5alpha-reductase deficiency


  • – Pathway/Axis:
    • Growth hormone
  • – Major cause:
    • tumor of the anterior pituitary gland called a pituitary adenoma.
    • Causes anterior pituitary to produce excess growth hormone after the closure of the epiphyseal plate during puberty.
  • – Major symptoms:
    • hands, feet, nose, lips, and ears show swelling of the soft tissue, and skin starts to thicken.
    • Swelling if internal organs, deep voice due to swelling of vocal cords, jaw or brow protrusion, and expansion of the skull at the fontanelle.
    • Enlargement of the tongue. Severe headaches, arthritis, hypertension, diabetes mellitus. Possible heart and kidney failure.

Addison’s disease (adrenal insufficiency/ hypocortisolism)

Androgen Insensitivity Syndrome

  • – Pathway/Axis:
    • HPG (hypothalamus/Pituitary/Gonad)
  • – Major cause:
    • Partial or complete inability of cells to respond to androgen hormones due to a mutation in the androgen receptor gene located on the X chromosome.
    • Not all AR mutations result in androgen insensitivity, this only occurs when other genetic factors are present.
  • – Major symptoms:
    • Genotypic makes presenting as phenotypic females, involving decreased masculinization of male genetalia, short vagina (if female), spermatogenic defects, regression of Mullerian structures, impaired conversion of testosterone to dihydrotestosterone.
    • Symptoms range from pseudohermaphroditism to normal male phenotype but infertility.

Androgenic Alopecia

  • – Pathway/Axis:
    • androgens (testosterone, DHT)
  • – Major cause:
    • Type II a-reductase activity at hair follicle coverts testosterone to DHT.
    • DHT binds to DHT receptors in the scalp and leads to decreased hair growth.
    • Increased activity of DHT receptors in the scalp leads to hair follicles to be more sensitive to DHT.
    • It can also be caused by hyperactive Type II 5 a-reductase. Decreased levels of sex hormone-binding globulin can also lead to more free testosterone available to be converted to DHT.
  • – Major symptoms:
    • In men- the gradual recession of frontal hairline, overtime, hairline recedes to form characteristic “M” shape, hair thins at the crown and often progresses to partial or complete baldness.
    • In women- hair becomes thinner all overhead, hairline does not recede

Aromatase deficiency

  • – Pathway/Axis:
    • HPG Axis/ Androgen steroidogenesis
  • – Major cause:
    • Loss-of-function mutation of the CYP19A1 gene encoding the aromatase enzyme causes a patient to lose the ability to convert androgens to estrogens in the estrogen steroidogenesis pathway.
    • Autosomal recessive inheritance.
  • – Major symptoms:
    • In females, patients are born with ambiguous external genitalia and rapidly develop ovarian cysts that prevent ovulation.
    • They also do not develop secondary sex characteristics in puberty.
    • All aromatase deficient patients suffer from hyperglycemia as well as abnormal bone growth causing bones to be long, thin, and osteoporotic due to slowed mineralization.

Congenital Adrenal Hyperplasia (CAH)

  • – Pathway/Axis:
    • steroidogenesis pathways in the adrenal gland
  • – Major cause:
    • excess production of androgens from the adrenal gland due to deficiency in enzyme 21-hydroxylase, during development.
  • _ Major symptoms:
    • Excess production of androgens after 12th weeks leads to the enlarged clitoris that resembles a penis.
    • Exposure at earlier stages may lead to labia fusing and forming a penile urethra.
    • Studies have also shown that females with CAH tend to behave more masculine.

Congenital Hypothyroidism

  • – Pathway/Axis:
    • Hypothalamic-pituitary-thyroid axis (HPT)
  • – Major cause:
    • shortage of thyroid hormone at birth.
    • Due to absent, reduced size, or improperly located thyroid.
    • May also be due to impaired step in thyroid hormone production pathways or improper stimulus at some point in the HPT axis.
  • – Major symptoms:
    • large anterior fontanelle, jaundice, reduced growth and activity, poor feeding, hoarse cry, hypotonia (low muscle tone), constipation, dry skin, umbilical hernia, coarse facial features, pallor, and macroglossia (enlarged tongue).

