THYROID GLAND

HYPERTHYROIDSIM

These 2 occur due to

activating mutation
in TSH receptors
4
Page
- Upto 60-80% pts with untreated hyperthyroidism develop myopathy
- Acute thyrotoxic myopathy: present with more severe distal or proximal muscle weakness, but usually
without bulbar or respiratory muscle involvement
- Chronic thyrotoxic mypopathy: usually proximal muscle weakness, weeks to months after onset of
hyperthyroidism
- Thyrotoxicosis can cause hypercalcemia due to increased bone resorption
- Objective findings: possible muscle atrophy, high-frequency and low-amplitude tremor with movement
P DTR T
myopathy
- Dx:
 TSHlowfree T4  hyperthyroidism24-hour thyroid radioiodine uptake and scan
G
 EKG rule out arrhythmia
- Rx:
I. Propranolol best initial treatmentsymptomatic relief until cause is identified and definitively
treatedrelieve tremor, tachycardia, sweating, anxiety starting dose: 10 mg orally
gradually until appropriate response achieved, usually 20mg 4 times a day is needed
II. Radioactive iodine definitive treatment, clinical improvement is achieved in approx. 6-18 wks. CI:
pregnancy and very severe ophthalmopathy. Young pts without cardiovascular dis. tolerate it well.
-
treated with ATDs
III. Subtotal thyroidectomy definitive treatment
6

IV. Propylthiouracil > 2/3rd recur after 6 months after stopping meds usually given only when
Page

radioiodine is CI like pregnancy. Most common side effect of anti-thyroid drugs is allergic reaction.
THYROID NODULE

toxic
adenoma

- Thyroid nodule evaluation is based on these factors: Cancer risk factors (e.g. family history, cervical
LAD, radiation exposure in childhood), compression symptoms (e.g. hoarseness, difficult swallowing)
and current thyroid status (e.g. euthyroid, hypo/hyperthyroidism)
- Suspicious US findings: hypoechoic, internal vascularity, microcalcifications etc

THYROID CANCERS

Risk factors: family history and

childhood exposure to radiation
11
Page
 Secondary hyperparathyroidism:

- Magnitude of rise in PTH directly correlate with severity of renal failure

HYPOPARATHYROIDISM

Primary hypoparathyroidism:

- Hypocalcemia+ hyperphosphatemia+ normal renal function tests

- Causes:
1. Post-surgical (most common) thyroidectomy or sub-total parathyroidectomy (i.e. removal of 3 ½
parathyroid glands for parathyroid hyperplasia)usually severe symptoms even with mild
hypocalcemia
2. Autoimmune most common non-surgical cause
3. Congenital absence or mal-development of parathyroid glands (eg DiGeorge)
4. Defective calcium sensing receptors on parathyroid glands
5. Non-autoimmune destruction of parathyroid gland sue to infiltrative dis. Such as hemochromatosis,
Wilson and neck irradiation
- C/F:
1. may be asymptomatic initiallyfound incidentally or may complain only of non-specific symptoms
like fatigue, anxiety, depression
2. Perioral tingling and numbness
3. Muscle cramps
4. Tetany
5. Carpopedal spasm
6. Seizures in severe cases
13

7. Can prolong QT interval

Page
CALCIUM METABOLISM

Hypercalcemia

most common cause

14
Page
 PTH resistance
Pseudo - hypoparathyroidism
Genetic
PTH gene or calcium sensing
receptor gene mutations
17
Page
 ADRENAL GLAND

