; therefore, higher calcium levels are required to suppress PTH secretion. Heterozygous patients generally have hypercalcemia, hypocalciuria, and mild hypermagnesemia at presentation. Fractional excretion of calcium is less than 1% despite the hypercalcemia, and the PTH level is normal or slightly elevated.

increased 1,25-dihydroxy vitamin D production

• Measurement of total testosterone, preferably from two blood samples collected in the early morning, is the initial diagnostic test for suspected hypogonadism. Although normal ranges are somewhat assay-dependent, values consistently less than 200 ng/dL (6.9 nmol/L) are considered low, and values consistently greater than 350 ng/dL (12.1 nmol/L) are considered normal. In patients with values that are between 200 and 350 ng/dL (6.9 and 12.1nmol/L) or that are inconsistent with the clinical situation, the free and/or bioavailable testosterone should be measured.
• Serum testosterone on two separate mornings before 1000 is ideal. Value less than 200 mg/dl confirms hypogonadism, and > 350 mg/dl rules it out. Values between 200-350 is equivocal.
• If equivocal, send free testosterone level, FSH, LH, PRL. If high or normal FSH, normal LH and prolactin, give Testosterone supplementation. However, if FSH and LH are low, and Prolactin high, the problem is in the pituitary and order MRI of pituitary and pituitary function testing.

Cerebral salt wasting, a syndrome characterized by hypovolemia and hyponatremia, usually occurs within 10 days of a neurosurgical procedure or disease, particularly subarachnoid hemorrhage.