Introduction

Cushing syndrome is a hormonal disorder which occurs when body has too much of the hormone cortisol over time 

-it more frequently affects women

-the most common cause of Cushing’s syndrome: use of glucocorticoids 

Symptoms & Signs 

General: fatigue, backache, headache, central obesity with a rounded, rosy face (moon face), a fat pad in the upper back between the clavicles (buffalo hump), protuberant abdomen  

CNS: irritability, emotional lability, depression, psychosis, insomnia   

Musculoskeletal: Proximal muscle weakness (Difficulty standing up from a seated position, or climbing stairs), osteopenia, osteoporosis 

Reproductive: Oligomenorrhea, amenorrhea, erectile dysfunction, infertility 

Cardiovascular: Hypertension, hypercoagulation 

Endocrine: Glucose intolerance, diabetes

Skin: purple striae, easy bruisability, hyperpigmentation, hirsutism

Diagnosis 

Labs: 24-hour urinary free cortisol and creatinine, Late-night (10–11 PM) salivary cortisol determinations, Petrosal sinus sampling, overnight dexamethasone suppression test, plasma ACTH level, plasma DHEAS (dehydroepiandrosterone sulfate (DHEAS) level

Imaging: CT of the adrenals, MRI of the pituitary

Treatment 

Medications: Spironolactone, eplerenone, flutamide, cabergoline, Pasireotide, Ketoconazole, Metyrapone, Mitotane 

Surgery: transsphenoidal selective resection of the pituitary adenoma (Pituitary Cushing disease), Adrenalectomy (Adrenal Cushing disease) 

Introduction

-Primary adrenocortical insufficiency (Addison disease) is a syndrome resulting from the chronic deficiency of cortisol caused by adrenocortical insufficiency 

-Secondary adrenocortical insufficiency is due to ACTH deficiency, caused by exogenous glucocorticoid therapy, pituitary or hypothalamic tumors 

-in primary adrenal insufficiency, low or absent cortisol level results in hypersecretion of ACTH by the pituitary

-ACTH stimulates melanocyte activity, resulting in generalized hyperpigmentation, which is the most specific sign of primary adrenal insufficiency

-Addison’s disease occurs when >90% of adrenal tissue is destroyed

-The most common cause is autoimmune destruction 

Symptoms & Signs 

General: Weakness, malaise, anorexia, weight loss, craving for salt 

Vascular: postural hypotension

GI: Nausea, vomiting, diarrhea, constipation, abdominal pain

Musculoskeletal: Myalgia, arthralgia 

Metabolic: Hypoglycemia, hyponatremia,hyperkalemia 

Psychiatric: Personality changes 

Dermatological: Hyperpigmentation of the buccal mucosa and gums preceded by generalized hyperpigmentation of the skin, loss of axillary and pubic hair, vitiligo,calcification of auricular cartilage (petrified ears), longitudinal pigmented bands in the nails  

Gynecological: Amenorrhea, ovarian failure, infertility

Obstetrical: preterm delivery, low-birth weight newborn, increase in cesarean delivery

Emergency: Shock, coma, and death, if untreated

Diagnosis 

Labs: hyponatremia, hyperkalemia, acidosis, elevated serum creatinine and blood urea nitrogen, hypoglycemia, hypercalcemia

Hematology: Normochromic, normochromic anemia, neutropenia, eosinophilia, and lymphocytosis

Best screening test/Definitive diagnosis: Failure to respond adequately to corticotropin stimulation test

-MRI to rule out pituitary or hypothalamic tumor 

-CT scan of the adrenal glands

-Secondary Adrenal insufficiency: Diminished pigmentation, Normal serum potassium 

Treatment 

-Register with a medical alert system 

-Patient should be instructed in the self-administration of steroids

-Lifelong replacement therapy of glucocorticoids and mineralocorticoids 

-Medications: Hydrocortisone, prednisone, dexamethasone, fludrocortisone 

-Acute adrenocortical insufficiency: Medical emergency, parenteral hydrocortisone, correction of fluid and electrolytes 

Primary adrenal deficiency	Secondary adrenal deficiency
ACTH elevated	ACTH low or inappropriately normal
Aldosterone level can be low	Aldosterone level is normal
Hyperpigmentation	Diminished pigmentation
Elevated Potassium	Normal Potassium
Mineralocorticoid replacement needed	Mineralocorticoid replacement not needed

Introduction

Paget disease (Osteitis deformans) is a chronic, localized bone-remodeling disorder of abnormal osteoclasts that drive increased bone resorption accompanied by accelerated, disordered bone formation that results in disorganized, fragile bone

-It was originally described by Sir James Paget in 1877 

-It most commonly involves the pelvis, vertebrae, skull, humerus, femur and tibia 

-it predominantly affects Caucasian individuals over the age of 40 

Symptoms & Signs 

-Most patients are asymptomatic 

-Most common presenting symptom is pain, often worse at night  

-Bowing of weight-bearing bones, stress fractures (Chalk stick fractures), 

-Enlargement of the parietal or frontal bones (frontal bossing), increased head size, softening of the base of the skull (platybasia)

Complications of Paget disease: 

Rheumatologic: Osteoarthritis, gout, vertebral collapse 

Neurologic: Basilar impression, peripheral nerve entrapment, spinal cord and root compression 

Otologic: Cranial nerve dysfunction (especially deafness) 

Ophthalmic: Loss of vision 

Neoplastic: Osteosarcoma, giant cell tumor 

Cardiac: High-output heart failure 

Metabolic: Hypercalcemia 

Diagnosis 

X rays: Focal lytic, radiolucent areas with a coarse trabecular pattern and bone thickening, described as osteoporosis circumscripta “cotton-wool” skull, enlarged “picture-frame” vertebrae, “ivory vertebrae”

Labs: Normal calcium, phosphate levels, Elevated serum alkaline phosphatase

Bone resorption markers: Elevated serum or urine N-telopeptide or C-telopeptide measured in the blood or urine

Treatment 

-Adequate calcium and vitamin D intake 

-Mainstay of pharmacologic therapy: Bisphosphonates 

-The treatment of choice: Zoledronic acid 

-Other medications: Pamidronate, Risedronate, Alendronate, Tiludronate

-Serial serum alkaline phosphatase determinations are done to evaluate the response to treatment