CUSHING SYNDROME

Possible causes:
-Cushing disease
<5pg/ml
-Ectopic ACTH
production

-Ectopic CRH
production

Possible causes:
-exogenous
glucocorticoids

-adrenal adenoma

-primary
pigmented
nodular
adrenocortical
hyperplasia

Symptoms:
-rapid onset of hypertension

-metabolic alkalosis

-hyperglycemia

-proximal muscle weakness

20

from hypokalemia
Page

-absence of typical Cushing

symptoms
 FSH) ACTH stimulation test exaggerated 17 hydroxyprogesterone response. Cosyntropin stimulation
test is gold standard for partial deficiencies
- in cortisol ACTHadrenal hyperplasia
- aldosterone salt wasting
- C/F: depend on degree of enzyme deficiency
1. Severe (classic) 21 hydroxylase def present in infancy with virilization and salt losing crisis
2. Late-onset (non-classic) 21 hydroxylase def (CYP21A2 deficiency) mild, females present in teens
or twenties with cystic acne non-responsive to meds, irregular menses, and hirsuitism, virilization
not seen; boys present with precocious puberty hyponatremia variable in both sexes

ADRENOCORTICAL CANCERS:
- Rare, aggressive
- Present in adulthood usually
- Types: androblastoma, arrhenoblastoma, stromal and hilus cell tumor
- C/F: rapidly progressive hirsuitism and sometimes virilization
- Labs: serum DHEA-S (adrenal androgen) Dl

HYPERALDOSTERONISM

26
Page
Page 27
Page 28
 PROLACTINOMA

- Pt: women→ glactorrhea, amenorrhea

men→ erectile dysfunction , ↓ libido

- significant elevations in the prolactin level (eg, serum prolactin level >200 ng/ml OR repeat level >100 ng/ml )
suggest a prolactin-secreting tumor (prolactinoma).
- Elevated prolactin levels suppress gonadotropin-releasing hormone, LH, and estradiol.

- Prolactinomas are usually detected early (<10-mm microadenomas) in premenopausal women due to
31

associated endocrine symptoms (oligo/amenorrhea, infertility, galactorrhea).

Page

- Men and postmenopausal women often have minimal early symptoms and are more likely to seek evaluation
when a large tumor (>1 cm, macroadenoma) causes mass-effect symptoms (eg, headache, visual field defects).
Qid: 3492 / 3493
GROWTH HORMONE SECRETING PITUITARY ADENOMA:

75 g oral glucose
can suppress GH
to < 1µg/dl in
normal
individual

- GH stimulates hepatic insulin-like growth factor 1 (IGF-1) secretion, which is responsible for most
32

of the clinical manifestations of acromegaly.

- MOST COMMON cause is pituitary adenoma.
Page
 Idiopathic hirsuitism:
- Due to excessive conversion of testosterone to DHT in hair follicles. Usually +ve family history, no
virilization. 17 OH-progesterone and androgens usually normal

Ovarian or Adrenal tumor:

- Rapidly progressing androgenic symptoms (hirsuitisim, virilization)ovarian or adrenal tumor secreting
excess androgen
- Measure testosterone and DHEAS as initial workup
- DHEASovarian tumor
- DHEAS and relatively normal testosteroneadrenal tumor
- DHEAS is specific for adrenal glands and is sulfated form of DHEA. DHEA is produced by both ovaries and
testes

SECONDARY AMENORRHEA

35
Page
 DIABETES INSIPIDUS

In central, thirst mechanism is

also affected. In nephrogenic,
thirst mechanism is intact
water intake normalize Na+
conc. to some extent
WATER DEPRIVATION TEST:

47 Page
-

REFEEDING SYNDROME

Carbohydrate ingestion whether enteral or IV

50

- Phosphorus main electrolyte that is depleted as needed for energy (ATP)

- Aggressive initiation of nutrition without adequate repletion of electrolytescardiopulmonary failure
Page
 ZOLLINGER- ELLISON SYNDROME

Dyspepsia, reflux sx, abdominal

pain, weight loss, diarrhea, frank
GI blood loss

To reveal ulcers and

occasionally may reveal
primary duodenal gastrinoma

- gastrin parietal cell hyperplasia  inactivation of pancreatic enzymes

and injury to mucosal brush borderdiarrhea and steatorrhea
- once gastrinoma is confirmed screen for MEN 1 with assays of parathyroid, ionized calcium and
prolactin

- Fasting gastrin levels should be measured

52

- Check gastric pH if gastrin is >1000 as gastrin may also be elevated due to failure of gastric acid secretion
(achlorhydria)
Page
Determining the etiology of primary adrenal
insufficiency in adults

This algorithm reviews the approach to determining the etiology of

primary adrenal insufficiency. It is based upon UpToDate content on
diagnosis of adrenal insufficiency and causes of primary adrenal
insufficiency.

