Endocrine Flashcards
Growth rate that suggests no underlying pathologic disorder?
5 cm per year between age 3 and puberty
Normal variant short stature versus pathologic short stature?
Height below 3rd percentile with normal growth velocity
versus
below 3rd percentile with sub optimal growth velocity (less than 2 inches per year)
Height estimate?
(Mothers height + father’s height +/-5 inches)/2
+/-4
Normal upper-to-lower body segment ratios?
Birth: 1.7
3 years: 1.3
>7: 1.0
Types of normal variant short stature?
- Familial – 2 SDs below mean but with normal bone age, normal onset of puberty, and minimal growth of 2 inches per year
- Constitutional – 2 SDs below mean and minimal growth of 2 inches per year but with: delayed puberty in parents, delayed bone age, late onset puberty
Proportionate versus disproportionate pathologic short stature?
Normal U/L ratio versus increased U/L ratio
Causes of prenatal onset proportionate short stature? Postnatal onset proportionate short stature?
- Environmental exposures (tobacco/alcohol in utero)
- Chromosome disorders (down/Turner)
- Genetic syndromes (Russell-silver, Prader-Willie)
- Borrow infections in early pregnancy (CMV, rubella)
- Malnutrition
- Psychosocial (neglect, child abuse)
- Organ system diseases (IBD, congenital heart disease, renal failure, cystic fibrosis, hypothyroid, GH deficiency, Cushing’s)
Causes of disproportionate short stature?
- Ricketts
2. Skeletal dysplasias
Laboratory studies to conduct with pathologic short stature? Radiographic studies?
- Common labs - CBC, ESR, T4, calcium, phosphorus, creatinine
- IGF- indirect test for growth hormone
- Chromosome analysis and girls (Turner)
- Bone age (AP of left hand and wrist)
- AP and lateral skull radiographs (for pituitary Island, craniopharyngioma)
Ddx if bone age equals chronologic age?
If bone age <chronological age?
- Familial short stature,
- Intrauterine growth retardation
- Turner
- Skeletal dysplasia
- Constitutional short stature
- Hypothyroid
- Hypercortisolisn
- Growth Hormone deficiency
- Chronic diseases
Growth hormone deficiency – clinical features? Causes? Evaluation? Management?
- Prolonged neonatal jaundice
- Cherubic facies, central obesity
- Microphallus, cryptorchidism
- Hypoglycemia
- Poor growth velocity
- Single central maxillary incisors or cleft palate
- Craniopharyngioma
- CNS irradiation, vascular malformations
- Autoimmune
- MRI of head
- IGF-1 levels, poor response to GH stimulation (glucagon, clonidine)
Daily subcutaneous injections of GH
Sexual precocity associated with?
Obesity
Precocious puberty? Causes?
Development before nine years
- premature thelarche
- Premature adrenarche
- Isosexual precocious puberty or central precocious puberty
- Peripheral precocious puberty or heterosexual gonadotropin-independent puberty
Premature Thelarche – definition, epidemiology, etiology, work up/treatment?
Breast tissue only, without other sexual secondary sex characteristics (Normal growth pattern, no pubic hair)
Common and benign, usually begins the first two years of life
Premature activation of HPGA, resulting in the release of low levels of estrogen
No workout/treatment unless pubic hair or rapid growth
Premature adrenarche – definition? Epidemiology? Classic presentation? Tx?
Early-onset pubic/axillary hair without development of breast/testing
More common in girls
Girl over 5 presents with pubic hair growth and a print order. No breast tissue/no clitorimegaly/normal growth
No Treatment
Isosexual precocious puberty or central precocious puberty – Definition? Epidemiology? Clinical features? Causes?
Are the activation of the hypothalamus
Higher incidence in girls
breast/testes development, pubic hair, rapid growth
Idiopathic in girls
Organic in boys – get MRI
1 CNS causes- Hydrocephalus, infection, cerebral palsy, hamartomas, astrocytomas/gliomas
2. Hypothyroidism – unlike other causes, poor growth and delayed bone age
Evaluation of a patient with suspected central precocious puberty?
- FSH, LH, sex steroids should be elevated into pubertal range
- GnRH stimulation test (measure LH/FSH response)
- Head MRI in males
Peripheral precocious puberty or heterosexual gonadotropin-independent puberty – definition? Features? Evaluation?
Precocious puberty that is independent of the HPGA (peripheral production of sex steroids and no increase in FSG/LH)
- Boys – present with feminization or premature pubic hair – no increase in FSH so no testicular enlargement
- Girls – virilization or breast development
- Boys – serum FSH, LH, testosterone, B-HCG
- Girls – serum FSH, LH, estradiol
- CNS imaging
Causes of peripheral precocious puberty?