Conn’s Syndrome (primary hyperaldosteronism)

  • – Pathway/Axis:
    • Hypothalamus/Pituitary/Adrenal gland (HPA axis)
  • – Major cause:
    • small tumor found on the adrenal cortex in the majority of patients.
    • Excess production of aldosterone by tumor leads to development of the disease with high blood pressure and low potassium levels.
  • Risk:
    • adrenal hyperplasia – an abnormal function of the adrenal cortex 
  • – Major symptoms:
    • High blood pressure with low potassium. Other symptoms can include muscle weakness and headaches.



  • – Pathway/Axis:
    • Hypothalamic/ Pituitary/ Thyroid (HPT axis)
  • – Major cause:
    • iodine deficiency causes problems with the production of thyroid hormones, defect in the development of thyroid gland (absent, underdeveloped, or placed in the wrong place)
  • – Major symptoms:
    • stunted growth, puffy or dull face, protruding tongue, and belly button, retarded mental development, jaundice, sleeps a lot, poor feeding, decreased muscle tone, constipation, difficulty breathing, short physique, decreased activity, “floppy” infant

Cushing’s Disease

  • – Pathway/Axis:
    • Hypothalamus/Pituitary/adrenal axis (HPA)
  • – Major cause:
    • tumor on the pituitary gland or pituitary hyperplasia.
    • Causes excess release of ACTH which acts on the adrenal gland to release cortisol.
    • Excess ACTH results in excess cortisol which is involved with the way the body uses carbohydrates, fats, and proteins during stressful situations.
  • – Major symptoms:
    • obesity of upper body and thin arms/legs.
    • Round red face and children may experience slow growth.
    • acne, easy bruising, and purple marks on the skin known as striae.
    • Suffer from muscle and bone pain including weakness, or backaches.
    • Excess fat collection between shoulder blades.
    • Fatigue, mental changes, headaches, polydipsia, and polyuria
    • Men – decreased libido and impotence.
    • Women – excess hair growth and irregular menstrual cycles.

de Quervain’s Thyroiditis

  • – Pathway/Axis:
    • hypothalamic/Pituitary/Thyroid (HPT) axis
  • – Major cause:
    • viruses such as mumps, influenza, and other respiratory viruses infect the thyroid gland and cause inflammation which damages the follicular cells of the thyroid.
  • – Major symptoms:
    • Neck pain, fever, fatigue.
    • Damage to the thyroid follicular cells can cause hyperthyroidism which leads to weight loss and anxiety.

Empty Sella Syndrome


  • – Pathway/Axis:
    • Growth hormone – Hypothalamic/ Pituitary/Liver (HPL) Axis
  • – Major cause:
    • overproduction of growth hormone by a tumor in the pituitary gland that occurs during childhood. L
    • ess commonly, tumors of the pancreas, lung, and adrenal glands can also lead to excess GH.
    • When GH is secreted into the bloodstream, it triggers the liver to produce a hormone called insulin-like Growth Factor-I, which stimulates the growth of bones and other tissues.
    • If the pituitary gland produces excess GH, excessive amounts of IGF-I can cause abnormal growth of soft tissues and skeleton.
  • – Major symptoms:
    • Progressive enlargement of head, face, hands, feet, and above average height

Kallman syndrome

  • – Pathway/Axis:
    • Hypothalamic/Pituitary/Gonads (HPG) Axis
  • – Major cause:
    • a form of HH, a condition affecting the production of hormones that direct sexual development.
    • Isolated deficiency of GnRH
  • – Major symptoms:
    • May not experience puberty or may experience incomplete puberty and symptoms of hypogonadism.
    • Men – decreased libido, erectile dysfunction, decreased muscle strength, and lack of aggressiveness and drive.
    • Women – dyspareunia and amenorrhea.
    • All patients have anosmia. fatigue, color blindness, hearing deficiency, and epilepsy. 

Klinefelter syndrome

  • – Pathway/Axis:
    • testosterone (HPG) axis
  • – Major cause:
    • random genetic error, most commonly nondisjunction of sex chromosomes during meiotic divisions, that result in a male being born with an extra copy of the x chromosome.
    • Extra X chromosome leads to abnormal development of the testis which results in underproduction of testosterone and elevated levels of FSH.
  • – Major symptoms:
    • low testosterone (hypogonadism), enlarged breasts, small penis, weak bones, taller stature, and reduced muscle mass, facial hair, and body hair.
    • Infertility/sterility- little or no sperm production.