PAI: primary adrenal insufficiency; 21-OH-Abs: 21-hydroxylase

antibodies; VLCFA: very-long-chain fatty acids; CT: computed
tomography.
* Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is
not included in the algorithm, because it presents in infancy or
childhood, not adulthood.
¶ The adrenocorticolytic drug mitotane causes PAI. Drugs that inhibit
cortisol biosynthesis (ketoconazole and metyrapone) do not usually
cause clinically important PAI unless the patient has limited pituitary
or adrenal reserve.
Δ In adults with autoimmune primary adrenal insufficiency, thyroid
disease and type 1 diabetes are the most likely endocrine disorders to
also be present (as part of polyglandular autoimmune syndrome type
II).
◊ To review the characteristic adrenal CT findings of these disorders,
refer to UpToDate topic on causes of primary adrenal insufficiency.

Adapted from: Bornstein SR, Allolio B, Arlt W, Barthel A, et al. Diagnosis and
treatment of primary adrenal insufficiency: An Endocrine Society clinical practice
guideline. J Clin Endocrinol Metab 2016; 101:364

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Approach to the patient with an adrenal
incidentaloma

This algorithm must be used in conjunction with the UpToDate topic on

the evaluation and management of the adrenal incidentaloma that
describes biochemical evaluation followed by confirmatory testing if
needed, as well as imaging features.

DHEAS: dehydroepiandrosterone sulfate; DST: dexamethasone

suppression test; CT: computed tomography; HU: Houndsfield units;
PAC: plasma aldosterone concentration; PRA: plasma renin activity; FNA:
fine-needle aspiration.
* The initial biochemical testing is to determine if the incidentaloma is
hormonally active. Testing is performed for subclinical hypercortisolism,
pheochromocytoma, and primary aldosteronism.
¶ If there is evidence of hormonal hypersecretion, additional
confirmatory testing is performed (refer to related UpToDate content on
the evaluation and management of the adrenal incidentaloma).

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Case-detection testing for diagnosis of
primary aldosteronism

HTN: hypertension; BP: blood pressure; PAC: plasma

aldosterone concentration; PRA: plasma renin activity;
PRC: plasma renin concentration.
* Patient out of bed for at least two hours and seated
for at least 5 to 15 minutes before sample is drawn.
¶ Direct PRC can be measured instead of PRA.
However, UpToDate authors prefer PRA. Refer to
UpToDate topic on diagnosis of primary aldosteronism
for interpretation of PRC cutoffs and normal values.
Δ Oral sodium loading over three days is one
confirmation test that many experts use. An alternative
is the saline infusion test. Details of both are reviewed
in the UpToDate topic on diagnosis of primary
aldosteronism.

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Evaluation and treatment of
catecholamine-producing tumors

Nmet: normetanephrine; Met: metanephrine; MRI:

magnetic resonance imaging; CT: computed
tomography; 68-Ga DOTATATE PET: gallium 68 1,4,7,10-
tetraazacyclododecane-1,4,7,10-tetraacetic acid-
octreotate; FDG: fluorodeoxyglucose; PET: positron
emission tomography.

Modified and reprinted with permission from: Young WF Jr.

Pheochromocytoma: 1926-1993. In: Trends in Endocrinology and
Metabolism, vol 4, Elsevier Science, Inc 1993. p.122.