Girls – adrenal tumors, virilizing ovarian tumors, feminizing ovarian tumors, nonclassical CAH, McCune-Albright syndrome
Boys – typically no teaticulat enlargement (no FSH): adrenal tumors, leydig cell tumors, nonclassical CAH, B-HCG tumors
Males with testicular enlargement:
- McCune-Albright syndrome (bony changes, café au lait spots endocrinopathy)
- Testicular toxicosis – testes enlarged but independent of HPGP
- B-hCG secreting tumors – chest, pineal gland, gonad, hepatoblastoma (B-HCG cross reacts with LH receptors, stimulating leydig cells)
Delayed puberty – definition? Classification? Evaluation?
No testicular enlargement by 14 or no breast tissue by each 13 or no menarche by age 14
- Hypogonadotropic hypogonadism – inactivity of hypothalamus and pituitary gland, causing low hormones and flat GnRH stimulation test
- Hypergonadotrophic hypogonadism – gonadal failure resulting in high FSH and LH with low testosterone/estradiol
CBC, ESR, T4, testosterone, estradiol, FSH, LH, prolactin level, bone age
Causes of hypogonadotrophic hypogonadism?
- Constitutional delay of puberty
- Chronic disease
- Hypopituitarism (brain tumors)
- Primary hypothyroidism
- Prolactinoma
- Genetic syndromes (Kallmann syndrome, Prader-Willi, Lawrence-Moon-Biedl)
Kallman syndrome?
Isolated gonadotropin deficiency with inability to smell
Lawrence-Moon-Biedl syndrome?
Obesity, retinitis pigmentosa, hypogonadism, polysyndactyly
Causes of hypergonadotrophic hypogonadism?
- Chromosome – Kleinfelter (boys) for Turner/gonadal dysgenesis (girls)
- Autoimmune (autoimmune oophoritis, Hashimoto’s, Addison’s)
Male sex differentiation?
- SRY gene differentiates testes
- Testosterone from Leydig cells stimulates wolffian ducts
- Anti-Mullerian hormone from Sertoli cells inhibits Mullerian structures
- DHT from 5a-reductase produces external genitalia
Causes of ambiguous genitalia in an undervirilized male?
- Inborn error of testosterone synthesis (XY)
- Mixed gonadal dysgenesis (XY mosaicism)
- True hermaphroditism – The biggest genitalia with both ovarian and testicular gonadal tissues ( XX, XY)
- Partial androgen insensitivity – defect in androgen receptor (XY)
Causes of ambiguous genitalia in virilized female?
- CAH called by 21-hydroxylase deficiency, 11 B-hydroxylase, 3V-hydroxysteroid dehydrogenase deficiency
- Virilizing drug used by mother during pregnancy
- Virilizing tumor in mother during pregnancy
Patient with ambiguous genitalia and increased blood pressure? Decreased blood pressure?
CAH with 11 B hydroxylase deficiency; adrenal insufficiency
Laboratory studies in patients with ambiguous genitalia?
- Males – DHT, testosterone
2. Females – electrolytes, testosterone, DHEA, 17 hydroxylase
Primary adrenal insufficiency – due to? Clinical features? Examples?
Destruction of adrenal cortex or enzyme deficiency
- Cortisol deficiency (anorexia, weakness, hyponatremia, hypotension, increased pigmentation)
- Aldosterone deficiency (failure to thrive, salt craving, hyponatremia, hyperkalemia)
Addison’s disease, CAH, adrenoleukodystrophy
Secondary adrenal insufficiency – due to? Clinical features? Examples?
Process that interviews with the release of CRH for ACTH
- Normal serum potassium because no aldosterone deficiency 2. Cortisol deficiency
Iatrogenic, Pituitary tumor, Craniopharyngioma, Langerhans cell histiocytosis
Most common cause of ambiguous genitalia with no public gonads? Mechanism? Main deficiencies?
Congenital adrenal hyperplasia – enzyme deficiency leading to shunting to another pathway increasing androgen production
- 21-hydroxylase deficiency (Mineralocorticoid +/- glucocorticoid deficiency)
- 11B-hydroxylase deficiency (Hypertensive and hypokalemic)
- 3B-hydroxysteroid deficiency (Salt wasting crisis, glucocorticoid deficiency, ambiguous genitalia)
Management of patients with congenital adrenal hyperplasia?
- Cortisone administration to depress ACTH levels
- Mineralocorticoid replacement (fluorocortisone)
- Monitor growth and development
Adrenal insufficiency – causes? Evaluation? Management?
- Steroid use
- Addison’s disease (autoimmune destruction)
- Waterhouse-Fredrickson syndrome
ACTH stimulation test
Steroids and IV fluids
Major causes of hypercortisolism? Diagnosis?
- Iatrogenic
- Cushing’s syndrome (adrenal tumor)
- Cushing disease (andenoma)
- 24 hour urine cortisol
- Overnight dexamethasone suppression test
Cushing’s versus obesity?