Lipoid congenital adrenal hyperplasia (lipoid CAH)

  • – Pathway/Axis:
    • steroid hormone synthesis
  • – Major cause:
    • arises from defects in the earliest stages of steroid hormone synthesis: the transport of cholesterol into the mitochondria and the conversion of cholesterol to pregnenolone- the first step in the synthesis of all steroid hormones.
  • – Major symptoms:
    • mineralocorticoid deficiency in affected infants and children. male infants are severely undervirilized causing their external genitalia to look feminine.
    • The adrenals are large and filled with lipid globules derived from cholesterol.



  • Pathway/Axis:
    • Calcitonin- Parathyroid hormone (PTH) feedback loop
  • – Major cause:
    • many different causes; typically due to a decrease in calcitonin secretion or an increase in PTH secretion.
  • – Major symptoms:
    • greatly increases risk in bone fractures. fractures occur in situations where healthy individuals wouldn’t normally break a bone, like the vertebral column, rib, hip, and wrist.


  • – Pathway/Axis:
    • catecholamines (mainly norepinephrine)
  • – Major cause:
    • neurohormone tumor of the medulla of the adrenal gland. Or extra adrenal chromaffin tissue that filed to curl up after birth, secreting high amounts of catecholamines, mainly norepinephrine and epinephrine.
  • – Major symptoms:
    • elevated heart rate/blood pressure, anxiety, excessive sweating, headaches, weight loss, palpitations. Spells vary from several times a day to monthly, lasting from seconds to hours, with spells occurring more frequently as the tumor grows.

Pituitary adenoma

Pituitary apoplexy

Pituitary during pregnancy

  • – Increased estrogen -> hyperplasia of prolactin-secreting cells -> increased prolactin -> INCREASED PITUITARY SIZE
  • – Vascular supply remains the same despite the increased pituitary size 

Pituitary dwarfism

Polycystic ovarian syndrome

  • – Pathway/Axis:
    • Hypothalamic/ Pituitary/Gonads (HPG) Axis
  • – Major cause:
    • increase in female production of male hormones.
    • Low estrogen levels result in incomplete development of the follicle, resulting in no ovulation and many small cysts remain on the ovary.
  • – Major symptoms:
    • irregular or absent menstrual cycle, polycystic ovaries, excessive body hair, and acne.
    • Obesity can cause symptoms to worsen.

Prader-Willi Syndrome

  • -Pathway/Axis:
    • growth hormone
  • – Major cause:
    • deletion or inexpression of a large region on parental chromosome 15
  • – Major symptoms:
    • extreme appetite which can lead to obesity, sleep disorders, short stature, delayed or incomplete sexual and physical development, cognitive disabilities, behavior problems, hypogonadism.

Seasonal Affective Disorder (SAD)

  • – Pathway/Axis:
    • Pineal gland/ hypothalamus
  • – Major cause:
    • lower levels of light common during seasons of the year (commonly winter) can disrupt the body’s internal clock, hypersecretion of melatonin, hypersecretion of serotonin
  • – Major symptoms:
    • overall sadness, anxiety, fatigue, increase in appetite, weight gain, social withdrawal, decreased sex drive, inability to concentrate, increased anxiety and need for sleep, and feelings of melancholy or despair.

Testicular feminizing syndrome

  • – Pathway/Axis:
    • Testosterone (gonads-HPG axis)
  • – Major cause:
    • mutations in androgen receptors due to abnormal androgen receptor gene
  • – Major symptoms:
    • XY chromosomal male with female external genitalia (complete androgen insensitivity) or micropenis, gynecomastia, hypospadias (incomplete androgen insensitivity) but no ovaries, fallopian tubes, or uterus (testes are present in the abdomen); normal production of testosterone and conversion to dihydrotestosterone. No menstruation during puberty.

True hermaphroditism

  • – Pathway/Axis:
    • HPG axis
  • – Major cause:
    • an individual has both testicular and ovarian tissue.
    • This can be caused by either SRY gene being expressed in one gonad but not the other or partial expression in the gonads during development
  • – Major symptoms:
    • ambiguous genitalia at birth, delayed or unexpected puberty, enlarged clitoris or micropenis, fused labia, or urethra opening is not in the correct position.

Turner Syndrome