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American Diabetes Association criteria for the diagnosis of diabetes

1. A1C ≥6.5%. The test should be performed in a laboratory using a method that is NGSP
certified and standardized to the DCCT assay.*
OR

2. FPG ≥126 mg/dL (7 mmol/L). Fasting is defined as no caloric intake for at least 8 hours.*
OR

3. 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be
performed as described by the World Health Organization, using a glucose load containing
the equivalent of 75 g anhydrous glucose dissolved in water.*
OR

4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random

plasma glucose ≥200 mg/dL (11.1 mmol/L).

A1C: glycated hemoglobin; NGSP: National Glycohemoglobin Standardization Program;

DCCT: Diabetes Control and Complications Trial; FPG: fasting plasma glucose; OGTT: oral
glucose tolerance test.
* In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test
results from the same sample or in two separate test samples.

Reprinted with permission from: American Diabetes Association. Standards of Medical Care in Diabetes
2011. Diabetes Care 2011; 34:S11. Copyright © 2011 American Diabetes Association. The content within
this table is still current as of the 2020 version of the Standards of Medical Care in Diabetes.

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Diagnosis of primary hyperparathyroidism in
adults

The most common clinical presentation of primary

hyperparathyroidism is asymptomatic hypercalcemia. The
diagnosis is usually first suspected because of the incidental
finding of an elevated serum calcium concentration on
biochemical screening tests. In addition, primary
hyperparathyroidism may be suspected in a patient with
nephrolithiasis.

PTH: parathyroid hormone; FHH: familial hypocalciuric

hypercalcemia.
* A PTH within the mid-upper normal range is inappropriately
normal given hypercalcemia.
¶ If the patient is taking a thiazide diuretic or lithium,
discontinue (if the drug can be stopped without exacerbating
the underlying condition) and remeasure calcium and PTH in 3
months. Persistent hypercalcemia with elevated or high-
normal PTH after drug withdrawal suggests that the drug has
unmasked primary hyperparathyroidism.
Δ Refer to UpToDate content on distinguishing between
primary hyperparathyroidism and FHH.
◊ Examples of non-PTH mediated hypercalcemia include
humoral hypercalcemia of malignancy, vitamin D intoxication,
granulomatous disease, vitamin A intoxication, and
hyperthyroidism.

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Distinguishing between asymptomatic
primary hyperparathyroidism and
familial hypocalciuric hypercalcemia in
adults

Both primary hyperparathyroidism and FHH may have

hypercalcemia with a PTH concentration that is mildly
elevated or in the upper part of the normal range.
Distinguishing between these two conditions is
important because FHH is a benign inherited condition
that typically does not require parathyroidectomy and
will not be cured by it. Refer to UpToDate content
related to differentiating primary hyperparathyroidism
and FHH.

Ca/Cr: calcium/creatinine ratio; FHH: familial

hypocalciuric hypercalcemia; PTH: parathyroid
hormone; CaSR: calcium-sensing receptor.
* If the patient is taking a thiazide diuretic or lithium,
discontinue (if the drug can be stopped without
exacerbating the underlying condition) and remeasure
calcium and PTH in 3 months. Persistent hypercalcemia
with elevated or high-normal PTH after drug
withdrawal suggests that the drug has unmasked
primary hyperparathyroidism.
¶ Refer to UpToDate content on treatment of vitamin D
deficiency. Adequate total calcium (diet plus
supplement) intake in this setting is approximately 800
to 1000 mg daily.
Δ A family history of asymptomatic hypercalcemia,
especially in young children, is supportive of FHH.
◊ The majority of patients with primary
hyperparathyroidism do not require genetic testing to
confirm diagnosis.

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Algorithm for the diagnosis of
acromegaly

IGF-1: insulin-like growth factor-1; OGTT: oral glucose

tolerance test; GH: growth hormone; MRI: magnetic
resonance imaging; CT: computed tomography: GHRH:
growth hormone-releasing hormone.