Growth Impairment and delayed bone age versus normal growth and advanced bone age
Protracted cases of monilial vulvovaginitis associated with? Disease Also associated with?
Diabetes; enterovirus (Coxsackie) and rubella
Somogyi phenomenon?
Evening dose of insulin is too high causing hypoglycemia resulting in increased release of epinephrine/quickly gone to cataract. Results in high blood glucose and ketones in the morning
Treatment: lower the bedtime insulin
Microvascular versus macrovascular complications of diabetes?
Retinopathy, nephropathy, neuropathy versus atherosclerosis, hypertension, heart disease, stroke
Added effect of repleting potassium with potassium phosphate?
Increased 2,3-DPG, causing right shift to oxygen dissociation curve, making oxygen more available to tissues
In DKA - target drop in glucose levels? Otherwise?
100 mg/dL/hr; cerebral edema
Congenital hypothyroidism – causes? Clinical features? Management?
- Thyroid dysgenesis (missing or atopic)
- Thyroiddyshormonogenesis (error of thyroid hormone synthesis)
- PTU during pregnancy (transient hypothyroidism of the Newmorn)
- Maternal autoimmune thyroid disease (transient hypothyroidism if cross placenta)
- Historical Sx: Prolonged jaundice and poor feeding
- Current Sx: Lethargy and constipation
- PE findings: large fontanelles, large tongue, umbilical hernia, myxedema, poor growth
L-thyroxine
Autoimmune polyendocrinopathies?
Hyperthyroid, vitiligo, alopecia, Addison’s disease, diabetes
Definition of hypocalcemia? Pseudohypocalcemia? Clinical Features? Causes in children? Tests? When to treat?
Serum calcium under 8 or ionized calcium under 2.5; low calcium due to low albumen (nephrotic syndrome)
- Tetany (carpopedal spasm, laryngeal spasm, paresthesias)
- Seizures (in pediatric patients)
- ionized calcium and phosphorus
- Serum magnesium
- EKG for prolonged QT
- PTH
- Vitamin D
- Radiographs for rickets
Treat if calcium under 7.5 in newborns or under 8 in children
Causes of hypocalcemia neonates under four? Over four? In children?
Under four days old:
- prematurity, IUGR
- Asphyxiation
- hypoMg
Older than four days: 1. hypoparathyroidism (mothers calcium suppresses fetus PTH)
- DiGeorge
- hyperphosphatemia (excessive intake from formula, uremia)
Childhood:
1. Hypoparathyroidism (parathyroid failure from chromosomal, autoimmune or DiGeorge)
If you will too. Pseudohypoparathyroidism (parathyroid resistance)
3. Hypomagnesium
4. Vitamin D deficiency
Symptoms of pseudo-hypoparathyroidism?
Short stature, short metacarpals, developmental delay, elevated PTH
Most common form of Rrckets in US? inheritance? Mechanism? Presentation? Labs? Treatment?
Familial hyperphosphatemia; X-linked dominant
Renal tubular phosphorus leak
Typical bowling of legs but never tetany
Normal calcium but low phosphorus
Phosphorus supplements and 1, 25 vitamin D analogues
Oncogenic rickets? Consider when?
Phosphate-deficient form of rickets caused by tumor
Patient presents with bone pain or myopathy
Clinical features of rickets?
- Occurs during first two years and adolescence
- Affects wrists, knees, ribs
- Legs become bowed when patient begins walking
- Short stature
- Richitic rosary and craniotabes
- Frontal bossing and delayed suture closure
Causes of central diabetes insipidus? Nephrogenic diabetes insipidus?
- Autoimmune against ADH-producing cells
- Trauma/ischemic brain injury
- Hypothalamic tumor (Craniopharyngioma, glioma, germinoma)
- Langerhans cell histiocytosis
- Granulomatous disease
- Vascular/genetic
X linked recessive
Evaluation and diagnosis of diabetes insipidus?
- Hyponatremic dehydration
- Move out if specific gravity greater than 1.018
- Water deprivation test (no water then give ddAVP)
- MRI of head (Check post pit)
- Bone scan (for Langerhans histiocytosis)
Neonatal hypoglycemia – transient vs Persistent? Causes of persistent hypoglycemia?
Less than versus greater than three days of hypoglycemia
- Hyperinsulinism (islet cell hyperplasia, Beckwith-Wiedemann syndrome)
- Defects in carbohydrate metabolism (glycogen storage disease, galactosemia) or amino acid metabolism (maple syrup urine disease, Tyrosinemia)
- Hormone deficiencies (GH deficiency, cortisol deficiency)
Hypoglycemia in infancy and childhood – Causes?
- Ketotic hypoglycemia (most common form: inability to adapt to fasting state)
- Ingestions (alcohol, oral hypoglycemic agents)
- Inborn errors of metabolism
- Hyperinsulinemia
