Adrenal/Pituitary

• Cushing's disease


  Pituitary adenomas typically in anterior pituitary, second most common cause of Cushing's
• Cushing's disease


  • Causes bilateral hyperplasia in adrenal gland due to constant stimulation from ACTH
• Cushing's Syndrome


  Excessive cortisol (production or administration)
• Cushing's Syndrome pathogenesis


  Hypothalamus produces CRH -> Anterior pituitary produces ACTH -> Adrenal gland produces cortisol (used to maintain BP, regulate BGL, decrease inflammation)
• Causes of Cushing's Syndrome

  • ACTH independent: Excess cortisol production anyway (normal/low ACTH)
  • ACTH dependent: Excess cortisol due to high ACTH
  • Ectopic: Tumor (not on pituitary gland) secreting ACTH
  • Cushing disease: ACTH producing tumor on pituitary gland
  • Excessive cortisol administration (corticosteroids)
• Exogenous Cushing's Syndrome


  Chronic corticosteroid use (most common cause)
• Endogenous Cushing's Syndrome


  Adrenal issue or ACTH issue
• Pituitary adenoma: Cushing Disease


  Second most common cause of Cushing syndrome
• Cushing's Syndrome is more common in females aged 25-45 years
• Adrenal tumors have a bimodal distribution
• Cushing's Syndrome clinical manifestations

  • Reproductive: Menstrual irregularities, hirsutism, oily face/acne, increased/decreased libido, virilization
  • Dermatologic: Easy bruising, striae, skin atrophy, fungal infections, hyperpigmentation (from excess ACTH)
  • Metabolic: Glucose intolerance, Progressive obesity (buffalo hump, moon face, central obesity), Sleep apnea
  • Cardiovascular/Musculoskeletal: HTN, increased CV risk, thromboembolic events, HF, dilated cardiomyopathy, Proximal muscle wasting and weakness, Bone loss
  • Neurologic: Emotional, depression, anxiety, irritability, panic attacks, mild paranoia
• Cushing's Syndrome lab findings

  • Increased glucose
  • Increased triglycerides
  • Increase WBC
  • Glucosuria
• Cushing's Syndrome diagnosis


  1. Eliminate exogenous corticosteroids

  2. Rule out other causes: pregnancy, severe obesity, extreme physical stress

  3. Salivary cortisol levels (test at late night, should be low unless Cushing's)

  4. 24 hr urinary free cortisol level (excess cortisol will spill into urine)

  5. Dexamethasone suppression test (low-dose and high-dose)
• Cushing's Syndrome imaging

  • Ectopic ACTH: MRI of thorax, abdomen, pelvis
  • Pituitary: MRI of head
  • Adrenals: CT abdomen
• Cushing's Syndrome treatment

  • Medical: Medications to inhibit steroid genesis
  • Surgical: Adrenal adenoma - surgical resection of adrenal gland, Adrenal carcinoma - surgical resection of adrenal gland + lymph nodes, Pituitary adenoma - trans-sphenoidal resection of tumor
• Adrenal insufficiency


  Chronic deficiency of cortisol/aldosterone
• Causes of adrenal insufficiency


  • Primary (Addison's): Autoimmune (most common), infectious, cancer, medications, etc. Destruction of adrenal cortex
  • Secondary: Pituitary failure from adenomas/steroid discontinuation (things that damage pituitary), Decreased ACTH and decreased/normal cortisol, normal aldosterone
  • Exogenous steroid use (most common secondary cause, hypopituitarism)
• Addison's disease (primary adrenal insufficiency)


  Adrenal cortex has high functional reserve, symptoms when majority of it is destroyed
• Addison's disease symptoms


  • Salty food cravings, nausea/vomiting, orthostatic hypotension
  • Decreased cortisol = decreased glucose in stress = weakness, disorientation
  • Hyperpigmentation over joints, bronze skin
  • Low androgen levels (more effect on women), loss of armpit/pubic hair, decreased sex drive
• Addison's disease lab findings

  • Elevated AM ACTH, potassium, renin
  • Low sodium, glucose
  • Low AM cortisol (<3 mg/dL at 8AM - diagnostic)
• Addison's disease special labs

  • Primary: Synthetic ACTH stimulation test, CRH stimulation test, adrenal antibodies, CT scan of adrenals
  • Secondary: CRH stimulation test
• Addison's disease treatment


  • Primary: Synthetic glucocorticoids (hydrocortisone), synthetic mineralocorticoids (fludrocortisone), androgen replacements if symptoms
  • Secondary: Pituitary adenoma resection, wean patient off steroids
• Acute adrenal crisis


  Can occur with primary insufficiency when there is additional stressor, or abrupt steroid/adrenal gland infection/damage
• Acute adrenal crisis symptoms


  • Pain in back, abdomen, legs
  • Vomiting, dehydration
  • Low blood pressure
  • Weakness, hyponatremia, hyperkalemia
• Acute adrenal crisis treatment

  1. Sugar, salt, steroids, search for cause

  2. IV fluid support (saline or 5% dextrose)

  3. IV hydrocortisone (steroids)
• • Pheochromocytoma
  • Rare catecholamine secreting tumor from chromaffin cells 
  • Secreting norepinephrine/epinephrine/both
• Pheochromocytoma


  • Paroxysmal HTN (most common s/s)
  • Pain (HA)
  • Pressure (HTN)
  • Palpitations
  • Perspiration
• Pheochromocytoma Classic triad


  • Episodic HA
  • Sweating (HA)
  • Tachycardia
• Pheochromocytoma Labs


  • Elevated 24 h urine metanephrines
  • Elevated plasma metanephrines
  • Urine catecholamines (dopamine, epi, norepi)
• Pheochromocytoma Imaging


  • MRI (> CT)
  • 10% = malignant tumor of adrenal medulla
• Pheochromocytoma Tx


  Surgical resection
• Diabetes Insipidus


  • An arginine vasopressin disorder
  • Deficiency/resistance to ADH
  • ADH stored in posterior pituitary and regulated water
  • Decreased in water reabsorption
• Diabetes Insipidus


  • High polyuria/polydipsia
  • Decreased urine osmolality
  • Increased plasma osmolality
• Diabetes Insipidus Types


  • Central (most common) -> problem with ADH secretion from posterior pituitary
  • Nephrogenic -> Collecting tubules have ADH resistance
  • Meds or chronic disease
  • Lithium is common cause
  • Gestational DI -> placental production of vasopressinase
  • Primary polydipsia -> psychogenic DI
• Diabetes Insipidus Symptoms


  • Polyuria/dipsia
  • Nocturia
  • Occasional hypovolemia
• Diabetes Insipidus Labs


  • High serum osmolality
  • Low urine osmolality
  • Elevated sodium
  • Normal glucose
• Diabetes Insipidus work-up


  1. Electrolytes, urine specific gravity, plasma ADH

  2. Water deprivation (Miller-Moses) test -> continuous urine production even with dehydration

  3. Desmopressin (ADH) stim test
• Diabetes Insipidus Tx


  • Central: Desmopressin (DDAVP)
  • Nephrogenic: Diuretics, DDAVP
  • Thiazide diuretics cause a hypovolemia induced increased in sodium/water reabsorption = less water to ADH sensitive sites in collecting tubules = reduced urine output
• Prolactinoma


  • Hyperprolactinemia from noncancerous adenoma of pituitary gland
  • Most common secretory tumor of pituitary (40%)
  • Excess prolactin causes decreased sex hormones
• Prolactinoma S/S (general)


  • Amenorrhea
  • Milky breast discharge
  • HA
  • Visual field losses