Adapted from: Melmed S, Anterior pituitary. In: Current Practice

of Medicine, Korenman S (Ed), 1996.

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Diagnostic approach to hypercalcemia in adults
PTH: parathyroid hormone; FHH: familial hypocalciuric hypercalcemia; PTHrp:
parathyroid hormone-related peptide; SPEP: serum protein electrophoresis; UPEP:
urine protein electrophoresis.
* Some medications associated with hypercalcemia include thiazide diuretics, lithium,
teriparatide, abaloparatide, excessive vitamin A, and excessive theophylline. If
possible, any medication or supplement that may be causing hypercalcemia should be
discontinued.
¶ Serum PTH typically ranging from 35 to 65 pg/mL in an assay whose normal range is
10 to 60 pg/mL.
Δ Refer to UpToDate content on primary hyperparathyroidism.
◊ Refer to UpToDate content on primary hyperparathyroidism and familial
hypocalciuric hypercalcemia for details.
§ Additional work-up is warranted to identify malignancy.
¥ Serum 25-hydroxyvitamin D must be markedly elevated before hypercalcemia
develops. Although the serum concentration of 25-hydroxyvitamin D at which
hypercalcemia typically occurs is undefined, many experts define vitamin D
intoxication as a value >150 ng/mL (374 nmol/L).

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Treatment of hyperkalemia in adults

ESKD: end-stage kidney disease; ACE: angiotensin-converting enzyme; CKD: chronic kidney
disease; RAS: renin-angiotensin system; NSAIDs: nonsteroidal antiinflammatory drugs; IV:
intravenous; ECG: electrocardiogram.
* Cardiac manifestations of hyperkalemia are discussed in detail in the topic on clinical
manifestations of hyperkalemia.
¶ Some experts given IV calcium only to patients with ECG changes. Details are presented in the
topic on treatment of hyperkalemia.

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Determining the cause of hyponatremia in adults
IVIG: intravenous immune globulin; TURP: transurethral resection of the prostate; BP: blood pressure; ACTH: adrenocorticotropic ho
ADH: antidiuretic hormone; TSH: thyroid-stimulating hormone; SIADH: syndrome of inappropriate antidiuretic hormone secretion.
* A simple and convenient correction of the serum sodium for hyperglycemia is as follows: Add 2 mEq/L to the serum sodium for ev
mg/dL (5.55 mmol/L) of serum glucose above the normal value.
¶ Impaired water excretion in renal failure occurs if there is severe impairment in glomerular filtration rate. Patients with mild-to-mo
impairment in glomerular filtration rate are typically able to excrete water loads. The measured plasma osmolality may be high in pa
renal failure because of high urea concentrations. However, urea is an ineffective osmole, and such patients have hypotonic hypona
even if the plasma osmolality is normal.
Δ Thiazide-induced hyponatremia may be protracted. An extensive evaluation for other etiologies can be delayed for several weeks
hyponatremic patients.
◊ Patients with hypovolemic hyponatremia due to diuretics may have a low urine sodium if the effect of the diuretic has worn off.
§ If the serum sodium is 125 mEq/L or less, we do not give isotonic saline. In such patients, the evaluation can be delayed until the s
slowly raised to higher levels.
¥ Although patients with hyponatremia due to heart failure or cirrhosis will usually have edema that is clinically apparent, hypovolem
not always be apparent by clinical exam. Thus, in a patient who appears to be euvolemic but whose urine chemistries are consistent
hypovolemia, infusion of isotonic saline (eg, 1 liter over one hour) can be helpful.

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Treatment of diabetic ketoacidosis in adults

DKA diagnostic criteria: Serum glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <18 mEq/L, and at least moderate ketonuria or
Normal laboratory values vary; check local lab normal ranges for all electrolytes.

