Multiple Endocrine Neoplasia (MEN)

- Usually family history of multiple endocrine tumours

- Patients are younger than those with single sporadic tumours
o Type 1 = (Wermer Syndrome)
 Combination of adenoma of the pituitary, parathyroid hyperplasia or adenoma, & islet
cell tumor of the pancreas
o Type 2A = (Sipple Syndrome)
 Combo of pheochromocytoma, and medullary carcinoma of the thyroid & parathyroid
hyperplasia
o Type 2B
 Combo of pheochromocytoma, and medullary carcinoma of the thyroid and mucosal
neruoma syndrome

Other Catacolamine Producing Tumors

- Paragangliomas
o chromaffin tumours that originate in extra-adrenal sites - more often malignant

Phenochromocytoma
- Rare tumor of the chromaffin cells that secretes catecholamines (adrenaline & and noradrenaline/ EPI
and norEPI)  produces high levels of both hormones and their breakdown products (VMA) which are
excreted in the urine in excess and used as diagnostic test.
- Majority are sporadic and cause is unknown
- In sporadic cases  80% tumors = unilateral, 10% bilateral and 10% extra-adrenal
- Metastases most common in regional lymph nodes. bone, LU, LV
- Occur at any age, high incidence in infancy
- In MEN  2/3rds are bilateral, in 5-10% of cases  tumours = malignant
- Sustained(2/3) or episodic(1/3) hypertension, & it’s complications
- May present with MI, aortic dissection, convulsions, anxiety & hyperventilation
- Crisis often precipitated by pressure on abdominal contents (lifting, bending etc…)
- ↑ BMR, sweating, heat intolerance & weight loss may mimic hyperthyroidism (send for thyroid panel)
o Cathecholamine Cardiomyopathy.
 Myocardial necrosis causing angina & MI in the absence of coronary artery disease
- Untreated  patients die of hypertensive complications

Neuroblastoma
- Malignant tumour of the adrenal medulla or sympathetic ganglia
- Readily infiltrate surrounding tissue, and metastasize to regional lymph nodes, LV, LU & bones
- Peak incidence in the first 3 years of life
- One of the most important malignant tumours of childhood
- Often = enlarging abdomen in a young child
- Firm, irregular, non-tender mass on abdominal palpation
- Highly variable depending on where it is, and where it metastasizes too
- Increased urinary levels of catecholamine metabolites (VMA)
o Only moderate catecholamine levels, vs. high in pheochromocytoma
- May differentiate into a more mature benign tumour = ganglioneuroma
o ganglioneruomas
 Generally found in older children & young adults

Parathyroid Glands and Parathyroid Hormone

- 90% of parathyroid masses in lower poles &/or posterior surface of thyroid = impalpable
- Parathyroid hormone breaks down bone, secreted by chief cells
- Regulates calcium concentration in extracellular fluid
 - Magnesium inhibits PTH secretion (b/c when you breakdown bone, you get Ca+ and Mg+)  so be
careful with long term Mg+ intake (Increase in Calcium = decrease in PTH, Decrease in Calcium =
Increase in PTH)
- Normal relationship lost in hyperparathyroidsm  PTH will be inappropriately high in relation to Ca+
(so, Ca+ high, but PTH still pumped out)
- Test Creatinine with all PTH assays for KI function (KI = target organ, so is it a problem with PTH or
with KI)
o Different Parathyroid Tests
 Increased PTH = Primary and pseudo hyperparathyroidism (renal insensitivity)
 Increased PTH-COOH = neoplasms, get renal failure
 Decreased PTH = most likely hypoparathyroidism
 Decreased PTH-NH2 = acute secretory changes best reflected by this variant
o Increased levels of PTH seen with milk ingestion, Vit A and D overdoses
o Decreased levels of PTH seen with Phosphate intake

Hypoparathyroidism
- Decreased secretion of PTH, or end organ insensitivity to the hormone (pseudohypoPTH)
- Most common cause is surgical resection of the parathyroids as a complication of thyroidectomy
- Symptoms are related to hypocalcemia (increased neuromuscular excitability and get mild hand/feet
tingling  severe muscle cramps, laryngeal stridor, & convulsions)
- Depression, paranoia, psychosis
- Elevated cerebrospinal fluid pressure & papilledema may mimic brain tumour
- PTH antibodies reported in idiopathic hypoPTH (IP)  suggests auto-immune basis
- All forms are successfully treated with Vitamin D & calcium supplementation

Pseudohypoparathyroidism (Secondary)
- Group of hereditary conditions in which hypocalcemia is caused by target organ insensitivity to PTH
- Inadequate resporption of Ca+ from the glomerular filtrate
- Resistant to other hormones : TSH, glucagons, FHS & LH
- Albright- hereditary osteodystrophy
o Short stature, abnormally short metacarpals/tarsals
o Obesity, mental retardation
o Resistance to PTH

Primary Hyperparathyroidism
- Excessive secretion of PTH by paraTh adenoma (80%), Primary hyperplasia of all the paraTh(15%) and
carcinoma (rare) (1%)
- With a functioning adenoma, the other paraTh glands tend to be atrophic
- See Hypercalcemia and hypophosphatemia
- Nervous system: see depression, Kidney: 10% renal colic and kidney stones
- Skeletal:
o Osteitis, fibrosa cystica:
 Minority of patients with a serious form of the disease, get bone pain, fractures, cysts,
bone swellings, chondrocalcinosis

Secondary Hyperparathyroidism
- Chronic hypocalcemia due to renal retention of phosphate, inadequate production of activated vitamin
D, & some degree of skeletal resistance to PTH  all lead to compensatory hyper secretion of PTH
- Chronic renal insufficiency associated with decreased phosphate excretion  hyperphosphatemia. High
serum phosphate directly depresses serum calcium  stimulates parathyroid gland activity
- Can get Renal osteodystrophy:
o Osseous manifestations of hyperparathyroidism (primary symptoms are those related to chronic
renal failure), Cause: chronic renal failure = m/c, vitamin D deficiency
 - Caused by any condition associated with a chronic depression in the serum calcium levels 
compensatory over activity of the parathyroid glands

Tertiary Hyperparathyroidism (Pseudo)

- Autonomous parathyroid hyperplasia after long-standing renal failure
- Parathyroid hyperplasia may not regress after renal transplantation surgical resection of parathyroid
necessary