Disorders of Calcium & Parathyroid Gland: Gosmanov

Question 1

Differentiate pathophysiology and clinical presentation of primary, secondary and tertiary hyperparathyroidism.

Answer 1

Primary- 
80-85% adenoma
-15% hyperplasia (MEN1,
MEN2A, HPT-Jaw Tumor
Syndrome, familial HPT)
-1% parathyroid carcinoma
S&S: symptoms are non-specific, maj. of pts. asymptomatic
Moans, groans, bones
*It's the PT gland's fault!*

Secondary-
Major causes of 2' PTH elevation:
-Hypocalcemia
-Hyperphosphatemia
-Vit. D Deficiency
*It's not the PT gland's fault! It's responding to an underlying pathology!*

Tertiary-
Occurs in the face of longstanding 2’ hyperparathyroidism.
Parathyroid glands develop hyperplasia due to chronically low levels of Ca and/or high PO4 levels.
At one point, these glands become autonomous.
Malignancy producing PTHrp
Someone else is pretending to be the PT gland!

Question 2

Formulate approach in initial work up of calcium disorders.

Answer 2

Primary Hyperparathyroidism- 
•Biochemical:
\::Calcium, Albumin (ionized calcium),
\::PTH
\::25-OH vitamin D,
\::24-hour urine calcium (to differentiate from FHH)
•Imaging:
\::Thyroid US
\::99Tc-sestamibi scan
\::DXA
\::Localization studies

Question 3

Describe clinical presentation and develop initial approach in management of patients with hypocalcemia and hypercalcemia

Answer 3

Initial Treatment of Acute HYPERcalcemia:

• Address Volume Status
• Saline Diuresis ± Furosemide (*only after volume status is corrected)
• Calcitonin – 3-4 days
• Bisphosphonates (Pamidronate IV - works for 2-3 wks or Zoledronic acid IV - works for 1-3 months)
• Glucocorticoids (*useful in myeloma, granulomatous disease, vitamin D toxicity)
• Dialysis

Initial Treatment of Acute Hypocalcemia:
–*Always correct Magnesium if low* (Mg resp. for PTH production)
–Calcium Gluconate
•1 - 2 ampules over ~10 – 20 minutes
•Followed by infusion if indicated

Long-term Management of HYPOcalcemia:
–Oral Calcium salts
–Vitamin D
•Ergocalciferol/Cholecalciferol (act in 10-14 days) - effective only if PTH is present
•Calcitriol – active vitamin D
–Hydrochlorothiazide – increases reabsorption of Calcium in the distal tubule

Question 4

Explain pathophysiology, clinical presentation, biochemical findings and therapeutic approaches in patients with Multiple Endocrine Neoplasia syndromes.

Answer 4

MEN – Multiple Endocrine Neoplasia
A syndrome in which 2 or more endocrine tumors occur in a single patient

MEN1
Affected gene: MENIN 11q12-13
80-95% Parathyroid
50% Pancreas (insulinoma, gastrinoma, VIPoma)
25% Pituitary (prolactinoma, Cushing's Dz, acromegaly)
S&S: Kidney stones, hyperCaemia, recurrent peptic ulcers, fasting hypoglycemia, hypogonadism, galactorrhea, weight gain, diarrhea
Screening: 
-Calcium, PTH
-gastrin
-insulin,glucose
-prolactin
-IGF-1
-ACTH, cortisol

Tx:

1. Definitive: resection of tumor(s) (e.g., 3 and ½ parathyroidectomy+/- thymectomy)
2. Symptomatic: proton pump inhibitors, octreotide

MEN2A
Gene affected: RET 10q11.2 Mutation at codon Cys634
Presentation/penetrance: 1/30,000, any age, more in adults, 80% of all MEN2
1. Medullary thyroid carcinoma – almost 100%
2. Pheochromocytoma – 40%
3. Primary HPT – 25%
S&S: Thyroid nodule, hypertension, spells, diaphoresis, hypercalcemia
Screening: -Calcitonin, CEA
-plasma and urine metanephrines
-Calcium, PTH
-Chromogranin A
Tx: 1. Definitive: total thyroidectomy with lymph node dissection, adrenalectomy, parathyroidectomy
2. Symptomatic: therapy of HTN

MEN2B
Gene affected: RET 10q11.2 Mutation at codon Met634
Presentation/penetrance: 1/30,000, early onset, 5% of all MEN2
1.Medullary thyroid carcinoma (more malignant) – 100%
2. Mucosal neuromas – 100%
3. Marfanoid habitus – 50%
4. Pheochromocytoma – 50%
S&S: Thyroid nodule, skin neuromas, Hirschsprung`s disease, hypertension, spells, diaphoresis, Mucosal neuromas
•marfanoid habitus
Screening: -Calcitonin, CEA
-plasma and urine metanephrines
-Chromogranin A
Tx: 1. Definitive: total thyroidectomy with lymph node dissection, adrenalectomy
2. Symptomatic: therapy of HTN