DKA: diabetic ketoacidosis; IV: intravenous; NaCl: sodium chloride; SC: subcutaneous; Na: sodium; NaHCO3: sodium bicarbonate; H2O: w
potassium chloride; HCO3: bicarbonate; K: potassium; BUN: blood urea nitrogen.
* After history and physical examination, obtain capillary glucose and serum or urine ketones. Begin 1 L of 0.9% NaCl over 1 hour, and d
gas (or mixed venous blood gas), complete blood count with differential, urinalysis, serum glucose, BUN, electrolytes, chemistry profile,
levels STAT. Obtain electrocardiogram and, if needed, chest radiograph and specimens for bacterial cultures.
¶ If initial serum K is <3.3 mEq/L, hold insulin and give KCl until K is >3.3 mEq/L.
Δ Serum Na + should be corrected for hyperglycemia (for each 100 mg/dL glucose >100 mg/dL, add 2 mEq to sodium value for corrected
value).
◊ 100 mmol NaHCO3 = 100 mEq NaHCO3.
§ An alternative IV insulin regimen is to give a continuous IV infusion of regular insulin at 0.14 units/kg/hour; at this dose, an initial IV bo
necessary.
¥ Please refer to the UpToDate topic on DKA for the definition of DKA resolution.
‡ This is an UpToDate clinical suggestion.

Copyright © 2006 American Diabetes Association. From Diabetes Care Vol 29, 2006; 2018-2022. Reprinted with permission from The American Diabetes Associa
Adapted and updated with additional information from:
 1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32:1335.
2. Umpierrez GE, Cuervo R, Karabell A, et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care 2004; 27:1873.

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Treatment of hyperosmolar hyperglycemic state in adults

HHS diagnostic criteria: Serum glucose >600 mg/dL, arterial pH >7.3, serum bicarbonate >15 mEq/L, and minimal ketonuria and
ketonemia. Normal laboratory values vary; check local lab normal ranges for all electrolytes.

HHS: hyperosmolar hyperglycemic state; IV: intravenous; NaCl: sodium chloride; K: potassium; Na: sodium; BUN: blood urea
nitrogen; SC: subcutaneous.
* After history and physical exam, obtain capillary glucose and serum or urine ketones (nitroprusside method). Begin 1 liter of 0.9%
NaCl over one hour, and draw arterial blood gases, complete blood count with differential, urinalysis, serum glucose, BUN,
electrolytes, chemistry profile, and creatinine levels STAT. Obtain electrocardiogram, chest radiograph, and specimens for bacterial
cultures, as needed.
¶ If initial serum K is < 3.3 mEq/L, hold insulin and give potassium chloride until K is >3.3 mEq/L.

Δ Serum Na + should be corrected for hyperglycemia (for each 100 mg/dL glucose >100 mg/dL, add 2.0 mEq to sodium value for
corrected serum sodium value).
◊ An alternative IV insulin regimen is to give a continuous intravenous infusion of regular insulin at 0.14 units/kg per hour; at this
dose, an initial intravenous bolus is not necessary.
§ This is an UpToDate clinical suggestion.

Copyright © 2006 American Diabetes Association From Diabetes Care Vol 29, Issue 12, 2006. Reprinted with permission from the American Diabetes
Association.
Adapted and updated with additional information from:
1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32:1335.

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Algorithm for the evaluation of a child with short stature*

This algorithm describes the detailed evaluation of a child with short stature. Some components of the evaluation can
reasonably be performed in the primary care setting, including initial interpretation and height velocity, and initial laboratory
screening for an underlying systemic disease, if suspected based on symptoms. Other components of the evaluation, including
bone age interpretation and the detailed evaluation for causes of short stature, are typically performed by a pediatric
endocrinologist, if available.

GDPP: gonadotropin-dependent precocious puberty (central sexual precocity); GIPP: gonadotropin-independent precocious
puberty (peripheral sexual precocity); ISS: idiopathic short stature; CDGP: constitutional delay of growth and puberty; SD:
standard deviation; GH: growth hormone.
* Short stature is defined as height that is 2 SD or more below the mean (Z-score ≤–2) for children of the same sex and
chronologic age in a given population. This corresponds to a height that is below the 2.3 rd percentile.
¶ Decreased height velocity is indicated by a growth rate <5.5 cm/year from 2 to 4 years of age, <5 cm/year from 4 to 6 years of
age, <4 cm/year from age 6 years to puberty, or crossing 2 major percentile lines on a standard height-by-age chart.
Δ Systemic diseases may present with signs and symptoms either before or after they affect height or height velocity. This is
especially true for inflammatory diseases (Crohn disease, juvenile idiopathic arthritis) or any disorder that affects nutrition.
◊ Bone age determination requires expert interpretation of the hand radiograph using the Greulich and Pyle Atlas. If bone age
is delayed or advanced, the height velocity percentile and projected height should be recalculated based on bone age.
§ Delayed or advanced bone age is defined as a bone age that is 2 SD or more below or above the mean, respectively. This
translates to difference between bone age and chronologic age of approximately 12 months between 2 and 4 years of
chronologic age, 18 months between 4 and 12 years, and 24 months after age 12.
¥ Evaluation for systemic, endocrine, or genetic disorders includes a focused history and physical examination (refer to topic
review on evaluation for short stature). In addition, patients with growth failure usually should have laboratory screening,
including a complete blood count, erythrocyte sedimentation rate or C-reactive protein, tissue transglutaminase, creatinine,
electrolytes, bicarbonate, calcium, phosphate, alkaline phosphatase, albumin, thyroid-stimulating hormone, free thyroxine (T4)
and insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3). A karyotype should be
performed in all girls with unexplained short stature and in short boys with associated genital abnormalities [1] . Some or all of
this evaluation is typically performed by a pediatric subspecialist but varies with the child's presenting symptoms and the
clinical setting.
‡ CDGP is particularly likely if there is a family history of this growth pattern (eg, relatively late puberty).

Reference:
1. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: A summary of
the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology
Workshop. J Clin Endocrinol Metab 2008; 93:4210.

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Determining the etiology of overt hyperthyroidism in nonpregnant, non-
breastfeeding adults

Overt hyperthyroidism in nonpregnant, non-breastfeeding adults is defined by a low serum TSH with high
free T4 and/or T3 (free or total T3) concentrations.

TRAb: thyrotropin receptor antibodies; TSI: thyroid-stimulating immunoglobulins; TBI/TBII: thyrotropin

receptor-binding inhibitory immunoglobulin; RAIU: radioactive iodine uptake; TSH: thyroid-stimulating
hormone; T4: thyroxine; T3: triiodothyronine.
* The presence of orbitopathy (ophthalmopathy) alone may be sufficient to diagnose Graves' disease.
¶ There is no formal definition of moderate to severe hyperthyroidism. A total T3 >300 ng/dL and/or free T4
>3 ng/dL suggests moderate to severe disease.
Δ We obtain a baseline TSI after diagnosis of Graves' disease to guide therapy with thionamides.

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Initial evaluation of a patient with a
thyroid nodule

This algorithm is intended to be used in conjunction

with additional UpToDate content on thyroid nodules.

TSH: thyroid-stimulating hormone; FT4: free thyroxine;

T3: triiodothyronine; FNA: fine-needle aspiration.
* Patients with TSH above the normal range require an
evaluation for hypothyroidism. Refer to UpToDate
content on hypothyroidism.
¶ Patients with TSH below the normal range require an
evaluation for hyperthyroidism. Refer to UpToDate
content on hyperthyroidism.
Δ Thyroid nodules that do not meet sonographic
criteria for FNA should be monitored with periodic
ultrasonography. The frequency of evaluation (ranging
from 6 to 24 months) depends upon the sonographic
features of the nodules.
◊ Selected cases of subclinical hyperthyroidism warrant
treatment. Refer to UpToDate content on subclinical
hyperthyroidism and toxic adenoma.

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